Contemporary Management of Diabetic Diabetes Cardiomyopathy - - PDF document

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Contemporary Management of Systolic Heart Failure

William T. Abraham, MD, FACP, FACC, FAHA

Professor of Medicine, Physiology, and Cell Biology Director, Division of Cardiovascular Medicine The Ohio State University Columbus, Ohio

Heart Failure Background

• Heart failure (HF) is a major public health problem

resulting in substantial morbidity and mortality

• 1/3 of pts with HF are hospitalized annually
• Major cost-driver of HF is high incidence of

hospitalizations1,2

• Despite treatment advances, large number of eligible

patients are not receiving optimal care

1American Heart Association. 2006 Heart and Stroke Statistical Update. Dallas, Tex: American Heart Association; 2002. 2Hunt SA et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. 2005.

$29.6 billion 1,100,000 50% at 5 years 550,000 5,000,000 Total population Cost Hospital Discharges Mortality Incidence Prevalence Population Group

1 Adapted with permission from: Vasan RS et al. Arch Intern Med. 1996;156:1790.

Two Types of Heart Failure

HTN

Smoking Lipids Diabetes Obesity Insulin Resistance

MI LVH

Normal LV Structure and Function LV Remodeling Subclinical LVD Overt HF

Diastolic Dysfunction Systolic Dysfunction HF

Diabetes Diabetic Cardiomyopathy

Determinants of Cardiac Performance

• Preload
• Afterload
• Heart Rate
• Contractility

Force, # of Contractile Units

• Ventricular (diastolic) Compliance

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• Based on Starling's observation that the mechanical energy released

between the resting and contracted state is a function of the resting muscle fiber length in isolated heart tissue.

• In the whole heart, preload is synonymous with end-diastolic volume.
• Practically, preload is estimated by the end-diastolic pressure

(the pulmonary capillary wedge pressure).

• Increases in preload, or end-diastolic pressure, are associated with

increases in both the extent and velocity of muscle fiber shortening, which combine to produce an increase in stroke volume.

• Failing hearts are less responsive to changes in preload.

Preload

Nonfailing Failing

Ventricular Performance Ventricular End-Diastolic Volume

Starling Curves for Failing and Nonfailing Hearts

Afterload

• The stress or tension distributed in the ventricular

wall during ventricular ejection.

• Afterload is not constant during ejection but

continually declines as ventricular volume and mid wall radius decrease.

• Inversely related to the velocity and extent of mid

wall shortening.

• The sum of forces contributing to ventricular

afterload are referred to as inpedance, which includes the resistance of small arteries and arterioles, the compliance of the large arteries, the viscosity of blood, and the forces of inertia.

Nonfailing Failing

Stroke Volume Aortic Impedance

Effects of Ventricular Afterload on Failing and Nonfailing Hearts

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RAS, renin-angiotensin system; SNS, sympathetic nervous system.

Heart failure symptoms

Pathophysiology of Heart Failure

Myocardial injury to the heart (MI, HTN, CMP, Valvular disease)

Morbidity and mortality Arrhythmias Pump failure Hemodynamic alterations Salt & water retention Remodeling and progressive worsening of LV function

Initial fall in LV performance, ↑ wall stress

Activation of RAS and SNS Fibrosis, apoptosis, hypertrophy, cellular/ molecular alterations, myotoxicity Dyspnea Edema Fatigue

Risk Factors

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic HF

Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

Class III

Risk ≥ Benefit No additional studies needed Procedure or treatment should NOT be performed or administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

Class IIb

Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure or treatment MAY BE CONSIDERED

Class IIa

Benefit >> Risk Additional studies with focused

• bjectives needed

IT IS REASONABLE to perform procedure

• r administer

treatment

Class I

Benefit >>> Risk Procedure or treatment SHOULD be performed or administered

AHA/ACC Applying Classification of Recommendations and Level of Evidence

Hunt SA et al. J Am Coll Cardiol. 2005

A: Multiple randomized controlled trials B: Single trial, non-randomized studies C: Expert opinion Level of Evidence

ACE Inhibitors

4 Effect of ACE Inhibitors on Mortality Reduction in Patients With Heart Failure

Trial ACEI Controls RR (95% CI) CONSENSUS I SOLVD (Treatment) SOLVD (Prevention) Chronic CHF Post-MI SAVE TRACE AIRE 39% 54% 0.56 (0.34–0.91) 40% 35% 0.82 (0.70–0.97) 15% 16% 0.92 (0.79–1.08) 25% 20% 0.81 (0.68–0.97) 17% 23% 0.73 (0.60–0.89) Average 0.78 (0.67–0.91) 35% 42% 23% 27%

Mortality

Data shown from individual trials—not direct comparison data. Garg R et al. JAMA. 1995;273:1450–1456. Pfeffer MA et al. N Engl J Med. 1992;327:669–677. The AIRE Study Investigators. Lancet. 1993;342:821–828. Køber L et al. N Engl J Med. 1995;333:1670–1676. The SOLVD Investigators. N Engl J Med. 1992;327:685–691.

ACE Inhibitor Recommendations

• Recommended for all pts with current or prior

symptoms of HF and reduced LVEF, unless contraindicated

• Indicated in all pts with a recent or remote history of

MI regardless of LVEF or presence of HF

• Should be used in pts with a reduced LVEF and no

symptoms of HF, even if they have not experienced an MI

• Can be useful to prevent HF in pts at risk for

developing HF with a history of atherosclerotic vascular disease, DM, or HTN with associated risk factors

• Can be beneficial in patients with HTN and LVH and

no symptoms of HF I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

MI=myocardial infarction; LVEF=ejection fraction; DM=diabetes mellitus; HTN=hypertension; LVH=left ventricular hypertrophy. Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

• Indicated for all patients with asymptomatic LV

dysfunction and for Class I to IV Heart Failure. (Contraindications: hyperkalemia, angioedema, pregnancy)

• Start at low dose and titrate to target doses

(example enalapril 10 mg bid, lisinopril 20 qd, ramipril 10 mg qd, benazepril 40 qd)

• Renal insufficiency is not a contraindication but

must start at very low dose and very closely monitor

• Monitor serum potassium and renal function.

Advise checking chemistry panel 1-2 weeks after first dose.

ACE Inhibition in Heart Failure

Hunt SA, et al. ACC/AHA 2005 Practice Guidelines

Beta-Blockers

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Target HF Dosage Study Drug Severity (mg) Outcome

US Carvedilol1 carvedilol mild/ 6.25-25 ↓48% disease progression† moderate BID (P=.007) CIBIS-II2 bisoprolol moderate/ 10 QD ↓34% mortality severe (P<.0001) MERIT-HF3 metoprolol mild/ 200 QD ↓34% mortality succinate moderate (P=.0062) COPERNICUS4 carvedilol severe 25 BID ↓35% mortality (P=.0014) CAPRICORN5 carvedilol Post-MI LVD 25 BID ↓23% mortality (P=.031)

Effect of β-Blockade on Outcome in Patients With HF and Post-MI LVD

β-Blockers Differ in Their Long- Term Effects on Mortality in HF

Bisoprolol1 Bucindolol2 Carvedilol3-5 Metoprolol tartrate6 Metoprolol succinate7 Nebivolol8 Xamoterol9 Beneficial No effect Beneficial Not well studied Beneficial No effect Harmful

344:1659-1667. 3Colucci WS, et al. Circulation 1996;94:2800-2806. 4Packer M, et al. N Engl J Med 2001;344:1651-1658. 5The CAPRICORN Investigators. Lancet. 2001;357:1385-1390. 6Waagstein F, et al. Lancet. 1993;342:1441-1446. 7MERIT-HF Study Group.

• Lancet. 1999;353:2001-2007. 8SENIORS Study Group. Eur Heart J. 2005; 26:215-225.

Time (years)

Mortality (%) Carvedilol Metoprolol Tartrate 10 20 30 40 1 2 3 4 5

Risk Reduction ↓ 17% P=.0017 Mortality rates: metoprolol 40%; Carvedilol 34%.

COMET: Primary Endpoint

• f Mortality

Poole-Wilson PA, et al. Lancet. 2003;362:7-13. Metoprolol tartrate mean dose: 85 mg QD; Carvedilol mean dose: 42 mg QD.

Extrapolation from the survival curves suggested that carvedilol extended median survival by 1.4 years as compared with metoprolol tartrate †

Βeta-Blocker Recommendations

• Use of 1 of the 3 beta blockers proven to reduce

mortality (i.e. bisoprolol, carvedilol, and sustained release metoprolol succinate) are recommended for all stable pts with current or prior symptoms of HF and reduced LVEF, unless contraindicated

• Indicated in all pts with a recent or remote history
• f MI regardless of EF or presence of HF
• Indicated in all patients without a history of MI

who have a reduced LVEF with no HF symptoms I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

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Beta Blocker Therapy in Heart Failure

• Indicated for all patients with asymptomatic LVD

dysfunction and for Class I to IV Heart Failure with LVEF < 0.40

• Contraindications: cardiogenic shock, severe

reactive airway disease, 2/3rd degree HB

• Use evidence-based beta blockers in HF:

carvedilol, metroprolol succinate, bisoprolol

• Start at very low HF doses and up-titrate to target

doses at two week intervals, or highest dose short

• f target dose that is well tolerated
• Monitor HR and BP

Hunt SA et al. J Am Coll Cardiol. 2005.

Angiotensin Receptor Blockers

CHARM and Val-HeFT Trials

• Addition of candesartan1 or valsartan2 to ACEI

and β-blocker in NYHA functional Class II-III

• 0%-10% lower risk of death (P>.05)
• 13%-15% lower risk of death or hospitalization

for HF in both trials (both P<.01)

• Higher risk for hypotension, renal

insufficiency, and hyperkalemia with ARB treatment

VALIANT: ACE Inhibitor, Angiotensin Receptor Blocker, or Both in Post-MI LVD

Pfeffer MA et al., N Engl J Med 2003; 349:1893-1906

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ARB Recommendations

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

• ARBs approved for the treatment of HF are recommended

in patients with current or prior symptoms of HF and reduced LVEF who are ACEI-intolerant

• An ARB should be administered to post-MI patients

without HF who are ACEI-intolerant and have a low LVEF

• Are reasonable to use as alternatives to ACEI as first-line

therapy for pts with mild to moderate HF and reduced LVEF, especially for pts already taking ARBs for other indications

• Can be beneficial in pts with low LVEF and no symptoms
• f HF who are ACEI-intolerant
• Addition of an ARB may be considered in persistently

symptomatic pts with reduced LVEF who are already being treated with conventional therapy I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Aldosterone Antagonists

RALES: Aldosterone Antagonist Reduces All-Cause Mortality in Chronic HF*

*Ejection fraction ≤35% Class III or IV symptoms at some point in prior 2 months.

Spironolactone (25 mg) + standard care (n = 822) Placebo + standard care (n = 841) Probability of Survival (%)

1.00 0.95 0.90 0.85 0.80 0.75 0.70 0.65 0.60 0.55 0.50 3 6 9 12 15 18 21 24 27

Months

HR = 0.70 (95% CI, 0.60 to 0.82)

0.45 30 33 36

P<.001

Pitt B et al. N Engl J Med. 1999;341:709-717. HR = hazard ratio; RR = risk reduction.

EPHESUS Co-Primary Endpoint: Total Mortality

Adapted from Pitt B et al. N Engl J Med. 2003;348:1309-1321.

Eplerenone + standard care (n = 3319) Placebo + standard care (n = 3313) Cumulative Incidence (%)

22 20 18 16 14 12 10 8 6 4 2 3 6 9 12 15 18 21 24 27

Months Since Randomization

HR = 0.85 (95% CI, 0.75 to 0.96) P = .008 (16.7%) (14.4%)

HR = hazard ratio.

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Aldosterone Antagonist Recommendations

• Recommended in selected pts with moderately

severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration.*

• Under circumstances where monitoring for

hyperkalemia and renal dysfunction is not anticipated to be feasible, the risks may

• utweigh the benefits.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

*Creatinine <2.5 mg/dL in men or <2.0 mg/dL in women and K+ <5.0 mEq/L Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

• Indicated for patients with moderately severe and severe HF

due to LVD (LVEF < 0.40). Contraindications: hyperkalemia, Cr > 2.5 in men and > 2.0 in women)

• Spironolactone 12.5 mg PO qd starting dose (or 6.25 mg in

higher risk patients) or Eplerenone 25 mg qd. Decrease potassium supplementation and loop diuretic dose at time of initiation.

• Critical to very closely monitor serum potassium and renal
• function. Advise checking chemistry panel at 48 hours, 1

week, and 4 weeks.

• Advance Spironolactone dose at 4 weeks to 25 mg PO qd or

Eplerenone 50 mg which is the target dose. Avoid higher doses due to risk of hyperkalemia.

Aldosterone Antagonists in Heart Failure

Hunt SA et al. J Am Coll Cardiol. 2005

Digoxin

Digoxin Placebo

4 8 12 16 20 24 28 32 36 40 44 48 52 10 20 30 40 50

Relative Risk 0.99 95% CI 0.91–1.07 P=.80 All-cause mortality rates: Placebo 35.1%; Digoxin 34.8% Mortality From Any Cause (%) Months

Number of patients at risk: Placebo 3,4033,2393,1052,9762,8682,7582,6522,5512,2051,8811,5061,168734339 Digoxin 3,3973,2693,1443,0192,8822,7592,6442,5312,1841,8401,4751,156737335

CV Mortality 0% HF Hospitalizations 28% Total Hospitalizations 6%

Effect of Digoxin on Mortality in Heart Failure: The Digitalis Investigation Group

DIG (Digitalis Investigation Group): 6,800 patients with LVEF <45% randomized to digoxin (n=3,403) or placebo (n=3,397) in addition to therapy with diuretics and ACEI followed for 37 months. The DIGITALIS Investigation Group. N Engl J Med. 1997;336:525–532.

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Digoxin Recommendations

• Digitalis can be beneficial in patients with current or

prior symptoms of HF and reduced LVEF to decrease hospitalizations for HF.

Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Special Populations

HYD/ISDN Placebo Cumulative Mortality Months

0% 10% 20% 30% 40% 50% 60% 70% 80% 42 54 66 6 18 30

Non-African Americans African Americans

Months

42 54 66 6 18 30 0% 10% 20% 30% 40% 50% 60% 70% 80%

Cumulative Mortality

n=324 n=128 Relative Risk Reduction 47%; P=.04 HYD/ISDN Superior

HYD/ISDN=hydralazine/isosorbide dinitrate. Carson P, et al. J Card Fail. 1999;5:178-187.

V-HeFT I: Survival Benefit in Subgroups

500

Days Since Baseline Visit Date Fixed-dose I/H 518 463 407 359 313 251 13 Placebo 532 466 401 340 285 232 24

A-HeFT: All-Cause Mortality

Taylor AL, et al. N Engl J Med. 2004;351:2049-2057.

100 200 300 400 600 85 90 95 100

Survival (%) P=.01 Fixed-dose Hydralazine / Isosorbide Dinitrate Placebo Hazard ratio=.57

43% Decrease in Mortality

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Combination Hydralazine- Nitrate Recommendations

• Addition to a standard medical regimen for HF,

including ACEIs and β−blockers is reasonable and can be effective in blacks with NYHA functional class III or IV HF. Others may benefit similarly, but this has not yet been tested.

• Addition is reasonable in pts with reduced LVEF

who are already taking an ACEI and β-blocker for symptomatic HF and who have persistent symptoms

• Might be reasonable in pts with current or prior

symptoms of HF and reduced LVEF who cannot be given an ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency

Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Device Therapy for Heart Failure

Cardiac resynchronization therapy (CRT) Implantable cardioverter-defibrillators (ICD)

Cardiac Resynchronization Therapy: Weight of Evidence

• > 4,000 patients evaluated in randomized controlled

trials

• Consistent improvement in quality of life, functional

status, and exercise capacity

• Strong evidence of reverse remodeling

↓ LV volumes and dimensions ↑ LVEF ↓ Mitral regurgitation

• Reduction in HF and all-cause morbidity and

mortality

Abraham WT. Circulation. 2003;108:2596-2603.

CARE-HF: Effect of CRT Without an ICD on All-Cause Mortality

5 71 192 321 365 404 Medical Rx 8 89 213 351 376 409 CRT plus meds Number at risk

500 1,000 1,500 .25 .50 .75 1.00

Event-Free Survival Medical Therapy

HR: 0.64 (95% CI: 0.48-0.85) P=.0019

CRT

Cleland JG, et al. N Engl J Med. 2005:352;1539-1549. Days

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CRT Recommendations

Recommended in patients with LVEF less than or equal to 35%, sinus rhythm, NYHA functional class III or ambulatory class IV symptoms despite recommended, optimal medical therapy and who have cardiac dyssynchrony (QRS duration greater than 120 ms) unless contraindicated

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org. 19.8% 14.2% 19.0% 12.0% 14.1% 7.9% 28.8% 22.0%

0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% % Mortality MADIT II COMPANION DEFINITE SCD-HeFT Control Therapy

SCD-HeFT and Other ICD Device Trials in HF

0.77 0.66 0.64 0.69 Hazard Ratio 45 months 24 months 12 months 20 months Follow-Up 2521 458 1520 1232

• No. Pts

< 35% < 35% < 35% < 30% LVEF II/III (71%/29%) I/II/III (20%/60%/20%) III/IV (87%/13%) I/II/III (35%/35%/30%) NYHA Class Ischemic: 52% Non-ischemic:48% Non-ischemic: 100% Ischemic: 59% Non-ischemic:41% Ischemic: 100% HF Etiology

P=0.007 P=0.065 P=0.004 P=0.016

ICD Recommendations*

• Recommended as secondary prevention to prolong

survival in pts with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, VF, or hemodynamically unstable VT

• Recommended for primary prevention to reduce

total mortality by a reduction in SCD in pts with ischemic heart disease who are at least 40 days post-MI, LVEF less than or equal to 30%, with NYHA functional class II or III symptoms*

• Recommended for primary prevention to reduce

total mortality by a reduction in SCD in pts with nonischemic cardiomyopathy, LVEF less than or equal to 30%, with NYHA functional class II or III symptoms* I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

*While undergoing chronic optimal medical therapy with reasonable expectation of survival with good functional status >1 year. Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

• Reasonable in pts with ischemic cardiomyopathy

who are at least 40 days post-MI, LVEF less than or equal to 30%, with NYHA functional class I symptoms

• Reasonable in pts with LVEF of 30% to 35% of any
• rigin with NYHA functional class II or III symptoms
• Might be considered in pts without HF who have

non-ischemic cardiomyopathy and an LVEF less than or equal to 30%, with NYHA functional class I symptoms

*For patients undergoing chronic optimal medical therapy with reasonable expectation of survival with good functional status >1 year. Underlining represents changes from 2001 guidelines. Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

ICD Recommendations*

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Evidence-Based Treatment Across the Continuum of LVD and Heart Failure

Assessment of volume status Titrate ACE and βb therapy Diuretic (Titrate to optivolemic state_ S&S of fluid retention In selected pts, aldo antagonists, Dig, hydralazine/nitrate

EF still < 35%

NYHA II-IV or EF < 30%; Post MI NYHA I NYHA II-IV, EF < 35%, QRS > 120ms

ICD CRT + D

EF < 40%

Summary Advances in the Treatment of HF

• Increased attention to prevention
• ACEI / β-blocker / aldosterone antagonist

combination established as the “triad” of therapy

• Evidence that β-blockers’ effects are not

homogeneous

• Downgrade in recommendation for use of digoxin
• Recognition that “special populations” of HF

patients may benefit from or require different approaches

• New strategies to improve utilization of evidence

based therapies