Key result
Cardiorenal and autoimmune early-onset HF phenotypes in women are linked to higher mortality.
Why the study?
Heart failure in younger women is understudied and may reflect heterogeneous pathways and risks that are not adequately captured by conventional classifications.
Do distinct clinical phenotypes of early-onset heart failure in young women stratify the risk of subsequent hospitalization and mortality compared with the hypertensive pregnancy phenotype?
Cohort (n=1,407)
Yes
Do distinct clinical phenotypes of early-onset heart failure in young women stratify the risk of subsequent hospitalization and mortality compared with the hypertensive pregnancy phenotype?
Early-onset heart failure in women comprises four reproducible phenotypes (hypertensive pregnancy, cardiorenal, autoimmune, and cardiometabolic-ischemic) with markedly different risks of hospitalization and mortality, supporting a life-course classification Incorporating pregnancy and systemic conditions.
Answers are grounded in this paper and cite their sources.
Phenotyping early-onset HF in young women may refine prognostication; leaves open whether clusters guide therapy or improve outcomes.
Background: Heart failure in younger women is understudied and may reflect heterogeneous pathways and risk not adequately captured by conventional classifications. We aimed to identify clinically distinct phenotypes of early-onset heart failure in women, assess their prognostic significance, and evaluate their transportability in an independent national cohort. Methods: We identified women aged 18-55 years with heart failure using electronic health record data from a large multi-hospital system. A variational deep embedding model incorporating 283 clinical features was used for unsupervised phenotyping. Associations with subsequent inpatient hospitalization, emergency department utilization, and mortality were evaluated using age-stratified Cox models. Phenotype transportability was assessed by both applying the institutionally trained model and by independent de novo clustering as a replication analysis in the All of Us cohort. Results: Among 1,407 young women with heart failure (median age, 45 years), four phenotypes were identified: hypertensive pregnancy (n=494), cardiorenal (n=276), autoimmune (n=394), and cardiometabolic-ischemic (n=243), with a bootstrap adjusted Rand index of 0.65 and silhouette score of 0.45. Compared with the hypertensive pregnancy phenotype, risks of inpatient hospitalization were highest for the cardiorenal (HR 2.86 [95% CI, 2.35?3.49]) and autoimmune (HR 2.25 [95% CI, 1.87?2.70]) phenotypes; mortality risks were similarly elevated (HR 4.65 [95% CI, 3.17?6.82] and HR 4.38 [95% CI, 3.03?6.31], respectively) in these two groups. In All of Us participants (n=682), transferred phenotypes retained their principal clinical characteristics and continued to stratify hospitalization risk. Independent clustering most strongly reproduced the cardiorenal phenotype (Jaccard index, 0.744). Conclusions: Early-onset heart failure in women comprises distinct cardio-obstetric, cardiorenal, autoimmune, and cardiometabolic-ischemic phenotypes with divergent clinical outcomes. These findings support a life-course approach to heart failure classification in women that complements conventional frameworks and incorporates pregnancy history and female-predominant systemic conditions.
No takes yet. Share an insight, caveat, or question.
Khorsandi et al. (2026) conducted a cohort in Early-onset heart failure in women (n=1,407). Cardiorenal, autoimmune, and cardiometabolic-ischemic heart failure phenotypes (identified via variational deep embedding model) vs. Hypertensive pregnancy heart failure phenotype was evaluated on Inpatient hospitalization and mortality (HR 2.86, 95% CI 2.35-3.49). Cardiorenal and autoimmune early-onset HF phenotypes in women had higher mortality vs the hypertensive pregnancy phenotype (HR 4.65; 95% CI 3.17-6.82 and HR 4.38; 95% CI 3.03-6.31).
Synapse has enriched 10 related papers. Consider them for comparative context: