Neurodevelopmental outcome in hypoplastic left heart syndrome after hybrid procedure

Abstract

Background: Little is known about the mid-term outcome and brain development in patients following the hybrid approach for hypoplastic left heart syndrome (HLHS). This study investigates neurodevelopmental outcome, quality of life (QoL) and brain MRI findings in HLHS preschoolers treated with the hybrid approach.

Methods: Twenty HLHS patients (60% males) have been examined after neonatal hybrid Stage I and comprehensive stage II operation at the Pediatric Heart Center Giessen, Germany, between 2012 and 2016. Patients were evaluated with the Bayley Scales of Infant and Toddler Development III (Bayley-III), neurological examination, the Preschool Children Quality of Life Questionnaire (TAPQOL) at age 26.5±3.6 months, and again at 39.7±3.9 months with the Pediatric Cardiac Quality of Life Inventory (PCQLI). Furthermore, brain volumetric measurements and conventional brain MRI findings (27.3±4.5 months) were analyzed and compared with six healthy controls (29.2±11.1 months, P=0.53). Children with verified genetic comorbidities were excluded.

Results: Mean cognitive, language, and motor composite scores on the Bayley-III were not different from healthy norms (100±15), and were 101±9.3 (P=0.48), 100±13 (P=0.93), and 98±11.7 (P=0.45), respectively. Status post stroke was the most common brain MRI abnormality, and was found in 3/19 (16%) patients, most common affecting the middle cerebral artery territory. In comparison to controls, total white matter volumes were reduced (P=0.014), and cerebrospinal fluid (CSF) volumes were increased (P=0.042) in patients. Overall health-related QoL in 2 to 3 years aged children HLHS was good, but inferior scores in the motor subscale were noted compared to healthy norms (P=0.007). However, at 3 to 4 years, parents reported comparable QoL for their children in the PCQLI to children with biventricular heart lesion.

Conclusions: HLHS patients followed by hybrid approach without major complications show a favorable neurodevelopment at 2-3 years of age. Despite extensive health-related burden, the vast majority of Fontan preschoolers with HLHS showed a good health-related QoL. Nevertheless, comprehensive care and establishing routine follow-up examinations are important to recognize long-term challenges and further improve neurodevelopmental outcome of this high-risk patient population.

Keywords: Congenital heart disease (CHD); brain development; hybrid procedure; hypoplastic left heart syndrome (HLHS); neurodevelopmental outcome.

Figure 1

Flow chart of patients included in the final analysis. Of 44 patients with left sided heart lesions, 16 patients with HLHC were excluded. Eight of the 28 eligible patients were excluded, leaving 20 patients with HLHS for final analysis. ^§, 16 patients with HLHC: n=11 biventricular repair, n=3 univentricular palliation, n=2 deceased (one case with cardiac failure and multi organ failure on second run on ECMO, one patient undiagnosed prenatally suffered cardiogenic shock). ^‡, 4 deceased HLHS patients. Palliative care in n=2; one case with obstructive TAPVR, one prenatally undiagnosed individual and parental decision of palliative treatment. One case with cardiogenic shock due to high-grade Re-ISTA after stage I, one case s/p reanimation after apnea/seizure at home after stage II. HLHC, hypoplastic left heart complex; ECMO, extracorporal membrane oxygenation; TAPVR, total anomalous pulmonary venous return; ISTA, aortic isthmus stenosis.

Figure 2

Median growth indices (weight, height, and head circumference) at birth, before stage II, and at the time of follow-up pre-Fontan of 20 children with HLHS following the hybrid approach. Horizontal lines depict 50^th percentile and lower and upper boundary of 3^rd and 97^th percentile, dashed horizontal lines depict lower and upper boundary of 10^th and 90^th percentile; dots represent outliers. *, P<0.05; **, P<0.01; ***, P<0.001. HLHS, hypoplastic left heart syndrome.

Figure 3

Percentage of development within the normal range and of moderate developmental delay and of good, intermediate and poor health-related quality of life. (A) Distribution of CCS, LCS and MCS Bayley-III scores of 2- to 3-year-old study patients. Y-axis shows percentage of scores below 85, that equates to 1 SD below the norm (dark gray bar). Light gray bars represent percentage of patients within the normal range (above 85); (B) frequency of total score and sub-scores of all patients evaluated at 3–4 years of age with the PCQLI, divided into three categories; good (light gray bar), intermediate (dark gray bar), and poor (black bar). CCS, cognitive composite score; LCS, language composite score; MCS, motor composite score.

Figure 4

Cerebral MRI scans of two HLHS patients before Fontan procedure. Coronar (A,B) and corresponding axial scans (C,D) of two HLHS patients. A and C, no detected abnormalities. B and D, residual ischemic stroke in the gray matter (right A. cerebri media, <1/3) and focal white matter injuries in the central white matter. MRI, magnetic resonance imaging; HLHS, hypoplastic left heart syndrome.