CT Academy of Family Physicians Scientific Symposium October 2012 Amit Pursnani, MD
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1 CT Academy of Family Physicians Scientific Symposium October 2012 Amit Pursnani, MD
2 Clinical syndrome resulting from a structural or functional cardiac disorder that impairs the ability of the heart to fill or eject blood. Cardinal manifestations Fluid retention Pulmonary congestion Peripheral edema Dyspnea and fatigue Limited exercise tolerance
3 Prevalence of HF -U.S. > 5,000,000 Worldwide > 15,000,000 New HF -U.S.: Mortality of HF: Hospital Days - U.S. Cost of HF: > 550,000/year 200,000/yr in U.S. 6.5 million $ 27.9 Billion/yr 80% of patients hospitalized for HF are over 65 years old
4 Loss of cardiomyocyte function due to: Ischemic Heart Disease Hypertension Infections (e.g., viral myocarditis, Chagas disease) Toxins (e.g., alcohol or cytotoxicdrugs) ValvularDisease Tachyarrhythmias Peripartum Cardiomyopathy Idiopathic Cardiomyopathy Other (thyroid, infiltrative, familial etc)
5 Stage A Asymptomatic with coronary artery disease, hypertension, or diabetes mellitus without impaired left ventricular function or hypertrophy Stage B Asymptomatic with LV hypertrophy and/or impaired LV function Stage C Current or past symptoms of HF associated with structural heart disease Stage D Refractory HF requiring continuous inotropicinfusion, mechanical circulatory support, procedures to facilitate fluid removal, cardiac transplantation or end-of-life care
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8 New York Heart Association Functional Classification CLASS 1 No limitations of physical activity, no symptoms with ordinary activities CLASS 2 Mild/slight limitation, symptoms with ordinary activities CLASS 3 Moderate/marked limitation, symptoms with less than ordinary activities CLASS 4 Severe limitation, symptoms of heart failure at rest Adapted from Criteria Committee of the New York Heart Association, 1994.
9 NHLBI: 35% of pts with HF are NYHA I 35% of pts with HF are NYHA II 25% of pts with HF are NYHA III 5% of pts with HF are NYHA IV About 85% of pts with HF are treated in the ambulatory setting
10 Early Ace Inhibitor Trials 4% 1 yr 9% 1 yr 12% 1 yr 36% 1yr I II III IV NYHA
11 Reduce excess myocardial oxygen demand Reduce mechanical stress on the heart Decrease afterload Decrease preload Increase myocardial contractility Reduce Neurohumoral cardiac toxicity Sympathetic blockade Renin-angiotensin blockade
12 Reduce afterload Reduce preload Inhibit RAS Inhibit SNS Increase Contractility Vasodilators Diuretics, NP activators ACEI, ARB, Aldo Blockers Beta blockers Digoxin, IV inotropes
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14 Included patients with LVEF < 45% RCT of 3397 patients in digoxingroup and 3403 patients in placebo group in addition to diuretics and Ace Inhibitors Found no effect on mortality (35% in both groups) Fewer hospitalizations for heart failure in digoxin group than placebo group (26.8% vs 34.7% The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure. NEJM 1997
15 I IIa IIb III Digitalis can be beneficial in patients with current or prior symptoms of HF and reduced LVEF to decrease hospitalizations for HF.
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17 SOLVD Prevention (Asymptomatic LVD) 20% Reduction in Death or HF Hospitalization 29% Reduction in Death or new heart failure SOLVD Treatment (Chronic Heart Failure) 16% Reduction in Mortality CONSENSUS (Severe Heart Failure) 40% Reduction in Mortality at 6 months, 31 % reduction at 1 year, and 27% reduction at end of study SOLVD Investigators. NEJM 1992 SOLVD Investigators NEJM 1991 CONSENSUS Study Trial Group NEJM 1987
18 I I IIa IIb III IIa IIb III Beta-blockers and ACEIsshould be used in all patients with a recent or remote history of MI regardless of EF or presence of HF. ACEI should be used in patients with a reduced EF and no symptoms of HF, even if they have notexperienced MI. I IIa IIb III ACEI or ARBscan be beneficial in patients with hypertension and LVH and no symptoms of HF.
19 I IIa IIb III ACEIs are recommended for all patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated. I IIa IIb III Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patients with current or prior symptoms of HF and reduced LVEF.
20 Mortality in Patients Receiving ACE Inhibitors SOLVD-Prevention Survival 0.6 PROMISE SOLVD-Treatment DIG 0.5 CONSENSUS PRAISE V-HeFT Year ACE inhibitor arms of CONSENSUS, V-HeFT, and SOLVD trials. Placebo arms of PRAISE, PROMISE, and DIG trials (all receiving ACE inhibitors).
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22 ValHeFt: 5010 patients No difference in mortality versus ace inhibitor (19.7% vs19.4%) Posthocanalysis revealed possible increased primary end-point if ARB used in addition to Ace inhibitor. CHARM: Candestartan in heart failure Alternative Added Preserved
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25 ARBS in Patients Not Taking ACE Inhibitors: Val-HeFT & CHARM-Alternative 100 Val-HeFT 50 CHARM-Alternative Surviva al % Valsartan Placebo CV Death or HF Hosp % Placebo Candesartan 50 p = HR 0.77, p = Months Months Maggioni AP et al. JACC 2002;40: Granger CB et al. Lancet 2003;362:772-6.
26 I IIa IIb III I IIa IIb III An ARB should be administered to post-mi patients without HF who are intolerant of ACEIsand have a low LVEF. ACEIsor ARBscan be beneficial in patients with hypertension and LVH and no symptoms of HF. I IIa IIb III ARBscan be beneficial in patients with low EF and no symptoms of HF who are intolerant of ACEIs.
27 I IIa IIb III ARBsapproved for the treatment of HF are recommended in patients with current or prior symptoms ofhf and reduced LVEF who are ACEIintolerant (see full text guidelines for information regarding patients with angioedema). I IIa IIb III 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 ARBsfor other indications.
28 I IIa IIb III The addition of an ARB may be considered in persistently symptomatic patients with reduced LVEF who are already being treated with conventional therapy. I IIa IIb III Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patientswith current or prior symptoms of HF and reduced LVEF.
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32 Reduction in sympathetic tone by a central effect Reduction in blood pressure (B2 receptors) Negative chronotropic effect Increase diastolic filling better myocardial perfusion Anti-ischemic effects Anti-arrhythmic properties Interaction (inhibitory) with RAS system
33 From: β-blocker Therapy in Heart Failure: Scientific Review JAMA. 2002;287(7): doi: /jama
34 Effect of Beta Blockade on Outcome in Patients With HF and Post-MI LVD Study Drug HF Severity Target Dose (mg) Outcome US Carvedilol 1 carvedilol mild/ moderate BID 48% disease progression (p=.007) CIBIS-II 2 bisoprolol moderate/ severe 10 QD 34% mortality (p <.0001) MERIT-HF 3 metoprolol succinate mild/ moderate 200 QD 34% mortality (p =.0062) COPERNICUS 4 carvedilol severe 25 BID 35% mortality (p =.0014) CAPRICORN 5 carvedilol post-mi LVD 25 BID 23% mortality (p =.031) 1. Colucci WS et al. Circulation 1196;94: CIBIS II Investigators. Lancet 1999;353: MERIT-HF Study Group. Lancet 1999;353: Packer M et al. N Engl J Med 2001; The CAPRICORN Investigators. Lancet 2001;357:
35 IMPACT-HF Primary End Point: Patients Receiving Beta Blocker at 60 Days Improvement 18% % Patients (%) P < % 0 Carvedilol Predischarge Initiation (n=185) Physician Discretion Postdischarge Initiation* (n=178) Gattis WA et al. JACC 2004;43:
36 I I IIa IIb III IIa IIb III Beta-blockers and ACEIsshould be used in all patients with a recent or remote history of MI regardless of EF or presence of HF. Beta-blockers are indicated in all patients without a history of MI who have a reduced LVEF with no HF symptoms.
37 I IIa IIb III Beta-blockers (using 1 of the 3 proven to reduce mortality, i.e., 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.
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39 Mortality Reduction ACE-I B-BlockerBlocker 16% 3 yr 40 % 1 yr 34 % 1 yr 65% ½ yr 35% 10 mos SOLVD II/III CONSENSUS IV MERIT HF II/III US CARVEDILOL II/III COPERNICUS IIIB
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41 Aldosterone Antagonists in HF RALES (Advanced HF) EPHESUS (Post-MI) Probability of Survival RR = 0.70 P < Placebo Spironolactone RR = 0.85 P < Placebo Epleronone Months Months Pitt B. N Engl J Med 1999;341: Pitt B. N Engl J Med 2003;348:
42 Trial stopped prematurely secondary to significant mortality reduction with eplerenone Zannad F et al. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. NEJM 2011.
43 Outcome Eplerenone (%) Placebo (%) Adjusted hazard ratio (95% CI) p Cardiovascular death/heartfailure hospitalization ( ) <0.001 Cardiovascular death ( ) 0.01 Heart-failure hospitalization ( ) <0.001 Hospitalization for hyperkalemia ( ) 0.85 Zannad F et al. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. NEJM 2011.
44 I IIa IIb III I IIa IIb III Addition of an aldosterone antagonist is recommended 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. Creatinine should be less than or equal to 2.5 mg/dlin men or less than or equal to 2.0 mg/dlin women and potassium should be less than 5.0 meq/l. Under circumstances where monitoring for hyperkalemia or renal dysfunction is not anticipated to be feasible, the risks may outweigh the benefits of aldosteroneantagonists. Routine combined use of an ACEI, ARB, and aldosterone antagonist is not recommended for patients with current or prior symptoms of HF and reduced LVEF.
45 Circulation 2011.
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47 A-HeFT All-Cause Mortality % Decrease in Mortality Surviva al % Placebo Fixed Dose ISDN/HDZN P = Days Since Baseline Visit Taylor AL et al. N Engl J Med 2004;351:
48 I IIa IIb III The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF who are already taking an ACEI and betablocker for symptomatic HF and who have persistent symptoms. I IIa IIb III A combination of hydralazine and a nitrate might be reasonable in patients 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.
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50 MADIT II: Prophylactic ICD in Ischemic LVD (LVEF 30%) 1.0 Probabili ity of Survival Defibrillator Conventional Therapy Number at Risk Defibrillator Conventional Year (.91) 274 (.84) 110 (.78) (.90) 170 (.78) 65 (.69) 3 Moss AJ et al. N Engl J Med 2002;346:
51 ICD Therapy in the SCD-HeFT Trial: Mortality by Intention-to-Treat.4 Amiodarone vs Placebo HR % Cl P Value.53 ICD vs Placebo Morta ality.2 22% 17%.1 0 Amiodarone ICD Therapy Placebo Months of Follow-Up Bardy GH et al. N Engl J Med 2005;352:
52 CRT in Patients with Advanced HF and a Prolonged QRS Interval: COMPANION Primary End Point: All-Cause Mortality Death or Hospitalization Due to HF Risk of all-cause mortality reduced by 19% in group with CRT and ICD (p =.014) Risk of death or hospitalization from HF reduced by 34% in ICD group and by 40% in ICD-CRT group (p <.001) Bristow MR et al. N Engl J Med 2004;350:
53 CRT Improves Quality of Life and NYHA Functional Class Average Change in Score (MLWHF) NYHA: Proportion Improving by 1 or More Class MIRACLE * * MUSTIC SR CONTAK CD * MIRACLE ICD * (%) * * MIRACLE CONTAK CD * MIRACLE ICD Control CRT * P <.05 Abraham WT et al. Circulation 2003;108:
54 Effect of CRT Without an ICD on All-Cause Mortality: CARE-HF 100 % Event- -Free Survival Number at risk CRT Medical Therapy HR = 0.64 (95% CI = ) p = CRT Medical Therapy ,000 1,500 Days Cleland JG et al. N Engl J Med 2005;352:
55 I I IIa IIb III IIa IIb III 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 hemodynamically destabilizing ventricular tachycardia. ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with ischemic heart disease who are at least 40 days post-mi, have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year.
56 I IIa IIb III I IIa IIb III ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with nonischemiccardiomyopathywho have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. Placement of an ICD is reasonable in patients with 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 reasonable expectation of survival with good functional status of more than 1 year.
57 I IIa IIb III Patients with LVEF less than or equal to 35%, sinus rhythm, and NYHA functional class III or ambulatory class IV symptoms despite recommended, optimal medical therapy and who have cardiac dyssynchrony, which is currently defined as a QRS duration greater than 120 ms, should receive cardiac resynchronization therapy unless contraindicated.
58 Evidence-Based Treatment Across the Continuum of Systolic LVD and HF Control Volume Diuretics Renal Replacement Therapy* Improve Clinical Outcomes ACEI Aldosterone β-blocker or ARB Antagonist or ARB CRT ± an ICD* *In selected patients HDZN/ISDN* Treat Residual Symptoms Digoxin
59 LVAD Destination therapy Bridge to transplant Heart Transplant
60 Treating known risk factors (e.g. hypertension) with therapy consistent with contemporary guidelines Ventricular rate control for all patients Drugs for all patients - Diuretics Drugs for appropriate patients ACEI ARBs Beta-Blockers Digitalis Coronary revascularization in selected patients Restoration/maintenance of sinus rhythm in appropriate patients
61 TOPCAT Trial: Multicenter RCT evaluating aldosteroneantagonist spironolactonefor patients with heart failure with normal EF.
62 Questions?
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