End-stage valvular heart disease requiring heart transplantation: risk profile, surgical modifiers, and myocardial pathology

BACKGROUND: End-stage valvular heart disease (VHD) constitutes a small but high-risk subset of heart transplant (HTx) recipients, and data describing their natural history and determinants of progression to HTx are limited. We aimed to characterize the clinical, genetic, surgical, and pathological substrates of patients undergoing HTx for end-stage VHD and to assess whether timely cardiac valvular surgery (CVS) mitigates progression to end-stage heart failure. METHODS: We retrospectively screened 961 consecutive recipients who underwent HTx for end-stage heart failure between January 2012 and December 2023. Patients with non-ischemic end-stage VHD due to a primary aortic valve lesion were identified by echocardiography and further adjudicated using cardiac magnetic resonance and explant pathology. After excluding ischemic and non-valvular cardiomyopathies and other predefined conditions, 45 patients constituted the final cohort. RESULTS: Of the 45 recipients, 78% had undergone prior CVS. CVS performed before heart failure or malignant ventricular arrhythmia was associated with a longer interval from symptom onset to HTx. In contrast, genetic variants were associated with earlier disease onset but did not significantly shorten the progression interval to HTx. Among 27 patients with prosthetic valves, 22 (77%) had structurally and hemodynamically preserved prostheses at the time of HTx, indicating that terminal HF predominantly reflected advanced myocardial disease rather than prosthetic failure. Explanted hearts consistently demonstrated extensive replacement fibrosis, and patients with malignant ventricular arrhythmias exhibited more prominent adipose replacement. CONCLUSIONS: Among patients transplanted for end-stage VHD, valve intervention performed prior to major clinical decompensation was associated with longer time intervals to HTx within this transplanted cohort. Most prosthetic valves showed preserved function at the time of HTx, supporting the concept that terminal heart failure in this setting often reflects advanced myocardial remodeling rather than prosthetic valve failure.