The Diabetic Heart Failure With Preserved Ejection Fraction Phenotype
Is it Real and Is It Worth Targeting Therapeutically?
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Article, see p 724
For investigators, physicians, and patients, the inability to identify therapies to improve clinical outcomes, particularly mortality, in patients with heart failure with preserved ejection fraction (HFpEF) has been particularly vexing and stands in stark contrast to the progress made in the treatment of patients with heart failure with reduced ejection fraction (HFrEF). This has prompted a return to the proverbial drawing board, forcing a reconsideration of long-held assumptions and paradigms. Despite different underlying etiologies, patients with HFrEF are generally responsive to several classes of medications that target the neurohormonal axis. Conversely, the lack of benefit of these therapies in patients with HFpEF has prompted a reevaluation of whether HFpEF is 1 disease or many. Is there a unifying pathophysiology of HFpEF or is it better characterized as an amalgamation of distinct, albeit overlapping, phenotypes?
Increasingly embraced is the notion that HFpEF is an umbrella term for distinct phenotypes, characterized by different clinical presentations and predisposing factors.1,2 Unbiased data-driven analytic strategies have identified distinct phenotypes or clusters of patients with HFpEF, including phenotypes that are clinically recognizable.3,4 Accordingly, there is movement away from a one-size-fits-all therapeutic strategy to more selective therapeutic strategies targeting these different phenotypes.1,2 Along with a focus on multiple phenotypes of HFpEF, there has been a re-examination of HFpEF as simply a disease of diastolic function to a reconceptualizing of it as more of a systemic disease, characterized by inflammation and microvasculature dysfunction with adverse sequelae in multiple organs, including, but not limited to, the heart.5,6 In line with this, attention has been directed at whether the presence of diabetes mellitus identifies an important phenotype of HFpEF that may have implications for therapeutic strategies.
Earlier studies have aimed to characterize the diabetic …