Congenital heart defects (CHD) are the most common congenital anomalies in liveborn children. In contrast to syndromic CHD (SCHD), the genetic basis of isolated CHD (ICHD) is complex, and the underlying pathogenic mechanisms appear intricate and are incompletely understood. Next to rare Mendelian conditions, somatic mosaicism or a complex multifactorial genetic architecture are assumed for most ICHD. We performed exome sequencing (ES) in 73 parent–offspring ICHD trios using proband DNA extracted from cardiac tissue. We identified six germline de novo variants and 625 germline rare inherited variants with ‘damaging’ in silico predictions in cardiac-relevant genes expressed in the developing human heart. There were no CHD-relevant somatic variants. Transmission disequilibrium testing (TDT) and association testing (AT) yielded no statistically significant results, except for the AT of missense variants in cilia genes. Somatic mutations are not a common cause of ICHD. Rare de novo and inherited protein-damaging variants may contribute to ICHD, possibly as part of an oligogenic or polygenic disease model. TDT and AT failed to provide informative results, likely due to the lack of power, but provided a framework for future studies in larger cohorts. Overall, the diagnostic value of ES on cardiac tissue is limited in individual ICHD cases.

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Although the conventional treatment of aortopulmonary (AP) window consists of reconstructive surgery with the use of cardiopulmonary bypass (CPB), some conditions like low birth weight or active respiratory tract bleeding may lead to diverting therapeutic options. We present a case of a premature 1.9 kg neonate with severe pulmonary arterial hypertension based on the association of an AP window and large patent ductus arteriosus. Because of intrabronchial hemorrhage, a conservative strategy was chosen excluding the need for heparinization and CPB. Through median sternotomy, the ductus arteriosus and AP window were clipped, effectively occluding both shunts. The postoperative course was uneventful with a rapid decrease of pulmonary artery pressure. Although classical surgical reconstruction is still advocated as primary therapy, this case illustrates the suitability of an alternative approach without the need for CPB and full heparinization in a patient with an increased risk of bleeding complications.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary anomaly commonly associated with severe but reversible left ventricular (LV) dysfunction. We present an ALCAPA case of persisting left ventricular failure with inability to wean off the ventilator and inotropes after successful coronary reimplantation, in whom pulmonary artery banding enabled bridging to myocardial recovery. Pulmonary artery banding may be considered as a bridge-to-recovery in selected cases of severe left ventricular dysfunction after ALCAPA-repair.

Case description: A 4-year old boy without significant prior history, presented with pronounced dyspnea. During clinical examination only mild hepatomegaly was present. Thoracic radiography showed significant cardiomegaly. Echocardiography revealed left ventricular dilatation and poor systolic function. Both Troponin and NT-pro-BNP level were elevated. Treatment with diuretics and inotropics was started with clinical improvement. The diagnosis of an anomalous left circumflex artery out of the right pulmonary artery was suspected by coronarography and confirmed by coronary CT. Coronary reimplantation was performed without complications. Subsequently, left ventricular dimensions normalized progressively in the next months. Discussion: Without congenital heart disease, an anomalous left circumflex artery arising from the pulmonary artery is rarely present. Symptoms and prognosis are determined by the amount of collateral circulation to provide adequate myocardial perfusion. Diagnosis of an anomalous left circumflex artery (LCx) is mostly made at adult age. However, our patient presented at young age. Even though the origin of both coronary arteries was normal, a coronary anomaly lies at the origin of his cardiac dysfunction. Treatment consisting of surgical reimplantation or coronary bypass is the primary choice. Conclusion: We present this case to highlight the importance of having a high index of suspicion of coronary artery abnormalities in children with dilated cardiomyopathy, as the prognosis can be very favorable after surgical repair. Transthoracic echocardiography is not always conclusive in showing a normal origin of both coronary arteries and certainly not for visualizing the LCx reliably. Therefore, further imaging should be considered in children with a new diagnosis of unexplained DCM.