{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:31:59Z","timestamp":1787059919777,"version":"build-2736575974"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016304","name":"Medtronic Netherlands","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016304","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Us2.ai"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In patients undergoing transcatheter aortic valve implantation (TAVI), low flow, low-gradient (LF-LG) often reflects reduced left ventricular ejection fraction (LVEF). However, characteristics and causes of worse outcomes in patients with paradoxical LF-LG and preserved ejection fraction (pEF) remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To phenotype LF-LG pEF patients using unsupervised echocardiographic clustering.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 827 patients undergoing TAVI (UMCG, the Netherlands). LF-LG pEF was defined as LVEF \u226550%, aortic valve area: \u22641.0\u2005cm2, mean gradient &amp;lt;40\u2005mmHg, and a stroke volume index &amp;lt;35\u2005ml\/m2. Principal component analysis on 323 AI-assessed echocardiographic parameters (US2.ai) was followed by K-means clustering, with internal (n = 405) and external (n = 173) (TUMunich, Germany) validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>216\/628 patients with complete data (34%) had LF-LG pEF (mean age of 78.8 (\u00b1 7.19) years, 57.9% female). Two clusters were identified: cluster 1 (n = 77) showed distinct echocardiographic features related to HFpEF, including larger left and right atrial dimensions (volume, area, length, width, and circumference), and impaired left ventricular global longitudinal strain and a reduced left atrial reservoir strain (across multiple views). They were older and had higher rates of atrial fibrillation (AF) and heart failure (HF), and higher HFpEF scores (49.4% H2FPEF score \u22656 and 71.4% HFA-pEFF score \u22655), versus cluster 2 (n = 139). Cluster 1 had higher 1- and 5-year cardiovascular mortality and HF-hospitalization risk, comparable to that of classical LF-LG patients. Validation reproduced theseresults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>One-third of TAVI patients with LF-LG aortic stenosis have an typical HFpEF\/AF phenotype and a poor prognosis. They may benefit from guideline-directed HFpEF therapy, including SGLT-2 inhibitors and MRA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eschf\/xvag146","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:50:06Z","timestamp":1780055406000},"source":"Crossref","is-referenced-by-count":0,"title":["Phenotyping patients with a low-flow, low-gradient aortic stenosis and a preserved ejection fraction undergoing transcatheter aortic valve implantation"],"prefix":"10.1093","volume":"13","author":[{"given":"Kees H","family":"van Bergeijk","sequence":"first","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinand","family":"Roski","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, TUM University Hospital German Heart Center , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantijn S","family":"Venema","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Rheude","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, TUM University Hospital German Heart Center , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bob","family":"Ophuis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6043-0713","authenticated-orcid":false,"given":"Jasper","family":"Tromp","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]},{"name":"Saw Swee Hock School of Public Health, National University of Singapore, and the National University Health System , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoran M","family":"Hummel","sequence":"additional","affiliation":[{"name":"Us2.ai , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Ouwerkerk","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Amsterdam Medical Centre , Amsterdam ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad F M","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik W","family":"van der Werf","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne L","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Adamo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia , Brescia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Trenkwalder","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, TUM University Hospital German Heart Center , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-8310","authenticated-orcid":false,"given":"Michael","family":"Joner","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, TUM University Hospital German Heart Center , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna J","family":"Wykrzykowska","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"2026081809215949100_xvag146-B1","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1093\/eurheartj\/ehab395","article-title":"2021 ESC\/EACTS guidelines for the management of valvular heart disease","volume":"43","author":"Vahanian","year":"2021","journal-title":"Eur Heart J"},{"key":"2026081809215949100_xvag146-B2","doi-asserted-by":"publisher","first-page":"e739","DOI":"10.1161\/CIRCULATIONAHA.111.075853","article-title":"Low-flow\/low-gradient aortic stenosis","volume":"124","author":"Awtry","year":"2011","journal-title":"Circulation"},{"key":"2026081809215949100_xvag146-B3","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1007\/s00392-022-02011-4","article-title":"TAVI in patients with low-flow low-gradient aortic stenosis\u2013short-term and long-term outcomes","volume":"111","author":"Steffen","year":"2022","journal-title":"Clin Res Cardiol"},{"key":"2026081809215949100_xvag146-B4","doi-asserted-by":"publisher","first-page":"8","DOI":"10.17925\/HI.2023.17.1.8","article-title":"Low-flow, low-gradient severe aortic stenosis: a review","volume":"17","author":"Sharma","year":"2023","journal-title":"Heart Int"},{"key":"2026081809215949100_xvag146-B5","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/EJHF.3018","article-title":"Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: a specific phenotype of heart failure with preserved ejection fraction?","volume":"25","author":"De Biase","year":"2023","journal-title":"Eur J Heart Fail"},{"key":"2026081809215949100_xvag146-B6","doi-asserted-by":"publisher","first-page":"S38","DOI":"10.4244\/EIJV9SSA8","article-title":"Low flow, low gradient severe aortic stenosis: diagnosis, treatment and prognosis","volume":"9","author":"Orwat","year":"2013","journal-title":"EuroIntervention"},{"key":"2026081809215949100_xvag146-B7","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1161\/CIRCULATIONAHA.113.005718","article-title":"Paradoxical low-flow, low-gradient aortic stenosis: new evidence, more questions","volume":"128","author":"Pibarot","year":"2013","journal-title":"Circulation"},{"key":"2026081809215949100_xvag146-B8","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1093\/EURHEARTJ\/EHW096","article-title":"Low-gradient aortic stenosis","volume":"37","author":"Clavel","year":"2016","journal-title":"Eur Heart J"},{"key":"2026081809215949100_xvag146-B9","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1111\/jocs.15265","article-title":"Recent trends in aortic valve interventions: data of The Netherlands heart registration","volume":"36","author":"Daeter","year":"2021","journal-title":"J Card Surg"},{"key":"2026081809215949100_xvag146-B10","doi-asserted-by":"publisher","first-page":"e46","DOI":"10.1016\/S2589-7500(21)00235-1","article-title":"Automated interpretation of systolic and diastolic function on the echocardiogram: a multicohort study","volume":"4","author":"Tromp","year":"2021","journal-title":"Lancet Digit Health"},{"key":"2026081809215949100_xvag146-B11","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1016\/J.JCMG.2019.01.045","article-title":"Why and how to measure aortic valve calcification in patients with aortic stenosis","volume":"12","author":"Pawade","year":"2019","journal-title":"JACC Cardiovasc Imaging"},{"key":"2026081809215949100_xvag146-B12","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1161\/CIRCULATIONAHA.118.034646","article-title":"A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction","volume":"138","author":"Reddy","year":"2018","journal-title":"Circulation"},{"key":"2026081809215949100_xvag146-B13","doi-asserted-by":"publisher","first-page":"3297","DOI":"10.1093\/EURHEARTJ\/EHZ641","article-title":"How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)","volume":"40","author":"Pieske","year":"2019","journal-title":"Eur Heart J"},{"key":"2026081809215949100_xvag146-B14","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.1016\/j.jacc.2021.02.038","article-title":"Valve academic research consortium 3: updated endpoint definitions for aortic valve clinical research","volume":"77","author":"G\u00e9n\u00e9reux","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2026081809215949100_xvag146-B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/JSS.V061.I06","article-title":"Nbclust: an R package for determining the relevant number of clusters in a data set","volume":"61","author":"Charrad","year":"2014","journal-title":"J Stat Softw"},{"key":"2026081809215949100_xvag146-B16","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1111\/DOM.14063","article-title":"Validation of distinct type 2 diabetes clusters and their association with diabetes complications in the DEVOTE, LEADER and SUSTAIN-6 cardiovascular outcomes trials","volume":"22","author":"Kahkoska","year":"2020","journal-title":"Diabetes Obes Metab"},{"key":"2026081809215949100_xvag146-B17","doi-asserted-by":"publisher","first-page":"E865","DOI":"10.4244\/EIJ-D-23-00590","article-title":"Prognostic impact of cardiac damage staging classification in each aortic stenosis subtype undergoing TAVI","volume":"19","author":"Nakase","year":"2023","journal-title":"EuroIntervention"},{"key":"2026081809215949100_xvag146-B18","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.1016\/J.JACC.2016.02.070","article-title":"Paradoxical low-gradient aortic stenosis: the HFpEF of aortic stenosis","volume":"67","author":"Chin","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"2026081809215949100_xvag146-B19","doi-asserted-by":"publisher","DOI":"10.18502\/jthc.v20i2.19706","article-title":"Comparing left atrial strain and the HFA-PEFF score in diagnosing heart failure with preserved ejection fraction: a cross-sectional study","volume":"20","author":"Dang","year":"2025","journal-title":"J Tehran Univ Heart Cent"},{"key":"2026081809215949100_xvag146-B20","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1093\/EURHEARTJ\/EHAE176","article-title":"2024 ESC guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): developed by the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC), with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Endorsed by the European Stroke Organisation (ESO)","volume":"45","author":"Van Gelder","year":"2024","journal-title":"Eur Heart J"},{"key":"2026081809215949100_xvag146-B21","doi-asserted-by":"publisher","first-page":"3452","DOI":"10.1093\/EURHEARTJ\/EHU193","article-title":"Right heart dysfunction in heart failure with preserved ejection fraction","volume":"35","author":"Melenovsky","year":"2014","journal-title":"Eur Heart J"},{"key":"2026081809215949100_xvag146-B22","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/J.JACCAS.2021.11.009","article-title":"Confirmation of aortic stenosis severity in case of discordance between aortic valve area and gradient","volume":"4","author":"Silva","year":"2022","journal-title":"JACC Case Rep"},{"key":"2026081809215949100_xvag146-B23","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1002\/EHF2.13774","article-title":"HFA-PEFF score: prognosis in patients with preserved ejection fraction after transcatheter aortic valve implantation","volume":"9","author":"Seoudy","year":"2022","journal-title":"ESC Heart Fail"},{"key":"2026081809215949100_xvag146-B24","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1002\/EHF2.13096","article-title":"Prognostic value of the H2 FPEF score in patients undergoing transcatheter aortic valve implantation","volume":"8","author":"Ludwig","year":"2021","journal-title":"ESC Heart Fail"},{"key":"2026081809215949100_xvag146-B25","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.27152","article-title":"Prognostic value of HFA-PEFF score in patients undergoing transcatheter aortic valve implantation 2022","volume":"14","author":"Alotaibi","year":"2022","journal-title":"Cureus"},{"key":"2026081809215949100_xvag146-B26","doi-asserted-by":"publisher","DOI":"10.3390\/JCM12165396","article-title":"Prognostic impact of modified H2FPEF score in patients receiving trans-catheter aortic valve replacement","volume":"12","author":"Akao","year":"2023","journal-title":"J Clin Med"},{"key":"2026081809215949100_xvag146-B27","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.124.038786","article-title":"Heart failure with preserved ejection fraction phenotype is associated with early symptom onset in aortic stenosis and residual symptoms after transcatheter aortic valve implantation","volume":"14","author":"Venema","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"2026081809215949100_xvag146-B28","doi-asserted-by":"publisher","DOI":"10.1371\/JOURNAL.PONE.0225473","article-title":"Outcome of patients with heart failure after transcatheter aortic valve implantation","volume":"14","author":"Fischer-Rasokat","year":"2019","journal-title":"PLoS One"},{"key":"2026081809215949100_xvag146-B29","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.017574","article-title":"Baseline nt-probnp accurately predicts symptom response to transcatheter aortic valve implantation","volume":"9","author":"Allen","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"2026081809215949100_xvag146-B30","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/EJHF.3024","article-title":"2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"26","author":"McDonagh","year":"2024","journal-title":"Eur J Heart Fail"},{"key":"2026081809215949100_xvag146-B31","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur Heart J"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eschf\/advance-article-pdf\/doi\/10.1093\/eschf\/xvag146\/68439311\/xvag146.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/13\/4\/xvag146\/68439311\/xvag146.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/13\/4\/xvag146\/68439311\/xvag146.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:22:04Z","timestamp":1787059324000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/doi\/10.1093\/eschf\/xvag146\/8698908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,31]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,5,31]]},"published-print":{"date-parts":[[2026,7,4]]}},"URL":"https:\/\/doi.org\/10.1093\/eschf\/xvag146","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,5,31]]},"article-number":"xvag146"}}