1. MANAGING CONGESTIVE HEART FAILURE
Annual Conference of the Lebanese Society of Family Medicine
Antoine Sarkis, MD
Associate Professor of Cardiology
Hotel Dieu de France Hospital

2. Guidelines ESC HFSA NYHA Classification CCS ACC/AHA
2005
NYHA Classification
2006
2006
Four stage classification
2005

3. A B C D Stages in the Evolution of Heart Failure.
Clinical Characteristics
Hypertension
Diabetes, Hyperchol.
Family Hx
Cardiotoxins A B
Heart disease
(any)
Asymptomatic
LV dysfunction
Systolic / Diastolic C
Dyspnea, Fatigue
Reduced exercise
Tolerance (current or past) D
Marked symptoms
at rest despite
max. therapy
AHA / ACC HF guidelines 2001 4

4. Classification of Recommendation
Class I: General agreement or evidence that a therapy is beneficial
►(therapy is recommended)
Class II: Conflicting evidence
IIa: evidence in favor of efficacy
►( therapy should be considered)
IIb: evidence less well established
►( therapy may be considered)
Class III: Not recommended, may be harmful

5. Level of evidence
Level A: multiple randomized clinical trials or meta-analysis
Level B: single randomized trial, or non randomized studies
Level C: Consensus opinion of experts

6. Treatment Objectives Mainly decrease symptoms and prolong life
But also:
Decrease morbidity (hospital admissions, embolism…)
Increase exercise capacity and improve quality of life
Control neurohormonal changes
Retard progression of CHF
Treatment of Heart Failure.
Objectives
The objectives of treatment of the patient with heart failure are many, but they may be summarized in two principles: decrease symptoms and prolong life. In daily practice, the first priority is symptom control and the best plan is to adjust to the individual patient’s particular circumstances over the course of therapy. Nevertheless, the rest of the listed objectives should not be forgotten, as medical therapy now has the potential for decreasing morbidity (hospital admissions, embolism, etc.), increasing exercise capacity (all of the usually prescribed drugs), improve the quality of life, control neurohormonal changes (ACE-I, beta blockers), retard progression (ACEI) and prolong life.

7. Treatment of CHF All Control of risk factors Life style
Treat etiologic cause / aggravating factors
Drug therapy
Revascularization
ICD (Implantable Cardiac Defibrillator)
Ventricular resynchronization (CRT)
Ventricular assist devices
Heart transplant
Artificial heart
Neoangiogenesis, Gene therapy
All
Selected patients

8. Correction of reversible causes
Ischaemia
Valvular heart disease
Thyrotoxicosis and other high output status
Shunts
Arrhythmia
Atrial fibrillation, flutter,
Medications
Ca channel blockers, some antiarrhythmics

9. Pharmacologic Therapy
Diuretics
ACE inhibitors
Beta Blockers
ARBs
Digitalis
Spironolactone
Other
Treatment of Heart Failure.
Drugs
This is a simple and pragmatic classification of the vast numbers and types of medications in the pharmacopoeia for the treatment of heart failure.

10. Diuretics. Indications
Symptomatic HF, with fluid retention
Peripheral edema
Dyspnea/ Pulmonary edema (Xray)
Jugular distension
Hepatomegaly
AHA / ACC HF guidelines 2005
ESC HF guidelines 2005 11

11. Adverse Effects of Diuretics.
K+, Mg+ ( %) (sudden death ???)
Na+
Hyperuricemia ( %)
Stimulation of neurohormonal activity
Hypotension. Pre-renal azotemia, Ototoxicity, Gastrointestinal, Metabolic Alkalosis.
Skin rashes, Neutropenia, Thrombocytopenia

12. Inhibitors of renin-angiotensin- aldosterone system
Renin-angiotensin-aldosterone system is activated early in the course of heart failure and plays an important role in the progression of the syndrome

13. Angiotensin Converting Enzyme Inhibitors Angiotensin Receptor Blockers
RAAS Blockade
Angiotensin Converting Enzyme Inhibitors
(ACE-I)
Angiotensin Receptor Blockers
(ARB)

14. ACE-I. Clinical Effects in CHF
Improve symptoms
Reduce remodeling / progression
Reduce hospitalization
Improve survival
Treatment of Heart Failure.
Angiotensin Converting-Enzyme Inhibitors (ACEI): Mechanisms of action
ACE-inhibitors cause arteriovenous vasodilatation. Venodilation is accompanied by reduction in PAD, PCWP, and LVEDP. Arterial vasodilatation decreases SVR and MAP and increases cardiac output, ejection fraction, and exercise tolerance. Heart rate and contractility do not change, and, thus, double product and myocardial oxygen demand are decreased. These effects are more noticeable in patients with low sodium levels, in whom there is an increased plasma renin activity. Vasodilatation is seen in various vascular territories: renal, coronary, cerebral, and musculoskeletal (increasing exercise capacity). Additionally, ACE-inhibitors cause diuretic and natriuretic effects that are a consequence of the inhibition of angiotensin II and aldosterone synthesis, as well as the increase in cardiac output and renal perfusion.
It is now known that the magnitude and duration of blood pressure reduction correlates better with the activity of ACE in certain tissues (heart, vessels, kidney, adrenal, etc.) than with its plasma levels, which indicates that ACE-inhibitors act by inhibiting local tissue production of angiotensin II. Plasma levels of ACE are not good predictors of the magnitude of hemodynamic effects of ACE-inhibition.

15. ACE-I Placebo Probability of Death Enalapril CONSENSUS 253 patients
N Engl J Med 1987;316:1429
ACE-I
0.8
0.7
Placebo
0.6
Probability of
Death
p< 0.001
0.5
0.4
p< 0.002
0.3
Enalapril
Treatment of Heart Failure.
Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival
CONSENSUS. Prolonged administration of ACE-inhibitors reduces mortality in symptomatic heart failure. The first study to demonstrate this effect was CONSENSUS I. This graph shows the cumulative mortality curves of the treatment and placebo group in this randomized, double-blind trial. The study analyzed the effect of enalapril on prognosis of 253 patients with class IV heart failure, who also received digitalis, diuretics, and conventional vasodilators. At the end of 6 months of treatment, there was a clear-cut improvement in functional class, a reduction in the need for medications, and a 40% reduction in mortality (p<0.002). After 12 months the mortality reduction was 31% (p<0.001). Nonetheless, there were no differences in the incidence of sudden death between the two groups, or in the sub-group that received other conventional vasodilators. Another characteristic of this study was variability of the dose that was used for each patient (adjusted for tolerance and symptoms): mg/day. This aspect shows the importance of individualized treatment for heart failure patients.
The CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429.
253 patients
NYHA IV
0.2
31 %
0.1 1 2 3 4 5 6 7 8 9 10 11 12
Months

16. ACE-I % Mortality SOLVD (Treatment) N Engl J M 1991;325:293 Placebo50 40 30 20 10
p =
Placebo
n=1284
% Mortality
Enalapril
n=1285
Treatment of Heart Failure
Angiotensin Converting-Enzyme Inhibitors (ACEI) : Survival
SOLVD study-symptomatic heart failure. Mortality curves in patients with clinical heart failure in the SOLVD treatment study. In this study, 2589 symptomatic heart failure patients with EFs<35% (90% in functional class II – III) were randomized to receive enalapril or placebo. Mortality over a 41 month follow-up period was 39.7% in the enalapril arm and 35.2% in the placebo arm (p<0.004). The mortality reduction was chiefly mediated through less progression of heart failure; deaths due to arrhythmia were not reduced. Additionally, the enalapril group required fewer hospitalizations for heart failure.
The SOLVD Investigators. N Engl J Med 1991;325:293
N = 2589 CHF
- NYHA II-III
- EF < 35 % 6 12 18 24 30 36 42 48
Months

17. ACE-I Mortality % Years SAVE 30 Placebo 20 Captopril 10 1 2 3 4
N Engl J Med 1992;327:669
ACE-I 30
Asymptomatic
ventricular
dysfunction post MI
Placebo
n=1116
Mortality % 20
Captopril
n=1115
Treatment of Heart Failure
Angiotensin Converting-Enzyme Inhibitors (ACEI): Survival
SAVE (Survival and Ventricular Enlargement). Mortality curves in the SAVE study in patients with varying degrees of post-infarct ventricular dysfunction. In this study, 2231 patients with EF < 40% were randomized to receive captopril or placebo between 3 to 16 days after experiencing a transmural infarct. After 42 months, the captopril group had a significant reduction in overall mortality (-19%), number of reinfarctions (-25%), hospitalizations (-22%), and in the number of patients who developed clinical congestive heart failure. The mortality reduction appeared after 1 year of treatment.
Pfeffer MA et al. Survival and Ventricular Enlargement (SAVE) Study. NEngl J Med 1992;327:669. 10
N = 2231
days post AMI
EF < 40 %
mg / day
² -19%
p=0.019 1 2 3 4
Years

18. ACE-I AIRE Mortality % Placebo Ramipril p = 0.002 Months N = 2006
Lancet 1993;342:821
ACE-I
Placebo 30
Mortality % 20
Ramipril 10
p = 0.002
N = 2006
HF after AMI 6 12 18 24 30
Months

19. ACE-I Indications Symptomatic heart failure (stage C)
Asymptomatic ventricular dysfunction
LVEF <35-40 % (stage B)
Patients with recent or remote history of MI regardless of EF or presence of HF (stage B)
Class I recommendation
Level of evidence A
AHA / ACC HF guidelines
ESC HF guidelines

20. ACE-I. Practical Use Start with very low dose
Renal function & serum K+ after 1-2 w
In the absence of fluid retention, ACE-I should be given first / In the presence of fluid retention together with diuretics
Dose NOT determined by symptoms. ACE-I should be up-titrated to dosages shown to be effective in clinical trials

21. ACE-I. Adverse Effects Hypotension (1st dose effect)
Worsening renal function, Hyperkalemia
Cough
Angioedema
Rash, ageusia, neutropenia, …
Pregnancy is a contra indication
Treatment of Heart Failure.
Angiotensin Converting-Enzyme Inhibitors (ACEI) : Undesirable Effects
These can be classified into two groups. One group includes those effects that are inherent to its mechanism of action, and therefore are common to all ACE-inhibitors. The other includes those effects that are related to the specific chemical structure of the drug. In this case, substitution of one ACE-inhibitor for another could possibly reduce the intensity of the adverse reaction (e.g. choosing an ACE-inhibitor without a sulfhydryl moiety).

22. Substitute or adjunctive therapy to ACE inhibitors ?
Angiotensin Receptor Blockers (ARBs) in Heart Failure
Substitute or adjunctive therapy to ACE inhibitors ?

23. Potential advantages of ARBs
ARBs more effective than ACE-I due to:
- Better RAAS Blockade
- Absence of angiotensin II escape
- Placebo like side effects

24. ELITE II: Endpoint Results
1.0
0.8
All-cause mortality
Probability of Survival
0.6
Losartan
0.4
P = .16
Captopril
0.2
0.0
1.0
0.8
Event-free Probability
0.6
Sudden death or resuscitated arrest
P = .08
0.4
0.2
1.0
The recommended treatment of HF due to left ventricular systolic dysfunction (ejection fraction, <0.35 to 0.40) ranges from monotherapy with ACEIs in patients with the mildest manifestations to the use of a combination of ACEI, digoxin, diuretic(s), and hydralazine HCl or isosorbide dinitrate for patients with severe HF.35 The efficacy of ACEIs in the treatment of HF is well established. However, some physicians do not prescribe these agents due to safety concerns surrounding the accumulation of bradykinin associated with these agents.36 Therefore, clinical studies with ARBs in HF were initiated in an effort to find out if similar efficacy was observed with better tolerability.
In 1997, the results of a 48-week study in HF patients demonstrated a 46% risk reduction in mortality with losartan therapy (an ARB) compared to captopril (an ACEI).36 However, these results were analyzed with caution because mortality was a secondary endpoint of the study and the number of events in this initial trial were small.36 Therefore, a larger study, including over 3,000 patients with HF, randomized patients to losartan or captopril and evaluated death from any cause as the primary endpoint.36 After a median follow-up period of 1.5 years, no differences in all-cause mortality, sudden death or resuscitated arrest, or all-cause mortality or hospital admission were observed between the two treatment groups.36 Interestingly, losartan therapy was associated with significantly fewer discontinuations due to adverse events attributed to study drug or due to cough compared to captopril (P<.001).36 Worsening HF was reported in 25% of patients in each group and the frequency of discontinuations did not differ for worsening of HF.36
Slide Reference
Pitt B, Poole-Wilson PA, Segal R, et al, on behalf of the ELITE II investigators. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomized trial–the Losartan Heart Failure Survival Study ELITE II. Lancet. 2000;355:
0.8
Event-free Probability
0.6
P = .18
0.4
All-cause mortality or hospital admission
0.2
100
200
300
400
500
600
700
Follow-up (days)
(Reprinted with permission from Pitt B, et al. Lancet. 2000)

25. Val-HeFT: Study Design and Inclusion Criteria
5010 patients
EF < 40%; NYHA II - IV
Receiving background therapy
ACEIs (93%), diuretics (86%), digoxin (67%), beta-blockers (35%)
Over 5,000 patients with chronic heart failure defined as NYHA class II (62%), III (36%), and IV (2%) with an ejection fraction of <40% and left ventricular diastolic transverse diameter (LVIDD) >2.0 cm/m2 were randomized to receive valsartan 40 mg twice daily titrated to 160 mg twice daily or placebo.38
At the time of randomization, 93% of patients were receiving an ACEI, 86% a diuretic, 67% digoxin, and 35% were receiving a beta-blocker.38
Slide Reference
Cohn JN, Tognoni G, for the Val-HeFT Investigators. A randomized trial of the angiotensin receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:
Randomized to
Valsartan 40 mg bid titrated to 160 mg bid
Placebo
(Cohn JN, et al. N Engl J Med. 2001)

26. Time since randomisation (months)
Effect of Valsartan on Combined Mortality and Morbidity End Point* in Overall Population
All-cause mortality and morbidity
All-cause mortality
1.0
1.0
0.9
0.8
0.7
Time since randomisation (months)
p = 0.80
Survival probability (%) 3 6 9 12 21 18 15 24 27
Valsartan
0.9
0.8
Event-free probability
Placebo
0.7
In the overall population, Val-HeFT showed a significant benefit on the primary endpoint combined morbidity and mortality, which was reduced by 13.2% (p=0.009), but a neutral effect on all-cause mortality.
13% risk reduction p= 0.009
0.6 3 6 9 12 15 18 21 24 27
Time since randomisation (months)
Cohn et al. NEJM 2001;345:1667

27. CHARM Program 3 component trials comparing Candesartan
to placebo in patients with symptomatic heart failure
CHARM Alternative
CHARM Added
CHARM Preserved
n=2028
LVEF £40% ACE inhibitor intolerant
n=2548
LVEF £40% ACE inhibitor treated
n=3025
LVEF >40% ACE inhibitor treated/not treated

28. CHARM Program Mortality and morbidity
CV Death or CHF Hospitalisation
All Cause Mortality
0.77
Alternative
p=0.0004
0.85
Added
p=0.011
0.89
Preserved
p=0.118
0.91
0.84
Overall
p=0.055
p<0.0001
0.7
0.8
0.9
1.0
1.1
1.2
0.6
0.7
0.8
0.9
1.0
1.1
1.2
Hazard ratio
Hazard ratio
p heterogeneity=0.37
p heterogeneity=0.43

29. ARB Indications in CHF Patients intolerant to ACE-Inhibitors:
(Class I recommendation in stage C)
On top of ACE I and B Blockers in patients who remain symptomatic: optional (discrepancy in guidelines):
Class I (ESC, CCS), IIa (HFSA), and IIb (ACC/AHA)
Use of ARB instead of ACE-I is a Class IIa recommendation (reasonable, should be considered) in stage C heart failure

30. Spironolactone Survival RALES Aldactone N = 1663 NYHA III-IV
NEJM 1999;341:709
Spironolactone
1.0
0.9
0.8
0.7
0.6
0.5
Annual Mortality
Aldactone 18%; Placebo 23%
Survival
Aldactone
N = 1663
NYHA III-IV
Mean follow-up 2 y
Mortality curves in the RALES study. (probably already shown by previous speaker). I will coment on the progressive increase in benefit and will made a comparation with the CIBIS-II results.
p <
months
Placebo 6 12 18 24 30 36

31. Spironolactone. Indications
Moderate-severe symptoms/advanced heart failure
Class I recommendation, level of evidence B
Routine combination of ACE-I, ARB and aldosterone antagonist is not recommended (Class III)

32. Spironolactone. Practical use
Do not use if hyperkalemia, renal insuficieny
Monitor serum K+ at “frequent intervals”
Start ACE-i first
Start with 25 mg / 24h

33. ß-Blockers Has been traditionally contraindicated in pts with CHF
Now they are a corner stone in treatment of CHF

34. ß-Adrenergic Blockers Mechanism of action
Density of ß1 receptors
Inhibit cardiotoxicity of catecholamines
Neurohormonal activation HR
Anti-ischemic
Anti-hypertensive
Anti-arrhythmic
Treatment of congestive heart failure.
Possible benefits of beta adrenergic blockers .

35. ß-Adrenergic Blockers Clinical Effects in CHF
Improve symptoms (only long term)
Reduce remodeling / progression
Reduce hospitalization
Reduce sudden death
Improve survival

36. ß-Adrenergic Blockers
US Carvedilol HF
NEJM 1996; 334:
ß-Adrenergic Blockers
1.0
1.0
Carvedilol
(n=696)
0.9
0.9
Survival %
p<0.001
Placebo
(n=398)
0.8
0.8
0.7
0.7
Risk reduction = 65%
I-II NYHA HF
0.6 50
100
150
200
250
300
350
400
Days

37. ß-Adrenergic Blockers
CIBIS-II
Lancet 1999;353:9
ß-Adrenergic Blockers 1
Bisoprolol
11.8%
0.9
0.8
P<
Survival
Placebo
17.3%
0.7
NYHA III-IV
n=2647
0.6
Annual Mortality: bisoprolol=8.2%; placebo=12%
Mean Follow-up 1.4 years
0.5
200
400
600
800
Days

38. ß-Adrenergic Blockers
MERIT-HF
Lancet 1999; 353: 2001
ß-Adrenergic Blockers
Placebo 15
p=0.0062
Mortality %
Metoprolol 10 5
Risk
Reduction 34%
NYHA II-IV
N=3991 3 6 9 12 15 18 21
Months

39. ß-Adrenergic Blockers
COPERNICUS
NEJM 2001;344:1651
ß-Adrenergic Blockers
100 90 80
Survival%
Carvedilol 70 p=
35% RR 60
Placebo
N = 2289
III-IV NYHA 50 4 8 12 16 20 24 28
Months

40. ß-Adrenergic Blockers
CAPRICORN
Lancet 2001;357:1385
ß-Adrenergic Blockers 1
HR 0.77 ( ) p<0.031
0.95
0.9
Carvedilol
116 / 975 (12%)
Survival
0.85
0.8
LVD / HF
Post AMI
Placebo
151 / 984 (15%)
0.75
0.7
0.5 1
1.5 2
2.5
Years

41. ß-Adrenergic Blockers Indications
Symptomatic heart failure (stage C)
Asymptomatic ventricular dysfunction
- LVEF < % (stage B)
After AMI
Class I recommendation
AHA / ACC HF guidelines 2005
ESC HF guidelines 2005

42. ß-Adrenergic Blockers When to start ?
Patient stable
No physical evidence of fluid retention
No need for I.V. inotropic drugs
Start ACE-I / diuretic first
Start Low, Increase Slowly
Increase the dose every weeks

43. ß-Adrenergic Blockers Drugs and Dose (mg)
Initial Target
Bisoprolol / 24h 10 / 24h
Carvedilol / 12h 25 / 12h
Metoprolol succinnate 12,5-25 / 24h 200 / 24h
Nebivolol (ESC, elderly) /24h mg/24h 25

44. ß-Adrenergic Blockers Adverse Effects
Hypotension
Fluid retention / worsening heart failure
Fatigue
Bradycardia / heart block
Review treatment (+/-diuretics, other drugs)
Reduce dose
Consider cardiac pacing
Discontinue beta blocker only in severe cases

45. Digitalis Glycosides
The role of digitalis has declined somewhat because of safety concern
Recent studies have shown that digitals does not affect mortality in CHF patients but causes significant
Reduction in hospitalization
Reduction in symptoms of HF

46. Digitalis DIG Mortality % 50 40 30 20 10 Placebo N=6800 NYHA II-III
N Engl J Med 1997;336:525 50 40 30 20 10
Mortality %
Placebo
n=3403
p = 0.8
N=6800
NYHA II-III
Treatment of heart failure.
Digoxin: Effect on survival
The results obtained from 3 controlled studies which included patients at low risk (The German and Austrian Xamoterol Study Group, 1988; The Captopril-Digoxin Multicenter Research Group, 1988; DiBianco et al., 1989) indicate that the mortality was similar in the group of patients with placebo. The results of the Digitalis Investigator Group-DIG study, which included 7788 patients with heart failure in sinus rhythm, functional class II-III and LVEF < 45%. The patients were treated with digoxin or placebo, in addition to conventional therapy over a mean of 37 months ( months). No differences in mortality were observed between the two treatment groups.
Am Coll Cardiol 1996
Digoxin
n=3397 12 24 36 48
Months

47. Digitalis. Indications
• Sinus rythm: When no adequate response to ACE-i + diuretics + beta-blockers
• Atrial Fibrillation: to slow AV conduction
Dose to mg / day
Narrow therapeutic to toxic ratio !!

48. Other Drugs. (only in selected patients)
Inotropics: refractory HF
Nitrates: ischemia, angina, pulmonary congestion
Antiarrhythmics: (only amiodarone) H risk arrhyth.
Anticoagulants: High risk of embolism e.g Atrial Fibr.
Ca channel blockers (only amlodipine): ischemia, hypertension 28

49. Devices Cardiac Resynchronization Therapy (CRT)
Implantable Cardiac Defibrillator (ICD)

50. Cardiac Resynchronization Therapy for Heart Failure (CRT)
Ventricular Dysynchrony
Electrical: Inter- or Intraventricular conduction delays typically manifested as left bundle branch block
Mechanical: Regional wall motion abnormalities compromising ventricular mechanics
Cardiac Resynchronization
Modification of interventricular, intraventricular, and atrio-ventricular activation sequences
Introduces “new” terms used in this slide series.
Ventricular dysynchrony is defined as the effect caused by intra- and inter-ventricular conduction defects or bundle branch block. Read Dr. Tavazzi’s editorial referenced here for a summary of the three potential causes of ventricular dysynchrony.
Cardiac resynchronization is defined as the therapeutic intent of atrial synchronized biventricular pacing for patients with heart failure and ventricular dysynchrony. The intent of the therapy is to resynchronize the ventricular activation sequence, and to better coordinate atrial-ventricular timing to improve pumping efficiency.
Cardiac resynchronization therapy is currently indicated for the reduction of symptoms of moderate to severe heart failure (NYHA Function Class III or IV) in those patients who remain symptomatic despite stable, optimal medical therapy, and have a left ventricular ejection fraction  35% and a QRS duration 130 ms. An ICD is also available for patients with a standard ICD indication who also meet the above listed criteria.
Using atrial-synchronized biventricular pacing in combination with optimal drug therapy has been shown to significantly improve a patient’s symptoms.
Tavazzi L. Eur Heart J 2000;21:

51. Primary and secondary outcomes in CARE-HF: 409 CRT-treated patients as compared with 404 control patients
Outcomes
Hazard ratio (95% CI) p
All-cause mortality
0.64
( )
0.0019
All-cause mortality/HF hospitalization
0.54
( )
<0.0001
Cleland JG. NEJM 2005; 352:

52. Cardiac Resynchronization Therapy (CRT)
NYHA class III or IV, LVEF < 0.35 and dyssynchrony (QRS >= 120 ms)
Class I recommendation, Level A

53. Intra Cardiac Defibrillator. Indications in Secondary Prevention
Patients with sustained VT or SCD → ICD

54. Intracardiac Defibrillator Mortality outcomes over five years in SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)
Parameter
ICD,
n=829
Amiodarone, n=845
Placebo, n=847
All-cause mortality (%) 22 28 29
Mortality risk vs placebo, HR (97.5% CI)
0.77
( ), p=0.007
1.06
( ), p=0.53 —
* randomized 2521 patients with NYHA class 2-3 HF and an LVEF <35%
Bardy GH et al. N Engl J Med 2005; 352:

55. ICD indications Primary prevention
NYHA class II or III and LVEF <= 30 %
With a reasonable life expectancy > 1 year
Class I recommendation
However may be indicated even in stage B (NYHA class I) especially in ischemic aetiology

56. Heart Transplant. Indications
Refractory cardiogenic shock
Documented dependence on IV inotropic support
Severe symptoms of ischemia not amenable to revascularization
Recurrent symptomatic ventricular arrhythmias refractory to all therapeutic modalities

57. Stages in the Evolution
of Heart Failure.
Treatment
Treat risk factors.
ACE-I (or ARB) in appropriate pts for vascular disease or diabetes A
AHA / ACC HF guidelines 2005
ACE-I, ARB,
-Blockers in appropriate pts.
ICD in selected pts. B
(Asymptomatic LV Systolic Dysfunction) C
(Symptomatic LV Systolic Dysfunction)
Routine: ACE-I,  blockers, Diuretics
In selected pts: aldost antag, ARB, Digitalis, nitrates
ICD, CRT D
(Refractory End-Stage HF)
CRT
Mech. Assist device
Heart Transplant 4

58. MERCI