Prognostic impact of cardiovascular-kidney-metabolic burden among heart transplant patients: insights from the swiss transplant cohort study

Introduction Cardiovascular-kidney-metabolic (CKM) multimorbidity is known to be associated with a gradual increase in the risk of adverse clinical outcomes in chronic heart failure (HF). However, the prognostic significance of CKM burden among patients who underwent heart transplantation (HT) remains unexplored. Purpose We aimed to assess the prognostic impact of CKM multimorbidity present at the time of pre-transplant evaluation on all-cause death (ACD), in HT recipients enrolled in the Swiss Transplant Cohort Study, a nationwide, comprehensive cohort with prospectively collected data on solid organ transplant recipients. Methods We analyzed consecutive patients who underwent HT between 2008 and 2024 across four Swiss tertiary-care centers. Patients were categorized based on the number of CKM conditions present at the time of pre-transplant evaluation (0, 1, 2, or 3 conditions). CKM conditions included atherosclerotic disease (ischemic heart disease, peripheral arterial disease, or ischemic stroke), impaired kidney function (documented chronic kidney disease or an estimated glomerular filtration rate <60 mL/min/1.73 m² at baseline), and documented diabetes. The association between the number of CKM conditions and the primary outcome of ACD during the post-transplant period was assessed with Cox proportional hazards models. Results Among 531 patients (76.8% male, age 50±13 years), 24.1% had no CKM conditions, 42.6% had one, 27.9% had two, and 5.4% had three. Atherosclerotic disease was the most prevalent CKM condition (n=270), followed by impaired kidney function (n=244) and diabetes (n=95) (Figure 1). Over a median follow-up of 5.9 (IQR: 1.8-10.3) years, 115 patients (21.7%) died of any cause (incidence rate of 3.5 per 100 patient-years). Compared to patients without CKM comorbidities, those with 2 or 3 CKM conditions exhibited a stepwise increase in the risk of the primary outcome, with hazard ratios of 2.26 (95% confidence interval [CI]: 1.24–4.09) and 3.64 (95% CI: 1.64–8.06), respectively (Figure 2). In contrast, patients with a single CKM condition did not have a significant difference in the risk of the primary outcome. Conclusion In this Swiss national cohort including over 530 HT recipients, CKM multimorbidity was common, and the presence of 2 or 3 CKM conditions was associated with an incremental risk of ACD. These findings highlight the prognostic significance of a high CKM burden in the post-HT setting, extending beyond its established impact in chronic HF, and highlight the need for close monitoring and targeted therapeutic strategies to address CKM health objectives in the management of HT recipients.