Background: Risk factors for diastolic dysfunction in hypertrophic cardiomyopathy (hcM) are poorly understood. We investigated the association of variants in hypoxia-response genes with phenotype severity in pediatric hcM. Methods: a total of 80 unrelated patients <21 y and 14 related members from eight families with hcM were genotyped for six variants associated with vascular endothelial growth factor a (VEGFA) downregulation, or hypoxia-inducible factor a (HIF1A) upregulation. associations between risk genotypes and leftventricular (LV) hypertrophy, LV dysfunction, and freedom from myectomy were assessed. Tissue expression was measured in myocardial samples from 17 patients with hcM and 20 patients without hcM. results: age at enrollment was 9 ± 5 y (follow-up, 3.1 ± 3.6 y). Risk allele frequency was 67% VEGFA and 92% HIF1A. Risk genotypes were associated with younger age at diagnosis (P < 0.001), septal hypertrophy (P < 0.01), prolonged e-wave deceleration time (eWDT) (P < 0.0001) and isovolumic relaxation time (IVRT) (P < 0.0001), and lower freedom from myectomy (P < 0.05). These associations were seen in sporadic and familial hcM independent of the disease-causing mutation. Risk genotypes were associated with higher myocardial hIF1a and transforming growth factor B1 (TGFB1) expression and increased endothelialfibroblast transformation (P < 0.05). conclusion: HIF1A-upregulation and/or VEGFA-downregulation genotypes were associated with more severe septal hypertrophy and diastolic dysfunction and may provide genetic markers to improve risk prediction in hcM.
Objective: Custodiol is an intracellular, crystalloid cardioplegia solution that is a single-dose alternative to multi-dose cold blood cardioplegia; however, there is scarce data regarding its use in infants and children. The objective of this study was to compare its impact on myocardial function in infants. Methods: Single-center retrospective review including 132 patients <12 months old undergoing biventricular repair. There were 106 patients who received single-dose Custodiol and 27 patients who received multi-dose blood cardioplegia. Demographic and echocardiographic data were compared between the two groups. Results: Patients receiving Custodiol were slightly younger (100 ± 62 days) and lower weight (4.7 ± 1.3 kg) compared to 152 ± 86 days and 5.2 ± 1.3 kg for blood cardioplegia (p < 0.05). The Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery Congenital Heart Surgery score was similar between both groups. Average cardiopulmonary bypass time was similar between both groups (Custodiol 93 ± 54 minutes vs. blood 81 ± 44 minutes, p = 0.46) as was aortic cross-clamp time (Custodiol 58 ± 33 minutes vs. cold blood 53 ± 33 minutes, p = 0.62). Pre-operative left ventricular ejection fraction was similar for blood 73 ± 8% versus Custodiol 70 ± 9%, p = 0.21. There was also no intergroup difference in left ventricular ejection fraction 24 hours post op (blood 64 ± 9% vs. Custodiol 65 ± 12%, p = 0.53) or at discharge (blood 66 ± 10% vs. Custodiol 66 ± 11%, p = 0.95). The pre-operative right ventricle function by fractional area change was also similar in blood cardioplegia (46 ± 13%) versus Custodiol (48 ± 9%, p = 0.38) and showed similar drops in parameters in the two groups 24 hours after surgery and at discharge. Conclusion: Single-dose Custodiol is as safe as blood cardioplegia for myocardial protection in congenital cardiac surgery for the cross-clamp times evaluated in this study. Evaluation at longer cross-clamp times would be helpful to determine if there is a greater benefit to single-dose Custodiol versus more repeated doses of blood cardioplegia for longer cross-clamp times.
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