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Heart Failure Update Based on 2013 ACC/AHA Guidelines

Heart Failure Update Based on 2013 ACC/AHA Guidelines. Lance Richards DO Cardiology Fellow Metro Heart and Vascular. Outline. Updated heart failure definitions Classification/stages of heart failure Use of BNP for diagnosis and prognosis Brief review of Stage A, B HF therapy

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Heart Failure Update Based on 2013 ACC/AHA Guidelines

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  1. Heart Failure UpdateBased on 2013 ACC/AHA Guidelines Lance Richards DO Cardiology Fellow Metro Heart and Vascular No Disclosures

  2. Outline • Updated heart failure definitions • Classification/stages of heart failure • Use of BNP for diagnosis and prognosis • Brief review of Stage A, B HF therapy • Stage C therapy • Stage D Advanced/Refractory heart failure therapies

  3. Classification of Recommendations and Levels of Evidence

  4. Definitions • HF is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. • Heart failure is a clinical diagnosis. • There is no single diagnostic test for HF. • Heart failure does not equal cardiomyopathy or LV dysfunction • These terms describe possible structural or functional reasons for the development of HF Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  5. Epidemiology • Growing and major public health issue • Population is getting older • Leading cause of hospitalization among patients >65 years of age • Largest percentage of expenditures related to HF are directly attributable to hospital costs • Hospitalization for acutely decompensated HF represents a sentinel prognostic event in the course of many patients with HF, with a high risk for recurrent hospitalization (e.g., 50% at 6 months) and a 1-year mortality rate of approximately 20-30%, 5 year around 50% Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  6. Definitions of Heart Failure Systolic Heart Failure Diastolic Heart Failure Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  7. Classification of Heart Failure

  8. Common Factors That Precipitate AcuteDecompensated HF • Non-adherence with medication regimen, dietary • Myocardial ischemia • Uncontrolled HTN • Atrial Fibrillation/arrhythmia • Drugs (Ca+ channel block, NSAIDS, TZD, Steroids) • Pulmonary embolus • Alcohol or illicit drug use • Surgery • Endocrine abnormalities (e.g., diabetes mellitus, hyperthyroidism, hypothyroidism) • Concurrent infections (e.g., pneumonia, viral illnesses) • Valve disorder • Myocarditis • Endocarditis Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  9. BNP • Brain natriuretic peptide (BNP) • Natriuretic hormone released primarily from the ventricles in response to myocardial stretch and high ventricular filling pressures • Cleavage of the prohormoneproBNP produces biologically active BNP and biologically inert N-terminal pro-BNP (NT-proBNP) • Elevated in multiple non-heart failure conditions • ACS, LVH, pericardial dz, valvulardz, AF, myocarditis, cardiac surgery, cardiversion • Pulmonary disease, renal failure, anemia, advancing age, sepsis, critical illness, metabolic and toxic states • May be lower in obese, HFpEF • NT-proBNP longer half life and excreted renally

  10. Using BNP for diagnosis • Useful for determination of dyspnea • Breathing Not Properly trial • 1586 patients presenting to the ED with dyspnea • BNP predicted HF better or equivalent to other clinical parameters • The diagnostic accuracy of B-type natriuretic peptide at a cutoff of 100 pg per milliliter was 83.4 percent • Values below 100 pg/mL have a very high negative predictive value for HF as a cause of dyspnea • Values > 400 pg/ml likely HF • 100-400 neither sensitive nor specific Maisel  A.S., Krishnaswamy  P., Nowak  R.M.; Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 347 2002:161-167

  11. Use to guide therapy • BNP guided therapy vs symptom guided therapy • Mixed results • Based on meta-analysis only, may be some mortality benefit with BNP guided therapy in pt’s < 75 years old • Adds prognostic value • Persistently elevated BNP suggests increased mortality risk

  12. I I I IIa IIa IIa IIb IIb IIb III III III BNP Measurement of BNP or NT-proBNP is useful to support clinical judgment for the diagnosis of acutely decompensated HF, especially in the setting of uncertainty for the diagnosis. Measurement of BNP or NT-proBNP and/or cardiac troponin is useful for establishing prognosis or disease severity in acutely decompensated HF. The usefulness of BNP- or NT-proBNP guided therapy for acutely decompensated HF is not well-established. A A Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  13. Stages, Phenotypes and Treatment of HF Population cohort study 5-year mortality data, survival for stage A, B, C, and D HF was 97%, 96%, 75%, and 20% Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  14. I I IIa IIa IIb IIb III III Stage AAt risk for structural heart disease Hypertension and lipid disorders should be controlled in accordance with contemporary guidelines to lower the risk of HF. Other conditions that may lead to or contribute to HF, such as obesity, diabetes mellitus, tobacco use, and known cardiotoxic agents, should be controlled or avoided. A Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  15. I I I IIa IIa IIa IIb IIb IIb III III III Stage BAsymptomatic structural heart disease In all patients with or without history of MI and reduced EF, ACE inhibitors should be used to prevent symptomatic HF and reduce mortality. In patients intolerant of ACE inhibitors, ARBs are appropriate unless contraindicated. (HOPE Trial) In all patients with or without history of MI or ACS and reduced EF, evidence-based beta blockers should be used to reduce mortality and reduce symptoms. To prevent sudden death, placement of an ICD is reasonable in patients with asymptomatic ischemic cardiomyopathy who are at least 40 days post-MI, have an LVEF of 30% or less, are on appropriate medical therapy and have reasonable expectation of survival with a good functional status for more than 1 year. A B B Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  16. Stage C Heart Failure Structural heart disease with prior or current symptoms

  17. I I IIa IIa IIb IIb III III Pharmacological Treatment for Stage C HFrEF Measures listed as Class I recommendations for patients in stages A and B are recommended where appropriate for patients in stage C. (Levels of Evidence: A, B, and C as appropriate) GDMT as depicted in Figure 1 should be the mainstay of pharmacological therapy for HFrEF. A Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  18. Pharmacologic Treatment for Stage C HFrEF

  19. Diuretics Mainstay of treatment for symptoms of fluid overload and symptoms relief

  20. I IIa IIb III Pharmacological Treatment for Stage C HFrEF Diuretics are recommended in patients with HFrEF who have evidence of fluid retention, unless contraindicated, to improve symptoms. Expert Opinion • Primary data consists of short term small scale chronic HF trials • reduce congestion, JVP, peripheral edema, body weight • Meta-analysis of a few small trials found that diuretics were associated with reduction in mortality as well as reduced admission for worsening heart failure Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  21. Loop Diuretics • Furosemide, Bumetanide, Torsemide, • Inhibit sodium reabsorption in the thick ascending loop of Henle • Threshold effect – adequate dose needed to achieve therapeutic effect • Rebound effect – post diuretic sodium retention

  22. Schematic of Dose-Response Curve of Loop Diuretics in Heart Failure Patients Compared With Normal Controls Felker, G. M. et al. J Am CollCardiol 2012;59:2145-2153 .

  23. Thiazides • Inhibit Na/Clcotransporter( block NA reabsoprtion) in the distal convoluted tubule • Help to overcome diuretic resistance by sequential nephron blocking and continued diuresis after loop diuretic wears off • Evidence: limited to 300 heart failure patients looking at weight loss, improvement in edema, urine Na excretion in combo with loop diuretics (LOE: C) • Metalozone2.5-10 mg (2-3 times weekly for OP), HCTZ 25-100 mg (30-60 mins before LD) Jentzer J, DeWald T, Hernandez A. Combination of Loop Diuretics with Thiazide-Type Diuretics in Heart Failure. JACC. Vol 56:19. 1527-1534

  24. I I IIa IIa IIb IIb III III Diuretics in Hospitalized Patients Patients with HF admitted with evidence of significant fluid overload should be promptly treated with intravenous loop diuretics to reduce morbidity. If patients are already receiving loop diuretic therapy, the initial intravenous dose should equal or exceed their chronic oral daily dose and should be given as either intermittent boluses or continuous infusion. Urine output and signs and symptoms of congestion should be serially assessed, and the diuretic dose should be adjusted accordingly to relieve symptoms, reduce volume excess, and avoid hypotension. B B Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  25. I IIa IIb III Diuretics in Hospitalized Patients (cont.) When diuresis is inadequate to relieve symptoms, it is reasonable to intensify the diuretic regimen using either: • higher doses of intravenous loop diuretics. • addition of a second (e.g., thiazide) diuretic. B Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  26. Bolus vs Continuous DOSE Trial • 308 pt’s ADHF to IV bolus BID vsgtt and high (2.5x oral dose) vs standard • IV Bolus every 12 hours vs continuous infusion - no significant difference in global assessment of symptoms scale (primary EP) • High dose vs standard dose - high dose did not meet PE of global symptom relief but increased dyspnea score, congestion, net output, BNP • High dose had transient increase in creatinine at 72 hours • Point: Higher doses may be more efficacious in relieving congestion at the cost of transient increase in Cr FelkerM, Lee K, Bull D. Diuretic Strategies in Patients with Acute Decompensated Heart Failure.NEJM. 2011; 364:797-805

  27. Key Points - Diuretics • Mainstay of heart failure therapy • Limited mortality data • Resistance caused by poor oral bioavailability, compensatory distal tubular Na reabsorption, renal insufficiency, low output state • Dietary sodium restriction • Diuretics activate SNS and RAS so use lowest effective dose possible • Discharging home • Optimized diuretic dose • Electrolyte replacement • Monitor renal function • Follow up

  28. Neurohormonal Activation/Sympathetic NS • The body’s adaptation to the disease becomes as important or more than the initial insult itself Good Bad

  29. ACE Inhibitors • Improve mortality • Improve symptoms, clinical status and exercise capacity • Improve LV function • Reduce hospitalization for HF • Prevent adverse ventricular remodeling

  30. ACEI Evidence • Consensus • 253 pt’sNYHA 3-4 EF <30% on diuretics, nitrates, digoxin randomized to enalaprilvsplacebo • 40% mortality reduction at 6 mos and 31% RRR at 12 mos • Average 30% RRR over 10 years • NYHA class improvement • SOLVD • 2569 pt’s NYHA class 2-3 EF < 35% on treatment for HF randomized to enalaprilvsplacebo • All cause mortality reduction 16% (35 vs 40%) • Meta-analysis of 5 trials including > 12,000 patients with HF and EF < 35-40% • Mortality benefit (23 versus 27 percent, odds ratio 0.80, 95% CI 0.74-0.87) • The CONSENSUS Trial Study Group. N Engl J Med • 1987;316:1429–35 • The SOLVD Investigators. N Engl J Med 1992;327:685–91

  31. I I IIa IIa IIb IIb III III Pharmacological Treatment for Stage C HFrEFACEI/ARB ACE inhibitors are recommended in patients with HFrEF and current or prior symptoms, unless contraindicated, to reduce morbidity and mortality. ARBs are recommended in patients with HFrEF with current or prior symptoms who are ACE inhibitor-intolerant, unless contraindicated, to reduce morbidity and mortality. A A Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  32. ACEI • Titrate to clinical trial doses • Adverse effects: Cough, angioedema, hyperkalemia, Bilateral RAS • Cr elevation 0.5 expected, stay the course • Studies exclude Cr > 2.5 • High dose > low dose > no dose (ATLAS) • Use ARB if intolerable to ACEI

  33. I IIa IIb III Pharmacological Treatment for Stage C HFrEFBeta Blockers Use of 1 of the 3 beta blockers proven to reduce mortality (i.e., bisoprolol, carvedilol, and sustained-release metoprolol succinate) is recommended for all patients with current or prior symptoms of HFrEF, unless contraindicated, to reduce morbidity and mortality. A • Mortality benefit • Symptomatic improvement • Reduction in hospitalization • Reduction in SCD • Anti-anginal Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  34. Beta Blocker Data • US Carvedilol Heart failure Program • 4 separate trials showed mortality reduction • COPERNICUS • 2289 pt’s with severe NYHA III or stable IV and EF < 25% randomized to carvedilolvs placebo. • Reduction in mortality (11.4 vs 18.5%), all cause hospitalization, HF hospitalization • MERIT-HF • 3991 pt’s with class II-IV HF with EF < 40%, receiving ACEI, dig, diuretic randomized to metoprolol succinate (titrated to 200 mg, ave dose 159 mg/day) vs placebo • 34% RRR all-cause mortality at 12 months ( 7. 2 vs 11%), hospitalization for HF, SCD -Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651–8. -Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERITHF). Lancet 1999;353:2001–7.

  35. 3029 pt’sNYHA II-IV HF, previous CV admission, EF < 35%, on ACEI , diuretic • Carvedilol25 mg BID (ave 41.8 mg) vsmetoprolol tartrate 50 mg BID(85 mg) • At 5 years, carvedilol lowered all-cause mortality (34-40%) entirely due to CV mortality (29-35%) • Greater reduction in HR (13.3 vs 11.7) and BP (3.8 vs 2.0) in carvedilol group. • Lower dose of metopolol used vs Merit HF trial ( 200 mg) • Metoprolol tartrate (short-acting) vs succinate (extended release) used in Merit HF Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 2003;362:7–13

  36. Effects of Beta blockade over time • When is it safe to start? • 26 pts with DCM EF < 45 NYHA II-IV started on metoprolol titrated to 50 mg BID at 1 month • Serial echocardiogram at baseline, 1 day, 1 mo, 3 mo Hall  S.A, Cigarroa  C.G, Marcoux  L, Risser  R.C, Grayburn  P.A, Eichorn  E.J; Time course of improvement in left ventricular function, mass and geometry in patients with congestive heart failure treated with beta-adrenergic blockade. J Am CollCardiol. 25 1995:1154-1161.

  37. Take home points • All patients with stable HF with reduced LVEF (<40%) should be started on beta blockers unless contraindication • Use studied drugs (Coreg, Metoprolol, Bisoprolol) at study doses • Start low with gradual titration (2-4 weeks)to target doses used in trials • If clinical decompensation with hypoperfusion or requirement of inotropic therapy, may need to halt or decrease dose • Initiate inpatient in stable heart failure (IMPACT –HF) • Acute bronchospasm - CI

  38. Which gets started first? ACEI vs BB • Historically, the major clinical BB trial were on ACEI • CIBIS III trial titrated BB first with similar outcomes • ACEI can provide rapid hemodynamic benefit • May be transient worsening EF with BB • Consider other indications and contraindications • All things equal ACEI first but try to start low dose BB

  39. Aldosterone Effects in Heart Failure • Promotes NA retention, K and Mg wasting • Aldosterone increases by 20X in HF • Induces myocardial and vascular fibrosis • Activates SNS and inhibits PNS • Aldosterone escape from ACEI

  40. RALES Study --1663 pts with NYHA III, IV HF and LVEF < 35 percent treated with ACEI, a loop diuretic, and digoxin allowed (Ex: Cr > 2.5 , K> 5.0) ( 10% on BB) --Randomly assigned to receive 25 mg of spironolactone daily + OMT vs placebo of OMT --At 24 months, 30% RRR in death EMPHASIS HF --2737 patients NYHA class 2 HF with EF <35% on ACEI/ARB or BB. --Eplerenone (up to 50 mg daily) or placebo (Ex: GFR < 30, K > 5.0) --37% reduction in composite death from cardiovascular causes or hospitalization for heart failure -Pitt B, Zannad F, et al. The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. NEJM. 1999; 341:709-717 -Zannad F, McMurray J, et al. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. NEJM. 2011; 364:11-21

  41. I IIa IIb III Pharmacological Treatment for Stage C HFrEF Aldosterone receptor antagonists are recommended in patients with NYHA class II-IV and who have LVEF of 35% or less, unless contraindicated, to reduce morbidity and mortality A --Start Spironolactone 12.5 to 25 mg daily, Eplerenone 25 mg/d, increasing to 50 mg daily. --Monitor K and renal function closely (2-3 d, 7 d, 3 m) --CI in K > 5.0, CrCl < 30 cc/min, Cr> 2.5 --Consider post MI (Ephesus) --Hypokalemic patients Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  42. Executive Summary: HFSA 2010 Comprehensive Heart Failure Practice Guideline

  43. I I IIa IIa IIb IIb III III Pharmacological Treatment for Stage C HFrEF The combination of hydralazine and isosorbidedinitrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III–IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated. (A-HeFT trial) A combination of hydralazine and isosorbidedinitrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated. A B Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

  44. I IIa IIb III Digoxin Digoxin may be beneficial in patients with HFrEF, unless contraindicated, to decrease hospitalizations for HF. DIG trial – 6800 patients with EF < 45% and sinus rhythm. Background therapy with ACEI and diuretics - No overall difference in mortality - Improvement in HF mortality and HF hospitalization B • The Digitalis Investigation Group. The Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure. NEJM. 1997:336(8)525-533.

  45. DIG Trial Subgroup analysis Rathore S, Curtis J, Wang Y. Association of Serum Digoxin Concentration and Outcomes in Patients with Heart Failure. JAMA. 2003;2897)871-878.

  46. Other important Stage C therapies • Device based therapy • ICD • CRT • Coronary revascularization • PCI • CABG • Renal Replacement therapy • Ultrafiltration IIB • Vasopressin antagonists IIB

  47. Stage D Heart Failure • Chronic HF patients whose symptoms persist or decline despite maximal GDMT. They will generally need: • Inotropic support • Mechanical circulatory device support • Transplant • Hospice/Palliative care

  48. Clinical Events and Findings Useful for Identifying Patients With Advanced HF Yancy C, Jessup M, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. JACC. 2013;62 (16):e147-e239.

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