Can Heart Failure with Reduced Ejection Fraction Improve?
Yes, HFrEF can substantially improve with guideline-directed medical therapy (GDMT), with evidence showing that contemporary quadruple therapy reduces mortality by 73% over 2 years and can extend life expectancy by approximately 6 years in a 55-year-old patient. 1
Evidence for Improvement in Ejection Fraction
Beta-blockers and aldosterone antagonists specifically improve ejection fraction in HFrEF patients. 2 This represents actual reverse remodeling of the heart, not just symptomatic improvement. The mechanism involves reversing left ventricular dilation through neurohormonal blockade. 3
Mortality and Hospitalization Benefits
The evidence for improvement in hard outcomes is robust:
ACE inhibitors reduce all-cause mortality by 11% and hospitalizations for heart failure by 30% in symptomatic HFrEF patients. 4
Quadruple therapy (ARNI/ACE inhibitor, beta-blocker, MRA, and SGLT2 inhibitor) provides additive mortality reduction of 73% over 2 years compared to no treatment. 1
In asymptomatic patients with reduced EF, enalapril reduced first hospitalizations for heart failure by 32% and prevented progression to symptomatic heart failure in 32% of patients. 4
Quality of Life Improvements
Beyond survival, HFrEF treatment improves how patients feel:
SGLT2 inhibitors produce small but consistent improvements in health-related quality of life (standardized mean difference 0.16). 1
Intravenous iron produces moderate improvements in quality of life (standardized mean difference 0.52), exceeding the minimal important difference threshold. 1
ARBs, ARNIs, ivabradine, and hydralazine-nitrate all produce small but meaningful quality of life improvements with high-certainty evidence. 1
Treatment with enalapril resulted in decreased systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure, heart size, and increased cardiac output and exercise tolerance. 4
Functional Capacity Improvements
Exercise training and cardiac rehabilitation improve functional capacity, exercise duration, and health-related quality of life in clinically stable HFrEF patients. 1 This represents improvement in real-world function, not just laboratory measurements.
Timeline for Improvement
Hemodynamic effects are observed after the first dose of ACE inhibitors, with effects on exercise tolerance, heart size, and symptoms observed in studies lasting from 8 weeks to over one year. 4 However, optimal blood pressure reduction may require several weeks of therapy in some patients. 4
Contemporary Treatment Approach
The modern approach emphasizes rapid implementation:
All four foundational drug classes (ARNI or ACE inhibitor/ARB, beta-blocker, MRA, SGLT2 inhibitor) should be initiated rapidly rather than sequentially. 1
In-hospital initiation of GDMT, simultaneous or rapid sequence initiation, and multidisciplinary titration clinics improve implementation. 1
The STRONG-HF trial demonstrated that rapid therapeutic implementation in recently hospitalized HFrEF patients is feasible, though hypotension occurred in 5% versus 1% with usual care. 1
Device Therapy Contributions
Cardiac resynchronization therapy (CRT) in selected patients with electrical dyssynchrony improves quality of life, reduces hospitalizations and mortality, and typically results in a 5% increase in blood pressure due to enhanced myocardial synchrony and improved ejection fraction from reverse remodeling. 1
Common Pitfall to Avoid
The poor outcomes associated with side effects of HF medications often stem from discontinuing therapy rather than the side effects themselves. 1 When hypotension or other side effects occur, the reflex to stop medications can be more harmful than the side effect itself. Strategies to manage side effects while maintaining therapy should be exhausted before discontinuation.
Patient Education Impact
Patient empowerment for self-care significantly increases adherence to GDMT and reduces mortality and hospitalizations. 1 This means that improvement depends not just on prescribing medications, but on ensuring patients understand their condition and treatment plan through multidisciplinary education efforts. 1