In a retrospective longitudinal analysis of 521 adults with repaired tetralogy of Fallot (ToF) — spanning 1,053 cardiovascular MRI observations from 2003–2026 — aortic sinus diameter, total arterial compliance (TAC), and systemic vascular resistance (SVR) emerged as independent determinants of left ventricular ejection fraction (LVEF). Critically, a within-between statistical decomposition revealed that TAC predicts LVEF changes within individual patients (β=0.90 per mL/mmHg, p=0.014) but not between patients, identifying pulsatile afterload as a dynamic, potentially reversible contributor rather than a static risk marker. SVR predicted LVEF at both levels (β≈−0.23–0.25, both p<0.001), while conventional blood pressure metrics failed to predict LVEF at all.
This finding reframes ToF's intrinsic aortopathy — long considered a structural curiosity — as a hemodynamically active driver of LV failure, the strongest independent mortality predictor in this population. For adult congenital cardiologists, the localization of effect to the aortic root rather than the ascending aorta sharpens the anatomical target for intervention. The 35% attenuation of TAC's within-patient association after adjusting for right ventricular function hints at biventricular coupling mechanisms that deserve mechanistic investigation. Practically, SVR's modifiability raises the question of whether vasodilator therapy — already standard in heart failure — could slow LV deterioration in ToF. This is a preprint not yet peer-reviewed, so conclusions warrant caution. The study is retrospective and observational; causal inference and therapeutic implications require prospective validation. Still, the scale and longitudinal depth make this among the most rigorous hemodynamic analyses in adult congenital cardiology.