Impact of Right Ventricular Pressure Load After Repair of Tetralogy of Fallot

Abstract

Background Right ventricular outflow tract (RVOT) stenosis after repair of tetralogy of Fallot has been linked with favorable right ventricular remodeling but adverse outcomes. The aim of our study was to assess the hemodynamic impact and prognostic relevance of right ventricular pressure load in this population. Methods and Results A total of 296 patients with repaired tetralogy of Fallot (mean age, 17.8±7.9 years) were included in a prospective cardiovascular magnetic resonance multicenter study. Myocardial strain was quantified by feature tracking technique at study entry. Follow-up, including the need for pulmonary valve replacement, was assessed. The combined end point consisted of ventricular tachycardia and cardiac death. A higher echocardiographic RVOT peak gradient was significantly associated with smaller right ventricular volumes and less pulmonary regurgitation, but lower biventricular longitudinal strain. During a follow-up of 10.1 (0.1-12.9) years, the primary end point was reached in 19 of 296 patients (cardiac death, n=6; sustained ventricular tachycardia, n=2; and nonsustained ventricular tachycardia, n=11). A higher RVOT gradient was associated with the combined outcome (hazard ratio [HR], 1.03; 95% CI, 1.00-1.06; P=0.026), and a cutoff gradient of ≥25 mm Hg was predictive for cardiovascular events (HR, 3.69; 95% CI, 1.47-9.27; P=0.005). In patients with pulmonary regurgitation ≥25%, a mild residual RVOT gradient (15-30 mm Hg) was not associated with a lower risk for pulmonary valve replacement. Conclusions Higher RVOT gradients were associated with less pulmonary regurgitation and smaller right ventricular dimensions but were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not protect from pulmonary valve replacement. These results may have implications for the indication for RVOT reintervention in this population.

Keywords: magnetic resonance imaging; prognosis; right ventricular pressure overload; strain; tetralogy of Fallot.

Figure 1. Graph displaying the study flow with the total number of 407 patients after repair of tetrology of Fallot (TOF) who were originally included in the national TOF multicenter cardiovascular magnetic resonance (CMR) study. A total of 70 patients were excluded because of an incomplete data set.

Of the 337 patients, another 36 had to be excluded as no follow‐up data were available within the database of the national registry for congenital heart disease (CHD). Finally, of 296 patients with a median follow‐up time of 10.1 (range, 0.1–12.9) years, 19 experienced adverse events. Note that 5 patients were excluded in the outcome analysis as these patients exhibited adverse events before the CMR study. Pulmonary valve replacement (PVR) procedures were performed in 119 of 292 patients during the follow‐up. CPET indicates cardiopulmonary exercise testing; echo, echocardiographic; EP, electrophysiologic study; ICD, implantable cardioverter‐defibrillator; N, number of patients; RVOT, right ventricular outflow tract; TOF/PA, pulmonary atresia with ventricular septal defect (Fallot type); and VT, ventricular tachycardia.

Figure 2. Graph displaying several linear correlations between the echocardiographic (echo) peak right ventricular outflow tract (RVOT) gradient and cardiovascular magnetic resonance measures of biventricular dimensions and function as well as results from cardiopulmonary exercise testing.

Higher RVOT gradients were significantly associated with smaller right ventricular end‐diastolic volumes (RVEDVI) and less pulmonary regurgitation (PR) but were also related with reduced global right ventricular (RV) and left ventricular (LV) longitudinal systolic (strain) and diastolic (strain rate) deformation. No significant correlation was observed between peak RVOT gradient and exercise capacity (peak oxygen uptake [VO₂] and percentage predicted). EDSR indicates early diastolic strain rate; EF, ejection fraction; LS, longitudinal strain; and VAT, ventilator anaerobic threshold.

Figure 3. Diagram showing freedom from the composite end point (cardiac death and sustained and nonsustained ventricular tachycardia) during follow‐up from the cardiovascular magnetic resonance (CMR) study using Kaplan‐Meier curves according to the peak right ventricular outflow tract (RVOT) gradient of ≥25 and <25 mm Hg.

Using Cox proportional hazard analysis, a peak RVOT gradient ≥25 mm Hg was associated with a >3‐fold increased risk for adverse cardiovascular events (hazard ratio [HR], 3.69; 95% CI, 1.47–9.27; P=0.005).

Figure 4. Graph displaying freedom from pulmonary valve replacement (PVR) procedures during follow‐up using Kaplan‐Meier curves (displayed with 95% CIs).

The study population was divided into different subgroups according to the peak right ventricular outflow tract (RVOT) gradient <15, 15 to 30, and >30 mm Hg and the severity of pulmonary regurgitation (PR; <25% and ≥25%). Statistical comparisons between the subgroups were made using the log‐rank (Mantel‐Cox) test (P values are displayed in Table S3). Note that in patients with PR ≥25% (top panel), no significant difference in the need for PVR surgery was observed between the subgroups, suggesting that mild residual RVOT stenosis seems not to protect from PVR. In patients with PR <25% (bottom panel), the subgroup with a peak RVOT gradient >30 mm Hg had a significant higher risk for PVR during follow‐up than those with a gradient <15 and 15 to 30 mm Hg (P<0.001, respectively). CMR indicates cardiovascular magnetic resonance.