Heart failure with reduced ejection fraction

Last revised by Dr Francis Deng on 01 May 2022

Heart failure with reduced ejection fraction (HFrEF) is a type of heart failure due to left ventricular dysfunction (left heart failure) classified by a left ventricular ejection fraction of 40% or less. Heart failure with reduced ejection fraction occurs when the left ventricle is unable to contract and effectively pump blood (also known as systolic heart failure), thus decreasing cardiac output.

The prevalence of heart failure worldwide is 23 million people, of which 50% are classified as heart failure with reduced ejection fraction 1. The number of cases is expected to rise due to the aging population. Compared to women, men are more likely to have heart failure with reduced ejection fraction. 

Comorbid risk factors include the following 2:

Heart failure is a clinical syndrome that has a similar clinical presentation regardless of ejection fraction. Symptoms can be conceptualized as those related to fluid overload (congestion) and those related to poor cardiac output (pump failure) 3. The former include dyspnea, orthopnea, peripheral edema, and abdominal discomfort. The latter include loss of appetite, fatigue, and weakness. Some patients have palpitations.

On physical exam, displaced apical impulse is the best predictor of reduced left ventricular ejection fraction due to its association with dilated cardiomyopathy 10. The palpated point of maximal impulse is displaced lateral to the midclavicular line.

ECG is usually abnormal in heart failure with reduced ejection fraction 11. For example, there may be evidence of prior or ongoing myocardial infarction.

Cardiac biomarkers such as NT-proBNP (N-terminal pro-B-type natriuretic peptide) and BNP are usually abnormally elevated in heart failure. Levels are more elevated in heart failure with reduced ejection fraction in particular as the left ventricular cavity enlarges, causing greater wall stress 4.

Acute myocardial injury or chronic overload of pressure or volume can lead to reduced cardiac output. Compensatory myocardial remodeling occurs in an attempt to restore blood flow but may progress to become maladaptive 5. Left ventricular contractility decreases, which leads to further diminished blood flow, retention of end-diastolic volume, and increased regurgitation.

Common causes of heart failure with reduced ejection fraction include the following 12,13

Other causes are less common 12,13:

Imaging has several roles in the diagnosis of heart failure with reduced ejection fraction: 

  • detecting the manifestations of heart failure
  • measuring the left ventricular ejection fraction
  • determining the etiology of heart failure

Chest radiographs show the presence of nonspecific findings of heart failure including cardiomegaly, pulmonary edema, and pleural effusions.

Echocardiography is the initial test for evaluating left ventricular structure, mass, and ejection fraction. Heart failure with reduced ejection fraction typically shows an increase in end-diastolic volume and end-systolic volume, an eccentric hypertrophy pattern, and low ejection fraction. Doppler echocardiography can also be used to evaluate for aortic and mitral valvular dysfunction 6

Coronary CTA is a noninvasive alternative to coronary catheter angiography to help distinguish ischemic and nonischemic etiologies of heart failure.  Cardiac CT can also evaluate the left ventricular function and regional wall motion to corroborate findings on echocardiography.

Coronary angiography (left heart catheterization) is indicated when ischemic cardiomyopathy may be the etiology of heart failure. Invasive angiography is the gold standard for detection of significant steno-occlusive disease in the coronary arteries that supply the left ventricular myocardium. 

When echocardiographic images are suboptimal, cardiac magnetic resonance should be considered as it is capable of evaluating ejection fraction, segmental dysfunction, valvular lesions, and myocardial fibrosis. However, utilization of cardiac magnetic resonance is challenging in patients with implantable cardiac devices 7.

Radionuclide myocardial perfusion imaging can risk stratify patients as a first step in evaluating for ischemic heart disease as the possible etiology of heart failure.

Substantial evidence-based treatment exists for symptomatic heart failure with reduced ejection fracture, including both pharmacotherapy and device-based therapies 1,8,9. First-line pharmacotherapy is a combination of diuretics (typically a loop diuretic) and neurohormonal therapy consisting of a beta blocker and a renin-angiotensin system blocker (angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, or angiotensin receptor-neprilysin inhibitor) 1. Secondary pharmacotherapy, such as vasodilators or a sodium-glucose cotransporter 2 inhibitor, is warranted in some patients 1.

A cardiac implantable electronic device is indicated for certain eligible patients with heart failure with reduced ejection fracture, consisting of either an implantable cardioverter defibrillator or cardiac resynchronization pacemaker 9. Additional interventions include coronary artery revascularization (surgical coronary artery bypass grafting or percutaneous coronary stenting) and valvular intervention (surgical or transcatheter aortic valve replacement for critical aortic stenosis, and surgical or transcatheter mitral valve repair for severe mitral regurgitation) 9.

In general, the prognosis of heart failure with reduced ejection fraction is worse than that with preserved ejective fraction.

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