Clinical Phenotypes in Heart Transplantation: Implications for Prognosis and Personalized Follow-up

BACKGROUND: Outcomes after heart transplantation remain highly variable, and traditional risk models perform poorly in this heterogeneous population. We sought to identify clinically meaningful recipient subgroups and assess their prognostic implications using latent class analysis (LCA). METHODS: We analyzed all adult recipients of a first isolated heart transplantation in Spain. LCA based on pretransplant characteristics identified recipient phenogroups, whose 5-y all-cause mortality was compared using Cox models and internally validated with bootstrap resampling and Harrell's C-statistics. RESULTS: Among 3683 recipients (74.5% male), 3 phenogroups were identified. Phenogroup 1 (41.3%) included younger patients, more women, dilated cardiomyopathy, and fewer comorbidities. Phenogroup 2 (22.1%) comprised older men with ischemic cardiomyopathy and high comorbidity burden. Phenogroup 3 (36.6%) represented urgent transplants with frequent circulatory support, ventilation, and longer ischemia. Five-year mortality was 24.0%, 28.5%, and 33.0% across groups (P < 0.001). Compared with phenogroup 1, mortality risk was higher in phenogroup 2 (HR = 1.20; 95% confidence interval, 1.02-1.41) and phenogroup 3 (HR = 1.47; 95% confidence interval, 1.28-1.69). Causes of death differed, graft failure predominating in phenogroup 1 and infection in phenogroups 2 and 3. Internal validation confirmed high model stability (entropy 0.99) and modest discrimination (optimism-adjusted C-statistic 0.55). CONCLUSIONS: LCA identified 3 reproducible clinical phenogroups with distinct prognoses and mechanisms of death. Recognizing these patterns may refine posttransplant surveillance and guide phenotype-based management strategies.

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Journal
Transplantation
Published
2026-06-16
DOI
https://doi.org/10.1097/tp.0000000000005789
Primary Topic
Transplantation: Methods and Outcomes
Type
article
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article

Clinical Phenotypes in Heart Transplantation: Implications for Prognosis and Personalized Follow-up

Sònia Mirabet, María G. Crespo‐Leiro, José González‐Costello, Manuel Crespín Crespín et al.
Transplantation
Transplantation: Methods and Outcomes
article

Clinical Phenotypes in Heart Transplantation: Implications for Prognosis and Personalized Follow-up

Sònia Mirabet, María G. Crespo‐Leiro, José González‐Costello, Manuel Crespín Crespín, Inés Ponz, Beatriz Díaz‐Molina, Pedro Caravaca Pérez, Juan F. Delgado, Francisco González Vílchez, Antonio García-Quintana, Luis De la Fuente-Galán, Iris P. Garrido-Bravo, Gregorio Rábago Juan-Aracil, Marta Farrero, Luis Almenar-Bonet, Manuel Gómez-Bueno, José M. Sobrino, Carlos Ortiz-Bautista, Teresa Blasco-Peiró
article en

Abstract

BACKGROUND: Outcomes after heart transplantation remain highly variable, and traditional risk models perform poorly in this heterogeneous population. We sought to identify clinically meaningful recipient subgroups and assess their prognostic implications using latent class analysis (LCA). METHODS: We analyzed all adult recipients of a first isolated heart transplantation in Spain. LCA based on pretransplant characteristics identified recipient phenogroups, whose 5-y all-cause mortality was compared using Cox models and internally validated with bootstrap resampling and Harrell's C-statistics. RESULTS: Among 3683 recipients (74.5% male), 3 phenogroups were identified. Phenogroup 1 (41.3%) included younger patients, more women, dilated cardiomyopathy, and fewer comorbidities. Phenogroup 2 (22.1%) comprised older men with ischemic cardiomyopathy and high comorbidity burden. Phenogroup 3 (36.6%) represented urgent transplants with frequent circulatory support, ventilation, and longer ischemia. Five-year mortality was 24.0%, 28.5%, and 33.0% across groups (P < 0.001). Compared with phenogroup 1, mortality risk was higher in phenogroup 2 (HR = 1.20; 95% confidence interval, 1.02-1.41) and phenogroup 3 (HR = 1.47; 95% confidence interval, 1.28-1.69). Causes of death differed, graft failure predominating in phenogroup 1 and infection in phenogroups 2 and 3. Internal validation confirmed high model stability (entropy 0.99) and modest discrimination (optimism-adjusted C-statistic 0.55). CONCLUSIONS: LCA identified 3 reproducible clinical phenogroups with distinct prognoses and mechanisms of death. Recognizing these patterns may refine posttransplant surveillance and guide phenotype-based management strategies.

Transplantation
Universitat Autònoma de Barcelona (ES), Universidad de Cantabria (ES), Hospital Universitario La Paz (ES), Hospital de Sant Pau (ES), Bellvitge University Hospital (ES), Hospital General Universitario Gregorio Marañón (ES), Hospital Universitari i Politècnic La Fe (ES), Research Institute Hospital 12 de Octubre (ES), Institut d'Investigació Biomédica de Bellvitge (ES), Instituto Maimónides de Investigación Biomédica de Córdoba (ES), Centro de Investigación en Red en Enfermedades Cardiovasculares (ES), Hospital Universitario de Gran Canaria Doctor Negrín (ES), Marqués de Valdecilla University Hospital (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Instituto de Investigación Marqués de Valdecilla (ES), Hospital Universitario Miguel Servet (ES), Hospital Clínic de Barcelona (ES), Leitat Technological Center (ES), Hospital Universitario Central de Asturias (ES), Clinica Universidad de Navarra (ES), Complexo Hospitalario Universitario A Coruña (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Universitario Virgen del Rocío (ES), Hospital Clínico Universitario de Valladolid (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
Gender equality
Openalex Percentile: Top 6%
Transplantation: Methods and Outcomes
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