Outline Chronic Heart Failure: • Diagnosis and Staging Update on Effective • Diastolic Heart Failure Monitoring and Treatment • Systolic Heart Failure Medications • Devices and End-Stage Heart Failure Michael G. Shlipak, MD, MPH Professor of Medicine, UCSF Chief, Division of General Internal Medicine, SFVA Medical Center August 12, 2016 Heart Failure Epidemiology 2013 ACCF/AHA Guideline for the Management of Heart Failure • Only cardiovascular outcome that continues to increase A Report of the American College of Cardiology Foundation/American Heart Association Task • Lifetime risk ~20% Force on Practice Guidelines • Complicated to manage with multiple other comorbidities CIRCULATION, 2013 • Treatments improve survival and reduce morbidity substantially. 2016 ACC/AHA/HFS • 4 5 classes of medications improve survival A Focused Update on New Pharmacological Therapy for • 2 3 classes of medications improve symptoms Heart Failure CIRCULATION, 2016 1
Why is Heart Failure Challenging to Manage? Question 1: Which of the following establishes a HF diagnosis? • Patients are very complicated and often frail 49% EF < 35% on echo a. • CHF travels with many other comorbidities: b. BNP > 300 on blood test − CAD, hypertension, diabetes, CKD 29% S3 on exam c. • Polypharmacy All of the above d. 17% • Diastolic heart failure becoming more common None of the above e. 3% 3% Heart Failure is a Clinical Diagnosis Diastolic vs. Systolic Heart Failure • Diastolic HF: • Essential Symptoms: dyspnea, fatigue, orthopnea − Official term is “Heart Failure with Preserved • Signs: rales , edema, JVD, S3 Ejection Fraction” • Physical exam : does not distinguish systolic vs. − Abbreviated as HFpEF diastolic − Pronounced “huff-puff” • Systolic HF: • Helpful features include: − Official term is “Heart Failure with Reduced − Chest X-Ray : pulmonary congestion Ejection Fraction” − Elevated BNP or Nt-proBNP − Abbreviated as HFrEF − Pronounced “huff-ruff” − Echo showing diastolic or systolic dysfunction 2
AHA (2009) Classification of Heart NYHA Functional Classes Failure Classes assume a prior diagnosis of heart failure Risk factors for heart failure- no clear A. signs/symptoms I. No limitation on ordinary physical activity Not HF Asymptomatic LV disease- LVH, diastolic B. Slight limitation – ordinary physical activity II. dysfunction, valve disease, low EF III. Marked limitation- < ordinary physical activity C. Symptomatic heart failure- dyspnea at rest or IV. Symptoms or discomfort at rest exertion, fluid retention Combines stages 1-3 D. Advanced heart failure - inotrope requirement, consideration for assist device or transplant Problems with these classes: • Patients vary across stages, going up and down • Can only progress down the classes • All class 4 at time of hospitalization • Emphasizes prevention over staging Outline Strategies that apply to all CHF Patients • Initial ECHO • Diagnosis and Staging Repeat only if major changes • • Diastolic Heart Failure Salt restriction • Daily weight monitoring • • Systolic Heart Failure Medications • Exercise • Devices and End-Stage Heart Failure • Diuretics for symptoms Avoid NSAIDS • Monitor: • − Volume status − Electrolytes, renal function 3
Question 2: Which of the following improve What is Diastolic Heart Failure? survival in diastolic heart failure? • “Stiff heart syndrome”- heart cannot relax in diastole ACE-I a. 41% to allow the left ventricle to fill b. ARB’s • Causes increased pressure in the left atrium, and Beta blockers c. 27% pulmonary edema Ca-channel blockers d. 20% • Defined by EF, yet actual stroke volume may be same e. All of the above as SHF None of the above f. 7% • Same signs and symptoms as systolic HF 3% 2% • Especially common in women and elderly ACC/AHA Guidelines for DHF Treatment Diastolic HF: Good and Bad News • BP control (SBP < 130) Good news: • Rate/rhythm control in AF • More favorable prognosis than SHF • Diuretics for pulmonary congestion • Simpler regimen, as diuretics cornerstone of therapy • Revascularization and other treatment for coronary Bad news: ischemia • Often progresses to SHF • European guideline recommends cardiac • No therapies improve DHF survival rehabilitation, though limited evidence Guideline for Management of Chronic HF, Ann Intern Med, 2011 − 4
Outline ACE Inhibitors • Improve symptoms and reduce hospitalizations • Diagnosis and Staging • Decrease mortality risk for all heart failure stages • Diastolic Heart Failure • Class effect- all ACE inhibitors • Systolic Heart Failure Medications • Aim for target dose (ATLAS finding) • Devices and End-Stage Heart Failure Kidney Function and ACE Inhibitors Meta-Analysis of ACE Trials in Heart Failure • 30 RCTs- ACE-I vs. placebo • Clinical trials show benefit if estimated GFR > 30 • Mortality • No evidence for lower GFR levels − 0.77 (0.67-0.88) • Expect the creatinine to rise at least 30% • Death or hospitalization for heart failure − 0.65 (0.57-0.74) • Even creatinine doubling is OK- typically returns near baseline • Specific ACE-I’s with benefits in RCT’s: • Worry about K increase (keep < 5.5); balance the K − Benzapril -Enalapril -Ramipril with diuretic dose. − Captopril -Lisinopril • Continue ACE-Is as eGFR declines unless cannot control K. Shlipak MG, Ann Intern Med 2003 5
ARBs in Systolic Heart Failure Question 3: What is an “ARNI”? A. Novel heart failure agent that slows A. • Generally equivalent to ACE inhibitors down the SA node to allow greater • Use for patients with cough on ACE inhibitors ventricular filling 67% B. New class of heart failure drugs that B. • Combination of ACE and ARB? prevents arrhythmias so patients will not require an ICD − Decreases hospitalization risk; increases adverse effect C. C. A combination of an Angiotensin risk (increased K) Receptor Blocker with a medication that − No survival difference 12% blocks neprilysin 9% 7% 5% D. A novel beta-blocker that has the D. − Generally, not recommended, as safety probably lower ability to increase ejection fraction in actual practice E. All of the above E. Yusuf S. et al. Lancet 2003 PARADIGM-HF Trial: Angiotensin- PARADIGM-HF Trial Receptor blocker/Neprilysin • N=8,442 Inhibitor (ARNI) vs. Enalapril • Class 2-4 HF symptoms • EF< 40% • The new drug: − LCZ696 − Valsartan/Sacubritril − Entresto − 2015 FDA approval • Sacubritril- blocks Neprilysin � • ↓ vasoconstriction, ↓ Na retention, ↓ remodeling • Prior ARNI- Omipatrilat (caused ↓ BP, angioedema, and cognitive dysfunction) 6
PARADIGM-HF Trial PARADIGM-HF Trial Baseline Characteristics of Patients • Inclusion Criteria: Mean Age 64 − EF< 40% % Female 22% − BNP > 150 Race − Prior ACE/ARBs White 66% • Exclusion Criteria: Black 5% Asian 18% − SBP< 95 Other 11% − eGFR< 30 Mean BP 122/72 − K> 5.2 Mean Creatinine 1.12 − ACE/ARB angioedema % eGFR<60 36% Class 2 70% Class 3 24% PARADIGM-HF Trial PARADIGM-HF Trial Baseline Characteristics of Patients (continued) Enrollment in 3 Phases 1.) Enalopril 10mg 2x/day: 2 weeks (N= 10,513) Medications -10% drop out (5.6%- adverse effects) ACE/ARB 100% 2.) LCZ696: 4 weeks (N=9,419) BB 93% -100 mg and 200 mg Diuretics 80% -10% drop out (5.8%- adverse effect) Aldo-Antagonist 55% Digitalis 30% 3.) RCT: Enalopril (10 mg 2x/day) vs. ARNI (200 mg 2x/day) (N=8,442) Devices ICD 15% -trial stopped early CRT 7% -median follow-up 27 months 7
PARADIGM Trial PARADIGM Trial Primary and Secondary Outcomes Adverse Events during Randomized Treatment LCZ696 Enalapril Hazard Ratio Event P-value LCZ696 Enalapril (N=4,187) (N=4,212) Outcome or Difference (N=4,187) (N=4,212) Hypotension (95% CI) Symptomatic 14.0% 9.2% <0.001 Primary composite outcome – (%) Elevated serum creatinine CV Death or HF 21.8% 26.5% 0.80 (0.73-0.87) ≥2.5 mg/dl 3.3% 4.5% 0.007 Hospitalization Elevated serum Death 13.3% 16.5% 0.80 (0.71-0.89) potassium HF Hospitalization 12.8% 15.6% 0.79 (0.71-0.89) >6.0 mmol/liter 4.3% 5.6% 0.007 Secondary outcomes – (%) Cough 11.3% 14.3% <0.001 Death 17.0% 19.8% 0.84 (0.76-0.93) Angioedema 0.5% 0.2% 0.19 Controversies around Entresto Recommendations around Entresto • Cost- $4,560/year Recommendations − Pay for performance models? 1.) Class 1 agent for systolic HF • Single trial 2.) For use in patients who are stable on maximum − Only 5% Blacks ACE or ARB − Low % with devices 3.) Never use in combination with ACE or ARB − Run in period required tolerance to the drug • Potential “off target” effects? − Hypotension − Cognitive decline a concern (with Omipatrilat) 8
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