A Witteveen-Kolk Syndrome Patient with Reflux Disease and a de novo Deletion of the SIN3A Gene.

Introduction: The Witteveen-Kolk syndrome (WITKOS) (OMIM: 613406) is a heterogeneous emerging disorder caused by pathogenic variants or microdeletions encompassing the SIN3A gene (SIN3 Transcription Regulator Family Member A). It is characterized by distinctive facial features, developmental delay, intellectual disability, microcephaly, short stature, and subtle anomalies on brain magnetic resonance imaging (MRI). To date, about 50 patients have been reported in the medical literature. Patient Presentation: In this article, we reported a patient with classic findings of WITKOS including global developmental delay, microcephaly, hypotonia, vomiting, malnutrition, autistic and dysmorphic facial features, and cardiac abnormalities. Also, a barium esophagogram suggested severe motility disorder and gastroesophageal reflux disease. Affymetrix CytoScan 750K microarray showed a de novo 1.6-Mb deletion at 15q24.1q24.2, including the whole SIN3A gene. We have also summarized the clinical features of WITKOS patients in the medical literature and cardiac abnormalities detected in 4 out of 10 patients in studies that clearly state that cardiac examination was performed in the patients. Conclusion: Our findings showed that cardiac defects are not uncommon findings in WITKOS. Physicians should also be aware of reflux disease and motility disorder in patients with feeding difficulty together with early cardiac examination in terms of an improved quality of life in WITKOS patients.

Diabetic myocardial disorder. A clinical consensus statement of the Heart Failure Association of the ESC and the ESC Working Group on Myocardial & Pericardial Diseases.

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) has been firmly established; however, the entity of diabetic myocardial disorder (previously called diabetic cardiomyopathy) remains a matter of debate. Diabetic myocardial disorder was originally described as the occurrence of myocardial structural/functional abnormalities associated with T2DM in the absence of coronary heart disease, hypertension and/or obesity. However, supporting evidence has been derived from experimental and small clinical studies. Only a minority of T2DM patients are recognized as having this condition in the absence of contributing factors, thereby limiting its clinical utility. Therefore, this concept is increasingly being viewed along the evolving HF trajectory, where patients with T2DM and asymptomatic structural/functional cardiac abnormalities could be considered as having pre-HF. The importance of recognizing this stage has gained interest due to the potential for current treatments to halt or delay the progression to overt HF in some patients. This document is an expert consensus statement of the Heart Failure Association of the ESC and the ESC Working Group on Myocardial & Pericardial Diseases. It summarizes contemporary understanding of the association between T2DM and HF and discuses current knowledge and uncertainties about diabetic myocardial disorder that deserve future research. It also proposes a new definition, whereby diabetic myocardial disorder is defined as systolic and/or diastolic myocardial dysfunction in the presence of diabetes. Diabetes is rarely exclusively responsible for myocardial dysfunction, but usually acts in association with obesity, arterial hypertension, chronic kidney disease and/or coronary artery disease, causing additive myocardial impairment.

Neurological, cardiac, musculoskeletal, and renal manifestations of scleroderma along with insights into its genetics, pathophysiology, diagnostic, and therapeutic updates.

Background: Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. Methodology: A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Results: Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti-centromere antibodies, and anti-topoisomerase antibodies, are important for classifying diseases and predicting their outcomes. Discussion: The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Conclusion: Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

Syncope in older adults: challenges, approach and treatment.

Syncope can have devastating consequences, resulting in injuries, accidents or even death. In our ageing society, the subsequent healthcare usage, such as emergency room presentations, surgeries and hospital admissions, forms a significant and growing socioeconomic burden. Causes of syncope in the older adult include orthostatic hypotension, carotid sinus syndrome, vasovagal syncope, structural cardiac abnormalities, cardiac arrhythmias and conduction abnormalities. As stated in the recently published World Falls Guidelines, syncope in older adults often presents as falls, which is either due to amnesia for loss of consciousness, or pre-syncope leading to a fall, especially in those prone to falls with several other risk-factors for falls present. This difference in presentation can hinder the recognition of syncope. In patients with unexplained falls, or in whom the history comprises red flags for potential syncope, special attention to (pre)syncope is therefore warranted. When syncope is mistaken for other causes of a transient loss of consciousness, such as epileptic seizures, or when syncope presents as falls, patients are often referred to multiple specialists, which may in turn lead to excessive and unnecessary diagnostic testing and costs. Specialist services that are able to provide a comprehensive assessment can improve diagnostic yield and minimise diagnostic testing, thus improving patient satisfaction. Comprehensive assessment also leads to reduced length of hospital stay. Increasingly, geriatricians are involved in the assessment of syncope in the older patient, especially given the overlap with falls. Therefore, awareness of causes of syncope, as well as state-of-the-art assessment and treatment, is of great importance.

Clinical features, imaging findings and molecular data of limb-girdle muscular dystrophies in a cohort of Chinese patients.

BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) are a group of heterogeneous inherited diseases predominantly characterized by limb-girdle muscle weakness and dystrophic changes on histological analysis. The frequency of LGMD subtypes varies among regions in China and ethnic populations worldwide. Here, we analyzed the prevalence of LGMD subtypes, their corresponding clinical manifestations, and molecular data in a cohort of LGMD patients in Southeast China. METHODS: A total of 81 consecutive patients with clinically suspected LGMDs from 62 unrelated families across Southeast China were recruited for targeted next-generation sequencing and whole-exome sequencing from July 2017 to February 2020. RESULTS: Among 50 patients (41 families) with LGMDs, the most common subtypes were LGMD-R2/LGMD2B (36.6%) and LGMD-R1/LGMD2A (29.3%). Dystroglycanopathies (including LGMD-R9/LGMD2I, LGMD-R11/LGMD2K, LGMD-R14/LGMD2N and LGMD-R20/LGMD2U) were the most common childhood-onset subtypes and were found in 12.2% of the families. A total of 14.6% of the families had the LGMD-R7/LGMD2G subtype, and the mutation c.26_33dupAGGTGTCG in TCAP was the most frequent (83.3%). The only patient with the rare subtype LGMD-R18/LGMD2S had TRAPPC11 mutations; had a later onset than those previously reported, and presented with proximal‒distal muscle weakness, walking aid dependency, fatty liver disease and diabetes at 33 years of age. A total of 22.0% of the patients had cardiac abnormalities, and one patient with LMNA-related muscular dystrophy/LGMD1B experienced sudden cardiac death at 37 years of age. A total of 15.4% of the patients had restrictive respiratory insufficiency. Muscle imaging in patients with LGMD-R1/LGMD2A and LGMD-R2/LGMD2B showed subtle differences, including more severe fatty infiltration of the posterior thigh muscles in those with LGMD-R1/LGMD2A and edema in the lower leg muscles in those with LGMD-R2/LGMD2B. CONCLUSION: We determined the prevalence of different LGMD subtypes in Southeast China, described the detailed clinical manifestations and distinct muscle MRI patterns of these LGMD subtypes and reported the frequent mutations and the cardiorespiratory involvement frequency in our cohort, all of which might facilitate the differential diagnosis of LGMDs, allowing more timely treatment and guiding future clinical trials.

Pregnancy outcomes of women with cardiac disease.

OBJECTIVE: To determine and predict the maternal and neonatal outcomes of pregnancies occurring in patients with cardiac disease. METHOD: This retrospective review included 147 pregnancies identified from antenatal, delivery, and nursery records. Information concerning the nature and severity of the pre-existing cardiac disease, comorbidities, risk scores, obstetric or cardiac complications, and pregnancy outcomes were collected. The data were analyzed using SPSS Windows version 22. RESULTS: In all, 111 (73.5%) of the cohort had acquired heart disease and 4 (2.7%) of patients belonged to WHO class IV, in which pregnancy is not recommended. Additionally, 12 (8.1%) were categorized as being at significant risk of having a cardiac complication. The proportion of patients that had maternal and perinatal mortality was 6 (4.0%) and 7 (4.8%), respectively. The WHO and CARPREG scoring systems were reliably able to predict cardiac events (P < 0.01). Mothers who received preconception counseling had significantly fewer occurrences of cardiac and obstetric events than those who did not. CONCLUSION: Cardiac disease in pregnancy in women managed at our center was most often an acquired disease. The baseline risk assessment scores accurately predicted the likelihood of adverse cardiac outcomes.

COVID-19 in congenital heart disease patients: what did we learn?!

Aim: COVID-19 pandemic has spread widely at unpreceded pace. Cardiovascular comorbidities are significantly correlated with severe and critical illness. Nevertheless, studies examining the impact of congenital heart disease on COVID-19 severity are scarce and restricted to hospitalized patients. This study aims to explore the course of COVID-19 illness, severity and complications in patients with concomitant congenital heart disease. Methodology: This study is a cross sectional survey that includes patients with congenital heart disease who are registered at the Children Heart Center at the American University of Beirut Medical Center. The survey was conducted in the pediatric cardiology outpatient clinics or remotely via phone calls. Results: A total of 238 patients participated in the study, of which 47.9% had suspected or confirmed diagnosis of SARS-CoV-2 infection. The majority of patients had mild illness. The symptoms ranged between rhinorrhea (15.6%), cough (15.6%), low-grade fever (11.2%), anosmia (2.7%), ageusia (2.5%), headache (9.8%), high-grade fever (8.5%), gastrointestinal symptoms (7.6%), lethargy (6.3%), muscle aches (5.6%), difficulty breathing (5.4%), joint pain (4.7%), and chills (4.7%). 20% of the surveyed patients required treatment at home. Hospitalization and oxygen therapy was required in 3.5% of cases, while only 1.5% demanded intensive care admission. Only one fatality was encountered. Conclusion: COVID-19 infection in pateints with congenital heart disease exhibits a mild to moderate course, and doesn't necessarily increase risk of complicated disease. No correlation could be found between specific congenital heart lesion and disease severity.

Cardiac findings in multisystem inflammatory syndrome in children: Short term follow up in a large Indian series.

Background: We present a large Indian series of Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) infection. The aim of the study is to present the incidence and pattern of cardiac involvement in children with MIS-C and their short-term follow-up. Methods and Results: Consecutive 144 children younger than 18 years of age diagnosed with MIS-C referred for cardiac evaluation between June 1 and November 30, 2021, were included and were followed up till February 2022. In addition to the demographics, details of COVID-19 infection, and biomarkers, their cardiovascular assessment (echocardiogram and electrocardiogram) was documented at baseline and on follow-up. The median age of children with MIS-C was 60 (24-104) months. Abnormal cardiac imaging was noted in 59% of children. Ventricular dysfunction was noted in 13.9% and coronary abnormalities were noted in 25.7% of children. The median duration when the first cardiac abnormality was reported was 7 (5-10) days. The distribution of age categories between children with and without cardiac abnormality was comparable. Children with cardiac abnormalities were followed up for a median duration of 47 (30-58) days. Complete resolution was documented in 92% of children after a median duration of 20 (9-38) days. There were no readmissions or deaths during follow-up. Conclusion: Cardiac involvement in children with MIS-C is frequent with coronary abnormalities and ventricular dysfunction being the most common manifestations. Most children exhibit complete clinical and myocardial recovery with appropriate anti-inflammatory therapy. Studies on long-term outcome of these children are needed.

RASopathies and cardiac manifestations.

As binary switches, RAS proteins switch to an ON/OFF state during signaling and are on a leash under normal conditions. However, in RAS-related diseases such as cancer and RASopathies, mutations in the genes that regulate RAS signaling or the RAS itself permanently activate the RAS protein. The structural basis of this switch is well understood; however, the exact mechanisms by which RAS proteins are regulated are less clear. RAS/MAPK syndromes are multisystem developmental disorders caused by germline mutations in genes associated with the RAS/mitogen-activated protein kinase pathway, impacting 1 in 1,000-2,500 children. These include a variety of disorders such as Noonan syndrome (NS) and NS-related disorders (NSRD), such as cardio facio cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML, also known as LEOPARD syndrome). A frequent manifestation of cardiomyopathy (CM) and hypertrophic cardiomyopathy associated with RASopathies suggest that RASopathies could be a potential causative factor for CM. However, the current supporting evidence is sporadic and unclear. RASopathy-patients also display a broad spectrum of congenital heart disease (CHD). More than 15 genes encode components of the RAS/MAPK signaling pathway that are essential for the cell cycle and play regulatory roles in proliferation, differentiation, growth, and metabolism. These genes are linked to the molecular genetic pathogenesis of these syndromes. However, genetic heterogeneity for a given syndrome on the one hand and alleles for multiple syndromes on the other make classification difficult in diagnosing RAS/MAPK-related diseases. Although there is some genetic homogeneity in most RASopathies, several RASopathies are allelic diseases. This allelism points to the role of critical signaling nodes and sheds light on the overlap between these related syndromes. Even though considerable progress has been made in understanding the pathophysiology of RASopathy with the identification of causal mutations and the functional analysis of their pathophysiological consequences, there are still unidentified causal genes for many patients diagnosed with RASopathies.

The incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis.

BACKGROUND: Congenital scoliosis(CS) is associated with multiple organs defect, and cardiac abnormalities have been reported commonly associated with CS. Hemivertebra is caused by the failure of vertebral formation, which is a major constitute of CS. Till now, few studies focus on the incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis. We aimed to analyze the cardiac defect in CS patients with or without hemivertebra, and further explore the incidence of cardiac defect between different types of hemivertebra. METHODS: The ultrasonic cardiography (UCG) results of surgically treated congenital scoliosis (CS) patients between 2015 and 2018 were retrospectively analyzed. Patients were divided into hemivertebra group and non-hemivertebra group according to preoperative CT. Patients with hemivertebra was further divided into sub-group by single/multiple or fully/partially/mixed segmented hemivertebra. Demographic information, radiographic data and cardiac abnormalities were statistically compared between groups. RESULTS: A total of 329 patients were analyzed, including 216 patients with hemivertebra and 113 patients without hemivertebra. UCG results were abnormal in 89 cases (27.1%), including 41 males(12.5%) and 48 females(14.6%). Hemivertebra group had comparable incidence of cardiac abnormalities with non-hemivertebra group (p = 0.517). No significant difference in the incidence of UCG abnormalities between single and multiple hemivertebra group (P = 0.246). Binary logistic regression analysis showed that female sex with multiple hemivertebra was a risk factor for abnormal UCG (P = 0.009, OR = 3.449). Cardiac abnormalities was comparable among fully, partially and mixed segmented hemivertebra group(P = 0.264). In abnormal UCG, 33 patients with hemivertebra had non-valvular abnormalities, and 48.5% (16/33) were septal defects. 28 patients had valvular abnormalities, most of them were mitral valve abnormalities, especially mitral valve redundancy, prolapse and insufficiency(82.1%, 23/28). No significant difference between the incidence of non-valvular and valvular abnormalities in patients with hemivertebra (P = 0.581). CONCLUSIONS: The incidence of abnormal UCG results was approximately 28.2% in CS patients with hemivertebra. Female patients with multiple hemivertebra had a higher risk of UCG abnormalities. Mitral valve abnormalities were the most common abnormality of UCG found in CS patients with hemivertebra. TRIAL REGISTRATION: retrospectively registered.

Cardiac evaluation of hospitalized children with 2019 coronavirus (COVID-19) infection at a single large quaternary center.

Background: Cardiac complications of serious SARS-CoV-2 infections, especially Multisystem Inflammatory Syndrome of Children (MIS-C) are well described, however current studies have not considered pediatric patients hospitalized with no cardiac concerns. We established a protocol for cardiac evaluation of all admitted COVID-19 patients three weeks post-discharge, irrespective of cardiac concerns. We assessed cardiovascular outcomes and hypothesized that patients with absent cardiac concerns are at lower risk for cardiac abnormalities. Methods: This was a retrospective study of 160 patients admitted for COVID-19 (excluding MIS-C) between March 2020 and September 2021 with subsequent echocardiogram(s) performed at our center. Patients were divided into 4 subgroups: Group 1 included patients with absent cardiac concerns, admitted to acute care (1a) and intensive care unit (ICU) (1 b). Group 2 included patients with cardiac concerns, admitted to acute care (2a) and ICU (2 b). Groups were compared based on clinical endpoints and echocardiographic measurements, including tissue Doppler imaging (TDI) assessment of diastolic function (z-score of septal Mitral E/TDI E' and lateral E/TDI E'). Chi-squared, Fisher's exact, and Kruskal-Wallis tests were used. Results: Traditional cardiac abnormalities varied significantly between the groups; with Group 2 b having the most (n = 8, 21%), but still found in Group 1a (n = 2, 3%) and Group 1 b (n = 1, 5%). No patients in Group 1 demonstrated abnormal systolic function, compared to Group 2a (n = 1, 3%) and Group 2 b (n = 3, 9%, p = 0.07). When including TDI assessment of diastolic function, the total incidence of abnormalities found on echocardiogram was increased in all groups. Conclusion: Cardiac abnormalities were found in pediatric patients admitted with COVID-19, even those without apparent cardiovascular concerns. The risk was greatest in ICU-admitted patients with cardiac concerns. The clinical significance of diastolic function assessment in these patients remains unknown. Further studies are needed to assess long-term cardiovascular sequelae of children with COVID-19, irrespective of cardiac concerns.

Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications.

Shock is a life-threatening condition, and its timely recognition is essential for adequate management. Pediatric patients with congenital heart disease admitted to a cardiac intensive care unit (CICU) after surgical corrections are particularly at risk of low cardiac output syndrome (LCOS) and shock. Blood lactate levels and venous oxygen saturation (ScVO2) are usually used as shock biomarkers to monitor the efficacy of resuscitation efforts, but they are plagued by some limitations. Carbon dioxide (CO2)-derived parameters, namely veno-arterial CO2 difference (ΔCCO2) and the VCO2/VO2 ratio, may represent a potentially valuable addition as sensitive biomarkers to assess tissue perfusion and cellular oxygenation and may represent a valuable addition in shock monitoring. These variables have been mostly studied in the adult population, with a strong association between ΔCCO2 or VCO2/VO2 ratio and mortality. In children, particularly in CICU, few studies looked at these parameters, while they reported promising results on the use of CO2-derived indices for patients' management after cardiac surgeries. This review focuses on the physiological and pathophysiological determinants of ΔCCO2 and VCO2/VO2 ratio while summarizing the actual state of knowledge on the use of CO2-derived indices as hemodynamical markers in CICU.

Omphalocele and Cardiac Abnormalities-The Importance of the Association.

Omphalocele is the most common ventral abdominal wall defect. Omphalocele is associated with other significant anomalies in up to 80% of cases, among which the cardiac ones are the most frequent. The aim of our paper is to highlight, through a review of the literature, the importance and frequency of association between the two malformations and what impact this association has on the management and evolution of patients with these pathologies. We reviewed the titles, the available abstracts, and the full texts of 244 papers from the last 23 years, from three medical databases, to extract data for our review. Due to the frequent association of the two malformations and the unfavorable effect of the major cardiac anomaly on the prognosis of the newborn, the electrocardiogram and echocardiography must be included in the first postnatal investigations. The timing of surgery for abdominal wall defect closure is mostly dictated by the cardiac defect severity, and usually the cardiac defect takes priority. After the cardiac defect is medically stabilized or surgically repaired, the omphalocele reduction and closure of the abdominal defect are performed in a more controlled setting, with improved outcomes. Compared to omphalocele patients without cardiac defects, children with this association are more likely to experience prolonged hospitalizations, neurologic, and cognitive impairments. Major cardiac abnormalities such as structural defects that require surgical treatment or result in developmental delay will significantly increase the death rate of patients with omphalocele. In conclusion, the prenatal diagnosis of omphalocele and early detection of other associated structural or chromosomal anomalies are of overwhelming importance, contributing to the establishment of antenatal and postnatal prognosis.

Subclinical cardiac abnormalities in children with biliary atresia correlate with outcomes after liver transplantation.

Objective: There are subclinical cardiac abnormalities (SCA) in children with biliary atresia (BA). However, data on the consequences of these cardiac changes after liver transplantation (LT) remain controversial in the pediatric field. We aimed to determine the relationship between outcomes and the subclinical cardiac abnormalities in pediatric patients with BA based on two-dimensional echocardiography (2DE) parameters. Methods: A total of 205 children with BA were enrolled in this study. The relationship between 2DE parameters and outcomes, including death and serious adverse events (SAE) after LT, was analyzed by regression analysis. Using receiver operator characteristic (ROC) curves to determine the optimal cut-off values of 2DE parameters for outcomes. Differences in the AUCs were compared using DeLong's test. The Kaplan -Meier method with log-rank testing was used to evaluate survival outcomes between groups. Results: Left ventricular mass index (LVMI) and relative wall thickness (RWT) were found to be independently associated with SAE (OR: 1.112, 95% CI: 1.061 - 1.165, P < 0.001 and OR: 1.193, 95% CI: 1.078 - 1.320, P = 0.001, respectively). The cutoff value of LVMI for predicting the SAE was 68 g/m2.7 (AUC = 0.833, 95% CI 0.727-0.940, P < 0.001), and the cutoff value of RWT for predicting the SAE was 0.41 (AUC = 0.732, 95% CI 0.641-0.823, P < 0.001). The presence of subclinical cardiac abnormalities (LVMI > 68 g/m2.7, and/or RWT > 0.41) was associated with lower patient survival (1-year, 90.5% vs 100.0%; 3-year, 89.7% vs 100.0, log-rank P = 0.001). and higher incidence of SAE events. Conclusions: Subclinical cardiac abnormalities were correlated with post-LT mortality and morbidity in children with BA. LVMI can predict the occurrence of death and serious adverse events after liver transplantation.

Immunologic, Molecular, and Clinical Profile of Patients with Chromosome 22q11.2 Duplications.

PURPOSE: Duplication of chromosome 22q11.2 due to meiotic non-allelic homologous recombination results in a distinct syndrome, chromosome 22q11.2 duplication syndrome that has some overlapping phenotypic features with the corresponding 22q11.2 deletion syndrome. Literature on immunologic aspects of the duplication syndrome is limited. We conducted a retrospective study of 216 patients with this syndrome to better define the key features of the duplication syndrome. METHODS: Single-center retrospective record review was performed. Data regarding demographics, clinical details, and immunological tests were compiled, extracted into a predetermined data collection form, and analyzed. RESULTS: This cohort comprised 113 (52.3%) males and 103 (47.7%) females. The majority (54.6%) of mapped duplications were between low copy repeat regions A-D (LCR22A to -D). Though T cell subsets were relatively preserved, switched memory B cells, immunoglobulins, and specific antibodies were each found to be decreased in a subset of the cohort. One-fifth (17/79, 21.5%) of patients had at least 2 low immunoglobulin values, and panhypogammaglobulinemia was found in 11.7% (9/79) cases. Four children were on regular immunoglobulin replacement therapy. Asthma and eczema were the predominant atopic symptoms in our cohort. CONCLUSION: Significant immunodeficiencies were observed in our cohort, particularly in B cells and antibodies. Our study expands the current clinical understanding and emphasizes the need of immunological studies and multidisciplinary approaches for these patients.

The Value of Concurrent Electrocardiography When Performing an Electroencephalograph.

Introduction. The use of concurrent, single lead electrocardiograph (ECG) recording, when performing a routine electroencephalograph (EEG), has been standard practice for many years. Previous studies have reported on the usefulness of concurrent EEG in assessing syncope and the detection of newly identified cardiac dysrhythmia but have relied on specialist cardiologist interpretation of the ECG trace. This study expands the understanding of concurrent ECG and provides demographic information regarding the incidence, nature of ECG changes and diagnostic utility of ECG interpretation, during routine EEGs, as evaluated by neurologists. Methods. A single center, retrospective study of routine concurrent EEG and ECG recordings was performed. All routine EEGs, performed within a 12 month period were analysed. Demographic data, underlying comorbidities, reasons for referral and ECG changes were assessed. Results. ECG abnormalities were identified in 147 (13.5%) of concurrent ECG/EEG routine recordings. The presence of ECG abnormalities was significantly associated with the reason for referral, namely being assessed for the evaluation of seizure activity and with increasing patient age. Thirty-eight patients (3.5%) had newly identified ECG abnormalities, of which atrial fibrillation (AF) (12 patients) and sinus bradycardia (9 patients) were the most common. Five patients (0.5%) had a change in their management consequent to the identified ECG changes. Conclusions. These findings support the value of neurologists' interpretation and need for ongoing concurrent ECGs, during routine EEG recordings. The study raises concern about the requesting clinician's response to the identification of newly diagnosed cardiac dysrhythmias.

Focused Cardiac Ultrasound to Guide the Diagnosis of Heart Failure in Pregnant Women in India.

BACKGROUND: Cardiac complications are a leading cause of maternal death. Cardiac imaging with echocardiography is important for prompt diagnosis, but it is not available in many low-resource settings. The aim of this study was to determine whether focused cardiac ultrasound performed by trained obstetricians and interpreted remotely by experts can identify cardiac abnormalities in pregnant women in low-resource settings. METHODS: A cross-sectional study was conducted among 301 pregnant and postpartum women recruited from 10 hospitals across three states in India. Twenty-two obstetricians were trained in image acquisition using a portable cardiac ultrasound device following a simplified protocol adapted from focus-assessed transthoracic echocardiography protocol. It included parasternal long-axis, parasternal short-axis, and apical four-chamber views on two-dimensional and color Doppler. Independent image interpretation was performed remotely by two experts, in the United Kingdom and India, using a standard semiquantitative assessment protocol. Interrater agreement between the experts was examined using Cohen's κ. Diagnostic accuracy of the method was examined in a subsample for whom both focused and conventional scans were available. RESULTS: Cardiac abnormalities identified using the focused method included valvular abnormalities (27%), rheumatic heart disease (6.6%), derangements in left ventricular size (4.7%) and function (22%), atrial dilatation (19.5%), and pericardial effusion (30%). There was substantial agreement on the cardiac parameters between the two experts, ranging from 93.6% (κ = 0.84) for left ventricular ejection fraction to 100% (κ = 1) for valvular disease. Image quality was graded as good in 79% of parasternal long-axis, 77% of parasternal short-axis and 64% of apical four-chamber views. The chance-corrected κ coefficients indicated fair to moderate agreement (κ = 0.28-0.51) for the image quality parameters. There was good agreement on diagnosis between the focused method and standard echocardiography (78% agreement), compared in 36 participants. CONCLUSIONS: The focused method accurately identified cardiac abnormalities in pregnant women and could be used for screening cardiac problems in obstetric settings.

Screening and prevalence of cardiac abnormalities on electro- and echocardiography in a large cohort of patients with mitochondrial disease.

BACKGROUND: In patients with primary mitochondrial disease (MD), screening with electrocardiogram (ECG) and transthoracic echocardiography (TTE) is warranted according to current guidelines as structural cardiac abnormalities are frequent. This study aims to evaluate the cardiac phenotype of a large Dutch cohort of patients with MD and investigates whether ECG alone is sufficient for predicting structural cardiac abnormalities on TTE. METHODS: In this retrospective cohort study, genetically confirmed MD patients >18 years old with an available ECG and TTE were included. Newcastle Mitochondrial Disease Scale for Adults (NMDAS) scores were assessed. ECG's were evaluated for rhythm and conduction disorders, voltage criteria for left ventricular hypertrophy (LVH) and repolarization disorders. Echocardiographic evaluation included left and right ventricular volumes and function, and presence of LVH or concentric remodeling. RESULTS: In total, 200 MD patients were included with a median age of 45 years (IQR; 37-57) of whom 36% were male. Of all MD patients, 35% had abnormalities on ECG and 61% on TTE. Most frequent structural cardiac abnormalities on TTE were: global longitudinal strain > - 18% (54%), concentric remodeling (27%) and left ventricular (LV) ejection fraction <52% (14%). Patients with maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) had the highest prevalence of ECG abnormalities (50% and 47%). TTE abnormalities were most prevalent in patients with MIDD (75%), followed by mitochondrial myopathy (MM) (55%), MELAS (47%) and Mitochondrial Epilepsy and Ragged Red Fibers (MERRF) (47%). MD patients with a high disease severity (NMDAS ≥21) had a higher prevalence of ECG abnormalities (44%, p = 0.039) and structural cardiac abnormalities (72%, p = 0.004) compared to patients with a NMDAS score of 11-20 and ≤ 10 (ECG: 34% and 19%; TTE: 63% and 39%). ECG abnormalities had a positive predictive value of 74% and a negative predictive value of 53% for structural cardiac abnormalities on TTE. CONCLUSION: MD patients frequently have cardiac involvement especially patients with MIDD, MELAS or high NMDAS score. ECG as sole screening parameter is insufficient to detect structural cardiac abnormalities.

Incidental Finding of Heterotaxy Syndrome in a Patient With Pulmonary Embolism: A Case Report and Concise Review.

Heterotaxy syndrome, also called atrial isomerism, is a rare congenital condition in which the internal organs are abnormally arranged across the left-right axis of the body. It is classified into polysplenia syndrome or left atrial isomerism and asplenia syndrome or right atrial isomerism. It is associated with high morbidity and mortality due to the severity of cardiac anomalies. It is important to be aware of the syndrome findings as they can be incidentally found on imaging in adults. Here, we report a case of a 33-year-old female who presented with worsening shortness of breath, found to have a pulmonary embolism, and heterotaxy was incidentally identified on her imaging. A concise review follows.

Diverse clinical manifestations and intrafamilial variability due to an inherited recurrent MYRF variant.

MYRF monoallelic variants have been described in syndromic forms characterized by cardiac-urogenital syndrome and isolated nanophthalmos with/without minor systemic manifestations. We describe a large family with a paternally inherited pathogenic variant in MYRF that manifested as congenital diaphragmatic hernia (CDH), cardiac and urogenital abnormalities, and/or nanophthalmos with significant intrafamilial variability.