Risk and Protective Factors of Poor Clinical Outcomes in Heart Failure with Improved Ejection Fraction Population: A Systematic Review and Meta-Analysis

Aims: Heart failure with improved ejection fraction (HFimpEF) patients could still develop adverse outcomes despite EF improvement. This study evaluates the risk and protective factors of poor clinical outcomes in HFimpEF patients.

Methods: Systematic searching was done to include studies that evaluate the risks of developing poor outcomes in HFimpEF patients. HFimpEF is defined as improvement of 5-10% EF within 6-12 months or normalization of EF > 40%. Poor clinical outcome is defined as a composite of all-cause mortality, cardiovascular events, HF rehospitalization, and requirement of LVAD/ transplant. Odds ratios of outcome are pooled with random effects model. A subgroup analysis of multivariate analysis-only studies was also conducted.

Results: 32 studies comprising 10,740 HFimpEF patients are included. Poor clinical outcomes followed up for approximately 3 years, are seen in 18.9% of HFimpEF patients. Twelve statistically significant factors that increase the risk of outcome are found. Among them, anemia (OR 7.69, CI 3.48-16.99, I² 0%) and baseline NT pro-BNP (OR 3.25) are the two most important predictors. Other significant risk factors are increasing age, ischemic heart disease, NYHA III/IV, diabetes mellitus, atrial fibrillation, dyslipidemia, cerebrovascular disease, hypertension, use of diuretics, and baseline LVEDD. Alternately, protective factors of poor clinical outcome are regression of left atrial diameter (LAD) (OR 0.33, CI: 0.18-0.61, p 0.0003, I² 0%), use beta-blockers, SGLT- 2 inhibitors, and baseline LVEF level (OR 0.60, 0.78, 0.90, respectively).

Conclusion: HFimpEF patients are not fully recovered and patient stratification based on risk and protective factors is recommended.