{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:56:32Z","timestamp":1790571392285,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The marked clinical and pathophysiological heterogeneity of HFpEF has repeatedly undermined uniform treatment strategies. Consequently, identifying distinct phenotypes and medication-associated patterns across phenotypes may inform future precision-medicine research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicohort retrospective study, patients with HFpEF were included from MIMIC-IV (derivation cohort, n = 2,511), the MIMIC-III CareVue subset (internal validation cohort, n = 1,524), and the Second Hospital of Hebei Medical University (external application cohort, n = 340). Unsupervised K-prototypes clustering was used to derive phenotypic groups, with K = 2 evaluated as a lower-resolution sensitivity solution. All phenotype-stratified medication analyses were exploratory. In the derivation and internal validation cohorts, overlap weighting was the primary weighted analysis and stabilized inverse probability of treatment weighting was a sensitivity analysis; external medication estimates were reported descriptively because adequate within-group covariate balance was not achieved. A TabPFN phenotype-assignment classifier was developed after recursive feature elimination, evaluated in internal validation against independently reclustered labels aligned by prespecified one-to-one Hungarian assignment on cluster-profile distances, and applied without refitting in the external cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The primary three-cluster solution identified clinically interpretable but partially overlapping cardiorenal-metabolic, hypertensive-pulmonary, and low-blood-pressure\/arrhythmia profiles. K = 2 had a higher mean silhouette width than K = 3 (0.083 versus 0.060), whereas both solutions showed high median resampling stability (ARI, 0.940 versus 0.924). A graded 365-day mortality difference was observed across the three clusters in the derivation cohort, but between-cluster survival differences were not statistically significant in the internal validation or external application cohorts. In the derivation and internal validation cohorts, no weighted cluster-specific medication association remained statistically significant after FDR correction, and all medication-by-cluster interaction tests were nonsignificant. External medication estimates were descriptive and were not used for confirmatory inference. The fixed TabPFN classifier achieved one-versus-rest AUCs of 0.951\u20130.969 in internal validation (10-bin multiclass ECE = 0.028).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Routinely collected ICU data supported an exploratory framework for describing overlapping HFpEF phenotypes and reproducibly assigning machine-derived labels. The analyses did not establish phenotype-specific medication effects, and the classifier should be regarded as a research tool pending prospective multicenter validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1838338","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:29:41Z","timestamp":1790569781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine-learning phenotyping and exploratory medication-outcome associations in heart failure with preserved ejection fraction: a multicohort retrospective study"],"prefix":"10.3389","volume":"17","author":[{"given":"Qianli","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaotong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjian","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Technology College, Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuchun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Physiology, Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"The Key Laboratory of Neural and Vascular Biology, Ministry of Education","place":["Shijiazhuang, China"]},{"name":"Hebei Key Laboratory of Cardiovascular Homeostasis and Aging","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, China"]},{"name":"Hebei Key Laboratory of Cardiovascular Homeostasis and Aging","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1161\/CIRCULATIONAHA.117.030112","article-title":"Worsening renal function in patients with acute heart failure undergoing aggressive diuresis is not associated with tubular injury","volume":"137","author":"Ahmad","year":"2018","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.jchf.2023.03.017","article-title":"Beta-Blocker use and heart failure outcomes in mildly reduced and preserved ejection fraction","volume":"11","author":"Arnold","year":"2023","journal-title":"JACC Heart Fail"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.1007\/s11831-025-10379-5","article-title":"Comparing bipartite convoluted and attention-driven methods for skin cancer detection: a review of explainable AI and transfer learning strategies","volume":"33","author":"Banerjee","year":"2026","journal-title":"Arch. 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