Defining Heart Failure with Reduced vs. Preserved Ejection Fraction
Heart failure with reduced ejection fraction (HFrEF) is defined as symptomatic heart failure with left ventricular ejection fraction (LVEF) ≤40%, while heart failure with preserved ejection fraction (HFpEF) is defined as symptomatic heart failure with LVEF ≥50%. 1
Key Diagnostic Distinctions
Ejection Fraction Thresholds
- HFrEF: LVEF ≤40% 2, 1
- HFpEF: LVEF ≥50% 1
- HFmrEF (mildly reduced): LVEF 41-49% represents an intermediate category, often in dynamic transition between HFrEF and HFpEF 1, 3
Additional Diagnostic Requirements for HFpEF
HFpEF diagnosis requires more than just preserved ejection fraction—it demands objective evidence of cardiac dysfunction 1:
- Elevated natriuretic peptides (BNP >35 pg/mL or NT-proBNP >125 pg/mL in ambulatory patients) 4
- Evidence of increased LV filling pressures (E/e' ≥15 on echocardiography or invasive hemodynamic confirmation) 4
- Structural heart disease (increased left atrial volume index or increased LV mass index) 4
Pathophysiological Differences
HFrEF Characteristics
- Predominantly systolic dysfunction with impaired ventricular contractility 5
- More common in younger males 6
- Higher prevalence of ischemic cardiomyopathy as the underlying etiology 5, 3
- Greater ventricular and atrial remodeling with chamber dilation 6
- Higher NT-proBNP levels compared to HFpEF 6
- Lower TAPSE values indicating right ventricular dysfunction 6
HFpEF Characteristics
- Diastolic dysfunction with impaired ventricular filling despite normal or near-normal systolic function 7
- More common in older females 6
- Strong association with cardiometabolic diseases including obesity, diabetes, and hypertension 7
- Higher prevalence of atrial fibrillation and arterial hypertension 6
- Heterogeneous presentation with multiple comorbidities driving pathophysiology 8
Treatment Paradigm Differences
HFrEF: Robust Evidence-Based Therapy
HFrEF has four pillars of guideline-directed medical therapy (GDMT) with proven mortality reduction 9:
- ACE inhibitors/ARBs or preferably ARNIs (sacubitril/valsartan) 9, 4
- Beta-blockers (reduce mortality by approximately 35%) 9
- Mineralocorticoid receptor antagonists (reduce mortality by 30%) 9
- SGLT2 inhibitors (reduce cardiovascular death and HF hospitalizations) 9, 4
- Device therapy (ICD and CRT) based on QRS duration and LVEF thresholds 9
HFpEF: Limited Disease-Modifying Options
HFpEF management centers on SGLT2 inhibitors for prognostic benefit, diuretics for symptom relief, and aggressive comorbidity control 9:
- SGLT2 inhibitors are the cornerstone, with dapagliflozin and empagliflozin reducing composite endpoint of worsening HF and cardiovascular death by 18% and 21%, respectively 9
- Loop diuretics for congestion management and symptom relief 9, 4
- Blood pressure control to <130/80 mmHg using ACE inhibitors, ARBs, or ARNIs combined with diuretics 9
- No therapies have proven survival benefit in large randomized controlled trials for HFpEF 8
Prognostic Differences
Cardiovascular vs. Non-Cardiovascular Risk
- HFrEF patients have higher risk of cardiovascular events including sudden cardiac death and progressive pump failure 3
- HFpEF and HFmrEF patients have similar or greater risk of non-cardiovascular adverse events compared to HFrEF 3
- In-hospital mortality rates are similar across all HF subtypes 6
Clinical Pitfalls
Dynamic Nature of Ejection Fraction
- LVEF can fluctuate with repeated measurements or recover after treatment, blurring the borders between HF categories 10
- Patients with HFrEF who improve LVEF to >40% are classified as HFimpEF and must continue HFrEF GDMT to prevent relapse, even if asymptomatic 4
- One EF measurement at one time point may not be adequate—the trajectory of LVEF over time and the underlying cause must be evaluated 1