Transplantation-free survival and interventions at 3 years in the single ventricle reconstruction trial

Abstract

Background: In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-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 transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups.

Methods and results: Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.8±1.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7±5.1% versus 44.7±6.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, -3.25±8.24% versus 0.99±8.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45-0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07-4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81-1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02-3.69); and >1 year, 2.48 (95% confidence interval, 1.28-4.80).

Conclusions: By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Keywords: Norwood procedures; cardiac surgical procedures; heart defects, congenital; heart diseases; heart ventricles.

Figure 1

Comparison of the shunt types by intention-to-treat analysis in their freedom from the composite endpoint of death or cardiac transplant (i.e., transplant-free survival).

Figure 2

Kaplan-Meier curve of the shunt types by intention-to-treat analysis in freedom from the composite endpoint of death or cardiac transplant, conditional on transplant-free survival to one year.

Figure 3

Panel A shows right ventricular ejection fraction, assessed by 2-dimensional echocardiography, at 14 months (age 14.1±1.0 months) and before Fontan surgery (age 2.7±0.8 years) according to shunt type; Panel B shows change in right ventricular ejection fraction (pre-Fontan minus 14 months) according to shunt type. There was a significant decline in the RVPAS group (P=0.004), but not in the MBTS group (R=0.40).