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left ventricular systolic dysfunction; heart failure with reduced ejection fraction (HFrEF)

Reduction in the pumping power of the left ventricle to the point where the left-ventricular ejection fraction (LVEF) is <35-40%; (<41%) [1] (normal range is 50-65%). Etiology: 1) coronary artery disease - myocardial hypocontractility due to previous myocardial infarction (most common) - hypertension - obesity - diabetes mellitus 2) dilated cardiomyopathy 3) valvular heart disease [2] Epidemiology: - underdiagnosed Pathology: 1) left ventricular dilatation 2) increased left ventricular end-diastolic volume 3) elevated resting filling pressures 4) reduced LVEF & cardiac index 5) left atrial enlargement predisposes to atrial fibrillation 6) pulmonary edema 7) left heart failure leads to right heart failure - peripheral edema Clinical manifestations: Framingham criteria for diagnosis of CHF* 1) major criteria a) paroxysmal nocturnal dyspnea b) jugular venous distension c) rales (pulmonary crackles) d) cardiomegaly e) acute pulmonary edema f) S3 gallop g) increased venous pressure (> 16 cm H2O) h) positive hepatojugular reflex 2) minor criteria a) edema of extremities b) cough at night c) dyspnea on exertion d) hepatomegaly e) pleural effusion f) vital capacity < 2/3 of normal g) tachycardia (> 120/min) 3) weight loss > 4.5 kg over 5 days of diuresis 4) dyspnea is most common initial manifestation 5) systolic murmur louder than 2/6 suggests structural rather than functional valvular heart disease 6) uncommon manifestations a) chest pain b) systemic or pulmonary emboli c) syncope d) sudden death * At least one major & two minor criteria are necessary for diagnosis of CHF (in reference to systolic heart failure) Laboratory: - basic metabolic panel (serum electrolytes & renal function testing) [2] - serum B-type natriuretic peptide may be elevated (> 50 pg/mL) [12]* * serum B-type natriuretic peptide guided therapy no better than optimal medical therapy alone [2,25] Special laboratory: - electrocardiogram using applied algorithm can identify LVSD in patients presenting with dyspnea [38] - echocardiography (every 1-2 years or when clinical status changes) [2] - coronary angiography [2] - new onset systolic heart failure with - angina pectoris - condition predisposing to silent myocardial ischemia [2] - high likelihood for ischemic heart disease [2] Radiology: - see dilated cardiomyopathy Management: 1) also see congestive heart failure 2) treat hypertension & volume overload a) target BP is < 120/80 (AHA) [2] - 30-day all-cause mortality higher for systolic BP < 130 mm Hg (7% vs 4%) in elderly discharged after hospitalization [32] b) ACE inhibitors or ARB reduce HF hospitalizations & mortality [51] - ARB if intolerant of ACE inhibitor [2,16] - except hyperkalemia or worsening renal function [2] - ARBs as effective as ACE inhibitors in preventing cardiovascular events & may be better tolerated [17] - sacubitril/valsartan for symptomatic patients (see below) [2] - optimize treatment of HFrEF before comorbidities [46] - hypotension is a contraindication [48] c) loop diuretic for volume overload (reduce HF hospitalizations) d) beta blocker (low dose) improve outcomes [9] - start low, go slow, increment dose in 1-2 week intervals - target heart rate 60/min limited by hypotension [2] - carvedilol 25 mg BID (target) - metoprolol succinate 200 mg QD (target) - bisoprolol 10 mg QD (target) - no beta-blocker better than other [9] - all age groups benefit [18] - ivabradine may be used in patients with heart rate > 70/min - ivabradine reduces HF hospitalization but not symptoms [51] despite maximal tolerated dose of beta-blocker [19] - reduced HF hospitalizations & mortality [51] - not effective for symptoms [51] e) aldosterone antagonists (eplerenone, spironolactone) - may diminish mortality & heart failure hospitalizations [2] - no survival advantage; conditional readmission advantage [8] - especially beneficial in patients with acute coronary syndrome or myocardial infarction [2] - indicated for patients with severe systolic heart failure [2] - indicated for class 3 NYHA systolic heart failure [46] - in patients with moderately impaired renal function, aldosterone antagonists do not increase risk for worsening renal function or all-cause mortality [49] - no increase in all-cause mortality even if eGFR falls below 30 ml/min [49] f) angiotensin receptor-neprilysin inhibitors (ARNI) also reduce mortality [37] - may be treatment of choice vs ACE inhibitor or ARB [2,40] - may be initiated in patients with new-onset heart failure (HFrEF) without trial of ACE inhibitor or ARB [2] - sacubitril/valsartan - may be agent of choice [2,19,21,22,28] - no better than valsartan for reducing serum NT-proBNP in patients with left ventricular systolic dysfunction (HFrEF) [42] - reduces cardiovascular & renal events in patients with mild HFrEF or HFpEF [45] - not for use in combination with ACE-inhibitor or ARB g) SGLT2 inhibitors (flozins) benefit patients with or without diabetes mellitus [33] - dapagliflozin FDA-approved for use with or without diabetes mellitus - dapagliflozin reduces days of potential full health lost due to death, hospitalizations, & impaired well-being - benefit increases over time during the first year [50] - empagliflozin 10 mg of benefit with or without diabetes mellitus [33] - flozins may improve maximal exercise capacity & quality of life in patients with heart failure HFrEF or HFpEF [47] - reduced HF hospitalizations & mortality [51] h) combination of ARNI, beta-blocker, aldosterone antagonist & SGLT2 inhibitor with or without loop diuretic suggested as new standard of care [2,19,37] i) hydralazine/isosorbide dinitrate (Bidil) may be drug of choice in African Americans - useful for patients with hyperkalemia or worsening renal function with ACE inhibitor [2] - indicated in addition to beta-blocker + ACE inhibitor + aldosterone antagonist for black patients with severe systolic heart failure [2] - maximize ACE inhibitor, beta-blocker, diuretic prior to addition of Bidil [2] - improves survival in black patients with class 3 or 4 HFrEF [44] j) for patients not at goal for blood pressure control, ACE inhibitor, beta-blocker & diuretic, calcium channel blockers amlodipine or felodipine may be useful [2] - amlodipine & felodipine - not negative inotropic agents - not AV nodal blocking agents - neutral effect on morbidity & mortality [2] k) vericiguat reduces HF hospitalization but not symptoms [51] 3) digoxin - can reduce hospitalizations [35,35,36] - used in patients with symptoms despite guideline-directed therapy [2] - useful for patients with low blood pressures - blocks AV node in patients with atrial fibrillation - of no mortality benefit 4) statin may be of benefit, even in non-ischemic heart failure [4] 5) antiplatelet agents a) treat comorbid cardiovascular disease b) aspirin better than warfarin for patients in sinus rhythm due to lower risk for hemorrhage [7] 6) cardiac pacemaker or implantable cardioverter defibrillator - ICD may benefit patients with LVEF < 35% [15] - recommended if LVEF < 35% & class II or III NYHA heart failure on guideline-recommended medical therapy [2] - ICD-related survival benefit is confined largely to LV systolic dysfunction related to coronary artery disease [20] - in non-ischemic heart disease with LVEF < 35%, ICD reduces risk for sudden cardiac death but does not improve overall survival [20] - risk of sudden death in trial participants without ICD declining [33] - biventricular pacing (cardiac resynchronization therapy or CRT) - sinus rhythm [2] - left bundle branch block (QRS > 150 ms) [2] - may benefit patients with AV block [11] 7) ablation for atrial fibrillation - associated with reduced all-cause mortality (9% vs 18%) & heart failure hospitalizations (16% vs 28%), - also beneficial in improving LV ejection fraction, 6-minute walk distances, & quality of life [31] - catheter ablation for atrial fibrillation reduces mortality & hospitalization for worsening heart failure [27] 8) respiratory support as needed - supplemental oxygen as needed - adaptive servo-ventilation as indicated ? 9) omega-3 fatty acids may reduce hospitalization & mortality [23] 10) consider transcatheter mitral valve repair for mitral valve disease [40] 11) no benefit for erythropoiesis-stimulating agent [10] 12) no benefit for rivaroxaban for patients with CAD in sinus rhythm [29] 13) cardiac transplantation may be an option if medical management exhausted [1] 14) prognosis a) worse for ischemic heart versus dilated cardiomyopathy for any given LV ejection fraction b) predictors of poor prognosis - syncope - persistent third heart sound (S3) - signs of chronic right-sided heart failure - extensive conduction system disease - left bundle branch block (LBBB) - bifascicular block - 2nd or 3rd degree AV block - also see end of life & impending death c) depression & antidepressant use associated with increased mortality & risk of hospitalization [5] 15) a quality of care initiative for hospitalized & postdischarge patients with HFrEF failed to improve outcomes [41] 16) patient education/engagement - 3-minute video & 1-page checklist, delivered electronically 1 week, 3 days, & 1 day before the clinic visit [39] - video explains - guideline-directed therapy intensification - gaps in prescribing - reasons for clinical inertia - importance of patient engagement in treatment discussions. - checklist allows patients to - itemize their medications - contrast them with recommendations

Interactions

disease interactions

Related

dilated cardiomyopathy

Useful

cardiac index left ventricular ejection fraction (LVEF) left ventricular end diastolic volume (LVEDV) or dimension

Specific

left ventricular outflow obstruction

General

systolic heart failure left ventricular failure

References

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