Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Jul 31;26(8):1452-1463.
doi: 10.1093/ehjci/jeaf141.

Phenotypic clustering analysis of patients rejected for mitral valve interventions: implications for future transcatheter technologies

Sebastian Ludwig  1   2   3 , Augustin Coisne  3   4 , Kenza Hamzi  5   6 , Walid Ben Ali  7 , Andrea Scotti  3   8 , Benedikt Koell  1   2 , Alison Duncan  9 , Raj Makkar  10 , Mariama Akodad  11   12 , Sabine Bleiziffer  13 , Georg Nickenig  14 , Tsuyoshi Kaneko  15 , Hendrik Ruge  16   17 , Matti Adam  18 , Lars Sondergaard  19 , Gry Dahle  20 , Maurizio Taramasso  21 , Thomas Walther  22 , Joerg Kempfert  23 , Jean-François Obadia  24 , Omar Chehab  25 , Gilbert H L Tang  26 , Sachin Goel  27 , Neil Fam  28 , Paolo Denti  29 , Fabien Praz  30 , Ralph Stephan von Bardeleben  31 , Jörg Hausleiter  32 , Azeem Latib  8 , Lenard Conradi  33 , Thomas Modine  34 , Théo Pezel  5   6 , Juan F Granada  3 ; CHOICE-MI Investigators
Collaborators, Affiliations
Multicenter Study

Phenotypic clustering analysis of patients rejected for mitral valve interventions: implications for future transcatheter technologies

Sebastian Ludwig et al. Eur Heart J Cardiovasc Imaging. .

Abstract

Aims: Although several treatment options are available for patients with severe mitral regurgitation (MR), a significant proportion of patients remain ineligible for any mitral valve (MV) intervention. We aimed to analyse the phenotypic characteristics of surgical high-risk patients ineligible for MV interventions using an unsupervised phenotypic clustering approach.

Methods and results: Between 2014 and 2022, the CHOICE-MI registry included 984 patients with MR undergoing screening for transcatheter MV replacement at 33 international sites. For this study, only patients with screening failure receiving medical therapy alone were included. Patients receiving transcatheter or surgical treatment were excluded. A cluster analysis using K-means was performed on baseline clinical, demographic, and imaging variables to identify different patient phenotypes. Among 284 patients with MR (77.4 ± 8.82 years, 56.0% female, EuroSCORE II: 6.6 ± 5.8%) considered ineligible for any MV intervention, two clinically distinct phenogroups (PGs) were identified using unsupervised hierarchical clustering of principal components: PG1, elderly women with primary MR, preserved left ventricular function, and annular calcification; and PG2, patients with secondary MR, advanced heart failure, and high prevalence of comorbidities. One-year all-cause mortality did not differ between the PGs (PG1: 21.4%, PG2: 23.4%, P = 0.89). Predictors of mortality were albumin, renal function, and extracardiac arteriopathy for PG1 and albumin, coronary artery disease, and prior myocardial infarction for PG2.

Conclusion: This study identified two major subgroups among patients ineligible for mitral interventions showing profound differences in clinical and anatomical profiles. Identifying these factors may drive technological evolution to address the unmet clinical need for therapeutic options in MR patients.

Clinicaltrials.gov identifier: NCT04688190 (CHOICE-MI Registry).

Keywords: clustering; medical therapy; mitral regurgitation; non-supervised machine learning; transcatheter mitral valve replacement.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: S.L. has received travel compensation from Edwards Lifesciences and Shockwave and honoraria from Bayer and Abbott, is a consultant for NVT, and was supported by research grants from the German Heart Foundation (DHS) and from 4C Medical. A.C. is proctor for Abbott Vascular and speaker for Abbot Vascular and GE Healthcare. W.B.A. has received research grants from Medtronic and Edwards Lifesciences. A.D. is a consultant for and has received honoraria from Abbott Laboratories, Edward Lifesciences, and Medtronic. D.K. has received speaker honoraria from Abbott Medical and Edwards Lifesciences, travel expenses from Abbott Medical and Edwards Lifesciences, and proctor fees from Edwards Lifesciences. T.K.R. has received speaker honoraria from Abbott Vascular. J.H. has received consulting fees, speaker honoraria, and support of research projects paid to the institution from Abbott Vascular and Edwards Lifesciences. H.R. is a member of the advisory board of Abbott and a physician proctor for Abbott and Edwards Lifesciences. M. Akodad has served as consultant for Edwards Lifesciences, Medtronic, and Abbott. M. Adam has received personal fees from Edwards and Boston Scientific and grants and personal fees from Medtronic. N.D. and D.T. have received proctoring and consultancy fees from Abbott Vascular, Boston Scientific, Edwards Lifesciences, and Medtronic. M. Adamo has received speaker fees from Abbott and Medtronic. G.D. is proctor and speaker for Abbott and speaker for Edwards. M.T. is a consultant for Abbott, Edwards Lifesciences, Boston Scientific, Shenqi Medical, Simulands, Occlufit, MTEx, MEDIRA, 4tech, and CoreMedic and has received fees from Cardiovalve. J.K. has received speaker honoraria from Edwards, Medtronic, Abbott, and CryoLife. G.H.L.T. is a physician proctor and consultant for Medtronic, consultant and TAVR physician advisory board member for Abbott Structural Heart, consultant for NeoChord, and advisory board member for JenaValve. S.G. is a consultant for Medtronic and part of the speakers bureau of Abbott Structural Heart. N.F. is a consultant for Edwards, Abbott, and Cardiovalve. M. Andreas is a proctor, consultant, and speaker for Edwards Lifesciences, Abbott, Medtronic, Boston, and Zoll and has received institutional research grants from Edwards Lifesciences, Abbott, Medtronic, and LSI. R.S.v.B. has received consulting and speaker honoraria from Abbott Vascular, Edwards Lifesciences, and Medtronic, as well as research project grants paid to the university from Abbott Vascular and Edwards Lifesciences. L.C. is advisory board member for Abbott, Medtronic, and Boston Scientific and has received personal fees from Edwards Lifesciences. T.P. is a consultant for and has received honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb (BMS)/Pfizer, Vifor Pharma, Novartis, Boehringer Ingelheim, Amarin Corporation, Siemens Healthineers, GE Healthcare, and MEDIS imaging and has received research grants from Bayer and Servier. The remaining authors have declared no conflicts of interest with regard to this manuscript.

Comment in

Publication types

Associated data

Grants and funding