Identification of De Novo and Rare Inherited Copy Number Variants in Children with Syndromic Congenital Heart Defects.

Congenital heart defects (CHDs) are the most common birth defects in neonatal life. CHDs could be presented as isolated defects or associated with developmental delay (DD) and/or other congenital malformations. A small proportion of cardiac defects are caused by chromosomal abnormalities or single gene defects; however, in a large proportion of cases no genetic diagnosis could be achieved by clinical examination and conventional genetic analysis. The development of genome wide array-Comparative Genomic Hybridization technique (array-CGH) allowed for the detection of cryptic chromosomal imbalances and pathogenic copy number variants (CNVs) not detected by conventional techniques. We investigated 94 patients having CHDs associated with other malformations and/or DD. Clinical examination and Echocardiography was done to all patients to evaluate the type of CHD. To investigate for genome defects we applied high-density array-CGH 2 × 400K (41 patients) and CGH/SNP microarray 2 × 400K (Agilent) for 53 patients. Confirmation of results was done using Fluorescent in situ hybridization (FISH) or qPCR techniques in certain cases. Chromosomal abnormalities such as trisomy 18, 13, 21, microdeletions: del22q11.2, del7q11.23, del18 (p11.32; p11.21), tetrasomy 18p, trisomy 9p, del11q24-q25, add 15p, add(18)(q21.3), and der 9, 15 (q34.2; q11.2) were detected in 21/94 patients (22%) using both conventional cytogenetics methods and array-CGH technique. Cryptic chromosomal anomalies and pathogenic variants were detected in 15/73 (20.5%) cases. CNVs were observed in a large proportion of the studied samples (27/56) (48%). Clustering of variants was observed in chromosome 1p36, 1p21.1, 2q37, 3q29, 5p15, 7p22.3, 8p23, 11p15.5, 14q11.2, 15q11.2, 16p13.3, 16p11.2, 18p11, 21q22, and 22q11.2. CGH/SNP array could detect loss of heterozygosity (LOH) in different chromosomal loci in 10/25 patients. Array-CGH technique allowed for detection of cryptic chromosomal imbalances that could not be detected by conventional cytogenetics methods. CHDs associated with DD/congenital malformations presented with a relatively high rate of cryptic chromosomal abnormalities. Clustering of CNVs in certain genome loci needs further analysis to identify candidate genes that may provide clues for understanding the molecular pathway of cardiac development.

Interprofessional learning experiences: Exploring the perception and attitudes of Saudi Arabian medical and dental students.

OBJECTIVE: The objective of this study is to evaluate the awareness and attitudes of medical and dental students regarding interprofessional learning (IPL). METHODS: A cross-sectional study was conducted with 278 female undergraduate Medical and Dental students from Princess Nourah bint Abdulrahman University, Riyadh. These students undertook IPL in the Foundation block, in basic science teaching, clinical skills' laboratories and in professionalism and learning skills' modules. A modified, validated RIPLS questionnaire with four subscales and 29 items was used to collect data regarding their perception and attitudes towards shared learning. A five-point Likert scale was used with a value ranging from 1 (strongly disagree) to 5 (strongly agree) for each item. Factor analysis was done using Varimox rotation. Student's t test was applied to detect difference between mean scores of medical and dental student's responses Results: The mean age of respondents was 19.8 ± 1.7 years with the majority in the second year of each program. There was no difference in mean responses of the medical and dental students. The respondents favored shared learning in the areas of professional skills and patient care. They agreed that IPL helps to develop respect, trust and appreciation for other professions; however, both groups preferred to learn uni-professionally with regard to developing discrete professional identities and roles. CONCLUSIONS: There is an overall positive response towards IPL and the value of team work; however, more attention needs to be paid to enabling students to learn about the specific roles of each profession in the healthcare team.

Health Care Delivery for Heart Failure Patients During The COVID-19 Pandemic; A Consensus of The Saudi Heart Failure Working Group (SAUDI-HF).

The Coronavirus disease 2019 (COVID-19) pandemic led to global and national rapid health system changes to treat the affected patients and prevent the spread of the virus. The social distancing, redirecting resources, and nationwide lockdown led to the cancellation of non-urgent hospital visits and interruption of continuity of care for patients with chronic cardiac conditions such as heart failure (HF). This consensus document addresses the domains of health care delivery that are affected by the pandemic. It explains the current situation of health care delivery to heart failure patients and further recommendation on how to overcome this. Thus, maintaining quality and continuity of care to the HF population.

Risk of sudden cardiac death in young athletes: which screening strategies are appropriate?

Resources are not available to comprehensively evaluate all young athletes before participation in competitive sports. Therefore, the cardiovascular evaluation of young athletes needs to be targeted at high-risk areas and focus on the individuals who are at greatest possible risk: those who have suggestive, even if minor, symptoms, and those who have a family history of sudden death or premature cardiac disease.

Evaluation of risk factors for prediction of outcome in fetal spectrum of atrioventricular septal defects.

BACKGROUND: Atrioventricular septal defects (AVSD) are very commonly diagnosed in utero. Heterotaxy/chromosomal abnormalities frequently coexist with AVSD. However, outcomes of fetal AVSD are not precisely known. We attempted to define mortality risk factors in AVSD. METHOD: We retrospectively searched our database, electronic records, and echocardiograms with diagnosis of fetal AVSD from 2003 to 2012. We investigated the following risk factors: atrial situs, heart rate/rhythm, ventricular dominance/morphology, atrioventricular valve regurgitation, cardiothoracic ratio, ejection fraction, and extracardiac anomalies. RESULTS: Forty-five fetuses with a median gestational age of 28 weeks (17.5-37.1) were determined to have AVSD during the 10 years, of which 12 were either lost to follow-up (6) or underwent termination (6). There were 16 deaths (48%); two died in utero. Isomerism was identified in 17 of 45 (37%) fetuses (11 left atrial, 6 right atrial isomerism) and chromosomal abnormalities were identified in 12 (27%). Twenty-eight of 33 fetuses, not lost to follow-up or terminated, had extracardiac anomalies which had associated increased mortality (57% vs. 0%, P = .04). Heart block (75% vs. 43%, P = .12), left ventricular noncompaction (80% vs. 43%, P = .17), and isomerism (63% vs. 41%, P = .28) were associated with mortality but without statistical significance. Twenty-five of 45 (56%) had unbalanced AVSD. Positional abnormalities of the great arteries or semilunar valve stenosis were present in 20/45 (44%) while venous anomalies were present in 16/45 (36%). Presence of ventricular dominance, atrioventricular valve regurgitation, elevated cardiothoracic ratio, or diminished ejection fraction were not associated with mortality. CONCLUSION: Overall mortality rate for fetuses with AVSD was 48%. The presence of extracardiac anomalies is an independent risk factor for prediction of fetal or neonatal demise. Heart block, isomerism, and noncompaction in fetal AVSD appear to be associated with poor outcomes as well but did not reach statistical significance. This information is useful for counseling parents with fetus AVSD.

A novel method for the assessment of the accuracy of computing laminar flow stroke volumes using a real-time 3D ultrasound system: In vitro studies.

AIMS: Laminar flow stroke volume (SV) quantification in the ascending aorta or pulmonary artery can provide a measure for determining cardiac output (CO). Comparing flows across different valves can also compute shunt volumes and regurgitant fractions. Quantification methods for 3D color Doppler laminar flow volumes have been developed using reconstructive 3D, but these are cumbersome and time-consuming both in acquisition and measurement. Our study evaluated newly developed color Doppler mapping with real-time live 3D echo to test velocity, spatial and temporal resolution for computing SV. METHODS AND RESULTS: Five rubber tubes (diameters=3.0, 2.25, 2.0, 1.9, 1.7 cm), a freshly dissected porcine aorta (Ao) and a pulmonary artery (PA) (both 2-3 cm diameter) were connected to a pulsatile pump in a water bath. Different SV, from 10 to 80 ml/beat, were studied at pump rates of 40-60 bpm in this phantom model with flow quantified by timed collection. The Nyquist limit was set between 43 and 100 cm/s and frame rate ranged from 14 to 23/s. ECG triggered 3D color Doppler volumes were acquired with a 2-4 MHz probe. The digital scan line data from the 3D volumes, with retained velocity assignments, was exported and analyzed offline by MatLab custom software. Close correlations were found between 3D calculated SV and reference data for all tubes (r=0.98, y=1.14x-1.69, SEE=2.82 ml/beat, p<0.0001). Both Ao and PA flows were also highly correlated with the reference measurements (PA: r=0.98, SEE=3.17 ml/beat; Ao: r=0.99, SEE=3.20 ml/beat). CONCLUSIONS: Real-time 3D color Doppler method could provide an efficient, accurate and reliable method for clinical evaluation and quantification of flow volumes in patients.

Fetal rhabdomyoma: prenatal diagnosis, clinical outcome, and incidence of associated tuberous sclerosis complex.

OBJECTIVES: We reviewed our institution's experience with fetal cardiac rhabdomyoma to document the clinical outcome and incidence of associated tuberous sclerosis complex (TSC) and compared our findings with those of patients diagnosed with cardiac rhabdomyoma after birth. STUDY DESIGN: We reviewed the medical records of all cases diagnosed prenatally and postnatally with cardiac rhabdomyoma between January 1990 and June 2002. RESULTS: Twenty fetuses with cardiac rhabdomyoma were diagnosed at 28.4+/-6.0 weeks' gestational age. Of 19 continued pregnancies, there was one spontaneous intrauterine death, and 18 were delivered at term. Although none had prenatal hemodynamic complications, after birth seven had cardiac symptoms requiring medical (n=4) or surgical intervention (n=3). On follow-up, 15 of 19 with available outcome had TSC (79%), including six with neurodevelopmental disease. Over the same period, 26 patients were diagnosed with cardiac rhabdomyoma postnatally. Most (77%) were referred for cardiac assessment after findings suggesting TSC. On follow-up, TSC was confirmed in 25 (96%), including 22 with neurodevelopmental disease. The incidence of cardiac symptoms and TSC was not statistically different between the prenatal and postnatal diagnosis groups. CONCLUSIONS: Cardiac rhabdomyomas are benign from the cardiovascular standpoint in most affected fetuses. As observed in postnatally diagnosed cardiac rhabdomyoma, TSC is diagnosed in most cases of fetal cardiac rhabdomyoma.