Heart Failure: COPYRIGHT. an overview

Transcription

1 Heart Failure: an overview James D Chang, MD Advanced Heart Failure Center The Cardiovascular Institute Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts disclosures: none

2 overview pathophysiology management of chronic HF (dilated LV and reduced LVEF) management of ADHF mitral regurgitation HFpEF (diastolic HF) nondilated LV with preserved LVEF

3 definition syndrome resulting from pathological reduction of cardiac output or elevation of ventricular filling pressures or both LV dysfunction (systolic or diastolic) heart failure HF is not a diagnosis made by echocardiography (although echo helps!) HF is the final common pathway for all cardiac disease

4 symptoms effort intolerance dyspnea, orthopnea, PND edema GI (anorexia, malabsorption, diarrhea, cardiac cachexia, visceral congestion, cirrhosis)

5 physical findings jugular venous distention (Kussmaul sign) peripheral edema S3, prominent P2, displaced LV/RV PMI pulmonary vascular congestion ascites, abdominojugular reflux weak arterial pulsations, reduced BP reduced skin perfusion reduced mental status

6 echocardiography reduced LVEF/SV LV chamber enlargement/lvh LA/RA enlargement valve dysfunction (MR/AS/AR/MS/TR) pulmonary hypertension diastolic filling abnormality (ranging from delayed relaxation to restrictive filling) pericardial thickening/constraint elevated LV/RV filling pressure

7 Scope of problem DRG 127: heart failure & shock represents 6% of the entire volume of all Medicare discharge diagnoses By far the highest volume Medicare DRG (next are 3.9%, 3.2%, and 3.2%) 5 million Americans have HF 550,000 new cases annually > 1 million hospitalizations/year for HF as 1 0 dx 2 million hospitalizations/year for HF as 2 0 dx $37 billion in direct and indirect costs per year in USA Mortality with HF is, respectively, 11%, 22%, and 42% at 30 days, 1 year, and 5 years post hospitalization for ADHF 30% readmission rate for ADHF within 3-6 months

8 etiology Coronary Hypertension Valvular Drugs and toxins Viral and other infectious pregnancy-assciated Idiopathic (contractile protein gene mutations) infiltrative radiation

9 HFSA 2006 Practice Guideline (3.2) HF Risk Factor Treatment Goals Risk Factor Goal Hypertension Generally < 130/80 Diabetes See ADA guidelines 1 Hyperlipidemia See NCEP guidelines 2 Inactivity min. aerobic 3-5 x wk. Obesity Alcohol Weight reduction < 30 BMI Men 2 drinks/day, women 1 Smoking Dietary Sodium Cessation Maximum 2-3 g/day 1. Diabetes Care 2006; 29: S4-S JAMA 2001; 285: Adapted from: Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

10 pathophysiology Initial insult (MI, HTN, valve, virus, toxin, etc) causes reduced SV/CO or increased LV/RV filling pressure reduced CO triggers compensatory mechanisms (adrenergic, RAAS, inflammatory cytokines) are adaptive in the short-term Persistent hyperactivation of these compensatory mechanisms leads to deleterious remodelling of cardiac structure and function at the molecular and cellular level, and eventually of the entire circulatory system, leading to decompensation in the long-term

11 medical therapy of HF diuretics (see ADHF) beta blockers vasodilators: ACE-inhibitors/ARBs aldosterone antagonists digoxin antiarrhythmics

12 HFSA 2006 Practice Guideline (7.23) Loop Diuretics Agent Furosemide Bumetanide Torsemide Ethacrynic acid Initial Daily Dose 20-40mg qd or bid mg qd or bid mg qd mg qd or bid Max Total Daily Dose 600 mg 10 mg 200 mg 200 mg Elimination: Renal Met. 65%R-35%M 62%R/38%M 20%R-80%M 67%R-33%M Duration of Action 4-6 hrs 6-8 hrs hrs 6 hrs absorption Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

13 HFSA 2006 Practice Guideline (7.3, 7.4) Pharmacologic Therapy: Beta Blockers Beta blockers shown to be effective in clinical trials are recommended for symptomatic and asymptomatic patients with an LVEF 40%. Strength of Evidence = A Beta blockers are recommended as routine therapy for asymptomatic patients with an LVEF 40%. Post MI Strength of Evidence = B Non Post-MI Strength of Evidence = C Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

14 Effect of Beta Blockade on Outcome in Patients With HF and Post-MI LVD Study US Carvedilol 1 CIBIS-II 2 MERIT-HF 3 COPERNICUS 4 CAPRICORN 5 Drug carvedilol bisoprolol metoprolol succinate carvedilol carvedilol HF Severity mild/ moderate moderate/ severe mild/ moderate severe post-mi LVD Target Dose (mg) BID 10 QD 200 QD 25 BID 25 BID Outcome 48% disease progression (p=.007) 34% mortality (p <.0001) 34% mortality (p =.0062) 35% mortality (p =.0014) 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:

15 HFSA 2006 Practice Guideline (7.5, 7.8) Pharmacologic Therapy: Beta Blockers RECENT DECOMPENSATION OR EXACERBATION Beta blocker therapy is recommended for patients with a recent decompensation of HF after optimization of volume status and successful discontinuation of IV diuretics and vasoactive agents. Whenever possible, beta blocker therapy should be initiated in the hospital at a low dose prior to discharge of stable patients. Strength of Evidence = B Continuation of beta blocker therapy is recommended in most patients experiencing a symptomatic exacerbation of HF during chronic maintenance treatment. If necessary, consider temporary dose reduction Avoid abrupt discontinuation Reinstate or gradually increase before discharge Strength of Evidence = C Adapted from: Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

16 metoprolol vs carvedilol: which one should I use? metoprolol (b 1 ) carvedilol (b 1, b 2, a 1 ) avoid carvedilol in patients with active bronchospasm or hypotension COMET: mortality (all-cause and CV) lower in carvedilol arm (34 and 29%, repectively) than in metoprolol arm (40 and 35%, respectively)

17 HFSA 2006 Practice Guideline (7.1, 7.4) Pharmacologic Therapy: ACE Inhibitors ACE inhibitors are recommended for symptomatic and asymptomatic patients with an LVEF 40%. Strength of Evidence = A ACE inhibitors should be titrated to doses used in clinical trials (as tolerated during uptitration of other medications, such as beta blockers). Strength of Evidence = C ACE inhibitors are recommended as routine therapy for asymptomatic patients with an LVEF 40%. Post MI Strength of Evidence = B Non Post-MI Strength of Evidence = C Adapted from: Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

18 ACE Inhibitors in Heart Failure: From Asymptomatic LVD to Severe HF SOLVD Prevention (Asymptomatic LVD) 20% death or HF hosp. 29% death or new HF SOLVD Treatment (Chronic Heart Failure) CONSENSUS (Severe Heart Failure) 40% mortality at 6 mos. 31% mortality at 1 year 16% mortality 27% mortality at end of study No difference in incidence of sudden cardiac death SOLVD Investigators. N Engl J Med 1992;327: SOLVD Investigators. N Engl J Med 1991;325: CONSENSUS Study Trial Group. N Engl J Med 1987;316:

19 HFSA 2006 Practice Guideline (7.10) Pharmacologic Therapy: Angiotensin Receptor Blockers ARBs are recommended for routine administration to symptomatic and asymptomatic patients with an LVEF 40% who are intolerant to ACE inhibitors for reasons other than hyperkalemia or renal insufficiency. Strength of Evidence = A Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

20 ARBS in Patients Not Taking ACE Inhibitors: Val-HeFT & CHARM-Alternative Survival % p = Val-HeFT Placebo Valsartan CV Death or HF Hosp % CHARM-Alternative Placebo Candesartan HR 0.77, p = Months Months Maggioni AP et al. JACC 2002;40: Granger CB et al. Lancet 2003;362:772-6.

21 Angiotensin Receptor Neprilysin Inhibition (ARNI) versus Enalapril in Heart Failure John J.V. McMurray, M.D., Milton Packer, M.D., Akshay S. Desai, M.D., M.P.H., Jianjian Gong, Ph.D., Martin P. Lefkowitz, M.D., Adel R. Rizkala, Pharm.D., Jean L. Rouleau, M.D., Victor C. Shi, M.D., Scott D. Solomon, M.D., Karl Swedberg, M.D., Ph.D., Michael R. Zile, M.D., for the PARADIGM-HF Investigators and Committees N Engl J Med Volume 371(11): September 11, 2014

22 Study Overview The ARNI LCZ696 was compared with the ACE inhibitor enalapril in patients with advanced heart failure. LCZ696 was superior to enalapril in all outcomes. Neprilysin inhibition may replace ACE inhibition for the treatment of heart failure.

23 Kaplan Meier Curves for Key Study Outcomes, According to Study Group. McMurray JJV et al. N Engl J Med 2014;371:

24 HFSA 2006 Practice Guideline (7.19) Pharmacologic Therapy: Hydralazine and Oral Nitrates A combination of hydralazine and isosorbide dinitrate is recommended as part of standard therapy, in addition to beta-blockers and ACE-inhibitors, for African Americans with LV systolic dysfunction: NYHA III or IV HF Strength of Evidence = A NYHA II HF Strength of Evidence = B Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

25 A-HeFT All-Cause Mortality Survival % P = % Decrease in Mortality Placebo Fixed Dose ISDN/HDZN Days Since Baseline Visit Taylor AL et al. N Engl J Med 2004;351:

26 aldosterone Promotes sodium retention and potassium excretion in the collecting tubule Promotes myocardial fibrosis and triggers inflammatory cell signaling in the myocardium in animal models of HF Is not completely blocked by ACE-I due to incomplete supression of angiotensin II production as well as non-angiotensin IItriggered production

27 HFSA 2006 Practice Guideline ( ) Pharmacologic Therapy: Aldosterone Antagonists An aldosterone antagonist is recommended for patients on standard therapy, including diuretics, who have: NYHA class IV HF (or class III, previously class IV) due to LV systolic dysfunction (LVEF 35%) One should be considered in patients post-mi with clinical HF or diabetes and an LVEF < 40% who are on standard therapy, including an ACE inhibitor or an ARB. Strength of Evidence = A Adapted from: Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

28 Aldosterone Antagonists in HF Probability of Survival RALES (Advanced HF) RR = 0.70 P < Placebo Months Spironolactone EPHESUS (Post-MI) RR = 0.85 P < Placebo Epleronone Months Pitt B. N Engl J Med 1999;341: Pitt B. N Engl J Med 2003;348:

29 HFSA 2006 Practice Guideline ( ) Aldosterone Antagonists and Renal Function Aldosterone antagonists are not recommended when: Creatinine > 2.5mg/dL (or clearance < 30 ml/min) Serum potassium> 5.0 mmol/l Therapy includes other potassium-sparing diuretics Strength of Evidence = A It is recommended that potassium be measured at baseline, then 1 week, 1 month, and every 3 months Strength of Evidence = A Supplemental potassium is not recommended unless potassium is < 4.0 mmol/l Strength of Evidence = A Adapted from: Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

30 digoxin reduces HF hospitalization improves effort tolerance mortality benefit not clear recommended for LVEF <40 (usually with dilated LV), NYHA II/III/IV recommended in HF with AF already on beta blockers and requiring further rate control or whose ventricular rate can tolerate addition of digoxin NOT FOR USE IN DIASTOLIC HF

31 HFSA 2010 Practice Guideline (9.1, 9.4) Device Therapy: Prophylactic ICD Placement Prophylactic ICD placement should be considered in patients with an LVEF 35% and mild to moderate HF symptoms: Ischemic etiology Strength of Evidence = A Non-ischemic etiology Strength of Evidence = B In patients who are undergoing implantation of a biventricular pacing device, use of a device that provides defibrillation should be considered. Strength of Evidence = B Decisions should be made in light of functional status and prognosis based on severity of underlying HF and comorbid conditions, ideally after 3-6 mos. of optimal medical therapy. Strength of Evidence = C Adapted from: Lindenfeld J, et al. HFSA 2010 Comprehensive Heart Failure Guideline. J Card Fail 2010;16:e1-e194.

32 MADIT II: Prophylactic ICD in Ischemic LVD (LVEF 30%) Probability of Survival Number at Risk Defibrillator Conventional (.91) 329 (.90) Year 274 (.84) 170 (.78) 110 (.78) 65 (.69) Defibrillator Conventional Therapy Moss AJ et al. N Engl J Med 2002;346:

33 Mortality ICD Therapy in the SCD-HeFT Trial: Mortality by Intention-to-Treat HR.4 Amiodarone vs Placebo 1.06 ICD vs Placebo % 97.5% Cl Months of Follow-Up 17% P Value Placebo Amiodarone ICD Therapy Bardy GH et al. N Engl J Med 2005;352:

34 cardiac resynchronization therapy (CRT)

35 HFSA 2006 Practice Guideline (9.7) Device Therapy: Biventricular Pacing Biventricular pacing therapy should be considered for patients with all of the following: Sinus rhythm A widened QRS interval ( 120 ms) Severe LV systolic dysfunction (LVEF 35% with LV dilation > 5.5 cm) Persistent, moderate-to-severe HF (NYHA III) despite optimal medical therapy. Strength of Evidence = A Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

36 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:

37 Number at risk CRT Medical Therapy Effect of CRT Without an ICD on % Event-Free Survival All-Cause Mortality: CARE-HF ,000 1, HR = 0.64 (95% CI = ) p = Days CRT Medical Therapy Cleland JG et al. N Engl J Med 2005;352:

38 normal QuickTime and a Microsoft Video 1 decompressor ar e needed to see this picture.

39 normal QuickTime and a Microsoft Video 1 decompressor ar e needed to see this picture.

40 normal QuickTime and a Cinepak decompressor ar e needed to see this picture.

41 normal

42 dilated cardiomyopathy LBBB

43 LBBB pre-crt

44 LBBB pre-crt

45 LBBB pre-crt

46 LBBB post-crt

47 LBBB post-crt

48 LBBB post-crt

49 Management of acutely decompensated heart failure

50 Inadequate volume unloading is common Clinicians tend to reduce/withhold diuretic therapy at the first sign of reduced effective arterial circulatory volume fear of low blood pressure fear of rising BUN and creatinine satisfaction after elimination of obvious physical signs of overload even in the presence of significant (less obvious) reservoirs of excess fluid (sacral edema, visceral edema, ascites)

51 Volume unloading does not necessarily result in reduced cardiac output decreasing MR/TR improves antegrade stroke volume shrinking the RV (by reducing pericardial constraint and ventricular interaction) allows improved LV filling Reduced myocardial edema improves systolic and diastolic function decreasing wall stress reduces myocardial oxygen demand and ischemia

52 Diuretics (thiazides) When thiazide diuretics are added to loop diuretics, synergistic diuresis often results, and can often overcome diuretic resistance through sequential nephron blockade Metolazone (Zaroxolyn) and HCTZ (Hydrodiuril) are the two most commonly used thiazides Diuril is the IV form of HCTZ ($200/dose)! 5 mg metolazone = 50 mg HCTZ

53 C P O G I R Y T H

54 Theoretical advantages of continuous infusion over intermittent bolus dosing less ototoxicity increased sodium excretion due to elimination of drug-free intervals Continuous maintenance of a moderate drug level allowing for continuous translocation of extravascular fluid back into the circulation (plasma refill) less hypotension and azotemia typical regimen consists of furosemide at 7-20 mg/h IV (max 100 mg/h) continuous infusion with or without an oral thiazide (metolazone or HCTZ) make sure to give an initial loading dose!

55 HFSA 2006 Practice Guideline (12.3, Table 12.3) Acute Decompensated Heart Failure (ADHF) Treatment Goals for Hospitalized Patients Improve symptoms, especially congestion and low-output symptoms Optimize volume status Identify etiology Identify precipitating factors Optimize chronic oral therapy; minimize side effects Identify who might benefit from revascularization Educate patients concerning medication and HF self-assessment Consider enrollment in a disease management program Strength of Evidence = C Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

56 HFSA 2006 Practice Guideline (8.7) Heart Failure Disease Management Patients recently hospitalized for HF and other patients at high risk should be considered for referral to a comprehensive HF disease management program that delivers individualized care. Strength of Evidence = A Adapted from: Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

57 HF Disease Management and the Risk of Readmission Risk Ratio Summary RR = 0.76 (95% CI ) Summary RR for randomized only = 0.75 (CI = )

58 HFSA 2006 Practice Guideline (8.13) End-of-Life Care in Heart Failure End-of-life care should be considered in patients who have advanced, persistent HF with symptoms at rest despite repeated attempts to optimize pharmacologic and nonpharmacologic therapy, as evidenced by one or more of the following: Frequent hospitalizations (3 or more per year) Chronic poor quality of life with inability to accomplish activities of daily living Need for intermittent or continuous intravenous support Consideration of assist devices as destination therapy Strength of Evidence = C Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.

59 Mitral regurgitation treatment target in advanced HF

60 QuickTime and a Microsoft Video 1 decompressor ar e needed to see this picture.

61 Otto et al, NEJM 2001

62 Romano and Bolling (2004) J Card Surg

63 Grigioni et al (2001) Circulation (103)

64 primary MR: survival with medical treatment (effect of ejection fraction) Isolated MR (3+/4+) due to flail leaflet Ling et al (1996) New Engl J Med

65 primary MR: survival with medical treatment (effect of symptoms) Ling et al (1996) New Engl J Med

66 Natural history of MR Chronic severe MR can persist for a number of years without overt symptoms Progressive LV and LA chamber dilation Symptoms: fatigue, DOE, PND, orthopnea Secondary consequences include phtn and AF MVR/HF/death is essentially unavoidable within 10 years

67 AHA/ACC guidelines for management of chronic severe MR Otto et al NEJM 2001

68 Adherence to guidelines works! 132 asymptomatic patients with severe MR from MVP or flail followed until a conventional endpoint indicating MV surgery occurred (HF, LVE, EF, phtn, AF) 35 patients underwent MV surgery: 29 repairs 6 replacements Rosenchek et al (2006) Circulation (113) 2238

69 HFpEF (diastolic HF) acute and chronic management of volume overload same as in systolic HF but (by definition) more preload sensitivity chronic management consists primarily of: (A) managing volume overload, and (B) addressing the underlying process leading to stiff LV and HF (aortic stenosis, HTN, infiltrative processes, pericardial disease)

70 There is a lot of DD out there 28% 8% Redfield et al (2003) JAMA

71 DD predicts all-cause mortality... Redfield et al (2003) JAMA

72 ...but only severe DD predicts HF Redfield et al (2003) JAMA

73 pharmacologic therapy for HFpEF Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial, By: Yusuf, Salim, Pfeffer, Marc A., Swedberg, Karl, Granger, Christopher B., Held, Peter, McMurray, John J. V., Michelson, Eric L., Olofsson, Bertil, ostergren, Jan, Lancet, , September 6, 2003, Vol. 362, Issue 9386

74 no difference in CV death between candesartan and placebo

75 cardiac transplantation and mechanical circulatory support Is the HF truly at end-stage? medical coronary valve rhythm resynchronization pericardium Are there contraindications? irreversible pulmonary hypertension active infection cancer nonadherent or unsupported patient

76 HF overview: conclusions (1) HF management increasingly guidelinedriven sticking to the guidelines reduces morbidity and mortality guideline adherence is low (<33% for guideline-recommended use of aldosterone antagonists) Consider continuous IV infusion of furosemide in patients who are difficult to diurese

77 HF overview: conclusions (2) Mitral regurgitation is a common problem in shf, and its presence confers significant incremental mortality and morbidity. However, when managed in accordance with AHA guidelines, the outcome is excellent DD is an echocardiographic/hemodynamic finding, and neither a diagnosis nor a disease. It is highly prevalent in the general population, especially in the aged, but not necessarily associated with or causative of HF HFpEF (DHF) is generally more difficult to treat than is HFrEF (SHF), due to the high preload-dependence that defines DHF and to the absence of proven efficacious therapies for DHF (unlike for SHF)