{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:58:31Z","timestamp":1790776711471,"version":"4.1.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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. Digit. Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pulmonary hypertension (PH) is a heterogeneous condition in which hemodynamic subtype directs management and specialist referral. PH can be identified non-invasively at the point of care by a previously developed, regulatory-cleared machine-learned diagnostic (area under the receiver operating characteristic curve 0.95, sensitivity 82%, specificity 92%), but a positive test result raises a second clinical question: which patients have pre-capillary disease and therefore warrant referral to a specialist PH center. A probabilistic post-test phenotyping model was developed to estimate hemodynamic subtype probabilities and support rule-out of pre-capillary PH among test-positive patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Subjects with right heart catheterization (RHC)-confirmed PH [mean pulmonary artery pressure (mPAP) \u226525\u2005mmHg] enrolled in a prospective multisite trial (NCT04031989) who tested positive on the previously validated point-of-care PH diagnostic formed the analysis cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009139). Hemodynamic subtypes were assigned per 2015 European Society of Cardiology\/European Respiratory Society (ESC\/ERS) criteria. A one-vs.-one (OvO) Gaussian mixture model (GMM) framework, combining unsupervised clustering with\n                      <jats:italic>post hoc<\/jats:italic>\n                      supervised assignment of subtype probabilities was applied to features derived from non-invasive orthogonal voltage gradient and photoplethysmographic signals to generate subject-level subtype probability estimates. Blinded validation in a large dataset has not yet been performed; development results are reported, supported by a small blinded independent dataset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At an exemplar\n                      <jats:italic>post-hoc<\/jats:italic>\n                      rule-out threshold of 16% pre-capillary probability, the GMM OvO approach yielded sensitivity 86% (95% CI: 71%\u201395%), specificity 51% (95% CI: 41%\u201361%), negative predictive value 88% (95% CI: 73%\u201396%) at an assumed pre-capillary prevalence of 34%, and a negative likelihood ratio (LR\u2212) of 0.27 (95% CI: 0.07\u20130.70) on the development cohort. Supportive out-of-sample discrimination was observed in the blinded independent cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A GMM OvO probabilistic model applied to non-invasive point-of-care signals can generate PH subtype probability estimates and may support rule-out of pre-capillary disease among true-positive patients. The model reuses signals already acquired for PH detection and can therefore be implemented as a software addition to an existing point-of-care workflow. Independent blinded validation is required to comprehensively characterize model performance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fdgth.2026.1955810","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:21:17Z","timestamp":1790774477000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond detection: developing probabilistic hemodynamic phenotyping after a positive point-of-care pulmonary hypertension test"],"prefix":"10.3389","volume":"8","author":[{"given":"Farhad","family":"Fathieh","sequence":"first","affiliation":[{"name":"Analytics for Life","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navid","family":"Nemati","sequence":"additional","affiliation":[{"name":"Analytics for Life","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Burton","sequence":"additional","affiliation":[{"name":"Analytics for Life","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horace R.","family":"Gillins","sequence":"additional","affiliation":[{"name":"CorVista Health","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Shadforth","sequence":"additional","affiliation":[{"name":"CorVista Health","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Ramchandani","sequence":"additional","affiliation":[{"name":"Analytics for Life","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Bridges","sequence":"additional","affiliation":[{"name":"CorVista Health","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e003973","DOI":"10.1161\/CIRCOUTCOMES.117.003973","article-title":"Increasing incidence and prevalence of World Health Organization groups 1 to 4 pulmonary hypertension: a population-based cohort study in Ontario, Canada","volume":"11","author":"Wijeratne","year":"2018","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"B2","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1111\/resp.13814","article-title":"The \u201cgreat wait\u201d for diagnosis in pulmonary arterial hypertension","volume":"25","author":"Weatherald","year":"2020","journal-title":"Respirology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"43","author":"Humbert","year":"2022","journal-title":"Eur Heart J"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1056\/NEJMoa2213558","article-title":"Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension","volume":"388","author":"Hoeper","year":"2023","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1056\/NEJMoa2008470","article-title":"Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease","volume":"384","author":"Waxman","year":"2021","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"957","DOI":"10.2147\/TCRM.S80131","article-title":"Treatment of patients with chronic thromboembolic pulmonary hypertension: focus on riociguat","volume":"12","author":"Smith","year":"2016","journal-title":"Ther Clin Risk Manag"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e32","DOI":"10.1164\/rccm.201709-1821ST","article-title":"Health disparities in patients with pulmonary arterial hypertension: a blueprint for action. 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