A new narrative review published in Cardiology Discovery summarizes current evidence supporting phenotype‑stratified care for heart failure, a leading global cause of illness and death marked by wide biological variability among patients. While ejection‑fraction‑based categories guide routine clinical work, the review points out that this framework masks important patient differences, particularly within the large and hard‑to‑treat group living with heart failure with preserved ejection fraction (HFpEF).
Heart failure is not a single uniform disease. For decades, clinicians have relied largely on left‑ventricular ejection fraction (LVEF) to assign patients into three broad groups: heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), and HFpEF. HFrEF patients have well‑validated guideline‑directed medicines proven to lower mortality. However, HFpEF continues to create major clinical challenges; many available therapies produce inconsistent benefits across patient groups, partly because HFpEF itself contains multiple biologically distinct patient subgroups.
This analysis represents a narrative review, not original clinical trial data. Researchers from Nanjing First Hospital conducted a comprehensive literature search across PubMed/MEDLINE, Embase and Cochrane Library through December 2024. The team synthesized human clinical studies, clinical‑trial outputs and established heart‑failure guidelines, while pre‑clinical laboratory findings were only included when corroborated by human tissue investigations. The paper covers normal cardiac mechanical function, core disease‑driving pathways, existing LVEF‑based classification, and emerging phenotype‑focused approaches for adult chronic heart failure.
The review identifies five recognizable clinical phenotypes within HFpEF: metabolic, hypertensive, cardiorenal, pulmonary vascular, and inflammatory‑autoimmune subtypes. Each subgroup arises from separate underlying disease drivers such as obesity‑related metabolic dysfunction, long‑standing high blood pressure, concurrent chronic kidney disease, pulmonary hypertension, or systemic autoimmune conditions. Authors note that newer agents including sodium‑glucose cotransporter 2 inhibitors show promising phenotype‑dependent effects, suggesting that matching therapy to patient clinical profile may improve outcomes for this hard‑to‑manage population.
Important limitations should be considered. This is a descriptive synthesis of existing published work, not new prospective clinical evidence. Direct head‑to‑head treatment comparisons for these five HFpEF subgroups are still lacking. Many emerging phenotype‑targeted therapies have modest absolute risk‑reduction effects, and long‑term safety and outcome data remain incomplete. Real‑world implementation will require validated biomarker tools, standardized phenotyping workflows and cost‑effectiveness studies. Future large‑scale prospective trials are needed to confirm whether phenotype‑guided care can meaningfully reduce heart‑failure hospitalizations and mortality in routine practice.
Article citation:
Jiang X, Wang X, Zhang J. Decoding Heart Failure: From Mechanisms to Phenotype‑Based Management. Cardiology Discovery. 2026. DOI: 10.1097/CD9.0000000000000210
Cardiology Discovery
Literature review
Not applicable
Decoding Heart Failure: From Mechanisms to Phenotype-Based Management
10-Aug-2026