Abstract Background Patients with a systemic right ventricle (SRV) and biventricular circulation experience high incidence of cardiovascular morbidities and decreased survival [1]. Non-invasive measures of subclinical ventricular dysfunction are needed to appropriately identify patients at increased risk for adverse outcomes. Ventricular-arterial coupling (VAC), the ratio between the effective arterial elastance (Ea) and ventricular end-systolic elastance (Ees), may predict clinical outcomes in patients with SRV [2]. Objectives To assess VAC in adults with SRV and evaluate its correlation with clinical outcomes. Methods Consecutive cardiovascular magnetic resonance (CMR) examinations of adults with D-loop transposition of great arteries (TGA) after atrial switch operation and L-loop TGA performed at Boston Children's Hospital between 2005 and 2019 were analyzed. VAC was calculated as Ea/Ees (Ea = mean arterial blood pressure (MBP)/ventricular stroke volume; Ees = MBP/end-systolic volume). Global myocardial strain was measured by feature tracking analysis on cine steady-state free precession sequences. Cox proportional hazards regression analysis was performed to assess the association of SRV functional parameters with clinical outcomes. The analysis was adjusted for age, sex, and body mass index. The primary outcome was defined as a composite of death, cardiovascular arrest, hospitalizations for heart failure (HF); the secondary outcome as atrial arrhythmias; the tertiary outcome included other causes of cardiovascular hospitalizations (percutaneous or surgical interventions, device implantation, other cardiovascular disease). Cumulative incidence of the study outcomes was estimated using Kaplan-Meier method. Results One hundred sixty-seven adults (mean age 32±10 years, 59% men) with SRV were analyzed. Patients with HF (n=48, 29%) had higher VAC values as compared to those without HF (1.4±0.8 vs. 1.1±0.5, p=0.01). Over a mean follow-up of 6.5±4.2 years, 15 over 139 patients (11%) experienced the primary outcome with an incidence rate of 1.7 per 100 patient-years (95% confidence interval (CI), 1.04–2.85). Higher VAC values were significantly associated with an increased risk of the primary outcome (p for trend = 0.01, Figure 1). VAC was the only functional parameter associated with the primary outcome (hazard ratio (HR) 1.99, 95% CI: 1.06–3.73, p=0.031), secondary outcome (HR 2.33, 95% CI: 1.12–4.82, p=0.023) and tertiary outcome (HR 1.63, 95% CI: 1.09–2.44, p=0.018) in the adjusted analysis (Table 1). Ejection fraction (EF) was not associated with the study outcomes in the adjusted analysis (p>0.05, Table 1) whereas global circumferential and radial strain showed an association limited to the tertiary endpoint (p=0.004, Table 1). Conclusions CMR-derived VAC is associated with adverse outcomes in SRV patients and may improve risk stratification of this unique population. Funding Acknowledgement Type of funding sources: None.