Transplantation-Free Survival and Interventions at 3 Years in the Single Ventricle Reconstruction Trial

Abstract

Background In the Single Ventricle Reconstruction (SVR) trial, one-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplant-free survival, echocardiographic right ventricular ejection fraction (RVEF), and unplanned interventions in the treatment groups. Methods and Results Vital status and medical history were ascertained from annual medical record, death index and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplant-free survival for the RVPAS vs. MBTS groups did not differ at 3 years (67% vs. 61%, P=.15) or with all available follow-up of 4.8±1.1 years (logrank P=.14). Pre-Fontan RVEF was lower in the RVPAS vs. MBTS group (41.7±5.1% vs. 44.7±6.0%, P=.007), and RVEF deteriorated in RVPAS (P=.004) but not MBTS subjects (P=.40) (pre-Fontan minus 14-month mean −3.25±8.24% vs. 0.99±8.80%, P=.009). The RVPAS vs. MBTS treatment effect had non-proportional hazards (P=.004); the hazard ratio (HR) favored the RVPAS before 5 months (HR=0.63; 95% CI 0.45–0.88), but the MBTS beyond one year (HR=2.22; 95% CI 1.07–4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<.001), with an increasing HR over time (P=0.005): <5 months HR= 1.14 (95% CI, 0.81–1.60); 5 months-1 year HR=1.94 (1.02–3.69), and >1 year HR=2.48 (1.28–4.80). Conclusions By 3 years, the Norwood procedure with RVPAS, compared with MBTS, was no longer associated with superior transplant-free survival. Moreover, RVPAS subjects had slightly worse RVEF and underwent more catheter interventions, with increasing hazard ratio over time. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT00115934.

Reduced cortical volume and thickness and their relationship to medical and operative features in post-Fontan children and adolescents

“…More recently, the Single Ventricle Reconstruction Trial found that overall 3-y transplant-free survival in HLHS patients was 64%. Among those who survive to Fontan in the current era, however, 10-y survival is over 90% (5,6). Consequently, focus has turned progressively toward neurologic injury and its effects on neurodevelopmental outcomes in the aging SV population.…”

Risk Factors for Death or Heart Transplant for Patients with Right Ventricular Dysfunction After the Norwood Procedure: A Secondary Analysis of the Single Ventricle Reconstruction Trial

“…Lower center Norwood volume was associated with sepsis, longer time to first extubation, as well as increased duration of ventilation and length of hospital stay after the stage II procedure (Schwartz et al, 2014). Similarly, lower surgeon volume, but not center volume was also associated with lower three-year transplant-free survival (OR 1.73, 95% CI 1.73 (1.05-2.85), p=0.001) (Newburger et al 2014). This is consistent with our study finding that surgeon volume is a significant predictor of outcomes in our HLHS population with ventricular dysfunction.…”

“…However, patients that died pre-Fontan procedure had lower mean RVEF (34 % +/-9 % vs. 43 % +/-7 %) (Newburger et al 2014 1.2.7.6 Association between ventricular dysfunction and mortality in other analyses Ventricular dysfunction was also identified as a risk factor for mortality in other analyses. The spike in moderate ventricular dysfunction incidence seen at three to six months post-Norwood was shown to coincides temporally with the early hazard for death or transplant using the Congenital Heart Surgeons' Society cohort (Wilder, McCrindle, et al 2015b).…”

“…Shunt type was also found to be associated with interstage death in an univariate analysis (OR 3.44, p<0.001), but only of those with mild or no AVVR in the multivariable analysis (OR 9.7, p<0.001) (Ghanayem et al 2012). RVPA conduit was no longer associated with superior transplant-free survival at three years post-randomization (Newburger et al 2014). …”

“…Another secondary analysis of the SVR trial identified that having a BT shunt compare to RVPA conduit was an independent risk factor for ventricular dysfunction on the post-Norwood echocardiogram (Tabbutt et al 2012). Another analysis of the SVR trial demonstrated an increase in late deaths and late heart transplants within the RVPA cohort while evaluating the three-year follow-up, and hypothesized that this was might be related to the longterm effect of the ventriculotomy (Newburger et al 2014). However, this finding was not replicated for CHSS cohort, which showed a long-term survival advantage of the RVPA conduit over BT shunt and the hybrid procedure (Wilder et al 2016) at the four-year follow-up.…”