Placement of permanent pacemaker in a low-birth-weight infant with congenital heart block: a case report.

One of the rare diseases with a high mortality rate in infants is congenital heart block (CHB) with neonatal lupus erythematosus (NLE) as the most common cause. A permanent pacemaker (PPM) is indicated for symptomatic bradycardia. The choice of PPM in the paediatric population is different from that in the adult population because of several reasons like small size, account of somatic growth, and difference in physiological changes. Here, we present a case in which a 2.6 kg and 45 days old baby with CHB secondary to NLE was successfully treated with a single-chambered adult-sized PPM with epicardial lead. According to our knowledge, this is the smallest baby in Pakistan in which PPM has been implanted.

Anomalous left coronary artery from pulmonary artery (ALCAPA) as a silent cause of mitral regurgitation in children.

Anomalous left coronary artery from pulmonary artery (ALCAPA), also known as Bland-White-Garland syndrome, is a rare cardiac disease. This condition may present with complications such as myocardial infarction, left ventricular dilatation, mitral regurgitation, and left heart failure in children. We report a case of a four-year-old boy who presented with shortness of breath, palpitations, and recurrent upper respiratory tract infections. He was diagnosed with mitral regurgitation. During the surgery, left coronary artery (LCA) was not present in its anatomical position and ALCAPA was identified. One should keep in mind the possibility of ALCAPA in presentation of mitral regurgitation in children despite not being reported in echocardiography.

Kawasaki Shock Syndrome and Covid-19.

Kawasaki disease (KD) is a systemic vasculitis of unknown cause affecting children under 5 years of age. It is thought to be triggered by several viruses. Recently, Kawasaki-like disease has been reported worldwide in patients with COVID-19, giving rise to a new term of multi-system inflammatory syndrome in children (MIS-C). We report a case of a previously healthy 7-year boy, referred to our hospital with provisional diagnosis of measles due to generalised erythematous, maculopapular rash and conjunctivitis. On detailed evaluation, the patient fulfilled the clinical and laboratory criteria of MIS-C, and COVID-19 antibodies were positive. He was treated successfully with high dose of intravenous immunoglobulins (IVIG) and methylprednisolone. Patient was followed one week later with repeat echocardiography, which showed improvement. In conclusion, early recognition and timely treatment can prevent adverse outcomes in MIS-C. Key Words: COVID-19, Kawasaki disease, MIS-C.

Evaluation of cardiac function in fetuses of mothers with gestational diabetes.

OBJECTIVE: The purpose of this study was to assess fetal cardiac function in normal fetuses (control group) compared to those who are exposed to gestational diabetes mellitus using different echocardiographic measurements, and to explore the application of left atrial shortening fraction in determination of fetal diastolic function with gestational diabetes mellitus. METHODS: A total of 50 women with gestational diabetes and 50 women with a healthy pregnancy were included in the study. Fetal echocardiography was performed and structural as well as functional fetal cardiac parameters were measured. Data were compared between with or without fetal myocardial hypertrophy and the control group. RESULTS: In the study group, out of 50 fetuses of gestational diabetic mothers, 18 had myocardial hypertrophy and 32 had normal septal thickness. Gestational age at time of examination did not differ significantly between the control and gestational diabetes group (p = 0.55). Mitral E/A ratio was lower in gestational diabetes group as compared to the control (p < 0.001). Isovolumetric relaxation and contraction times and myocardial performance index were greater in fetuses of gestational diabetic mothers (p < 0.001). In fetuses of gestational diabetic mothers with myocardial hypertrophy, left atrial shortening fraction was lower as compared to those without myocardial hypertrophy and those of the control group (p < 0.001). CONCLUSIONS: The results of this study suggest that fetuses of gestational diabetic mothers have altered cardiac function even in the absence of septal hypertrophy, and that left atrial shortening fraction can be used as a reliable alternate parameter in the assessment of fetal diastolic function.

Clinical Screening for Congenital Heart Disease in Newborns at a Tertiary Care Hospital of a Developing Country.

OBJECTIVE: To screen all newborns admitted to a tertiary care hospital to rule out congenital heart disease before discharge and to find out the utility of pulse oximetry to detect congenital heart disease. METHODOLOGY: This prospective study was done at Aga Khan University Hospital from January 2014 to December 2014 in 1,650 newborns over a period of 12 months. Pulse oximetry and clinical examination were done. Persistent oxygen saturation less than 95% was considered as positive pulse oximetry. Newborns who had positive pulse oximetry or abnormal clinical examinations findings were subjected to echocardiography. RESULTS: Pulse oximetry was performed on 1,650 newborns, out of which 25 (1.5%) had congenital heart disease. Positive pulse oximetry cases were 16 (0.97%), out of which 10 had only positive pulse oximetry (negative clinical examination). Positive clinical examination cases were 45 (2.7%), out of which 39 cases had only positive clinical examinations (negative pulse oximetry). Six newborns had both positive pulse oximetry and positive clinical examination. Out of the 25 diagnosed cases of congenital heart disease, ventricular septal defect (VSD) was the most common congenital heart disease, followed by patent ductus arteriosus (PDA). The sensitivity, specificity, positive predictive value, and negative predictive value of pulse oximetry were 32%, 99.5%, 50%, and 98.9% respectively. CONCLUSION: In the community setting of a developing country, a combination of pulse oximetry screening and clinical examination are better at detecting congenital heart defects than either test alone.

Anomalous Left Coronary Artery from Pulmonary Artery: An Important Cause of Ischemic Mitral Regurgitation in Children.

INTRODUCTION:  Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly. The usual presentation in infancy is inconsolable crying or congestive cardiac failure, both due to myocardial ischemia. Survivors after infancy have improved left ventricular function but continue to have mitral regurgitation due to papillary muscle ischemia. The present study emphasizes the importance of unexplained mitral regurgitation as a clue to the diagnosis. PATIENTS AND METHODS:  Patients with the diagnosis of ALCAPA operated between June 2017 and May 2018 were enrolled. Their ages at diagnosis, electrocardiography, and echocardiography findings were noted. A selective angiogram of the right coronary artery was done in all. Results of surgical reimplantation were analyzed. Postoperative data were collected, including ventricular function and mitral regurgitation. RESULTS:  Six patients were included. Clinical signs of cardiac failure were present in two patients, and a systolic murmur was heard in all. The mean left ventricular ejection fraction was 52 ± 12%. Mitral regurgitation was present in all of the patients. The right coronary artery was dilated (Z score > 2.5) in all except one. Selective right coronary angiogram and cardiac computerized tomography angiogram (CTA) were performed in all. Coronary reimplantation was successfully done. Follow-up echocardiography showed improved left ventricular ejection fraction and degree of mitral regurgitation in all patients. CONCLUSION:  ALCAPA is an uncommon congenital anomaly, the diagnosis of which can be missed, particularly in late presenters. Unexplained mitral regurgitation should always raise the suspicion of this anomaly. Surgical intervention has excellent results with an improvement of left ventricular function and mitral regurgitation.

Accuracy of echocardiography in diagnosing total anomalous pulmonary venous return.

OBJECTIVE: Total anomalous pulmonary venous return is an uncommon cyanotic congenital heart defect. Echocardiography is the initial diagnostic tool. Complimentary non-invasive modalities like cardiac computerized tomographic angiography and cardiac magnetic resonance imaging have replaced the need for cardiac catheterization in difficult cases. This study aimed to determine the accuracy of echocardiography in diagnosing total anomalous pulmonary venous return, and to determine the factors that may decrease its sensitivity. METHODS: This was a cross-sectional study conducted at the Aga Khan University Hospital Karachi, Pakistan from January 2010 to August 2016. All patients who were diagnosed with Total anomalous pulmonary venous return on echocardiography and had subsequent confirmation either on cardiac CT angiography or surgery were included. The diagnostic accuracy of echocardiography was expressed as sensitivity. Previously described taxonomy was used to define diagnostic error. Univariate and multivariate analysis were done by logistic regression OR (95% CI) were reported to identify factors causing the diagnostic error. RESULTS: High diagnostic sensitivity (81%) was found in isolated total anomalous pulmonary venous return and low (27%) in heterotaxy and mixed (20%) varieties. Poor acoustic windows and right isomerism were found to be significant factors responsible for the diagnostic error on multivariate analysis. CONCLUSION: Echocardiography can diagnose isolated total anomalous pulmonary venous return with high accuracy. Use of additional modalities may be required for a complete diagnosis in cases with mixed variety, heterotaxy and poor acoustic windows.

Congenitally Corrected Transposition of the Great Arteries in a Septuagenarian from the Developing Country of Pakistan.

Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital cardiac defect with atrioventricular and ventriculoarterial discordance which leads to heart failure and limits patients' lifespan. We report the case of a 70-year-old lady, from a poor province in Pakistan, who presented for the first time with palpitations and was diagnosed to have CCTGA. She had moderate pulmonic valve stenosis which was protective against heart failure. She had six children all born via spontaneous vertex delivery in her local village. This case exemplifies the fact that pulmonic stenosis is favourable for patients with CCTGA. In a country where the average life expectancy of females is only 68 years, the survival of our patient with CCTGA beyond the average lifespan is indeed interesting.

Phosphine induced acute cardiotoxicity in children: A need for health awareness.

Aluminum Phosphate (AP) is a cheap and highly effective pesticide. Phosphine is the active pesticidal component which is highly toxic. Mortality is high and ranges between 40-70%. There is a desperate need for creating awareness. We report a case series with a mortality of 40% and emphasize the need for public awareness.

Assessment of Cardiac Function in Fetuses of Gestational Diabetic Mothers During the Second Trimester.

Fetuses of diabetic mothers may have structural or functional cardiac abnormalities which increase morbidity and mortality. Isolated functional abnormalities have been identified in the third trimester. The aim of the present study was to assess fetal cardiac function (systolic, diastolic, and global myocardial performance) in the second trimester in mothers with gestational diabetes, and also to relate cardiac function with glycemic control. Mothers with gestational diabetes mellitus referred for fetal cardiac evaluation in the second trimester (between 19 and 24 weeks) from March 2015 to February 2016 were enrolled as case subjects in this study. Non-diabetic mothers who had a fetal echocardiogram done between 19 and 24 weeks for other indications were enrolled as controls. Functional cardiac variables showed a statistically significant difference in isovolumetric relaxation and contraction times and the myocardial performance index and mitral E/A ratios in the gestational diabetic group (p = 0.003). Mitral annular plane systolic excursion was significantly less in the diabetic group (p = 0.01). The only functional cardiac variable found abnormal in mothers with poor glycemic control was the prolonged isovolumetric relaxation time. Functional cardiac abnormalities can be detected in the second trimester in fetuses of gestational diabetic mothers and timely intervention can improve postnatal outcomes.

Epac-Rap1-activated mesenchymal stem cells improve cardiac function in rat model of myocardial infarction.

INTRODUCTION: Rap1, a member of Ras superfamily of small GTP-binding proteins, is involved in cardiovascular biology in numerous ways. It is an evolutionary conserved regulator of adhesion, polarity, differentiation and growth. AIMS: Our aim was to analyze Rap1-activated rat bone marrow mesenchymal stem cells (MSCs) for their potential role in adhesion and cardiac differentiation. METHODS: Myocardial infarction (MI) was produced in Sprague Dawley (SD) rats through occlusion of the left anterior descending coronary artery. MSCs were treated with 8-pCPT-2'-O-Me-cAMP (CPT) to activate Rap1. Normal (untreated) and CPT-treated MSCs were transplanted through intramyocardial injection in respective groups. Cardiac function was assessed by echocardiography at 2 and 4 weeks after cell transplantation. Histological analysis was performed to observe changes at tissue level. RESULTS: Homing of CPT-treated MSCs was significantly (***P<.001) higher as compared to normal MSCs in the infarcted hearts. This may be due to increase in the gene expression of some of the cell adhesion molecules as evident by qRT-PCR analysis. Significant (***P<.001) improvement in the restoration of heart function in terms of left ventricular diastolic and systolic internal diameters (LVIDd, LVIDs), % ejection fraction, % fraction shortening and end-systolic and end-diastolic volumes were observed in CPT-treated MSCs as compared to the MI model. Histological analyses showed significant (***P<.001) reduction in scar formation in the CPT-treated group. Differentiation of treated MSCs into functional cardiomyocytes was evident through immunohistochemical staining. LV wall thickness was also preserved significantly (***P<.001). Blood vessel formation was more pronounced in CPT-treated group although both cell therapy groups showed significant increase as compared to MI model. CONCLUSION: Our findings showed that pharmacological activation of Epac-Rap1 improves cardiac function through better survival, adhesion and differentiation of transplanted cells. Transplantation of these MSCs in the infarct area restored functional myocardium.

Dissecting aneurysm of the interventricular septum due to rupture of the sinus of Valsalva.

Aneurysm of the sinus of Valsalva is a rare congenital cardiac anomaly. It occurs as an outpouching that progresses like a windsock, and it may rupture producing aortic regurgitation, cardiac tamponade, congestive heart failure, conduction abnormalities, and stroke. We describe a case of rupture of the sinus of Valsalva into the interventricular septum producing a large dissecting aneurysm. Despite the location, it did not produce a conduction abnormality.

Clinicodemographic features and outcome of acute myocarditis in children admitted at tertiary care hospital.

BACKGROUND: Myocarditis is an inflammatory disorder of myocardium associated with high mortality and morbidity. It is often difficult to diagnose because it can either be asymptomatic or mimic other illnesses. This study is conducted to evaluate clinicodemographic features and outcome of acute myocarditis in children admitted at a tertiary care hospital. METHODS: Medical records of all children aged 1month to 16years who were admitted between 2005 and 2013 at Aga Khan University Hospital, Karachi and discharged with a diagnosis of myocarditis were reviewed retrospectively. Clinical and demographic features, management and outcome were recorded. RESULTS: Records of a total of 62 patients with the diagnosis of myocarditis were reviewed retrospectively between 2005 and 2013. Median age of patients was 12.5months with 28 (45%) females and 34 (55%) males. The main presenting complaint observed was irritability (73%) and least common symptom was abdominal pain (23%) while the most frequently occurring examination finding was tachycardia (90%). Length of the hospital stay was 8±4.7days with 21 (34%) admissions in the ward and 41 (66%) in intensive care unit. CONCLUSION: The most frequent presentation in our study was irritability, followed by difficulty in breathing while the least common symptom was abdominal pain. Tachycardia was the commonest clinical sign observed so it is important to look for heart rate and rhythm in a sick child with irritability.

The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease.

BACKGROUND: Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects. METHODS: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors. RESULTS: We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, p.(Leu435Phe); c.830+1G>A and c.1317+1G>T. Together with all previously published cases (n=32), we show that congenital sensorineural deafness, hypotonia, developmental delay and lactic acidaemia are common clinical manifestations with disease onset under 2 years. Renal involvement is more prevalent than seizures (66% vs 44%). In addition, median survival time was longer in patients with renal involvement compared with those without renal disease (6 years vs 8 months, p=0.009). The neurological phenotype also appears milder in patients with renal involvement. CONCLUSIONS: The clinical phenotypes and prognosis associated with RMND1 mutations are more heterogeneous than that were initially described. Regular monitoring of kidney function is imperative in the clinical practice in light of nephropathy being present in over 60% of cases. Furthermore, renal replacement therapy should be considered particularly in those patients with mild neurological manifestation as shown in our study that four recipients of kidney transplant demonstrate good clinical outcome to date.

Sarcoidosis with Arteriovenous Malformation in a 15-Year-Old Girl - The Rarest of the Rare.

INTRODUCTION: Sarcoidosis is an uncommon multi-system disorder with many possible complications. Arteriovenous malformations (AVMs) are a rare vascular complication of sarcoidosis. CASE DESCRIPTION: A 15-year-old girl presented to the Pediatric Clinic at AKUH with pulmonary, hepatic, joint, and skin manifestations. Physical examination and investigations pointed toward sarcoidosis, including raised erythrocyte sedimentation rate, angiotensin converting enzyme (ACE), and alanine transaminase (ALT). An incidental finding of pulmonary arteriovenous malformation (PAVM) was noticed on echocardiography. She responded to oral corticosteroids, her ACE and ALT levels improved. There was lack of indication for pulmonary angio-embolization for her PAVM. On a 3-year follow-up, her condition improved and she is clinically well. DISCUSSION: Pulmonary arteriovenous malformation is an extremely rare complication of sarcoidosis, especially among the pediatric population. Hence, this is the first reported case of its kind. The relation between sarcoidosis and PAVM is difficult to establish; however, there are some theories. This condition may be treated depending on the symptoms. Since our patient did not have any significant symptoms of PAVM, she was treated for the underlying disease, i.e., sarcoidosis. CONCLUSION: While dealing with patients having multi-system disorders like sarcoidosis, one must be very vigilant so as not to miss out on any complication. Regular follow-up visits should be scheduled to rule out new complications and to monitor the past ones.

Intraoperative air embolism originating from a pulmonary vein.

Air embolism entering the systemic arterial system originating from the pulmonary circuit itself is an extremely rare occurrence. We report the case of an 18-year-old female undergoing correction of an atrial septal defect, who had an air embolism that is believed to have originated from the right superior pulmonary vein. Although the exact mechanism of air entry remains a matter of speculation, several plausible hypotheses are proposed and discussed. Injury to a pulmonary vein may lead to air entry with migration to the left atrium and ultimately to systemic embolism.

Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients.

BACKGROUND: Sengers syndrome is an autosomal recessive condition characterized by congenital cataract, hypertrophic cardiomyopathy, skeletal myopathy and lactic acidosis. Mutations in the acylglycerol kinase (AGK) gene have been recently described as the cause of Sengers syndrome in nine families. METHODS: We investigated the clinical and molecular features of Sengers syndrome in seven new families; five families with the severe and two with the milder form. RESULTS: Sequence analysis of AGK revealed compound heterozygous or homozygous predicted loss-of-function mutations in all affected individuals. A total of eight different disease alleles were identified, of which six were novel, homozygous c.523_524delAT (p.Ile175Tyrfs*2), c.424-1G > A (splice site), c.409C > T (p.Arg137*) and c.877 + 3G > T (splice site), and compound heterozygous c.871C > T (p.Gln291*) and c.1035dup (p.Ile346Tyrfs*39). All patients displayed perinatal or early-onset cardiomyopathy and cataract, clinical features pathognomonic for Sengers syndrome. Other common findings included blood lactic acidosis and tachydyspnoea while nystagmus, eosinophilia and cervical meningocele were documented in only either one or two cases. Deficiency of the adenine nucleotide translocator was found in heart and skeletal muscle biopsies from two patients associated with respiratory chain complex I deficiency. In contrast to previous findings, mitochondrial DNA content was normal in both tissues. CONCLUSION: We compare our findings to those in 21 previously reported AGK mutation-positive Sengers patients, confirming that Sengers syndrome is a clinically recognisable disorder of mitochondrial energy metabolism.

Transcatheter versus surgical closure of atrial septum defect: a debate from a developing country.

INTRODUCTION: This study compares the effectiveness and cost of trans-catheter verses surgical closure of secundum atrial septum defect (ASD). ASD accounts for 10% of congenital cardiac defects. Trans-catheter closure of secundum ASD is increasingly used as the primary intervention. Surgical repair is advised in a proportion of secundum type defects which are unsuitable for device closure. METHODS: We reviewed the clinical course of 176 patients who underwent closure of isolated secundum ASD. The patients were assigned to either the device or surgical group depending upon the treatment they received. Successful closure was assessed immediately after the procedure. The following outcomes were studied: mortality, morbidity, hospital stay, and costs. RESULTS: Ninety five patients were in the surgical group and 81 patients were in the group undergoing device closure. The median age was 14.0 years (range 1.1-61.0) for surgical group and 24.0 years (range 0.5-68.0) for the device group. The mortality in both groups was 0. The procedure success rate was 100% for the surgical group and 96.3% for the device group. The complication rate was 13.7% for surgical group and 7.4% for the device group. The mean length of hospital stay was 5.0 ± 2.7 days for surgical group and 3.0 ± 0.4 days for device group. The procedure cost for surgery was found to be 12.3% lower than that of trans-catheter closure. CONCLUSION: Successful closure is achieved by both methods. Trans-catheter closure results in lower rate of complication and hospital stay but the cost of the procedure tends to be higher than surgery.

Pulmonary arteriovenous malformation in cryptogenic liver cirrhosis.

The cause in 10 - 20% cases of liver cirrhosis (LC) cannot be elucidated, and are thus termed cryptogenic. Pulmonary arteriovenous malformations (PAVMs) are relatively rare, but the most common anomaly involving the pulmonary tree. Although the rare correlation between LC and PAVM is well-known, there have been no reports of PAVMs occurring in cryptogenic LC. We report a case of PAVM that occurred in cryptogenic liver cirrhosis in a 3 years old male child. The child presented with complaints of malena, hematemesis and variceal bleed. The examination revealed a child with respiratory distress, irritability, tachycardia, clubbing and abdominal distention. He was worked up for recurrent variceal bleeding secondary to portal hypertension but the oxygen saturation during hospital stay kept deteriorating. The diagnosis of hepatopulmonary syndrome as the cause of persistent hypoxemia in the absence of other cardio-pulmonary causes was then made by enhanced echocardiogram using agitated saline. He improved significantly after liver transplantation performed abroad. At a 6 months follow-up, the child was stable with no evidence of intrapulmonary shunting on repeat echo.

Midterm results of bovine jugular vein conduit for right ventricular outflow tract reconstruction.

OBJECTIVE: To evaluate the midterm results of Contegra conduit. METHODS: The retrospective study comprised patient record at Aga Khan University Hospital, Karachi, of conduits implanted between May 2007 and June 2012. Data collection was made from the clinical notes and from serial echocardiograms by a single cardiologist. The last followup echocardiography was done at the time of data collection in June 2012. SPSS 19 was used for statistical analysis. RESULTS: A total of 18 conduits had been implanted (16-22 mm) during the study period. Median age at the time of surgery was 9 years (range: 2.5-16 years). Early mortality was seen in 3 (16.66%) patients, but none was Contegra related. Of the remaining 15 patients, 2 (13.33%) with a diagnosis of Pulmonary Atresia-Ventricular Septal Defect with hypoplastic peripheral Pulmonary Arteries (PA), developed severe distal pressure gradient (50 mmHg) across Contegra over a median period of 18 months (range: 12-24 months), with resultant severe regurgitation and needed percutaneous intervention. There was no thrombosis, calcification, anuerysmal dilation or late deaths. CONCLUSION: At midterm followup, Contegra conduit was associated with low re-intervention rates with satisfactory haemodynamic results. However, long-term durability must be determined for this conduit, especially in patients with Pulmonary Atresia-Ventricular Septal Defect with hypoplastic peripheral Pulmonary Arteries.