Acute Decompensated Heart Failure Acute Decompensated Heart Failure for Generalistsfor Generalists

Eric M. Siegal, M.D.Eric M. Siegal, M.D.

University of Wisconsin, MadisonUniversity of Wisconsin, Madison

Overview

Evolving definitionsEvolving definitions Epidemiology of ADHFEpidemiology of ADHF Goals of acute managementGoals of acute management Evolving management paradigms:Evolving management paradigms:

Acute vasoactive therapyAcute vasoactive therapy Prevention of SCDPrevention of SCD Biventricular pacingBiventricular pacing Beta-blockers in the hospitalBeta-blockers in the hospital How “dry” is “dry”?How “dry” is “dry”?

Why “ADHF”?

Growing recognition that “CHF” does not adequately Growing recognition that “CHF” does not adequately describe a broad spectrum of disease with multiple causes, describe a broad spectrum of disease with multiple causes, presentations and clinical courses.presentations and clinical courses.

Describe Describe acuityacuity, , severityseverity and underlying and underlying pathophysiologypathophysiology:: ““ADHF with severe systolic dysfunction due to ADHF with severe systolic dysfunction due to

ischemic cardiomyopathy and mitral regurgitation”ischemic cardiomyopathy and mitral regurgitation” ““Compensated NYHA Class II HF with moderate Compensated NYHA Class II HF with moderate

diastolic dysfunction due to hypertension and diabetes”diastolic dysfunction due to hypertension and diabetes” Where possible, treatment is tailored to the definitionWhere possible, treatment is tailored to the definition

Epidemiology and Economic Burden of HFAmerican Heart Association. Heart Disease and Stroke Statistics – 2005 Update.

IncidenceIncidence 550,000/year550,000/year

PrevalencePrevalence 5.0 million (2.3%)5.0 million (2.3%)

HospitalizationsHospitalizations 1,000,000 per year1,000,000 per year

CostCost $27.9 billion$27.9 billion

More Medicare Dollars Spent on HF Than Any Other Diagnosis

American Heart Association. Heart Disease and Stroke Statistics – 2005 Update.Hunt SA et al. Circulation 2001;104:2996-3007.Krumholz HM et al. Arch Intern Med. 1997;157:99-104.Miller LW et al. Cardiol Clin. 2001;19:547-555.

Average inpatient Medicare paymentAverage inpatient Medicare payment $5,456/patient$5,456/patient

Percent of Medicare patients with HF Percent of Medicare patients with HF readmitted within 6 monthsreadmitted within 6 months

44%44%

Estimated Direct and Indirect Costs of HF: $27.9 BillionAmerican Heart Association. Heart Disease and Stroke Statistics – 2005 Update.

Hospitalization$14.7

Lost Productivity/Morbidity

$2.6

Home Healthcare$2.2

Drugs/Durables$2.9

Providers$1.9

Nursing Home$3.6

60% of heart failure costs are incurred in the hospital

Prevalence of HF Increases With Age

US, 1988–1994AHA. Heart Disease and Stroke Statistics—2004 Update

0

2

4

6

8

10

20–24 25–34 35–44 45–54 55–64 65–74 75+

Age (yr)

Pop

ulat

ion

(%)

Males

Females

Explosive Increase in HFAHA.Heart Disease and Stroke Statistics – 2005 Update

1979 – 2002: Hospital discharges from HF rose from 1979 – 2002: Hospital discharges from HF rose from 377,000 to 970,000 per year377,000 to 970,000 per year

1992 – 2002: Deaths increased 35.3%1992 – 2002: Deaths increased 35.3%

Number of patients with HF is expected to double in 30 Number of patients with HF is expected to double in 30 yearsyears

What is a “Typical” Presentation of ADHF?

Median age: 75Median age: 75 HTN: 72%HTN: 72% DM: 44%DM: 44% COPD: 31%COPD: 31% CKD: 30%CKD: 30%

NYHA class at admission:NYHA class at admission:(N=11,555)(N=11,555)

I: I: 2%2% II:II: 11%11% III:III: 40%40% IV:IV: 47%47%

ADHERE Registry: 10/01-1/04ADHERE Registry: 10/01-1/04

What is a “Typical” Presentation of ADHF?

Blood Pressure at admission (N=104,573)Blood Pressure at admission (N=104,573)

<90 mmHg: 2%<90 mmHg: 2% 90-140 mmHg: 48%90-140 mmHg: 48% >140 mmHg: 50%>140 mmHg: 50%

ADHERE Registry: 10/01-1/04ADHERE Registry: 10/01-1/04

They’re Sicker Than We Think

In-hospital: 3%In-hospital: 3%30-day: 7.9%30-day: 7.9%One year: 30%One year: 30%Five years: Five years: 60%60%

Baker, DW et al. Am Heart J 2003; 146(2): 258-64Baker, DW et al. Am Heart J 2003; 146(2): 258-64

Ho KK, et al. Circulation 1993; 88(1): 107-15Ho KK, et al. Circulation 1993; 88(1): 107-15

Jong P, et al. Arch Int Med 2002; 162(15) 1689-94Jong P, et al. Arch Int Med 2002; 162(15) 1689-94

Narang R ,et al. Eur Heart J 1996; 17(9) 1390-1403Narang R ,et al. Eur Heart J 1996; 17(9) 1390-1403

Mortality risk after 1Mortality risk after 1stst hospitalization for ADHF: hospitalization for ADHF:(Age, male gender, ischemia and decreased LVEF worsen prognosis)(Age, male gender, ischemia and decreased LVEF worsen prognosis)

Comparative Five Year Mortality

Adenocarcinoma of the colon (IIIB): 36%Adenocarcinoma of the colon (IIIB): 36% COPD (FEVCOPD (FEV11 30-39% predicted): 53% 30-39% predicted): 53%

ESRD (dialysis-dependent): 60-80%ESRD (dialysis-dependent): 60-80%

Summary

Incidence of ADHF is skyrocketing. Huge strain on Incidence of ADHF is skyrocketing. Huge strain on hospitals and health care financinghospitals and health care financing

Patients are extremely sickPatients are extremely sick There are not enough cardiologists to manage ADHFThere are not enough cardiologists to manage ADHF Generalists will need to become expert in managing all but Generalists will need to become expert in managing all but

the sickest patients with ADHFthe sickest patients with ADHF

Heart Failure: A Vicious Cycle

Myocardial Injury LV dysfunction

Activation of RAS and SNS

Vasoconstriction, TachycardiaSodium/Water Retention

Oxidative stress, IschemiaRemodeling

Hypotension

Renal hypoperfusion

A 2, ADH,aldosteronenorepi, epiANP, BNP

Temporary restoration of BPand renal perfusion

Heart Failure: A Vicious Cycle

Myocardial Injury Decreased LV function

Activation of RAS and SNS

Vasoconstriction,TachycardiaSodium/Water Retention

Oxidative stressRemodeling

Hypotension

Renal hypoperfusion

A 2, ADH,aldosteronenorepi, epiANP, BNP

Temporary restoration of BPand renal perfusion

Pharmacotherapy to Break the Cycle

Myocardial Injury Decreased LV function

Activation of RAS and SNS

Angiotensin II Epi, NorepiAldosterone

VasoconstrictionNa retention

H2O retention Increased CardiacOutput

B-blockerARB

Spironolactone,eplerenone

ACE

Goals of Acute Management

Rapidly improve symptoms while preserving organ Rapidly improve symptoms while preserving organ functionfunction

Restore function to pre-morbid levelsRestore function to pre-morbid levels Educate patient and familyEducate patient and family Initiate therapies/interventions shown to reduce long-term Initiate therapies/interventions shown to reduce long-term

mortalitymortality Control costsControl costs Improve quality of lifeImprove quality of life Reduce mortalityReduce mortality

Vasoactive Therapy for ADHF

Parenteral Drugs for ADHF

DiureticsDiuretics MorphineMorphine Vasodilators: nitroglycerin, nesiritide, enalaprilatVasodilators: nitroglycerin, nesiritide, enalaprilat Afterload reducers: nitroprusside, hydralazineAfterload reducers: nitroprusside, hydralazine Inotropes: dobutamine, milrinone, amrinone, digoxinInotropes: dobutamine, milrinone, amrinone, digoxin

What Does the Literature Tell Us?

Very littleVery little Almost no randomized, placebo-controlled trials of ANY Almost no randomized, placebo-controlled trials of ANY

agent for the management of ADHF.agent for the management of ADHF. ““Standard of care” is based almost entirely upon expert Standard of care” is based almost entirely upon expert

opinion and case studiesopinion and case studies

NoNo YesYes

NoNo

Warm and DryWarm and Dry

CI: NlCI: Nl

PCWP: NlPCWP: Nl

Warm and WetWarm and Wet

CI: NlCI: Nl

PCWP: HighPCWP: High

YesYes

Cold and DryCold and Dry

CI: LowCI: Low

PCWP: NlPCWP: Nl

Cold and WetCold and Wet

CI: LowCI: Low

PCWP: HighPCWP: High

Congestion

Hyp

op

erfu

sio

n

•Diuretics•Vasodilators

•Fluids•Inotropes

•Inotropes•Vasodilators•+/- Diuretics

•Diuretics•Vasodilators•Inotropes

Conceptual Model For ADHFAdapted from Stevenson, LW. Eur J Heart Failure 1999; 1: 251-257

What About Inotropes?Abraham WT, et al. JACC 2005;46(1):57-64.

Retrospective review of 15,230 patients in ADHERE registry Retrospective review of 15,230 patients in ADHERE registry who received milrinone, dobutamine, nitroglycerin or nesiritidewho received milrinone, dobutamine, nitroglycerin or nesiritide

Risk factor and propensity-score adjusted odds ratios for in-Risk factor and propensity-score adjusted odds ratios for in-hospital mortalityhospital mortality

DrugsDrugs Mortality: Odds Mortality: Odds RatioRatio

NTG vs:NTG vs:milrinonemilrinonedobutaminedobutamine

0.69 (0.53-0.89)0.69 (0.53-0.89)

0.46 (0.37-0.57)0.46 (0.37-0.57)

nesritide vs:nesritide vs:milrinonemilrinonedobutaminedobutamine

0.59 (0.48-0.73)0.59 (0.48-0.73)

0.46 (0.39-0.56)0.46 (0.39-0.56)

More Bad News for InotropesCuffe MS, et al. JAMA 2002; 287:1541-47

OPTIME-CHF Trial:OPTIME-CHF Trial: Entry criteria: 951 patients with ADHF and systolic dysfxn Entry criteria: 951 patients with ADHF and systolic dysfxn

who did not require inotropic support.who did not require inotropic support. Intervention: Milrinone or placebo x 48 hoursIntervention: Milrinone or placebo x 48 hours Patients who received Milrinone:Patients who received Milrinone:

Trend to increased deaths in-hospital and after 60 daysTrend to increased deaths in-hospital and after 60 days Trend to higher incidence of worsening HF, Trend to higher incidence of worsening HF,

symptomatic hypotension, new atrial arrhythmiassymptomatic hypotension, new atrial arrhythmias Combined endpoint of death or rehospitalization Combined endpoint of death or rehospitalization

significantly higher in subgroup with ischemia (36% vs significantly higher in subgroup with ischemia (36% vs 42%: p=0.01)42%: p=0.01)

Inotropes: Robbing Peter to Pay Paul?

Pro-arrhythmicPro-arrhythmic Probably increase mortality in ischemic patientsProbably increase mortality in ischemic patients Ischemic/injured myocardium may “hibernate” as a Ischemic/injured myocardium may “hibernate” as a

protective mechanismprotective mechanism Inotropes recruit hibernating myocytes and may hasten Inotropes recruit hibernating myocytes and may hasten

cell injury or apoptosiscell injury or apoptosis Short-term gains appear to be offset by higher mid and Short-term gains appear to be offset by higher mid and

long-term mortalitylong-term mortality

Vasodilators: Overview

I.V. vasodilators are a class IB recommendation for I.V. vasodilators are a class IB recommendation for treatment of ADHFtreatment of ADHF

Beneficial effects:Beneficial effects: Decrease pulmonary vascular congestionDecrease pulmonary vascular congestion Decrease BP and improve the efficiency of cardiac Decrease BP and improve the efficiency of cardiac

workwork Speed symptom reliefSpeed symptom relief Possibly decrease risk for CCU, mechanical ventilationPossibly decrease risk for CCU, mechanical ventilation No RCTsNo RCTs

Eur Heart Journal 2005; 26: 384-416Eur Heart Journal 2005; 26: 384-416

IV Vasoactives StartedIV Vasoactives Started

ED In-patient Unit ED In-patient Unit

(n = 4096) (n = 3499)(n = 4096) (n = 3499)

PP Value Value

Mortality (%)Mortality (%) 4.34.3 10.910.9 <0.0001<0.0001

Hospital LOS (days, median)Hospital LOS (days, median) 4.54.5 7.07.0 <0.0001<0.0001

Transfer to ICU/CCU (%)Transfer to ICU/CCU (%) 44 2020 <0.0001<0.0001

ICU/CCU time (days, median)ICU/CCU time (days, median) 2.12.1 3.03.0 <0.0001<0.0001

Invasive procedure (%)Invasive procedure (%) 1919 2727 <0.0001<0.0001

Prolonged hospitalization Prolonged hospitalization

(>7.1 days, 3(>7.1 days, 3rdrd quartile) quartile)2626 4949 <0.0001<0.0001

Peacock WF, et al. Ann Emerg Med. 2003;42(4):S26.

Emerman C et al. Ann Emerg Med. 2003;42:S36Fonarow GC for ADHERE Scientific Advisory Committee. Rev Cardiovasc Med. 2003;4(suppl 7):S21

Early Initiation of Vasoactive Therapy: Clinical Outcomes

Choices of I.V. Vasodilators

NitroglycerinNitroglycerin NitroprussideNitroprusside ACE inhibitors (enalaprilat)ACE inhibitors (enalaprilat) Morphine?Morphine? Nesiritide (Natrecor)Nesiritide (Natrecor)

Nesiritide: Overview

Recombinant B-naturetic peptideRecombinant B-naturetic peptide BNP is released when myocardium is stretchedBNP is released when myocardium is stretched Effects:Effects:

Natriuresis / diuresisNatriuresis / diuresis Arterial and venous vasodilatationArterial and venous vasodilatation Suppression of RAS and catecholsSuppression of RAS and catechols Indirect increase of cardiac outputIndirect increase of cardiac output

Nesiritide: NSGET TrialColucci W, et al. NEJM 2000; 343(4): 246-53

Open label efficacy trial of 432 patients with ADHF—vast Open label efficacy trial of 432 patients with ADHF—vast majority with NYHA III or IV sxmajority with NYHA III or IV sx

6 hour infusion of nesiritide decreased PCWP and 6 hour infusion of nesiritide decreased PCWP and improved symptomsimproved symptoms

No acute difference when compared with standard No acute difference when compared with standard vasoactive agents (inotropes, nitroglycerin, nitroprusside)vasoactive agents (inotropes, nitroglycerin, nitroprusside)

Not powered to look at outcomes Not powered to look at outcomes Conclusion: “Intravenous nesiritide is useful for the short-Conclusion: “Intravenous nesiritide is useful for the short-

term treatment of decompensated CHF”term treatment of decompensated CHF”

Nesiritide: VMAC TrialJAMA 2002; 287(12) 1531-40

Randomized, placebo-controlled, double-dummy trial. 489 Randomized, placebo-controlled, double-dummy trial. 489 patients, all with NYHA class IV CHF.patients, all with NYHA class IV CHF.

Nesiritide vs nitroglycerin vs placebo x 3 hours, followed Nesiritide vs nitroglycerin vs placebo x 3 hours, followed by nesiritide or NTG x 24 hoursby nesiritide or NTG x 24 hours

Outcomes:Outcomes: Nesiritide decreased PCWP more effectively than NTGNesiritide decreased PCWP more effectively than NTG Nesiritide offered faster symptom reliefNesiritide offered faster symptom relief No difference in outcomes btwn nesiritide and NTGNo difference in outcomes btwn nesiritide and NTG

Not So Fast…Sackner-Bernstein JD, et al. Circulation 2005. 29;111(12):1487-91.

Retrospective review of 1,269 patientsRetrospective review of 1,269 patients Risk of worsening renal function compared to control Risk of worsening renal function compared to control

therapy (inotrope or no inotrope)therapy (inotrope or no inotrope) Results:Results:

High dose nesiritide (<3 mcg/kg/min): (RR 1.54; 95% High dose nesiritide (<3 mcg/kg/min): (RR 1.54; 95% CI, 1.19 to 1.98; P=0.001).CI, 1.19 to 1.98; P=0.001).

Statistically significant effect also noted with any dose Statistically significant effect also noted with any dose nesiritidenesiritide

No differences in mortality or risk of dialysisNo differences in mortality or risk of dialysis

And Then The Kicker…Sackner-Bernstein et al. JAMA 2005;293(15) 1900-1905.

Meta-analysis of 3 randomized nesiritide trials (VMAC, Meta-analysis of 3 randomized nesiritide trials (VMAC, NSGET, PROACTION)NSGET, PROACTION)

Nesiritide vs non-inotrope controls (vasodilators or Nesiritide vs non-inotrope controls (vasodilators or diuretics)diuretics)

Results: 30 day mortality: 7.2% vs 4.0%, P=0.05Results: 30 day mortality: 7.2% vs 4.0%, P=0.0599 Lots of debate over choices of trials and assumptions made Lots of debate over choices of trials and assumptions made

by the authorsby the authors ““As this is not an analysis based on an adequatelyAs this is not an analysis based on an adequately powered powered

prospective trial but rather an analysis pooling dataprospective trial but rather an analysis pooling data from from existing trials, our finding should be viewed as hypothesisexisting trials, our finding should be viewed as hypothesis

generating rather than as conclusive evidence of harm.”generating rather than as conclusive evidence of harm.”

What About the Other Vasodilators?

Are there better choices than nesiritide?Are there better choices than nesiritide?

Nitroglycerin

AdvantagesAdvantages

EffectiveEffective High comfort levelHigh comfort level Established safety profileEstablished safety profile Cost (?)Cost (?)

DisadvantagesDisadvantages

Rapid tachyphylaxisRapid tachyphylaxis Frequently underdosedFrequently underdosed Requires titration in Requires titration in

CCU/IMCUCCU/IMCU Dose-limiting sx (20%)Dose-limiting sx (20%) Limited dataLimited data

Elkayam U, et al. Circulation 1987;76(3):577-84.

Nitroprusside

AdvantagesAdvantages

Afterload reductionAfterload reduction Fine titrationFine titration Useful adjunct to Useful adjunct to

inotropes in cardiogenic inotropes in cardiogenic shockshock

DisadvantagesDisadvantages

ICU and arterial lineICU and arterial line Thiocyanate toxicity (esp Thiocyanate toxicity (esp

in renal/hepatic in renal/hepatic insufficiency)insufficiency)

No randomized trialsNo randomized trials

Nesiritide

AdvantagesAdvantages

Faster than NTGFaster than NTG Easy dosing (no CCU)Easy dosing (no CCU) Few side effectsFew side effects Theoretical hemodynamic Theoretical hemodynamic

and neurohormonal and neurohormonal advantagesadvantages

DisadvantagesDisadvantages

Safety concerns:Safety concerns: MortalityMortality Renal functionRenal function

Cost: $380/dayCost: $380/day

Conclusions

Inotropes may increase mortality and are unnecessary for Inotropes may increase mortality and are unnecessary for the vast majority of class III-IV ADHFthe vast majority of class III-IV ADHF

IV vasodilators are underutilized, especially in “wet” IV vasodilators are underutilized, especially in “wet” patients with preserved BP who do not respond to diureticspatients with preserved BP who do not respond to diuretics

Early initiation of vasodilators Early initiation of vasodilators maymay improve outcomes improve outcomes If you stick with nitroglycerin:If you stick with nitroglycerin:

Rapid dose escalation is often necessaryRapid dose escalation is often necessary Side effects may limit titration and efficacySide effects may limit titration and efficacy Patients must go to CCU or ICUPatients must go to CCU or ICU

Jury is still out on nesiritideJury is still out on nesiritide

Vasodilator Algorithm

Class III or IV ADHFClass III or IV ADHF

ANDAND

preserved BPpreserved BP

Impending resp.Impending resp.

failurefailure

Chest painChest pain

ImmediateImmediate Immediate or earlyImmediate or early

ADHF and HTNADHF and HTN

(? first-line)(? first-line)

ExpectantExpectant

Poor responsePoor response

to diureticsto diuretics

Prevention of Sudden Cardiac Death

Implantable Cardioverter- Defibrillators (ICDs)

ICDs: Rationale

Sudden cardiac death (SCD) is the second most common Sudden cardiac death (SCD) is the second most common cause of death in patients with HF (after pump failure)cause of death in patients with HF (after pump failure)

Antiarrhythmics are ineffective if not outright dangerousAntiarrhythmics are ineffective if not outright dangerous

Despite Proven Benefit, ICDs are Underutilized

4.6 million managed care and Medicare patients 4.6 million managed care and Medicare patients analyzed for diagnosis of SCD and previous MI or analyzed for diagnosis of SCD and previous MI or CHF.CHF.

Estimated 736 to 1,140 ICD candidates per million Estimated 736 to 1,140 ICD candidates per million population.population.

Actual implantations: 416 per million populationActual implantations: 416 per million population Probably even worse for primary preventionProbably even worse for primary prevention

Ruskin JN, et al. J Cardiovasc Electrophysiol. 2002;13(1):38-43.Ruskin JN, et al. J Cardiovasc Electrophysiol. 2002;13(1):38-43.

Primary Prevention Trials

MADIT-IMADIT-I MADIT-IIMADIT-II CABG PatchCABG Patch MUSTTMUSTT DINAMITDINAMIT CATCAT AMIOVERTAMIOVERT

ICDs: MADIT-I

196 patients enrolled196 patients enrolled Entry criteria:Entry criteria:

Prior MI, NSVT, LVEF <35%, EPS: Inducible Prior MI, NSVT, LVEF <35%, EPS: Inducible sustained VT not suppressed with procainamidesustained VT not suppressed with procainamide

Intervention: ICD vs amiodaroneIntervention: ICD vs amiodarone Average survival at 4 years:Average survival at 4 years:

ICD: 3.7 years ICD: 3.7 years Conventional therapy: 2.8 yearsConventional therapy: 2.8 years

Moss AJ, et al. NEJM 1996; 335: 1933

MUSTT

704 patients enrolled704 patients enrolled Entry criteria:Entry criteria:

Prior MI, Inducible VT, LVEF Prior MI, Inducible VT, LVEF <<40%40% Intervention: No therapy vs EPS-guided antiarrhythmic tx Intervention: No therapy vs EPS-guided antiarrhythmic tx

(drug or AICD)(drug or AICD) Outcomes:Outcomes:

Death at 2 years: 12% vs 18%Death at 2 years: 12% vs 18% Death at 5 years: 25% vs 32 %Death at 5 years: 25% vs 32 % Mortality reduction due to ICDs, not medicationMortality reduction due to ICDs, not medication

Buxton AE, et al. Circulation 2002; 106: 2466

MADIT-II

1232 patients enrolled1232 patients enrolled Entry criteria:Entry criteria:

MI >30 days prior to enrollment, LVEF<30%MI >30 days prior to enrollment, LVEF<30% No EPS done. Presence of VT not an entry criterionNo EPS done. Presence of VT not an entry criterion

Intervention: ICD vs conventional therapyIntervention: ICD vs conventional therapy Outcomes:Outcomes:

Prematurely terminatedPrematurely terminated Mortality 14.2% (ICD) vs 19.8% (no ICD)Mortality 14.2% (ICD) vs 19.8% (no ICD) Sudden death 3.8% vs 10.0%Sudden death 3.8% vs 10.0%

Moss AJ, et al. NEJM 2002; 346:877Moss AJ, et al. NEJM 2002; 346:877

SCD-HeFT

2521 patients enrolled 2521 patients enrolled Entry criteria:Entry criteria:

LVEF <35%: ischemic and LVEF <35%: ischemic and nonnonischemic CMPischemic CMP NYHA II or III CHFNYHA II or III CHF

Intervention: ICD, amiodarone or placeboIntervention: ICD, amiodarone or placebo Outcomes:Outcomes: Five year mortality:Five year mortality:

ICD: 29%ICD: 29% Placebo and amiodarone: 36%Placebo and amiodarone: 36% Benefit only seen with LVEF <30%Benefit only seen with LVEF <30%

Bardy, et al. NEJM 2005; 352:225Bardy, et al. NEJM 2005; 352:225

More for Everyone!

Increasingly broad indications for ICDs:Increasingly broad indications for ICDs: Ischemic CMP with inducible VTIschemic CMP with inducible VT Ischemic CMP with or without VTIschemic CMP with or without VT Nonischemic CMPNonischemic CMP

Who Should Get an ICD?

Nonischemic cardiomyopathy:Nonischemic cardiomyopathy: NYHA class II to III sxNYHA class II to III sx LVEF LVEF << 35% 35%

Ischemic cardiomyopathy:Ischemic cardiomyopathy: NYHA class II to III sxNYHA class II to III sx LVEF LVEF << 35% 35% At least 40 days post-MI (DINAMIT)At least 40 days post-MI (DINAMIT) No reversible ischemiaNo reversible ischemia No recent revascularizationNo recent revascularization

Bardy GH et al. NEJM 2005. 20;352(3):225-37.Bardy GH et al. NEJM 2005. 20;352(3):225-37.

ICDs: Other Recommendations

Unclear whether or not ICDs are beneficial in patients with Unclear whether or not ICDs are beneficial in patients with NYHA class IV HFNYHA class IV HF

Waiting period after MI is controversialWaiting period after MI is controversial Amiodarone doesn’t improve survival, but does appear to Amiodarone doesn’t improve survival, but does appear to

decrease number of shocks in patients with ICDsdecrease number of shocks in patients with ICDs Patients who meet criteria should at least be referred to a Patients who meet criteria should at least be referred to a

cardiologist for further evaluationcardiologist for further evaluation

Mechanical Resynchronization

Cardiac Resynchronization Therapy (CRT) What it is:What it is:

Using biventricular pacing to re-synchronize LV and RV Using biventricular pacing to re-synchronize LV and RV contraction in patients with HF and IVCDcontraction in patients with HF and IVCD

Rationale:Rationale: IVCD and LBBB worsen HF by causing ventricular IVCD and LBBB worsen HF by causing ventricular

dyssynchronydyssynchrony Patients with HF and IVCD/BBB have increased sx and Patients with HF and IVCD/BBB have increased sx and

worse outcomes than patients with normal ventricular worse outcomes than patients with normal ventricular conduction.conduction.

Dual-chamber pacing is associated with poor outcomes.Dual-chamber pacing is associated with poor outcomes.

Biventricular Pacer

Coronary sinus (LV) lead

RV lead

CRT: Outcomes

Meta-analysis of 3216 patientsMeta-analysis of 3216 patients Increased likelihood of improving at least one NYHA class Increased likelihood of improving at least one NYHA class

(58% vs 37%)(58% vs 37%) Reduced hospitalization for CHF (RR 0.65) for patients Reduced hospitalization for CHF (RR 0.65) for patients

with NYHA III or IV CHFwith NYHA III or IV CHF Reduced mortality (RR 0.79) due to fewer deaths from Reduced mortality (RR 0.79) due to fewer deaths from

progressive HFprogressive HF

McCalister FA, et al. Ann Int Med 2004; 141:381-390.McCalister FA, et al. Ann Int Med 2004; 141:381-390.

CRT: CARE-HF Trial

Randomized, controlled trial of 813 patientsRandomized, controlled trial of 813 patients Entry criteria:Entry criteria:

IVCDIVCD NYHA III or IV CHFNYHA III or IV CHF LVEF <35%LVEF <35%

Outcomes:Outcomes: Decreased mortality: 8.1% vs 13.9% at 29 monthsDecreased mortality: 8.1% vs 13.9% at 29 months At 90 days: Improved quality of life (NYHA class 2.1 vs At 90 days: Improved quality of life (NYHA class 2.1 vs

2.7)2.7)

Cleland JGF, et al. NEJM 2005; 352(15):1539-1549

CRT: Recommendations

Indicated for patients with LBBB or IVCD and:Indicated for patients with LBBB or IVCD and: LVEF < 35%LVEF < 35% Sinus rhythmSinus rhythm NYHA III-IV symptoms despite optimal medical mgmtNYHA III-IV symptoms despite optimal medical mgmt

These patients are also candidates for ICD placement and These patients are also candidates for ICD placement and

shouldshould be considered for a dual-function device.be considered for a dual-function device.

J Am Coll Cardiol. 2005 Sep 20;46(6):1116-43.

Neurohormonal Modulation in the Hospital

Acute Use of Beta Blockers:Cognitive Dissonance?

Chronic use of beta blockers clearly shown to decrease Chronic use of beta blockers clearly shown to decrease mortalitymortality

All studies initiated therapy in patients with All studies initiated therapy in patients with stablestable patients, patients, most of whom had class II-III CHFmost of whom had class II-III CHF

Starting beta-blockers in decompensated patients is risky.Starting beta-blockers in decompensated patients is risky.

But…But… Initiation of beta blockers a quality measure, especially Initiation of beta blockers a quality measure, especially

post-MIpost-MI If we don’t start therapy in the hospital, will the ball get If we don’t start therapy in the hospital, will the ball get

dropped?dropped?

Bristow, MR et al. Circulation 1996;94:2807-2816

MOCHA: six-month crude mortality as deaths per randomized patientsx100

Dose-Response Effect of Carvedilol

Beta Blockers Are Not Equal

Four beta-blockers shown to decrease mortality in systolic Four beta-blockers shown to decrease mortality in systolic HF:HF:

CarvedilolCarvedilol MetoprololMetoprolol BisoprololBisoprolol BucindololBucindolol

COMET Trial: Carvedilol vs MetoprololPoole- Wilson PA, et al. Lancet 2003; 362: 7-13

Multicenter, randomized, controlled trial of 3,029 patientsMulticenter, randomized, controlled trial of 3,029 patients—mean study duration: 58 months—mean study duration: 58 months

Entry criteria:Entry criteria: NYHA II- IV CHFNYHA II- IV CHF LVEF <35%LVEF <35% Previous admission for ADHFPrevious admission for ADHF

Intervention:Intervention: Metoprolol (target dose: 50 mg bid)Metoprolol (target dose: 50 mg bid) Carvedilol (target dose: 25 mg bid)Carvedilol (target dose: 25 mg bid)

COMET: Mortality

39.50%

33.90%

0%

10%

20%

30%

40%

50%

Metoprolol Carvedilol

MetoprololCarvedilol

Huge Cost Differential

One month supply at doses per COMET Trial:One month supply at doses per COMET Trial:

AWP (drugstore.com)AWP (drugstore.com)

Metoprolol tartrate (50 mg bid) $12.09Metoprolol tartrate (50 mg bid) $12.09 Carvedilol (25 mg bid) $95.00Carvedilol (25 mg bid) $95.00

Beta Blockers: Bottom Line

Most of the benefit from carvedilol occurs at low doseMost of the benefit from carvedilol occurs at low dose It’s probably reasonable to start beta-blockers in-house, It’s probably reasonable to start beta-blockers in-house,

especially if patient is hypertensiveespecially if patient is hypertensive In non-hypertensive and elderly patients: Start low and In non-hypertensive and elderly patients: Start low and

titrate slowlytitrate slowly Metoprolol is good, but carvedilol is betterMetoprolol is good, but carvedilol is better Many patients cannot afford carvedilolMany patients cannot afford carvedilol

Conclusions

Acute and chronic HF may be the single most common Acute and chronic HF may be the single most common inpatient dx managed by hospitalists/internistsinpatient dx managed by hospitalists/internists

Economic burden is huge and growingEconomic burden is huge and growing Consider vasodilators in patients with ADHF, preserved BP.Consider vasodilators in patients with ADHF, preserved BP. Inotropes should be reserved for patients with hypotension Inotropes should be reserved for patients with hypotension

and evidence of end-organ hypoperfusion.and evidence of end-organ hypoperfusion. Think ICD in any patient with symptomatic HF, EF <35% Think ICD in any patient with symptomatic HF, EF <35%

and no reversible etiology.and no reversible etiology. Think CRT for patients with EF <35%, IVCD and sx not Think CRT for patients with EF <35%, IVCD and sx not

improved with medical therapyimproved with medical therapy Choose the right beta-blocker and titrate slowly in-houseChoose the right beta-blocker and titrate slowly in-house