Whole genome sequencing of families diagnosed with cardiac channelopathies reveals structural variants missed by whole exome sequencing.

Cardiac channelopathies are a group of heritable disorders that affect the heart's electrical activity due to genetic variations present in genes coding for ion channels. With the advent of new sequencing technologies, molecular diagnosis of these disorders in patients has paved the way for early identification, therapeutic management and family screening. The objective of this retrospective study was to understand the efficacy of whole-genome sequencing in diagnosing patients with suspected cardiac channelopathies who were reported negative after whole exome sequencing and analysis. We employed a 3-tier analysis approach to identify nonsynonymous variations and loss-of-function variations missed by exome sequencing, and structural variations that are better resolved only by sequencing whole genomes. By performing whole genome sequencing and analyzing 25 exome-negative cardiac channelopathy patients, we identified 3 pathogenic variations. These include a heterozygous likely pathogenic nonsynonymous variation, CACNA1C:NM_000719:exon19:c.C2570G:p. P857R, which causes autosomal dominant long QT syndrome in the absence of Timothy syndrome, a heterozygous loss-of-function variation CASQ2:NM_001232.4:c.420+2T>C classified as pathogenic, and a 9.2 kb structural variation that spans exon 2 of the KCNQ1 gene, which is likely to cause Jervell-Lange-Nielssen syndrome. In addition, we also identified a loss-of-function variation and 16 structural variations of unknown significance (VUS). Further studies are required to elucidate the role of these identified VUS in gene regulation and decipher the underlying genetic and molecular mechanisms of these disorders. Our present study serves as a pilot for understanding the utility of WGS over clinical exomes in diagnosing cardiac channelopathy disorders.

Transcatheter closure of ventricular septal defects: preliminary results in children weighing 10 kg or less.

INTRODUCTION: Ventricular septal defect is one of the commonest heart defect in children and closure of this defect with devices has seen a rapid progression over a period of time. The availability of new and safer devices has made the transcatheter closure of ventricular septal defect a suitable option even in young children. AIM: The study was done to evaluate the feasibility and complications of device closure of ventricular septal defect in children weighing 10 kg or less with different types of devices. METHODS: The present study was undertaken in a newly established dedicated Paediatric Cardiac Unit at a Tertiary Care Hospital. Relevant data were obtained retrospectively from the case files and the catheterisation records and data were analysed for first 50 patients with ventricular septal defect weighing 10 kg or less between March 2018 and March 2021. RESULTS: Among these 50 patients selected, device closure was successfully done in 45 (90%) cases while 5 (10%) attempts were unsuccessful for various reasons. The mean weight in this study was 7.46 ± 1.89 kg (2.3-10 kg), 21 (42%) cases were females while 29 (58%) were males; mean age was 19.4 ± 11.88 months (4-48 months). Right heart catheterisation study showed 21 (42%) patients with normal pulmonary artery pressures (no pulmonary artery hypertension). Among 29 patients with pulmonary arterial hypertension, 13 patients (22%) were having mild pulmonary arterial hypertension, 4 (8%) were with moderate pulmonary arterial hypertension, and 12 (24%) were with severe pulmonary arterial hypertension. Mean Qp/Qs was 2.73 ± 0.72 (2.5-4.5) and mean pulmonary vascular resistance was 1.5 ± 1.04 (0.6-4.6 WU). Amplatzer Duct Occluder (ADOI) was used in 15 (30%) cases, 27 (52%) cases were closed with Amplatzer Duct Occluder (ADOII), and the 3 (6%) cases closure was done with Amplatzer muscular ventricular septal defect occluder. CONCLUSIONS: Transcatheter closure of ventricular septal defect in children 10 kg or less is feasible and safe alternative to surgical ventricular septal defect closure. The immediate and short-term outcomes have proven this method to be safe and valid.

Anomalies Unveiled: A Fascinating Case Study of Type I Pulmonary Artery-to-Left Atrium Fistula.

The pulmonary artery-to-left atrium (LA) fistula is one of the rare and unique structural causes of silent cyanosis. This correctable abnormality can be identified by having a high index of clinical suspicion and appropriate investigations using echocardiography and cardiac computed tomography (CT). We report an eight-year-old child who had worsening exertional dyspnea, long-standing central cyanosis, and recurrent infections. A large-sized fistula connecting the right pulmonary artery (RPA) to the LA with all the right- and left-sided pulmonary veins showed normal drainage into the LA, suggesting a type I RPA-to-LA fistula, which was diagnosed on cardiac CT. Percutaneous closure using the occluder device is planned as further management for the patient.

Double Outlet of Both Ventricles With an Unusual Relationship of the Great Arteries.

Double outlet both ventricles (DOBV) is a rare form of ventriculo-arterial connection wherein the outlet septum is perpendicular to the crest of the apical muscular ventricular septum, thus committing both arterial roots equally to both ventricles. The anomaly has been described in very few reports, with clinical reports being even rarer. We report perhaps the first case of DOBV in which the relationship of the arterial roots themselves is discordant relative to the ventricular topology.

Impact of COVID-19 pandemic on pediatric cardiac services in India.

BACKGROUND: COVID-19 pandemic has disrupted pediatric cardiac services across the globe. Limited data are available on the impact of COVID.19 on pediatric cardiac care in India. AIMS: The aims are to study the impact of COVID-19 pandemic on the care of children with heart disease in India in terms of number of outpatient visits, hospitalizations, catheter-based interventions, and cardiac surgeries. SETTINGS AND DESIGN: This is a retrospective, multicentric, observational study. METHODS: We collected monthly data on the number and characteristics of outpatient visits, hospitalizations, catheter-based interventions, and cardiac surgeries and major hospital statistics, over a period of 5 months (April to August 2020), which coincided with the first wave of COVID-19 pandemic in India and compared it with data from the corresponding months in 2019. RESULTS: The outpatient visits across the 24 participating pediatric cardiac centers decreased by 74.5% in 2020 (n = 13,878) as compared to the corresponding period in 2019 (n = 54,213). The reduction in the number of hospitalizations, cardiac surgeries, and catheterization procedures was 66.8%, 73.0%, and 74.3%, respectively. The reduction in hospitalization was relatively less pronounced among neonates as compared to infants/children (47.6% vs. 70.1% reduction) and for emergency surgeries as compared to elective indications (27.8% vs. 79.2%). The overall in-hospital mortality was higher in 2020 (8.1%) as compared to 2019 (4.8%), with a higher postoperative mortality (9.1% vs. 4.3%). CONCLUSIONS: The current COVID-19 pandemic significantly impacted the delivery of pediatric cardiac care across India with two-third reduction in hospitalizations and cardiac surgeries. In an already resource-constrained environment, the impact of such a massive reduction in the number of surgeries could be significant over the coming years. These findings may prove useful in formulating strategy to manage subsequent waves of ongoing COVID-19 pandemic.

Clinical score to detect congenital heart defects: Concept of second screening.

INTRODUCTION: Neonatal screening for congenital heart defects at birth can miss some heart defects, sometimes few critical ones, and the scenario is even worse in those neonates who had never undergone a neonatal checkup (home deliveries). Immunization clinic can serve as a unique opportunity as the second checkpoint for the screening of the children. A history- and examination-based test can serve as an effective tool to screen out children with heart defects. AIMS AND OBJECTIVES: The aim of this study was to establish the sensitivity and specificity of a clinical screening tool for the identification of congenital heart defects at the first visit of an infant after birth for immunization. MATERIALS AND METHODS: This is a cross-sectional observational study which the consecutive children presenting at 6 weeks of age for immunization or any child presenting for the first time (outborn delivery) till 6 months of age in the immunization clinic were subjected to detailed history and examination and findings were recorded on a predesigned pro forma and a clinical score was calculated. All these children were then subjected to echocardiography for confirmation of the diagnosis of congenital heart disease (CHD), and the sensitivity and specificity of the test were recorded. OBSERVATIONS AND RESULTS: A total of 970 babies were screened, out of them 31 were diagnosed with CHD and 18 had undergone neonatal screening at birth. A clinical score of 3 or more had more chances of detecting CHD. The sensitivity of the cutoff score as 3 was 96.77% and specificity was 98.72, with a positive predictive value of 71.43%, a negative predictive value of 99.89%, and an accuracy of 98.66%. CONCLUSIONS: The history- and examination-based tool is an effective method for early identification of CHD and can easily be used by peripheral workers working in remote places with poor resources enabling prompt referral.

Common inflammatory markers after cardiac surgery in infants and their relation to blood stream sepsis.

BACKGROUND: Limited information exists on trends of common inflammatory markers after infant heart surgery and their role in identifying post-operative sepsis. METHODS: 275 consecutive infants undergoing cardiac surgery (231 with and 44 without Cardiopulmonary Bypass) were studied prospectively. Daily trends (0-4 day post-operative) of leucocyte counts, platelet counts and C-reactive protein were recorded. Association of these trends with early post-operative bloodstream sepsis, Cardiopulmonary Bypass and surgical outcomes were studied. OBSERVATIONS: Trends of these inflammatory markers were noted. While off-Cardiopulmonary Bypass Surgery, and sepsis were associated with a statisticaly insignificant rise in total leucocyte count peaking on first post-operative day, Cardiopulmonary Bypass exposure was associated with significant decline (p = 0.002), more pronounced with Cardiopulmonary Bypass-exposure exceeding 150 min. Percentage of neutrophils showed a rise (maximum on first post-operative day) but no significant association with sepsis or Cardiopulmonary Bypass.Platelet counts significantly declined after surgery, with nadir on 2nd POD (p < 0.001), the drop being more marked in patients operated on Cardiopulmonary Bypass (p < 0.005). Counts were significantly lower in patients exposed to >150 min Cardiopulmonary Bypass compared to those with shorter Cardiopulmonary Bypass. Septic patients had significantly lower platelet counts than uninfected patients, decline >2 SD from mean pre-operative level strongly associated with sepsis (p < 0.001).C-Reactive Protein levels rose markedly after surgery, peaking on 2nd POD; levels were significantly higher if operated on Cardiopulmonary Bypass. Cardiopulmonary Bypass >150 min was associated with lower mean C-Reactive Protein on first post-operative day, but significantly higher values on third and fourth post-operative days, as compared to Cardiopulmonary Bypass <150 min. Comparison of infected versus non-infected patients showed significantly higher mean C-Reactive Protein in the former group. CONCLUSION: While leucocyte count, platelet count and C-Reactive Protein emerged as useful markers of post-operative inflammatory response and reaction to Cardiopulmonary Bypass, they proved unsatisfactory predictors of early post-operative sepsis.

Profile and risk factors for congenital heart defects: A study in a tertiary care hospital.

INTRODUCTION: Congenital heart defects (CHDs) are an important cause of mortality and morbidity in children representing a major global health burden. It is thus important to determine their prevalence and spectrum and identify risk factors associated with the development of heart defects. MATERIALS AND METHODS: A case-control study was carried out in the Department of Pediatrics and Center of Cardiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India, from February 2014 to August 2015. All patients referred with complaints or clinical examination suggestive of CHDs were further evaluated with echocardiography. On Echocardiography, patients having CHDs were included as cases and those having a normal echocardiographic study were included as controls. Healthy controls were also included. 400 cases and 400 controls were thus identified; preterms having patent ductus arteriosus and patent foramen ovale and those with acquired heart defects were excluded. Risk factors among cases and controls were further studied. RESULTS: Acyanotic heart defects were 290 (72.50%) of the total heart defects, whereas the contribution of cyanotic heart defects was 110 (27.50%). Out of all CHDs, ventricular septal defect was the most common lesion with contribution of 152 (38%) cases, whereas among the cyanotic heart defects, Tetralogy of Fallot was the most common lesion (18% of total cases). Out of the total 400 cases, 261 were males (65.25%). On univariate analysis, paternal age (odds ratio, OR, 2.01), bad obstetric history (OR, 2.65), antenatal febrile illness (OR, 4.12), and advanced maternal age (OR, 3.28) were found to increase the risk of CHD whereas intake of multivitamin (OR, 3.02) was found to be protective. The risk factors were further analyzed with multivariate logistic regression analysis and all the above factors were found to be significantly associated. CONCLUSION: We noted that the profile of CHD in our population was similar to the published literature although many were missed during infancy and detected later in life. Several antenatal factors were found to be associated with the incidence of congenital heart disease emphasizing the need to prioritize antenatal care and counseling to pregnant mothers along with good maternal nutrition and folic acid supplementation.

Evaluation of salivary anti-Salmonella typhi lipopolysaccharide IgA ELISA for serodiagnosis of typhoid fever in children.

This observational study was conducted to determine the diagnostic accuracy of ELISA for the detection of anti-Salmonella typhi lipopolysaccharide (LPS) salivary immunoglobulin A (IgA) antibodies in 37 children with culture confirmed typhoid, 30 febrile controls with an alternative diagnosis and 30 healthy controls. The test was positive in 33/37 (89.2%) cases of typhoid, but negative in all patients in the two control groups. Maximum absorbance of anti-LPS IgA was observed during the second and third weeks of typhoid, with a progressive decline thereafter. The sensitivity of ELISA was 71.4%, 100%, 100%, 9.1% and 0%, in first, second, third, fourth and fifth week of illness, respectively. Further large scale studies measuring salivary anti-LPS IgA antibodies are needed to confirm the potential of saliva-based serology in children with suspected typhoid.

Spectrum of Cyanotic Heart Defects and Their Modes of Presentation at Cardiology Clinic in a Tertiary Care Hospital.

Background: Cyanotic Congenital heart defect (CHD) is the high risk group which requires prompt medical attention. Immediate management can drastically alter the natural history otherwise most of the children will succumb to their defect very early in infancy. It is thus important to have reliable information of the profile of various cyanotic CHDs as well as their mode of presentation for the early detection. Methods: The study was carried out in Department of Pediatrics and Center of Cardiology, Jawaharlal Nehru Medical College, Aligarh. All patients referred with complaints or clinical examination suggestive of congenital heart defects were further evaluated with echocardiography. On echocardiography patients having congenital heart defects were included as cases which were further divided into cyanotic and acyanotic heart defects, preterms having PDA and PFO and those with acquired heart defects were excluded. The profile and mode of presentation of various cyanotic CHDs was further described in detail. Results: Acyanotic heart defects were 290(72.50%) of the total heart defects, while the contribution of cyanotic heart defects was 110 (27.50%). Out of all CHDs, VSD was the most common lesion with contribution of 152 (38.00%) cases, while among the cyanotic heart defect, Tetralogy of Fallot (TOF) was the most common lesion (18% of total cases). Spectrum of various cyanotic lesions were TOF 65.45%, Single Ventricle 12.72%, TAPVC (Total Anomalous Pulmonary Venous Connection) 8.18%, TGA(Transposition of Great Arteries) 7.27%, Tricuspid Atresia 3.63%, Ebsteins malformation 1.81% and Truncus Arteriosus 0.90%. Conclusion: Profile of various cyanotic CHDs was similar to the previous studies, however spectrum of various CHDs was quite wide, a large number of cases were missed in infancy and presented late.

Profile of Acyanotic Congenital Heart Defects

Background: Acyanotic CHD constitute majority of heart defect with significant morbidity, Profile of various defects is essential for identifying children who need urgent intervention and who need to be medically followed. Methods: The study was carried out in Department of Pediatrics and Center of Cardiology, Jawaharlal Nehru Medical College, Aligarh. All patients referred with complaints or clinical examination suggestive of congenital heart defects were further evaluated with echocardiography. On echocardiography patients having congenital heart defects were included as cases which were further divided into cyanotic and acyanotic heart defects, preterms having PDA and PFO and those with acquired heart defects were excluded. The profile and mode of presentation of various acyanotic CHDs was further described in detail. Results: Acyanotic heart defects were 290(72.50%) of the total heart defects, while the contribution of cyanotic heart defects was 110 (27.50%). Out of all CHDs, VSD was the most common lesion with contribution of 152 (38.00%) cases, followed by ASD (20.34%) , PDA (13.10%), PS (6.90%), Subaortic Membrane (2.00%), AV Canal valve defect (1.00%), RSOV (1.00%), Bicuspid Aortic Valve (1.00%), PAPVC (0.66%), Cortriatriatum (0.33%), Coarctation of Aorta(0.33%), ALCAPA(0.33%) and Aortic stenosis (0.33%). Age of presentation for most of the children was between 1 to 5 years. Conclusions: The profile and mode of presentation of various acyanotic heart defects was similar to other studies but diagnosis was delayed in majority of cases. The prevelance of various obstructive lesions like AS, coarctation and bicuspid aortic valve was much lower.

Profile and Clinical Spectrum of Congenital Heart Defects in NICU

Introduction: Congenital heart defects are commonest birth defects and is an important cause of mortality and morbidity in newborns. The current study was done aiming at determining profile and clinical spectrum of various congenital heart diseases (CHD) in neonatal period. Methodology: An observational study was carried out in the NICU, Department of Pediatrics, Jawaharlal Nehru Medical College, Aligarh from Feb 2014 to Aug 2015 with the objective to determine profile of various congenital heart defects. All patients with clinical suspicion of congenital heart defect were further evaluated with echocardiography.  Patients who were preterm having PDA and PFO were excluded from cases. Prevalence of various congenital heart defects was calculated. Clinical Spectrum of various congenital heart defects was observed. Observations: Total newborns screened 238 and 52 congenital hearts defect were detected. Acyanotic heart defect contributed 67% while cyanotic heart defect contributed 23%. VSD was the most common lesion while TOF (11.5%) was commonest among cyanotic heart defects. Most of the cyanotic heart defects were detected on screening as murmur on auscultation while PDA of bigger size presented as fast breathing. In cyanotic heart, defect classical TOF presented with only murmur while TOF with PA presented as cyanosis. Conclusion: VSD was the most common congenital heart defect detected while Tetralogy of Fallot was commonest among the cyanotic heart defects.

Changing antibiotic sensitivity pattern and scope of chloramphenicol in the management of hospitalised patients of typhoid fever.

Enteric fever is a global health problem and there is emerging drug resistance with some reports of re-emerging sensitivity to previously used antibiotics eg, chloramphenicol. This study was done to compare the drug sensitivity pattern of enteric fever over a decade period. Twenty-five culture positive patients for S typhi from one study done between October 1993 to February 1995 and 35 positive patients from another study done between September 2005 and August 2006 in the same hospital were taken into account and their sensitivity pattern was compared. A total of 36% of cases were sensitive to all the drugs and equal number were multidrug resistant in the study in 1995, while in 2006 only 14.2% (p<0.05) were sensitive to all drugs and percentage of multidrug resistance has increased to 42% (p>0.05). Sensitivity to chloramphenicol had decreased from 68.00% to 54.30% (p>0.05). With the emergence of resistant strains there is significant decline in overall sensitivity to all first line drugs. However there is no change in chloramphenicol sensitivity of Salmonella enterica serovar typhi 10 years back and now, this alone is not the sufficient reason for reintroduction of this drug especially in younger patients.