The Clinical Significance of Extra-Valvular Remodelling in Patients With Severe Symptomatic Aortic Stenosis

Abstract Background Extra-valvular remodelling is a key determinant of adverse outcomes following transcatheter aortic valve implantation, yet prior research has largely focused on left-sided disease. The aim was to address critical knowledge gaps regarding the prognostic and functional impact of right-sided cardio-pulmonary remodelling in severe aortic stenosis. Methods Five complementary studies were performed. Study 1 was a meta-analysis evaluating the association between right ventricle-pulmonary artery coupling (tricuspid annular plane systolic excursion/pulmonary artery systolic pressure) and clinical outcomes following valvular heart interventions. Study 2 retrospectively examined the prognostic impact of prosthesis–patient mismatch after transcatheter aortic valve implantation in relation to baseline pulmonary hypertension and right ventricular dysfunction. Study 3 prospectively quantified physical activity using consumer-wearable devices in transcatheter aortic valve implantation recipients, stratified by extra-valvular remodelling stage. Study 4 assessed the agreement and reproducibility of computed tomography and echocardiography-derived longitudinal strain and its association with pulmonary hypertension. Study 5 used invasive bi-ventricular pressure-volume loops to characterise haemodynamic changes following transcatheter aortic valve implantation. Results Reduced tricuspid annular plane systolic excursion/pulmonary artery systolic pressure was independently associated with increased adverse events following valve interventions, with optimal predictive thresholds identified. Baseline pulmonary hypertension and right ventricular dysfunction independently predicted mortality in ≥ moderate prosthesis–patient mismatch. Furthermore, severe prosthesis–patient mismatch conferred particularly high risk in those with advanced right-sided remodelling. Patients with pulmonary hypertension and right ventricular dysfunction demonstrated persistently reduced physical activity and attenuated functional recovery after transcatheter aortic valve implantation. Computed tomography and echocardiography-derived strain showed moderate-strong agreement and were reduced in pulmonary hypertension. Transcatheter aortic valve implantation resulted in acute bi-ventricular unloading and improved ventriculo-arterial coupling. Conclusions Right-sided cardio-pulmonary remodelling is a major determinant of mortality and functional recovery after transcatheter aortic valve implantation, supporting comprehensive right-heart assessment in all candidates. Funding Clinical Research Training Fellowship, British Heart Foundation (FS/CRTF/22/24328).