Association of Myocardial Muscle Non-Compaction and Multiple Ventricular Septal Defects by Echocardiography.

The aim of this study is to examine the possible high association between multiple ventricular septal defect (mVSDs) and noncompaction cardiomyopathy (NCM) as same embryological origin, and the effect of depressed ventricular function in NCM cases during the follow-up, using echocardiography. A total of 150 patients with mVSDs were diagnosed in a single center in Saudi Arabia; 40 cases with isolated or associated with minor congenital heart disease were recruited. Three specialist echocardiography consultants confirmed the NCM diagnosis separately using Jenni, Chin and Patrick criteria, and myocardial function was estimated by ejection fraction at admission and at follow-up after surgery. Stata-14 to analyze the data was used. In our cohort of 40 cases with mVSD (median age at diagnosis = 0.5 years; mean follow-up = 4.84 years), 13(33%) had criteria of non-compaction confirmed by the three specialist consultants. All were operated by surgery and 11 hybrid approach (interventional & surgery). A significant relationship between abnormal trabeculations and mVSD with or without non-compaction was observed, 34% vs 66% respectively (p < 0.03, Fisher's exact test). A repeated-measures t-test found the difference between follow-up and preoperative ejection-fractions to be statistically significant (t (39) = 2.07, p < 0.04). Further, the myocardial function in the mVSD non-compaction group normalized substantially postoperatively compared with preoperative assessment (mean difference (MD) 11.77, 95% CI: 4.40-19.14), whilst the mVSD group with normal myocardium had no significant change in the myocardium function (MD 0.74, 95% CI: -4.10-5.58). Thus, treatment outcome appears better in the mVSD non-compaction group than their peers with normal myocardium. Acknowledging the lack of genetic data, it is evident the high incidence of non-compaction in this cohort of patients with mVSD and supports our hypothesis of embryonic/genetic link, unlikely to be explained by acquired cardiomyopathy.

Categorized Genetic Analysis in Childhood-Onset Cardiomyopathy.

BACKGROUND: Childhood-onset cardiomyopathy is a heterogeneous group of conditions the cause of which is largely unknown. The influence of consanguinity on the genetics of cardiomyopathy has not been addressed at a large scale. METHODS: To unravel the genetic cause of childhood-onset cardiomyopathy in a consanguineous population, a categorized approach was adopted. Cases with childhood-onset cardiomyopathy were consecutively recruited. Based on the likelihood of founder mutation and on the clinical diagnosis, genetic test was categorized to either (1) targeted genetic test with targeted mutation test, single-gene test, or multigene panel for Noonan syndrome, or (2) untargeted genetic test with whole-exome sequencing or whole-genome sequencing. Several bioinformatics tools were used to filter the variants. RESULTS: Two-hundred five unrelated probands with various forms of cardiomyopathy were evaluated. The median age of presentation was 10 months. In 30.2% (n=62), targeted genetic test had a yield of 82.7% compared with 33.6% for whole-exome sequencing/whole-genome sequencing (n=143) giving an overall yield of 53.7%. Strikingly, 96.4% of the variants were homozygous, 9% of which were found in 4 dominant genes. Homozygous variants were also detected in 7 novel candidates (ACACB, AASDH, CASZ1, FLII, RHBDF1, RPL3L, ULK1). CONCLUSIONS: Our work demonstrates the impact of consanguinity on the genetics of childhood-onset cardiomyopathy, the value of adopting a categorized population-sensitive genetic approach, and the opportunity of uncovering novel genes. Our data suggest that if a founder mutation is not suspected, adopting whole-exome sequencing/whole-genome sequencing as a first-line test should be considered.

Current outcomes of the Glenn bidirectional cavopulmonary connection for single ventricle palliation.

OBJECTIVES: The Glenn bidirectional cavopulmonary connection (BCPC) is an established procedure in multistage palliation of various single ventricle (SV) anomalies. We aimed to report the current outcomes following BCPC and to examine risk factors affecting survival and progression to the next palliation stage. METHODS: Two hundred and twenty-seven consecutive children with variable SV pathologies underwent BCPC from 2002 to 2007. Competing risk analyses were performed to model events after BCPC (death and transition to Fontan) and subsequently after Fontan (death and cardiac reoperation) and to examine the associated risk factors for poor outcomes. RESULTS: There were 139 males (61%) with a median age of 7.6 months [interquartile range (IQR) 6.0-10.8] and median weight of 6.2 kg (IQR 5.2-7.4). Forty-three patients (19%) had primary BCPC and 184 (81%) had prior palliation: aortopulmonary shunt (APS) (n=83), Norwood (n=55), pulmonary artery (PA) band (n=48), atrial septectomy (n=25), PA reconstruction (n=14), anomalous pulmonary venous connection repair (n=7) and other (n=8). Predominant ventricle was left morphology (n=122, 54%), right morphology (n=95, 42%) and two equally developed ventricles (n=10, 4%). Twenty-six patients (12%) had bilateral superior vena cava. Concomitant surgery included atrioventricular valve repair (n=18), PA augmentation (n=80), percutaneous Fontan preparation (n=34) and other (n=24). Competing risk analysis showed that 5 years following BCPC, ∼17% have died, 76% have undergone Fontan and 7% were alive awaiting or not qualifying for Fontan. On multivariable analysis, risk factors for death prior to Fontan were pulmonary vascular resistance (PVR) index of >3 WU/M2 [hazard ratio (HR) 3.9, P=0.001], dominant right ventricle (HR 2.1, P=0.03) and prior palliation other than APS (HR 0.4, P=0.03). Competing risk analysis showed that 3 years following 172 Fontan operations, ∼10% have died, 6% have undergone further cardiac surgery and 84% were alive and free from reoperation. Overall, 8-year survival following BCPC was only 74%. CONCLUSIONS: Despite established selection criteria and improved surgical technique and medical management, there is a continuous failure and attrition risk following BCPC. Outcomes are influenced by underlying cardiac anomaly; patients with dominant left ventricle (i.e. tricuspid atresia, double inlet left ventricle) having the best survival while those with dominant right ventricle (i.e. hypoplastic left heart syndrome, double outlet right ventricle with heterotaxy) having the worst survival. Increased PVR remains a significant factor affecting mortality.

Hybrid management strategy for percutaneous Fontan completion without surgery: early results.

BACKGROUND: We report early results of surgical preparation and subsequent percutaneous Fontan completion strategy for the treatment of single-ventricle defects. METHODS: Two hundred twenty-seven patients underwent bidirectional cavopulmonary connection (BDCPC) between 2002 and 2007. Thirty-four patients had lateral tunnel created at time of BDCPC, fenestrated with 10 to 14 mm openings with the cardiac superior vena cava end patched to maintain BDCPC physiology. At second stage, Fontan circulation was established by superior vena cava patch perforation, tunnel dilatation, and stenting plus fenestration device closure. RESULTS: Thirty-four patients underwent Fontan preparation with BDCPC. Median age was 7.7 months (5 to 51) and 29 patients (85%) had previous palliation. Mean bypass and ischemic times were 141 and 72 minutes, respectively. Median ventilation, intensive care, and hospital stay durations were 1, 5, and 10 days, respectively. There was one early death and two take-downs. Twenty-eight patients underwent Fontan procedure: surgical (n = 3), percutaneous (n = 25). None of the patients who underwent percutaneous Fontan completion required inotropes, chest tube insertion, or mechanical ventilation. Median intensive care and hospital stay durations were 1 and 6 days, respectively. There were no early mortalities after percutaneous Fontan but one late death and one surgical revision. Overall survival after BDCPC with Fontan preparation was 77%. CONCLUSIONS: Despite longer bypass and ischemic times, Fontan preparation at time of BDCPC is feasible and associated with encouraging early outcomes. Percutaneous Fontan completion is associated with short recovery, low morbidity and excellent early dynamics, and echocardiographic and clinical outcomes. Further follow-up is needed to confirm those favorable results.