How to improve left ventricular ejection fraction (LVEF)?

Improving Left Ventricular Ejection Fraction (LVEF)

For patients with heart failure and reduced ejection fraction (HFrEF, LVEF ≤40%), initiate the four pillars of guideline-directed medical therapy (GDMT): an ACE inhibitor or ARNI (sacubitril/valsartan), a beta-blocker (bisoprolol, carvedilol, or metoprolol succinate), a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor—all of which have been proven to improve LVEF, reduce mortality, and decrease hospitalizations. 1, 2

Core Pharmacological Strategy

First-Line Therapy: The Four Pillars

ACE Inhibitors or ARNI:

• Start an ACE inhibitor (such as enalapril 2.5-5 mg twice daily) and uptitrate to target dose (10-20 mg twice daily) over 2-4 weeks unless contraindicated 1, 2
• Sacubitril/valsartan (ARNI) is superior to ACE inhibitors alone for improving LVEF and reducing mortality in HFrEF patients 1, 3
• In the PRIME trial, ARNI produced significantly larger reductions in mitral regurgitation and better LV reverse remodeling compared to valsartan alone 1
• Starting dose for sacubitril/valsartan is 49/51 mg twice daily, with uptitration to target dose of 97/103 mg twice daily after 2-4 weeks 3
• Critical: Allow a 36-hour washout period when switching from an ACE inhibitor to sacubitril/valsartan to avoid angioedema 3

Beta-Blockers:

• Use one of the three proven beta-blockers: bisoprolol, carvedilol, or sustained-release metoprolol succinate 1, 2
• These agents improve LVEF by an average of 5.7-7.4 ejection fraction units across multiple studies 4
• Titrate to at least 50% of maximum guideline-recommended dose to achieve optimal medical therapy score 1
• Beta-blockers reduce mortality and hospitalization when added to ACE inhibitors 2

Mineralocorticoid Receptor Antagonists:

• Add spironolactone 12.5-25 mg once daily (maximum 50 mg) or eplerenone in patients with symptomatic HFrEF 1, 2
• Monitor serum creatinine (should be ≤2.5 mg/dL in men, ≤2.0 mg/dL in women) and potassium (should be <5.0 mEq/L) closely 5

SGLT2 Inhibitors:

• Provide mortality benefit in both HFrEF and HFpEF 2
• Improve adverse LV remodeling and should be initiated in all eligible patients 1

Optimal Medical Therapy Scoring

To achieve "optimal" therapy status (score ≥5), patients must receive: 1

• A heart failure-specific beta-blocker at ≥50% maximum dose (2 points)
• An ACE inhibitor, ARB, or ARNI at ≥50% maximum dose (2 points) OR sacubitril/valsartan at any dose (2 points)
• A mineralocorticoid receptor antagonist at any dose (1 point)

Device Therapy for LVEF Improvement

Cardiac Resynchronization Therapy (CRT):

• Indicated for patients with LVEF ≤35%, NYHA Class II-IV symptoms on optimal medical therapy, and QRS ≥150 ms with left bundle branch block morphology 2
• CRT improves LVEF even in patients with very low baseline ejection fraction (5-15%) 6
• Response rate to CRT is approximately 71% overall, with similar response rates across all baseline LVEF subgroups 6
• There is no lower limit for baseline LVEF to predict non-response to CRT in eligible patients 6

Implantable Cardioverter-Defibrillator (ICD):

• Recommended for primary prevention in patients with LVEF ≤30-35%, NYHA Class II-III symptoms on optimal medical therapy for ≥3 months, and life expectancy >1 year 2
• Also indicated for secondary prevention in patients with history of cardiac arrest, ventricular fibrillation, or hemodynamically unstable ventricular tachycardia 1, 2

Management of Specific Conditions

Atrial Fibrillation with HFrEF:

• Catheter ablation for AF in HFrEF patients significantly improves LVEF (average increase of 8-18% depending on baseline characteristics) 1
• In the CASTLE-AF trial, 63% of ablation patients maintained sinus rhythm at 5 years versus 22% in the medical therapy group 1
• AF ablation led to significant improvements in LVEF (+8% vs. 0%), all-cause mortality (13% vs. 25%), and HF hospitalization (21% vs. 36%) 1
• Patients without late gadolinium enhancement on cardiac MRI have the best LVEF improvement after ablation 1

Rapid Supraventricular Arrhythmias:

• Pay particular attention to patients with cardiomyopathy associated with rapid atrial flutter or atrial fibrillation, as these rhythm disorders may lead to or exacerbate ventricular dysfunction 1
• Rate control to <80 beats/min is recommended 1

Critical Medications to Avoid

The following drugs adversely affect clinical status and should be avoided or withdrawn: 1, 7

• NSAIDs (cause sodium and water retention, counteract diuretic effects, can precipitate acute decompensation even with single-dose exposure)
• Most antiarrhythmic drugs
• Calcium channel blockers with negative inotropic effects (especially in patients with EF <40% post-MI)

Adjunctive Therapies

Diuretics:

• Use loop diuretics (furosemide 20-40 mg once or twice daily, bumetanide 0.5-1.0 mg once or twice, or torsemide 10-20 mg once daily) for patients with current or prior symptoms and evidence of fluid retention 1, 2
• Combine with salt restriction to <2-3 g/day 2

Exercise Training:

• Beneficial as an adjunctive approach to improve clinical status in ambulatory patients with current or prior symptoms of HFrEF 1, 2
• Improves functional capacity and quality of life 2

Monitoring Parameters

Essential monitoring includes: 7, 2

• Renal function (creatinine, GFR) and electrolytes (potassium) at baseline, 1-2 weeks after dose changes, and every 3-6 months
• Signs of fluid retention: weight gain, peripheral edema, worsening dyspnea, or orthopnea
• Symptoms and functional capacity regularly to guide diuretic dosing
• Natriuretic peptides (BNP or NT-proBNP) at baseline and serially to guide therapy and assess prognosis 2

Expected Outcomes and LVEF Recovery

Patients who improve their LVEF from ≤40% to >40% are classified as having "heart failure with improved ejection fraction" (HFimpEF): 1

• These patients should continue HFrEF treatment, as EF can decrease after withdrawal of pharmacological therapy 1
• Nearly 60% of patients with HFrEF may have significant improvement in MR and LVEF after treatment with GDMT 1
• Improvement in LVEF does not mean full myocardial recovery; cardiac structural abnormalities often persist 1

Common Pitfalls to Avoid

• Do not discontinue GDMT in patients whose LVEF improves to >40%, as many will experience a decrease in EF after medication withdrawal 1
• Do not use adaptive servo-ventilation (ASV) in CHF patients with LVEF ≤45%, as it increases cardiac death risk (relative risk 1.25) 1
• Do not undertitrate medications—aim for at least 50% of maximum guideline-recommended doses to achieve optimal therapy 1
• Do not delay device therapy in eligible patients while waiting for maximal medical therapy response 2