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Congestive Heart Failure: Strategic vs. Tactical Approaches while in the Trenches Alan Kono, MD FACC Cardiology Dartmouth-Hitchcock Medical Center Faculty Disclosure • I have no financial relationships with vendors • Even if I do own stock in said vendors, I’ve lost whatever I put in • I live pay check to pay check • I am not prejudiced towards minorities • I am not prejudiced towards religion • I am not prejudiced towards gender What do you see? A Approaching the Bermuda Triangle B Hussein’s Oil Fields Burning C Armageddon D Not sure, give me more info Hurricane Isabel September 2003 What are you thinking? A “Go to Warp Factor 3, Scotty” -Captain Kirk’s view B “Now what did I do to deserve this? -Catholic view C “Oh Shit” -Buddhist view D “Not sure, give me more info” -Agnostic view “I see some really good surfing weather” Alan Kono, surfing dude Audience Disclosure • Choose one of the Following: • I grew up singing the songs of – – – – – Joan Baez Peter, Paul, and Mary Doobie Brothers Blink 182 Who are these people? CHF OVERVIEW • • • • • Demographics Pathophysiology Therapy Delivery of Care Strategic vs. Tactical approaches Strategic vs. Tactical • Strategic- of pertaining to…large scale planning and directing of operations in adjustments to combat areas • Tactical- of pertaining to… technique or science of securing objectives designated by strategy; clever or adroit maneuvers Webster’s New Collegiate Dictionary American Heritage Dictionary CHF OVERVIEW • • • • • Demographics Pathophysiology Therapy Delivery of Care Strategic vs. Tactical approaches Heart Failure A clinical syndrome in which the heart is unable to pump sufficient blood to meet the metabolic demands of the body. Heart Failure • Approximately 5 million Americans have CHF (male to female ratio 1:1) • 550,000 new cases annually • Incidence of 10/1000 > 65 years of age • Hospital discharges 1,000,000 (2001) • Single largest expense for Medicare • Five-year mortality rate as high as 50% AHA. 2001 Heart and Stroke Statistical Update CHF Patient Population by NYHA Class Class III 1.20 M (25%) Class IV 240 K (5%) Class I 1.68 M (35%) Class II 1.68 M (35%) AHA Heart and Stroke Statistical Update 2001 Class I No limitations of physical activity Class II Slight limitations of physical activity Class III Marked limitations of physical activity Class IV Inability to carry out physical activities without discomfort and/or symptoms at rest New Approach to the Classification of Heart Failure A B C D Stage Patient Description High risk for developing heart failure (HF) Asymptomatic HF • • • • • • • • • • • Symptomatic HF Refractory end-stage HF Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113. Hypertension CAD Diabetes mellitus Family history of cardiomyopathy Previous MI LV systolic dysfunction Asymptomatic valvular disease Known structural heart disease Shortness of breath and fatigue Reduced exercise tolerance Marked symptoms at rest despite maximal medical therapy (eg, those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions) Classification of HF: Comparison Between ACC/AHA HF Stage and NYHA Functional Class ACC/AHA HF Stage1 A At high risk for heart failure but without structural heart disease or symptoms of heart failure (eg, patients with hypertension or coronary artery disease) B Structural heart disease but without symptoms of heart failure C Structural heart disease with prior or current symptoms of heart failure D Refractory heart failure requiring specialized interventions NYHA Functional Class2 None I Asymptomatic II Symptomatic with moderate exertion III Symptomatic with minimal exertion IV Symptomatic at rest 1Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113. 2New York Heart Association/Little Brown and Company, 1964. Adapted from: Farrell MH et al. JAMA. 2002;287:890–897. Historical Perspective • Hemodynamic model – Preload – Afterload – Contractility • Neurohormonal model Remodeling model Risk Factors for Heart Failure • CAD or history of MI • Hypertension • Valvular heart disease • Alcoholism • Diabetes • Congenital heart defects • Other: – Obesity – Age – Smoking – High or low hematocrit level – Obstructive Sleep Apnea CAD=coronary artery disease; LVH=left ventricular hypertrophy. CHF OVERVIEW • • • • • Demographics Pathophysiology Therapy Delivery of Care Strategic vs. Tactical approaches Hypertension Viral Ischemia Myocardial Injury Toxins Valvular Post Partum CAD HTN VHD VIRAL Pathophysiologic Effects of Compensatory Mechanisms in Heart Failure As ventricular function deteriorates, the heart relies on a variety of adaptive mechanisms to help maintain adequate cardiac output • Frank-Starling Law of the Heart • Renin-angiotensin-aldosterone system • Sympathetic nervous system Compensatory Mechanisms: Frank-Starling Law Stroke Volume Maximal Normal LV Mild LVD Normal Resting Severe LVD Low-Output Symptoms Normal Resting Pulmonary Edema Congestive Symptoms Left Ventricular End-Diastolic Pressure Neurohormonal Activation in Heart Failure Myocardial injury to the heart (CAD, HTN, MCP, Valvular disease) Initial fall in LV performance, wall stress Activation of RAS and SNS Remodeling and progressive worsening of LV function Fibrosis, apoptosis, hypertrophy, cellular/ molecular alterations, myotoxicity Morbidity and mortality Arrhythmias Pump failure RAS, renin-angiotensin system; SNS, sympathetic nervous system. Peripheral vasoconstriction Hemodynamic alterations Heart failure symptoms Fatigue Activity altered Chest congestion Edema Shortness of breath SNS Activation Leads Directly to Impaired Cardiac Function CNS sympathetic outflow Cardiac sympathetic activity Sympathetic activity to kidneys + blood vessels 121receptors receptors receptors Myocyte hypertrophy, dilation, ischemia, arrhythmias, death Disease progression Adapted from Packer M. Prog Cardiovasc Dis. 1998;39(suppl I):39–52. Activation of RAS Vasoconstriction Sodium retention Remodeling 1 week 3 months Chamber Enlargement EDV 137 mL ESV 80 mL EF 41% EDV 189 mL ESV 146 mL EF 23% Apical 4 Chamber View Remodeling Prognosis-Volume Gaasch, et al CPC 1995 CHF OVERVIEW • • • • • Demographics Pathophysiology Therapy Delivery of Care Strategic vs. Tactical approaches The following therapies have been shown to improve mortality in CHF • • • • • • Digoxin ACE inhibitors Angiotensin Receptor Blockers Calcium Channel Blockers B-blockers Loop Diuretics CHF THERAPY ACE-Inhibitors B-blockers Pathogenesis and Therapeutic Approaches Vasodilators ACE Inhibitors Imepdance LV Function Digoxin Cardiac Output ACE Inhibitor Salt and Water Retention Neurohormone Activation { RAA System ANF Catecholamines Diuretics Progressive Heart Failure B-blockers Effect of ACE Inhibitors on Mortality Reduction in Patients With CHF Mortality Trial ACEI Controls RR (95% CI) CONSENSUS I 39% 54% 0.56 (0.34–0.91) SOLVD (Treatment) 35% 40% 0.82 (0.70–0.97) SOLVD (Prevention) 15% 16% 0.92 (0.79–1.08) SAVE 20% 25% 0.81 (0.68–0.97) AIRE 17% 23% 0.73 (0.60–0.89) TRACE 35% 42% 0.78 (0.67–0.91) Chronic CHF Post MI SMILE Average 6.5% 21% Garg R et al. JAMA. 1995;273:1450–1456. Data shown from individual trials–not direct comparison data. 8.3% 25% 0.78 (0.52–1.12) ACE Inhibition in Heart Failure Consensus Recommendations All patients with heart failure due to left ventricular systolic dysfunction should receive an ACE inhibitor unless they have a contraindication to its use or cannot tolerate treatment with the drug. Treatment with an ACE inhibitor should not be delayed until the patient is found to be resistant to treatment with other drugs. Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure. Am J Cardiol. 1999;83(suppl 2A):1A–39A. Angiotensin II • One of the most potent pressor agents known. • Produced by conversion of angiotensin I by ACE (and alternative pathways). • Overall increase in systemic blood pressure results from A-II synergistic effects on various systems. • Inhibits the release of renin. • Increases the secretion of aldosterone. PATHOPHYSIOLOGIC ROLE OF ANGIOTENSIN II Angiotensin II Vasoconstriction AT1 Receptor Aldosterone Production Cell Growth PVR BP LVH Vascular Remodeling Sodium/Water Retention BP Hypertension. Feb. 1994;23(2):258 ARB Angiotensin Receptor Blockers • This-a-sartan and that-a-sartan? Elite II Primary All Cause Mortality 1.0 0.8 # of Events Captopril=250 Losartan = 280 Hazards Ratio(95%) 0.88 (.75,1.05) p= 0.16 mortality rate = 11% 0 100 200 300 400 Days of Follow Up 500 600 700 Presented at the AHA, Atlanta 1999 by B.Pitt M.D. Effect of Valsartan on Mortality by ACE Inhibitor/-Blocker Subgroups (Val-HeFT) n Not Receiving ACEI Favors valsartan Favors placebo 366 Receiving ACEI* 4,644 Receiving ACEI without -Blockade 3,034 Receiving ACEI and -Blockade 1,610 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 Relative Risk (95% CI) *Data presented at FDA Cardio-Renal Advisory Panel. Adapted from: Cohn JN et al. N Engl J Med. 2001;345:1667–1675. HF NOT AN APPROVED INDICATION FOR VALSARTAN ACC/AHA Guidelines on the Role of ARBs in HF Several clinical trials with ARBs failed to show mortality benefit in heart failure • ARBs should not be considered equivalent or superior to ACE inhibitors in the treatment of HF • ARBs should not be used for the treatment of HF in patients who have had no prior use of an ACE inhibitor • -Blockers, rather than ARBs, should be added to therapy for patients with HF who are taking an ACE inhibitor until further data are available Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113. CHARM Trial • Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity – CHARM Alternative – CHARM Added – CHARM Preserved Lancet 362; 759-776 September 2003 CHARM Lancet 362; 759-776 September 2003 VALIANT • Valsartan, Captopril or Both in MI complicated by Heart Failure, LV dysfunction or Both – EF<35% (echo or LV gram) <40% (MUGA) • 14,808 pts enrolled • No significant difference in – Cardiovascular Death – Combined Cardiovascular endpoints • Valsartan showed non-inferiority Pfeffer. NEJM; 359 (20) 11/03 VALIANT Pfeffer. NEJM; 359 (20) 11/03 B-Blockers in CHF Historical Perspective • 1975- 1980 First reports of clinical benefit* • High NE associated with high mortality • B receptor down-regulation • ?Are B-Adrenergic-blocking agents useful in the treatment of DCM** * Waagstein Br Heart Journal 1975, Swedberg Br Heart Journal 1980 **Alderman Grossman Circulation 1985 B-Blockers in CHF • Are B-Blockers effective in CHF? -Yes ( that’s what the experts say) -No (they didn’t teach that to me in my training) • Is it a class effect? -Yes (a B-blocker is a B-blocker) -No (Designer Drugs are cool) • Is it safe to use in advanced CHF (FTC IV)? -Yes, the bookies have the odds -No, it’s better in less severe patients • When should you initiate B-blockers? -In the ER -In the Hospital -In the Clinic • Are B-blockers safe to use post MI & CHF? -Yes, I’m feeling lucky -No, you’re pulling my leg ß-Blockers: Use in Heart Failure is Now Supported by Overwhelming Evidence • >15,000 patients evaluated in long-term placebocontrolled clinical trials • Improvement in cardiac function and symptoms; equivocal effects on exercise tolerance • Decrease in all-cause mortality by 30%–65% (P<.0001) • Decrease in combined risk of death and hospitalization by 35%–40% (P<.001) • Effect shown in patients already receiving ACE inhibitors Selectivity of -Blocking Agents MI, HTN, DM, Insulin Resistance Sympathetic Activation 1 receptors 2 receptors 1 selective blockade non-selective blockade 1 receptors 1 , 2, 1 blockade Cardiotoxicity Major Placebo Controlled Trials of Beta-Blockade in Heart Failure HF Severity Patients (n) Follow-up (yrs) Target Dosage (mg) Mean Dosage Achieved (mg/day) Effects on Outcomes Study Drug CIBIS bisoprolol* moderate/ severe 641 1.9 5 qd 3.8 All-cause mortality NS bisoprolol* moderate/ severe 2647 1.3 10 qd 7.5 All-cause mortality 34% (P<.0001) metoprolol tartrate* mild/ moderate 383 1 200 qd 108 Death or need for transplant (primary endpoint)NS mild/ moderate 3991 1 200 qd 159 Lancet 1999 metoprolol succinate# All-cause mortality 34% (P=.0062) BEST4 bucindolol* moderate/ severe 2708 2 50-100 bid 152 All-cause mortality NS carvedilol mild/ moderate 1094 6.5 months 6.25 to 50 bid 45 All-cause mortality† 65% (P=.0001) carvedilol severe 2289 10.4 months 25 bid 37 All-cause mortality 35% (P =.0014) Circ. 1994 CIBIS-II3 Lancet 1999 MDC Lancet 1993 MERIT-HF1 NEJM 2001 US Carvedilol2 NEJM 1996 COPERNICUS5 NEJM 2001 †Not a planned end point. *NOT AN APPROVED INDICATION; #METOPROLOL SUCCINATE NOT APPROVED FOR SEVERE HF OR FOR MORTALITY REDUCTION ALONE Probability of event-free survival Effect of Carvedilol on Disease Progression in Mild or Moderate Heart Failure 1.0 Carvedilol (n=232) 0.8 Risk reduction Placebo 48% (n=134) P=.008 0.6 0 0 50 100 150 200 Days 250 300 350 400 *Disease progression was defined as HF death or hospitalization or the need for sustained increase in medications for HF. Patients were on a background of diuretics, ACE inhibitors, ± digoxin. Colucci WS et al. Circulation. 1996;94:2800–2806. Study Results Total Mortality Risk reduction: 34% Percent of patients 2 0 P=0.0062 15 Placebo n=2001 Metoprolol XL n=1990 10 5 0 0 3 6 9 12 15 18 21 Months of follow-up -Blockers in Class IV Heart Failure Proportion of patients with class IV heart failure US Carvedilol Program1 3% MERIT-HF2 4% (Metoprolol succinate) CIBIS II3 16% (Bisoprolol)* BEST4 (Bucindolol)* *HF not an approved indication. 1Packer M. N Engl J Med. 1996;334:1349–1355. 2MERIT-HF Study Group. Lancet. 1999;353:2001–2007. 3CIBIS II Investigators. Lancet. 1999;353:9–13. 4The BEST Investigators. N Engl J Med. 2001;344:1659–1667. 8% COPERNICUS All-Cause Mortality 100 % Survival 90 Carvedilol 80 Placebo 70 35% in risk 60 P=.00013 (unadjusted) P=.0014 (adjusted) 0 0 3 6 9 12 Months Packer M et al. N Engl J Med. 2001;344:1651–1658. 15 18 21 COMET* • More than 3000 patients with class II–IV† heart failure due to ischemic or nonischemic cardiomyopathy • Randomized to carvedilol or metoprolol tartrate§ (in addition to usual therapy) for over 3 years • Prespecified end points: all-cause mortality, combined risk of all-cause mortality and hospitalization • Results expected 2003 Lancet 362 (9377); 7-13, July 2003 †NYHA *Carvedilol or Metoprolol European Trial CLASS IV HF NOT APPROVED USE FOR ANY -BLOCKER §HF NOT AN APPROVED INDICATION FOR METOPROLOL TARTRATE COMET Study Design 3029 patients with stable heart failure, New York Heart Association Class II-IV, receiving standard treatment including ACE inhibitors (n1500) Metoprolol 50 mg bid Randomized (No run-in phase) (n1500) Carvedilol 25 mg bid Time to 1020 deaths Estimated to be 4 to 6 years Screening Titration to Assessments every four months maximum during maintenance phase tolerated or target dose (Start: carvedilol 3.125 mg bid, metoprolol tartrate 5 mg bid) Poole-Wilson PA et al. Eur J Heart Fail 2002;4:321-329. Primary Endpoint of Mortality 40 Metoprolol 30 20 Carvedilol Hazard ratio 0.83, 95% CI 0.74-0.93, P = 0.0017 10 0 0 Number at risk Carvedilol 1511 Metoprolol 1518 1 2 3 4 5 Time (years) 1366 1359 Poole-Wilson PA et al. Lancet 2003;362:7-13. 1259 1234 1155 1105 1002 933 383 352 -Blocker Trials Intervening Within 24 Hours of an Acute Myocardial Infarction Study # of Patients Treatment Groups Duration of therapy Effect on Mortality Effect on Reinfarction Göteborg1 Study 1,395 Placebo vs Metoprolol 3 months 36% (P=.03) NS MIAMI2 Trial 5,778 Placebo vs Metoprolol 15 days NS NS ISIS-13 Trial 16,027 Control vs Atenolol 1 week 15% (P<.04) NS 1Hjalmarson A et al. Lancet. 1981;2(8251):823–827. Miami Trial Research Group. Am J Cardiol.1985;56(14):15G–22G. 3First International Study of Infarct Survival Collaborative Group. Lancet. 1986;2(8498):57–66. 2The Rationale for CAPRICORN • -Blocker trials in acute myocardial infarction were conducted mostly during the 1970s and 1980s – No thrombolysis or primary angioplasty – Much less use of aspirin – No ACE inhibitors • Patients with heart failure were usually excluded – Left ventricular function was not assessed – Study populations were mostly lower risk Dargie HJ et al. Eur J Heart Fail. 2000;2:325–332. CAPRICORN: All-Cause Mortality Proportion EvenPt-free 1.00 Carvedilol n=975 0.90 Risk reduction 23% 0.80 Placebo n=984 (2%, 40%) 0.70 P=.031 0.60 0 0 0.5 1 1.5 2 2.5 Years The CAPRICORN Investigators. Lancet. 2001;357:1385–1390. Mortality rates: Placebo 15%; Carvedilol 12% COPERNICUS: Death, Hospitalization, or Withdrawal During First 8 Weeks % Patients With Event 20 15 Placebo n=1133 10 Carvedilol n=1156 5 0 0 2 Weeks 4 6 Weeks Weeks Post Randomization Hazard ratio (95% confidence interval): 0.83 (0.68–1.03) 8 Weeks A double-blind, randomized, placebo-controlled study of 2289 euvolemic patients who had symptoms of heart failure at rest or on minimal exertion for at least 2 months and an ejection fraction of <25%. Krum H et al. JAMA. 2003;289:712–718. At 2 weeks, 97% of patients were either receiving or titrated to 6.25 mg bid B-Blockers in CHF • Are B-Blockers Effective in CHF? -Yes • Is it a class effect? -Effficacy seen with Bisoprolol, Metoprolol XL, Carvedilol • Is it safe to use in advanced CHF (FTC IV)? -Efficacy and safety established with Carvedilol • When should you initiate B-blockers? -May be started in the hospital when euvolemic (IMPACT-HF) • Are B-blockers safe to use post MI & CHF? -May be initiated post MI with CHF/LV dysfunction (CAPRICORN) B-Blockers in CHF New Paradigms • May initiate early rather than late – Start low, go slow – Initiate in the hospital • If on a B-blocker and decompensates – Continue or reduce dosage – Rarely discontinue CHF THERAPY Calcium Channel Blockers Digoxin Diuretics PRAISE2 1652 patients with CHF of non-ischemic etiology 10 mg amlodipine 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% HR = 1.09 31.7% 33.7% placebo amlodipine Presented at ACC; Anaheim March 2000 Digoxin: Use to Improve Symptoms and Clinical Status DIG Trial • 6800 patients followed over 3 years • No benefit seen in overall mortality – 34.8% with digoxin vs 35.1% with placebo (P=NS) • 28% significant decrease in CHF hospitalizations compared with placebo (P<.001) The Digitalis Investigation Group. N Engl J Med. 1996; 335:490–498. Digoxin Does NOT Decrease Mortality... but decreases hospitalization (6%) 50 Mortality (%) 40 30 placebo Digoxin 20 10 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Months Digitalis Investigation Group, N Engl J Med 1997;336:525-33 Randomized Trials of Loop Diuretics Randomized Trials of Aldosterone Blocking Diuretics • RALES Trial • EPHESUS Trial Randomized Aldactone Evaluation Study (RALES) 1.00 0.95 0.90 Probability of Survival 0.85 0.80 0.75 0.70 Spironolactone* 0.65 0.60 P<.001 0.55 Placebo 0.50 0.45 0.00 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Pitt B., et al. N Engl J Med. 1999;341:709–717. *NOT INDICATED TO REDUCE MORTALITY IN HF EPHESUS: Design AMI, LVEF 40%, Rales, Standard Therapy Eplerenone 25–50 mg qd n = 3100 Randomize 3–14 Days Post–AMI 1012 Deaths Placebo n = 3100 • Total mortality • CV mortality/CV hospitalization* Secondary End Points: • CV mortality • Total mortality/total hospitalizations Primary End Points: *CV hospitalization = hospitalization for heart failure, MI, stroke, or ventricular arrhythmia Relative Risk of Total Mortality 22 20 18 16 14 Placebo Eplerenone Cumulative 12 Incidence (%) 10 8 RR = 0.85 (95% CI, 0.75-0.96) P = 0.008 6 4 2 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Since Randomization Remodeling Afterload Reduction Remodeling Therapy Remodeling and Survival Effects by Drug Class Established Rx Remodeling Effects ACE-I ARB Aldo-B Beta-B Survival Effects Benefit Benefit Benefit (+ACEI better) Benefit (+ACEI better) Benefit Benefit Benefit Benefit Other Rx Vasop-I ET-1-B TNF-B Ibopamine Benefit (ACEI-neutral) Benefit (ACEI-neutral) No Benefit No Benefit No Benefit No Benefit Adverse Adverse CHF NEW THERAPIES New Therapies • Biventricular pacing-LV pacing via the coronary sinus • TNF-alpha blockers- for Class III-IV CHF • Endothelin blockers • Neutral endopeptidase blockers • Vasopressin Biventricular Pacing Ventricular Dysynchrony • Abnormal ventricular conduction resulting in a mechanical delay – Wide QRS (IVCD); typically LBBB morphology – Poor systolic function – Impaired diastolic function ECG depicting interventricular conduction delay Overview of Device Therapy 102 Wide QRS – Proportional Mortality Increase QRS Duration (msec) • • • • • Vesnarinone Study1 (VEST study analysis) NYHA Class II-IV patients 3,654 ECGs digitally scanned Age, creatinine, LVEF, heart rate, and QRS duration found to be independent predictors of mortality Relative risk of widest QRS group 5x greater than narrowest Cumulative Survival 100% <90 90% 90-120 80% 120-170 170-220 70% >220 60% 0 60 120 180 240 300 360 Days in Trial Adapted from Gottipaty et al. 1 Gottipaty V, Krelis S, et al. ACC 1999 [Abstr];847-4. Issues Associated with Heart Failure Abnormal local wall strain Dilated Cardiomyopathy (DCM) Healthy Longer SEPTUM SEPTUM BASE BASE Relaxed APEX APEX Shorter Courtesy of D. Kass, MD, Johns Hopkins University, Maryland. Mechanisms Ventricular Dysynchrony Click to Start/Stop Clinical Consequences of Ventricular Dysynchrony Abnormal interventricular septal wall motion Grines C, et al. (1989) Reduced dP/dt 4-Chamber.avi Xiao H, et al. 1992 Reduced diastolic filling times Grines, et al. (1989); Xiao, et al. (1991) Prolonged MR duration Grines, et al. (1989); Xiao, et al. (1991) LV Reverse Remodeling after CRT MR area LV End Systolic and Diastolic Volumes Pacing No pacing 40 No pacing Pacing † * 200 * 175 * * 150 125 † * * 100 Mitral regurgitation (%) Left ventricular volume (mL) 225 † 35 *† * † 30 * 25 * * 1mo 3mo 20 15 * * 10 Baseline 1wk 1mo 3mo N = 25 off-immed off-1wk off-4wk Baseline 1wk off-immed off-1wk off-4wk Yu CM, et al, Circulation. 2002;105:438-445. Cardiac Resynchronization Therapy Effect on LV Size and Function (MIRACLE) Paired, Median Changes from Baseline cm 3 0 -10 -20 -30 3M 6M p< 0.001 4 3 MR Jet Area p= 0.008 1 2 -2 0 -3 6M Control (n=151) CRT (n=172) St. John Sutton M, et al. Circulation. 2003;107:1985-1990. Doug Smith: p< 0.001 3M 6M -1 1 3M p< 0.001 0 cm p< 0.001 Absolute % 10 p< 0.001 LVEF 2 LVEDV Effect of Beta Blocker Therapy Paired, Median Changes from Baseline at 6 Months * * BB MR Jet Area 0 4 * 2 -3 BB No BB Control CRT * p < 0.05, CRT vs. Control within subgroups † p < 0.05, CRT vs. CRT between subgroups St. John Sutton M, et al. Circulation. 2003;107:1985-1990. Doug Smith: -1 -2 0 No BB 1 * 6 2 0.2 LVEF cm 10 0 -10 -20 -30 -40 8 Absolute % cm 3 LVEDV * *† BB No BB COMPANION Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure Hypothesis •CRT with optimal pharmacologic therapy (OPT), alone or in combination with ICD backup, can: – Reduce all-cause hospitalization and mortality – Reduce cardiac morbidity – Increase total survival – Improve exercise performance (sub-study) …when compared to OPT alone Study design COMPANION •Parallel, randomized • OPT Randomization • OPT • CRT • OPT • CRT-D 1 2 + 2 + Bi-Ventricular Pacing Criteria for referral • • • • NYHA FTC III-IV CHF EF<30-35% QRS >130ms (LBBB>RBBB) Failing “optimal” medical Therapy • Less data on patients with permanent pacers • Less data on patients with Afib CHF OVERVIEW • • • • • Demographics Pathophysiology Therapy Delivery of Care Strategic vs. Tactical approaches Approach to the Patient With Heart Failure Assessment of LV function (echocardiogram, radionuclide ventriculogram) EF 40% Assessment of fluid volume status Signs and symptoms of fluid retention No signs and symptoms of fluid retention Diuretic (titrate to euvolemic state) ACE inhibitor ? Digoxin Aldosterone Antagonist B-Blocker Adapted from Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure. Am J Cardiol. 1999;83(suppl 2A):1A–39A. New Approach to the Classification of Heart Failure A B C D Stage Patient Description High risk for developing heart failure (HF) Asymptomatic HF • • • • • • • • • • • Symptomatic HF Refractory end-stage HF Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113. Hypertension CAD Diabetes mellitus Family history of cardiomyopathy Previous MI LV systolic dysfunction Asymptomatic valvular disease Known structural heart disease Shortness of breath and fatigue Reduced exercise tolerance Marked symptoms at rest despite maximal medical therapy (eg, those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions) New Approach to the Treatment of Heart Failure A B C D Stage Treatment High risk for developing heart failure (HF) Asymptomatic HF • Diabetes • Hypertension • Hyperlipidemia Symptomatic HF Refractory end-stage HF Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113. • Identify and correct underlying cause Modifiy risk factors • Aggressive Medical Rx • Slow progression • Caremanagement • Advanced Therapies • Cardiac Transplant • Device • Palliative Care ACE-I ARB Statins ACE ?B-blocker ACE ARB B-blocker Aldosterone CHF OVERVIEW • • • • • Demographics Pathophysiology Therapy Delivery of Care Strategic vs. Tactical approaches How do we deliver this care? CHF Tribulations • How long does it take Physicians to change practice behaviors from the time evidence based literature emerges? – – – – – 15 days 15 weeks 15 months 15 years they never change Examples of the “Molasses Effect” • • • • Therapy for MI* Thrombolysis in Acute MI ACE inhibitor use in CHF Therapy for Hyperlipidemia *Antman.JAMA.1993 : 269(2):214 Potential Reasons for “Treatment Time Lag” • Access to Information • Insufficient or inconclusive data • Expert Opinion* • Individual Practitioner Behavior • System or Hospital resistance • Financial Constraints • Patient Biases Medications Perceived Effective for Improving HF Prognosis by Officebased Physicians* 100 90 Physicians (%) 80 70 60 50 40 30 20 10 0 Cleland JGF et al. Lancet. 2002;360:1631–1639. *1363 Physicians provided data for 11,062 patients Slow Translation of Clinical Trials Results Into Routine Clinical Practice Use of Lipid-Lowering Medications 100 80 60 4S Study 40 20 10 14 18 1995 1996 24 28 1997 1998 32 38 42 48 0 1994 1999 2000 2001 Year 4S Study=Scandinavian Simvastatin Survival Study; AMI/ACS patients discharged on lipid-lowering medications. NRMI 3 and 4, PRISM, PURSUIT, GUSTO II, TIMI 16, ACCEPT. 2002 Utilization of Evidence Based Therapies in Heart Failure Percent of Patients 100 80 69 60 40 29 19 20 0 ACE Inhibitors Beta Blockers Spironolactone University Hospital Consortium HF Registry: 33 Centers, 1239 patients, Year 2000 Discharge Medications Hospitalization: The Predominant Contributor to Heart Failure Costs 60.6% Inpatient care $23.1 billion Total = $38.1 billion (5.4% of total healthcare costs) O’Connell JB et al. J Heart Lung Transplant. 1994;13:S107-S112 38.6% Outpatient care $14.7 billion (3.4 visits/year /patient) 0.7% Transplants $270 million Causes of Hospital Readmission for Congestive Heart Failure Diet Noncompliance 24% 16% Inappropriate Rx Rx Noncompliance 24% 19% Failure to Seek Care Vinson J Am Geriatr Soc 1990;38:1290-5 17% Other Hospital Admissions for Acute CHF Remain on the Increase Due to… • Inevitable progression of disease • Rising incidence of chronic heart failure (population aging, improved survival with AMI/revascularization) • Incomplete treatment during hospitalization • Poor application of chronic heart failure management guidelines • Noncompliance with diet and drugs MODELS OF CARE CHF • Community Based Physician – Home Nursing – Telemedicine • Clinic Based – Primary Care – Specialty Care • Hospital Based Nurse or Pharmacist – Primary Care – Specialty Care Registry CHF Model of Care NP/CNS Coordinator Hospital Home Nursing ER Pharmacist Social Worker Dietician Psychiatry Primary Care Team MD, NP, RN, /Pharmacist Care Coordinator Cardiology MD mentored NP Transplant Coordinator Clinic Multidiscipline Treatment of Decompensated Heart Failure: CHF Disease Management Program 85% Reduction p=0.0001 214 patients 6 months pre-evaluation vs 6 months post-evaluation ACEI dose increased (151 mg), diuresed (4 liters), flexible diuretic, home exercise Ahmanson-UCLA Cardiomyopathy Center Fonarow JACC;1997;30:725-32 Impact of Management Programs on the Hospitalization Rate in Heart Failure Multidisciplinary Medical + Multidisciplinary Randomized Trials of Disease Management Programs for Heart Failure RR 95% CI P value Specialized Care + M ultidisciplinary Program 0.77 0.69-0.86 <0.01 Telephone Management + Coordinated Primary Care 1.15 0.96-1.37 NS 11 Randomized Trials, 2,067 Patients McAlister Am J Med 2001;110:378-84 Key Elements to Quality Improvement Why Do Some Hospitals Succeed? Access to current and accurate data on treatment and outcomes Have stated goals Administrative support Support among clinicians Use of pre-printed orders, care maps Use of data to provide feedback Bradley JAMA 2001;285:2604-2611 CHAMP Sustained Impact Over an 8-Year Period UCLA: 100 1992–93 1994–95 1996–97 1998–99 NRMI Rx rates (1437 hospitals): 1 96 92 91 94 91 88 89 90 85 78 80 77 68 68 72 70 75 64 65 60 2000–01 2000–01 52 42 37 40 20 12 6 4 0 Aspirin Beta-Blocker Fonarow GC et al. Circulation. 2001;104:II-711. ACE Inhibitor LipidLowering Treatment Impact of In-Hospital Initiation of Lipid-Lowering Medications on Compliance 12-Month Discontinuation of Therapy Rate 50 41 Percent 40 P<0.0001 30 20 10 10 0 Outpatient Initiation of Statin After Acute 1* Coronary Syndrome N=22,379 Statin Initiation Prior to 2† Hospital Discharge N=3883 *Canadian cohort study: Patients with ACS 66 years or older newly started on statin as outpatients (cost to patient $2 per prescription) †OPUS-TIMI 16: 3883 (38%) patients with ACS (N=10,238) started on statin prior to hospital discharge. 1. Jackevicius CA et al. JAMA. 2002;288:462-467. 2. Cannon CP. J Am Coll Cordiol. 2001;35:334A. IMPACT-HF Trial Initiation Management Predischarge: process for Assessment of Coreg Therapy for Heart Failure Objective To determine if initiating Carvedilol therapy prior to hospital discharge in patients admitted with a primary diagnosis of heart failure and LVEF 40% is safe and effective in improving the overall use of beta-blockers at 60 days after randomization, as compared to initiation of any beta-blocker 2 weeks postdischarge at physician discretion. Presented at AHA Scientific Sessions, GSK Satellite Symposium, Nov. 18th, 2002, Chicago, IL. Gattis W, O’Connor C, Gheorghiade M. The Initiation Management of Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) Study: Design and Implications. Rev Cardiovasc Med. 2002, 3(Suppl 3); S48-S54. IMPACT-HF Primary End Point: Patients Receiving a beta-blocker at 60 days Carvedilol Pre-Discharge Ititiation (N=185) 91% Physician Discretion Post-Discharge Initiation (N=178) 73% P<.0001 Presented at AHA Scientific Sessions, GSK Satellite Symposium, Nov. 18th, 2002, Chicago, IL. Patient Treatment With Beta-Blockers (%) Comparative Percentages of HF Patients Receiving a BetaBlocker 100 91 75 67 50 27 25 0 16 Usual Care Provider/Patient Notification Nurse Facilitator IMPACT-HF Carvedilol Predischarge Initiation Ansari M et al. Circulation. 2003;107:2799-2804 IMPACT-HF Presented by Gheorghiade M, O’Connor C, and Gattis W, at GSK Satellite Symposium at Scientific Sessions of the American Heart Association, November 18, 2002, Chicago, Ill. Beta-Blocker Users (%) Outpatient Compliance to Beta-Blocker Therapy Post-Acute MI 80 Discharged on Beta-Blockers 60 40 20 Not discharged on Beta-Blockers 0 0 30 90 180 Days Since Discharge Butler J et al. J Am Coll Cardiol. 2002;40:1589-1595. 270 365 Why a Hospital-Based System for Cardiac Treatment? • Patients – Patient capture point – Have patients/family attention: “teachable moment” – Predictor of care in community • Hospital Structure – Standardized processes/protocols/orders/teams – JCAHO-ORYX • Process improvement examples – CMS—Quality Improvement Organizations JCAHO=Joint Commission on the Accreditation of Healthcare Organizations; ORYX=Like the JCAHO’s initiative for incorporating outcomes and measures into accreditation; CMS=Centers for Medicare and Medicaid Services. Outpatient Management Tactical Approaches • Identify patients and develop a registry – May represent ~2-3% of your patient panel • Chronic Disease Management – Clinic nurse, NP, PA, pharmacist – Multidiscipline approach • Patient Education and Involvement – Scales and BP cuffs – Diary Telemedicine Solution Overview Patient’s Home Health Plan Clinic Customer Intranet LAN Server Home Hub Vital Sign Data Scale Blood Pressure Unit Rhythm Strip Recorder Clinical Review Software Clinical Intervention as Necessary Outcomes: Nurse Outreach Program Plus Telemedicine Hospital Readmission Rate/CHF Patient 1.7 Prior to trial Telemedicine 0.13 UMass Memorial Health Center Trial Source: Theo E. Meyer, M.D., D. Phil., UMass Memorial Health Center, Division of Cardiology CHF Chronic Disease Management • Disease management programs reduce hospitalizations and costs • Inconclusive data but a trend towards reducing mortality • Trends towards better QOL • Successful Models – – – – Multidisciplinary Team Patient Education Improved prescribing practices Specialized follow-up procedures McAlister. AM J Med.2001:110:378-384 A systematic review of randomized trials of disease management programs in heart failure. CHF- Easy or Hard Therapies of Demonstrated Benefit Across the Cardiovascular Continuum CAD Post-MI Mild, Mod, Post-MI LV Dysfunction Severe HF ACE Inhibitor HOPE (ramipril) HOPE (ramipril) Beta-Blocker TIBBS (bisoprolol) BHAT/Norwegian (propranolol/timolol) Aldosterone Antagonist AIRE/SAVE (ramipril/captopril) CAPRICORN (carvedilol) EPHESUS (eplerenone) SOLVD /CONSENSUS (enalapril) COPERNICUS (carvedilol, Toprol XL) RALES (spironolactone) HOPE=Heart Outcomes Prevention Evaluation; AIRE=AcuteInfarction Ramipril Efficacy; SAVE=Survival and Ventricular Enlargement; SOLVD=Studies of Left Ventricular Dysfunction; CONSENSUS=Cooperative North Scandinavian Enalapril Survival Study; TIBBS=Total Ischemic Burden Bisoprolol Study; BHAT=Beta-Blocker Heart Attack Trial; CAPRICORN=Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction; COPERNICUS=Carvedilol Prospective Randomized Cumulative Survival; EPHESUS=Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study; RALES=Randomized Aldactone Evaluation Study. Heart Failure-Oncology Model Surgery Chemotherapy CHF, LV Fx CHF, LV Fx improves improves with with surgery medical Rx, time CABG, Valve Transplant Mech Heart 5-10% Remission Terminal CHF symptoms CHF worsens improve, LV Fx despite Rx, does not QOL poor Diuretics, ACEI,BB Spironolactone Rx HTN New Therapies Time! Diuretics, ACEI,BB Spironolactone New Therapies QOL issues Time! 20-30% 50-60% Frank disc About prognosis Hospice Supportive Care 1% CHF SUMMARY Strategic vs. Tactical Evidence Based Therapies ACE-I, B-Blocker Care Management Multidiscipline Education CHF Nurse By using • Better Compliance with therapies • Improved Mortality-91% one year survival • Less than 1 out of 5 patients admitted for heart failure per year