Distinct Prognostic Trajectories of Heart Failure Phenotypes Following Kidney Transplantation

Heart failure (HF) drives post-kidney transplant (KT) morbidity. While KT reverses components of uremic cardiomyopathy, the persistence of post-transplant risk in HF with preserved (HFpEF) versus HF with reduced ejection fraction (HFrEF) remains unclear. We evaluated phenotype-specific remodeling and clinical outcomes.

Retrospective cohort of adult KT recipients stratified by pre-transplant echocardiography: HFpEF (left ventricular ejection fraction [LVEF] ≥ 50% with elevated filling pressures), HFrEF (LVEF <50%), or controls. Longitudinal echocardiographic remodeling and post-transplant outcomes were analyzed using multivariable Cox regression.

Of 442 recipients, 64 (14.5%) had HFpEF, 44 (10.0%) HFrEF, and 334 (75.5%) controls. Over a 49-month median follow-up, HFpEF was independently associated with HF hospitalization (adjusted hazard ratio [aHR] 9.57; 95% confidence interval [CI] 3.37-27.2, p < 0.001) and composite death/HF hospitalization (aHR 4.46; 95% CI 2.36-8.42, p < 0.001). Paired longitudinal echocardiography demonstrated persistent diastolic stiffness within the HFpEF group (E/e': 12.7 ± 4.6 to 11.8 ± 5.3, p = 0.117). Conversely, HFrEF patients exhibited systolic recovery (ΔLVEF +8.7 ± 10.2%, p = 0.003), remaining independently associated with all-cause mortality (aHR 2.9; 95% CI 1.16-7.25, p = 0.023) but not HF hospitalization (aHR 3.11; 95% CI 0.71-13.6, p = 0.13). Mechanistically, ΔLVEF predicted lower HF hospitalization risk (aHR 0.94; 95% CI 0.90-0.99, p = 0.02), whereas mortality tracked with continuous changes in hemoglobin (aHR 0.71; 95% CI 0.60-0.83, p < 0.001) and calcium (aHR 0.69; 95% CI 0.50-0.96, p = 0.027).

Post-KT trajectories differ by pre-transplant HF phenotype. Uremic HFpEF is a persistent, non-reversible phenotype driving severe post-KT morbidity. HFrEF demonstrates systolic reversibility. Pre-transplant evaluation should incorporate targeted diastolic profiling beyond standard LVEF-centered assessment to identify KT candidates at high risk for recurrent post-transplant HF morbidity.