Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study

Abstract

Objective: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age.

Methods: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival.

Results: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo₂ for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications.

Conclusions: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo₂, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT0245531.

Keywords: hypoplastic left heart syndrome; longitudinal outcomes; single ventricle reconstruction.

Figure 1.

SVR overall study participation. A total of 549 individuals were enrolled and randomly assigned to a right ventricle-to-pulmonary artery shunt (RVPAS) or a modified Blalock-Taussig-Thomas shunt (mBTTS), and 76% of transplant-free survivors (237 of 313) were enrolled in SVR III (Single Ventricle Reconstruction III). Cardiac magnetic resonance imaging (CMR) was completed for 177 participants, echocardiograms for 226 participants, and ramped cycle ergometry exercise testing for 181 participants. SVR indicates Single Ventricle Reconstruction.

Figure 2.

Comparison by received shunt type of right ventricle ejection fraction as measured by cardiac magnetic resonance imaging. There is no significant difference in right ventricular ejection fraction between those with a modified Blalock-Taussig-Thomas shunt (mBTTS; blue) and those with a right ventricle-to-pulmonary artery shunt (RVPAS; red). For each shunt type, the median is marked by a bold center line and the mean is marked by a diamond. Interquartile range is demarcated by the rectangle, and whiskers extend to the 5th and 95th percentiles. Outliers are marked by blue+ for the mBTTS group and red circles for the RVPAS group. Comparison by Student t test (P=0.43).

Figure 3.

Comparison of received shunt type in freedom from the composite end point of death or cardiac transplantation. Comparison by log-rank test shows no difference with all data considered (P=0.11). Percentage of survival at 1, 6, and 12 years of age by shunt type is shown in the top right quadrant. Hazard ratios (HRs) of right ventricle-to-pulmonary artery shunt (RVPAS) vs modified Blalock-Taussig-Thomas shunt (mBTTS) and CIs during 3 time periods (before stage 2 operation, between stage 2 and Fontan [stage 3], and after Fontan [stage 3]) are compared in the lower left quadrant. Because this analysis was by shunt type received, the 5 participants who had both an RVPAS and mBTTS at the conclusion of the Norwood operation were excluded from this portion of the analysis.

Figure 4.

Competing risks of death, transplant, and no event (transplant-free survival). A, Competing risk for those who received a modified Blalock-Taussig-Thomas shunt (mBTTS). B, Competing risk for those who received a right ventricle-to-pulmonary artery shunt (RVPAS).

Figure 5.

Comparison of probability of events over time. A, Atrial arrhythmia. B, Ventricular arrhythmia. C, Protein-losing enteropathy (PLE). D, Seizure. E, Stroke. P value for each comparison by log-rank test. Probability of atrial arrhythmias and of ventricular arrhythmias starts at 1 year, as seen by the x axis in A and B. For PLE, seizure, and stroke, data collection and x axis starts at the time of the Norwood operation. mBTTS indicates modified Blalock-Taussig-Thomas shunt; and RVPAS, right ventricle-to-pulmonary artery shunt.