(Un)natural history of right ventricular function and exercise tolerance during adolescence following tetralogy of fallot repair

Patients with repaired tetralogy of Fallot (rTOF) develop progressive right ventricular (RV) dilatation and dysfunction in adulthood, which may have origins in childhood. Cohorts from previous eras studied patients who underwent primary repair at an older age with frequent use of palliative shunts. The trajectory of RV functional decline and its relation to exercise capacity and outcomes over childhood is poorly characterized.

We sought to delineate changes in RV size, function, and exercise tolerance and occurrence of ventricular arrhythmia in a contemporary cohort of pediatric and adolescent rTOF.

We retrospectively reviewed serial echo, cardiac magnetic resonance (CMR) and clinical data from all rTOF patients between 2010-2020. We excluded patients with significant residual lesions, RV pressure overload (RVSP> half systemic) or without CMR data. Clinical data was recorded at 2-year intervals. We then compared CMR data and exercise tolerance at 10 to 16 years of age. Ventricular arrhythmias were defined based on Holter monitoring.

We studied 95 rTOF patients (61% male). Pulmonary insufficiency fraction (31% vs 32%, p=0.8), RV size (RV end diastolic indexed volume 130 ml/m2 (117 – 167) vs. 140 ml/m2 (124 – 166), p=0.6) and RV free wall longitudinal strain (19.4±4.3% vs. 19.3±4.7%, p=0.86) remained stable at 10 and 16 years of age. CMR RVEF (51±6% vs. 47±5.3%, p=0.01) and exercise tolerance (95±17% vs. 81±14.4%, % predicted VO2, p=0.002, figure B) decreased with the advent of incident ventricular arrhythmias (figure A). There were no deaths.

Despite excellent survival in childhood, patients with rTOF develop worsening RV function, exercise intolerance and ventricular arrhythmias during adolescence. These are worrisome findings given the known increase in sudden death in the 3-4th decades of life that warrant further investigation into the underlying causes, their temporal development and therapeutic approaches.

Figure 1: A-Kaplan-Meier curve of incident ventricular and atrial arrhythmias. B- percentage of predicted VO2 during childhood.