Differences in Right Ventricular-Pulmonary Vascular Coupling between Standard Tetralogy of Fallot (TOF) vs. TOF with Pulmonary Atresia: Association with Other CMR and Clinical Indices

Background: The failing right ventricle (RV) in repaired tetralogy of Fallot (TOF) patients undergoes complex adaptation. We hypothesized that ventricular vascular coupling ratio (VVCR) assessed noninvasively by cardiac magnetic resonance (CMR) may provide unique insights, because uncoupling of vascular and ventricular properties is an important determinant of RV failure as reported in pulmonary hypertension. We sought to measure VVCR in standard TOF versus TOF with Pulmonary Atresia (TOF/PA) given the potential differences in vascular compliance.

Methods: TOF patients aged >8 years were recruited in a nationwide prospective trial. Sanz's method was used to calculate VVCR as RV end-systolic volume/ pulmonary artery stroke volume, and indexed to body surface area to account for somatic growth. Subgroup analysis was performed for TOF versus TOF/PA. Univariate and multivariate regressions examined associations with exercise test parameters, NYHA class, RV size and biventricular systolic function.

Results: 260 subjects were included, 232 with TOF and 28 with TOF/PA, mean age 15.8 ± 4.9 years. Mean non-indexed VCCR in our whole TOF study cohort was 1.64 ± 0.83, and higher (abnormal) compared with published values in healthy controls (0.5–1.0).

Mean indexed VVCR (VCCRi) in the whole patient cohort was 1.08 ± 0.59; it was more abnormal in the TOF/PA subgroup (1.35 ± 0.71) versus standard TOF (1.04 ± 0.53; p < 0.01), while traditional measures of RV size and function were not different. VCCRi had significant correlation with peak oxygen pulse on exercise testing (r = −0.33; p < 0.001), RV EF (r = −0.44; p =< 0.001), RV mass/volume ratio (r = −0.331; p < 0.001), pulmonary regurgitation fraction (r = 0.52; p < 0.001) and LV EF (r = −0.31, p < 0.001). VCCRi was higher in subjects with NYHA class II (1.31 ± 0.70; n = 69) versus NYHA class I (1.00 ± 0.52; n = 191; p < 0.001). VCCRi also had independent association with peak oxygen pulse and NYHA class on multivariable analysis (R ² = 0.14); and this association improved with addition of RV EF and RV EDV to the model (R ² = 0.33).

Conclusion: VCCRi is worse in subjects with TOF/PA compared with standard TOF. It has independent association with peak oxygen pulse and NYHA class, and this association improves when used in conjunction with RV volume and EF. Correlation with NYHA class and measures of exercise testing suggests its potential clinical value as an indicator of pulmonary arterial compliance and cardiovascular performance in this cohort.