What is heart failure with reduced ejection fraction (HFrEF) in older adults with a history of hypertension, coronary artery disease, or diabetes?

What is Heart Failure with Reduced Ejection Fraction (HFrEF)?

Heart failure with reduced ejection fraction (HFrEF) is a clinical syndrome characterized by symptoms of dyspnea, fatigue, or exertional limitation caused by impaired ventricular filling or ejection of blood, occurring when the left ventricular ejection fraction (LVEF) is ≤40%, accompanied by progressive left ventricular dilatation and adverse cardiac remodeling. 1, 2

Defining Characteristics

HFrEF represents one of three main subtypes of heart failure, distinguished specifically by the degree of left ventricular systolic dysfunction:

• LVEF ≤40% defines HFrEF, differentiating it from HF with mildly reduced EF (HFmrEF, LVEF 41-49%) and HF with preserved EF (HFpEF, LVEF ≥50%) 1
• The reduced ejection fraction reflects the heart's inability to pump adequate blood volume with each contraction 2
• Progressive left ventricular dilatation occurs as a compensatory mechanism that ultimately worsens cardiac function 2

Clinical Presentation in Older Adults with Comorbidities

In older adults with hypertension, coronary artery disease, or diabetes, HFrEF presents with specific epidemiological and clinical features:

• Coronary artery disease is the most common etiology, particularly in men and younger age groups, often manifesting as myocardial scarring, stunning, or hibernation from prior infarctions 1
• Hypertension contributes to HFrEF development through chronic pressure overload, though it is more commonly associated with HFpEF in elderly populations 1
• Diabetes mellitus independently increases HFrEF risk by 80-100%, with mechanisms including neurohormonal activation, inflammation, and impaired skeletal muscle function 1
• The prevalence rises sharply after age 75, reaching 10-20% in those aged 70-80 years 1

Pathophysiological Mechanisms

The underlying pathophysiology involves multiple interconnected systems:

• Reduced cardiac output from impaired left ventricular contractility leads to inadequate tissue perfusion 1
• Neurohormonal activation (renin-angiotensin-aldosterone system and sympathetic nervous system) initially compensates but ultimately perpetuates disease progression through sodium retention and vasoconstriction 1
• Venous congestion develops from elevated filling pressures, causing pulmonary edema (left-sided failure) and peripheral edema (right-sided failure) 1
• Kidney dysfunction results from reduced renal perfusion pressure (decreased arteriovenous gradient) and increased venous pressure transmitted to the renal tubules 1

Symptoms and Signs

Clinical manifestations include both specific and non-specific features:

• Cardinal symptoms: Dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, and early-onset fatigue with mild physical activity 1, 3
• Physical examination findings: Elevated jugular venous pressure, displaced apical impulse, pulmonary rales, peripheral edema, and third heart sound (S3 gallop) 1, 3
• Important caveat: Symptoms are often non-specific and difficult to interpret in obese individuals, the elderly, and patients with chronic lung disease 1

Prognosis and Disease Burden

HFrEF carries substantial morbidity and mortality:

• Overall mortality: 50% of patients are dead at 4 years, with worse prognosis than certain common cancers 1
• Post-hospitalization outcomes: 40% of patients admitted with HFrEF are dead or readmitted within 1 year 1
• Five-year survival: Only 25% after hospitalization for HFrEF 2
• The condition accounts for 5% of acute hospital admissions and 2% of national healthcare expenditure 1

Diagnostic Approach

Diagnosis requires integration of clinical and objective findings:

• Elevated natriuretic peptides (BNP/NT-proBNP) above age- and context-specific thresholds support the diagnosis 2
• Echocardiography is essential to document LVEF ≤40% and assess cardiac structure and function 2
• Assessment must identify underlying etiology: ischemic heart disease, toxic damage (alcohol, chemotherapy), immune-mediated damage, metabolic derangements, genetic abnormalities, or abnormal loading conditions 1

Common Pitfalls

Critical diagnostic and management considerations:

• Accuracy of clinical diagnosis by symptoms and signs alone is inadequate, particularly in women, elderly, and obese patients—objective testing with echocardiography is mandatory 1
• HFrEF differs fundamentally from HFpEF in epidemiology, etiology, and treatment response—these conditions cannot be managed identically 1, 4
• Symptoms may resolve quickly with diuretic therapy, but this does not address the underlying disease-modifying need for neurohormonal blockade 1