What can increase ejection fraction?

What Can Increase Ejection Fraction

For patients with heart failure and reduced ejection fraction (HFrEF), beta-blockers (particularly metoprolol, carvedilol, and bisoprolol), ACE inhibitors or angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists, SGLT2 inhibitors, cardiac resynchronization therapy (CRT), and exercise training can increase ejection fraction. 1, 2

Evidence-Based Pharmacological Interventions

Beta-Blockers

• Beta-blockers consistently increase ejection fraction by an average of 5-8 percentage points across multiple studies, with metoprolol showing a mean increase of 7.4 EF units, carvedilol 5.7 EF units, and other beta-blockers averaging 8.6 EF units over 4-9 months of treatment 3
• Metoprolol succinate extended-release has been shown to improve left ventricular ejection fraction and delay increases in left ventricular end-systolic and end-diastolic volumes after 6 months of treatment 2
• The improvement occurs regardless of whether the cardiomyopathy is ischemic or idiopathic (8.5 vs 6.0 EF units respectively) 3

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• ARNIs improve health-related quality of life compared to ACE inhibitors (SMD 0.09,95% CI 0.02-0.17) with high certainty evidence, suggesting improved cardiac function 1
• Valsartan (an ARB) in patients not receiving ACE inhibitors demonstrated increased ejection fraction and reduction in left ventricular internal diastolic diameter 4

SGLT2 Inhibitors

• SGLT2 inhibitors improve health-related quality of life (SMD 0.16,95% CI 0.08-0.23) with high certainty evidence, indicating functional cardiac improvement 1

Other Pharmacological Agents

• Levosimendan was superior to placebo for increasing LVEF% (-3.77,95% CI -4.96 to -2.43) and ranked as the best intervention for improving ventricular contraction 5
• Ivabradine improved health-related quality of life (SMD 0.14,95% CI 0.04-0.23) with high certainty evidence 1
• Hydralazine-nitrate combination improved quality of life (SMD 0.24,95% CI 0.04-0.44) versus placebo 1
• Intravenous iron improved quality of life (SMD 0.52,95% CI 0.04-1.00) with high certainty evidence 1

Device-Based Interventions

Cardiac Resynchronization Therapy (CRT)

• CRT significantly increases left ventricular ejection fraction in patients with HFrEF and wide QRS complex (≥120 ms), with improvements observed across all NYHA functional classes 1
• The improvement in ejection fraction is greater with longer follow-up periods, with substantial increases seen at 3-6 months and even more during extended follow-up 1
• CRT is contraindicated in patients with narrow QRS complex (<120 ms) even with mechanical dyssynchrony, as multiple randomized trials showed neutral or negative results 1

Exercise Training

Structured Exercise Programs

• Exercise training in patients with coronary artery disease significantly improves peak exercise left ventricular ejection fraction and fractional shortening between baseline and 6 months 1
• High-intensity training (85% VO2 max) for 1 year improved the increment in rest-to-peak LV ejection fraction in men with CAD, effective in both those with depressed (≤50%) and normal (>50%) baseline ejection fractions 1
• Low-intensity training (50% VO2 max) did not produce the same improvement in ejection fraction 1
• The increase in stroke volume with training is attributed to augmentation of blood volume and ventricular preload, though in severe LV systolic dysfunction, peripheral adaptations predominate over central changes 1

Pathophysiological Context for Aortic Regurgitation

Vasodilator Therapy in Chronic Severe AR

• In patients with chronic severe aortic regurgitation who are poor surgical candidates, vasodilator therapy (particularly nifedipine and hydralazine) can reduce end-diastolic volume and increase ejection fraction over 1-2 years 1
• Acute administration of sodium nitroprusside, hydralazine, nifedipine, or felodipine augments forward cardiac output, decreases regurgitant volume, and increases ejection fraction 1
• LV systolic dysfunction in AR is initially reversible when related predominantly to afterload excess, with potential for full recovery of ejection fraction after appropriate intervention 1

Critical Considerations for Optimization

Dosing Requirements

• Few patients achieve target doses of disease-modifying medications, with only 30.6% reaching ≥100% target dose for ACE inhibitors, 13.9% for beta-blockers, and 26.2% for ivabradine at baseline 6
• Uptitration is more likely in younger patients, those with higher systolic blood pressure, and absence of chronic kidney disease or diabetes for ACE inhibitors/ARBs 6
• For beta-blockers, uptitration is more likely with younger age, higher BMI, higher heart rate, lower LVEF, and absence of coronary artery disease 6

Patient Selection

• The benefit of interventions varies by ejection fraction range, with medications efficacious in HFrEF showing decreased effectiveness at higher LVEF ranges 7
• Older patients and those with significant comorbidities (chronic kidney disease, COPD, diabetes) may have attenuated responses to interventions 1, 6