low-output heart failure systolic heart failure (hfref):
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Low-Output Heart Failure Systolic Heart Failure (HFREF): Decreased Left ventricular ejection fraction Diastolic Heart Failure (HFPEF): Elevated Left and Right ventricular end-diastolic pressures Normal LVEF High-Output Heart Failure - PowerPoint PPT PresentationTRANSCRIPT
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Low-Output Heart Failure– Systolic Heart Failure (HFREF):
– Decreased Left ventricular ejection fraction
– Diastolic Heart Failure (HFPEF): – Elevated Left and Right ventricular end-diastolic pressures– Normal LVEF
• High-Output Heart Failure– Seen with peripheral shunting, low-systemic vascular resistance,
hyperthryoidism, beri-beri, carcinoid, anemia– Often have normal cardiac output
• Right-Ventricular Failure– Seen with pulmonary hypertension, large RV infarctions.
Chronic Congestive Heart FailureChronic Congestive Heart FailureCauses of Low-Output Heart Failure
• Systolic Dysfunction• Coronary Artery Disease• Idiopathic dilated cardiomyopathy (DCM)
» 50% idiopathic (at least 25% familial)» 9 % myocarditis (viral)» tachycardia, peripartum, hypertension, HIV, connective tissue
disease, substance abuse (alcohol), doxorubicin/herceptin• Hypertension• Valvular Heart Disease
• Diastolic Dysfunction• Hypertension• Coronary artery disease• Hypertrophic obstructive cardiomyopathy (HCM)• Restrictive cardiomyopathy
Chronic Congestive Heart FailureChronic Congestive Heart Failure(Mal)adaptation-hemodynamic
Chronic Congestive Heart FailureChronic Congestive Heart Failure(Mal) adaptation-neurohormonal
• Activation of the sympathetic nervous system– Vasoconstriction/increased afterload– Tolerance– Arhythmogenic
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Activation of renin-angiotensin system– Na resorption– Vasoconstriction– Apoptosis/fibrosis
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Antidiuretic hormone
• Proinflammatory cytokines– TNFalpha– IL-6
Chronic Congestive Heart FailureChronic Congestive Heart FailureClinical Presentation of Heart Failure
• Due to excess fluid accumulation:– Dyspnea (most sensitive symptom)
– Edema
– Hepatic congestion
– Ascites
– Orthopnea, Paroxysmal Nocturnal Dyspnea (PND)
• Due to reduction in cardiac ouput:– Fatigue (especially with exertion)
– Weakness
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• S3 gallop – Low sensitivity, but highly specific
• Cool, pale, cyanotic extremities– Have sinus tachycardia, diaphoresis and peripheral vasoconstriction
• Crackles or decreased breath sounds at bases (effusions) on lung exam
• Elevated jugular venous pressure• Lower extremity edema• Ascites• Hepatomegaly• Splenomegaly• Displaced PMI
• Apical impulse that is laterally displaced past the midclavicular line is usually indicative of left ventricular enlargement>
Chronic Congestive Heart FailureChronic Congestive Heart FailureLab Analysis in Heart Failure
• CBC– Since anemia can exacerbate heart failure
• Serum electrolytes and creatinine– before starting high dose diuretics
• Fasting Blood glucose– To evaluate for possible diabetes mellitus
• Thyroid function tests– Since thyrotoxicosis can result in A. Fib, and hypothyroidism can results in HF.
• Iron studies– To screen for hereditary hemochromatosis as cause of heart failure.
• ANA– To evaluate for possible lupus
• Viral studies – If viral mycocarditis suspected
Chronic Congestive Heart FailureChronic Congestive Heart FailureLaboratory Analysis (cont.)
• BNP– With chronic heart failure, atrial mycotes secrete increase
amounts of atrial natriuretic peptide (ANP) and brain natriuretic pepetide (BNP) in response to high atrial and ventricular filling pressures
– Usually is > 400 pg/mL in patients with dyspnea due to heart failure.
Chronic Congestive Heart FailureChronic Congestive Heart FailureChest X-ray in Heart Failure
• Cardiomegaly
• Cephalization of the pulmonary vessels
• Kerley B-lines
• Pleural effusions
Chronic Congestive Heart FailureChronic Congestive Heart FailureCardiomegaly
Chronic Congestive Heart FailureChronic Congestive Heart FailurePulmonary Edema due to Heart Failure
Chronic Congestive Heart FailureChronic Congestive Heart FailureKerley B lines
Chronic Congestive Heart FailureChronic Congestive Heart FailureCardiac Testing in Heart Failure
• Electrocardiogram:– May show specific cause of heart failure:
– Ischemic heart disease– Dilated cardiomyopathy: first degree AV block, LBBB,
Left anterior fascicular block– Amyloidosis: pseudo-infarction pattern– Idiopathic dilated cardiomyopathy: LVH
• Echocardiogram:– Left ventricular ejection fraction– Structural/valvular abnormalities
Chronic Congestive Heart FailureChronic Congestive Heart FailureFurther Cardiac Testing in Heart Failure
• Coronary arteriography– Should be performed in patients presenting with heart failure who
have angina or significant ischemia– Reasonable in patients who have chest pain that may or may not
be cardiac in origin, in whom cardiac anatomy is not known, and in patients with known or suspected coronary artery disease who do not have angina.
– Measure cardiac output, degree of left ventricular dysfunction, and left ventricular end-diastolic pressure.
Chronic Congestive Heart FailureChronic Congestive Heart FailureFurther testing in Heart Failure
• Endomyocardial biopsy• Not frequently used
• Amyloidosis, giant-cell myocarditis
Chronic Congestive Heart FailureChronic Congestive Heart FailureClassification of Heart Failure
ACCF/AHA Stages of HF NYHA Functional ClassificationA At high risk for HF but without structural
heart disease or symptoms of HF.None
B Structural heart disease but without signs or symptoms of HF.
I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.
C Structural heart disease with prior or current symptoms of HF.
I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.
II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF.
III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF.
IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.
D Refractory HF requiring specialized interventions.
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Aggravating FactorsAggravating Factors• Medications
• New heart disease• Myocardial ischemia
• Medications• New heart disease
• Myocardial ischemia
• Endocarditis
• Obesity
• Hypertension
• Physical activity
• Dietary excess
• Endocarditis
• Obesity
• Hypertension
• Physical activity
• Dietary excess
• Pregnancy
• Arrhythmias (AF)
• Infections
• Thromboembolism
• Hyper/hypothyroidism
• Pregnancy
• Arrhythmias (AF)
• Infections
• Thromboembolism
• Hyper/hypothyroidism
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Heart Failure and Myocardial IschemiaHeart Failure and Myocardial Ischemia
• Coronary HD is the cause of 2/3 of HFCoronary HD is the cause of 2/3 of HF
• Segmental wall motion abnormalities are not Segmental wall motion abnormalities are not specific if ischemiaspecific if ischemia
• Angina coronary angio and revascularizationAngina coronary angio and revascularization
• No anginaNo angina• Search for ischemia and viability in all Search for ischemia and viability in all ??• Coronary angiography in all Coronary angiography in all ??
Chronic Congestive Heart FailureChronic Congestive Heart Failure
VASOCONSTRICTIONVASOCONSTRICTION VASODILATATION VASODILATATION
KininogenKininogen
KallikreinKallikrein
Inactive FragmentsInactive Fragments
AngiotensinogenAngiotensinogen
Angiotensin IAngiotensin I
RENINRENIN
Kininase IIKininase IIInhibitorInhibitor
ALDOSTERONEALDOSTERONE
SYMPATHETICSYMPATHETICVASOPRESSINVASOPRESSIN
PROSTAGLANDINSPROSTAGLANDINS
tPAtPA
ANGIOTENSIN IIANGIOTENSIN II
BRADYKININBRADYKININ
ACE-i. Mechanism of ActionACE-i. Mechanism of Action
A.C.E.A.C.E.
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ACE-I. Clinical EffectsACE-I. Clinical Effects
• Improve symptoms
• Reduce remodelling / progression
• Reduce hospitalization
• Improve survival
• Improve symptoms
• Reduce remodelling / progression
• Reduce hospitalization
• Improve survival
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Mortality Reduction with ACE-iMortality Reduction with ACE-i
StudyStudy ACE-iACE-i Clinical SetingClinical Seting
CONSENSUSCONSENSUS EnalaprilEnalapril CHFCHF
SOLVD treatment SOLVD treatment EnalaprilEnalapril CHFCHF
AIREAIRE RamiprilRamipril CHFCHF
Vheft-IIVheft-II EnalaprilEnalapril CHFCHF
TRACETRACE TrandolaprilTrandolapril CHF / LVDCHF / LVD
SAVESAVE CaptoprilCaptopril LVDLVD
SMILESMILE ZofenoprilZofenopril High risk High risk
HOPEHOPE RamiprilRamipril High risk High risk
Chronic Congestive Heart FailureChronic Congestive Heart Failure
PlaceboPlacebo
EnalaprilEnalapril
1212111110109988776655
ProbabiilityofDeath
ProbabiilityofDeath
MonthsMonths
0.10.1
0.80.8
00
0.20.2
0.30.3
0.70.7
0.40.4
0.50.5
0.60.6p< 0.001p< 0.001
p< 0.002p< 0.002
CONSENSUSN Engl J Med 1987;316:1429CONSENSUSN Engl J Med 1987;316:1429
4433221100
ACE-iACE-i
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Mortality,%
Mortality,%
44SAVEN Engl J Med 1992;327:669
SAVEN Engl J Med 1992;327:669 YearsYears
3030
2020
1010
0011 22 33
PlaceboPlacebo
CaptoprilCaptopril
00
n=1115n=1115
n=1116n=1116
p=0.019p=0.019² -19%² -19%
n = 22313 - 16 days post AMIEF < 4012.5 --- 150 mg / day
n = 22313 - 16 days post AMIEF < 4012.5 --- 150 mg / day
Asymptomatic ventriculardysfunction post MI
Asymptomatic ventriculardysfunction post MI
ACE-iACE-i
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Symptomatic heart failure
• Asymptomatic ventricular dysfunction- LVEF < 35 - 40 %
• Selected high risk subgroups
• Symptomatic heart failure
• Asymptomatic ventricular dysfunction- LVEF < 35 - 40 %
• Selected high risk subgroups
ACE-i. IndicationsACE-i. Indications
AHA / ACC HF guidelines 2001 AHA / ACC HF guidelines 2001
ESC HF guidelines 2001ESC HF guidelines 2001
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ACE-i. Practical UseACE-i. Practical Use
• Start with very low doseStart with very low dose
• Increase dose if well toleratedIncrease dose if well tolerated
• Renal function & serum KRenal function & serum K++ after 1-2 w after 1-2 w
• Avoid fluid retention / hypovolemia Avoid fluid retention / hypovolemia (diuretic use)(diuretic use)
• Dose NOT determined by symptomsDose NOT determined by symptoms
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ACE-i. Dose (mg)ACE-i. Dose (mg) InitialInitial MaximumMaximum
CaptoprilCaptopril 6.25 / 8h 6.25 / 8h 50 / 8h50 / 8h
EnalaprilEnalapril 2.5 / 12 h 2.5 / 12 h 10 to 20 / 12h10 to 20 / 12h
FosinoprilFosinopril 5 to 10 / day 5 to 10 / day 40 / day40 / day
LisinoprilLisinopril 2.5 to 5.0 / day 2.5 to 5.0 / day 20 to 40 / day20 to 40 / day
QuinaprilQuinapril 10 / 12 h10 / 12 h 40 / 12 h40 / 12 h
RamiprilRamipril 1.25 to 2.5 / day 1.25 to 2.5 / day 10 / day10 / day
AHA / ACC HF guidelines 2001 AHA / ACC HF guidelines 2001
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ACE-I. Adverse EffectsACE-I. Adverse Effects
• Hypotension (1st dose effect)Hypotension (1st dose effect)
• Worsening renal functionWorsening renal function
• HyperkalemiaHyperkalemia
• CoughCough
• AngioedemaAngioedema
• Rash, ageusia, neutropenia, …Rash, ageusia, neutropenia, …
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ACE-I. ContraindicationsACE-I. Contraindications
• Intolerance (angioedema, anuric renal fail.)
• Bilateral renal artery stenosis
• Pregnancy
• Renal insufficiency (creatinine > 3 mg/dl)
• Hyperkalemia (> 5,5 mmol/l)
• Severe hypotension
ACE-I. ContraindicationsACE-I. Contraindications
• Intolerance (angioedema, anuric renal fail.)
• Bilateral renal artery stenosis
• Pregnancy
• Renal insufficiency (creatinine > 3 mg/dl)
• Hyperkalemia (> 5,5 mmol/l)
• Severe hypotension
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ß-Adrenergic BlockersMechanism of actionß-Adrenergic BlockersMechanism of action• Density of ß1 receptors
• Inhibit cardiotoxicity of catecholamines
• Neurohormonal activation
• HR
• Antiischemic
• Antihypertensive
• Antiarrhythmic
• Antioxidant, Antiproliferative
• Density of ß1 receptors
• Inhibit cardiotoxicity of catecholamines
• Neurohormonal activation
• HR
• Antiischemic
• Antihypertensive
• Antiarrhythmic
• Antioxidant, Antiproliferative
Chronic Congestive Heart FailureChronic Congestive Heart Failure
100100
9090
8080
6060
7070
5050242400 2020161612128844 2828
PlaceboPlacebo
CarvedilolCarvedilol
MonthsMonths
N = 2289N = 2289III-IV NYHAIII-IV NYHA
COPERNICUSCOPERNICUSNEJM 2001;344:1651NEJM 2001;344:1651
SurvivalSurvival%%
ß-Adrenergic Blockersß-Adrenergic Blockers
pp=0.00014=0.0001435% RR 35% RR
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Patient Patient stablestable• No physical evidence of fluid retentionNo physical evidence of fluid retention• No need for i.v. inotropic drugsNo need for i.v. inotropic drugs
• No contraindicationsNo contraindications
• In hospital or notIn hospital or not
ß-Adrenergic Blockersß-Adrenergic BlockersWhen to startWhen to start
Chronic Congestive Heart FailureChronic Congestive Heart Failure
InitialInitial TargetTarget
BisoprololBisoprolol 1.25 / 24h1.25 / 24h 10 / 24h 10 / 24h
CarvedilolCarvedilol 3.125 / 12h3.125 / 12h 25 / 12h25 / 12h
Metoprolol Metoprolol succinnatesuccinnate 12,5-25 / 24h12,5-25 / 24h 200 / 24h200 / 24h
• Start Low, Increase SlowlyStart Low, Increase Slowly• Increase the dose every 2 - 4 weeksIncrease the dose every 2 - 4 weeks
ß-Adrenergic Blockersß-Adrenergic BlockersDose (mg)Dose (mg)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• HypotensionHypotension• Fluid retention / worsening heart failureFluid retention / worsening heart failure• FatigueFatigue• Bradycardia / heart blockBradycardia / heart block
ß-Adrenergic Blockersß-Adrenergic BlockersAdverse EffectsAdverse Effects
Chronic Congestive Heart FailureChronic Congestive Heart Failure
ALDOSTERONEALDOSTERONE
• Retention Na+
• Retention H2O
• Excretion K+
• Excretion Mg2+
• Retention Na+
• Retention H2O
• Excretion K+
• Excretion Mg2+
• Collagen Collagen depositiondeposition
FibrosisFibrosis - - myocardiummyocardium
- - vesselsvessels
SpironolactoneSpironolactone
Edema Edema
Arrhythmias Arrhythmias
Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)
Competitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney)
Aldosterone InhibitorsAldosterone Inhibitors
-
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Aldactone
Placebo
SurvivalSurvival
1.0
0.9
0.8
0.7
0.6
0.5
0 6 12 18 24 30 36
months
p < 0.0001
Annual MortalityAldactone 18%; Placebo 23%
N = 1663N = 1663NYHA III-IVNYHA III-IV
Mean follow-up 2 yMean follow-up 2 y
RALESRALESNEJM 1999;341:709NEJM 1999;341:709
SpironolactoneSpironolactone
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Spironolactone.Spironolactone. IndicationsIndications
• Recent or current symptoms despite Recent or current symptoms despite ACE-i, diuretics, dig. and ACE-i, diuretics, dig. and -blockers-blockers
AHA / ACC HF guidelines 2001AHA / ACC HF guidelines 2001
• Recommended in advanced heart failure Recommended in advanced heart failure (III-IV), in addition to ACE-i and diuretics(III-IV), in addition to ACE-i and diuretics
• HypokalemiaHypokalemiaESC HF guidelines 2001ESC HF guidelines 2001
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Spironolactone.Spironolactone. Practical use Practical use
• Do not use if hyperkalemia, renal insuf.Do not use if hyperkalemia, renal insuf.
• Monitor serum KMonitor serum K++ at “frequent intervals” at “frequent intervals”
• Start ACE-i firstStart ACE-i first
• Start with 25 mg / 24hStart with 25 mg / 24h
• If KIf K++ >5.5 mmol/L, reduce to 25 mg / 48h >5.5 mmol/L, reduce to 25 mg / 48h
• If KIf K++ is low or stable consider 50 mg / day is low or stable consider 50 mg / day
New studies in progressNew studies in progress
Chronic Congestive Heart FailureChronic Congestive Heart Failure
RENINRENIN
AngiotensinogenAngiotensinogen Angiotensin I
ANGIOTENSIN II
Angiotensin I
ANGIOTENSIN II
ACEACEOther pathwaysOther pathways
VasoconstrictionVasoconstriction Proliferative Action
Proliferative Action
VasodilatationVasodilatation Antiproliferative Action
Antiproliferative Action
AT1 AT1 AT2AT2
AT1 Receptor Blockers
AT1 Receptor Blockers
RECEPTORSRECEPTORS
Angiotensin II Receptor Blockers (ARB)Angiotensin II Receptor Blockers (ARB)
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Candesartan, Eprosartan, IrbesartanCandesartan, Eprosartan, IrbesartanLosartan, Telmisartan, ValsartanLosartan, Telmisartan, Valsartan
• Not indicated with beta blockersNot indicated with beta blockers
• Indicated in patients intolerant to ACE-IIndicated in patients intolerant to ACE-I
Angiotensin II Receptor Blockers (ARB)Angiotensin II Receptor Blockers (ARB)
AHA / ACC HF guidelines 2001AHA / ACC HF guidelines 2001ESC HF guidelines 2001ESC HF guidelines 2001
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Positive InotropesPositive Inotropes
• DigitalisDigitalis
• SympathomimeticsSympathomimetics• CatecholaminesCatecholamines• B-adrenergic agonistsB-adrenergic agonists
• Phosphodiesterase inhibitorsPhosphodiesterase inhibitors• Amrinone, Milrinone, EnoximoneAmrinone, Milrinone, Enoximone
• Calcium sensitizersCalcium sensitizers• Levosimendan, PimobendanLevosimendan, Pimobendan
Chronic Congestive Heart FailureChronic Congestive Heart Failure
•May increase mortality Exception: Digoxin, Levosimendan
•Use only in refractory CHF
•NOT for use as chronic therapy
•May increase mortality Exception: Digoxin, Levosimendan
•Use only in refractory CHF
•NOT for use as chronic therapy
Positive Inotropic TherapyPositive Inotropic Therapy
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Digitalis. Mechanism of ActionDigitalis. Mechanism of Action
Blocks NaBlocks Na++ / K / K++ ATPase => Ca ATPase => Ca+ ++ +
•• Inotropic effectInotropic effect
•• NatriuresisNatriuresis
•• Neurohormonal controlNeurohormonal control-- PlasmaPlasma NoradrenalineNoradrenaline
- - Peripheral nervous system activityPeripheral nervous system activity
-- RAAS activity RAAS activity
-- VagalVagal tonetone
-- Normalizes arterial baroreceptors Normalizes arterial baroreceptorsNEJM 1988;318:358 NEJM 1988;318:358
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Digitalis. Clinical EffectsDigitalis. Clinical Effects
• Improve symptoms
• Modest reduction in hospitalization
• Does not improve survival
• Improve symptoms
• Modest reduction in hospitalization
• Does not improve survival
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Digitalis. IndicationsDigitalis. Indications
• • When no adequate response toWhen no adequate response to ACE-i + diuretics + beta-blockersACE-i + diuretics + beta-blockers AHA / ACC Guidelines 2001AHA / ACC Guidelines 2001
• • In combination with ACE-i + diureticsIn combination with ACE-i + diuretics
if persisting symptomsif persisting symptoms ESC Guidelines 2001ESC Guidelines 2001
• • AF, to slow AV conductionAF, to slow AV conduction
Dose 0.125 to 0.250 mg / dayDose 0.125 to 0.250 mg / day
Chronic Congestive Heart FailureChronic Congestive Heart Failure
5050
4040
3030
2020
1010
00
Placebon=3403
Placebon=3403
Digoxinn=3397
Digoxinn=3397
484800 1212 2424 3636
Mortality%Mortality%
DIGN Engl J Med 1997;336:525
DIGN Engl J Med 1997;336:525 MonthsMonths
p = 0.8p = 0.8
DigitalisDigitalis
N=6800
NYHA II-III
N=6800
NYHA II-III
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Diuretics. IndicationsDiuretics. Indications1.1. Symptomatic HF, with fluid retentionSymptomatic HF, with fluid retention
• EdemaEdema• DyspneaDyspnea• Lung RalesLung Rales• Jugular distensionJugular distension• HepatomegalyHepatomegaly• Pulmonary edema (Xray)Pulmonary edema (Xray)
AHA / ACC HF guidelines 2001 AHA / ACC HF guidelines 2001
ESC HF guidelines 2001ESC HF guidelines 2001
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Loop Diuretics / Thiazides. Practical Use Loop Diuretics / Thiazides. Practical Use
• Start with variable dose. Titrate to achieve Start with variable dose. Titrate to achieve dry weightdry weight
• Monitor serum KMonitor serum K++ at “frequent intervals” at “frequent intervals”
• Reduce dose when fluid retention is controlledReduce dose when fluid retention is controlled
• Teach the patient when, how to change Teach the patient when, how to change dosedose
• Combine to overcome “resistance”Combine to overcome “resistance”
• Do not use aloneDo not use alone
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Thiazides, Loop Diuretics. Adverse EffectsThiazides, Loop Diuretics. Adverse Effects
•• KK++, Mg, Mg++ (15 - 60%) (sudden death ???) (15 - 60%) (sudden death ???)
•• NaNa++
• • Stimulation of neurohormonal activityStimulation of neurohormonal activity
•• Hyperuricemia (15 - 40%)Hyperuricemia (15 - 40%)
•• Hypotension. Ototoxicity. Gastrointestinal. Hypotension. Ototoxicity. Gastrointestinal.
Alkalosis. MetabolicAlkalosis. MetabolicSharpe N. Heart failure. Martin Dunitz 2000;43Sharpe N. Heart failure. Martin Dunitz 2000;43Kubo SH , et al. Am J Cardiol 1987;60:1322Kubo SH , et al. Am J Cardiol 1987;60:1322MRFIT, JAMA 1982;248:1465MRFIT, JAMA 1982;248:1465Pool Wilson. Heart failure. Churchill Livinston 1997;635Pool Wilson. Heart failure. Churchill Livinston 1997;635
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Diuretic ResistanceDiuretic Resistance• Neurohormonal activationNeurohormonal activation
• Rebound NaRebound Na++ uptake after volume loss uptake after volume loss
• Hypertrophy of distal nephronHypertrophy of distal nephron
• Reduced tubular secretion Reduced tubular secretion (renal failure, NSAIDs)(renal failure, NSAIDs)
• Decreased renal perfusion (low output)Decreased renal perfusion (low output)
• Altered absortion of diureticAltered absortion of diuretic
• Noncompliance with drugsNoncompliance with drugs
Brater NEJM 1998;339:387 Brater NEJM 1998;339:387 Kramer et al. Am J Med 1999;106:90Kramer et al. Am J Med 1999;106:90
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Managing Resistance to DiureticsManaging Resistance to Diuretics
•• Restrict NaRestrict Na++/H/H22O intake (Monitor Natremia)O intake (Monitor Natremia)
•• Increase dose Increase dose (individual dose, frequency, i.v.)(individual dose, frequency, i.v.)
• • Combine: Combine: furosemide + thiazide / spiro / metolazonefurosemide + thiazide / spiro / metolazone
•• Dopamine (increase cardiac output)Dopamine (increase cardiac output)
•• Reduce dose of ACE-iReduce dose of ACE-i
•• UltrafiltrationUltrafiltration
Motwani et al Circulation 1992;86:439Motwani et al Circulation 1992;86:439
Chronic Congestive Heart FailureChronic Congestive Heart Failure
• Inotropes, long term / intermittentInotropes, long term / intermittent
• Antiarrhythmics (except amiodarone)Antiarrhythmics (except amiodarone)
• Calcium antagonists (except amlodipine)Calcium antagonists (except amlodipine)
• Non-steroidal antiinflammatory drugs (NSAIDS)Non-steroidal antiinflammatory drugs (NSAIDS)
• Tricyclic antidepressantsTricyclic antidepressants
• CorticosteroidsCorticosteroids
• LithiumLithium
Drugs to Avoid Drugs to Avoid (may increase symptoms, mortality)(may increase symptoms, mortality)
ESC HF guidelines 2001ESC HF guidelines 2001
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Refractory End-Stage HFRefractory End-Stage HF• Review etiology, treatment & aggrav. factorsReview etiology, treatment & aggrav. factors
• Control fluid retentionControl fluid retention• Resistance to diureticsResistance to diuretics• Ultrafiltration ?Ultrafiltration ?
• iv inotropics / vasodilators during iv inotropics / vasodilators during decompensationdecompensation
• Consider resynchronizationConsider resynchronization
• Consider mechanical assist devicesConsider mechanical assist devices
• Consider heart transplantationConsider heart transplantation
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Cardiac Resynchronization Therapy* in Patients With Severe Systolic Heart Failure
• For patients who have left ventricular ejection fraction (LVEF) less than or equal to 35%, a QRS duration greater than or equal to 0.12 seconds, and sinus rhythm, cardiac resynchronization therapy (CRT) with or without an ICD is indicated for the treatment of New York Heart Association (NYHA) functional Class III or ambulatory Class IV heart failure symptoms on optimal recommended medical therapy
Chronic Congestive Heart FailureChronic Congestive Heart Failure Indications for CRT TherapyPatient with cardiomyopathy on GDMT for >3 mo or on GDMT and >40 d after MI, or
with implantation of pacing or defibrillation device for special indications
LVEF <35%
Evaluate general health statusComorbidities and/or frailty
limit survival with good functional capacity to <1 y
Continue GDMT without implanted device
Acceptable noncardiac health
Evaluate NYHA clinical status
NYHA class I
· LVEF ≤30%· QRS ≥150 ms· LBBB pattern· Ischemic
cardiomyopathy· QRS ≤150 ms· Non-LBBB pattern
NYHA class II
· LVEF ≤35%· QRS 120-149 ms· LBBB pattern· Sinus rhythm
· QRS ≤150 ms· Non-LBBB pattern
· LVEF ≤35%· QRS ≥150 ms· LBBB pattern· Sinus rhythm
· LVEF ≤35%· QRS ≥150 ms· Non-LBBB pattern· Sinus rhythm
Colors correspond to the class of recommendations in the ACCF/AHA Table 1.
Benefit for NYHA class I and II patients has only been shown in CRT-D trials, and while patients may not experience immediate symptomatic benefit, late remodeling may be avoided along with long-term HF consequences. There are no trials that support CRT-pacing (without ICD) in NYHA class I and II patients. Thus, it is anticipated these patients would receive CRT-D unless clinical reasons or personal wishes make CRT-pacing more appropriate. In patients who are NYHA class III and ambulatory class IV, CRT-D may be chosen but clinical reasons and personal wishes may make CRT-pacing appropriate to improve symptoms and quality of life when an ICD is not expected to produce meaningful benefit in survi val.
NYHA class III & Ambulatory class IV
· LVEF ≤35%· QRS 120-149 ms· LBBB pattern· Sinus rhythm
· LVEF ≤35%· QRS 120-149 ms· Non-LBBB pattern· Sinus rhythm
· LVEF ≤35%· QRS ≥150 ms· LBBB pattern· Sinus rhythm
· LVEF≤35%· QRS ≥150 ms· Non-LBBB pattern· Sinus rhythm
· Anticipated to require frequent ventricular pacing (>40%)
· Atrial fibrillation, if ventricular pacing is required and rate control will result in near 100% ventricular pacing with CRT
Special CRT Indications
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Heart Transplant. IndicationsHeart Transplant. Indications• Refractory cardiogenic shockRefractory cardiogenic shock
• Documented dependence on IV inotropic support Documented dependence on IV inotropic support to maintain adequate organ perfusionto maintain adequate organ perfusion
• Peak VO2 < 10 ml / kg / min Peak VO2 < 10 ml / kg / min
• Severe symptoms of ischemia not amenable to Severe symptoms of ischemia not amenable to revascularizationrevascularization
• Recurrent symptomatic ventricular arrhythmias Recurrent symptomatic ventricular arrhythmias refractory to all therapeutic modalitiesrefractory to all therapeutic modalities
Contraindications: age, severe comorbidityContraindications: age, severe comorbidity
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Ventricular Arrhythmias / Sudden DeathVentricular Arrhythmias / Sudden Death• Antiarrhythmics ineffective Antiarrhythmics ineffective (may increase mortality)(may increase mortality)
Amiodarone do not improve survivalAmiodarone do not improve survival
• -blockers reduce all cause mortality and SD-blockers reduce all cause mortality and SD
• Control ischemiaControl ischemia
• Control electrolyte disturbancesControl electrolyte disturbances
• ICD (Implantable Cardiac Defibrillator)ICD (Implantable Cardiac Defibrillator)• In secondary prevention of SDIn secondary prevention of SD• In sustained, hemodynamic destabilizing VTIn sustained, hemodynamic destabilizing VT• Ongoing research will establish new indicationsOngoing research will establish new indications
Chronic Congestive Heart FailureChronic Congestive Heart FailureDevice Therapy for Stage C HFrEF (cont.)
Recommendations COR LOEICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 days post-MI with LVEF ≤35%, and NYHA class II or III symptoms on chronic GDMT, who are expected to live ≥1 year*
I A
CRT is indicated for patients who have LVEF ≤35%, sinus rhythm, LBBB with a QRS ≥150 ms
I
A (NYHA class III/IV)
B (NYHA class II)
ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 days post-MI with LVEF ≤30%, and NYHA class I symptoms while receiving GDMT, who are expected to live ≥1 year*
I B
CRT can be useful for patients who have LVEF ≤35%, sinus rhythm, a non-LBBB pattern with a QRS ≥150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT.
IIa A
CRT can be useful for patients who have LVEF ≤35%, sinus rhythm, LBBB with a QRS 120 to 149 ms, and NYHA class II, III or ambulatory IV symptoms on GDMT
IIa
B
CRT can be useful in patients with AF and LVEF ≤35% on GDMT if a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) AV nodal ablation or rate control allows near 100% ventricular pacing with CRT
IIa B
Chronic Congestive Heart FailureChronic Congestive Heart Failure
Diastolic Heart FailureDiastolic Heart Failure• Incorrect diagnosis of HFIncorrect diagnosis of HF• Inaccurate measurement of LVEFInaccurate measurement of LVEF• Primary valvular diseasePrimary valvular disease• Restrictive (infiltrative) cardiomyopathies (Amyloidosis…)Restrictive (infiltrative) cardiomyopathies (Amyloidosis…)• Pericardial constrictionPericardial constriction• Episodic or reversible LV systolic dysfunctionEpisodic or reversible LV systolic dysfunction• Severe hypertension, ischemiaSevere hypertension, ischemia• High output states: Anemia, thyrotoxicosis, etcHigh output states: Anemia, thyrotoxicosis, etc• Chronic pulmonary disease with right HFChronic pulmonary disease with right HF• Pulmonary hypertension Pulmonary hypertension • Atrial myxomaAtrial myxoma• LV HypertrophyLV Hypertrophy• Diastolic dysfunction of uncertain originDiastolic dysfunction of uncertain origin
Chronic Congestive Heart FailureChronic Congestive Heart FailureTreatment of HFpEF
Recommendations COR LOESystolic and diastolic blood pressure should be controlled according to published clinical practice guidelines I B
Diuretics should be used for relief of symptoms due to volume overload
I C
Coronary revascularization for patients with CAD in whom angina or demonstrable myocardial ischemia is present despite GDMT
IIa
C
Management of AF according to published clinical practice guidelines for HFpEF to improve symptomatic HF
IIa C
Use of beta-blocking agents, ACE inhibitors, and ARBs for hypertension in HFpEF IIa C
ARBs might be considered to decrease hospitalizations in HFpEF
IIb B
Nutritional supplementation is not recommended in HFpEF
III: No Benefit
C
Chronic Congestive Heart FailureChronic Congestive Heart FailureStages, Phenotypes and Treatment of HF
STAGE AAt high risk for HF but without structural heart
disease or symptoms of HF
STAGE BStructural heart disease
but without signs or symptoms of HF
THERAPYGoals· Control symptoms· Improve HRQOL· Prevent hospitalization· Prevent mortality
Strategies· Identification of comorbidities
Treatment· Diuresis to relieve symptoms
of congestion· Follow guideline driven
indications for comorbidities, e.g., HTN, AF, CAD, DM
· Revascularization or valvular surgery as appropriate
STAGE CStructural heart disease
with prior or current symptoms of HF
THERAPYGoals· Control symptoms· Patient education· Prevent hospitalization· Prevent mortality
Drugs for routine use· Diuretics for fluid retention· ACEI or ARB· Beta blockers· Aldosterone antagonists
Drugs for use in selected patients· Hydralazine/isosorbide dinitrate· ACEI and ARB· Digoxin
In selected patients· CRT· ICD· Revascularization or valvular
surgery as appropriate
STAGE DRefractory HF
THERAPYGoals· Prevent HF symptoms· Prevent further cardiac
remodeling
Drugs· ACEI or ARB as
appropriate · Beta blockers as
appropriate
In selected patients· ICD· Revascularization or
valvular surgery as appropriate
e.g., Patients with:· Known structural heart disease and· HF signs and symptoms
HFpEF HFrEF
THERAPYGoals· Heart healthy lifestyle· Prevent vascular,
coronary disease· Prevent LV structural
abnormalities
Drugs· ACEI or ARB in
appropriate patients for vascular disease or DM
· Statins as appropriate
THERAPYGoals· Control symptoms· Improve HRQOL· Reduce hospital
readmissions· Establish patient’s end-
of-life goals
Options· Advanced care
measures· Heart transplant· Chronic inotropes· Temporary or permanent
MCS· Experimental surgery or
drugs· Palliative care and
hospice· ICD deactivation
Refractory symptoms of HF at rest, despite GDMT
At Risk for Heart Failure Heart Failure
e.g., Patients with:· Marked HF symptoms at
rest · Recurrent hospitalizations
despite GDMT
e.g., Patients with:· Previous MI· LV remodeling including
LVH and low EF· Asymptomatic valvular
disease
e.g., Patients with:· HTN· Atherosclerotic disease· DM· Obesity· Metabolic syndrome orPatients· Using cardiotoxins· With family history of
cardiomyopathy
Development of symptoms of HF
Structural heart disease