Why HFpEF is the chapter cardiology has been waiting to write

Heart failure with preserved ejection fraction (HFpEF) is the form of heart failure where the heart's pumping function looks normal but the heart fails to fill properly. It accounts for roughly half of all heart failure and predominantly affects older patients, women, and those with metabolic risk factors. For thirty years it was the diagnostic and therapeutic poor cousin of HFrEF, where the contractility deficit was easier to define and the therapies easier to develop.

The HFpEF pivot started in 2020-2021 with SGLT2 inhibitor trials in heart failure. EMPEROR-Preserved and DELIVER showed cardiovascular outcome benefit in HFpEF that the prior generation of trials with renin-angiotensin-aldosterone agents had not achieved at the same level of consistency. The mechanism story is mixed - the SGLT2 class works through pathways that are still being fully mapped - but the trial result was unambiguous enough to change practice.

The second pivot came from the GLP-1 class. The cardiovascular outcomes trial program with GLP-1 receptor agonists in obesity included subgroups with HFpEF, and the readouts showed meaningful benefit on heart-failure events in the obesity-HFpEF phenotype. This is the kind of data that re-frames a disease: HFpEF in patients with obesity may, in part, be a treatable manifestation of metabolic disease rather than an isolated cardiac syndrome.

What is changing now is the phenotype frame itself. The field is moving toward distinguishing HFpEF subtypes - the obesity-driven, the hypertensive, the amyloid-related, the post-infectious, the unclassified - and matching therapies accordingly. This is the same shift that happened in HFrEF a decade earlier, and it tends to be a sign that the disease has crossed from neglected-condition to contested-commercial-category.

The practical clinician question is who to start on what, and at what disease severity. Guidelines have been updated; payer coverage has lagged in some markets. The patient-experience picture is also evolving: patients with HFpEF often present at older ages with multiple comorbidities, and the experience of being managed for HFpEF specifically (rather than for 'heart failure' as an undifferentiated condition) is a relatively new clinical pattern.

The pipeline behind these two classes is now substantial - novel anti-inflammatory mechanisms, mineralocorticoid receptor modulators, cardiac myosin inhibitors with HFpEF programs, and several earlier-stage assets. The chapter is being written. The next five years will define how dense it becomes.