In adults with repaired tetralogy of Fallot (rTOF) and preserved left ventricular ejection fraction (≥50%), reduced exercise capacity—measured by percent-predicted peak VO2—correlated significantly with larger left atrial volume index (ρ = -0.27, p = 0.003), elevated E/e' ratios, reduced e' velocity, and impaired right ventricular systolic function. Notably, pulmonary regurgitation severity and myocardial fibrosis detected by late gadolinium enhancement were not associated with exercise limitation. Patients with two or more diastolic dysfunction abnormalities showed meaningfully lower ppVO2 than those with one or fewer (p < 0.01).
This finding reframes the dominant clinical narrative around rTOF, which has historically focused on pulmonary regurgitation and RV dilation as the primary drivers of functional decline. That fibrosis—long considered a downstream marker of chronic volume overload—shows no association with exercise capacity here is genuinely surprising and challenges assumptions about when intervention is needed. The diastolic-atrial remodeling phenotype identified suggests that subclinical left-heart dysfunction may accumulate early, before overt structural damage appears. For clinicians managing adult congenital heart disease, this underscores the value of comprehensive echocardiographic diastolic assessment alongside standard RV surveillance. Practically, adults with rTOF experiencing unexplained fatigue or exercise intolerance may benefit from earlier multimodal imaging rather than waiting for classic RV failure markers. Important caveats apply: this is a retrospective, single-center analysis, and as a preprint not yet peer-reviewed, findings require independent replication before changing clinical protocols. The effect sizes are modest, and causality cannot be established.