Heart Failure Update 2012

John Hakim MD FACCSouthern Maryland

HospitalFood for thought

Outlineof CHF Talk

Definition Pathophysiology Medical Treatment Mechanical Treatment Device Treatment Transplantation Option Future Hopes and Dreams

Definition of Heart Failure

bull HF is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood

In systolic heart failure the dominant feature is a reduction in cardiac output

In diastolic heart failure the dominant feature is impaired filling of the left ventricle

Heart Failure is a Major and Growing Public Health Problem in the US

middot Approximately 5 million patients in this country have HF

middot Over 550000 patients are diagnosed with HF for the first time each year

middot Primary reason for 12 to 15 million office visits and 65 million hospital days each year

middot In 2001 nearly 53000 patients died of HF as a primary cause

Heart failure is a major cause of Hospitalization

Heart Failure is Primarily a Condition of the Elderly

middot The incidence of HF approaches 10 per 1000 population after age 65

middot HF is the most common Medicare diagnosis-related group

middot More dollars are spent for the diagnosis and treatment of HF than any other diagnosis by Medicare

New York Heart Association Classification

Class I Physical activity is not limited and does not cause significant fatigue heart palpitations trouble breathing or chest pain

Class II Physical activity is somewhat limited You are comfortable at rest but ordinary activity causes fatigue heart palpitations trouble breathing or chest pain

Class III Physical activity is markedly limited You are comfortable at rest but less-than-ordinary activities cause fatigue heart palpitations trouble breathing or chest pain

Class IV All physical activity causes discomfort Symptoms also are present at rest Minor physical activity always makes symptoms worse

Prognosis

Class IV has 30 to 70 annual mortality

Class III has 10 to 20 annual mortality

Class II has 5 to 10 annual mortality

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Outlineof CHF Talk

Definition Pathophysiology Medical Treatment Mechanical Treatment Device Treatment Transplantation Option Future Hopes and Dreams

Definition of Heart Failure

bull HF is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood

In systolic heart failure the dominant feature is a reduction in cardiac output

In diastolic heart failure the dominant feature is impaired filling of the left ventricle

Heart Failure is a Major and Growing Public Health Problem in the US

middot Approximately 5 million patients in this country have HF

middot Over 550000 patients are diagnosed with HF for the first time each year

middot Primary reason for 12 to 15 million office visits and 65 million hospital days each year

middot In 2001 nearly 53000 patients died of HF as a primary cause

Heart failure is a major cause of Hospitalization

Heart Failure is Primarily a Condition of the Elderly

middot The incidence of HF approaches 10 per 1000 population after age 65

middot HF is the most common Medicare diagnosis-related group

middot More dollars are spent for the diagnosis and treatment of HF than any other diagnosis by Medicare

New York Heart Association Classification

Class I Physical activity is not limited and does not cause significant fatigue heart palpitations trouble breathing or chest pain

Class II Physical activity is somewhat limited You are comfortable at rest but ordinary activity causes fatigue heart palpitations trouble breathing or chest pain

Class III Physical activity is markedly limited You are comfortable at rest but less-than-ordinary activities cause fatigue heart palpitations trouble breathing or chest pain

Class IV All physical activity causes discomfort Symptoms also are present at rest Minor physical activity always makes symptoms worse

Prognosis

Class IV has 30 to 70 annual mortality

Class III has 10 to 20 annual mortality

Class II has 5 to 10 annual mortality

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Definition of Heart Failure

bull HF is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood

In systolic heart failure the dominant feature is a reduction in cardiac output

In diastolic heart failure the dominant feature is impaired filling of the left ventricle

Heart Failure is a Major and Growing Public Health Problem in the US

middot Approximately 5 million patients in this country have HF

middot Over 550000 patients are diagnosed with HF for the first time each year

middot Primary reason for 12 to 15 million office visits and 65 million hospital days each year

middot In 2001 nearly 53000 patients died of HF as a primary cause

Heart failure is a major cause of Hospitalization

Heart Failure is Primarily a Condition of the Elderly

middot The incidence of HF approaches 10 per 1000 population after age 65

middot HF is the most common Medicare diagnosis-related group

middot More dollars are spent for the diagnosis and treatment of HF than any other diagnosis by Medicare

New York Heart Association Classification

Class I Physical activity is not limited and does not cause significant fatigue heart palpitations trouble breathing or chest pain

Class II Physical activity is somewhat limited You are comfortable at rest but ordinary activity causes fatigue heart palpitations trouble breathing or chest pain

Class III Physical activity is markedly limited You are comfortable at rest but less-than-ordinary activities cause fatigue heart palpitations trouble breathing or chest pain

Class IV All physical activity causes discomfort Symptoms also are present at rest Minor physical activity always makes symptoms worse

Prognosis

Class IV has 30 to 70 annual mortality

Class III has 10 to 20 annual mortality

Class II has 5 to 10 annual mortality

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Heart Failure is a Major and Growing Public Health Problem in the US

middot Approximately 5 million patients in this country have HF

middot Over 550000 patients are diagnosed with HF for the first time each year

middot Primary reason for 12 to 15 million office visits and 65 million hospital days each year

middot In 2001 nearly 53000 patients died of HF as a primary cause

Heart failure is a major cause of Hospitalization

Heart Failure is Primarily a Condition of the Elderly

middot The incidence of HF approaches 10 per 1000 population after age 65

middot HF is the most common Medicare diagnosis-related group

middot More dollars are spent for the diagnosis and treatment of HF than any other diagnosis by Medicare

New York Heart Association Classification

Class I Physical activity is not limited and does not cause significant fatigue heart palpitations trouble breathing or chest pain

Class II Physical activity is somewhat limited You are comfortable at rest but ordinary activity causes fatigue heart palpitations trouble breathing or chest pain

Class III Physical activity is markedly limited You are comfortable at rest but less-than-ordinary activities cause fatigue heart palpitations trouble breathing or chest pain

Class IV All physical activity causes discomfort Symptoms also are present at rest Minor physical activity always makes symptoms worse

Prognosis

Class IV has 30 to 70 annual mortality

Class III has 10 to 20 annual mortality

Class II has 5 to 10 annual mortality

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Heart failure is a major cause of Hospitalization

Heart Failure is Primarily a Condition of the Elderly

middot The incidence of HF approaches 10 per 1000 population after age 65

middot HF is the most common Medicare diagnosis-related group

middot More dollars are spent for the diagnosis and treatment of HF than any other diagnosis by Medicare

New York Heart Association Classification

Class I Physical activity is not limited and does not cause significant fatigue heart palpitations trouble breathing or chest pain

Class II Physical activity is somewhat limited You are comfortable at rest but ordinary activity causes fatigue heart palpitations trouble breathing or chest pain

Class III Physical activity is markedly limited You are comfortable at rest but less-than-ordinary activities cause fatigue heart palpitations trouble breathing or chest pain

Class IV All physical activity causes discomfort Symptoms also are present at rest Minor physical activity always makes symptoms worse

Prognosis

Class IV has 30 to 70 annual mortality

Class III has 10 to 20 annual mortality

Class II has 5 to 10 annual mortality

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Heart Failure is Primarily a Condition of the Elderly

middot The incidence of HF approaches 10 per 1000 population after age 65

middot HF is the most common Medicare diagnosis-related group

middot More dollars are spent for the diagnosis and treatment of HF than any other diagnosis by Medicare

New York Heart Association Classification

Class I Physical activity is not limited and does not cause significant fatigue heart palpitations trouble breathing or chest pain

Class II Physical activity is somewhat limited You are comfortable at rest but ordinary activity causes fatigue heart palpitations trouble breathing or chest pain

Class III Physical activity is markedly limited You are comfortable at rest but less-than-ordinary activities cause fatigue heart palpitations trouble breathing or chest pain

Class IV All physical activity causes discomfort Symptoms also are present at rest Minor physical activity always makes symptoms worse

Prognosis

Class IV has 30 to 70 annual mortality

Class III has 10 to 20 annual mortality

Class II has 5 to 10 annual mortality

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

New York Heart Association Classification

Class I Physical activity is not limited and does not cause significant fatigue heart palpitations trouble breathing or chest pain

Class II Physical activity is somewhat limited You are comfortable at rest but ordinary activity causes fatigue heart palpitations trouble breathing or chest pain

Class III Physical activity is markedly limited You are comfortable at rest but less-than-ordinary activities cause fatigue heart palpitations trouble breathing or chest pain

Class IV All physical activity causes discomfort Symptoms also are present at rest Minor physical activity always makes symptoms worse

Prognosis

Class IV has 30 to 70 annual mortality

Class III has 10 to 20 annual mortality

Class II has 5 to 10 annual mortality

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Prognosis

Class IV has 30 to 70 annual mortality

Class III has 10 to 20 annual mortality

Class II has 5 to 10 annual mortality

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Character of Heart failure

Signs and symptoms of intravascular and interstitial volume overload including shortness of breath rales and edema

Manifestations of inadequate tissue perfusion such as impaired exercise tolerance fatigue and renal dysfunction

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Right Sided Heart failure

Fluid retention without dyspnea or rales

Often associated with weight gain dilation of the right ventricle

The focus of this talk is Chronic Left Sided Heart failure

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Types of Left sided Heart failure

Systolic dysfunction- reduced LV ejection fraction

Diastolic dysfunction- increased ventricular stiffness or impaired myocardial relaxation Often with preserved LV ejection fraction

Physiologic states where the heart cannot compensate for increased circulation or metabolic requirements (Regurgitatant valvular disease intra cardiac shunts disorders of heart rate or rhythm)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Causes of CHF

Structural abnormalities (congenital or acquired) that affect the peripheral and coronary arterial circulation pericardium myocardium or cardiac valves thus leading to the increased hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure

Fundamental causes comprising the biochemical and physiological mechanisms through which either an increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction and

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Etiology of Heart failure

Any condition that causes myocardial necrosis or chronic pressure or volume overload can cause CHF

Hypertension is a factor in 75 of patients

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Classical Symptoms of Heart Failure

Fatigue or inability to exercise well having less energy feeling more tired than usual

Dyspnea at rest or exertion Paroxysmal nocturnal dyspnea shortness of breath while sleeping or

that wakes you at night Orthopnea-Shortness of breath while lying down gets worse when you lie flat Cough ndash can be wet or dry with crackles and usually worse with lying

down

Weight gain bull Swelling in the feet or ankles usually worse at the end of the day or

after standing for long periods shoes may no longer fitbull Sometimes edma is painful but usually pressure indents the skin bull Abdominal swelling with decreased appetite and decreased muscle

strenght (Cardiac Chachectia)bull Abdominal distention (Ascites) usually a sign of right heart failure

Urination bull frequent urination usually at night Increased urination (Due to high

BNP)

Signs of heart failure

Exertional dyspnea Orthopnea Gallup sounds Lung Crepitations Pulmonary edema Edema

Acute Heart Failure Symptoms

Caused by rapid fluid buildup in the lungs (congestion pulmonary edema) Symptoms develop suddenly and may include

Severe shortness of breath An irregular or rapid heartbeat Coughing up foamy pink mucus

COMMON CAUSES OFSYSTOLIC FAILURE

Ischemic Heart disease and Prior MI account for

23 of systolic heart failure Essential Hypertension is a major cause of

ischemic and non ischemic systolic heart failure Hypertension increases afterload and accelerates

the progression of heart failure HTN causes chronic pressure overload

Other causes of Non ischemic heart failure aregenetic diseases Toxicdrug induced Immune mediated infiltrative process Metabolic disorders

All-cause Mortality vs LVEF (Median 29)

SurvivalProbability

Time (days)

LVEFlt30

LVEFge30

p=0005 vs LVEFlt30

Cause of Systolic Heart failureAcquired vs Genetic Causes

bull Acquired Causesbull Hypertensionbull Diabetesbull Dyslipidemiabull Valvular heart diseasebull Coronary or peripheral vascular

diseasebull Myopathybull Rheumatic feverbull Mediastinal irradiationbull Sleep Apneabull Exposure to cardiotoxic agents

(Adrianomycin Danaurubicin Embrel)

bull Current and past alcohol consumption

bull Smokingbull Collagen vascular diseasebull Exposure to sexually transmitted

diseasesbull Thyroid disorderbull Pheochromocytomabull Obesity

Genetic Causes Predisposition to

atherosclerotic disease or Valvular disease

(Hx of MIs strokes PAD) Sudden cardiac death Myopathy Conduction system disease

(need for pacemaker) Tachyarrhythmia Cardiomyopathy

(unexplained HF) Skeletal Myopathy

Complications of Chronic Heart failure

An irregular heartbeat leading to death (VT)

A stroke leading to death A heart attack leading to death Deep vein thrombosis Pulmonary embolism Anemia Cognitive impairment Mitral valve regurgitation

Acute Heart Failure Symptoms

Caused by rapid fluid buildup in the lungs (congestion pulmonary edema) Symptoms develop suddenly and may include

Severe shortness of breath An irregular or rapid heartbeat Coughing up foamy pink mucus

COMMON CAUSES OFSYSTOLIC FAILURE

Ischemic Heart disease and Prior MI account for

23 of systolic heart failure Essential Hypertension is a major cause of

ischemic and non ischemic systolic heart failure Hypertension increases afterload and accelerates

the progression of heart failure HTN causes chronic pressure overload

Other causes of Non ischemic heart failure aregenetic diseases Toxicdrug induced Immune mediated infiltrative process Metabolic disorders

All-cause Mortality vs LVEF (Median 29)

SurvivalProbability

Time (days)

LVEFlt30

LVEFge30

p=0005 vs LVEFlt30

Cause of Systolic Heart failureAcquired vs Genetic Causes

bull Acquired Causesbull Hypertensionbull Diabetesbull Dyslipidemiabull Valvular heart diseasebull Coronary or peripheral vascular

diseasebull Myopathybull Rheumatic feverbull Mediastinal irradiationbull Sleep Apneabull Exposure to cardiotoxic agents

(Adrianomycin Danaurubicin Embrel)

bull Current and past alcohol consumption

bull Smokingbull Collagen vascular diseasebull Exposure to sexually transmitted

diseasesbull Thyroid disorderbull Pheochromocytomabull Obesity

Genetic Causes Predisposition to

atherosclerotic disease or Valvular disease

(Hx of MIs strokes PAD) Sudden cardiac death Myopathy Conduction system disease

(need for pacemaker) Tachyarrhythmia Cardiomyopathy

(unexplained HF) Skeletal Myopathy

Complications of Chronic Heart failure

An irregular heartbeat leading to death (VT)

A stroke leading to death A heart attack leading to death Deep vein thrombosis Pulmonary embolism Anemia Cognitive impairment Mitral valve regurgitation

COMMON CAUSES OFSYSTOLIC FAILURE

Ischemic Heart disease and Prior MI account for

23 of systolic heart failure Essential Hypertension is a major cause of

ischemic and non ischemic systolic heart failure Hypertension increases afterload and accelerates

the progression of heart failure HTN causes chronic pressure overload

Other causes of Non ischemic heart failure aregenetic diseases Toxicdrug induced Immune mediated infiltrative process Metabolic disorders

All-cause Mortality vs LVEF (Median 29)

SurvivalProbability

Time (days)

LVEFlt30

LVEFge30

p=0005 vs LVEFlt30

Cause of Systolic Heart failureAcquired vs Genetic Causes

bull Acquired Causesbull Hypertensionbull Diabetesbull Dyslipidemiabull Valvular heart diseasebull Coronary or peripheral vascular

diseasebull Myopathybull Rheumatic feverbull Mediastinal irradiationbull Sleep Apneabull Exposure to cardiotoxic agents

(Adrianomycin Danaurubicin Embrel)

bull Current and past alcohol consumption

bull Smokingbull Collagen vascular diseasebull Exposure to sexually transmitted

diseasesbull Thyroid disorderbull Pheochromocytomabull Obesity

Genetic Causes Predisposition to

atherosclerotic disease or Valvular disease

(Hx of MIs strokes PAD) Sudden cardiac death Myopathy Conduction system disease

(need for pacemaker) Tachyarrhythmia Cardiomyopathy

(unexplained HF) Skeletal Myopathy

Complications of Chronic Heart failure

An irregular heartbeat leading to death (VT)

A stroke leading to death A heart attack leading to death Deep vein thrombosis Pulmonary embolism Anemia Cognitive impairment Mitral valve regurgitation

All-cause Mortality vs LVEF (Median 29)

SurvivalProbability

Time (days)

LVEFlt30

LVEFge30

p=0005 vs LVEFlt30

Cause of Systolic Heart failureAcquired vs Genetic Causes

bull Acquired Causesbull Hypertensionbull Diabetesbull Dyslipidemiabull Valvular heart diseasebull Coronary or peripheral vascular

diseasebull Myopathybull Rheumatic feverbull Mediastinal irradiationbull Sleep Apneabull Exposure to cardiotoxic agents

(Adrianomycin Danaurubicin Embrel)

bull Current and past alcohol consumption

bull Smokingbull Collagen vascular diseasebull Exposure to sexually transmitted

diseasesbull Thyroid disorderbull Pheochromocytomabull Obesity

Genetic Causes Predisposition to

atherosclerotic disease or Valvular disease

(Hx of MIs strokes PAD) Sudden cardiac death Myopathy Conduction system disease

(need for pacemaker) Tachyarrhythmia Cardiomyopathy

(unexplained HF) Skeletal Myopathy

Complications of Chronic Heart failure

An irregular heartbeat leading to death (VT)

A stroke leading to death A heart attack leading to death Deep vein thrombosis Pulmonary embolism Anemia Cognitive impairment Mitral valve regurgitation

Cause of Systolic Heart failureAcquired vs Genetic Causes

bull Acquired Causesbull Hypertensionbull Diabetesbull Dyslipidemiabull Valvular heart diseasebull Coronary or peripheral vascular

diseasebull Myopathybull Rheumatic feverbull Mediastinal irradiationbull Sleep Apneabull Exposure to cardiotoxic agents

(Adrianomycin Danaurubicin Embrel)

bull Current and past alcohol consumption

bull Smokingbull Collagen vascular diseasebull Exposure to sexually transmitted

diseasesbull Thyroid disorderbull Pheochromocytomabull Obesity

Genetic Causes Predisposition to

atherosclerotic disease or Valvular disease

(Hx of MIs strokes PAD) Sudden cardiac death Myopathy Conduction system disease

(need for pacemaker) Tachyarrhythmia Cardiomyopathy

(unexplained HF) Skeletal Myopathy

Complications of Chronic Heart failure

An irregular heartbeat leading to death (VT)

A stroke leading to death A heart attack leading to death Deep vein thrombosis Pulmonary embolism Anemia Cognitive impairment Mitral valve regurgitation

Complications of Chronic Heart failure

An irregular heartbeat leading to death (VT)

A stroke leading to death A heart attack leading to death Deep vein thrombosis Pulmonary embolism Anemia Cognitive impairment Mitral valve regurgitation

Common test ordered in CHF

medical history and a physical exam Lab testsElectrocardiogram Chest X-ray EchocardiogramBrain natriuretic peptide (BNP) TSH Nuclear stress testMUGA Cardiac catheterization

Diastolic Heart Failure

DIASTOLIC HEART FAILURE

Patients with symptoms and signs of Heart Failure with normal systolic function and diastolic dysfunctionbull 30 to 50 of patients with Heart failure

symptoms have normal LV systolic function bull Abnormal LV filling and elevated filling

pressuresbull Usually due to Impaired relaxation of the LV

and increased stiffness of the cardiac muscle

Most prevalent in patients over 75 years old

Copyright copy2000 BMJ Publishing Group Ltd

Jackson G et al BMJ 2000320167-170

Hypertrophic Cardiomyopathy

Pathogenesis of Diastolic Heart Failure

Pathologic Myocardial hypertrophybull HTN Hypertrophic Cardiomyopathy

Aging Ischemic fibrosis Restrictive Cardiomyopathy

bull Infiltrative disorders (Amyloid Sarcoid)bull Storage Diseases (Hemochromatosis)

Endomyocardial disorders Valvular heart disease

bull (obstructive or regurgitation)

DIASTOLIC HEART FAILUREusually due to Hemodynamic stress

Patients with diastolic heart failure do not tolerate hemodynamic stress well

Atrial fibrillation causes loss of atrial contraction and often leads to Diastolic CHF

Tachycardia shortens diastole and leads to CHF Elevation in BP worsens myocardial relaxation Ischemia worsens diastolic function raising

LA and PA pressures (This is why ischemia causes SOB)

Aortic Stenosis causes worsening diastolic function

Diastolic CHFAll treatments are empiric

(No trial data)

2005 ACCAHA guidelines supports 4 treatments of diastolic CHFbull Control of systolic and diastolic HTNbull Control of atrial rate in patients with A

fibbull Control of pulmonary congestion and

edema with diureticsbull Coronary revascularization of patients

with CAD where ischemia causes worse diastolic function

Diastolic Heart Failure often presents with Acute Pulmonary Edema

Treatmentbull Loop diuretics (furosemide)

Both immediate action to dilate pulmonary arteries and longer action to diurese

bull Afterload Reduction Nitrates Morphine Ace inhibitors (Captopril enalapril etc)

Systolic Heart Failure

The ballooning of the Heart

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

DIASTOLIC HEART FAILURE

Patients with symptoms and signs of Heart Failure with normal systolic function and diastolic dysfunctionbull 30 to 50 of patients with Heart failure

symptoms have normal LV systolic function bull Abnormal LV filling and elevated filling

pressuresbull Usually due to Impaired relaxation of the LV

and increased stiffness of the cardiac muscle

Most prevalent in patients over 75 years old

Copyright copy2000 BMJ Publishing Group Ltd

Jackson G et al BMJ 2000320167-170

Hypertrophic Cardiomyopathy

Pathogenesis of Diastolic Heart Failure

Pathologic Myocardial hypertrophybull HTN Hypertrophic Cardiomyopathy

Aging Ischemic fibrosis Restrictive Cardiomyopathy

bull Infiltrative disorders (Amyloid Sarcoid)bull Storage Diseases (Hemochromatosis)

Endomyocardial disorders Valvular heart disease

bull (obstructive or regurgitation)

DIASTOLIC HEART FAILUREusually due to Hemodynamic stress

Patients with diastolic heart failure do not tolerate hemodynamic stress well

Atrial fibrillation causes loss of atrial contraction and often leads to Diastolic CHF

Tachycardia shortens diastole and leads to CHF Elevation in BP worsens myocardial relaxation Ischemia worsens diastolic function raising

LA and PA pressures (This is why ischemia causes SOB)

Aortic Stenosis causes worsening diastolic function

Diastolic CHFAll treatments are empiric

(No trial data)

2005 ACCAHA guidelines supports 4 treatments of diastolic CHFbull Control of systolic and diastolic HTNbull Control of atrial rate in patients with A

fibbull Control of pulmonary congestion and

edema with diureticsbull Coronary revascularization of patients

with CAD where ischemia causes worse diastolic function

Diastolic Heart Failure often presents with Acute Pulmonary Edema

Treatmentbull Loop diuretics (furosemide)

Both immediate action to dilate pulmonary arteries and longer action to diurese

bull Afterload Reduction Nitrates Morphine Ace inhibitors (Captopril enalapril etc)

Systolic Heart Failure

The ballooning of the Heart

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Copyright copy2000 BMJ Publishing Group Ltd

Jackson G et al BMJ 2000320167-170

Hypertrophic Cardiomyopathy

Pathogenesis of Diastolic Heart Failure

Pathologic Myocardial hypertrophybull HTN Hypertrophic Cardiomyopathy

Aging Ischemic fibrosis Restrictive Cardiomyopathy

bull Infiltrative disorders (Amyloid Sarcoid)bull Storage Diseases (Hemochromatosis)

Endomyocardial disorders Valvular heart disease

bull (obstructive or regurgitation)

DIASTOLIC HEART FAILUREusually due to Hemodynamic stress

Patients with diastolic heart failure do not tolerate hemodynamic stress well

Atrial fibrillation causes loss of atrial contraction and often leads to Diastolic CHF

Tachycardia shortens diastole and leads to CHF Elevation in BP worsens myocardial relaxation Ischemia worsens diastolic function raising

LA and PA pressures (This is why ischemia causes SOB)

Aortic Stenosis causes worsening diastolic function

Diastolic CHFAll treatments are empiric

(No trial data)

2005 ACCAHA guidelines supports 4 treatments of diastolic CHFbull Control of systolic and diastolic HTNbull Control of atrial rate in patients with A

fibbull Control of pulmonary congestion and

edema with diureticsbull Coronary revascularization of patients

with CAD where ischemia causes worse diastolic function

Diastolic Heart Failure often presents with Acute Pulmonary Edema

Treatmentbull Loop diuretics (furosemide)

Both immediate action to dilate pulmonary arteries and longer action to diurese

bull Afterload Reduction Nitrates Morphine Ace inhibitors (Captopril enalapril etc)

Systolic Heart Failure

The ballooning of the Heart

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Pathogenesis of Diastolic Heart Failure

Pathologic Myocardial hypertrophybull HTN Hypertrophic Cardiomyopathy

Aging Ischemic fibrosis Restrictive Cardiomyopathy

bull Infiltrative disorders (Amyloid Sarcoid)bull Storage Diseases (Hemochromatosis)

Endomyocardial disorders Valvular heart disease

bull (obstructive or regurgitation)

DIASTOLIC HEART FAILUREusually due to Hemodynamic stress

Patients with diastolic heart failure do not tolerate hemodynamic stress well

Atrial fibrillation causes loss of atrial contraction and often leads to Diastolic CHF

Tachycardia shortens diastole and leads to CHF Elevation in BP worsens myocardial relaxation Ischemia worsens diastolic function raising

LA and PA pressures (This is why ischemia causes SOB)

Aortic Stenosis causes worsening diastolic function

Diastolic CHFAll treatments are empiric

(No trial data)

2005 ACCAHA guidelines supports 4 treatments of diastolic CHFbull Control of systolic and diastolic HTNbull Control of atrial rate in patients with A

fibbull Control of pulmonary congestion and

edema with diureticsbull Coronary revascularization of patients

with CAD where ischemia causes worse diastolic function

Diastolic Heart Failure often presents with Acute Pulmonary Edema

Treatmentbull Loop diuretics (furosemide)

Both immediate action to dilate pulmonary arteries and longer action to diurese

bull Afterload Reduction Nitrates Morphine Ace inhibitors (Captopril enalapril etc)

Systolic Heart Failure

The ballooning of the Heart

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

DIASTOLIC HEART FAILUREusually due to Hemodynamic stress

Patients with diastolic heart failure do not tolerate hemodynamic stress well

Atrial fibrillation causes loss of atrial contraction and often leads to Diastolic CHF

Tachycardia shortens diastole and leads to CHF Elevation in BP worsens myocardial relaxation Ischemia worsens diastolic function raising

LA and PA pressures (This is why ischemia causes SOB)

Aortic Stenosis causes worsening diastolic function

Diastolic CHFAll treatments are empiric

(No trial data)

2005 ACCAHA guidelines supports 4 treatments of diastolic CHFbull Control of systolic and diastolic HTNbull Control of atrial rate in patients with A

fibbull Control of pulmonary congestion and

edema with diureticsbull Coronary revascularization of patients

with CAD where ischemia causes worse diastolic function

Diastolic Heart Failure often presents with Acute Pulmonary Edema

Treatmentbull Loop diuretics (furosemide)

Both immediate action to dilate pulmonary arteries and longer action to diurese

bull Afterload Reduction Nitrates Morphine Ace inhibitors (Captopril enalapril etc)

Systolic Heart Failure

The ballooning of the Heart

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Diastolic CHFAll treatments are empiric

(No trial data)

2005 ACCAHA guidelines supports 4 treatments of diastolic CHFbull Control of systolic and diastolic HTNbull Control of atrial rate in patients with A

fibbull Control of pulmonary congestion and

edema with diureticsbull Coronary revascularization of patients

with CAD where ischemia causes worse diastolic function

Diastolic Heart Failure often presents with Acute Pulmonary Edema

Treatmentbull Loop diuretics (furosemide)

Both immediate action to dilate pulmonary arteries and longer action to diurese

bull Afterload Reduction Nitrates Morphine Ace inhibitors (Captopril enalapril etc)

Systolic Heart Failure

The ballooning of the Heart

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Diastolic Heart Failure often presents with Acute Pulmonary Edema

Treatmentbull Loop diuretics (furosemide)

Both immediate action to dilate pulmonary arteries and longer action to diurese

bull Afterload Reduction Nitrates Morphine Ace inhibitors (Captopril enalapril etc)

Systolic Heart Failure

The ballooning of the Heart

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Systolic Heart Failure

The ballooning of the Heart

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Copyright copy2000 BMJ Publishing Group Ltd

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Neurohormonal activation

Decreased cardiac output activates many neuro-hormonal compensatory systems that in the short term act to preserve circulatory hemostasis and maintain arterial pressure

When in excess these systems play a role in worsening of CHF

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Medical Treatment of Systolic Heart Failure

What Improves Survival ACE inhibitors Beta Blockers Spironolactone (Aldactone)

Eplenrone (Inspira) -Hydralazine and Nitrates (V-Heft) Angiotensin Receptor Blockers (ARB) Device Therapy (AICD)

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

DIURETICS

Sodium and Water retention are the hallmark of CHF and diuretics are mandatory treatment for patients with pulmonary or Peripheral edema

Patients with CHF should be encouraged to weigh themselves daily and seek advice if a weigh gain of more than 15kg in 24 hrs

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Why give ACE inhibitors

Directics activate the Renin Angiotensis system and should be given in combination with and ACE inhibitor

Correction of fluid overload with diuretics should be undertaken before starting an ACE inhibitor

Adding an ACE inhibitor to a patient on high dose diuretic may result in significant first dose hypotension

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

ACE-INHIBITORS

ACE inhibitors relieve symptoms reduce hospitalizations and improve survival in patients with systolic and diastolic heart failure and should be used regardless of the severity of CHF

Patients with the lowest EF derive the greatest benefits from ACE inhibitors

The evidence that ACE inhibitors improve survival and symptomatic wellbeing is incontrovertible

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Beta Blocker- Why do they work

In heart failure the nervous system is over stimulated Norepinephrine levels rise

Increased levels of circulating norepinephrine cause heart remodeling and arrhythmias

High levels of norepinephrine are directly toxic to heart cells and increase risk of death

Beta Blockers ndash block the toxic effect of nervous system over stimulation and norepinephrine

Normal

The Normal Heart is a b1-Organ That Functions in a b1 -Environment

b1

b1

b1 b2

b1

b1

b2

b1

b1b1

b1 b1b1

Normal Heart failure

Heart Failure Converts the Circulation From a b1- to a b1b2 a1- Environment

b1

b1

b1 b2

b1

b1

b2

b1

b1b1

b1 b1b1

b2

b1

b1 b1

b2

b1

b1

b1

b2b2

b1 b2b1 b2a1

a1

NE NE

NE

Cardiac cell toxicity

Carvedilol

b1 b2 a1

Metoprolol

Cofactors

[123I]mIBG Planar Imaging for Cardiac Assessment

Normal innervation NHYA Class II NYHA Class IV

Quantitation of cardiac uptake of [123I]mIBG expressed in terms of the ratio of countspixel between regions of interest (ROIs) drawn around the heart (H) and in the upper mediastinum (M) the HM ratio

HM ratio 22 17 11

Results of Direct Comparison Trials withMetoprolol and Carvedilol in CHF Patients

LV EjectionFraction ()

0

+2

+4

+6

+8

+10

+12

Metoprolol(n=123)

Carvedilol(n=125)

Packer M et al Am Heart J 2001141(6)899-907

P = 0009

BETA-BLOCKERS

BETA-BLOCKERS inhibit the adverse effects of chronic activation of the sympathetic nervous system acting on the myocardium

Patients with minimal symptoms (NYHA 2) derive little symptomatic benefit from beta blockers

BETA-BLOCKERS

Beta-BLOCKERS approved for the management of CHF are Carvedilol Metoprolol and bisoprolol

All three drugs have been shown to prolong survival but they are not the same

Primary Argument Supporting the Belief That Only b1 -Blockade is Important

Mortality results in earlier large-scale trials

MERIT-HF (metoprolol) 34 in risk

CIBIS-2 (bisoprolol) 34 in risk

COPERNICUS (carvedilol) 35 in risk

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Normal Heart failure

Heart Failure Converts the Circulation From a b1- to a b1b2 a1- Environment

b1

b1

b1 b2

b1

b1

b2

b1

b1b1

b1 b1b1

b2

b1

b1 b1

b2

b1

b1

b1

b2b2

b1 b2b1 b2a1

a1

NE NE

NE

Cardiac cell toxicity

Carvedilol

b1 b2 a1

Metoprolol

Cofactors

[123I]mIBG Planar Imaging for Cardiac Assessment

Normal innervation NHYA Class II NYHA Class IV

Quantitation of cardiac uptake of [123I]mIBG expressed in terms of the ratio of countspixel between regions of interest (ROIs) drawn around the heart (H) and in the upper mediastinum (M) the HM ratio

HM ratio 22 17 11

Results of Direct Comparison Trials withMetoprolol and Carvedilol in CHF Patients

LV EjectionFraction ()

0

+2

+4

+6

+8

+10

+12

Metoprolol(n=123)

Carvedilol(n=125)

Packer M et al Am Heart J 2001141(6)899-907

P = 0009

BETA-BLOCKERS

BETA-BLOCKERS inhibit the adverse effects of chronic activation of the sympathetic nervous system acting on the myocardium

Patients with minimal symptoms (NYHA 2) derive little symptomatic benefit from beta blockers

BETA-BLOCKERS

Beta-BLOCKERS approved for the management of CHF are Carvedilol Metoprolol and bisoprolol

All three drugs have been shown to prolong survival but they are not the same

Primary Argument Supporting the Belief That Only b1 -Blockade is Important

Mortality results in earlier large-scale trials

MERIT-HF (metoprolol) 34 in risk

CIBIS-2 (bisoprolol) 34 in risk

COPERNICUS (carvedilol) 35 in risk

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

NE NE

NE

Cardiac cell toxicity

Carvedilol

b1 b2 a1

Metoprolol

Cofactors

[123I]mIBG Planar Imaging for Cardiac Assessment

Normal innervation NHYA Class II NYHA Class IV

Quantitation of cardiac uptake of [123I]mIBG expressed in terms of the ratio of countspixel between regions of interest (ROIs) drawn around the heart (H) and in the upper mediastinum (M) the HM ratio

HM ratio 22 17 11

Results of Direct Comparison Trials withMetoprolol and Carvedilol in CHF Patients

LV EjectionFraction ()

0

+2

+4

+6

+8

+10

+12

Metoprolol(n=123)

Carvedilol(n=125)

Packer M et al Am Heart J 2001141(6)899-907

P = 0009

BETA-BLOCKERS

BETA-BLOCKERS inhibit the adverse effects of chronic activation of the sympathetic nervous system acting on the myocardium

Patients with minimal symptoms (NYHA 2) derive little symptomatic benefit from beta blockers

BETA-BLOCKERS

Beta-BLOCKERS approved for the management of CHF are Carvedilol Metoprolol and bisoprolol

All three drugs have been shown to prolong survival but they are not the same

Primary Argument Supporting the Belief That Only b1 -Blockade is Important

Mortality results in earlier large-scale trials

MERIT-HF (metoprolol) 34 in risk

CIBIS-2 (bisoprolol) 34 in risk

COPERNICUS (carvedilol) 35 in risk

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

[123I]mIBG Planar Imaging for Cardiac Assessment

Normal innervation NHYA Class II NYHA Class IV

Quantitation of cardiac uptake of [123I]mIBG expressed in terms of the ratio of countspixel between regions of interest (ROIs) drawn around the heart (H) and in the upper mediastinum (M) the HM ratio

HM ratio 22 17 11

Results of Direct Comparison Trials withMetoprolol and Carvedilol in CHF Patients

LV EjectionFraction ()

0

+2

+4

+6

+8

+10

+12

Metoprolol(n=123)

Carvedilol(n=125)

Packer M et al Am Heart J 2001141(6)899-907

P = 0009

BETA-BLOCKERS

BETA-BLOCKERS inhibit the adverse effects of chronic activation of the sympathetic nervous system acting on the myocardium

Patients with minimal symptoms (NYHA 2) derive little symptomatic benefit from beta blockers

BETA-BLOCKERS

Beta-BLOCKERS approved for the management of CHF are Carvedilol Metoprolol and bisoprolol

All three drugs have been shown to prolong survival but they are not the same

Primary Argument Supporting the Belief That Only b1 -Blockade is Important

Mortality results in earlier large-scale trials

MERIT-HF (metoprolol) 34 in risk

CIBIS-2 (bisoprolol) 34 in risk

COPERNICUS (carvedilol) 35 in risk

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Results of Direct Comparison Trials withMetoprolol and Carvedilol in CHF Patients

LV EjectionFraction ()

0

+2

+4

+6

+8

+10

+12

Metoprolol(n=123)

Carvedilol(n=125)

Packer M et al Am Heart J 2001141(6)899-907

P = 0009

BETA-BLOCKERS

BETA-BLOCKERS inhibit the adverse effects of chronic activation of the sympathetic nervous system acting on the myocardium

Patients with minimal symptoms (NYHA 2) derive little symptomatic benefit from beta blockers

BETA-BLOCKERS

Beta-BLOCKERS approved for the management of CHF are Carvedilol Metoprolol and bisoprolol

All three drugs have been shown to prolong survival but they are not the same

Primary Argument Supporting the Belief That Only b1 -Blockade is Important

Mortality results in earlier large-scale trials

MERIT-HF (metoprolol) 34 in risk

CIBIS-2 (bisoprolol) 34 in risk

COPERNICUS (carvedilol) 35 in risk

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

BETA-BLOCKERS

BETA-BLOCKERS inhibit the adverse effects of chronic activation of the sympathetic nervous system acting on the myocardium

Patients with minimal symptoms (NYHA 2) derive little symptomatic benefit from beta blockers

BETA-BLOCKERS

Beta-BLOCKERS approved for the management of CHF are Carvedilol Metoprolol and bisoprolol

All three drugs have been shown to prolong survival but they are not the same

Primary Argument Supporting the Belief That Only b1 -Blockade is Important

Mortality results in earlier large-scale trials

MERIT-HF (metoprolol) 34 in risk

CIBIS-2 (bisoprolol) 34 in risk

COPERNICUS (carvedilol) 35 in risk

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

BETA-BLOCKERS

Beta-BLOCKERS approved for the management of CHF are Carvedilol Metoprolol and bisoprolol

All three drugs have been shown to prolong survival but they are not the same

Primary Argument Supporting the Belief That Only b1 -Blockade is Important

Mortality results in earlier large-scale trials

MERIT-HF (metoprolol) 34 in risk

CIBIS-2 (bisoprolol) 34 in risk

COPERNICUS (carvedilol) 35 in risk

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Primary Argument Supporting the Belief That Only b1 -Blockade is Important

Mortality results in earlier large-scale trials

MERIT-HF (metoprolol) 34 in risk

CIBIS-2 (bisoprolol) 34 in risk

COPERNICUS (carvedilol) 35 in risk

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

060 080 100b-blocker

betterb-blocker

worse

b-1 only

32 Post-InfarctionTrials (n=26580)

Usualantisympathetic blockade

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

32 Post-InfarctionTrials (n=26580)

More than usualantisympathetic blockade

Less than usualantisympathetic blockade

Usualantisympathetic blockade

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

b-1 + b-2andor a-1

060 080 100b-blocker

betterb-blocker

worse

050 075 100b-blocker

betterb-blocker

worse

b-1 only

b-blockerswith ISA

D = 13 D = 13

32 Post-InfarctionTrials (n=26580)

27 Heart FailureTrials (n=15851)

125

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Metoprolol

(selective blockade)

Carvedilol

(comprehensive blockade)

Baseline

1020 deaths

COMET Study Design

3029 ptsclass II-III CHF

LVEF lt 35

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Metoprolol tartrate

Carvedilol

3125 mg BID

Baseline

625 mg BID

125 mg BID

1020 deaths

COMET Study Design

5 mg BID

125 mg BID

25 mg BID

3029 ptsclass II-III CHF

LVEF lt 35

25 mg BID

50 mg BID

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Packer M et al Am Heart J 2001141884ndash888

+ 12

+ 6

0

ndash 6

ndash 12

ndash 18

ndash 24

P=009 P=072

LV EjectionFraction ()

LV End-DiastolicVolume (mLm2)

+ 12

+ 10

+ 8

+ 6

+ 4

+ 2

0

Metoprolol (n=123)

Carvedilol (n=125)

Mean duration 875 mos

Comparison of Carvedilol With Metoprolol on LV Function

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

COMET(Carvedilol or Metoprolol European Trial)

Compares comprehensive 1- 2- 1-blockade with carvedilol to 1-selective blockade with metoprolol tartrate

Prespecified end points all-cause mortality combined risk of all-cause mortality and hospitalization

More than 3000 patients with class IIndashIV heart failure due to ischemic or nonischemic Cardiomyopathybull With over 1020 events COMET is the largest

trial ever conducted in heart failure Intended follow-up was at least 35 years

bull 10000 patient-years makes COMET the longest trial ever conducted in heart failure

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Randomized(No run-in phase)

3029 patients with stable heart failure New York Heart AssociationClass IIndashIV receiving standard treatment including ACE inhibitors

Time to 1020 deathsEstimated to be 4 to 6 years

Screening Titration to maximum tolerated

or target dose

(Start carvedilol 3125 mg bid metoprolol tartrate 5 mg bid)

Assessments every 4 months during maintenance phase

(n1500) Metoprolol 50 mg bid

(n1500) Carvedilol 25 mg bid

Poole-Wilson PA et al Eur J Heart Fail 20024321ndash329 Poole-Wilson PA et al Lancet 20033627ndash13

COMET Study Design

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Time (years)

Per

cen

tag

e M

ort

alit

y (

)

0

10

20

30

40

0 1 2 3 4 5

Relativerisk

95 CI P value

Carvedilol vs Metoprolol

083 074ndash093 0017

Metoprolol

Carvedilol

Effect of Carvedilol vs Metoprolol on Mortality

Poole-Wilson PA et al Lancet 20033627ndash13

macr17Risk reduction

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

COMET Median Survival

Carvedilol 80 yearsMetoprolol 66 years

Carvedilol prolonged median survival by 14 years beyond that achieved with metoprolol

Assuming constant hazard

Poole-Wilson PA et al Lancet 20033627ndash13

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

EPHESUS TRIAL Inspra

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Spironolactone and Epelnerone

ALDOSTERONE RECEPTORS WITHINTHE HEART MEDIATE FIBROSIS

HYPERTROPHY AND ARRHYTHMOGENESIS

REDUCTION IN ALL CAUSE MORTALITY AND SYMPTOMATIC RELIEF IN PATIENTS WITH ADVANCED CHF AT DOSES 25MGMDAY

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Spironolactone and Epelnerone

HYPERKALAEMIAPARTICULARLY WHEN USED WITH ACE-INHIBITORSATRAs

IN PATIENTS WITH IMPAIRED RENAL FUNCTIONMONITORING OF POTASSIUM LEVELS ESSENTIAL

USED IN COMBINATION WITH ACEINHIBITORLOOP DIURETIC +-DIGOXIN

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Digoxin

BLOCKAGE OF THE SODIUMPOTASSIUM ATPase PUMP RESULTS IN INCREASED INOTROPIC RESPONSIVENESS

THE DATA SUGGESTS THAT DIGOXIN HAS NO INFLUENCE ON SURVIVAL BUT REDUCES HOSPITALISATION AND IMPROVED THE QUALITY OF LIFE OF MANY PATIENTS

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Heart Failure-Medical Treatment

Digoxin improves Symptoms and prevents hospitalizations in men but not women

Niseritide (Natracor) induces diuresis and improves symptoms but does not improve longevity

Amiodarone helps prevent arrythmic events

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Heart Failure Device Treatment

Bi-Ventricular pacemaker helps improve cardiac output and improves symptoms sometimes

Automatic Implantable Defibrillator improves survival in patients with EF less than 35 (Better than drug therapy alone)

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

COMPANION Secondary End Point of All-cause Mortality

Bristow MR et al Paper presented at American College of Cardiology March 31 2003 Chicago Ill

12-monthOPT Event Rate(1-y) = 190

P=12 CRT vs OPT

P=002 CRT-D vs OPT

12-month event rate reductionsCRT = by 239CRT-D = by 434

Any Death

P

atie

nts

Eve

nt-

Fre

e

Days from Randomization

0 120 240 360 480 600 720 840 960 1080

60

50

70

80

90

100

CRT = cardiac resynchronization therapy CRT-D = cardiac resynchronization therapy plus implantable cardioverter defibrillator OPT = optimal drug therapy

CRT-D

OPT

CRT

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

REMATCH-LVADs in Extremely Severe Heart Failure

100

80

60

40

20

00000 6 12 18 24 30

No at Risk

LV assist device

Medical therapy68 18 22 11 5 1

61 27 11 4 3 0

Months

Su

rviv

al (

)

Medical therapy

LV assist device

Rose EA N Engl J Med 20013451435ndash1443

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

People Donrsquot want and LVAD they want a Heart

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Heart Transplant Waiting ListJanuary 9th 2012

73 people Washington DC metropolitan area waiting for heart transplant

3155 people In USA waiting for heart Transplant

2011 1760 patients on the heart wait list received heart transplants That figure represents a decrease from the 2333 hearts transplanted in 2010 and the 2211 in 2009

Heart Transplantation There were 2125 heart transplants performed in

the United States in 2005 and 2016 in 2004 Each year thousands more adults would benefit

from a heart transplant if more donated hearts were available

In the United States 724 percent of heart transplant patients are male 700 percent are white 191 percent are ages 35-49 and 450 percent are ages 50-64

As of Aug 11 2006the one-year survival rate was 861 percent for males and 839 percent for females the three-year survival rate was about 783 percent for males and 749 percent for females The five-year survival rate was 712 percent for males and 669 percent for females

Markers of Heart Failure

Identify Markers and we can better treat the disease

Albumin BNP Chest to HEART MIBG ratio- a marker for denervation of the

heart and loss of sympathic tone- assessment of myocardial sympathetic innervation as determined by the heart to mediastinum (HM) ratio on planar 123I‑mIBG imaging as either normal (gt16) or abnormal (lt16) for identifying HF subjects at higher risk of experiencing an adverse cardiac event

UACR= urinary albumin to creatinine ratio Macroalbuminuria=UACR gt25 mgmmol Microalbuminuria=UACR 25ndash250 mgmmol (men) or 35ndash250 mgmmol (women)compared with normoalbuminuria (UACRlt25 mgmmol) n=1349

End point Microalbuminuria n=704

Macroalbuminuria n=257

Per 100-mgmmol UACR increment

CV death or HF hospitalization

143 (121ndash169) 175 (139ndash220) 107(100ndash114)

All-cause mortality

162 (132ndash199) 176 (132ndash2middot35) 108(100ndash117)

HF hospitalization

131 (107ndash159) 167 (128ndash2middot17) 107 099ndash115)

Albumin excretion is prognostic marker in heart failure (Analysis from CHARM Study)

Adjusted hazard ratios (95 CI) for clinical outcomes by degree of albuminuria (defined by UACR with cut points and as continuous variable) in CHARM

Jackson CE et al Lancet 2009 374543ndash550

All-cause Mortality vs BNP (Median 140)

SurvivalProbability

Time (days)

ltMedianLess than 140 BNP

gtMedianGreater Than 140BNP

plt000001

HM=096Died at 8 moHF Progression

HM=138

Died at 8 mo SCD (No ICD)

HM=167

No event

1 2 3

Three Patients with NYHA Class II HF and LVEF between 20 and 25 Patient 1 has highly elevated BNP (gt1000) BNP in patients 2 and 3 is normal (lt100)

Based upon the results of ADMIRE-HF 2-year cardiac mortality risk for patient 1 is 10 times that of patient 3(IF your Chest to HEART MIBG ratio is greater than 16 you donrsquot die)

All-cause Mortality vs BNP (Median 140) amp HM

Time (days)

BNPgt140amp HM ge160

BNPgt140amp HMlt160

BNPlt140amp HMlt160

BNPlt140amp HM ge160

SurvivalProbability

p=0024 vs BNPgt140 amp HM ge160

Current and Future Therapies

Drugs CHF disease

management programs

Resynchronizatin therapy + ICD

Renal Denervation

ultrafiltration does not work if diuretic resistant

LVADs bull Total artificial heart

Cardiac transplantbull (batistacardiomyoplast

y amp ldquoacornrdquo does not work)

Early-stage Treatment Late-stage Treatment

Resynchronization therapy is an effective early-stage therapy

Curing Heart failure by curing hypertension- Denervating the Kidney

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

Markers of Heart Failure

Identify Markers and we can better treat the disease

Albumin BNP Chest to HEART MIBG ratio- a marker for denervation of the

heart and loss of sympathic tone- assessment of myocardial sympathetic innervation as determined by the heart to mediastinum (HM) ratio on planar 123I‑mIBG imaging as either normal (gt16) or abnormal (lt16) for identifying HF subjects at higher risk of experiencing an adverse cardiac event

UACR= urinary albumin to creatinine ratio Macroalbuminuria=UACR gt25 mgmmol Microalbuminuria=UACR 25ndash250 mgmmol (men) or 35ndash250 mgmmol (women)compared with normoalbuminuria (UACRlt25 mgmmol) n=1349

End point Microalbuminuria n=704

Macroalbuminuria n=257

Per 100-mgmmol UACR increment

CV death or HF hospitalization

143 (121ndash169) 175 (139ndash220) 107(100ndash114)

All-cause mortality

162 (132ndash199) 176 (132ndash2middot35) 108(100ndash117)

HF hospitalization

131 (107ndash159) 167 (128ndash2middot17) 107 099ndash115)

Albumin excretion is prognostic marker in heart failure (Analysis from CHARM Study)

Adjusted hazard ratios (95 CI) for clinical outcomes by degree of albuminuria (defined by UACR with cut points and as continuous variable) in CHARM

Jackson CE et al Lancet 2009 374543ndash550

All-cause Mortality vs BNP (Median 140)

SurvivalProbability

Time (days)

ltMedianLess than 140 BNP

gtMedianGreater Than 140BNP

plt000001

HM=096Died at 8 moHF Progression

HM=138

Died at 8 mo SCD (No ICD)

HM=167

No event

1 2 3

Three Patients with NYHA Class II HF and LVEF between 20 and 25 Patient 1 has highly elevated BNP (gt1000) BNP in patients 2 and 3 is normal (lt100)

Based upon the results of ADMIRE-HF 2-year cardiac mortality risk for patient 1 is 10 times that of patient 3(IF your Chest to HEART MIBG ratio is greater than 16 you donrsquot die)

All-cause Mortality vs BNP (Median 140) amp HM

Time (days)

BNPgt140amp HM ge160

BNPgt140amp HMlt160

BNPlt140amp HMlt160

BNPlt140amp HM ge160

SurvivalProbability

p=0024 vs BNPgt140 amp HM ge160

Current and Future Therapies

Drugs CHF disease

management programs

Resynchronizatin therapy + ICD

Renal Denervation

ultrafiltration does not work if diuretic resistant

LVADs bull Total artificial heart

Cardiac transplantbull (batistacardiomyoplast

y amp ldquoacornrdquo does not work)

Early-stage Treatment Late-stage Treatment

Resynchronization therapy is an effective early-stage therapy

Curing Heart failure by curing hypertension- Denervating the Kidney

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

UACR= urinary albumin to creatinine ratio Macroalbuminuria=UACR gt25 mgmmol Microalbuminuria=UACR 25ndash250 mgmmol (men) or 35ndash250 mgmmol (women)compared with normoalbuminuria (UACRlt25 mgmmol) n=1349

End point Microalbuminuria n=704

Macroalbuminuria n=257

Per 100-mgmmol UACR increment

CV death or HF hospitalization

143 (121ndash169) 175 (139ndash220) 107(100ndash114)

All-cause mortality

162 (132ndash199) 176 (132ndash2middot35) 108(100ndash117)

HF hospitalization

131 (107ndash159) 167 (128ndash2middot17) 107 099ndash115)

Albumin excretion is prognostic marker in heart failure (Analysis from CHARM Study)

Adjusted hazard ratios (95 CI) for clinical outcomes by degree of albuminuria (defined by UACR with cut points and as continuous variable) in CHARM

Jackson CE et al Lancet 2009 374543ndash550

All-cause Mortality vs BNP (Median 140)

SurvivalProbability

Time (days)

ltMedianLess than 140 BNP

gtMedianGreater Than 140BNP

plt000001

HM=096Died at 8 moHF Progression

HM=138

Died at 8 mo SCD (No ICD)

HM=167

No event

1 2 3

Three Patients with NYHA Class II HF and LVEF between 20 and 25 Patient 1 has highly elevated BNP (gt1000) BNP in patients 2 and 3 is normal (lt100)

Based upon the results of ADMIRE-HF 2-year cardiac mortality risk for patient 1 is 10 times that of patient 3(IF your Chest to HEART MIBG ratio is greater than 16 you donrsquot die)

All-cause Mortality vs BNP (Median 140) amp HM

Time (days)

BNPgt140amp HM ge160

BNPgt140amp HMlt160

BNPlt140amp HMlt160

BNPlt140amp HM ge160

SurvivalProbability

p=0024 vs BNPgt140 amp HM ge160

Current and Future Therapies

Drugs CHF disease

management programs

Resynchronizatin therapy + ICD

Renal Denervation

ultrafiltration does not work if diuretic resistant

LVADs bull Total artificial heart

Cardiac transplantbull (batistacardiomyoplast

y amp ldquoacornrdquo does not work)

Early-stage Treatment Late-stage Treatment

Resynchronization therapy is an effective early-stage therapy

Curing Heart failure by curing hypertension- Denervating the Kidney

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

All-cause Mortality vs BNP (Median 140)

SurvivalProbability

Time (days)

ltMedianLess than 140 BNP

gtMedianGreater Than 140BNP

plt000001

HM=096Died at 8 moHF Progression

HM=138

Died at 8 mo SCD (No ICD)

HM=167

No event

1 2 3

Three Patients with NYHA Class II HF and LVEF between 20 and 25 Patient 1 has highly elevated BNP (gt1000) BNP in patients 2 and 3 is normal (lt100)

Based upon the results of ADMIRE-HF 2-year cardiac mortality risk for patient 1 is 10 times that of patient 3(IF your Chest to HEART MIBG ratio is greater than 16 you donrsquot die)

All-cause Mortality vs BNP (Median 140) amp HM

Time (days)

BNPgt140amp HM ge160

BNPgt140amp HMlt160

BNPlt140amp HMlt160

BNPlt140amp HM ge160

SurvivalProbability

p=0024 vs BNPgt140 amp HM ge160

Current and Future Therapies

Drugs CHF disease

management programs

Resynchronizatin therapy + ICD

Renal Denervation

ultrafiltration does not work if diuretic resistant

LVADs bull Total artificial heart

Cardiac transplantbull (batistacardiomyoplast

y amp ldquoacornrdquo does not work)

Early-stage Treatment Late-stage Treatment

Resynchronization therapy is an effective early-stage therapy

Curing Heart failure by curing hypertension- Denervating the Kidney

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

HM=096Died at 8 moHF Progression

HM=138

Died at 8 mo SCD (No ICD)

HM=167

No event

1 2 3

Three Patients with NYHA Class II HF and LVEF between 20 and 25 Patient 1 has highly elevated BNP (gt1000) BNP in patients 2 and 3 is normal (lt100)

Based upon the results of ADMIRE-HF 2-year cardiac mortality risk for patient 1 is 10 times that of patient 3(IF your Chest to HEART MIBG ratio is greater than 16 you donrsquot die)

All-cause Mortality vs BNP (Median 140) amp HM

Time (days)

BNPgt140amp HM ge160

BNPgt140amp HMlt160

BNPlt140amp HMlt160

BNPlt140amp HM ge160

SurvivalProbability

p=0024 vs BNPgt140 amp HM ge160

Current and Future Therapies

Drugs CHF disease

management programs

Resynchronizatin therapy + ICD

Renal Denervation

ultrafiltration does not work if diuretic resistant

LVADs bull Total artificial heart

Cardiac transplantbull (batistacardiomyoplast

y amp ldquoacornrdquo does not work)

Early-stage Treatment Late-stage Treatment

Resynchronization therapy is an effective early-stage therapy

Curing Heart failure by curing hypertension- Denervating the Kidney

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

All-cause Mortality vs BNP (Median 140) amp HM

Time (days)

BNPgt140amp HM ge160

BNPgt140amp HMlt160

BNPlt140amp HMlt160

BNPlt140amp HM ge160

SurvivalProbability

p=0024 vs BNPgt140 amp HM ge160

Current and Future Therapies

Drugs CHF disease

management programs

Resynchronizatin therapy + ICD

Renal Denervation

ultrafiltration does not work if diuretic resistant

LVADs bull Total artificial heart

Cardiac transplantbull (batistacardiomyoplast

y amp ldquoacornrdquo does not work)

Early-stage Treatment Late-stage Treatment

Resynchronization therapy is an effective early-stage therapy

Curing Heart failure by curing hypertension- Denervating the Kidney

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

Current and Future Therapies

Drugs CHF disease

management programs

Resynchronizatin therapy + ICD

Renal Denervation

ultrafiltration does not work if diuretic resistant

LVADs bull Total artificial heart

Cardiac transplantbull (batistacardiomyoplast

y amp ldquoacornrdquo does not work)

Early-stage Treatment Late-stage Treatment

Resynchronization therapy is an effective early-stage therapy

Curing Heart failure by curing hypertension- Denervating the Kidney

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

Curing Heart failure by curing hypertension- Denervating the Kidney

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

Stem Cells trial Shows Promise for Ischemic heart failure

-1162012 AHA Encouraging two-year follow-up from the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial

-c-KIT-positive Ccardiac stem Cells in patients with left ventricular dysfunction (LVEF lt40) following an MI In the trial the cells were harvested from the patients right atrial appendage isolated and expanded and then infused to repair an infarction during coronary bypass surgery

-Echocardiography showed the average LVEF in the 18 patients treated with the CSC infusion increased from 290 before infusion to 360 (p lt0001) four months after the procedure During that period LVEF improved only from 292 to 294 in 13 control patients

Balloon Pump to augment Coronary Perfusion

eecp

EECP Reduced frequency or complete elimination of

angina symptoms Better ability to exercise free from chest pain and

breathlessness Decrease in need for anti-angina nitrate

medication Clinical tests show Decreased exercise-induced signs of angina on

ECG (prolonged time to ST depression on exercise stress testing)

Increased blood supply to heart muscle demonstrated by myocardial perfusion scan techniques before and after EECP (Technetium scan Cardiovascular MRI stress ECHO)

Improvement of EF in some Patients

eecp

EECP Reduced frequency or complete elimination of

angina symptoms Better ability to exercise free from chest pain and

breathlessness Decrease in need for anti-angina nitrate

medication Clinical tests show Decreased exercise-induced signs of angina on

ECG (prolonged time to ST depression on exercise stress testing)

Increased blood supply to heart muscle demonstrated by myocardial perfusion scan techniques before and after EECP (Technetium scan Cardiovascular MRI stress ECHO)

Improvement of EF in some Patients

EECP Reduced frequency or complete elimination of

angina symptoms Better ability to exercise free from chest pain and

breathlessness Decrease in need for anti-angina nitrate

medication Clinical tests show Decreased exercise-induced signs of angina on

ECG (prolonged time to ST depression on exercise stress testing)

Increased blood supply to heart muscle demonstrated by myocardial perfusion scan techniques before and after EECP (Technetium scan Cardiovascular MRI stress ECHO)

Improvement of EF in some Patients

Future Horizons and Pipe Dreams

Heart Transplantation- A viable option for a select few patients

Left Ventricular Assist devices and the Artificial heart are available options and used mainly as a bridge to transplant and not destination therapy

Stem cell transplantation and myocaridal cell imlantation have not yet proven viable

Worldwide REGISTRY DATABASENumber of Transplants Reported

ORGANTransplants Reported from 712006 through

6302007

Total Transplants Reported through

6302007

Heart 3114 80106

Heart-Lung 63 3341

Lung 2099 25950

ISHLT 2008J Heart Lung Transplant 200827 937-983

The HeartMateII is a continuous flow cardiac assist device Heart surgeon Bud Frazier and his team are working with two such devices to develop a continuous flow artificial heart (Courtesy Texas Heartreg Institute)

Artificial Heart

Evidence-Based Treatment Across the Continuum of Systolic LVD and HF

Control Volume Improve Clinical Outcomes

DiureticsRenal ReplacementTherapy

Digoxin

-BlockerACEIor ARB

AldosteroneAntagonist

or ARB

Treat Residual Symptoms

CRT an ICD

HDZNISDNIn selected patients

Drugs to avoid in heart failure

NSAID ndash I buprophen( Advil Motrin) Naproxen ( Alieve Naprosyn) Cox-2 inhibitors (Celebrex)

The NSAID can cause kidney to retain salt and water and Interfere with ACEARB class

Use Acetemenphen Or Narcotics instead for pain and aches

Drugs to Avoid in CHF

Anti-Arrhythmics in Class 1 ( Sodium Blockers and Class 3 ( Potassium Channel blockers)

The only heart rhythm drugs safe in Systolic dysfuction are Amiodarone and Dofeditilide (Tikosyn)

Drugs to Avoid in CHF

Avoid Non Dihydropyridine Calcium Channel blockers

Non- dihydropridine Calcium Channel blockers (Verapamil amp Diltiazem) decrease the strength of myocardial contractility and decrease heart rate

Verapamil and Diltiazem can worsen Heart failure and do not improve survival

15 Dihydropiridines are neutral in Heart failure as Anti-hypertensives

Amlodipine and Felodipine have not been shown to decrease survival in heart failure

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Worldwide REGISTRY DATABASENumber of Transplants Reported

ORGANTransplants Reported from 712006 through

6302007

Total Transplants Reported through

6302007

Heart 3114 80106

Heart-Lung 63 3341

Lung 2099 25950

ISHLT 2008J Heart Lung Transplant 200827 937-983

The HeartMateII is a continuous flow cardiac assist device Heart surgeon Bud Frazier and his team are working with two such devices to develop a continuous flow artificial heart (Courtesy Texas Heartreg Institute)

Artificial Heart

Evidence-Based Treatment Across the Continuum of Systolic LVD and HF

Control Volume Improve Clinical Outcomes

DiureticsRenal ReplacementTherapy

Digoxin

-BlockerACEIor ARB

AldosteroneAntagonist

or ARB

Treat Residual Symptoms

CRT an ICD

HDZNISDNIn selected patients

Drugs to avoid in heart failure

NSAID ndash I buprophen( Advil Motrin) Naproxen ( Alieve Naprosyn) Cox-2 inhibitors (Celebrex)

The NSAID can cause kidney to retain salt and water and Interfere with ACEARB class

Use Acetemenphen Or Narcotics instead for pain and aches

Drugs to Avoid in CHF

Anti-Arrhythmics in Class 1 ( Sodium Blockers and Class 3 ( Potassium Channel blockers)

The only heart rhythm drugs safe in Systolic dysfuction are Amiodarone and Dofeditilide (Tikosyn)

Drugs to Avoid in CHF

Avoid Non Dihydropyridine Calcium Channel blockers

Non- dihydropridine Calcium Channel blockers (Verapamil amp Diltiazem) decrease the strength of myocardial contractility and decrease heart rate

Verapamil and Diltiazem can worsen Heart failure and do not improve survival

15 Dihydropiridines are neutral in Heart failure as Anti-hypertensives

Amlodipine and Felodipine have not been shown to decrease survival in heart failure

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

The HeartMateII is a continuous flow cardiac assist device Heart surgeon Bud Frazier and his team are working with two such devices to develop a continuous flow artificial heart (Courtesy Texas Heartreg Institute)

Artificial Heart

Evidence-Based Treatment Across the Continuum of Systolic LVD and HF

Control Volume Improve Clinical Outcomes

DiureticsRenal ReplacementTherapy

Digoxin

-BlockerACEIor ARB

AldosteroneAntagonist

or ARB

Treat Residual Symptoms

CRT an ICD

HDZNISDNIn selected patients

Drugs to avoid in heart failure

NSAID ndash I buprophen( Advil Motrin) Naproxen ( Alieve Naprosyn) Cox-2 inhibitors (Celebrex)

The NSAID can cause kidney to retain salt and water and Interfere with ACEARB class

Use Acetemenphen Or Narcotics instead for pain and aches

Drugs to Avoid in CHF

Anti-Arrhythmics in Class 1 ( Sodium Blockers and Class 3 ( Potassium Channel blockers)

The only heart rhythm drugs safe in Systolic dysfuction are Amiodarone and Dofeditilide (Tikosyn)

Drugs to Avoid in CHF

Avoid Non Dihydropyridine Calcium Channel blockers

Non- dihydropridine Calcium Channel blockers (Verapamil amp Diltiazem) decrease the strength of myocardial contractility and decrease heart rate

Verapamil and Diltiazem can worsen Heart failure and do not improve survival

15 Dihydropiridines are neutral in Heart failure as Anti-hypertensives

Amlodipine and Felodipine have not been shown to decrease survival in heart failure

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Evidence-Based Treatment Across the Continuum of Systolic LVD and HF

Control Volume Improve Clinical Outcomes

DiureticsRenal ReplacementTherapy

Digoxin

-BlockerACEIor ARB

AldosteroneAntagonist

or ARB

Treat Residual Symptoms

CRT an ICD

HDZNISDNIn selected patients

Drugs to avoid in heart failure

NSAID ndash I buprophen( Advil Motrin) Naproxen ( Alieve Naprosyn) Cox-2 inhibitors (Celebrex)

The NSAID can cause kidney to retain salt and water and Interfere with ACEARB class

Use Acetemenphen Or Narcotics instead for pain and aches

Drugs to Avoid in CHF

Anti-Arrhythmics in Class 1 ( Sodium Blockers and Class 3 ( Potassium Channel blockers)

The only heart rhythm drugs safe in Systolic dysfuction are Amiodarone and Dofeditilide (Tikosyn)

Drugs to Avoid in CHF

Avoid Non Dihydropyridine Calcium Channel blockers

Non- dihydropridine Calcium Channel blockers (Verapamil amp Diltiazem) decrease the strength of myocardial contractility and decrease heart rate

Verapamil and Diltiazem can worsen Heart failure and do not improve survival

15 Dihydropiridines are neutral in Heart failure as Anti-hypertensives

Amlodipine and Felodipine have not been shown to decrease survival in heart failure

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Drugs to avoid in heart failure

NSAID ndash I buprophen( Advil Motrin) Naproxen ( Alieve Naprosyn) Cox-2 inhibitors (Celebrex)

The NSAID can cause kidney to retain salt and water and Interfere with ACEARB class

Use Acetemenphen Or Narcotics instead for pain and aches

Drugs to Avoid in CHF

Anti-Arrhythmics in Class 1 ( Sodium Blockers and Class 3 ( Potassium Channel blockers)

The only heart rhythm drugs safe in Systolic dysfuction are Amiodarone and Dofeditilide (Tikosyn)

Drugs to Avoid in CHF

Avoid Non Dihydropyridine Calcium Channel blockers

Non- dihydropridine Calcium Channel blockers (Verapamil amp Diltiazem) decrease the strength of myocardial contractility and decrease heart rate

Verapamil and Diltiazem can worsen Heart failure and do not improve survival

15 Dihydropiridines are neutral in Heart failure as Anti-hypertensives

Amlodipine and Felodipine have not been shown to decrease survival in heart failure

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Drugs to Avoid in CHF

Anti-Arrhythmics in Class 1 ( Sodium Blockers and Class 3 ( Potassium Channel blockers)

The only heart rhythm drugs safe in Systolic dysfuction are Amiodarone and Dofeditilide (Tikosyn)

Drugs to Avoid in CHF

Avoid Non Dihydropyridine Calcium Channel blockers

Non- dihydropridine Calcium Channel blockers (Verapamil amp Diltiazem) decrease the strength of myocardial contractility and decrease heart rate

Verapamil and Diltiazem can worsen Heart failure and do not improve survival

15 Dihydropiridines are neutral in Heart failure as Anti-hypertensives

Amlodipine and Felodipine have not been shown to decrease survival in heart failure

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Drugs to Avoid in CHF

Avoid Non Dihydropyridine Calcium Channel blockers

Non- dihydropridine Calcium Channel blockers (Verapamil amp Diltiazem) decrease the strength of myocardial contractility and decrease heart rate

Verapamil and Diltiazem can worsen Heart failure and do not improve survival

15 Dihydropiridines are neutral in Heart failure as Anti-hypertensives

Amlodipine and Felodipine have not been shown to decrease survival in heart failure

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

15 Dihydropiridines are neutral in Heart failure as Anti-hypertensives

Amlodipine and Felodipine have not been shown to decrease survival in heart failure

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

KaplanndashMeier Plots of the Time to the First Primary Event (Death or Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure

Receiving Amlodipine and 582 Receiving Placebo

Packer M et al N Engl J Med 19963351107-1114

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Drugs to Avoid In CHF Antacids that contain sodium (salt) To relieve heartburn or

indigestion Why Just like eating salty foods sodium from medications can cause

your body to retain fluid making swelling and shortness of breath worse and raising blood pressure

Alternatives Some companies produce low-sodium antacids Look at the ingredients list and warning statements to see if sodium is listed (companies are required to put it on the label if there are 5 mg or more of sodium per dose) If you are not sure ask your doctor or pharmacist

Other Drugs to Avoid Decongestants containing pseudoephedrine (such as Sudafed) which

can raise blood pressure and force the heart to work harder Alcohol and illicit drugs they are a common cause of hospitalization for

heart failure Some nutritional supplements and growth hormone therapies (talk to

your doctor about any you are considering taking)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Other drugs to Avoid in Heart failure

Pain relievers called NSAIDs Ibuprofen such as Advil and Motrin Naproxen such as Aleve Aspirin such as Bayer

bull If your doctor has told you to take a low-dose aspirin every day for your heart problems its probably okay to take it Low-dose aspirin can help prevent blood clots and may prevent a stroke or a heart attack

bull Higher doses of aspirin may make your heart failure worse Do not take aspirin for pain such as from headaches or arthritis Use acetaminophen such as Tylenol instead

Pain relievers Celecoxib Etodolac Indomethacin Ibuprofen Ketoprofen Nabumetone Naproxen Piroxicam Sulindac

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Drugs to Avoid in heart failure Cold cough flu or sinus medicines Be sure to check the label Do not take medicines that contain

pseudoephedrine ephedrine phenylephrine or oxymetazoline such as bull Sudafedbull Nose sprays (decongestants) such as Afrin and Dristanbull Herbal remedies such as ma huang and Herbalife

Make sure your cough and cold medicines dont contain aspirin or ibuprofen

Antiarrhythmics These are drugs used to treat a fast or uneven heart rhythm You may

need to avoid the following bull Disopyramidebull Dofetilidebull Flecainidebull Procainamide bull Propafenonebull Quinidinebull Sotalol

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Drugs not to take with Heart failure

Antacids or laxatives that contain sodium Check the label for sodium or saline Examples include

bull Antacids such as Alka-Seltzer bull Laxatives such as Fleet Phospho-Soda

Calcium channel blockers People with a certain kind of heart failure may need to avoid the

following medicines bull Diltiazem bull Verapamil

If you need to take a calcium channel blocker for another health problem such as high blood pressure your doctor will watch your health carefully

Certain diabetes medicines Most diabetes drugs are safe to take but you may need to avoid the

following bull Metformin bull Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Biggest Myth Vitamins prevent CVD risk or heart failure risk

The largest randomized double-blind trial to date has confirmed what smaller studies have suggested and what many physicians have long believed a daily multivitamin does not reduce the risk of CVD

Physcians Health Study II results presented at AHA Nov 2012 PHS II launched in 1997 with a total of 14 641 US male physicians

age 50 or older at the outset randomized to different vitamin arms or placebo The other three arms of the studymdashlooking at beta-carotene vitamin E or vitamin C

Over a median follow-up of 112 years 1732 CV events occurred but the rate of events was no higher among men taking placebo than those taking a daily multivitamin

Ultrafiltration- doesnrsquot work 1142012 AHA meeting- Ultrafiltration was associated with

worsening renal function and more severe adverse events compared with optimum drug therapy in patients with acute decompensated heart failure in the CARRESS-HF trial

CARRESS-HF trial involved 188 patients with acute decompensated heart failure with worsening renal failure who were randomized to stepped pharmacological care or ultrafiltration The primary end point was change in serum creatinine and change in weight (reflecting fluid offload) at 96 hours

-similar weight loss occurred in both groups (average about 12 pounds) but while there was little change in creatinine levels in the drug-treated group there was a significant increase in creatinine in the ultrafiltration group There was no difference between the two groups in death or hospitalization for heart failure but there were more severe adverse events in the ultrafiltration group (72 vs 57) mainly due to kidney failure Bleeding and and IV-catheter-related complications

What doesnrsquot HelpAliskarin for dual ARB-Renin Blocade

November 3 2012 in the New England Journal of Medicine

Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial testing Aliskiren (Tekturna Novartis Pharmaceuticals) as an adjunct to renin-angiotensin-aldosterone system (RAAS) blockade

The drug not only failed to provide benefit to patients with type 2 diabetes at high risk of CV and renal events but may actually have been harmful

In ALTITUDE 8561 patients were randomly assigned to aliskiren (n=4274) or placebo (n=4287) on a background of an ACE inhibitor or ARB for approximately four years

The primary end point was a composite of CV death resuscitation from sudden death nonfatal MI or stroke unplanned hospitalization for heart failure ESRD or renal death or a doubling of serum creatinine for at least one month

There was no statistical difference in the primary end point between the treatment groups but the aliskiren group experienced more adverse events especially hyperkalemia and hypertension

Neseritide- Doesnrsquot make a difference

ACC- 2010 - Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure(ASCEND-HF) there was no evidence for a major benefit from nesiritide vs placebo on top of standard care

Primary results and renal-function safety end point in ASCEND-HF IV nesiritide in ADHF

ASCEND-HF-

End points Placebo () n=3511 Nesiritide () n=3496 p

30-d deathHF hospitalization 101 94 031

bull30-d death 40 36

bull30-d HF rehospitalization 61 60

Dyspnea at 6 h 421 445 0030

bullModerately better 287 295

bullMarkedly better 134 150

Dyspnea at 24 h 661 682 0007

bullModerately better 386 378

bullMarkedly better 275 304

gt25 decrease eGFR 295 314 011

a Condashprimary end pointseGFR=estimated glomerular filtration

rate

Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure 1142010 American Heart Association

The EndQuestions

HFSA 2010 Practice Guideline (32)

HF Risk Factor Treatment Goals

Risk Factor Goal

Hypertension Generally lt 13080

Diabetes See ADA guidelines1

Hyperlipidemia See NCEP guidelines2

Inactivity 20-30 min aerobic 3-5 x wk

Obesity Weight reduction lt 30 BMI

Alcohol Men le 2 drinksday women le 1

Smoking Cessation

Dietary Sodium Maximum 2-3 gday 1Diabetes Care 2006 29 S4-S42

2JAMA 2001 2852486-97

Adapted from

Common precursors of chronic heart failure

bullCoronary artery disease (for example consequent upon acute myocardial infarction) bullChronic hypertension bullCardiomyopathy (for example dilated hypertrophic alcoholic and idiopathic) bullValve dysfunction (for example diseases of the aortic and mitral valve) bullCardiac arrhythmiasconduction disturbance (for example heart block and atrial fibrillation) bullPericardial disease (for example constrictive pericarditis) bullInfection (for example rheumatic fever Chagas disease viral myocarditis and HIV

History of Beta Blockade for CHF

1993 The Metoprolol in Dilated Cardiomyopathy Trial studied 383 patients with class 2-3 CHF for 18 months The target dose of immediate-release metoprolol was 100 to 150mg per day The metoprolol group showed reduced all-cause mortality compared to the placebo group but the difference was small

The major benefit was in need for heart transplant Two metoprolol patients needed a heart transplant but 19 in the placebo group did Metoprolol improved EF quality of life and exercise capacity compared to placebo

HFSA 2010 Practice Guideline (32)

HF Risk Factor Treatment Goals

Risk Factor Goal

Hypertension Generally lt 13080

Diabetes See ADA guidelines1

Hyperlipidemia See NCEP guidelines2

Inactivity 20-30 min aerobic 3-5 x wk

Obesity Weight reduction lt 30 BMI

Alcohol Men le 2 drinksday women le 1

Smoking Cessation

Dietary Sodium Maximum 2-3 gday 1Diabetes Care 2006 29 S4-S42

2JAMA 2001 2852486-97

Adapted from

Common precursors of chronic heart failure

bullCoronary artery disease (for example consequent upon acute myocardial infarction) bullChronic hypertension bullCardiomyopathy (for example dilated hypertrophic alcoholic and idiopathic) bullValve dysfunction (for example diseases of the aortic and mitral valve) bullCardiac arrhythmiasconduction disturbance (for example heart block and atrial fibrillation) bullPericardial disease (for example constrictive pericarditis) bullInfection (for example rheumatic fever Chagas disease viral myocarditis and HIV

History of Beta Blockade for CHF

1993 The Metoprolol in Dilated Cardiomyopathy Trial studied 383 patients with class 2-3 CHF for 18 months The target dose of immediate-release metoprolol was 100 to 150mg per day The metoprolol group showed reduced all-cause mortality compared to the placebo group but the difference was small

The major benefit was in need for heart transplant Two metoprolol patients needed a heart transplant but 19 in the placebo group did Metoprolol improved EF quality of life and exercise capacity compared to placebo

Common precursors of chronic heart failure

bullCoronary artery disease (for example consequent upon acute myocardial infarction) bullChronic hypertension bullCardiomyopathy (for example dilated hypertrophic alcoholic and idiopathic) bullValve dysfunction (for example diseases of the aortic and mitral valve) bullCardiac arrhythmiasconduction disturbance (for example heart block and atrial fibrillation) bullPericardial disease (for example constrictive pericarditis) bullInfection (for example rheumatic fever Chagas disease viral myocarditis and HIV

History of Beta Blockade for CHF

1993 The Metoprolol in Dilated Cardiomyopathy Trial studied 383 patients with class 2-3 CHF for 18 months The target dose of immediate-release metoprolol was 100 to 150mg per day The metoprolol group showed reduced all-cause mortality compared to the placebo group but the difference was small

The major benefit was in need for heart transplant Two metoprolol patients needed a heart transplant but 19 in the placebo group did Metoprolol improved EF quality of life and exercise capacity compared to placebo

History of Beta Blockade for CHF

1993 The Metoprolol in Dilated Cardiomyopathy Trial studied 383 patients with class 2-3 CHF for 18 months The target dose of immediate-release metoprolol was 100 to 150mg per day The metoprolol group showed reduced all-cause mortality compared to the placebo group but the difference was small

The major benefit was in need for heart transplant Two metoprolol patients needed a heart transplant but 19 in the placebo group did Metoprolol improved EF quality of life and exercise capacity compared to placebo

USING BETA BLOCKERS IN PATIENTSWITH COMORBIDITIES

1048708 AFTER MI-USE IN ALL PATIENTS WITHOUT A CONTRAINDICATION 1048708 COPD IS NOT A CONTRAINDICATION UNLESS THERE IS SEVERE REACTIVE AIRWAYS DISEASE 1048708 PERIPHERAL VASCULAR DISEASE-USE LOWER DOSES OF METOPROLOL OR BISOPROLOL 1048708 DIABETIC PATIENTS DERIVE SIGNIFICANT BENEFIT-CARVEDILOL MAY BE PREFERRED

Digoxin 1048708 BLOOD LEVEL MONITORING REQUIRED 1048708 LEVELS FOR HEART FAILURE ARE USUALLY 05-08NGMl FOR HEART FAILURE AND UP TO 2NGML FOR ATRIAL FIBRILLATION 1048708 DOSE DEPENDS ON DEGREE OF RENAL FUNCTION 1048708 LOADING DOSES REQUIRED FOR MORE RAPID RESPONSE 1048708 MONITOR FOR NAUSEA AND VOMITING WHICH ARE OFTEN EARLY SIGNS OF TOXICITY

Treatment of Diastolic CHF

APART FROM A FEW EXCEPTIONSDATA FROM LONG TERMINVESTIGATIONS OF ANY AGENTCOMPARED TO PLACEBO INPATIENTS WITH DIASTOLIC FAILUREARE LACKING

Diastolic CHF

REDUCTION IN LFT VENTRICULAR FILLING PRESSURES WITH THE USE OF DIURETICS ANDOR NITRATES

SLOWING OF THE HEART RATE WITH BETABLOCKERS AND OR RATE LIMITING CALCIUM CHANNEL BLOCKERS SUCH AS VERAPAMIL (WHICH IS GENERALLY CONTRAINDICATED IN SYSTOLIC FAILURE)

Diastolic CHF

RECENT STUDY WITH CANDERSARTANIN PATIENTS WITH LVEFgt40DEMONSTRATED A SIGNIFICANTREDUCTION IN HOSPITALISATIONSFOR HEART FAILURE THERE WAS NOSIGNIFIACNT DIFFERENCE IN THE RISKOF STROKES OR MYOCARDIALINFARCTION

Predictors of Mortality Based on Analysis of ADHERE Database

Classification and Regression Tree (CART) analysis of ADHERE data shows

Three variables are the strongest predictors of mortality in hospitalized ADHF patients

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

Fonarow GC et al JAMA 2005293572-80

• Heart Failure Update 2012
• Outline of CHF Talk
• Slide 3
• Definition of Heart Failure
• Slide 5
• Slide 6
• Heart Failure is a Major and Growing Public Health Problem in t
• Heart failure is a major cause of Hospitalization
• Heart Failure is Primarily a Condition of the Elderly
• New York Heart Association Classification
• Slide 11
• Prognosis
• Character of Heart failure
• Slide 14
• Slide 15
• Right Sided Heart failure
• Slide 17
• Types of Left sided Heart failure
• Causes of CHF
• Etiology of Heart failure
• Classical Symptoms of Heart Failure
• Signs of heart failure
• Slide 23
• Acute Heart Failure Symptoms
• COMMON CAUSES OF SYSTOLIC FAILURE
• Slide 26
• Slide 27
• Cause of Systolic Heart failure Acquired vs Genetic Causes
• Complications of Chronic Heart failure
• Common test ordered in CHF
• Diastolic Heart Failure
• DIASTOLIC HEART FAILURE
• Slide 33
• Slide 34
• Pathogenesis of Diastolic Heart Failure
• DIASTOLIC HEART FAILURE usually due to Hemodynamic stress
• Diastolic CHF All treatments are empiric (No trial data)
• Diastolic Heart Failure often presents with Acute Pulmonary Ede
• Systolic Heart Failure
• Slide 40
• Slide 41
• Slide 42
• Neurohormonal activation
• Slide 44
• Medical Treatment of Systolic Heart Failure What Improves Survi
• DIURETICS
• Why give ACE inhibitors
• ACE-INHIBITORS
• Beta Blocker- Why do they work
• Slide 50
• Slide 51
• Slide 52
• Slide 53
• Slide 54
• BETA-BLOCKERS
• BETA-BLOCKERS (2)
• Slide 57
• Slide 58
• Slide 59
• Slide 60
• Slide 61
• Slide 62
• Slide 63
• COMET Study Design
• COMET Study Design (2)
• Comparison of Carvedilol With Metoprolol on LV Function
• COMET (Carvedilol or Metoprolol European Trial)
• COMET Study Design (3)
• Effect of Carvedilol vs Metoprolol on Mortality
• COMET Median Survival
• Slide 71
• EPHESUS TRIAL Inspra
• Spironolactone and Epelnerone
• Spironolactone and Epelnerone (2)
• Slide 75
• Digoxin
• Heart Failure-Medical Treatment
• Heart Failure Device Treatment
• COMPANION Secondary End Point of All-cause Mortality
• REMATCH-LVADs in Extremely Severe Heart Failure
• People Donrsquot want and LVAD they want a Heart
• Heart Transplant Waiting List
• Heart Transplantation
• Markers of Heart Failure
• Albumin excretion is prognostic marker in heart failure (Analys
• Slide 86
• Slide 87
• Slide 88
• Current and Future Therapies
• Curing Heart failure by curing hypertension- Denervating the K
• Slide 91
• Stem Cells trial Shows Promise for Ischemic heart failure
• Balloon Pump to augment Coronary Perfusion
• eecp
• EECP
• Future Horizons and Pipe Dreams
• Worldwide REGISTRY DATABASE Number of Transplants Reported
• Artificial Heart
• Evidence-Based Treatment Across the Continuum of Systolic LVD a
• Drugs to avoid in heart failure
• Drugs to Avoid in CHF
• Drugs to Avoid in CHF
• 15 Dihydropiridines are neutral in Heart failure as Anti-hyper
• Slide 104
• Slide 105
• Drugs to Avoid In CHF
• Other drugs to Avoid in Heart failure
• Drugs to Avoid in heart failure
• Drugs not to take with Heart failure
• Biggest Myth Vitamins prevent CVD risk or heart failure risk
• Ultrafiltration- doesnrsquot work
• Slide 112
• What doesnrsquot Help Aliskarin for dual ARB-Renin Blocade
• Neseritide- Doesnrsquot make a difference
• Slide 115
• The End Questions
• HFSA 2010 Practice Guideline (32) HF Risk Factor Treatment Goa
• Slide 118
• Slide 119
• Slide 120
• Slide 121
• Slide 122
• Slide 123
• Common precursors of chronic heart failure
• Slide 125
• Slide 126
• History of Beta Blockade for CHF
• USING BETA BLOCKERS IN PATIENTS WITH COMORBIDITIES
• Digoxin (2)
• Treatment of Diastolic CHF
• Diastolic CHF
• Diastolic CHF (2)
• Predictors of Mortality Based on Analysis of ADHERE Database

Digoxin 1048708 BLOOD LEVEL MONITORING REQUIRED 1048708 LEVELS FOR HEART FAILURE ARE USUALLY 05-08NGMl FOR HEART FAILURE AND UP TO 2NGML FOR ATRIAL FIBRILLATION 1048708 DOSE DEPENDS ON DEGREE OF RENAL FUNCTION 1048708 LOADING DOSES REQUIRED FOR MORE RAPID RESPONSE 1048708 MONITOR FOR NAUSEA AND VOMITING WHICH ARE OFTEN EARLY SIGNS OF TOXICITY

Treatment of Diastolic CHF

APART FROM A FEW EXCEPTIONSDATA FROM LONG TERMINVESTIGATIONS OF ANY AGENTCOMPARED TO PLACEBO INPATIENTS WITH DIASTOLIC FAILUREARE LACKING

Diastolic CHF

REDUCTION IN LFT VENTRICULAR FILLING PRESSURES WITH THE USE OF DIURETICS ANDOR NITRATES

SLOWING OF THE HEART RATE WITH BETABLOCKERS AND OR RATE LIMITING CALCIUM CHANNEL BLOCKERS SUCH AS VERAPAMIL (WHICH IS GENERALLY CONTRAINDICATED IN SYSTOLIC FAILURE)

Diastolic CHF

RECENT STUDY WITH CANDERSARTANIN PATIENTS WITH LVEFgt40DEMONSTRATED A SIGNIFICANTREDUCTION IN HOSPITALISATIONSFOR HEART FAILURE THERE WAS NOSIGNIFIACNT DIFFERENCE IN THE RISKOF STROKES OR MYOCARDIALINFARCTION

Predictors of Mortality Based on Analysis of ADHERE Database

Classification and Regression Tree (CART) analysis of ADHERE data shows

Three variables are the strongest predictors of mortality in hospitalized ADHF patients

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

Fonarow GC et al JAMA 2005293572-80

• Heart Failure Update 2012
• Outline of CHF Talk
• Slide 3
• Definition of Heart Failure
• Slide 5
• Slide 6
• Heart Failure is a Major and Growing Public Health Problem in t
• Heart failure is a major cause of Hospitalization
• Heart Failure is Primarily a Condition of the Elderly
• New York Heart Association Classification
• Slide 11
• Prognosis
• Character of Heart failure
• Slide 14
• Slide 15
• Right Sided Heart failure
• Slide 17
• Types of Left sided Heart failure
• Causes of CHF
• Etiology of Heart failure
• Classical Symptoms of Heart Failure
• Signs of heart failure
• Slide 23
• Acute Heart Failure Symptoms
• COMMON CAUSES OF SYSTOLIC FAILURE
• Slide 26
• Slide 27
• Cause of Systolic Heart failure Acquired vs Genetic Causes
• Complications of Chronic Heart failure
• Common test ordered in CHF
• Diastolic Heart Failure
• DIASTOLIC HEART FAILURE
• Slide 33
• Slide 34
• Pathogenesis of Diastolic Heart Failure
• DIASTOLIC HEART FAILURE usually due to Hemodynamic stress
• Diastolic CHF All treatments are empiric (No trial data)
• Diastolic Heart Failure often presents with Acute Pulmonary Ede
• Systolic Heart Failure
• Slide 40
• Slide 41
• Slide 42
• Neurohormonal activation
• Slide 44
• Medical Treatment of Systolic Heart Failure What Improves Survi
• DIURETICS
• Why give ACE inhibitors
• ACE-INHIBITORS
• Beta Blocker- Why do they work
• Slide 50
• Slide 51
• Slide 52
• Slide 53
• Slide 54
• BETA-BLOCKERS
• BETA-BLOCKERS (2)
• Slide 57
• Slide 58
• Slide 59
• Slide 60
• Slide 61
• Slide 62
• Slide 63
• COMET Study Design
• COMET Study Design (2)
• Comparison of Carvedilol With Metoprolol on LV Function
• COMET (Carvedilol or Metoprolol European Trial)
• COMET Study Design (3)
• Effect of Carvedilol vs Metoprolol on Mortality
• COMET Median Survival
• Slide 71
• EPHESUS TRIAL Inspra
• Spironolactone and Epelnerone
• Spironolactone and Epelnerone (2)
• Slide 75
• Digoxin
• Heart Failure-Medical Treatment
• Heart Failure Device Treatment
• COMPANION Secondary End Point of All-cause Mortality
• REMATCH-LVADs in Extremely Severe Heart Failure
• People Donrsquot want and LVAD they want a Heart
• Heart Transplant Waiting List
• Heart Transplantation
• Markers of Heart Failure
• Albumin excretion is prognostic marker in heart failure (Analys
• Slide 86
• Slide 87
• Slide 88
• Current and Future Therapies
• Curing Heart failure by curing hypertension- Denervating the K
• Slide 91
• Stem Cells trial Shows Promise for Ischemic heart failure
• Balloon Pump to augment Coronary Perfusion
• eecp
• EECP
• Future Horizons and Pipe Dreams
• Worldwide REGISTRY DATABASE Number of Transplants Reported
• Artificial Heart
• Evidence-Based Treatment Across the Continuum of Systolic LVD a
• Drugs to avoid in heart failure
• Drugs to Avoid in CHF
• Drugs to Avoid in CHF
• 15 Dihydropiridines are neutral in Heart failure as Anti-hyper
• Slide 104
• Slide 105
• Drugs to Avoid In CHF
• Other drugs to Avoid in Heart failure
• Drugs to Avoid in heart failure
• Drugs not to take with Heart failure
• Biggest Myth Vitamins prevent CVD risk or heart failure risk
• Ultrafiltration- doesnrsquot work
• Slide 112
• What doesnrsquot Help Aliskarin for dual ARB-Renin Blocade
• Neseritide- Doesnrsquot make a difference
• Slide 115
• The End Questions
• HFSA 2010 Practice Guideline (32) HF Risk Factor Treatment Goa
• Slide 118
• Slide 119
• Slide 120
• Slide 121
• Slide 122
• Slide 123
• Common precursors of chronic heart failure
• Slide 125
• Slide 126
• History of Beta Blockade for CHF
• USING BETA BLOCKERS IN PATIENTS WITH COMORBIDITIES
• Digoxin (2)
• Treatment of Diastolic CHF
• Diastolic CHF
• Diastolic CHF (2)
• Predictors of Mortality Based on Analysis of ADHERE Database

Treatment of Diastolic CHF

APART FROM A FEW EXCEPTIONSDATA FROM LONG TERMINVESTIGATIONS OF ANY AGENTCOMPARED TO PLACEBO INPATIENTS WITH DIASTOLIC FAILUREARE LACKING

Diastolic CHF

REDUCTION IN LFT VENTRICULAR FILLING PRESSURES WITH THE USE OF DIURETICS ANDOR NITRATES

SLOWING OF THE HEART RATE WITH BETABLOCKERS AND OR RATE LIMITING CALCIUM CHANNEL BLOCKERS SUCH AS VERAPAMIL (WHICH IS GENERALLY CONTRAINDICATED IN SYSTOLIC FAILURE)

Diastolic CHF

RECENT STUDY WITH CANDERSARTANIN PATIENTS WITH LVEFgt40DEMONSTRATED A SIGNIFICANTREDUCTION IN HOSPITALISATIONSFOR HEART FAILURE THERE WAS NOSIGNIFIACNT DIFFERENCE IN THE RISKOF STROKES OR MYOCARDIALINFARCTION

Predictors of Mortality Based on Analysis of ADHERE Database

Classification and Regression Tree (CART) analysis of ADHERE data shows

Three variables are the strongest predictors of mortality in hospitalized ADHF patients

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

Fonarow GC et al JAMA 2005293572-80

• Heart Failure Update 2012
• Outline of CHF Talk
• Slide 3
• Definition of Heart Failure
• Slide 5
• Slide 6
• Heart Failure is a Major and Growing Public Health Problem in t
• Heart failure is a major cause of Hospitalization
• Heart Failure is Primarily a Condition of the Elderly
• New York Heart Association Classification
• Slide 11
• Prognosis
• Character of Heart failure
• Slide 14
• Slide 15
• Right Sided Heart failure
• Slide 17
• Types of Left sided Heart failure
• Causes of CHF
• Etiology of Heart failure
• Classical Symptoms of Heart Failure
• Signs of heart failure
• Slide 23
• Acute Heart Failure Symptoms
• COMMON CAUSES OF SYSTOLIC FAILURE
• Slide 26
• Slide 27
• Cause of Systolic Heart failure Acquired vs Genetic Causes
• Complications of Chronic Heart failure
• Common test ordered in CHF
• Diastolic Heart Failure
• DIASTOLIC HEART FAILURE
• Slide 33
• Slide 34
• Pathogenesis of Diastolic Heart Failure
• DIASTOLIC HEART FAILURE usually due to Hemodynamic stress
• Diastolic CHF All treatments are empiric (No trial data)
• Diastolic Heart Failure often presents with Acute Pulmonary Ede
• Systolic Heart Failure
• Slide 40
• Slide 41
• Slide 42
• Neurohormonal activation
• Slide 44
• Medical Treatment of Systolic Heart Failure What Improves Survi
• DIURETICS
• Why give ACE inhibitors
• ACE-INHIBITORS
• Beta Blocker- Why do they work
• Slide 50
• Slide 51
• Slide 52
• Slide 53
• Slide 54
• BETA-BLOCKERS
• BETA-BLOCKERS (2)
• Slide 57
• Slide 58
• Slide 59
• Slide 60
• Slide 61
• Slide 62
• Slide 63
• COMET Study Design
• COMET Study Design (2)
• Comparison of Carvedilol With Metoprolol on LV Function
• COMET (Carvedilol or Metoprolol European Trial)
• COMET Study Design (3)
• Effect of Carvedilol vs Metoprolol on Mortality
• COMET Median Survival
• Slide 71
• EPHESUS TRIAL Inspra
• Spironolactone and Epelnerone
• Spironolactone and Epelnerone (2)
• Slide 75
• Digoxin
• Heart Failure-Medical Treatment
• Heart Failure Device Treatment
• COMPANION Secondary End Point of All-cause Mortality
• REMATCH-LVADs in Extremely Severe Heart Failure
• People Donrsquot want and LVAD they want a Heart
• Heart Transplant Waiting List
• Heart Transplantation
• Markers of Heart Failure
• Albumin excretion is prognostic marker in heart failure (Analys
• Slide 86
• Slide 87
• Slide 88
• Current and Future Therapies
• Curing Heart failure by curing hypertension- Denervating the K
• Slide 91
• Stem Cells trial Shows Promise for Ischemic heart failure
• Balloon Pump to augment Coronary Perfusion
• eecp
• EECP
• Future Horizons and Pipe Dreams
• Worldwide REGISTRY DATABASE Number of Transplants Reported
• Artificial Heart
• Evidence-Based Treatment Across the Continuum of Systolic LVD a
• Drugs to avoid in heart failure
• Drugs to Avoid in CHF
• Drugs to Avoid in CHF
• 15 Dihydropiridines are neutral in Heart failure as Anti-hyper
• Slide 104
• Slide 105
• Drugs to Avoid In CHF
• Other drugs to Avoid in Heart failure
• Drugs to Avoid in heart failure
• Drugs not to take with Heart failure
• Biggest Myth Vitamins prevent CVD risk or heart failure risk
• Ultrafiltration- doesnrsquot work
• Slide 112
• What doesnrsquot Help Aliskarin for dual ARB-Renin Blocade
• Neseritide- Doesnrsquot make a difference
• Slide 115
• The End Questions
• HFSA 2010 Practice Guideline (32) HF Risk Factor Treatment Goa
• Slide 118
• Slide 119
• Slide 120
• Slide 121
• Slide 122
• Slide 123
• Common precursors of chronic heart failure
• Slide 125
• Slide 126
• History of Beta Blockade for CHF
• USING BETA BLOCKERS IN PATIENTS WITH COMORBIDITIES
• Digoxin (2)
• Treatment of Diastolic CHF
• Diastolic CHF
• Diastolic CHF (2)
• Predictors of Mortality Based on Analysis of ADHERE Database

Diastolic CHF

REDUCTION IN LFT VENTRICULAR FILLING PRESSURES WITH THE USE OF DIURETICS ANDOR NITRATES

SLOWING OF THE HEART RATE WITH BETABLOCKERS AND OR RATE LIMITING CALCIUM CHANNEL BLOCKERS SUCH AS VERAPAMIL (WHICH IS GENERALLY CONTRAINDICATED IN SYSTOLIC FAILURE)

Diastolic CHF

RECENT STUDY WITH CANDERSARTANIN PATIENTS WITH LVEFgt40DEMONSTRATED A SIGNIFICANTREDUCTION IN HOSPITALISATIONSFOR HEART FAILURE THERE WAS NOSIGNIFIACNT DIFFERENCE IN THE RISKOF STROKES OR MYOCARDIALINFARCTION

Predictors of Mortality Based on Analysis of ADHERE Database

Classification and Regression Tree (CART) analysis of ADHERE data shows

Three variables are the strongest predictors of mortality in hospitalized ADHF patients

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

Fonarow GC et al JAMA 2005293572-80

• Heart Failure Update 2012
• Outline of CHF Talk
• Slide 3
• Definition of Heart Failure
• Slide 5
• Slide 6
• Heart Failure is a Major and Growing Public Health Problem in t
• Heart failure is a major cause of Hospitalization
• Heart Failure is Primarily a Condition of the Elderly
• New York Heart Association Classification
• Slide 11
• Prognosis
• Character of Heart failure
• Slide 14
• Slide 15
• Right Sided Heart failure
• Slide 17
• Types of Left sided Heart failure
• Causes of CHF
• Etiology of Heart failure
• Classical Symptoms of Heart Failure
• Signs of heart failure
• Slide 23
• Acute Heart Failure Symptoms
• COMMON CAUSES OF SYSTOLIC FAILURE
• Slide 26
• Slide 27
• Cause of Systolic Heart failure Acquired vs Genetic Causes
• Complications of Chronic Heart failure
• Common test ordered in CHF
• Diastolic Heart Failure
• DIASTOLIC HEART FAILURE
• Slide 33
• Slide 34
• Pathogenesis of Diastolic Heart Failure
• DIASTOLIC HEART FAILURE usually due to Hemodynamic stress
• Diastolic CHF All treatments are empiric (No trial data)
• Diastolic Heart Failure often presents with Acute Pulmonary Ede
• Systolic Heart Failure
• Slide 40
• Slide 41
• Slide 42
• Neurohormonal activation
• Slide 44
• Medical Treatment of Systolic Heart Failure What Improves Survi
• DIURETICS
• Why give ACE inhibitors
• ACE-INHIBITORS
• Beta Blocker- Why do they work
• Slide 50
• Slide 51
• Slide 52
• Slide 53
• Slide 54
• BETA-BLOCKERS
• BETA-BLOCKERS (2)
• Slide 57
• Slide 58
• Slide 59
• Slide 60
• Slide 61
• Slide 62
• Slide 63
• COMET Study Design
• COMET Study Design (2)
• Comparison of Carvedilol With Metoprolol on LV Function
• COMET (Carvedilol or Metoprolol European Trial)
• COMET Study Design (3)
• Effect of Carvedilol vs Metoprolol on Mortality
• COMET Median Survival
• Slide 71
• EPHESUS TRIAL Inspra
• Spironolactone and Epelnerone
• Spironolactone and Epelnerone (2)
• Slide 75
• Digoxin
• Heart Failure-Medical Treatment
• Heart Failure Device Treatment
• COMPANION Secondary End Point of All-cause Mortality
• REMATCH-LVADs in Extremely Severe Heart Failure
• People Donrsquot want and LVAD they want a Heart
• Heart Transplant Waiting List
• Heart Transplantation
• Markers of Heart Failure
• Albumin excretion is prognostic marker in heart failure (Analys
• Slide 86
• Slide 87
• Slide 88
• Current and Future Therapies
• Curing Heart failure by curing hypertension- Denervating the K
• Slide 91
• Stem Cells trial Shows Promise for Ischemic heart failure
• Balloon Pump to augment Coronary Perfusion
• eecp
• EECP
• Future Horizons and Pipe Dreams
• Worldwide REGISTRY DATABASE Number of Transplants Reported
• Artificial Heart
• Evidence-Based Treatment Across the Continuum of Systolic LVD a
• Drugs to avoid in heart failure
• Drugs to Avoid in CHF
• Drugs to Avoid in CHF
• 15 Dihydropiridines are neutral in Heart failure as Anti-hyper
• Slide 104
• Slide 105
• Drugs to Avoid In CHF
• Other drugs to Avoid in Heart failure
• Drugs to Avoid in heart failure
• Drugs not to take with Heart failure
• Biggest Myth Vitamins prevent CVD risk or heart failure risk
• Ultrafiltration- doesnrsquot work
• Slide 112
• What doesnrsquot Help Aliskarin for dual ARB-Renin Blocade
• Neseritide- Doesnrsquot make a difference
• Slide 115
• The End Questions
• HFSA 2010 Practice Guideline (32) HF Risk Factor Treatment Goa
• Slide 118
• Slide 119
• Slide 120
• Slide 121
• Slide 122
• Slide 123
• Common precursors of chronic heart failure
• Slide 125
• Slide 126
• History of Beta Blockade for CHF
• USING BETA BLOCKERS IN PATIENTS WITH COMORBIDITIES
• Digoxin (2)
• Treatment of Diastolic CHF
• Diastolic CHF
• Diastolic CHF (2)
• Predictors of Mortality Based on Analysis of ADHERE Database

Diastolic CHF

RECENT STUDY WITH CANDERSARTANIN PATIENTS WITH LVEFgt40DEMONSTRATED A SIGNIFICANTREDUCTION IN HOSPITALISATIONSFOR HEART FAILURE THERE WAS NOSIGNIFIACNT DIFFERENCE IN THE RISKOF STROKES OR MYOCARDIALINFARCTION

Predictors of Mortality Based on Analysis of ADHERE Database

Classification and Regression Tree (CART) analysis of ADHERE data shows

Three variables are the strongest predictors of mortality in hospitalized ADHF patients

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

Fonarow GC et al JAMA 2005293572-80

• Heart Failure Update 2012
• Outline of CHF Talk
• Slide 3
• Definition of Heart Failure
• Slide 5
• Slide 6
• Heart Failure is a Major and Growing Public Health Problem in t
• Heart failure is a major cause of Hospitalization
• Heart Failure is Primarily a Condition of the Elderly
• New York Heart Association Classification
• Slide 11
• Prognosis
• Character of Heart failure
• Slide 14
• Slide 15
• Right Sided Heart failure
• Slide 17
• Types of Left sided Heart failure
• Causes of CHF
• Etiology of Heart failure
• Classical Symptoms of Heart Failure
• Signs of heart failure
• Slide 23
• Acute Heart Failure Symptoms
• COMMON CAUSES OF SYSTOLIC FAILURE
• Slide 26
• Slide 27
• Cause of Systolic Heart failure Acquired vs Genetic Causes
• Complications of Chronic Heart failure
• Common test ordered in CHF
• Diastolic Heart Failure
• DIASTOLIC HEART FAILURE
• Slide 33
• Slide 34
• Pathogenesis of Diastolic Heart Failure
• DIASTOLIC HEART FAILURE usually due to Hemodynamic stress
• Diastolic CHF All treatments are empiric (No trial data)
• Diastolic Heart Failure often presents with Acute Pulmonary Ede
• Systolic Heart Failure
• Slide 40
• Slide 41
• Slide 42
• Neurohormonal activation
• Slide 44
• Medical Treatment of Systolic Heart Failure What Improves Survi
• DIURETICS
• Why give ACE inhibitors
• ACE-INHIBITORS
• Beta Blocker- Why do they work
• Slide 50
• Slide 51
• Slide 52
• Slide 53
• Slide 54
• BETA-BLOCKERS
• BETA-BLOCKERS (2)
• Slide 57
• Slide 58
• Slide 59
• Slide 60
• Slide 61
• Slide 62
• Slide 63
• COMET Study Design
• COMET Study Design (2)
• Comparison of Carvedilol With Metoprolol on LV Function
• COMET (Carvedilol or Metoprolol European Trial)
• COMET Study Design (3)
• Effect of Carvedilol vs Metoprolol on Mortality
• COMET Median Survival
• Slide 71
• EPHESUS TRIAL Inspra
• Spironolactone and Epelnerone
• Spironolactone and Epelnerone (2)
• Slide 75
• Digoxin
• Heart Failure-Medical Treatment
• Heart Failure Device Treatment
• COMPANION Secondary End Point of All-cause Mortality
• REMATCH-LVADs in Extremely Severe Heart Failure
• People Donrsquot want and LVAD they want a Heart
• Heart Transplant Waiting List
• Heart Transplantation
• Markers of Heart Failure
• Albumin excretion is prognostic marker in heart failure (Analys
• Slide 86
• Slide 87
• Slide 88
• Current and Future Therapies
• Curing Heart failure by curing hypertension- Denervating the K
• Slide 91
• Stem Cells trial Shows Promise for Ischemic heart failure
• Balloon Pump to augment Coronary Perfusion
• eecp
• EECP
• Future Horizons and Pipe Dreams
• Worldwide REGISTRY DATABASE Number of Transplants Reported
• Artificial Heart
• Evidence-Based Treatment Across the Continuum of Systolic LVD a
• Drugs to avoid in heart failure
• Drugs to Avoid in CHF
• Drugs to Avoid in CHF
• 15 Dihydropiridines are neutral in Heart failure as Anti-hyper
• Slide 104
• Slide 105
• Drugs to Avoid In CHF
• Other drugs to Avoid in Heart failure
• Drugs to Avoid in heart failure
• Drugs not to take with Heart failure
• Biggest Myth Vitamins prevent CVD risk or heart failure risk
• Ultrafiltration- doesnrsquot work
• Slide 112
• What doesnrsquot Help Aliskarin for dual ARB-Renin Blocade
• Neseritide- Doesnrsquot make a difference
• Slide 115
• The End Questions
• HFSA 2010 Practice Guideline (32) HF Risk Factor Treatment Goa
• Slide 118
• Slide 119
• Slide 120
• Slide 121
• Slide 122
• Slide 123
• Common precursors of chronic heart failure
• Slide 125
• Slide 126
• History of Beta Blockade for CHF
• USING BETA BLOCKERS IN PATIENTS WITH COMORBIDITIES
• Digoxin (2)
• Treatment of Diastolic CHF
• Diastolic CHF
• Diastolic CHF (2)
• Predictors of Mortality Based on Analysis of ADHERE Database

Predictors of Mortality Based on Analysis of ADHERE Database

Classification and Regression Tree (CART) analysis of ADHERE data shows

Three variables are the strongest predictors of mortality in hospitalized ADHF patients

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

BUN gt 43 mgdL

Systolic blood pressure lt 115 mmHg

Serum creatinine gt 275 mgdL

Fonarow GC et al JAMA 2005293572-80

• Heart Failure Update 2012
• Outline of CHF Talk
• Slide 3
• Definition of Heart Failure
• Slide 5
• Slide 6
• Heart Failure is a Major and Growing Public Health Problem in t
• Heart failure is a major cause of Hospitalization
• Heart Failure is Primarily a Condition of the Elderly
• New York Heart Association Classification
• Slide 11
• Prognosis
• Character of Heart failure
• Slide 14
• Slide 15
• Right Sided Heart failure
• Slide 17
• Types of Left sided Heart failure
• Causes of CHF
• Etiology of Heart failure
• Classical Symptoms of Heart Failure
• Signs of heart failure
• Slide 23
• Acute Heart Failure Symptoms
• COMMON CAUSES OF SYSTOLIC FAILURE
• Slide 26
• Slide 27
• Cause of Systolic Heart failure Acquired vs Genetic Causes
• Complications of Chronic Heart failure
• Common test ordered in CHF
• Diastolic Heart Failure
• DIASTOLIC HEART FAILURE
• Slide 33
• Slide 34
• Pathogenesis of Diastolic Heart Failure
• DIASTOLIC HEART FAILURE usually due to Hemodynamic stress
• Diastolic CHF All treatments are empiric (No trial data)
• Diastolic Heart Failure often presents with Acute Pulmonary Ede
• Systolic Heart Failure
• Slide 40
• Slide 41
• Slide 42
• Neurohormonal activation
• Slide 44
• Medical Treatment of Systolic Heart Failure What Improves Survi
• DIURETICS
• Why give ACE inhibitors
• ACE-INHIBITORS
• Beta Blocker- Why do they work
• Slide 50
• Slide 51
• Slide 52
• Slide 53
• Slide 54
• BETA-BLOCKERS
• BETA-BLOCKERS (2)
• Slide 57
• Slide 58
• Slide 59
• Slide 60
• Slide 61
• Slide 62
• Slide 63
• COMET Study Design
• COMET Study Design (2)
• Comparison of Carvedilol With Metoprolol on LV Function
• COMET (Carvedilol or Metoprolol European Trial)
• COMET Study Design (3)
• Effect of Carvedilol vs Metoprolol on Mortality
• COMET Median Survival
• Slide 71
• EPHESUS TRIAL Inspra
• Spironolactone and Epelnerone
• Spironolactone and Epelnerone (2)
• Slide 75
• Digoxin
• Heart Failure-Medical Treatment
• Heart Failure Device Treatment
• COMPANION Secondary End Point of All-cause Mortality
• REMATCH-LVADs in Extremely Severe Heart Failure
• People Donrsquot want and LVAD they want a Heart
• Heart Transplant Waiting List
• Heart Transplantation
• Markers of Heart Failure
• Albumin excretion is prognostic marker in heart failure (Analys
• Slide 86
• Slide 87
• Slide 88
• Current and Future Therapies
• Curing Heart failure by curing hypertension- Denervating the K
• Slide 91
• Stem Cells trial Shows Promise for Ischemic heart failure
• Balloon Pump to augment Coronary Perfusion
• eecp
• EECP
• Future Horizons and Pipe Dreams
• Worldwide REGISTRY DATABASE Number of Transplants Reported
• Artificial Heart
• Evidence-Based Treatment Across the Continuum of Systolic LVD a
• Drugs to avoid in heart failure
• Drugs to Avoid in CHF
• Drugs to Avoid in CHF
• 15 Dihydropiridines are neutral in Heart failure as Anti-hyper
• Slide 104
• Slide 105
• Drugs to Avoid In CHF
• Other drugs to Avoid in Heart failure
• Drugs to Avoid in heart failure
• Drugs not to take with Heart failure
• Biggest Myth Vitamins prevent CVD risk or heart failure risk
• Ultrafiltration- doesnrsquot work
• Slide 112
• What doesnrsquot Help Aliskarin for dual ARB-Renin Blocade
• Neseritide- Doesnrsquot make a difference
• Slide 115
• The End Questions
• HFSA 2010 Practice Guideline (32) HF Risk Factor Treatment Goa
• Slide 118
• Slide 119
• Slide 120
• Slide 121
• Slide 122
• Slide 123
• Common precursors of chronic heart failure
• Slide 125
• Slide 126
• History of Beta Blockade for CHF
• USING BETA BLOCKERS IN PATIENTS WITH COMORBIDITIES
• Digoxin (2)
• Treatment of Diastolic CHF
• Diastolic CHF
• Diastolic CHF (2)
• Predictors of Mortality Based on Analysis of ADHERE Database