Congestive Heart Failure 2015

Transcription

1 Definition Congestive Heart Failure 215 JP Mehegan/ Mercy Cardiology n Cardiac failure; Congestive heart failure; Chronic heart failure (synonyms) n When the heart is unable to pump sufficiently and at the appropriate pressure to meet the bodies needs n Symptoms; dyspnea, edema, fatigue; activity intolerance n STARTING POINT Types of Heart Failure n Systolic ; heart failure with abnormal LV function; ejection fraction < 4% n Diastolic; heart failure with normal LV systolic function and abnormal cardiac relaxation (diastolic function); 5% n Other; valvular, ischemia, MI, constriction/pericardial disease The Problem (USA) 5,, patients 6,5, hospital days / year 3, deaths / year More than half of those diagnosed will be dead in 5 years 6% of health care budget (38 billion) Incidence doubling in last ten years 6% Inpatient care $23.1 billion Heart Failure Costs Total = $38.1 billion (5.4% of total healthcare costs) 39% Outpatient care $14.7 billion 1% Transplants $27 million Stages in the evolution of Heart Failure n A. HF risk factors; no documented heart disease or symptoms n B. Heart disease; no symptoms. Asymptomatic LV dysfunction n C. Prior or current symptomatic CHF n D. Refractory HF symptoms AHA / ACC HF guidelines 25 O Connell JB et al. J Heart Lung Transplant. 1994;13:S17-S112 1

2 Stages in Prevention and Treatment of Heart Failure n A. Treat risk factors, avoid toxins. ACE-I n B. ACE-I, Beta blockers n C. ACE-I, Beta blockers, dig, diuretics, aldosterone antagonists, ARB, resynchronization (Bi-V pacing), new therapies n D. Ultrafiltration, inotrope therapy, VADs and transplant Classification of Functional Status; NYHA n 1. No physical limitations n 2. Symptoms with moderate activity, exercise. n 3. Symptoms with mild activity; activities of daily living n 4. Symptoms at rest n H&P Initial / Ongoing Evaluation n Assess functional capacity (NYHA, 6 min walk) n Assess volume status: (edema, rales, jugular, hepatomegaly, body weight) n Lab assessment: routine: electrolytes, renal function, ECHO, X ray,tsh, EKG n BNP Causes of Cardiomyopathy/ CHF n 135 Causes of cardiomyopathy n CAD; prior MI, diffuse ischemia (7%) n Hypertension n Endocrine; diabetes, thyroid n Drugs/ Toxins; ETOH, cocaine, chemo n Afib/ flutter; rate related n Infection, familial, nutritional, idiopathic B type natriuretic peptide! BNP n Role in the emergency room 7 yo with PND, orthopnea, edema and vascular congestion on CXR 7 yo with COPD, wheezing, rales and edema, clear CXR n Role in the clinic Treatment Objectives n Increase Survival n Improve LV function n Improve symptoms/ Quality of Life n Improve exercise capacity n Block neurohormonal changes and prevent progressive HF n CHF Trials App ($2.99) 2

3 % Decrease in Mortality Drugs That Reduce Mortality in Heart Failure With Reduced Ejection Fraction % 1% 2% 3% 4% Angiotensin receptor blocker ACE inhibitor Drugs that inhibit the renin-angiotensin system have modest effects on survival Mineralocorticoid Beta receptor blocker antagonist Based on results of SOLVD-Treatment, CHARM-Alternative, COPERNICUS, MERIT-HF, CIBIS II, RALES and EMPHASIS-HF Treatment Pharmacologic Therapy n ACE inhibitors/arbs/ Vasodilators n Beta Blockers n Diuretics n Digitalis n Spironolactone/ Eplerenome ACE-I. Clinical Effects n Improve symptoms n Reduce remodeling / progression n Reduce hospitalization n Improve survival ACE-i Practical Use n Start with low dose n Increase dose as tolerated n Renal function & serum K + after 1-2 weeks n Dose NOT determined by symptoms n Target randomized trial doses n Reduce diuretics if possible Mortality Reduction with ACE-i ACE-i Dose (mg) Study ACE-i Clinical Setting CONSENSUS (1987) Enalapril CHF SOLVD treatment Enalapril CHF AIRE Ramipril CHF Vheft-II Enalapril CHF TRACE Trandolapril CHF SAVE Captopril LVD/MI SMILE Zofenopril High risk HOPE (2) Ramipril High risk Initial Maximum Captopril 6.25 / 8h 5 / 8h Enalapril 2.5 / 12 h 1 to 2 / 12h Fosinopril 5 to 1 / day 4 / day Lisinopril 2.5 to 5. / day 2 to 4 / day Quinapril 1 / 12 h 4 / 12 h Ramipril 1.25 to 2.5 / day 1 / day AHA / ACC HF guidelines 25 3

4 ACE-i Adverse Effects n Hypotension n Worsening renal function n Hyperkalemia n Cough 5-1%(iron pill may prevent) n Angioedema (1/1) n Rash, ageusia, neutropenia (1-2%) n ACE intolerant use ARB Angiotensin Receptor Blockers! ARBs n As added therapy n As alternative therapy (ACEi intolerant) n FDA approved; Valsartan 4 mg BID start, 16 mg BID target n Candesartan; 4 mg QD start, 32 mg QD target n Most commonly used ( not approved and underdosed), Losartan, target 15 mg QD Val-HeFT 51 patients 18 years; EF <4%; NYHA II-IV; LVIDd >2.9 cm/m 2 Valsartan 4 mg bid titrated to 16 mg bid ACE inhibitors, diuretics, digoxin, β-blockers Cohn JN et al. Eur J Heart Fail. 2;2: Randomized to Receiving background therapy Placebo Effect of Valsartan on Combined Morbidity/ Mortality Endpoint* Probability 8 of Event- 75 Free 7 Survival Months *All-cause mortality, sudden death with resuscitation, hospitalization for worsening heart failure, or therapy with IV inotropes or vasodilators. Cohn JN et al. N Engl J Med. 21;345: Valsartan Placeb 13.2% Risk o Reduction P =.9 3 Reduction in Combined Morbidity/Mortality Endpoint* with Valsartan (No ACE-I Subgroup) CHARM 1 9 Valsartan, n=185 Placebo, 8 n=181 Probability 7 of Event- Free 6 44.% Risk probability5 reduction P < Time Since Randomization (months) Hazard ratio (Cox model) :.56 *First morbid event, including death or hospitalization Maggioni et al. J Am Coll Cardiol 22;4: ,61 patients with heart failure 3 Individual component randomized trials with the ARB candesartan (4 or 8 mg/day, titrated to target dose of 32 mg) or placebo CHARM Added Patients with LVEF <4% and treated with an ACE-inhibitor CHARM Alternative Patients with LVEF <4% and ACE-inhibitor intolerant Endpoints (follow-up minimum 2 years): CHARM Preserved Patients with LVEF >4% with or without ACEinhibitor! Primary Component trials: cardiovascular mortality or HF hospitalization! Primary Overall trial results: All-cause mortality 4

5 At risk, n % NNT = 23 Primary Outcome! CV Death or CHF Hospitalization! CHARM Added Placebo Time, yr Candesartan HR.85 (95% CI:.75,.96), p =.11 Adjusted HR =.85, p = Placebo Candesartan SS (42.3%) 483 (37.9%) 15% risk reduction ß-Adrenergic Blockers Mechanism of action n Increase Density of ß 1 receptors n Inhibit cardiotoxicity of catecholamines n Block Neurohormonal activation n HR n Antiischemic n Antihypertensive Antiarrhythmic Antioxidant, Antiproliferative ß-Adrenergic Blockers Clinical Effects n Improve symptoms (only long term) n Reduce remodeling / progression n Improve LV systolic function n Reduce hospitalization n Reduce sudden death n Improve survival n Patient stable ß-Adrenergic Blockers When to start n Not volume overloaded n No need for i.v. inotropic drugs n Stable dose of ACEi /Diuretic/ Dig ß-Adrenergic Blockers Contraindications n Asthma (not COPD) n AV block n Symptomatic hypotension / Bradycardia n PVD and Diabetes are NOT contraindications n Hypotension ß-Adrenergic Blocker Adverse Effects n Fluid retention / worsening heart failure n Fatigue n Bradycardia / heart block n Reduce dose n Consider cardiac pacing n DON T GIVE UP 5

6 ß-Adrenergic Blockers Dose (mg) Carvedilol Effect on Survival Initial Target Bisoprolol 1.25 / 24h 1 / 24h Carvedilol / 12h 25 / 12h Carvedilol XL 1/ 24h 8/24h 35% Reduction In death Metoprolol succinnate / 24h 2 / 24h Start Low, Increase Slowly Increase the dose every 2-4 weeks What is Target Dose? What is Target Dose Which Agent Should We Use? n Substantial differences in Beta Blocking Agents n Beta-1 Selectivity n Alpha-1 blockade n Ancillary Properties n Antioxidant n Endothelin regulation n 5.7%mortality n reduction COMET! Carvedilol vs Metoprolol Tartrate 6

7 Digitalis. Clinical Effects DIG trial n Improve symptoms and measured exercise n Reduction in hospitalization for CHF n Does not improve survival N=68 NYHA II-III N Engl J Med 1997;336:525 Digitalis. Indications In combination with ACE-i + diuretics if persisting symptoms AF, to slow AV conduction Dose.125 to.25 mg / day Diuretics. Indications 1.Symptomatic HF, with fluid retention Edema Dyspnea Lung Rales Jugular distension Hepatomegaly Pulmonary edema (Xray) AHA / ACC Guidelines 25 Loop Diuretics / Thiazides. Practical Use n Start with low dose. Titrate to achieve dry weight n Monitor serum K + / renal function at frequent intervals n Reduce dose when fluid retention is controlled n Teach the patient when, how to change dose Loop diuretics. Dose (mg) Initial Maximum Bumetanide.5 to 1. / 12-24h 1 / day Furosemide 2 to 4 / 12-24h 4 / day Torsemide 1 to 2 / 12-24h 2 / day n Combine to overcome resistance n Do not use alone 7

8 Thiazides, Loop Diuretics. Adverse Effects K +, Mg + wasting (sudden death???) Na + Stimulation of neurohormonal activity Hyperuricemia (15-4%) Hypotension. Ototoxicity. Metabolic Alkalosis. Diuretic Resistance n Neurohormonal activation n Hypertrophy of distal nephron n Reduced tubular secretion (renal failure, NSAIDs) n Decreased renal perfusion (low output) n Altered absortion of diuretic n Noncompliance with drugs/ Dennys biscuits and gravy Managing Resistance to Diuretics Restrict Na + /H 2 O intake (Monitor Sodium) Increase dose (individual dose, frequency, i.v.) Combine: furosemide + thiazide / spiro / metolazone Reduce dose of ACE-I Stop NSAIDS Dopamine (increase cardiac output) Aldosterone in Heart Failure n Levels up 2X from normal n Produces adverse effects n Cardiac remodeling n Na++ retention n Up SNS n Down arterial compliance RALES Trial RALES Trial; Mortality Data n 1663 patients n LVEF greater than or equal to 35 n NYHA III-IV n Spitonolactone or placebo in addition to standard therapy 8

9 Adverse Effects of Spironolactone RALES Clinical Hyperkalemia NA 34% Mild NA 34% Severe 2% 11% Azotemia NA 12% EMPHASIS-HF EMPHASIS- HF: Major results Outcome Eplerenone (%) Placebo (%) Adjusted hazard ratio (95% CI) Cardiovascular death/heartfailure (.54.74) <.1 hospitalization Cardiovascular death (.61.94).1 Heart-failure hospitalization (.47.7) <.1 Hospitalization for hyperkalemia ( ).85 NYHA Class II HF (N=2737) LV EF < 3% Eplerenone 25-5mg QD vs. Placebo p Aldosterone Antagonist Recomendations n Add to standard treatment if: n Advanced symptoms n No contraindications n Increased K + n Azotemia n Follow K+ and BUN/Cr Aldosterone Antagonist Recomendations n Decrease KCL by 5% n Lab Follow-up n Low risk n K+ and BUN/Cr level at week 1& 4 n High Risk n K+ and BUN/Cr level at day 3 and at week 1 & 4 PARADIGM-HF n Entresto formerly LCZ696 n Approved July 215 n ARB-Neprilysin inhibition vs enalapril 1 mg BID n Valsartan-Sacubitril n Starting dose 49/51 mg BID, target 97/13 BID Neprilysin Inhibition Potentiates Actions of Endogenous Vasoactive Peptides That Counter Maladaptive Mechanisms in Heart Failure Neprilysin Neurohormonal activation Vascular tone Cardiac fibrosis, hypertrophy Sodium retention Neprilysin inhibition Inactive metabolites 9

10 PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint) Kaplan-Meier Estimate of Cumulative Rates LCZ696 Enalapril (%) 16 Patients at Risk 8 Enalapril (n=4212) Days After Randomization LCZ696 (n=4187) HR =.8 ( ) P =.2 Number needed to treat = PARADIGM-HF: Adverse Events Prospectively identified adverse events LCZ696 (n=4187) Enalapril (n=4212) P Value Symptomatic hypotension <.1 Serum potassium > 6. mmol/l Serum creatinine 2.5 mg/dl Cough <.1 Discontinuation for adverse event Discontinuation for hypotension NS Discontinuation for hyperkalemia NS Discontinuation for renal impairment Angioedema (adjudicated) Medications, no hospitalization 16 9 NS Hospitalized; no airway compromise 3 1 NS Airway compromise ---- Angiotensin Neprilysin Inhibition With LCZ696 Doubles Effect on Cardiovascular Death of Current Inhibitors of the Renin-Angiotensin System % Decrease in Mortality % 1% 2% 3% 4% Angiotensin receptor blocker 15% ACE inhibitor 18% 2% Angiotensin neprilysin inhibition Effect of ARB vs placebo derived from CHARM-Alternative trial Effect of ACE inhibitor vs placebo derived from SOLVD-Treatment trial Effect of LCZ696 vs ACE inhibitor derived from PARADIGM-HF trial ENTRESTO Biventricular pacing n Entresto $4/month, $48/year n Enalapril $4/ month $48/ year 1

11 Cardiac resynchronization 11