Multimodal Imaging Identifies Cardiac Remodeling Phenotype With Reduced Exercise Capacity in Repaired Tetralogy of Fallot

Background Exercise intolerance is common in adults with repaired tetralogy of Fallot (rTOF) despite preserved left ventricular ejection fraction (LVEF [&ge;]50%). Whether reduced exercise capacity is associated with early cardiac remodeling remains unclear. Objectives To determine whether reduced exercise capacity in rTOF with preserved LVEF is associated with diastolic dysfunction, atrial remodeling, right ventricular (RV) dysfunction, and myocardial fibrosis. Methods We retrospectively studied adults with rTOF and preserved LVEF who underwent cardiopulmonary exercise testing (CPET) and transthoracic echocardiography (TTE) and/or cardiac MRI (CMR) within 18 months. Exercise capacity was assessed by percent-predicted peak VO2 (ppVO2). Diastolic function and atrial remodeling were evaluated by TTE, and CMR assessed RV function and myocardial fibrosis. Results Reduced exercise capacity was associated with larger left atrial volume index (LAVI; p < 0.001), elevated E/e' and reduced e' velocity (both p < 0.05), and reduced RV systolic function (p < 0.001). LAVI correlated inversely with ppVO2 ({rho} = -0.27, p = 0.003). A composite diastolic dysfunction score showed a graded relationship with exercise capacity, with patients exhibiting [&ge;]2 abnormalities having lower ppVO2 than those with [&le;]1 abnormality (both p < 0.01). In contrast, pulmonary regurgitation (PR) severity and myocardial fibrosis by late gadolinium enhancement (LGE) were not associated with exercise capacity. Conclusions In adults with rTOF and preserved LVEF, reduced exercise capacity is associated with atrial remodeling, diastolic dysfunction, and RV dysfunction despite the absence of overt myocardial fibrosis. This suggests that multimodal imaging identifies an imaging-defined cardiac remodeling phenotype associated with early functional impairment.