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This review and update on heart failure covers outpatient therapy, gaps in HF treatment, HF classifications and stages, HF therapies and guideline updates, and the importance of medication titration and guideline adherence.
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Heart Failure Review and Update Mark Garcia, MD Assistant Professor University of New Mexico School of Medicine Division of Cardiology
Learning Objectives • Outpatient therapy focused • Understand gaps in HF therapy • Review HF classification and stages • Review HF therapies and guideline updates • Understand the importance of medication titration and guideline adherence
“Heart failure is the price we pay for the successful treatment of heart disease.” - Eugene Braunwald, MD Lecture 2017: “The war on heart failure”
A common and serious condition: • 6.5 million Americans adults have HF • Will increase to >8 million by 2030 • Lifetime risk of developing HF for both men and women is 1 in 5 • ~50% of people diagnosed with HF will die within 5 years • HF is the leading cause of hospitalizations annually Benjamin et al. Heart disease and stroke statistics—Heart Disease and Stroke Statistics - 2018 update: A report from the American Heart Association. Circulation 2018; 137:e67–e492.
Gaps in Heart Failure Treatment Cleland JG, Cohen-Solal A, Aguilar JC, et al. Management of heart failure in primary care (the IMPROVEMENT of Heart Failure Programme): an international survey. Lancet. 2002;360:1631-1639.
The Gap in Applying Guidelines James E. Calvin, MD; Sujata Shanbhag, MD; Elizabeth Avery, MS; John Kane, MS; Dejuran Richardson, PhD; Lynda Powell, PhD. Adherence to Evidence-Based Guidelines for Heart Failure in Physicians and Their Patients: Lessons From the Heart Failure Adherence Retention Trial (HART). Congest Heart Fail. 2012;18:73–78. Guarnaccia Francoa, Fimiani Biagioa, Zito Giovanni Battistaa, De Simone Antoniob, Stabile Giuseppeb, Bossone Edoardoc,d, Volpe Ercolee, BossoGiorgiof, Sacca` Luigif, OlivieroUgof, and the ALERT-HF Investigators. ALERT-HF: adherence to guidelines in the treatment of patients with chronic heart failure. J Cardiovasc Med 2014, 15:491–497
Heart Failure Definition • Heart Failure (HF): syndrome that results from structural or functional impairment of ventricular filling or ejection of blood • Cardinal features of HF: • Dyspnea and fatigue which limit exercise tolerance • Fluid retention which may lead to pulmonary and/or systemic congestion • Clinical diagnosis mostly based on history and physical exam with no single diagnostic test
Classifications of HF by Ejection Fraction • Heart Failure with reduced Ejection Fraction (HFrEF) • Left ventricular Ejection Fraction (EF) <40% • Heart Failure with preserved Ejection Fraction (HFpEF) • EF >50% • HFpEF borderline • EF 41 to 49% • HFpEF improved • EF >40% (previously reduced EF)
HF Stages • Stage A • At risk for heart failure (HTN, CAD, cardiotoxins) • No structural disease • Stage B • Structural disease/reduced EF • No heart failure symptoms • Stage C • Heart failure symptoms • Stage D • End-stage disease (recurrent hosp, need for Tx/LVAD)
Functional ClassificationNew York Heart Association Functional Class (NYHA) • NYHA class I • No physical limitations • NYHA class II • Slight limitation of physical activity • NYHA class III • Marked limitation of physical activity • NYHA class IV • Symptoms at rest
Brent N. Reed and Carla A. Sueta. A Practical Guide for the Treatment of Symptomatic Heart Failure with Reduced Ejection Fraction (HFrEF). Current Cardiology Reviews, 2015, 11, 23-32
Pathology to therapy • Neurohumoral activation leads to: • Vasoconstriction • Sodium retention • Maladaptive remodeling • Therapeutic interventions combat neurohumoral activation: • Reverse remodeling • Improve survival, symptoms, and QOL
Therapy by stage Stage A (at risk) • Treat BP to <130/80mmHg (new update) • Treat lipid disorders according to existing guidelines • Address/treat obesity, DM, tobacco use • Avoid/control cardiotoxic agents
Therapy by stage Stage B (reduced EF, no HF) • ACEi or ARB and evidence-based beta blockers • Reduce mortality (post-MI) and prevent HF • Statins according to existing guidelines • ICD in EF <30% while on appropriate guideline therapy and >40 days post-MI • Reduce mortality
Therapy by stage Stage C HFrEF and HFpEF • Initial labs • CBC, electrolytes, BUN/Cr, LFTs, lipid panel, TSH • Screen for hemochromatosis and HIV • New onset HF obtain CXR and TTE
BNP or NT-proBNP Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;
Diuretic dosing in HF Stage C HFrEF and HFpEF • Use diuretics to relieve volume overload • Sodium restriction Generic name and dosing range • Bumetanide 0.5–10 mg daily in one or two doses • Furosemide 20–600 mg daily in one or two doses • Torsemide 10–200 mg once daily
Therapy by stage Stage C HFrEF • ACEi/ARB, evidence based beta blockers • Aldosterone antagonist • ICD/CRT • Other therapies • ARNI
ACE-I and ARBs for managing HF Stage C HFrEF • Reduce mortality and hospitalizations • Improve symptoms • Asymptomatic LV dysfunction (LVEF < 40%) to class IV symptoms • ARBs are not superior to ACEi • Reasonable substitute if not tolerant to ACEi • Use with caution when Cr>3, SBP<80mmHg, and K>5
ACE-I for managing HF Stage C HFrEF Generic name and dosing range • Benazepril 5–40 mg once a day • Captopril 6.5–50 mg three times a day • Enalapril 2.5–20 mg twice a day • Fosinopril 5–40 mg once a day • Lisinopril 2.5–40 mg once a day • Quinapril 5–20 mg once a day • Ramipril 1.25–10 mg once a day • Trandolapril 1–4 mg once a day
ARBs for managing HF Stage C HFrEF Generic name and dosing range • Candesartan 4–32 mg once a day • Losartan 25–150 mg once a day • Valsartan 20–160 mg twice a day
Beta-blockers for managing HF Stage C HFrEF • Reduce mortality and hospitalizations • Improve symptoms • Asymptomatic LV dysfunction (LVEF < 40%) to class IV symptoms • In new onset HF, initiate beta blocker once congestion is resolved
Beta-blockers for managing HF Stage C HFrEF Generic name and dosing range • Carvedilol 3.125–25mg twice a day (50mg if >85Kg) • Metoprolol succinate 12.5–200 mg once a day • Bisoprolol 1.25–10 mg once a day
Dose Does Matter:Importance of titration Stage C HFrEF • Lisinopril titrated to trial doses decreased hospitalizations and fewer CV events • No change in mortality with higher dose • Beta blocker benefit increases relative to the degree of heart rate reduction • Reduced mortality and hospitalizations
Aldosterone receptor antagonistsfor managing HF Stage C HFrEF • Reduce mortality and hospitalizations • NYHA II-IV and EF < 35% • Class II with prior hospitalization or BNP elevation • Post acute MI and EF < 40% with HF or DM • Cr <2.5 in men or <2.0 in women, K<5.0
Aldosterone receptor antagonistsfor managing HF Stage C HFrEF Generic name and dosing range • Spironolactone 12.5–25 mg once a day • Eplerenone 25–50 mg once a day
Gregg C. Fonarow, MD. How Well Are Chronic Heart Failure Patients Being Managed? Rev Cardiovasc Med. 2006;7(suppl 1):S3-S11.
Device Therapy in HF Stage C HFrEF • Implantable Cardioverter-Defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) • Reduce mortality • EF <35% and NYHA class II or III • On chronic guideline therapy • Dilated cardiomyopathy • Ischemic cardiomyopathy >40 days post-MI • Life expectancy >1 yr
Device Therapy in HF Stage C HFrEF • Cardiac Resynchronization Therapy (CRT) • EF <35% and NYHA II-IV on guideline therapy • LBBB (QRS duration >150ms) • Reduce mortality and hospitalizations • Improve EF and reverse remodeling
Additional Therapies Stage C HFrEF • Hydralazine-Nitrate combination • Hydralazine and isosorbide dinitrate • Reduce HF mortality and morbidity • NYHA Class III-IV symptoms • Self described as African American • Already on optimal ACEi and beta blocker • ACEi/ARB intolerant
Additional Therapies Stage C HFrEF • Digoxin can be beneficial to decrease HF hospitalizations • ASA and statin (based on primary and secondary prevention recommendations) • Omega-3 polyunsaturated fatty acid (PUFA) for NYHA class II–IV symptoms (IIa) • May reduce mortality and CV hospitalizations
New Therapy Stage C HFrEF • Angiotensin-neprilysin inhibition (ARNI) • Further reduce mortality and morbidity • ACEi and ARB class I indication • Head to head comparison to ACEi resulted in ARNI being superior (further reduced mortality and hospitalizations) • NYHA class II or III who tolerate ACEi/ARB
Angiotensin-neprilysin inhibition Scott A. Hubers, MD; Nancy J. Brown, MD. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition. Circulation. 2016;133:1115-1124.
Angiotensin-neprilysin inhibition (ARNI) for managing HF Stage C HFrEF • Do not administer with ACEi • Do not give if history or angioedema
Angiotensin-neprilysin inhibitionfor managing heart failure Stage C HFrEF Generic name and dosing range • Sacubitril-valsartan 24–26 mg, 49–51 mg, or 97–103 mg twice daily • Recommend to replace ACEi/ARB with sacubitril-valsartan for further reduction of morbidity and mortality (class I indication) • If tolerated for 2–4 weeks, double the daily dose until target dose of 97–103 mg twice daily is reached • For patients converting from an ACEi, start 36 hours after discontinuation of the ACEi
Additional Therapies Stage C HFrEF and HFpEF • Exercise in HF is safe and recommended • Cardiac rehab • Improve functional capacity, QOL, and mortality • Clinically stable patients
Additional Therapies Stage C HFrEF and HFpEF • Sleep disordered breathing (new update) • NYHA class II-IV and suspicion of sleep disordered breathing • Referral for sleep evaluation • Obstructive sleep apnea • CPAP beneficial • Central sleep apnea and NYHA II-IV HFrEF • Adaptive servo-ventilation can be harmful
Therapy by stage Stage C HFpEF • Hypertension treat according to GDMT and titrated to attain SBP <130 mm Hg (new update) • Omega-3 polyunsaturated fatty acid (PUFA) for NYHA class II–IV symptoms (IIa) • May reduce mortality and CV hospitalizations
Therapy by stage Stage C HFpEF (new update IIb) • Aldosterone receptor antagonist • EF ≥45% • Elevated BNP levels or HF admission within 1 year • GFR >30 mL/min or creatinine <2.5 mg/dL and potassium <5.0 mEq/L • Consider Spironolactone to decrease hospitalizations
Drugs to avoid in HF • Verapamil, diltiazem, nicardipine • NSAIDs • Thiazolidinediones
Therapy by stage Stage D (End-stage disease) • >2 Hospitalization in the past year • Persistent symptoms with ADLs • Weight loss (cardiac cachexia) • Intolerance to ACEi or beta blockers • Frequent SBP <90mmHg • Decline in serum sodium (<133) • Progressive decline in renal function • Frequent ICD shocks
Therapy by stage Stage D (End-stage disease) • In carefully selected patients consider advanced options: • Ionotropic support • Mechanical circulatory support • Transplant • Palliative care and hospice • ICD deactivation
Strategies for success • Closely monitor vital signs (include postural changes), renal function, and electrolytes • Continual education of patients and families • Use a multidisciplinary team • Continual assessment and management of comorbidities • DM, depression, COPD, etc.
Strategies for success • Reducing HF readmissions: • In-hospital initiation of HF therapies • Resolution of congestion • HF education • Medication titration and adherence • Close monitoring and follow up
References • Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJV, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WHW, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240–e327.ABCs of Heart Failure • Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017 • Ike S. Okwuosa, MD , OluseyiPrincewill, MD, MPH , ChiemekeNwabueze, MD , Lena Mathews, MD , Steven Hsu, MD , Nisha A. Gilotra, MD , Sabra Lewsey, MD, MPH , Roger S. Blumenthal, MD, Stuart D. Russell, MD. The ABCs of managing systolic heart failure: Past, present, and future. Cleveland Clinic Journal of Medicine. 2016 October;83(10):753-765 • Benjamin et al, “Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association” Circulation. 2018;137:e67–e492. • Gregg C. Fonarow, MD, FACC, FAHA. How Well Are Chronic Heart Failure Patients Being Managed? Rev Cardiovasc Med. 2006;7(suppl 1):S3-S11 • 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., and Michael R. Zile, M.D., Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure. N Engl J Med 2014;371:993-1004. • Clyde W. Yancy, MD, Comprehensive Treatment of Heart Failure: State-of-the-Art Medical Therapy. Rev Cardiovasc Med. 2005;6(suppl 2):S43-S57 • Bozkurt B. “What is new in Heart Failure Management in 2017? Update on ACC/AHA Heart Failure Guidelines.” Current Cardiology Reports 2018; 20: 39. • Hartley-Rayner E. et al “Update on the management of acute heart failure.” Current Opinion in Cardiology 2018; 33:225-231.