Distinct Prognostic Trajectories of Heart Failure Phenotypes Following Kidney Transplantation
Maor Bril, Ashraf Imam, Elchanan Parnasa, Michael Rivin, Suha Shabaneh, Keren Tzukert, Abel Roai, Offer Amir, Abed Khalaileh, Rabea AslehAbstract
Background and Aims
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.
Methods
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.
Results
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).
Conclusions
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.