2 Case 1A 56 year old man with known CAD with NSTEMI x2 and stents in the LAD and LCx presents with 2 months of progressive DOE, LE edema and
3 Question #1Which of the following therapies will improve this patient’s mortality?A. LasixB. CarvedilolC. SpironolactoneE. DigoxinD. All of the above
4 Question #2PVCs are noted in the hospital. An echocardiogram has moderatey-severely decreased systolic function (EF 28%). What should you do next?Increase the lisinopril and carvedilol doseImplant and AICDStart amiodaronePut the defibrilator patches on himD/C telemetry
5 Heart Failure Is a Big Problem Prevalence: >5,000,000Incidence: >650,000 new cases/year in the USMost common discharge diagnosisMost common cause of readmission < 60 daysCost: > 34.8 billion annualyFIGURE 25-1 Prevalence rates of heart failure by gender and age in the United States between 1988 and 1994—the Third National Health and Nutrition Examination Survey (NHANES III). Among men (blue), the prevalence increased from 18 cases per 1000 in those aged 45 to 54 years to 98 cases per 1000 in those aged 75 years and older. Among women (purple), the prevalence increased from 13 cases per 1000 in those aged 45 to 54 years to 97 cases per 1000 in those aged 75 years and older. (Data from American Heart Association: Heart Disease and Stroke Statistics—2003 Update. Dallas, American Heart Association, 2002.)Rosamond. Circulation, 2008.Braunwald
6 Heart Failure Incidence Has Increased, But No By Much Levy. NEJM, 2002.
7 Survival has improved, but not dramatically 10,311 patients enrolledTemporal Trends in Age-Adjusted Survival after the Onsetof Heart Failure among Men (Panel A) and Women (Panel B).Values were adjusted for age (<55, 55 to 64, 65 to 74, 75 to 84,and »85 years). Estimates are shown for subjects who were 65to 74 years of age.Levy. NEJM, 2002.
8 What is Heart Failure?Definition: Any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.Cardinal manifestations: Dyspnea, fatigue, fluid retention
9 LV Dysfunction Is Necessary But Not Sufficient For Heart Failure
10 Acute Compensatory Mechanisms Cause Long Term Damage Activation of renin-angiotensin-aldosteroneSalt and water retentionMyocyte hypertrophy, death and myocardial fibrosisSympathetic nervous system stimulationIncrease contractility
11 Cardiac Remodeling Following Injury McMurray. NEJM, 2010.
12 Activation of the RAS Leads to Remodeling Renin, excreted in response to adrenergic stimulation of the juxtaglomerular (J-g) cells of the kidney, cleaves plasma angiotensinogen to produce angiotensin I (Ang I). Angiotensin II (Ang II) is formed through the cleavage of Ang I by angiotensin-converting enzyme (ACE). Most of the known biological effects of Ang II are mediated by the type 1 angiotensin receptor (AT1). In general, the AT2 receptor appears to counteract the effects of Ang II mediated by activation of the AT1 pathway. Ang II also may be formed through ACE-independent pathways. These pathways, and possibly incomplete inhibition of tissue ACE, may account for persistence of angiotensin in patients treated with ACE inhibitors. AT1 receptor antagonists have been postulated to provide more complete blockade of the renin-angiotensin-aldosterone system than ACE inhibition alone. ACE inhibition reduces bradykinin degradation, thus enhancing its levels and biological effects, including the production of nitric oxide (NO) and prostaglandin I2 (PGI2). Bradykinin may mediate some of the biological effects of ACE inhibitors.
14 Clinical Classification of Heart Failure Gheorghiade. JACC, 2007.
15 Initial Evaluation Decreased exercise tolerance Volume overload Asymptomatic or other complaints
16 Symptoms To Ask About Major Symptoms Minor Symptoms Dyspnea Orthopnea PNDAnkle edemaPulmonary edemaFatigueExercise intoleranceCachexiaMinor SymptomsWeight lossCoughNocturiaPalpitationsPeripheral cyanosisDepression
17 Physical Exam Findings To Look For JVPCracklesPulmonary edemaDisplaced PMI, S3 and S4,
18 Measurement of the JVP 5 cm Clinical Methods. Walker. 1990.
19 How To Measure JVP Clinical Methods. Walker. 1990.
21 Brain Natriuretic Peptide Natriuretic peptidesANP- atrium, BNP- ventricles, CNP- endothelial cellsIncreased well stress -> pre-proBNP-> pro-BNP-> BNP+NTproBNP (longer t1/2, higher levels,slower fluctuation)From the heartInduce vasodilation, natriuresis and diuresisUseful and systolic and diastolic heart failureDaniels. JACC, 2007.
22 Differential Diagnosis BNP Elevation LV dysfunctionPrevious CHFAdvanced ageRenal dysfunctionACSPulmonary diseasePEHigh outputAFLower then expectedObesityFlash pulmonary edemaHeart failure upstream from the LVCardiac tamponadePericardial constriction
23 BNP Can Help Differentiate Causes of Dyspnea Maisel. NEJM, 2002.
24 Higher BNP Is Associated With Higher Mortality FIGURE 23-2 Plasma brain natriuretic peptide (BNP) was measured before randomization and during follow-up in approximately 4300 patients in the Valsartan Heart Failure Trial. The baseline values for BNP in quartiles were less than 41, 41 to less than 97, 97 to less than 238, and greater than or equal to 238pg/ml. Kaplan-Meier curves show a significant quartile-dependent increase in mortality and first morbid events. (From Anand IS, Fisher LD, Chiang YT, et al: Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (Val-HeFT). Circulation 107:1278, 2003.)Braunwald
25 New York Heart Association Functional Classification Class I: No symptoms with ordinary activityClass II: Some symptoms with ordinary activityClass III: Symptoms with minimal activityClassIV: Symptoms at rest
26 Drugs That May Worsen Heart Failure: Na Retention, Cardiotoxicity, Negative Inotropy NSAIDSCalcium channel blockers- non-dihydropyridineMetforminThiazolidinedionesPDE-3 inhibitorsAntiarrhythmic drugsChemotherapyTHF alpha inhibitorsNa Containing drugsSupplements
27 Goals Of Therapy Heart Failure Relieve symptomsSlow or reveres deterioration of myocardial functionDecrease mortality
28 Heart Failure Therapy: A Timeline William Harvey describes circulation1628William Withering describes medical use of digoxin1785Thiazide Diuretics1950sFurosemide1967First Heart TransplantNitroprusside1974Hydralazine1976Enalapril reduces mortality1987Bisoprolol reduces mortality1994
29 Dietary and Lifestyle Modification: No Randomized Trials Sodium Restriction 2-3 gm dailyWeight lossSmoking cessationRestriction of alcoholDaily weight monitoring
30 Diuretics Used to manage volume status Dosing is based on response Intravenous versus oral therapyAgents can be combined for better efficacyNo effect on mortalityLibby. Braunwald’s Heart Disease
31 Digoxin In Heart Failure Inhibits the Na-K-ATPase pump-> increased Ca-> inc LV functionInhibition of sympathetic outflow
32 Digoxin Does Not Improve Mortality EF < dig, 3403 placeboDigitalis Investigation Group. NEJM, 1997.
34 Digoxin Level > 1.2 ng/ml Is Associated With Increased Mortality Figure 2 Plot of the adjusted point estimates and 95% confidence intervals of women and men for the hazard ratio for death on digoxin versus placebo at various serum digoxin concentrations (ng/ml) with concentration modeled as a continuous variable. The 95% confidence intervals for the women are offset to allow better depiction of results.Adams. JACC, 2005.
35 Enalapril Reduces Mortality in NYHA Class IV Heart Failure 253 patients randomized double blindConsensus trial study group. NEJM, 1987.
36 Meta Analysis: ACE-I Improve Mortality After MI 23% ACE vs 26.9% controlFlather. Lancet, 2000.
37 Candesartan Is An Reasonable Substitute In Patients Who Cannot Tolerate ACE-I Granger.Lancet, 2003.
38 Mortality Benefit With Hydralazine+ Isordil vs Placebo or Prazosin 642 men, on dig and diuretics, cardiac enlargement or EF < 45%Cohn. NEJM, 1986.
39 Bidil Improved Survival In Blacks With Heart Failure Taking ACE-I 1050 blacks, NYHA III or IV, on standard therapyTaylor. NEJM, 2004.
40 Beta BlockersMetoprolol: NYHA II-IV, EF <40%, metop succinate 200 dailyAll cause mortality dec by 34% independent of age, sex etiology of CHF or EFMerit-HF study group. Lancet, 1999.
41 Carvedilol Is Superior to Short Acting Metoprolol 1511 patients NYHA II-IV carvedilol 25 BID, metop 50 BIDPoole-Wilson. L:ancet, 2000.
42 Improvement of Systolic Function is Related to Beta Blocker Dose Bristow. Circulation, 1996.
43 Rales Trial: Spironolactone Improves Mortality In Severe Heart Failure 1663 patients ACE, loop, dig, EF < 35%,46 vs 35% death, RRR 30%, NYHA III or IV at enrollment, NYHA IV within 6 monthsPitt. NEJM, 1999.
44 Ephesus: Epleronone Improves Mortality In Heart Failure Following AMI 6642 After AMI with EF < 40%Pitt. NEJM, 2003.
45 Treat With Proven Dosages McMurray. NJEM, 2010.
46 Oral Milrinone Causes A 28% Increase In Mortality Class III or IV symptoms 1088 patients randomizedPacker. NEJM, 1991.
47 Take Home Messages About Medical Management of CHF Use proven therapiesTreat with proven dosages
48 How Do I Start These Drugs? DiureticACE Inhibitor or ARBBeta BlockerHydralazine and NitratesSpironolactone or eplerenoneDigoxin
49 AICD For Primary Prevention Of Sudden Cardiac Death In Patients With Heart Failure Ischemic cardiomyopathyEF<30%, prior MINon-ischemic cardiomyopathyEF < 35%, NYHA II or IIIEF<35%, NYHA III or IV and QRS>120 AICD with CRTSurvival of sudden death or with VT
50 Mortality Reduction In Patients Post MI: MADIT II Moss. NEJM, 2002.
51 Reduction in Mortality in NICM With ICD: ScD Heft Bardy. NEJM, 2005.