Genetic Insights from Consanguineous Cardiomyopathy Families.

Inherited cardiomyopathies are a prevalent cause of heart failure and sudden cardiac death. Both hypertrophic (HCM) and dilated cardiomyopathy (DCM) are genetically heterogeneous and typically present with an autosomal dominant mode of transmission. Whole exome sequencing and autozygosity mapping was carried out in eight un-related probands from consanguineous Middle Eastern families presenting with HCM/DCM followed by bioinformatic and co-segregation analysis to predict the potential pathogenicity of candidate variants. We identified homozygous missense variants in TNNI3K, DSP, and RBCK1 linked with a dilated phenotype, in NRAP linked with a mixed phenotype of dilated/hypertrophic, and in KLHL24 linked with a mixed phenotype of dilated/hypertrophic and non-compaction features. Co-segregation analysis in family members confirmed autosomal recessive inheritance presenting in early childhood/early adulthood. Our findings add to the mutational spectrum of recessive cardiomyopathies, supporting inclusion of KLHL24, NRAP and RBCK1 as disease-causing genes. We also provide evidence for novel (recessive) modes of inheritance of a well-established gene TNNI3K and expand our knowledge of the clinical heterogeneity of cardiomyopathies. A greater understanding of the genetic causes of recessive cardiomyopathies has major implications for diagnosis and screening, particularly in underrepresented populations, such as those of the Middle East.

Different outcomes of balloon atrial septostomy and the association of C677T polymorphism in MTHFR gene on TGA children.

Balloon atrial septostomy (BAS) remains an essential palliative interventional procedure in neonates with transposition of great arteries (TGA) and restrictive inter-circulatory mixing (low saturation) that does not respond to prostaglandin E1 therapy for maintaining ductal patency. The short- and intermediate-term outcomes of BAS were evaluated in patients with TGA, and the association of C677T polymorphism in the MTHFR gene was considered on these patients at Solemani Center for Heart Diseases, Dr. Jamal Ahmad Rasheed Pediatric Teaching Hospital, and Shar Hospital in Sulaymaniyah city. For this purpose, a retrospective study was used to evaluate short- and intermediate-term outcomes of BAS in 65 consecutive neonates who have been diagnosed with TGA and restrictive inter-circulatory mixing using echocardiography in three leading hospitals in Sulaymaniyah city, during the study period from June 2011 until January 2020. Also, for genetic polymorphism assessments, in addition to 65 patients, 65 healthy children were included in the study. 2ml of intravenous blood was collected and genomic DNA was purified from peripheral blood using the Blood genomic DNA extraction kit (Life Science, USA). PCR-RFLP method was used to determine the genotype of the subjects. All 65 of the neonates diagnosed with TGA were included in this study; 61 of the cases underwent the Rashkind procedure at a median age of 15 days, and four of the neonates died before the process. Prostaglandin E1 infusion was implemented on five of the cases before the procedure, three of whom remained hypoxic. All procedures were performed successfully under the echocardiography guide, but in 26 cases, the process was conducted with the aid of fluoroscopy with an improvement of mean SPO2 (52.59% ±7.84 to 86.57% ±3.39). An excellent short-term outcome was seen in 85.2% of the cases. Forty-three of the cases underwent the operation at the median age of six months. At the median age of 32 months, 60.7% of the cases had a good outcome on the follow-up. The results also showed a significant difference between the two groups in genotypes and alleles (P<0.05). This result confirms the relationship between C667T polymorphism of the MTHFR gene and transposition of great arteries disease. BAS is an effective palliative procedure in neonates with dextro-transposition of the great arteries (d-TGA) and can be safely performed at the bedside using echocardiography. It has an excellent short-term outcome and has a relatively good intermediate-term effect, but this depends on the later performed correction operation.

Early Detection of Iron Overload Cardiomyopathy in Transfusion Dependent Thalassemia Patients in Sulaimaniyah City, Iraq.

Background: Lifelong blood transfusion is recommended for patients with transfusion-dependent thalassemia (TDT) that lead to iron overload and results in cardiomyopathy (CM). Aim: To assess the accuracy of several electrocardiographic (ECG) data in patients at high risk of arrhythmia, early detection of structural and functional changes in left atrium and ventricle using ECG and echocardiography (two dimensional, M-mode echocardiography along with Doppler studies), and to observe the correlations between plasma B-type atrial natriuretic peptide (BNP)/serum ferritin and ECG with Doppler as well as echocardiographic changes in patients with TDT. Methods: The current prospective case-control study included 75 TDT patients and 74 control subjects with the mean age of 9.55 and 9.93 years, respectively. Participants were assessed for the socio-demographic, physical examinations, serum ferritin, plasma BNP, ECG, 2D echocardiography, and tissue/pulse wave Doppler. Results: The mean of serum ferritin and plasma BNP were significantly (p<0.001) higher in the cases (1475.19 ng/mL and 47.63 pg/mL, respectively) than controls (41.3 ng/mL and BNP 23.37 pg/mL, respectively). ECG findings showed significant higher P-wave dispersion, QRS duration, QT duration and dispersion, and JTc dispersion in cases than controls. Echocardiography findings revealed diastolic dysfunction with preserved ejection fraction (EF) in thalassemia cases, as well as significant higher left ventricular (LV) mass, LV internal diameters during systole and diastole (LVIDs and d) and LV posterior wall thickness during diastole (LVPWd) in cases than controls (p<0.05). Also, a significant (p<0.05) correlation between BNP and QT dispersion was found in patients. Conclusion: These findings suggest the usefulness of ECG, 2D echocardiographic, Doppler studies and plasma BNP, with no significant beneficial effect of serum ferritin level in detecting early cardiac changes in patients with TDT.

Pediatric COVID-19 infection in Sulaimaniyah Governorate, Iraq.

BACKGROUND: COVID-19 is a severe acute respiratory syndrome caused by SARS-CoV-2. OBJECTIVE: To study the demographic and clinical presentations of COVID-19 with their types including MIS-C and Kawasaki among children who were admitted to Doctor Jamal Ahmad Rashid Pediatric Teaching Hospital (DJARPTH) at Sulaimaniyah city, Iraq. PATIENTS AND METHODS: A prospective cohort study was conducted from June to December 2020 in which 50 cases suspected of COVID-19 were enrolled in the study that was admitted at the first visit to the emergency department of DJARPTH and their age ranged between 3 months to 14 years. Then, the collected data were divided into 3 groups: COVID-19, Kawasaki disease (KD), and MIS-C. RESULTS: The fever was the most common presented symptom in all cases with COVID-19 regardless of the severity. COVID-19 may be presented as KD as well as MIS-C. There is an increase in the number of Kawasaki cases since 2019 by 6.7 fold due to the increased number of COVID-19 cases in children. Death was more related to MIS-C and primary COVID-19 diseases. Most COVID-19 cases presented with pericardial effusion; although coronary involvement and LV dysfunction mostly seen with MIS-C cases. CONCLUSION: COVID-19 is not uncommon in pediatric patients and it presents as either primary, MIS-C, and KD. Most of the deaths and ICU outcomes were related to MIS-C presentations.