Cumulative Multidomain Vulnerability and Early Mortality After Heart Transplantation: Development and Temporal Evaluation of the RIGHT-HTx Framework
- 1Institute of Heart and Lung Transplant & Mechanical Circulatory Support, MGM Healthcare
Abstract
BACKGROUND Risk models from high-income transplant programmes may not generalise to resource-constrained settings with different recipient acuity, donor characteristics and access to mechanical circulatory support. We developed RIGHT-HTx, a parsimonious framework integrating clinical and physiological vulnerabilities, and evaluated its prognostic performance in a subsequent same-centre cohort. METHODS This retrospective single-centre study included 436 consecutive adult heart transplant recipients (2012-2026). Of 357 development recipients, 341 (95.5%) were score-evaluable. RIGHT-HTx incorporated three vulnerability domains: clinical acuity (INTERMACS 1-2), graded renal dysfunction (eGFR 30-59 or <30 mL/min/1.73 m2) and haemodynamic-donor mismatch (TPG >12 mmHg combined with donor-to-recipient weight ratio <1.0). A seven-point Cox-derived score underwent internal validation using 1,000 bootstrap resamples and was applied unchanged to 79 subsequent recipients. Low-, intermediate- and high-risk categories represented zero, one and 2 affected domains, respectively. RESULTS Among development recipients, 75/341 (22.0%) died within one year. Mortality increased across low-, intermediate- and high-risk categories (8.1%, 20.3% and 55.6%; log-rank P<0.001). Elevated TPG was not significantly associated with mortality individually, whereas its combination with donor undersizing was independently associated with mortality (adjusted HR 2.87, 95% CI 1.53-5.40; P=0.001). The full model improved discrimination beyond renal dysfunction alone (optimism-corrected C-index 0.067), and the simplified score achieved an optimism-corrected C-index of 0.732. The temporal cohort more often had 1 affected domain (75.9% versus 60.4%; P=0.010). Discrimination was comparable (C-index 0.738, 95% CI 0.643-0.833), although observed Kaplan-Meier one-year mortality exceeded original predictions (35.4% versus 25.4%; calibration slope 0.929). In pooled analyses (n=420), mortality increased from 8.4% (13/154) with no affected domain to 57.3% (47/82) with two or more. CONCLUSIONS RIGHT-HTx identifies cumulative multidomain vulnerability associated with early mortality after heart transplantation. Temporal discrimination was comparable, but absolute-risk calibration differed. The framework may support risk recognition and mitigation, not transplant eligibility or allocation; independent multicentre validation is required before clinical implementation.
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BibTeX
@misc{balakrishnan2026cumulative,
title = {{Cumulative Multidomain Vulnerability and Early Mortality After Heart Transplantation: Development and Temporal Evaluation of the RIGHT-HTx Framework}},
author = {K. R. Balakrishnan and S. R. Kemundel Genny and M. Tungatru and N. Davidson and A. Sahayaraj and A. Aravind and S. Vanga and N. Singh and N. Nallamuthu and A. Jegdish and K. Krithika and R. K. Ratnagiri and R. Chandrasekaran and R. K. RAMASWAMY and V. Manikala and A. Kumar},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.26367231},
url = {https://www.medrxiv.org/content/10.64898/2026.11.03.26367231v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cumulative Multidomain Vulnerability and Early Mortality After Heart Transplantation: Development and Temporal Evaluation of the RIGHT-HTx Framework
AU - K. R. Balakrishnan
AU - S. R. Kemundel Genny
AU - M. Tungatru
AU - N. Davidson
AU - A. Sahayaraj
AU - A. Aravind
AU - S. Vanga
AU - N. Singh
AU - N. Nallamuthu
AU - A. Jegdish
AU - K. Krithika
AU - R. K. Ratnagiri
AU - R. Chandrasekaran
AU - R. K. RAMASWAMY
AU - V. Manikala
AU - A. Kumar
PY - 2026
DA - 2026/11/03
PB - medRxiv
DO - 10.64898/2026.11.03.26367231
UR - https://www.medrxiv.org/content/10.64898/2026.11.03.26367231v1
AB - BACKGROUND Risk models from high-income transplant programmes may not generalise to resource-constrained settings with different recipient acuity, donor characteristics and access to mechanical circulatory support. We developed RIGHT-HTx, a parsimonious framework integrating clinical and physiological vulnerabilities, and evaluated its prognostic performance in a subsequent same-centre cohort. METHODS This retrospective single-centre study included 436 consecutive adult heart transplant recipients (2012-2026). Of 357 development recipients, 341 (95.5%) were score-evaluable. RIGHT-HTx incorporated three vulnerability domains: clinical acuity (INTERMACS 1-2), graded renal dysfunction (eGFR 30-59 or <30 mL/min/1.73 m2) and haemodynamic-donor mismatch (TPG >12 mmHg combined with donor-to-recipient weight ratio <1.0). A seven-point Cox-derived score underwent internal validation using 1,000 bootstrap resamples and was applied unchanged to 79 subsequent recipients. Low-, intermediate- and high-risk categories represented zero, one and 2 affected domains, respectively. RESULTS Among development recipients, 75/341 (22.0%) died within one year. Mortality increased across low-, intermediate- and high-risk categories (8.1%, 20.3% and 55.6%; log-rank P<0.001). Elevated TPG was not significantly associated with mortality individually, whereas its combination with donor undersizing was independently associated with mortality (adjusted HR 2.87, 95% CI 1.53-5.40; P=0.001). The full model improved discrimination beyond renal dysfunction alone (optimism-corrected C-index 0.067), and the simplified score achieved an optimism-corrected C-index of 0.732. The temporal cohort more often had 1 affected domain (75.9% versus 60.4%; P=0.010). Discrimination was comparable (C-index 0.738, 95% CI 0.643-0.833), although observed Kaplan-Meier one-year mortality exceeded original predictions (35.4% versus 25.4%; calibration slope 0.929). In pooled analyses (n=420), mortality increased from 8.4% (13/154) with no affected domain to 57.3% (47/82) with two or more. CONCLUSIONS RIGHT-HTx identifies cumulative multidomain vulnerability associated with early mortality after heart transplantation. Temporal discrimination was comparable, but absolute-risk calibration differed. The framework may support risk recognition and mitigation, not transplant eligibility or allocation; independent multicentre validation is required before clinical implementation.
ER -