Intermediate-term mortality and cardiac transplantation in infants with single-ventricle lesions: Risk factors and their interaction with shunt type

Abstract

Objectives We sought to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor either the modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery shunt (RVPAS). Methods We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors. Results Data from 549 subjects (follow-up, 2.7±0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated with death included lower socioeconomic status (SES; P=.01), obstructed pulmonary venous return (P<.001), smaller ascending aorta (P=.02), and anatomic subtype. Constant phase factors associated with death included genetic syndrome (P<.001) and lower gestational age (GA, P<.001). The RVPAS had better survival in the 51% who were full term with aortic atresia (P<.001). The MBTS was better among the 4% who were preterm with a patent aortic valve (P =.003). Lower pre-Norwood right ventricular fractional area change, pre-Norwood surgery, and anatomy other than hypoplastic left heart syndrome were independently associated with transplantation (all P<.03); but shunt type was not (P=.43). Conclusions Independent risk factors for intermediate-term mortality include lower SES, anatomy, genetic syndrome, and lower GA. Term infants with aortic atresia benefited from a RVPAS and preterm infants with a patent aortic valve benefited from a MBTS. Right ventricular function and anatomy, but not shunt type, were associated with transplantation.

Neighborhood Socioeconomic Status and Outcomes Following the Norwood Procedure: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set

“…Tweddell et al evaluated the role of neighborhood SES as one of the preoperative risk factors for 1‐year death and found that lower SES was associated with higher early mortality within the first year but not late phase mortality over 3 years 5. In contrast, Ghanayem et al used a census‐based neighborhood poverty level and found an inverted U‐shaped relationship between poverty level and interstage mortality 8.…”

“…Therefore, risk factors for adverse outcome in the SV population have been the subject of many investigations. Among these, innate risk factors, such as low birth weight, anatomy, preterm birth, genetic abnormalities, and associated noncardiac congenital anomalies, are well‐established predictors for early mortality and transplantation 3, 4, 5, 6, 7, 8. Recently, societal factors such as poverty, medical insurance, and maternal education have emerged as predictors of adverse outcomes in children with complex congenital heart disease (CHD) and may explain some of the difference in survival between children with similar clinical characteristics 9.…”

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

“…There were 72 events in the RVPA cohort with 68 deaths (25%), four (1 %) heart transplants, and 100 events in the BT shunt group with 91 (33 %) deaths and nine (3 %) heart transplants (p=0.01) . After three years of follow-up, the transplant-free survival was 67% for the RVPA group versus 61 % for the BT shunt group (p=0.15) (Tweddell et al 2012 The SVR trial investigators examined the preoperative mortality and its associated risk factors using all 921 infants with HLHS screened as part of the SVR trial (Atz et al 2010). Major extracardiac congenital abnormality (OR 10.0,p<0.0001), gestational age at birth (OR 1.3, 95% CI 1.1-1.5), p=0.02), and presence of obstructed pulmonary venous return (OR 4.0,p=0.02) were associated with preoperative death pre-Norwood procedure.…”

“…Multiple secondary analyses have been published using this dataset. Examples include evaluation of the interstage mortality (Ghanayem et al 2012), risk factors for death or transplant in the intermediate term (Tweddell et al 2012) and 3 years term (Newburger et al 1993), as well as shunt type effect on the cardiac function, ventricular size (Frommelt et al 2012), and ventricular deformation (Hill et al 2015). However, the group of patients with ventricular dysfunction has not been evaluated separately.…”

Growth in Congenital Heart Disease: Outcome or Predictor?

“…In the era of personalized medicine, premature and small neonates should not be considered a homogeneous high‐risk category. Although prematurity (<37 weeks’ gestation) and low birth weight (<2.5 kg) increase risk1, 2, 3, 4 on a population basis, the individual preterm or small infant may actually do well. Extrapolating risk from the outcomes of a diverse cohort to an individual is unreliable and potentially misleading, whether it be for counseling a family or discovering novel interventions to improve outcomes.…”