Guideline Recommended Approach to the Evaluation and Management of Heart Failure William T. Abraham, MD, FACP, FACC Professor of Medicine Chief, Division.

Guideline Recommended Approach tothe Evaluation and Management of

Heart Failure

William T. Abraham, MD, FACP, FACCProfessor of Medicine

Chief, Division of Cardiovascular MedicineAssociate Director, Davis Heart & Lung Research Institute

The Ohio State UniversityColumbus, Ohio

Heart FailureAt Risk for Heart Failure

Therapy: Goals

• All measures under Stage A

Therapy: Drugs

• ACEI or ARB in appropriate patients

• -blockers in appropriate patients

Therapy: Goals• All measures under Stages

A, B, and C• Discussion re: appropriate

level of careTherapy: Options• Compassionate end-of-life

care/hospice• Extraordinary measures

• Heart transplant• Chronic inotropes• Permanent

mechanical support• Experimental surgery

or drugs


A and B• Dietary salt restrictionTherapy: Drugs—Routine• Diuretics for fluid retention• ACEIs • -blockersTherapy: Drugs—Select Pts• Aldosterone antagonist• ARBs• Digitalis• Hydralazine/nitratesTherapy: Devices—Select Pts• Biventricular pacing• Implantable defibrillators

ACC/AHA 2005 Guideline: HF Stages

Stage AAt high risk for HF but without structural heart disease or Sx of HF

Stage BStructural heart disease but without Sx of HF

Stage CStructural heart disease with prior or current Sx of HF

Stage DRefractory HF requiring specialized inter-ventions

Therapy: Goals

• Treat hypertension

• Encourage smoking cessation

• Treat lipid disorders

• Encourage regular exercise

• Discourage alcohol intake, illicit drug use

• Control metabolic syndrome

Therapy: Drugs

• ACEI or ARB in appropriate patients for vascular disease or diabetes

Therapy: Goals• All measures under Stages A, B, and

C• Discussion re: appropriate level of

careTherapy: Options• Compassionate end-of-life

care/hospice• Extraordinary measures

• Heart transplant• Chronic inotropes• Permanent mechanical support• Experimental surgery or drugs

Therapy: Goals

• All measures under Stage A

Therapy: Drugs

• ACEI or ARB in appropriate patients

• -blockers in appropriate patients

Therapy: Goals

• Treat hypertension

• Encourage smoking cessation

• Treat lipid disorders

• Encourage regular exercise

• Discourage alcohol intake, illicit drug use

• Control metabolic syndrome

Therapy: Drugs

• ACEI or ARB in appropriate patients for vascular disease or diabetes


A and B• Dietary salt restrictionTherapy: Drugs—Routine• Diuretics for fluid retention• ACEIs • -blockersTherapy: Drugs—Select Pts• Aldosterone antagonist• ARBs• Digitalis• Hydralazine/nitratesTherapy: Devices—Select Pts• Biventricular pacing• Implantable defibrillators

Hunt SA, Abraham WT, Chin MH, et al, J Am Coll Cardiol, 2005

Heart Failure Prevention

A careful and thorough clinical assessment, with appropriate investigation for known or potential risk factors, is recommended in an effort to prevent development of LV remodeling, cardiac dysfunction, and HF.

Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122

HF Risk Factor Treatment Goals

Risk Factor Goal

Hypertension Generally < 130/80

Diabetes See ADA guidelines

Hyperlipidemia See NCEP guidelines

Inactivity 20-30 min. aerobic 3-5 x wk.

Obesity Weight reduction < 30 BMI

Alcohol Men ≤ 2 drinks/day, women ≤ 1

Smoking Cessation

Dietary Sodium Maximum 2-3 g/day


Treating Hypertension to Prevent HF

• Aggressive blood pressure control:

• Aggressive BP control in patients with prior MI:

Decreasesrisk of new HF

by ~ 80%


by ~ 50%56% in DM2


by ~ 50%56% in DM2

Lancet 1991;338:1281:1281-5 (STOP-HypertensionJAMA 1997;278:212-6 (SHEP)UKPDS Group. UKPDS 38. BMJ 1998;317:703-713

Prevention: ACEI and Beta Blockers

• ACE inhibitors are recommended for prevention of HF in patients at high risk for this syndrome, including those with:• Coronary artery disease• Peripheral vascular disease• Stroke• Diabetes and another major risk factor

• ACE inhibitors and beta blockers are recommended for all patients with prior MI


Management of Patients with Known Atherosclerotic Disease But No HF

• Treatment with ACE inhibitors decreases the risk of CV death, MI, stroke, or cardiac arrest

0

5

10

15

20

0 1 2 3 4

Years

% MI,Stroke,

CV Death

0

3

6

9

12

15

0 1 2 3 4 5

Years

% MI, CV Death,

Cardiac Arrest

Placebo

Ramipril

Placebo

Perindopril

20% rel. risk red. p = .0003

22% rel. risk red. p < .001

HOPE

EUROPA

NEJM 2000;342:145-53 (HOPE)

Lancet 2003;362:782-8 (EUROPA)

Treatment of Post-MI Patients with Asymptomatic LV Dysfunction (LVEF ≤ 40%)

• SAVE Study

• All-cause mortality ↓19%

• CV mortality ↓21%• HF development ↓37%• Recurrent MI ↓25%

0

0.1

0.2

0.3

0 0.5 1 1.5 2 2.5 3 3.5 4

Placebo

Captopril

Years

MortalityRate

19% rel. risk reduction

p = 0.019

Pfeffer et al. NEJM 1992;327:669-77

The Additional Value of Beta Blockers Post-MI: CAPRICORN

• Studied impact of beta blocker (carvedilol) on post-MI patients with LVEF ≤ 40% already receiving contemporary treatments, including revascularization, anticoagulants, ASA, and ACEI:• All-cause mortality reduced (HR = 0.077; p = 0.03)• Cardiovascular mortality reduced

(HR = 0.75; p = .024)• Recurrent non-fatal MIs reduced (HR =.59; p = .014)

Dargie HJ. Lancet 2001;357:1385-90

Heart Failure Patient Evaluation

• Recommended evaluation for patients with a diagnosis of HF:

• Assess clinical severity and functional limitation by history, physical examination, and determination of functional class*

• Assess cardiac structure and function

• Determine the etiology of HF

• Evaluate for coronary disease and myocardial ischemia

• Evaluate the risk of life threatening arrhythmia

• Identify any exacerbating factors for HF

• Identify co-morbidities which influence therapy

• Identify barriers to adherence and compliance

*Metrics to consider include the 6-minute walk test and NYHA functional class


Evaluation: Follow Up Assessments

• Recommended Components of Follow-Up Visits

• Signs and symptoms evaluated during initial visit

• Functional capacity and activity level

• Changes in body weight

• Patient understanding of and compliance with dietary sodium restriction

• Patient understanding of and compliance with medical regimen

• History of arrhythmia, syncope, pre-syncope or palpitation

• Compliance and response to therapeutic interventions

• Exacerbating factors for HF, including worsening ischemic heart disease, hypertension, and new or worsening valvular disease


Rationale for Evidence-Based Drug Selection in Heart Failure

• Within drug classes, agents may differ pharmacologically

• These pharmacological differences may translate into differences in clinical outcomes

• When multiple agents within a class produce discordant results on clinical outcomes, class effect cannot be presumed (e.g., -blockers)

Hunt SA, Abraham WT, Chin MH, et al., Circulation and JACC, Sept. 2005Available beginning August 15, 2005 at www.acc.org and www.americanheart.org.

http://www.acc.org/

http://www.americanheart.org/

TargetHF 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% mortalitysevere (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)

1Colucci WS, et al. Circulation. 1996;94:2800-2806. 2CIBIS II Investigators and Committees. Lancet. 1999;353:9-13. 3MERIT-HF Study Group. Lancet. 1999;353:2001-2007. 4Packer M, et al. N Engl J Med. 2001;344:1651-1658. 5The CAPRICORN Investigators. Lancet. 2001;357:1385-1390.

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

-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

No effect

Beneficial

No effect

Harmful

1CIBIS II Investigators and Committees. Lancet. 1999;353:9-13. 2The BEST Investigators. N Engl J Med 2001; 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. 9The Xamoterol in Severe heart Failure Study Group. Lancet. 1990;336:1-6.

COMET: Primary Endpoint of Mortality

Poole-Wilson PA, et al. Lancet. 2003;362:7-13.

Metoprolol mean dose: 85 mg QD; Coreg mean dose: 42 mg QD.

Time (years)

Mo

rtal

ity

(%)

Carvedilol

MetoprololTartrate

0

10

20

30

40

0 1 2 3 4 5

Risk Reduction 17%

(7%, 26%)

P=.0017

Metoprolol Tartrate 1,359 1,234 1,105 933 3521,518

1,366 1,259 1,155 1,002 383Carvedilol 1,511

Number at Risk:

Mortality rates: metoprolol 40%; carvedilol 34%.

-Blockers: Stage C Heart Failure

• Class I Indication: -blockers (using 1 of 3 proven to reduce mortality, ie, bisoprolol, carvedilol, and sustained-release metoprolol succinate) are recommended for all stable patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated Level of Evidence: A


http://www.acc.org/


1Pfeffer MA, et al. Lancet. 2003;362:759-766. 2Cohn JN, et al. N Engl J Med. 2001;345:1667-1675.

CHARM and Val-HeFT Trials

• Addition of candesartan1 or valsartan2 to ACEI and -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

Months

Pro

bab

ility

of

Eve

nt

Valsartan Valsartan captopril Captopril

0 6 12 18 24 30 360

.1

.2

.3

.4

Valsartan 4,464 4,272 4,007 2,648 1,4374,909

4,414 4,265 3,994 2,648 1,435Valsartan captopril 4,885

Number at Risk:

4,428 4,241 4,018 2,635 1,432Captopril 4,909

357

382

364

3,921 3,667 3,391 2,188 1,2044,909

3,887 3,646 3,391 2,221 1,1854,885

3,896 3,610 3,355 2,155 1,1484,909

290

313

295

1Pfeffer MA et al. N Engl J Med. 2003;349:1893-1906.

Death From Any CauseCombined Cardiovascular

End Point

0 6 12 18 24 30 360

.1

.2

.3

.4

ARBs: Stage C Heart Failure

• Class I Indication: ARBs approved for HF are recommended in patients with current or prior symptoms of HF and reduced LVEF who are ACEI intolerant

Level of Evidence: A• Class IIa Indication: ARBs are reasonable to use

as alternatives to ACEIs as first-line therapy for patients with mild to moderate HF and reduced LVEF, especially for patients already taking ARBs for other indications

Level of Evidence: AHunt SA, Abraham WT, Chin MH, et al., Circulation and JACC, Sept. 2005Available beginning August 15, 2005 at www.acc.org and www.americanheart.org.

http://www.acc.org/


ARBs: Stage C Heart Failure (cont’d)

• Class IIb Indication: The addition of an ARB may be considered in persistently symptomatic patients with reduced LVEF who are already being treated with conventional therapy (ie, ACEI and -blocker)

Level of Evidence: B


http://www.acc.org/


554/3,319 478/3,313 .85 .008(.75, .96)

Hazard Log-rank Placebo

AldosteroneAntagonist Ratio P Value

Primary Endpoint: All-Cause Mortality

EPHESUS

284/822 386/841 .70 <.001(.60, .82)

RALES

Trial

Pitt B. N Engl J Med. 2003;348:1309-1321. Pitt B. N Engl J Med. 1999;341:709-717.

Trials With Aldosterone Antagonist

Aldosterone Antagonists:Stage C Heart Failure

• Class I Indication: Addition of an aldosterone antagonist is reasonable in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration



http://www.acc.org/


A-HeFT: All-Cause Mortality

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

Days Since Baseline Visit Date

Fixed-dose I/H 518 463 407 359 313 251 13

Placebo 532 466 401 340 285 232 24

0 100 200 300 400 500 60085

90

95

100

Su

rviv

al (%

)

P=.01

Fixed-dose I/H

Placebo

Hazard ratio=.57

43% Decrease in Mortality

Nitrates/Hydralazine: Stage C Heart Failure

• Class IIa Indication: The addition of isosorbide dinitrate and hydralazine to a standard medical regimen for HF, including ACEIs and -blockers, is reasonable and can be effective in blacks with NYHA functional Class III or IV HF

Level of Evidence: A• Class IIb Indication: A combination of hydralazine and

a nitrate might be reasonable in patients with current or prior symptoms of HF and a reduced LVEF who cannot be given an ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency

Level of Evidence: CHunt SA, Abraham WT, Chin MH, et al., Circulation and JACC, Sept. 2005Available beginning August 15, 2005 at www.acc.org and www.americanheart.org.

http://www.acc.org/


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

CRT Improves Quality of Life and NYHA Functional Class

Average Change in Score (MLWHF)

-20

-15

-10

-5

0

Control CRT

* * * *

*P<.05

NYHA: Proportion Improving by 1 or More Class

0

20

40

60

80

MIRACLE CONTAKCD

MIRACLEICD

Control CRT

**

*

Abraham et al. 2003.

(%)

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

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

571192321365404Medical Therapy

889213351376409CRT

Number at risk0 500 1,000 1,500

.25

.50

.75

1.00

Ev

ent-

Fre

e S

urv

iva

l

Medical Therapy

HR: .64 (95% CI: .48-.85)

P=.0019CRT

Days

0

CRT: Stage C Heart Failure

• Class I Indication: Patients with LVEF 35%, sinus rhythm, and NYHA functional Class III or ambulatory Class IV symptoms despite recommended optimal medical therapy and who have cardiac dysynchrony, which is currently defined as a QRS 120 msec, should receive CRT, unless contraindicated

Level of Evidence: A


http://www.acc.org/


MADIT II: Effect of Prophylactic ICD in Ischemic LVD (LVEF 30%)

Moss AJ, et al. N Engl J Med. 2002;346;877-883.

365 (.69)170 (.78)329 (.90)490Conventional

9110 (.78)274 (.84)503 (.91)742Defibrillator

Number at Risk

0 1 2 3

.7

.8

.9

1.0P

rob

abili

ty o

f S

urv

ival

Conventional

Defibrillator

Year

.6

04

Bardy GH, et al. N Engl J Med. 2005;352:225-237.

SCD-HeFT: Enrollment Scheme

DCM CAD and CHF

EF 35%

NYHA Class II or III

6-minute walk, Holter

®Placebo Amiodarone ICD

SCD-HeFT Trial: Mortality by Intention-to-Treat

HR 97.5% Cl P Value

Amiodarone vs Placebo 1.06 .86-1.30 .53

ICD vs Placebo .77 .62-.96 .007

Months of Follow-Up

Mo

rtal

ity

0 6 12 18 24 30 36 42 48 54 600

.1

.2

.3

.4

Amiodarone

ICD Therapy

Placebo

17%

22%

Bardy GH, et al. N Engl J Med. 2005;352:225-237.

ICDs: Stage C Heart Failure

• Class I Indication: An ICD is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamic destabilizing ventricular tachycardia


• Class I Indication: ICD therapy is recommended for primary prevention to reduce total mortality by reducing sudden cardiac death in patients with ischemic heart disease who are at least 40 days post-MI, have an LVEF 30% with NYHA functional Class II or III symptoms while undergoing chronic optimal medical therapy, and have a reasonable expectation of survival



http://www.acc.org/


ICDs: Stage C Heart Failure (cont’d)

• Class I Indication: ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with nonischemic cardiomyopathy who have an LVEF 30%, with NYHA functional Class II or III symptoms while undergoing chronic optimal medical therapy, and have a reasonable expectation of survival


• Class IIa Indication: Placement of an ICD is reasonable in patients with an LVEF of 30% to 35% of any origin with NYHA functional Class II or III symptoms who are taking chronic optimal medical therapy and who have a reasonable expectation of survival

Level of Evidence: BHunt SA, Abraham WT, Chin MH, et al., Circulation and JACC, Sept. 2005Available beginning August 15, 2005 at www.acc.org and www.americanheart.org.

http://www.acc.org/


Evidence-Based Treatment Across the Continuum of LVD and HF

Control Volume Reduce Mortality

Diuretics

Digoxin

-BlockerACEIor ARB

AldosteroneAntagonist

or ARB

Treat Residual Symptoms

CRT an ICD*

Hyd/ISDN*

*For all indicated patients.

Abraham WT, 2005.

Acute Decompensated Heart Failure: Treatment Goals for Hospitalized Patients

• Improve symptoms, especially congestion and low-output symptoms

• Optimize volume status• Identify etiology• Identify precipitating factors• Optimize chronic oral therapy; minimize side effects• Identify who might benefit from revascularization• Education patients concerning medication and HF

self-assessment• Consider enrollment in a disease management

program


Overview of Treatment Options for Patients with Acute Decompensated HF

• Fluid and sodium restriction• Diuretics, especially loop diuretics• Ultrafiltration/renal replacement therapy

(in selected patients only) • Parenteral vasodilators *

(nitroglycerin, nitroprusside, nesiritide)• Inotropes * (milrinone or dobutamine)

*See recommendations for stipulations and restrictions.


Discharge Criteria for Hospitalized ADHF Patients

• Recommended prior to discharge for all patients with HF:• Exacerbating factors addressed• Near optimum fluid status achieved• Transition from IV to oral diuretic completed• Near optimum pharmacologic therapy achieved• Follow-up clinic visit scheduled, usually 7-10 days

• Should be considered prior to discharge for patients with advanced HF or a history of recurrent admissions:• Oral regimen stable for 24 hours• No IV inotrope or vasodilator for 24 hours• Ambulation before discharge to assess functional

capacity• Plans for post-discharge management• Referral to a disease management program


Predictors of Mortality Based on Analysis of ADHERE Database

• Classification and Regression Tree (CART) analysis of ADHERE data shows:

• Three variables are the strongest predictors of mortality in hospitalized ADHF patients:

BUN > 43 mg/dL

Systolic blood pressure < 115 mmHg

Serum creatinine > 2.75 mg/dL

BUN > 43 mg/dL

Systolic blood pressure < 115 mmHg

Serum creatinine > 2.75 mg/dL

Fonarow GC et al. JAMA 2005;293:572-80

Heart Failure Patient Education

• It is recommended that patients with HF and their family members or caregivers receive individualized education and counseling that emphasizes self-care.

• This education and counseling should be delivered by providers using a team approach.

• Teaching should include skill building and target behaviors


The Potential Impact of Effective Education on Patient Compliance

Noncompliance rate when patients . . .

Recall MD advice Don’t recall advice

Medications 8.7% 66.7%

Diet 23.6% 55.8%

Activity 76.4% 84.5%

Smoking 60.0% 90.4%

Alcohol 60.0% 81.8%

Kravitz et al. Arch Int Med 1993;153:1869-78

Sample Target Behavior: Be Able to Read and Understand Food Labels

Labels from cups of soup

Heart Failure Disease Management

• Patients recently hospitalized for HF and other patients at high risk should be considered for referral to a comprehensive HF disease management program that delivers individualized care

HF Disease Management and the Risk of Readmission

Cline

Jaarsma

Rich

Naylor

Stewart

Rauh

Lasater

Ekman

Venner

Fonarow0.5

0.6

0.7

0.8

0.9

1

1.1

RiskRatio

Summary RR = 0.76 (95% CI .68-.87)Summary RR for randomized only = 0.75 (CI = .60-.95)

End-of-Life Care in Heart Failure

• End-of-life care should be considered in patients who have advanced, persistent HF with symptoms at rest despite repeated attempts to optimize pharmacologic and non-pharmacologic therapy, as evidenced by one or more of the following:

• Frequent hospitalizations (3 or more per year)• Chronic poor quality of life with inability to

accomplish activities of daily living• Need for intermittent or continuous intravenous

support• Consideration of assist devices as destination

therapy


Heart Failure:A Practical Approach to Treatment

Guideline Recommended Approach to the Evaluation and Management of Heart Failure William T. Abraham, MD, FACP, FACC Professor of Medicine Chief, Division.

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