Therapeutic Algorithm in Heart Failure

Joseph Elias, MDMay 22, 2004

Beirut - LEBANON

Prevalence and Prognosis of HF in USA

• 2 million Heart Failure patients in the US in 1997

• 28 billions US$ in 1996 for congestive HF

• 400,000 new cases per year

• Sudden cardiac death (SCD) may occur in as many as 40% of all Heart Failure patients

Prevalence and Prognosis of HF in Europe

• Estimates range from 0.4% to 2%• Increase rapidly with age• High prevalence

– 10 million patients with HF– 10 million patients with myocardial dysfunction

• 50% of patients with HF will die within 4 years• > 50% of patients with severe HF will die within 1

year

Task force for the Diagnostic and Treatment of Chronic Heart Failure

ESC. European Heart Journal 2001;22:1527-1560

Prevalence and Prognosis of HF in France

• 500,000 Heart Failure patients in France in 2001• Increase by 120,000 per year• The incidence rises from:

– 0.4% of male and 0.3% of females aged between 55 and 64 years to– 5% of males and 8.5% of females aged between 85 to 94 years

• 3.5 million consultations and 150,000 hospitalizations for HF per year

• The cost linked to HF represents more than 1% of total medical cost

Prevalence and Prognosis of HF in Lebanon

                      

The Epidemiological Aspects and Etiological Basis of Heart Failure

Alan J. Cowley in: International Handbook of Heart Failure, 1994, pp 13-17

0

10

20

30

40

50

60

70percent

Ischemic Heart Disease (IHD)

Dilated cardiomyopathy (CMO)

Primary valvular disease

n = 552

IHD CMO Valvular Hypertension Other

R.W. Timmers, M.D.

The two main endpoints in progressive Heart Failure are:

Sudden Cardiac Death (SDC) is the leading cause of death in NYHA class I and II

Progressive left ventricular dysfunction leading to death by pump failure, occurring mainly in

NYHA class III and IV

R.W. Timmers, M.D.

R.W. Timmers, M.D.

Sudden Death by severity of Heart Failure symptoms

NYHA Class Annual Mortality(%) SCD (%)

II 5-15 50-80(Mainly arrythmias)

III 20-50 30-50

IV 30-70 5-30(Mainly pump failures)

Primary prevention of Sudden Cardiac Death (SCD) in Heart Failure

B. F. Uretsky et al. J. Am Coll. Cardiol. Dec 1997;30:1589-97

Aim of the Treatment

• Prevention of disease leading to heart failure.

• Prevention of progression to heart failure.

• Morbidity: maintenance or improvement in quality of life.

• Mortality: increase duration of life.The aims of CHF therapy are to improve hemodynamics and tolerance of exercise.

Non Pharmacological Therapy

• General advise and measures.

• Educate patients and family.

• Weight Control.

• Dietary Measures.

• Smoking

• Travelling

• Sexual activity

• Exercise and exercise training

Pharmacological Therapy• Diuretics.• ACE inhibitors.• Cardiac Glycosides.• β-Blockers.• ARBS• Aldosterone antagonists• Vasodialtor agents• Positive inotropic agents• Anticoagulation• Antiarrhythmic agents• Oxygen

Device and surgery Therapy

• Pace maker therapy

• Biventricular stimulation

• Heart Surgery

• Circulation Support Systems

• AICD

Diuretics

LOOP DIURETICS, THIAZIDES AND METOLAZONEDiuretics are essential for symptomatic treatment when fluid overload is

present, although there are no controlled randomized trials that have assessed the effect on survival of these agents

They should always be administered in combination with ACE inhibitors

Aldosterone receptor Antagonists – SpironolactoneAldosterone antagonist is recommended in advance HF in addition to

ACE inhibitors and Diuretics to improve survival and morbidityThe RALES mortality trial showed that low dose Spironolactone (12.5 – 50

mg) on top of an ACE inhibitor and a loop diuretic markedly and progressively improved survival of patients in advanced NYHA III/IV

HF, irrespective of aetiology

β-BLOCKERS

There are different types of β-Blockers:

• Those that selectively inhibit Beta1 receptors.

• Those that inhibit Beta1 and Beta2 receptors.• Those that inhibit Beta1, Beta2 and Alpha1

receptors.

β-BLOCKERS

Interfere with the endogenous nervous system.

Inhibit the effects of the sympathetic nervous system (epinephrine and nor epinephrine).

Reduce sympathetic activity:

- Prevention of catecholamine toxicity.

- Reduction of myocardial ischemia.

- Reduction of arrhythmias.

β Blockade in Heart Failure

• Consensus recommendations– all patients with class II-III heart failure due to left ventricular

systolic dysfunction should receive a β blocker (in addition to an ACE inhibtor) unless they have contraindication to its use or cannot tolerate treatment with the drug

– The results fo the CIBIS II study with Bisoprolol and the COPERNICUS study with Carvedilol have considerably contributed to increasing the evidence regarding the use of β-blockers in NYHA IV patients

R.W. Timmers, M.D.

ACE inhibitors for the prevention of SDC in Heart Failure

SUDDEN DEATH MORTALITY

Study NYHA Follow-up Mortality ACE no ACE pClass (mo) Decrease

Consensus 1 IV 12 27% (p=0.003) 11.0 11.0 > 0.25

SOLVD RX II, III 41 16% (p=0.004) 8.2 8.8 > 0.25

SOLVD Prev. I, II 37 8% (p=0.30) 4.6 5.0 0.10

Overall 6.2 6.6 0.09

Primary prevention of Sudden Cardiac Death (SCD) in Heart Failure

B. F. Uretsky et al. J. Am Coll. Cardiol. Dec 1997;30:1589-97

R.W. Timmers, M.D.

ACE inhibitors for the prevention of SDC in Post-MI w/o clinical signs of heart failure (early intervention)

SUDDEN DEATH MORTALITY

Study NYHA Follow-up Mortality ACE no ACE pClass (mo) Decrease

SAVE I 42 19% (p=0.019) 5.6 6.7 > 0.25

TRACE I, II 24-50 22% (p=0.001) 12.0 15.2 0.025

SMILE. I, II 1.5 22% (p=0.17) 0.5 1.4 0.17

Overall (Including AIRE Study) 7.7 9.7 0.015

Primary prevention of Sudden Cardiac Death (SCD) in Heart Failure

B. F. Uretsky et al. J. Am Coll. Cardiol. Dec 1997;30:1589-97

ACE inhibition in Myocardial Infarction, LV Dysfunction and Heart Failure: Mortality Studies

Treatment effect 2P = 0.003

Trials Odds Ratio (& C. Limits) Risk Reduction %

Myocardial infarction< 24 hrs Consensus-2

GISSI-3ISIS-4Chinese AMI

Subtotal:

MI with LV dysfunction

Days SAVETRACE

Months SOLVDSubtotal:

MI and Heart FailureDays AIRE

Overall

+ 10 + 9- 11 + 5- 5 + 3- 3 + 6

- 6 + 2

- 19 + 9- 22 + 7- 8 + 8

- 13 + 6

- 27 + 9

- 8 %+ 2

0.5 0.75 1.0 1.25

R.W. Timmers, M.D.

Angiotensin Receptor Blockers (ARBs) in Heart

Failure

Substitute or adjunctive therapy to ACE inhibitors ?

ARBs in Heart Failure

A meta-analysis of 17 studies in HF (n=12 469)

Patients with HF NYHA class II to IVPatients with HF NYHA class II to IV

Studies comparing ARBs to placebo or ACE inhibitorsStudies comparing ARBs to placebo or ACE inhibitors

Randomized, blinded, parallel-group studiesRandomized, blinded, parallel-group studies

Treatment duration of at least 4 weeksTreatment duration of at least 4 weeks

Studies reporting death and hospitalization for HFStudies reporting death and hospitalization for HF

Jong P et al. J Am Coll Cardiol 2002;39:463-70

ARBs in Heart Failure Conclusions of the Meta-

analysis

Jong P et al. J Am Coll Cardiol 2002;39:463-70

ARBs were not superior to controls in the pooled ARBs were not superior to controls in the pooled rates of death or hospitalizationrates of death or hospitalization

There was a NS trend in favor of ARBs over placebo in There was a NS trend in favor of ARBs over placebo in reducing mortality and hospitalization when given reducing mortality and hospitalization when given without without background ACEIsbackground ACEIs

When compared directly with ACEIs, ARBS were not When compared directly with ACEIs, ARBS were not superior in reducing either mortality or hospitalizationsuperior in reducing either mortality or hospitalization

ARB+ACEI combinations were superior to ACEIs alone ARB+ACEI combinations were superior to ACEIs alone in in reducing hospitalization but not mortalityreducing hospitalization but not mortality

CHARM-Alternative: Primary outcome CV death or CHF

hospitalisation

0 1 2 3 years0

10

20

30

40

50

Placebo

Candesartan

%

HR 0.77 (95% CI 0.67-0.89), p=0.0004Adjusted HR 0.70, p<0.0001

Number at risk

Candesartan 1013 929 831 434 122

Placebo 1015 887 798 427 126

3.5

406 (40.0%)

334 (33.0%)

CHARM-Alternative Secondary outcomes

CV death 219 252

CHF hosp. 207 286

CV death, CHF hosp, 353 420 MI

CV death, CHF hosp, 369 432 MI, stroke

CV death, CHF hosp, 396 456 MI, stroke, revasc

Candesartan Placebo

candesartan better

Hazard ratio

placebo better

0.6 0.8 1.0 1.2 1.4

p-value

0.072

<0.0001

0.0007

0.001

0.002

0.85

0.68

0.78

0.80

0.81

CHARM-Added: Primary outcomeCV death or CHF hospitalisation

0 1 2 3 years0

10

20

30

40

50

Placebo

Candesartan

Number at risk

Candesartan 1276 1176 1063 948 457

Placebo 1272 1136 1013 906 422

3.5

HR 0.85 (95% CI 0.75-0.96), p=0.011Adjusted HR 0.85, p=0.010

483 (37.9%)538 (42.3%)

%

CHARM-Added Secondary outcomes

CV death 302 347

CHF hosp. 309 356

CV death, CHF hosp, 495 550 MI

CV death,CHF hosp, 512 559 MI, stroke

CV death,CHF hosp, 548 596MI, stroke, revasc

candesartan better

Hazard ratio

placebo better

0.6 0.8 1.0 1.2 1.4

p-value

0.029

0.014

0.010

0.020

0.015

Candesartan Placebo0.84

0.83

0.85

0.87

0.87

Captopril

VALLIANT studyCV Death, MI, or HF by Treatment

Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349

Months

Valsartan vs. Captopril: HR = 0.96; P = 0.198

Valsartan + Captopril vs. Captopril: HR = 0.97; P = 0.369

0

0.1

0.2

0.3

0.4

0 6 12 18 24 30 36

Pro

bab

ilit

y o

f E

ven

t

Valsartan

Valsartan + Captopril

Summing up ACEI & ARBs in post MIMortality in SAVE, TRACE, AIRE, and VALIANT

Hazard Ratio for Mortality

FavorsActive Drug

FavorsPlacebo

Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349

0.5 1 2

Combined

TRACE

SAVE

AIRE

VALIANT(imputed placebo)

Valsartan

preserves

99.6% of

mortality

benefit of

captopril.

Primary prevention of Sudden Cardiac Death (SCD) in Heart Failure

B. F. Uretsky et al. J. Am Coll. Cardiol. Dec 1997;30:1589-97

R.W. Timmers, M.D.

Antiarrythmics for the prevention of SDC in Heart Failure

Class I Antiarrythmics:

CAST 1 & 2 showed no evidence of preventing SCD in Heart Failure (Encainide, Flecainide)BASIS study (moricizine) showed a non significant increase in mortality...

Amiodarone showed mixed results in primary SCD prevention in Heart Failure:

CHF-STAT (US) trial showed no difference, except for non-ischemic cardiomyopathy Heart Failure patients (trend-wise)GESICA (Argentina) showed a significant mortality reduction for both pump failure and SCD. (60% of patients had non-ischemic cardiomyopathy)CAMIAT(Canada), and EMIAT(UK) trials in post MI showed a significant 35% reduction in SCD but no decrease in overall mortality...

Cardiac Glycosides

• Cardiac glycosides are indicated in AF and at any degree of symptomatic HF

• In sinus rhythm, cardiac glycosides are recommended to improve the clinical status of patients with persisting HF symptoms due to LV systolic dysfunction despite ACE inhibitors and diuretic treatments

• In the DIG Trial in 6,800 patients wth an ischaemic and non-ischaemic cardiomyopathy and mild to moderate HF, with long term digoxin, reduced symptoms, improved clinical status without any impact on survival

Surgery

• Surgical treatment should be directed towards the underlying aetiology and mechanisms. In addition to revascularization, it is important to approach patients with significant valvular disease before they develop significant LV dysfunction

• Cardiomyoplsty cannot be recommended for treatment of HF

• Heart transplantation is an accepted mode of treatment for end stage HF. Although, controlled trials have never been conducted, it is considered to significantly increase survival and quality of life (5 years survival70-80%)

Cardiac Resynchronization Therapy for Heart Failure

Mechanisms, Clinical Outcomesand Patient Selection

Ventricular Dysynchrony and Cardiac Resynchronization

• Ventricular Dysynchrony1 – Electrical: Inter- or

Intraventricular conduction delays typically manifested as left bundle branch block

– Structural: disruption of myocardial collagen matrix impairing electrical conduction and mechanical efficiency

– Mechanical: Regional wall motion abnormalities with increased workload and stress—compromising ventricular mechanics

• Cardiac Resynchronization

– Therapeutic intent of atrial synchronized biventricular pacing» Modification of interventricular, intraventricular, and atrial-

ventricular activation sequences in patients with ventricular dysynchrony

» Complement to optimal medical therapy

11 Tavazzi L. Tavazzi L. Eur HeartEur Heart J 2000;21:1211-1214 J 2000;21:1211-1214

Proposed Mechanisms of Cardiac Resynchronization

Cardiac ResynchronizationCardiac Resynchronization

Improved Intraventricular Improved Intraventricular SynchronySynchrony

Improved Atrioventricular Improved Atrioventricular SynchronySynchrony

Improved Interventricular Improved Interventricular SynchronySynchrony

Yu C-M, Chau E, Sanderson J, et al. Yu C-M, Chau E, Sanderson J, et al. CirculationCirculation 2002;105:438-445 2002;105:438-445

Summary of Proposed Mechanisms

Yu C-M, Chau E, Sanderson J, et al. Yu C-M, Chau E, Sanderson J, et al. CirculationCirculation 2002;105:438-445 2002;105:438-445

IntraventricularIntraventricularSynchronySynchrony

AtrioventricularAtrioventricularSynchronySynchrony

InterventricularInterventricularSynchronySynchrony

LALAPressurePressure

LV DiastolicLV DiastolicFillingFilling

RV StrokeRV StrokeVolumeVolume

LVESVLVESV LVEDVLVEDV

Reverse RemodelingReverse Remodeling

Cardiac ResynchronizationCardiac Resynchronization

MRMR dP/dt, dP/dt, EF, EF, COCO(( Pulse Pressure)Pulse Pressure)

HF and CRT Clinical Studies – Observational and Randomized

CRT Improves Quality of Life Score and NYHA Functional Class

QoLQoL NYHA NYHA

PATH-CHFPATH-CHF1 1 (n=41)(n=41) ++ ++

InSync (Europe)InSync (Europe)2 2 (n=103)(n=103) ++ ++

InSync ICD (Europe)InSync ICD (Europe)3 3 (n=84)(n=84) ++ ++

MUSTICMUSTIC4 4 (n=67)(n=67) ++

MIRACLEMIRACLE5 5 (n=453)(n=453) ++ ++

MIRACLE ICDMIRACLE ICD6 6 (n=364)(n=364) ++ ++

1 Auricchio A. Stellbrink C, Sack S., et al. Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol J Am Coll Cardiol 2002;39:2026-2002;39:2026- 2033 203322 Gras D, Leclercq C, Tang A, et al. Gras D, Leclercq C, Tang A, et al. Eur J Heart FailureEur J Heart Failure 2002;4:311-320 2002;4:311-32033 Kuhlkamp V. Kuhlkamp V. JACCJACC 2002;39:790-797 2002;39:790-7974 4 Linde C, Leclercq C, Rex S, et al. Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol J Am Coll Cardiol 2002;40:111-118 2002;40:111-118

5 Abraham W, Fisher W, Smith A, et al.Abraham W, Fisher W, Smith A, et al. N Engl J Med.N Engl J Med. 2002;346:1845-1853 2002;346:1845-185366 Leon A. Leon A. NASPE Scientific Sessions – Late BreakingNASPE Scientific Sessions – Late Breaking Clinical Trials. Clinical Trials. May 2002; Medtronic Inc. data on fileMay 2002; Medtronic Inc. data on file

++ Statistically significant improvement with CRT (p Statistically significant improvement with CRT (p 0.05) 0.05) Not statistically significant or No statistical analysis performed on dataNot statistically significant or No statistical analysis performed on data

Blank Blank Indicates test neither performed nor reported Indicates test neither performed nor reported

CRT Improves Exercise Capacity 6 Min Walk6 Min Walk Peak VO Peak VO2 2 ExerciseExercise

Time Time

PATH-CHFPATH-CHF1 1 (n=41)(n=41) ++ ++

InSync (Europe)InSync (Europe)2 2 (n=103)(n=103) ++

InSync ICD (Europe)InSync ICD (Europe)3 3 (n=84)(n=84) ++

MUSTICMUSTIC4 4 (n=67)(n=67) ++

MIRACLEMIRACLE5 5 (n=453)(n=453) ++ ++ ++

MIRACLE ICDMIRACLE ICD6 6 (n=364)(n=364) ++ ++

1 Auricchio A. Stellbrink C, Sack S., et al. Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol J Am Coll Cardiol 2002;39:2026-2002;39:2026- 2033 203322 Gras D, Leclercq C, Tang A, et al. Gras D, Leclercq C, Tang A, et al. Eur J Heart FailureEur J Heart Failure 2002;4:311-320 2002;4:311-320

33 Kuhlkamp V. Kuhlkamp V. JACCJACC 2002;39:790-797 2002;39:790-7974 4 Linde C, Leclercq C, Rex S, et al. Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol J Am Coll Cardiol 2002;40:111-118 2002;40:111-118

5 Abraham W, Fisher W, Smith A, et al.Abraham W, Fisher W, Smith A, et al. N Engl J Med.N Engl J Med. 2002;346:1845-1853 2002;346:1845-185366 Leon A. Leon A. NASPE Scientific Sessions – Late BreakingNASPE Scientific Sessions – Late Breaking Clinical Trials. Clinical Trials. May 2002; Medtronic Inc., data on fileMay 2002; Medtronic Inc., data on file

++ Statistically significant improvement with CRT (p Statistically significant improvement with CRT (p 0.05) 0.05) Not statistically significant or No statistical analysis performed on dataNot statistically significant or No statistical analysis performed on data

Blank Blank Indicates test neither performed nor reported Indicates test neither performed nor reported

CRT Improves Cardiac Function/Structure

1 Auricchio A. Stellbrink C, Sack S., et al. Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol J Am Coll Cardiol 2002;39:2026-2002;39:2026- 2033 203322 Gras D, Leclercq C, Tang A, et al. Gras D, Leclercq C, Tang A, et al. Eur J Heart FailureEur J Heart Failure 2002;4:311-320 2002;4:311-32033 Kuhlkamp V. Kuhlkamp V. JACCJACC 2002;39:790-797 2002;39:790-7974 4 Linde C, Leclercq C, Rex S, et al. Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol J Am Coll Cardiol 2002;40:111-118 2002;40:111-118

5 Abraham W, Fisher W, Smith A, et al.Abraham W, Fisher W, Smith A, et al. N Engl J Med.N Engl J Med. 2002;346:1845-1853 2002;346:1845-185366 Young J. Young J. ACC Scientific Sessions – Late BreakingACC Scientific Sessions – Late Breaking Clinical Trials III. Clinical Trials III. March 2002; Medtronic Inc., March 2002; Medtronic Inc., data on file data on file

LVEF MR Other

PATH-CHF1 (n=41) + LVEDP + LV dP/dtmax

InSync (Europe)2 (n=103) + + Filling Time

InSync ICD (Europe)3 (n=84) + + Filling Time

MUSTIC4 (n=67) LVEDD,LVESD Filling Time

MIRACLE5 (n=453) + + + LVEDD, + LVEDV, LVESV

MIRACLE ICD6 (n=362) + + LVESV, + LVEDV

++ Statistically significant improvement with CRT (p Statistically significant improvement with CRT (p 0.05) 0.05) Not statistically significant or No statistical analysis performed on dataNot statistically significant or No statistical analysis performed on data

Blank Blank Indicates test neither performed nor reported Indicates test neither performed nor reported

11 Gras D, Leclercq C, Tang A, et al. Gras D, Leclercq C, Tang A, et al. Eur J Heart FailEur J Heart Fail 2002;4:311-320 2002;4:311-3202 Auricchio A. Stellbrink C, Sack S., et al. Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol J Am Coll Cardiol 2002;39:2026-20332002;39:2026-20333 3 Linde C, Leclercq C, Rex S, et al. Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol J Am Coll Cardiol 2002;40:111-118 2002;40:111-118

NYHA QoL 6 Minute

WalkPeak VO2

InSync European and Canadian Study1

(n=67, followed to 12 months) + + +

PATH-CHF Study2

(n=29, followed to 12 months)+ + +

+

MUSTIC Study3

(n=42 in sinus rhythm group, n=33 in atrial fibrillation groupfollowed to 12 months)

+ + +

Cardiac Resynchronization Outcomes

Sustained for at least 12 months

++ Statistically significant improvement with CRT (p Statistically significant improvement with CRT (p 0.05) 0.05) No statistically significant improvement with CRT No statistically significant improvement with CRT

Blank Indicates test neither performed nor reportedBlank Indicates test neither performed nor reported

1 Auricchio A. Stellbrink C, Sack S., et al. Auricchio A. Stellbrink C, Sack S., et al. J Am Coll Cardiol J Am Coll Cardiol 2002;39:2026-20332002;39:2026-20332 2 Linde C, Leclercq C, Rex S, et al. Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol J Am Coll Cardiol 2002;40:111-118 2002;40:111-1183 Abraham W, Fisher W, Smith A, et al. Abraham W, Fisher W, Smith A, et al. N Engl J Med.N Engl J Med. 2002;346:1845-1853 2002;346:1845-185344 Leon A. DeLurgioD, Smith A, et al. Leon A. DeLurgioD, Smith A, et al. PACEPACE 2002;25(4), Part II:647 2002;25(4), Part II:647

Cardiac Resynchronization Benefits

Relative to HospitalizationPATH-CHF1

MUSTIC2

MIRACLE3

MIRACLE ICD4

• 1 year prior to implant, 22 patients hospitalized for HF with average stay of 18.5 days

• One year following implant, 9 patients hospitalized for HF with average stay of 4.5 days

• Sinus Rhythm Group: 7 times fewer hospitalizations for HF (12 month F/U)

• AF Group: 4 times fewer hospitalizations for HF (12 m/fu)

• Number of HF-hospitalizations significantly reduced (p = 0.02)

• Length of stay for HF-hospitalizations significantly reduced (p = 0.05)

In Summary

Cardiac Resynchronization therapy offers an adjunctive approach for treating selected patients with ventricular dysynchrony and moderate to severe heart failure who remain symptomatic despite optimal, stable medical therapy.

CHF- Choice of Pharmacological therapy

LV Systolic Dysfunction

ACE inhibitors

Beta-blocker Diuretic Aldosterone antagonists

Asymptomatic LV Dysfunction

Indicated Post MI Not indicated Not indicated

Symptomatic HF NYHA II

Indicated Indicated Indicated if fluid retention

Not indicated

Worsening HF

NYHA III/IV

Indicated Indicated

(under specialist care)

Indicated combination of diuretics

Indicated

End stage HF

NYHA IV

Indicated Indicated

(under specialist care)

Indicated combination of diuretics

Indicated

CHF- Choice of Pharmacological therapy

LV Systolic Dysfunction

Angiotensin II receptor antagonist

Cardiac Glygosides Vasodilator

(Hydralazine/isosorbide dinitrate)

Asymptomatic LV Dysfunction

Not indicated With AF Not indicated

Symptomatic HF NYHA II

If ACE inhibitors are not tolerated and +/- added to ACE

a. With AF

b. When improved from more severe HF in sinus ryhthm

If ACE inhibitors and ARBs not tolerated

Worsening HF

NYHA III/IV

If ACE inhibitors are not tolerated and +/- added to ACE

Indicated If ACE inhibitors and ARBs not tolerated

End stage HF

NYHA IV

If ACE inhibitors are not tolerated and +/- added to ACE

Indicated If ACE inhibitors and ARBs not tolerated

ConclusionTherapeutic Algorithm in Heart Failure

For symptoms For survival/morbidity

For symptoms if intolerance to ACE or -

NYHA I Reduce/stop diuretic Continue ACE inhibitor if asymptomic. Add - if post MI

NYHA II +/- diuretic depending on fluid retention

ACE inhibitor as first line treatment Add - if still symptomatic

ARB if ACE inhibitor intolerant Or ACE inhibitor + ARB if - intolerant

NYHA III + diuretics + digitalis if still symptomatic + nitrates/hydralzine if tolerated

ACE inhibitor and - and spironolactone

ARB if ACE inhibitor intolerant Or ACE inhibitor + ARB if - intolerant

NYHA IV Diuretic + digitalis + nitrates/hydralazine if tolerated + temporary inotropic support +/- devices

ACE inhibtor and - and spironolactone +/- devices

ARB if ACE inhibitor intolerant Or ACE inhibitor + ARB if - intolerant