Goldstein BH, Petit CJ, Qureshi AM, McCracken CE, Kelleman MS, Nicholson GT, Law MA, Meadows JJ, Zampi JD, Shahanavaz S, Mascio CE, Chai PJ, Romano JC, Batlivala SP, Maskatia SA, Asztalos IB, Kamsheh AM, Healan SJ, Smith JD, Ligon RA, Pettus JA, Juma S, Raulston JEB, Hock KM, Pajk AL, Eilers LF, Khan HQ, Merritt TC, Canter M, Juergensen S, Rinderknecht FA, Bauser-Heaton H, Glatz AC.
J Am Coll Cardiol. 2021 Mar 2;77(8):1093-1106. doi: 10.1016/j.jacc.2020.12.048.
- In children with symptomatic Tetralogy of Fallot, needing neonatal intervention, a comparison made between those managed with staged repair (SR) vs. primary repair (PR) showed balanced results.
- Upon adjusting for patient factors, early mortality risk was higher in the PR group; however, the overall risk of death did not differ between treatment groups.
- Lesser neonatal morbidity was reported in the SR group. In contrast, the overall cumulative morbidity burden (combining the initial palliation and complete repair in the SR group) favored the primary repair group.
- Reintervention risk was higher in the SR group, but late reintervention risk (>3 months) and reintervention burden following deﬁnitive repair did not differ between groups.
- Both strategies have potential benefits, and hence an individualized case-based approach is warranted based on patient, procedural and institutional factors.
Commentary from Dr. Venu Amula (Salt Lake City, UT, USA), section editor of Pediatric & Fetal Cardiology Journal Watch: Tetralogy of Fallot (TOF) is a congenital heart disease with a spectrum of cyanosis based on the degree of right ventricular outflow tract obstruction. Neonates can be symptomatic early, with cyanosis needing an intervention. Early intervention in symptomatic neonates can be palliative – both surgical and transcatheter procedures to provide additional pulmonary blood flow, or some may consider primary repair of the intracardiac defect. In this study by Goldstein et al., the investigators seek to compare the two treatment strategies of staged repair (SP) ( initial palliation [IP] followed by complete repair [CP]) and Primary repair (PR).
The authors performed a retrospective cohort study using a multicenter collaborative with good sample size and practice variability to compare outcomes adjusted for patient-level differences and reduce confounding by indication. Study subjects included all neonates with tetralogy of Fallot who underwent an initial intervention < or = 30 days at the nine centers of the Congenital Cardiac Research Collaborative. The indication of intervention was cyanosis, ductal dependent pulmonary blood flow, or hyper cyanotic episodes. Cases with discontinuous pulmonary arteries, TOF associated with Atrioventricular canal, Absent Pulmonary Valve, and Major Aortopulmonary Collaterals were excluded. The index procedure ( Initial Palliation or Primary Repair ) was the exposure, with the primary outcome being death or heart transplantation. Secondary outcomes included in-hospital mortality, procedural and hospital complications, reinterventions, and other measures of morbidity.
The five variables most likely associated with treatment strategy ( SR vs. PR) – center, preintervention mechanical ventilation, prematurity, DiGeorge syndrome, and presence of antegrade blood flow were used in a logistic regression model to estimate propensity scores. Inverse probability of treatment weighting using propensity scores was used to adjust for potential confounders between groups. The effect of treatment strategy on dichotomous outcomes was evaluated by logistic regression weighted by propensity score. Time-dependent outcomes were analyzed with survival analysis.
The overall study cohort consisted of 572 patients, 230 treated with primary repair and 345 with initial palliation.
Adjusted comparison of the primary outcome of death ( none got transplanted in this cohort) showed no difference in the overall hazard of death (HR: 0.82; 95% CI: 0.49 to 1.38; p = 0.459), although early mortality hazard (<4 months post-intervention) was lower in the SR group (HR: 0.5; 95% CI: 0.25 to 0.97; p =0.041).
Propensity score-adjusted differences in continuous secondary outcomes of neonatal morbidities, including procedural complications, duration of mechanical ventilation and inotrope use, procedural support times (CPB, cross-clamp, anesthesia), and ICU LOS, remained lower in the SR group at the index procedure. As was the case in the observed data, the adjusted cumulative burden of the SR strategy was associated with greater exposure to procedural, ICU, and post-procedural secondary outcomes than in the PR group.
Adjusted differences in the outcomes of in-hospital mortality and complications showed that the risk of in-hospital mortality was lower in the SR group at the index procedure (OR: 0.37; 95% CI: 0.15 to 0.88; p = 0.025) and again at deﬁnitive repair (OR: 0.25; 95% CI: 0.09 to 0.69; p = 0.008), but when the entirety of the SR strategy was compared with PR, there was no difference in the risk of in-hospital mortality between groups (OR: 0.57; 95% CI: 0.26 to 1.24; p = 0.16). Similarly, although components of the SR pathway demonstrated lower rates of complications, there were no differences in the rate of procedural complications (OR: 0.84;95%CI:0.6to1.19; p = 0.33) or hospital complications (OR: 1.13; 95% CI: 0.79 to 1.61; p =0.51) between the treatment groups when the cumulative therapeutic pathways were compared.
The authors tried to address the vital issue of comparing staged repair vs. primary repair in the setting of symptomatic neonates with tetralogy of Fallot. While a well-designed Randomized Controlled Trial would make the treatment groups well balanced to make an unbiased comparison of two treatment strategies – the large sample size from a research collaborative gave the authors unique opportunity to apply statistical methodology to adjust patient differences and provide a meaningful comparison of outcomes. Given that early mortality, neonatal morbidity, and procedural complications were lower in the SR group, whereas cumulative morbidity and reinterventions favored the PR group, the authors conclude that an individualized, case-based approach to the initial interventional strategy is warranted.