Pediatric Cardiology

Impact of Right Ventricular Pressure Load After Repair of Tetralogy of Fallot. Latus H, Stammermann J, Voges I, Waschulzik B, Gutberlet M, Diller GP, Schranz D, Ewert P, Beerbaum P, Kühne T, Sarikouch S; German Competence Network for Congenital Heart Defects Investigators *.J Am Heart Assoc. 2022 Apr 5;11(7):e022694. doi: 10.1161/JAHA.121.022694. Epub 2022 Mar 18.PMID: 35301850   Take Home Points: In patients with repaired tetralogy of Fallot, higher right ventricular outflow tract gradients were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not reduce the risk for later pulmonary valve replacement. These findings may affect the timing and indication of pulmonary valve replacement procedures in patients after repair of tetralogy of Fallot. Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch.   Introduction Following surgical repair of tetralogy of Fallot (TOF), pulmonary regurgitation (PR) frequently emerges as the predominant residual lesion causing progressive right ventricular (RV) enlargement, functional impairment, and, potentially, sudden cardiac death. Surgical management of patients after TOF repair has therefore shifted toward a pulmonary valve-sparing repair technique with the aim of preserving RV integrity. Subsequently, some degree of residual pulmonary stenosis is typically accepted after repair and has been shown to have beneficial effects on the described adverse RV remodeling process by reducing PR and RV enlargement without compromising RV function. Furthermore, mild residual RV outflow tract (RVOT) gradients may also postpone the need for pulmonary valve replacement (PVR). In contrast, recent data from several studies demonstrated elevated RV pressure as an independent predictor for adverse outcome after TOF repair.   Study Population: Patients with repaired TOF were enrolled in a prospective nationwide study by the German Competence Network for Congenital Heart Defects between 2003 and 2009. For the current study, patients with cardiopulmonary exercise testing data (peak oxygen uptake and percentage predicted and peak heart rate), echocardiographic assessment of the peak systolic RVOT gradient, and a comprehensive initial CMR examination (including biventricular volumetry and quantification of pulmonary regurgitation fraction using phase-contrast flow measurements) were considered for further analysis. These examinations were performed within a close time interval at study entrance, and the patients were then prospectively followed up until July 2018. To further assess the prognostic impact of residual RV pressure load, the study population was divided into 2 groups according to a cutoff RVOT gradient of <25 and ≥25 mm Hg.   Results From the total population of 407 patients with repaired TOF enrolled in the multicenter study, 337 had a suitable data set for the intended analysis that included echocardiographic peak RVOT gradient, a comprehensive CMR analysis, and a completed cardiopulmonary exercise testing examination. The mean peak echocardiographic RVOT gradient was 20.7±14.9 mm Hg (median, 16mmHg; range, 2–83mmHg).     Figure 1: Graph displaying the study flow with the total number of 407 patients after repair of tetralogy of Fallot (TOF) who were originally included in the national TOF multicenter cardiovascular magnetic resonance (CMR) study. Note that 5 patients were excluded in the outcome analysis as these patients exhibited adverse events before the CMR study. 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.   Correlations Peak RVOT gradient was significantly associated with smaller RV volumes (r=−0.16; P=0.004) and less PR (r=−0.12; P=0.026), but lower RV (r=−0.23; P=0.0004) and left ventricular (LV) longitudinal systolic strain (r=−0.15; P=0.016), and lower early diastolic strain rate (r=−0.17 [P=0.01] and r=−0.22 [P=0.0006]. No significant relationships were found between RVOT gradient and RV ejection fraction (RVEF), RV mass, and RV mass/volume ratio. LV dimensions and LV ejection fraction were not related to the RVOT gradient. Although not of statistical significance, a trend toward reduced exercise capacity (both peak oxygen uptake and oxygen uptake at ventilator anaerobic threshold) was observed with increasing RVOT gradients.   Prognostic Relevance of RVOT Gradient A higher RVOT gradient was significantly associated with the combined outcome (HR, 1.03; 95% CI, 1.01–1.06; P=0.006). Other significant predictors were New York Heart Association functional class >1, peak oxygen uptake, PVR during follow-up, right ventricular end-systolic volume (RVESVi), left ventricular end- diastolic volume (LVEDVi), left ventricular end-systolic volume (LVESVi), RV longitudinal strain, RV circumferential strain, LV circumferential strain, and LV radial strain. A peak RVOT gradient of ≥ 25mmHg was associated with a >3-fold increase in adverse cardiovascular events. Patients with moderate PR and a peak RVOT gradient ≥25 mm Hg demonstrated significantly more adverse events than patients with moderate PR and a peak RVOT gradient <25 mm Hg (P<0.001). In patients with severe PR ≥25%, RVOT gradients >25 or <25 mm Hg led to no significant difference (P=0.38).   Role of Peak RVOT Gradient in the Need for PVR Data on PVR procedures during follow- up were available in 292 of the 296 patients. Using univariable Cox-regression analysis, a higher RVOT gradient was significantly associated with the need for PVR (HR, 1.02; 95% CI, 1.01–1.03; P=0.002). Other significant factors predictive for PVR were initial palliation, poorer New York Heart Association functional class, increased RV volumes and RV mass, PR severity, as well as lower RVEF and LV ejection fraction.   Discussion Our study demonstrated that a higher peak RVOT gradient was associated with less PR and smaller RV volumes in patients with repaired TOF, but also negatively affected biventricular systolic and diastolic longitudinal strain at study entry, even in a relatively young study population, and emerged as a univariate predictor for adverse cardiovascular events. More importantly, peak RVOT pressure gradients of >25mmHg were associated with a >3-fold higher risk for death and ventricular tachyarrhythmia, even in this young cohort.     Table 3. Cox Proportional Hazard Analysis Using a Bivariable Model of the Parameters That Reached a Significant Level on Univariable Testing to Identify Their Prognostic Relevance in Conjunction With the Peak RVOT Gradient   Conclusions Although higher peak RVOT gradients were associated with less PR and smaller RV dimensions, an inverse relationship with reduced systolic and diastolic biventricular longitudinal strain was present. Increased RVOT gradients also emerged as univariate predictors of adverse cardiovascular events in the long-term course. Mildly increased pressure gradients had no protective effect on later PVR procedures. These results may have implications for the indication and timing of RVOT reintervention in patients with repaired TOF. An optimal degree of pressure load, which ensures a protective effect on RV remodeling without compromising ventricular function and outcome, still needs to be determined.