Systemic Venous Reconstructions During Pediatric Heart Transplantation

Background: Congenital heart disease continues to be an important indication for pediatric heart transplantation (HT) and is often complicated by systemic venous anomalies. The need for reconstruction, surgical technique used, as well as the outcomes of these have limited documentation. Methods: Descriptive, retrospective study of patients transplanted at Emory University between 2006 and 2017. We reviewed surgical data, follow-up, and interventions for patients necessitating venous reconstruction during transplantation. Results: A total of 179 transplants were performed during the time period of which 74 (41%) required systemic venous reconstruction. Mean age at transplant was 6.3 (±6.16) years, and 74.3% of these patients carried a diagnosis of single ventricle; 51 (68.9%) of 74 patients required pulmonary artery reconstruction at the time of HT. Forty patients required superior vena caval reconstruction, while 22 patients required inferior vena caval reconstruction due to prior palliation or anomaly. Venous anomalies along with other anatomic features necessitated biatrial transplantation in four patients. Posttransplant evaluation revealed systemic venous stenosis in 14 (18.9%) of 74 patients. Eight (10.8%) patients required 12 interventions for the systemic veins. Patients with bilateral Glenn anastomosis prior to transplant were at high risk for the development of stenosis and needing interventions. Systemic venous complications were uncommon in those with native systemic veins without Glenn or Fontan procedure. Conclusion: Systemic venous reconstruction needs are high in pediatric HT. Posttransplant stenosis and the need for interventions are relatively common. Current techniques for systemic venous reconstruction for complex congenital heart disease patients may deserve further review to optimize these outcomes.

Developmental Venous Anomalies are a Genetic Primer for Cerebral Cavernous Malformations

Cerebral cavernous malformations (CCM) are a neurovascular anomaly that may occur sporadically in otherwise healthy individuals, or be inherited by autosomal dominant mutations in the genes that encode the proteins of the CCM signaling complex (KRIT1, CCM2, or PDCD10)1–4. CCMs have long been known to follow a genetic two-hit model where lesion formation is initiated by somatic mutations resulting in biallelic loss of a CCM complex gene5–8. Recent studies have shown that somatic mutations in MAP3K3 and PIK3CA also contribute to CCM pathogenesis9–11; however, it remains unclear how these mutations contribute to sporadic versus familial cases. Here we show that somatic mutations in MAP3K3 are mutually exclusive with mutations in CCM complex genes and that mutations in MAP3K3 contribute to sporadic, but not familial CCM. Using single-nucleus DNA sequencing, we show that co-occurring MAP3K3 and PIK3CA mutations are present within the same clonal population of cells. Furthermore, we identify PIK3CA mutations in CCM-associated developmental venous anomalies (DVA). It has long been known that sporadic CCM often develop in the vicinity of a DVA. However, the underlying cause of this association is unknown12–14. In this first report of the molecular pathology of CCM-associated DVA, we find that the identical PIKC3A mutation is found in both the DVA and its associated CCM, but that an activating MAP3K3 mutation appears only in the CCM. These results support a mechanism where DVA develop as the result of a PIK3CA mutation, creating a region of the brain vasculature that functions as a genetic primer for CCM development following acquisition of an additional somatic mutation.

Spontaneous regression of a symptomatic developmental venous anomaly with capillary stain

Background Developmental venous anomalies are considered benign lesions; however, they can become symptomatic. A capillary stain, which is an atypical angiographical feature of developmental venous anomalies, is reported to be relevant to symptomatic developmental venous anomalies. Case description A 20-year-old man with no pertinent medical history had an epileptic seizure. Magnetic resonance imaging showed severe focal oedema and gadolinium contrast enhancement in the right precentral gyrus and inferior frontal gyrus adjacent to the Sylvian fissure, indicating venous congestion; these presentations had not been observed on magnetic resonance imaging 8 months before. Digital subtraction angiography revealed a developmental venous anomaly with capillary stain. After conservative treatment, the brain oedema resolved spontaneously and contrast enhancement of the lesion reduced significantly. Conclusion We report a rare case of a symptomatic developmental venous anomaly with unique radiological characteristics and its natural and clinical evolution. Despite the presence of a capillary stain, our patient exhibited temporary exacerbations and spontaneous regression, suggesting that the capillary stain was associated with a reversible condition. This is the first report to detail the spatiotemporal changes of a developmental venous anomaly with capillary stain through imaging, suggesting that regular follow-up imaging is warranted in the management of patients with developmental venous anomalies.