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

Introduction

Reduction in the pumping power of the left ventricle to the point where the left-ventricular ejection fraction (LVEF) is <35-40%; (<41%) (normal range is 50-65%).

Etiology

• coronary artery disease
  • myocardial hypocontractility due to previous myocardial infarction (most common)
    • hypertension
    • obesity
    • diabetes mellitus
• dilated cardiomyopathy
• valvular heart disease

Epidemiology

• underdiagnosed

Pathology

• left ventricular dilatation
• increased left ventricular end-diastolic volume
• elevated resting filling pressures
• reduced LVEF & cardiac index
• left atrial enlargement predisposes to atrial fibrillation
• pulmonary edema
• left heart failure leads to right heart failure
  • peripheral edema

Clinical manifestations

Framingham criteria for diagnosis of CHF*

• major criteria
  • paroxysmal nocturnal dyspnea
  • jugular venous distension
  • rales (pulmonary crackles)
  • cardiomegaly
  • acute pulmonary edema
  • S3 gallop
  • increased venous pressure (> 16 cm H2O)
  • positive hepatojugular reflex
• minor criteria
  • edema of extremities
  • cough at night
  • dyspnea on exertion
  • hepatomegaly
  • pleural effusion
  • vital capacity < 2/3 of normal
  • tachycardia (> 120/min)
• weight loss > 4.5 kg over 5 days of diuresis

• dyspnea is most common initial manifestation
• systolic murmur louder than 2/6 suggests structural rather than functional valvular heart disease
• uncommon manifestations
  • chest pain
  • systemic or pulmonary emboli
  • syncope
  • 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)
• serum B-type natriuretic peptide may be elevated (> 50 pg/mL)*

* serum B-type natriuretic peptide guided therapy no better than optimal medical therapy alone

Diagnostic procedures

• electrocardiogram using applied algorithm can identify LVSD in patients presenting with dyspnea
• echocardiography (every 1-2 years or when clinical status changes)
• coronary angiography
  • new onset systolic heart failure with
    • angina pectoris
    • condition predisposing to silent myocardial ischemia
    • high likelihood for ischemic heart disease

Radiology

• see dilated cardiomyopathy

Complications

• disease interaction(s) of LV systolic dysfunction with chronic renal failure

Management

• also see congestive heart failure
• treat hypertension & volume overload
  • target BP is < 120/80 (AHA)
    • 30-day all-cause mortality higher for systolic BP < 130 mm Hg (7% vs 4%) in elderly discharged after hospitalization
  • ACE inhibitors or ARB reduce HF hospitalizations & mortality
    • ARB if intolerant of ACE inhibitor
      • except hyperkalemia or worsening renal function
    • ARBs as effective as ACE inhibitors in preventing cardiovascular events & may be better tolerated
    • sacubitril/valsartan for symptomatic patients (see below)
      • optimize treatment of HFrEF before comorbidities
    • hypotension is a contraindication
  • loop diuretic for volume overload (reduce HF hospitalizations)
  • beta blocker (low dose) improve outcomes
    • start low, go slow, increment dose in 1-2 week intervals
    • target heart rate 60/min limited by hypotension
    • carvedilol 25 mg BID (target)
    • metoprolol succinate 200 mg QD (target)
    • bisoprolol 10 mg QD (target)
    • no beta-blocker better than other
    • all age groups benefit
    • ivabradine may be used in patients with heart rate > 70/min
      • ivabradine reduces HF hospitalization but not symptoms despite maximal tolerated dose of beta-blocker
    • reduced HF hospitalizations & mortality
    • not effective for symptoms
  • aldosterone antagonists (eplerenone, spironolactone)
    • may diminish mortality & heart failure hospitalizations
    • no survival advantage; conditional readmission advantage
    • especially beneficial in patients with acute coronary syndrome or myocardial infarction
    • indicated for patients with severe systolic heart failure
    • indicated for class 3 NYHA systolic heart failure
    • in patients with moderately impaired renal function, aldosterone antagonists do not increase risk for worsening renal function or all-cause mortality
      • no increase in all-cause mortality even if eGFR falls below 30 ml/min
  • angiotensin receptor-neprilysin inhibitors (ARNI) also reduce mortality
    • may be treatment of choice vs ACE inhibitor or ARB
      • may be initiated in patients with new-onset heart failure (HFrEF) without trial of ACE inhibitor or ARB
    • sacubitril/valsartan
      • may be agent of choice
      • no better than valsartan for reducing serum NT-proBNP in patients with left ventricular systolic dysfunction (HFrEF)
      • reduces cardiovascular & renal events in patients with mild HFrEF or HFpEF
    • not for use in combination with ACE-inhibitor or ARB
  • SGLT2 inhibitors (flozins) benefit patients with or without diabetes mellitus
    • 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
    • empagliflozin 10 mg of benefit with or without diabetes mellitus
    • flozins may improve maximal exercise capacity & quality of life in patients with heart failure HFrEF or HFpEF
    • reduced HF hospitalizations & mortality
  • combination of ARNI, beta-blocker, aldosterone antagonist & SGLT2 inhibitor with or without loop diuretic suggested as new standard of care
  • hydralazine/isosorbide dinitrate (Bidil) may be drug of choice in African Americans
    • useful for patients with hyperkalemia or worsening renal function with ACE inhibitor
    • indicated in addition to beta-blocker + ACE inhibitor + aldosterone antagonist for black patients with severe systolic heart failure
    • maximize ACE inhibitor, beta-blocker, diuretic prior to addition of Bidil
    • improves survival in black patients with class 3 or 4 HFrEF
  • for patients not at goal for blood pressure control, ACE inhibitor, beta-blocker & diuretic, calcium channel blockers amlodipine or felodipine may be useful
    • amlodipine & felodipine
      • not negative inotropic agents
      • not AV nodal blocking agents
      • neutral effect on morbidity & mortality
  • vericiguat reduces HF hospitalization but not symptoms
• digoxin
  • can reduce hospitalizations
  • used in patients with symptoms despite guideline-directed therapy
  • useful for patients with low blood pressures
  • blocks AV node in patients with atrial fibrillation
  • of no mortality benefit
• statin may be of benefit, even in non-ischemic heart failure
• antiplatelet agents
  • treat comorbid cardiovascular disease
  • aspirin better than warfarin for patients in sinus rhythm due to lower risk for hemorrhage
• cardiac pacemaker or implantable cardioverter defibrillator
  • ICD may benefit patients with LVEF < 35%
    • recommended if LVEF < 35% & class II or III NYHA heart failure on guideline-recommended medical therapy
  • ICD-related survival benefit is confined largely to LV systolic dysfunction related to coronary artery disease
  • in non-ischemic heart disease with LVEF < 35%, ICD reduces risk for sudden cardiac death but does not improve overall survival
  • risk of sudden death in trial participants without ICD declining
  • biventricular pacing (cardiac resynchronization therapy or CRT)
    • sinus rhythm
    • left bundle branch block (QRS > 150 ms)
    • may benefit patients with AV block
• 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
  • catheter ablation for atrial fibrillation reduces mortality & hospitalization for worsening heart failure
• respiratory support as needed
  • supplemental oxygen as needed
  • adaptive servo-ventilation as indicated ?
• omega-3 fatty acids may reduce hospitalization & mortality
• consider transcatheter mitral valve repair for mitral valve disease
• no benefit for erythropoiesis-stimulating agent
• no benefit for rivaroxaban for patients with CAD in sinus rhythm
• cardiac transplantation may be an option if medical management exhausted
• prognosis
  • worse for ischemic heart versus dilated cardiomyopathy for any given LV ejection fraction
  • 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
  • depression & antidepressant use associated with increased mortality & risk of hospitalization
• a quality of care initiative for hospitalized & postdischarge patients with HFrEF failed to improve outcomes
• patient education/engagement
  • 3-minute video & 1-page checklist, delivered electronically 1 week, 3 days, & 1 day before the clinic visit
    • 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

More general terms

• systolic heart failure
• left ventricular failure

More specific terms

• left ventricular outflow obstruction

Additional terms

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