Congestive Heart Failure- Etiologies, Prognosis and Treatment

C. Bradley Rash MD FACC

Medical Director, Cardiology

Sentara RMH Medical Center

ACVP Conference

March 10, 2018

Types of Heart Failure

▪ Systolic (or squeezing) heart failure – EF <50% ▪ Decreased pumping function of the heart, which results in fluid

back up in the lungs and heart failure

▪ Diastolic (or relaxation) heart failure – EF >50% ▪ Involves a thickened and stiff heart muscle

▪ As a result, the heart does not fill with blood properly

▪ This results in fluid backup in the lungs and heart failure

▪ BP = CO x SVR

▪ CO = SV x HR

Stage A: Those at risk for heart failure, but who have not yet developed

structural heart changes (diabetics, those with coronary disease without

prior infarct).

Stage B: Individuals with structural heart disease (i.e. reduced ejection

fraction, left ventricular hypertrophy, chamber enlargement), however

no symptoms of heart failure have ever developed.

Stage C: Patients who have developed clinical heart failure.

Stage D: Patients with refractory heart failure requiring advanced

intervention (biventricular pacemakers, left ventricular assist device, or

transplantation).

Class I: No symptoms of heart failure

Class II: Symptoms of heart failure with

moderate exertion

Class III: Symptoms of heart failure with

minimal exertion

Class IV: Symptoms of heart failure at rest

Underlying causes of SYSTOLIC heart failure include

the following:

•Coronary artery disease

•Diabetes mellitus

•Hypertension

•Valvular heart disease (stenosis or regurgitant lesions)

•Arrhythmia (supraventricular or ventricular)

•Infections and inflammation (myocarditis)

•Peripartum cardiomyopathy

•Congenital heart disease

•Drugs (either recreational, such as alcohol and cocaine,

or therapeutic drugs with cardiac side effects, such as

doxorubicin)

•Idiopathic cardiomyopathy

•Rare conditions (endocrine abnormalities, rheumatologic

disease, neuromuscular conditions)

Underlying causes of DIASTOLIC heart failure

include the following:

•Coronary artery disease

•Diabetes mellitus

•Hypertension

•Valvular heart disease (aortic stenosis)

•Hypertrophic cardiomyopathy

•Restrictive cardiomyopathy (amyloidosis, sarcoidosis)

•Constrictive pericarditis

•Aging

•Obesity

Underlying causes of ACUTE heart failure include the

following:

•Acute valvular (mitral or aortic) regurgitation

•Myocardial infarction

•Myocarditis

•Arrhythmia

•Drugs (eg, cocaine, calcium channel blockers, or beta-

blocker overdose)

•Sepsis

•Medical or dietary non-compliance

Underlying causes of HIGH-OUTPUT heart failure

include the following:

•Obesity

•Anemia

•Systemic arteriovenous fistulas

•Hyperthyroidism

•Beriberi heart disease

•Paget disease of bone

•Albright syndrome (fibrous dysplasia)

•Multiple myeloma

•Pregnancy

•Glomerulonephritis

•Polycythemia vera

•Carcinoid syndrome

Underlying causes of RIGHT heart failure include the following:

•Left ventricular failure (Most common)

•Coronary artery disease (ischemia)

•Pulmonary hypertension

•Pulmonary valve stenosis

•Pulmonary embolism

•Chronic pulmonary disease

•Neuromuscular disease

LEFT AND RIGHT HEART FAILURE

▪Left Heart Failure ▪Dyspnea

▪Orthopnea (+/- cough)

▪ PND

▪ Tachycardia

▪Right Heart Failure ▪ Lower extremity edema

▪ Ascites

▪ Hepatomegaly (+/- elevated LFTs)

▪ JVD / elevated JVP

▪ Cyanosis

▪ Abdominal swelling (gut edema / poor appetite)

TREATMENT OF SYSTOLIC CHF

▪DRUGS

▪DEVICES ▪CRT

▪Defibrillators

-- Lowers heart rate at the sinus

node

SHIFT TRIAL

-- Lancet (2010)

(all comparisons are versus

enalapril 20 mg daily, not versus placebo)

2 weeks 1-2 weeks 2-4 weeks

Single-blind run-in period Double-blind period

(1:1 randomization)

Enalapril

10 mg BID

100 mg BID

200 mg BID

Enalapril 10 mg BID

LCZ696 200 mg BID

PARADIGM-HF: Study Design

Randomization

LCZ696

10,521 patients screened at 1043 centers in 47 countries

Did not fulfill criteria for randomization

(n=2079)

Randomized erroneously or at sites closed due to GCP violations (n=43)

8399 patients randomized for ITT analysis

LCZ696 (n=4187)

At last visit

375 mg daily 11 lost to follow-up

Enalapril (n=4212)

At last visit

18.9 mg daily 9 lost to follow-up

median 27 months of follow-up

PARADIGM-HF: Patient Disposition

0

16

32

40

24

8

Enalapril (n=4212)

360 720 1080 0 180 540 900 1260

Days After Randomization

4187

4212

3922

3883

3663

3579

3018

2922

2257

2123

1544

1488

896

853

249

236

LCZ696

Enalapril

Patients at Risk

1117 K

ap

lan

-Me

ier

Es

tim

ate

of

Cu

mu

lati

ve

Rate

s (

%)

914

LCZ696 (n=4187)

PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint)

0

16

32

40

24

8

Enalapril (n=4212)

360 720 1080 0 180 540 900 1260

Days After Randomization

4187

4212

3922

3883

3663

3579

3018

2922

2257

2123

1544

1488

896

853

249

236

LCZ696

Enalapril

Patients at Risk

1117 K

ap

lan

-Me

ier

Es

tim

ate

of

Cu

mu

lati

ve

Rate

s (

%)

914

LCZ696 (n=4187)

HR = 0.80 (0.73-0.87)

P = 0.0000002

Number needed to treat = 21

PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint)

Enalapril (n=4212)

LCZ696 (n=4187)

HR = 0.80 (0.71-0.89)

P = 0.00004

Number need to treat = 32

Ka

pla

n-M

eie

r E

sti

ma

te o

f C

um

ula

tive

Rate

s (

%)

Days After Randomization

4187

4212

4056

4051

3891

3860

3282

3231

2478

2410

1716

1726

1005

994

280

279

LCZ696

Enalapril

Patients at Risk

360 720 1080 0 180 540 900 1260 0

16

32

24

8

693

558

PARADIGM-HF: Cardiovascular Death

PARADIGM-HF: All-Cause Mortality

4187

4212

4056

4051

3891

3860

3282

3231

2478

2410

1716

1726

1005

994

280

279

LCZ696

Enalapril

Enalapril (n=4212)

LCZ696 (n=4187)

HR = 0.84 (0.76-0.93)

P<0.0001 K

ap

lan

-Me

ier

Es

tim

ate

of

Cu

mu

lati

ve

Rate

s (

%)

Days After Randomization Patients at Risk

360 720 1080 0 180 540 900 1260 0

16

32

24

8

835

711

Clyde W. Yancy et al. JACC 2018;71:201-230 ©2018 by American College of Cardiology

DOSE TRIAL

-

NEJM 2011

Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial – Lancet Jan 2013

More definitive RELAX AHF 2 Trial is ongoing …

How about Cor Pulmonale?

▪Defined as an alteration in the structure and function of the right ventricle (RV) of the heart caused by a primary disorder of the respiratory system.

▪ Pulmonary hypertension is often the common link between lung dysfunction and the heart in cor pulmonale.

Pulmonary hypertension- WHO Classifciation

▪ Group 1: Pulmonary artery hypertension, including heritable causes; connective-tissue disorders, including scleroderma; and other idiopathic causes

▪ Group 2: pulmonary artery hypertension due to left ventricular [LV] dysfunction

▪ Group 3: Pulmonary hypertension due to lung disease and/or hypoxia; these disorders include chronic obstructive pulmonary disease (COPD), which is the most common cause of cor pulmonale. There have been studies correlating the degree of hypoxia with the severity of cor pulmonale. Other disorders that can result in cor pulmonale in this group include interstitial lung sisease (ILD) and obstructive sleep apnea (OSA)

▪ Group 4: Chronic thromboembolic pulmonary hypertension; blood clots that form in the lungs can lead to increased resistance, pulmonary hypertension and, subsequently, cor pulmonale

▪ Group 5: Pulmonary hypertension caused by other diseases or conditions, including sarcoidosis, polycythemia vera (which can lead to increased blood viscosity and, subsequently, pulmonary hypertension), vasculitis, and other disorders.

Cor Pulmonale

▪ The end result of the above mechanisms is increased pulmonary arterial pressure and resistance.

▪ The RV is a thin-walled chamber that is a better volume pump than a pressure pump. It is better suited to adapt to changing preload than afterload. With an increase in afterload, the RV systolic pressure is increased to maintain the circulatory gradient. At a critical point, a further increase in pulmonary arterial pressure and resistance produces significant RV dilatation, an increase in RV end-diastolic pressure, and RV circulatory failure.

Clyde W. Yancy et al. JACC 2018;71:201-230 ©2018 by American College of Cardiology

(Important in thinking

about strategies to

reduce readmission…)