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

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Presentation on theme: "MANAGING CONGESTIVE HEART FAILURE Annual Conference of the Lebanese Society of Family Medicine Antoine Sarkis, MD Associate Professor of Cardiology Hotel."— Presentation transcript:

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 ESC HFSA HFSA CCS CCS ACC/AHA ACC/AHA NYHA Classification Four stage classification

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

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

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

6 Treatment Objectives Mainly decrease symptoms and prolong life Mainly decrease symptoms and prolong life But also: But also: Decrease morbidity (hospital admissions, embolism…) Decrease morbidity (hospital admissions, embolism…) Increase exercise capacity and improve quality of life Increase exercise capacity and improve quality of life Control neurohormonal changes Control neurohormonal changes Retard progression of CHF Retard progression of CHF

7 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 Treatment of CHF

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

9 Pharmacologic Therapy Diuretics ACE inhibitors Beta Blockers ARBs Digitalis Spironolactone Other

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

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

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

14 Improve symptoms Reduce remodeling / progression Reduce hospitalization Improve survival ACE-I. Clinical Effects in CHF

15 Placebo Enalapril Probability of Death Months p< p< CONSENSUS N Engl J Med 1987;316: ACE-I 253 patients NYHA IV 31 %

16 Months 0612 p = % Mortality Enalapril n=1285 Placebo n=1284 SOLVD (Treatment) N Engl J M 1991;325:293 N = 2589 CHF - NYHA II-III - EF < 35 % ACE-I

17 Mortality % 4 SAVE N Engl J Med 1992;327:669 Years Placebo Captopril 0 n=1115 n=1116 p=0.019 ² -19% Asymptomatic ventricular dysfunction post MI ACE-I N = days post AMI EF < 40 % mg / day

18 Months Placebo Ramipril p = Mortality % AIRE Lancet 1993;342:821 ACE-I N = 2006 HF after AMI

19 ACE-I Indications Symptomatic heart failure (stage C) Symptomatic heart failure (stage C) Asymptomatic ventricular dysfunction Asymptomatic ventricular dysfunction LVEF <35-40 % (stage B) LVEF <35-40 % (stage B) Patients with recent or remote history of MI regardless of EF or presence of HF (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 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 ACE-I. Practical Use

21 Hypotension (1st dose effect) Hypotension (1st dose effect) Worsening renal function, Hyperkalemia Worsening renal function, Hyperkalemia Cough Cough Angioedema Angioedema Rash, ageusia, neutropenia, … Rash, ageusia, neutropenia, … Pregnancy is a contra indication Pregnancy is a contra indication ACE-I. Adverse Effects

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

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

24 (Reprinted with permission from Pitt B, et al. Lancet. 2000) All-cause mortality Probability of Survival All-cause mortality or hospital admission Event-free Probability Sudden death or resuscitated arrest Event-free Probability Follow-up (days) P =.16 P =.08 P =.18 Losartan Captopril ELITE II: Endpoint Results

25 Val-HeFT: Study Design and Inclusion Criteria Randomized to Receiving background therapy 5010 patients EF < 40%; NYHA II - IV ACEIs (93%), diuretics (86%), digoxin (67%), beta-blockers (35%) Valsartan 40 mg bid titrated to 160 mg bid Placebo (Cohn JN, et al. N Engl J Med. 2001)

26 % risk reduction p= Event-free probability Placebo Valsartan Time since randomisation (months) Time since randomisation (months) p = 0.80 Survival probability (%) All-cause mortality and morbidity All-cause mortality Cohn et al. NEJM 2001;345:1667 Effect of Valsartan on Combined Mortality and Morbidity End Point* in Overall Population

27 CHARM Added CHARM Preserved CHARM Program 3 component trials comparing Candesartan to placebo in patients with symptomatic heart failure CHARM Alternative 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 All Cause Mortality CV Death or CHF Hospitalisation Hazard ratio p heterogeneity=0.43 Alternative Added Preserved Overall p heterogeneity=0.37 p= p=0.055 p=0.011 p=0.118 p<

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 Aldactone Placebo Survival months p < Annual Mortality Aldactone 18%; Placebo 23% N = 1663 NYHA III-IV Mean follow-up 2 y RALES NEJM 1999;341:709 Spironolactone

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

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

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

34 Density of ß 1 receptors Inhibit cardiotoxicity of catecholamines Neurohormonal activation HR Anti-ischemic Anti-hypertensive Anti-arrhythmic ß-Adrenergic Blockers Mechanism of action

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

36 US Carvedilol HF NEJM 1996; 334: Carvedilol(n=696) Placebo(n=398) Risk reduction = 65% p< ß-Adrenergic Blockers Survival % Days I-II NYHA HF

37 P< Annual Mortality: bisoprolol=8.2%; placebo=12% Mean Follow-up 1.4 years Days Bisoprolol11.8% Placebo17.3% Survival NYHA III-IV n= CIBIS-II Lancet 1999;353:9 ß-Adrenergic Blockers

38 MERIT-HF Lancet 1999; 353: 2001 Months Mortality % Placebo Metoprolol p= Risk Reduction 34% ß-Adrenergic Blockers NYHA II-IV N=3991

39 Placebo Carvedilol Months N = 2289 III-IV NYHA COPERNICUS NEJM 2001;344:1651 Survival% ß-Adrenergic Blockers p= % RR

40 1 Survival Years Carvedilol 116 / 975 (12%) Placebo 151 / 984 (15%) HR 0.77 ( ) p<0.031 CAPRICORN Lancet 2001;357:1385 ß-Adrenergic Blockers LVD / HF Post AMI

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

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

43 InitialTarget Bisoprolol 1.25 / 24h 10 / 24h Carvedilol / 12h25 / 12h Metoprolol succinnate 12,5-25 / 24h200 / 24h Nebivolol (ESC, elderly) 1.25/24h 10 mg/24h ß-Adrenergic Blockers Drugs and Dose (mg)

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

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 Placebo n=3403 Digoxin n= Mortality % DIG N Engl J Med 1997;336:525 Months p = 0.8 Digitalis N=6800 NYHA II-III

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

48 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 Other Drugs. (only in selected patients)

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 Tavazzi L. Eur Heart J 2000;21: Tavazzi L. Eur Heart J 2000;21:

51 Cleland JG. NEJM 2005; 352: 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( ) All-cause mortality/HF hospitalization 0.54( )<0.0001

52 Cardiac Resynchronization Therapy (CRT) NYHA class III or IV, LVEF = 120 ms) NYHA class III or IV, LVEF = 120 ms) Class I recommendation, Level A Class I recommendation, Level A

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

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

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

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

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

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