Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart malformations, characterized by underdevelopment of the structures in the left heart-aorta complex. The majority of cases are sporadic. Although multiple genetic loci have been tentatively implicated in HLHS, no gene or pathway seems to be specifically associated with the disease. To elucidate the genetic basis of HLHS, we analyzed 53 well-characterized patients with isolated HLHS using an integrated genomic approach that combined DNA sequencing of five candidate genes (NKX2-5, NOTCH1, HAND1, FOXC2 and FOXL1) and genome-wide screening by high-resolution array comparative genomic hybridization. In 30 patients, we identified two novel de novo mutations in NOTCH1, 23 rare patients inherited gene variants in NOTCH1, FOXC2 and FOXL1, and 33 rare patients mostly inherited copy-number variants. Some of the identified variations coexisted in the same patient. The biological significance of such rare variations is unknown, but our findings strengthen the role of NOTCH pathway in cardiac valve development, indicating that HLHS is, at least in part, a 'valve' disease. This is the first report of de novo mutations associated with isolated HLHS. Moreover, the coexistence of multiple rare variants suggests in some cases a cumulative effect, as shown for other complex disease.

After a valve sparing procedure there is a reduction of Prv/Plv ratio at medium-term follow-up; in our study this reduction was statistically significant in all patients and in the subgroup with higher postoperative ratios. A valve sparing strategy reduces pulmonary regurgitation, preserves RV function and decreases the incidence of late arrhythmias, which are the determinants of long-term outcome.

OBJECTIVES The aim of this study was to assess the incidence of vocal cord paralysis (VCP) in children after cardiovascular surgery. The secondary aims were to identify the factors potentially associated with VCP and to assess the diagnostic utility of laryngeal ultrasound (US). METHODS This study is a retrospective review of patients who underwent aortic repair, patent ductus arteriosus ligation and left pulmonary artery surgeries from 2007 to 2017. The following data were collected: patient demographics, gestational age, weight and age at surgery, comorbidities, cardiovascular anomaly and type of procedure, laryngoscopic and US evaluation results. Univariable and multivariable logistic regression models were used to identify the variables associated with VCP. RESULTS Two hundred and six patients were included in the study. Seventy-two patients (35%) were preterm and 32.5% showed comorbidities. At surgery, median age and weight were 0.6 months [interquartile range (IQR) 0.3–2.1] and 3.0 kg (IQR 1.3–4.0), respectively. Postoperatively, symptomatic patients underwent endoscopic evaluation and VCP was detected in 25 cases (12.1%). Laryngeal US was performed in 8 of these showing an excellent diagnostic relationship. On univariable analysis, factors significantly associated with VCP were prematurity, young age and lower weight at surgery and the presence of comorbidities. The presence of comorbidities and weight at surgery exhibited a significant risk of developing VCP postoperatively on multivariable analysis. CONCLUSIONS VCP is not an unusual complication of cardiovascular surgery. Certain factors were associated with VCP development but only the presence of comorbidities and weight at surgery were statistically significant on multivariable analysis. Flexible laryngoscopy is the standard diagnostic technique and laryngeal US appears to be a reliable complement.

Our data confirmed that remodeling and growth potential of the small intestine submucosal biomaterial are time dependent. Additional experiments are required to investigate the stability of the patch material over a longer period.

Background and aim. The optimal management of tracheal disruptions is still controversial. It is usually postulated that lesions wider than 1 or 2 centimetres and/or lesions of full-thickness should be treated by surgery at an early stage. Such a statement is not supported by any proven evidence. On the contrary, the conservative management of such injuries has also produced very good results according to recent reports. The aim of this study is to investigate whether conservative treatment can be safely used for wide tracheal lacerations and to assess any possible association between clinical features and modality of treatment. Methods. Records of all patients with iatrogenic and traumatic tracheal disruptions observed between January 1992 and December 2006 were collected and retrospectively reviewed. Data regarding mechanism of injury, clinical and morphological features and modalities of treatment were registered. All possible associations between clinical features and modalities of treatment were investigated. Results. 23 patients were observed overall. There were 6 males and 17 females with a median age of 58 years (range 20-84 yrs). 15 patients had undergone single tube intubation. One patient had his trachea injured during an esophagectomy. Ruptures were secondary to blunt (n=5) and open (n=2) trauma in 7 patients. Lesions varied in length between 1 and 7 centimetres (median length 3 centimetres) and all were full-thickness. The time interval until diagnosis varied between 0 and 72 hours (median 6 hours). Respiratory failure was evident in 7 patients. 16 patients (69.5%) with lacerations ranging in length between 1 and 5.5 centimetres (median length 2.75 cm) underwent conservative treatment. Seven patients (30.5%) underwent surgery. The follow up was completed for 16 patients and varied between 15 and 105 months (median 22.5). One patient died after surgical treatment. No mortality or late major sequelae were registered after conservative treatment. Female sex, absence of respiratory failure and delayed diagnosis was associated with the conservative treatment. Conclusions. Conservative treatment can play a major role even in cases of wide tracheal lacerations. Clinical rather than morphological features should be regarded as main criteria for treatment. The conservative treatment is particularly indicated in the case of stable respiratory parameters independent of the size and the depth of the lesion.