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Abstract
Aims
Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk.
Methods and results
From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2‐year follow‐up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow‐up paths, as well as specific end‐stages conditions of the disease. Finally, we conducted a 5‐year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n = 527) and external (n = 777) populations. We analyzed 4876 patients (age = 63 [53–71], male gender n = 3973 (81.5%), NYHA class I–II n = 3576 (73.3%), III–IV n = 1300 (26.7%), LVEF = 33 [25.5–39.9], atrial fibrillation n = 791 (16.2%), peak VO2% pred = 54.8 [43.8–67.2]), with a minimum 2‐year follow‐up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end‐stage points. Clusters survival rate varied from 44% to 100% at 2 years and from 20% to 100% at 5 years, respectively. The event frequency at 5‐year follow‐up for each study cohort cluster was successfully compared with those in the validation cohorts (R = 0.94 and R = 0.84, P < 0.001, for internal and external cohort, respectively). Finally, we conducted a 5‐year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant observed in 22% of cases).
Conclusions
Each HF phenotype has a specific disease progression and prognosis. These findings allow to individualize HF patient evolutions and to tailor assessment.
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Details
1 Centro Cardiologico Monzino, IRCCs, Milan, Italy, Department of Clinical Sciences and Community Health, Section of Cardiology, University of Milan, Milan, Italy
2 Centro Cardiologico Monzino, IRCCs, Milan, Italy, Department of Electronics, Information and Biomedical Engineering, Politecnico di Milano, Milan, Italy
3 Centro Cardiologico Monzino, IRCCs, Milan, Italy
4 Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, Pisa, Italy, Cardio‐Thoracic Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
5 Department of Clinical Cardiology, IRCCS Policlinico San Donato, Milan, Italy, Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
6 Department of Cardiology, ‘Azienda Sanitaria Universitaria Giuliano‐Isontina’, Trieste, Italy
7 Department of Cardiology, Unit of Cardiology, ASST Papa Giovanni XXIII, Bergamo, Italy
8 Heart Failure and Heart Transplant Units, Onassis Cardiac Surgery Centre, Attica, Greece
9 Federico II University, Naples, Italy
10 Università degli studi di Trieste, Trieste, Italy
11 Università degli studi Milano Bicocca, Milan, Italy
12 Department of Clinical and Molecular Medicine, Azienda Ospedaliera Sant'Andrea, ‘Sapienza’ Università degli Studi di Roma, Rome, Italy
13 Dipartimento di scienze biomediche avanzate, Federico II University, Naples, Italy
14 Department of Cardiology, Istituti Clinici Scientifici Maugeri, IRCCS, Veruno Institute, Veruno, Italy
15 Divisione di Cardiologia Riabilitativa, Istituti Clinici Scientifici Maugeri, Varese, Italy
16 Department of Translational Medical Sciences, Federico II University, Naples, Italy, Interdepartmental Center for Gender Medicine Research ‘GENESIS’, Naples, Italy
17 Cardiac Unit, AORN A Cardarelli, Naples, Italy, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
18 UOC Cardiologia di Riabilitativa, Mater Dei Hospital, Bari, Italy
19 Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari, ‘Sapienza’, Rome University, Rome, Italy
20 Department of Advanced Biomedical Sciences, Federico II University of Naples and Mediterranea CardioCentro, Naples, Italy
21 Department of Cardiology, University of Foggia, Foggia, Italy
22 Dipartimento cardio‐toraco‐vascolare, Ospedale Cà Granda‐ A.O. Niguarda, Milan, Italy
23 Department of Cardiology, Department of Medical and Surgical Specialities, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
24 Unità Operativa Cardiologia Riabilitativa, IRCCS Multimedica, Milan, Italy
25 University of Milano, Milan, Italy
26 Cardiologia SUN, Ospedale Monaldi (Azienda dei Colli), Seconda Università di Napoli, Naples, Italy
27 Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy, Department of Medicine and Surgery, University of Milano‐Bicocca, Milan, Italy
28 Unità funzionale di cardiologia, Casa di Cura Tortorella, Salerno, Italy
29 Department of Cardiology, Division of Cardiac Intensive Care Unit‐Cardiology, Ospedali Riuniti di Ancona, Ancona, Italy
30 Department of Biomedical Sciences for Health, University of Milano, Milan, Italy, Department of Cardiology, IRCCS Policlinico San Donato, Milan, Italy
31 Cardiac Rehabilitation Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Scientific Institute of Milan, Milan, Italy
32 Division of Cardiology, Cardiac Arrhythmia Center and Cardiomyopathies Unit, San Camillo‐Forlanini Hospital, Rome, Italy
33 Division of Cardiology, Santo Spirito Hospital, Rome, Italy
34 Division of Cardiology, Istituti Clinici Scientifici Maugeri, Institute of Bari, Bari, Italy
35 Clinica Hildebrand, Centro di Riabilitazione Brissago, Brissago, Switzerland
36 Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, Pisa, Italy
37 Centro Cardiologico Monzino, IRCCs, Milan, Italy, Programa de Pós‐Graduação em Fisioterapia, UDESC, Florianópolis, Brazil
38 Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, University of Brescia Medical School, Brescia, Italy
39 Centro Cardiologico Monzino, IRCCs, Milan, Italy, Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy





