Optimizing the Management of Heart Failure With Preserved Ejection Fraction in the Elderly by Targeting Comorbidities (OPTIMIZE-HFPEF)

Aims: The pathophysiology of heart failure with preserved ejection fraction (HFPEF) is not fully understood. A recently proposed mechanism for HFPEF is that it is a systemic pro-inflammatory state induced by comorbidities, leading to microvascular endothelial dysfunction and subsequent cardiac remodeling and dysfunction. We hypothesize that targeting comorbidities will improve outcomes in elderly patients with HFPEF. Thus, the aim of this study is to determine whether the combination of systematic screening and optimal management of prespecified comorbidities associated with HFPEF improves outcomes. Methods: This multicenter, prospective, randomized intervention trial uses an open procedure with blinded endpoint assessment. Patients with HFPEF aged >60 years (n = 360) will be randomized 1:1 to the usual care or intervention arm of the trial. When randomized to the intervention arm, all patients will be systematically screened and optimally treated for the most frequent cardiovascular, metabolic, respiratory, and renal comorbidities. The primary endpoint is a composite clinical score that classifies each randomized patient as improved or deteriorated based on objective and subjective data at a 24-month follow-up performed by a blinded endpoint committee. Conclusion: Rather than targeting cardiac dysfunction, our study aims to present evidence for a possible paradigm shift in the management of HFPEF. Our novel concept focuses on the management of comorbidities as predisposing factors in HFPEF.