Discriminating factors excluding patients from a catheter-based left atrial appendage closure and an outcome analysis of non-intervened and intervened patients.

Introduction: The catheter-based left atrial appendage closure (LAAC) has evolved as an alternative to oral anticoagulation (OAC) among non-valvular atrial fibrillation (AF) patients in whom long-term OAC is contraindicated. In daily practice, however, a sizeable number of patients who have been referred for an LAAC do not receive this intervention. This study aimed primarily to investigate the factors deterring the practice of an LAAC in referred AF patients, and secondarily to compare the complication rates of intervened patients with those who had refused the intervention within 1 year. Material and methods: This retrospective single-centre study includes 200 patients. After a thoroughly conducted clinical selection process, 161 of these patients (80.5%) were excluded from receiving an LAAC intervention. Results: An analysis comparing these patients to those receiving an LAAC reveales that a higher proportion of intervened patients had suffered a prior gastrointestinal bleeding (48.7 vs. 28.0%; p = 0.013) as well as a haemorrhagic stroke (12.8 vs. 2.5%; p = 0.015), and was not anticoagulated at the time of presentation (35.9 vs. 14.9%; p = 0.006). The main reason for not conducting the procedure was patient refusal (62.1%) followed by multimorbidity (16.8%). The annual rate of ischaemic strokes and bleedings among patients refusing the intervention was 2.1% and 29.5%, respectively, and this was not statistically different from the intervened patients (each p > 0.05). Conclusions: The reasons why patients did not undergo the catheter-based LAAC were mainly reluctance for the procedure and multimorbidity. Furthermore, it could be assumed that the potential benefit of the LAAC may not be realised within the first year.

A protein-miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs).

Chemical-induced neurotoxicity is increasingly recognized to accelerate the development of neurodegenerative disorders (NDs), which pose an increasing health burden to society. Attempts are being made to develop drugs that can cross the blood-brain barrier and have minimal or no side effects. Nobiletin (NOB), a polymethoxylated flavonoid with anti-oxidative and anti-inflammatory effects, has been demonstrated to be a promising compound to treat a variety of NDs. Here, we investigated the potential role of NOB in sodium arsenate (NA)-induced deregulated miRNAs and target proteins in human neural progenitor cells (hNPCs). The proteomics and microRNA (miRNA) profiling was done for different groups, namely, unexposed control, NA-exposed, NA + NOB, and NOB groups. Following the correlation analysis between deregulated miRNAs and target proteins, RT-PCR analysis was used to validate the selected genes. The proteomic analysis showed that significantly deregulated proteins were associated with neurodegeneration pathways, response to oxidative stress, RNA processing, DNA repair, and apoptotic process following exposure to NA. The OpenArray analysis confirmed that NA exposure significantly altered miRNAs that regulate P53 signaling, Wnt signaling, cell death, and cell cycle pathways. The RT-PCR validation studies concur with proteomic data as marker genes associated with autophagy and apoptosis (HO-1, SQSTM1, LC-3, Cas3, Apaf1, HSP70, and SNCA1) were altered following NA exposure. It was observed that the treatment of NOB significantly restored the deregulated miRNAs and proteins to their basal levels. Hence, it may be considered one of its neuroprotective mechanisms. Together, the findings are promising to demonstrate the potential applicability of NOB as a neuroprotectant against chemical-induced neurotoxicity.

LAA occlusion is effective and safe in very high-risk atrial fibrillation patients with prior stroke: results from the multicentre German LAARGE registry.

BACKGROUND: Interventional left atrial appendage occlusion (LAAO) mitigates the risk of thromboembolic events in nonvalvular atrial fibrillation (AF) patients with contraindication for long-term oral anticoagulation (OAC). Patients with prior stroke have a relevantly increased risk of recurrent stroke, so the effectiveness of LAAO could be reduced in this specific very high-risk patient group. AIM: This sub-study of the LAARGE registry investigates the effectiveness and safety of LAAO for secondary prevention in nonvalvular AF patients with a history of stroke. METHODS: LAARGE is a prospective, non-randomised registry on the clinical reality of LAAO. The current sub-study employs data from index procedure and 1-year follow-up. Effectiveness and safety were assessed by documentation of all-cause mortality, non-fatal thromboembolism, procedure-related complications, and bleeding events. RESULTS: A total of 638 patients were consecutively included from 38 hospitals in Germany and divided into two groups: 137 patients with a history of stroke (21.5%) and 501 patients without. Successful implantation was consistent between both groups (98.5% vs. 97.4%, p = NS), while peri-procedural MACCE and other complications were rare (0% vs. 0.6% and 4.4% vs. 4.0%, respectively; each p = NS). Kaplan-Meier estimate showed no significant difference in primary effectiveness outcome measure (freedom from all-cause death or non-fatal stroke) between both groups at follow-up (87.8% vs. 87.7%, p = NS). The incidence of transient ischemic attack or systemic embolism at follow-up was low (0% vs. 0.5% and 0.9% vs. 0%, respectively; each p = NS). Severe bleeding events after hospital discharge were rare (0% vs. 0.7%, p = NS). CONCLUSIONS: Patients with prior stroke demonstrated similar effectiveness and safety profile for LAAO as compared to patients without prior stroke. LAAO could serve as a feasible alternative to OAC for secondary stroke prevention in this selected group of nonvalvular AF patients. GOV IDENTIFIER: NCT02230748.

Determinants of immunization in polio super high-risk union councils of Pakistan.

BACKGROUND: The current polio epidemiology in Pakistan poses a unique challenge for global eradication as the country is affected by ongoing endemic poliovirus transmission. Across the country, 40 union councils (UCs) which serve as core reservoirs for poliovirus with continuous incidences of polio cases are categorized as super-high-risk union councils (SHRUCs). METHODOLOGY: A cross-sectional survey was conducted in 39 SHRUCs using a two-stage stratified cluster sampling technique. 6,976 children aged 12-23 months were covered. A structured questionnaire was used for data collection. Data were analyzed using STATA version 17. RESULTS: Based on both vaccination records and recall, 48.3% of children were fully-, 35.4 % were partially-, and 16.3% were non-vaccinated in the SHRUC districts. A child is considered fully vaccinated when h/she completed vaccination for BCG, OPV0, OPV 1-3, Penta 1-3, PCV 1-3, IPV, and MCV1. Vaccination cards were seen for over half of the children in the SHRUC districts of Khyber Pakhtunkhwa (KP) and the majority of the SHRUC districts in Sindh, except for the SHRUC district of Malir the districts of Balochistan. Results for polio vacancies show that 60.9% of children from the SHRUC districts were vaccinated with at least three doses of OPV and one dose of IPV, while 20.4% were vaccinated with any OPV doses or IPV and 18.7% of children did not receive any polio vaccines. The dropout rate between vaccine visits was higher than the WHO-recommended cutoff point of 10% for all vaccine doses in the SHRUC districts. The likelihood of being fully vaccinated was higher among the children of educated parents. Full vaccination was found significant among the children of any SHRUC districts compared to district Killa Abdullah. CONCLUSION: Context-specific strategies with more focus on community engagement and targeted mobilization, along with robust monitoring mechanisms, would help address the underlying challenges of under-immunization in the SHRUCs.

Exploring the long-term seroprevalence of SARS-CoV-2 antibodies in infants born to women with clinical or laboratory-confirmed COVID-19.

INTRODUCTION: Infants are at a higher risk of severe illness with COVID-19 infection compared to older children. While COVID-19 vaccination is not recommended for young infants, they can acquire maternally-derived anti-SARS-CoV-2 antibodies passively through the placenta and breastmilk. We described the persistence of infection-induced maternal antibodies in infant circulation at 9-12 months of age. METHODOLOGY: This was a cross-sectional study nested within the INTERCOVID multinational cohort study. For each COVID positive pregnant woman, two unmatched consecutive COVID negative pregnant women were enrolled between April and September 2020. Women with a positive PCR test, radiographic signs consistent with COVID-19, or at least 2 predefined symptoms of COVID-19 were considered as COVID positive. For this nested cross-sectional study, all COVID positive and either one of the COVID negative participants recruited from the Aga Khan University, Pakistan were approached 9-12 months after delivery, and maternal and infant sera were collected for antibody detection. RESULTS: Altogether, 83 mothers provided consent, of whom 32 (38.6 %) were COVID positive and 51 (61.4 %) were COVID negative during pregnancy. Anti-SARS-CoV-2 antibodies were present in 13 (41 %) infants born to COVID positive and 19 (39 %) infants born to COVID negative mothers (p = 0.87). The presence of reactive antibodies in infants at follow-up was associated with maternal antibodies at follow-up (OR:9.50, 95 % CI:2.03-44.42; p = 0.004). COVID infection occurred in 3 (6 %) infants born to COVID negative mothers while no infant born to a COVID positive mother had a history of infection (p = 0.27). CONCLUSION: The presence of reactive anti-SARS-CoV-2 antibodies in infants at 9-12 months of age is associated with maternal seropositivity 9-12 months after delivery rather than maternal infection during pregnancy. Further studies are required to validate these findings and assess whether passive immunity in infants is protective against COVID-19 infection.

TORC1 mediated regulation of mitochondrial integrity and calcium ion homeostasis by Wat1/mLst8 in S. pombe.

The mTOR complexes play a fundamental role in mitochondrial biogenesis and cellular homeostasis. Wat1, an ortholog of mammalian Lst8 is an important component of TOR complex and is essential for the regulation of downstream signaling. Earlier we reported the role of Wat1 in oxidative stress response. Here, we have shown that the abrogation of wat1 causes respiratory defects and mitochondrial depolarization that leads to a decrease in ATP production. The confocal and electron microscopy in wat1Δ cells revealed the fragmented mitochondrial morphology implying its role in mitochondrial fission. Furthermore, we also showed its role in autophagy and the maintenance of calcium ion homeostasis. Additionally, tor2-287 mutant cells also exhibit defects in mitochondrial integrity indicating the TORC1-dependent involvement of Wat1 in the maintenance of mitochondrial homeostasis. The interaction studies of Wat1 and Tor2 with Por1 and Mmm1 proteins revealed a plausible cross-talk between mitochondria and endoplasmic reticulum through the Mitochondria-associated membranes (MAM) and endoplasmic reticulum-mitochondria encounter structure (ERMES) complex, involving TORC1. Taken together, this study demonstrates the involvement of Wat1/mLst8 in harmonizing various mitochondrial functions, redox status, and Ca2+ homeostasis.

Description of a new clinical syndrome: thoracic constriction without evidence of the typical funnel-shaped depression-the "invisible" pectus excavatum.

Pectus excavatum (PE) is a congenital malformation with a funnel-shaped depression of the sternum that can lead to cardiac symptoms. However, there are patients with thoracic constriction (defined as elevated Haller-Index > 3.25 determined by cardiac magnetic resonance imaging (CMR)) without visible evidence of PE, leading to similar complaints. Between January 2004 till June 2020, patients who underwent CMR for further evaluation of the heart, due to cardiac symptoms were enrolled and compared to controls. Biventricular global strain analysis was assessed using feature tracking (CMR-FT). ECG and/or Holter recordings were performed to detect rhythm events. Cardiac symptoms were evaluated in detail using a questionnaire. Finally, 88 patients (male 35, female 53) with elevated Haller-Index (3.9 ± 0.8) were included and compared to CMR data from 25 individuals with confirmed PE and 25 healthy controls (HC). Mean age at time of CMR was 35 ± 16 years. The most common symptoms at presentation were palpitations (41%), followed by dyspnea (24%) and atypical chest pain (14%). Three patients (3%) had atrial fibrillation or atrial flutter. Concomitant phenomena were pericardial effusion in 39% and mitral valve prolapse (MVP) in 27% of the study cohort. While there were no differences in left ventricular function or volumes, right ventricular function (RVEF) was significantly lower in patients with internal PE compared to HC (RVEF (%) 50 ± 5 vs 59 ± 4, p < 0.01). Strain analysis revealed only discrete changes in RV strain, implying a purely mechanical problem in the absence of structural changes. RV dimensions were negatively correlated with the size of thoracic indices (r = 0.41), reflecting the extent of thoracic constriction. MVP was more prevalent in patients with greater thoracic indices (r = 0.24). The described cohort, referred to as internal PE because of the absence of external changes, showed similar CMR morphologic findings as patients with real PE (especially altered dimensions of the right heart and a lower RVEF). In addition, there was a high incidence of rhythm disturbances, such as extrasystoles or arrhythmias. In one-third of the study cohort additional abnormalities such as pericardial effusion or MVP were present, with MVP being found more frequently in patients with larger thoracic indices, suggesting a possible common pathogenesis.Trial registration: ISRCTN registry, ISRCTN15355937, retrospectively registered 03.06.2022, https://www.isrctn.com/ISRCTN15355937?q=15355937&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10 .

Routine Immunization Coverage and Immunization Card Retention in Pakistan: Results From a Cross-sectional National Survey.

BACKGROUND: Immunization is one of the most successful public health interventions available, saving millions of lives from death and disability each year. Therefore, improving immunization coverage is a high priority for the Government of Pakistan and essential to progress toward universal health coverage. This survey reports the national and provincial/regional coverage and determinants of fully, partially, and not-vaccinated children 12-23 months of age, antigen-wise coverage, percentage of home-based vaccination records (HBR) retention, and reasons for nonretention; dropout, timeliness, and prevalence of missed opportunities for simultaneous vaccination (MOSV). METHODS: The survey was a descriptive cross-sectional national household survey carried out across Pakistan. The survey included 110,790 children 12-23 months old and their caregivers. A World Health Organization (WHO)-Expanded Program on Immunization (EPI) Survey questionnaire was adapted to collect information. Data were analyzed using the WHO Vaccination Coverage Quality Indicators (VCQI) software and Stata version 17. RESULTS: Nationally excluding Azad Jammu and Kashmir (AJK) and Gilgit Baltistan (GB), the coverage of fully vaccinated children was 76.5%. The likelihood of being fully vaccinated was higher among children of educated parents who belonged to higher wealth quintiles and resided in any province/region other than Balochistan. The main reasons for unimmunization were no faith in immunization, rumors about vaccines, and distance to the facility. About two-thirds (66.2%) of the children had their HBR available, and the main reasons for not having a card were never visiting a health facility and having no awareness about the importance of a card. Dropout was discernible for later doses of vaccines compared with earlier ones. Higher proportions of children received the last doses late by more than two months. Of the 218,002 vaccination visits documented on HBR in the provinces, MOSVs occurred in 17.6% of the visits. CONCLUSION: The immunization coverage rates provide a direction to strategize the progress to improve the vaccination rates in Pakistan. The country needs to outline the immediate and long-term actions to combat vaccine-preventable diseases, such as escalating integrated immunization campaigns and outreach activities, provision of mobility support, and deploying behavioral interventions as a cross-cutting strategy to improve awareness and reduce misconceptions.

Sparse 3D contrast-enhanced whole-heart imaging for coronary artery evaluation.

BACKGROUND: We investigated the feasibility of evaluating coronary arteries with a contrast-enhanced (CE) self-navigated sparse isotropic 3D whole heart T1-weighted magnetic resonance imaging (MRI) study sequence. METHODS: A total of 22 consecutive patients underwent coronary angiography and/or cardiac computed tomography (CT) including cardiac MRI. The image quality was evaluated on a 3-point Likert scale. Inter-reader variability for image quality was analyzed with Cohen's kappa for the main coronary segments (left circumflex [LCX], left anterior descending [LAD], right coronary artery [RCA]) and the left main trunk (LMT). RESULTS: Inter-reader agreement for image quality of the coronary tree ranged from substantial to perfect, with a Cohen's kappa of 0.722 (RCAmid) to 1 (LCXprox). The LMT had the best image quality. Image quality of the proximal vessel segments differed significantly from the mid- and distal segments (RCAprox vs. RCAdist, p < 0.05). The LCX segments showed no significant difference in image quality along the vessel length (LCXprox vs. LCXdist, p = n.s.). The mean acquisition time for the study sequence was 553 s (±46 s). CONCLUSION: Coronary imaging with a sparse 3D whole-heart sequence is feasible in a reasonable amount of time producing good-quality imaging. Image quality was poorer in distal coronary segments and along the entire course of the LCX.

Impact of age on the prognosis of patients with ventricular tachyarrhythmias and aborted cardiac arrest.

BACKGROUND: This study evaluated the prognostic impact of age on patients presenting with ventricular tachyarrhythmias (VTA) and aborted cardiac arrest. MATERIAL AND METHODS: The present registry-based, monocentric cohort study included all consecutive patients presenting at the University Medical Center Mannheim (UMM) between 2002 and 2016 with ventricular tachycardia (VT), ventricular fibrillation (VF) and aborted cardiac arrest. Middle-aged (40-60 years old) were compared to older patients (> 60 years old). Furthermore, age was analyzed as a continuous variable. The primary endpoint was all-cause mortality at 2.5 years. The secondary endpoints were cardiac death at 24 h, all-cause mortality at index hospitalization, all-cause mortality after index hospitalization and the composite endpoint at 2.5 years of cardiac death at 24 h, recurrent VTA, and appropriate implantable cardioverter defibrillator (ICD) treatment. RESULTS: A total of 2259 consecutive patients were included (28% middle-aged, 72% older). Older patients were more often associated with all-cause mortality at 2.5 years (27% vs. 50%; hazard ratio, HR = 2.137; 95% confidence interval, CI 1.809-2.523, p = 0.001) and the secondary endpoints. Even patient age as a continuous variable was independently associated with mortality at 2.5 years in all types of VTA. Adverse prognosis in older patients was demonstrated by multivariate Cox regression analyses and propensity score matching. Chronic kidney disease (CKD), systolic left ventricular dysfunction (LVEF) < 35%, cardiopulmonary resuscitation (CPR) and cardiogenic shock worsened the prognosis for both age groups, whereas acute myocardial infarction (STEMI/NSTEMI) and the presence of an ICD improved prognosis. CONCLUSION: The results of this study suggest that increasing age is associated with increased mortality in VTA patients. Compared to the middle-aged, older patients were associated with higher all-cause mortality at 2.5 years and the secondary endpoints.

Distance-quality trade-off and choice of family planning provider in urban Pakistan.

BACKGROUND: There is limited evidence between contraceptive use, availability of commodities and distance to the facility in developing countries. Distance to the facility is an essential determinant of contraceptive use. Still, women may not seek family planning services from the nearest facility and may be prepared to travel the farthest distance to receive quality family planning services. METHODS: We analyzed women's survey data linked to health facility data and applied an alternate specific conditional logit model to examine the distance a woman is prepared to travel and the quality of services offered by facilities in urban areas in Karachi, Pakistan. RESULTS: This study analyzed data from 336 women and 28 facilities and identified that the mean distance to the nearest facility was 0.44 km; the chosen facility was, on average, 5 km away. Women preferred facilities that offered a range of contraceptive methods and additional services provided by female healthcare providers only. Furthermore, on average, women are willing to travel a further 1.7 km for a facility that offers more family planning methods, 1.4 km for a facility that offers additional health services and 11 km for a facility that offers services delivered by female healthcare providers. CONCLUSIONS: The findings highlight the quality measures women prioritize over distance and consider essential when choosing a family planning facility.

Septal myocardial scar burden predicts the response to cardiac contractility modulation in patients with heart failure.

We hypothesized that myocardial septal scarring, assessed by cardiac magnetic resonance (CMR) using late gadolinium enhancement (LGE), at the site of cardiac contractility modulation (CCM) lead placement may predict treatment response. Eligible heart failure (HF) patients underwent LGE CMR imaging before CCM device implantation. The response to CCM therapy at follow-up was determined by a change in NYHA class and echocardiographic left ventricular ejection fraction (LVEF) assessment. Patients were classified as responders, if they showed an improvement in either NYHA class or improvement of LVEF by ≥ 5%. 58 patients were included. 67% of patients were classified as responders according to improved NYHA; 55% according to LVEF improvement. 74% of patients were responders if either NYHA class or LVEF improvement was observed. 90% of responders (according to NYHA class) showed septal LGE < 25% at septal position of the leads, while 44% of non-responders showed septal LGE > 25% (p < 0.01). In patients treated with CCM, an improvement of NYHA class was observed when leads were placed at myocardial segments with a CMR- LGE burden less than 25%.

Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan.

BACKGROUND: Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5-10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. METHODS: Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher's exact, Pearson's chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. RESULTS: Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5-48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42-5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. CONCLUSIONS: In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.

Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs.

Environmental exposure to arsenic has been profoundly associated with chronic systemic disorders, such as neurodegeneration, in both experimental models and clinical studies. The neuronal cells of the brain and the nervous system have a limited regeneration capacity, thus making them more vulnerable to exposure to xenobiotics, leading to long-lasting disabilities. The functional and anatomical complexity of these cells hinders the complete understanding of the mechanisms of neurodegeneration and neuroprotection. The present investigations aimed to evaluate the neuroprotective efficacy of a herbal formulation of Nobiletin (NOB) against the toxic insult induced by sodium arsenate (NA) in human neural progenitor cells (hNPCs) derived from human induced pluripotent stem cells (hiPSCs). Prior to the neuroprotective experiments, biologically safe doses of both NOB and NA were ascertained using standard endpoints of cytotoxicity. Thereafter, the hNPCs were exposed to either NOB (50 µM) or NA (50 µM) and co-exposed to biologically safe concentrations of NA (50 µM) with NOB (50 µM) for a period of up to 48 h. NOB treatment restored the morphological damage (neurite damage), the levels of stress granule G3BP1 (Ras-GTPase-activating protein (SH3 domain)-binding protein) and TIA1 (T cell-restricted intracellular antigen), and the expression of neuronal markers (Tuj1, Nestin, MAP2, and PAX6) when compared to NA-exposed cells. A substantial restoration of reactive oxygen species and mitochondrial membrane potential was also witnessed in the co-exposure group (NA + NOB) in comparison to the NA-exposed group. The findings suggest that NOB possesses a significant restorative/protective potential against the NA challenge in hNPCs under experimental conditions and imply that nobiletin may impart a potential therapeutic impact if studied adequately using in vivo studies.

Case Report: Transient Increase of CMR T1 Mapping Indices in a Patient With COVID-19 mRNA Vaccine Induced Acute Myocarditis.

Background: Acute myocarditis is commonly associated with viral infections, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Myocarditis following mRNA COVID-19 vaccination has also been reported, however this is rare and usually resolves within days or weeks. We present a case of acute myocarditis reported after vaccination with mRNA-1273 COVID-19 vaccine (Moderna) diagnosed using cardiac magnetic resonance imaging (CMR). This report describes the utility of CMR in the diagnosis and follow-up of such patients using parameters which could suggest the clinical course of myocarditis. Case Summary: A 23-year-old male presented in the emergency department with complaints of chest pain radiating to the left arm following vaccination with the second dose of COVID-19 mRNA-1273 vaccine (Moderna). Patient's history revealed an incidence of myocarditis in the past. CMR showed a mid-range left ventricular ejection fraction (38%) and subepicardial late gadolinium enhancement (LGE) in the inferolateral and apical myocardial segments with diffuse elevation of native T1 mapping relaxation times in all myocardial segments. The patient was admitted briefly in the intensive care unit and after a favorable clinical course was discharged from the hospital in stable condition. A follow-up CMR after 3 months revealed normalization of LVEF (57%) and native T1- times in most segments. Scarred myocardium reflecting chronic myocarditis continued to show elevated T1 times. Conclusions: Our patient presenting with acute myocarditis after recent COVID-19 mRNA vaccination reported a favorable clinical course. CMR revealed increased T1 mapping relaxation times diffusely spread across the myocardium and an impairment of the left ventricular function (LVEF) during the acute phase. However, the LVEF as well as the T1 times normalized at follow-up in all segments except for myocardium affected by chronic myocarditis.

Diagnostic accuracy of point-of-care ultrasound compared to standard-of-care methods for endotracheal tube placement in neonates.

INTRODUCTION: Point-of-care ultrasound (POCUS) is a valuable tool to determine endotracheal tube (ETT) placement; however, few studies have compared it with standard confirmation methods. We evaluated the diagnostic accuracy of POCUS and time-to-interpretation for correct identification of tracheal versus esophageal intubations compared to a composite of standard-of-care methods in neonates. METHODS: A cross-sectional study was conducted in the Neonatal Intensive Care Unit (NICU) at Aga Khan University Hospital Karachi, Pakistan. All required intubations were performed as per NICU guidelines. The clinical team simultaneously determined the ETT placement using standard-of-care methods (auscultation, colorimetric capnography, and chest X-ray) by POCUS. In addition, the clinical team was blinded to the POCUS images. Timings were recorded for each method by independent study staff. RESULTS: A total of 348 neonates were enrolled in the study. More than half (58%) of intubations were in an emergency scenario. POCUS user interpretation showed 100% sensitivity and 94% specificity using an expert as the reference standard. We found a 99.4% agreement (Kappa: 0.96; p < 0.001). Diagnostic accuracy of POCUS compared with at least two standard-of-care methods demonstrated 99.7% sensitivity, 91% specificity, and 98.9% agreement (Kappa:0.93; p < 0.001). The median time required for POCUS interpretation was 3.0 (interquartile range [IQR] 3.0-4.0) seconds for tracheal intubation. The time recorded for auscultation and capnography was 6.0 (IQR 5.0-7.0) and 3.0 (IQR 3.0-4.0), respectively. CONCLUSION: POCUS is a rapid and reliable method of identifying ETT placement in neonates. Early and correct identification of airway management is critical to save lives and prevent mortality and morbidity.

Cardiac disease and prognosis associated with ventricular tachyarrhythmias in young adults and adults.

BACKGROUND: This study evaluates cardiac diseases and prognosis in young adults and adults presenting with ventricular tachyarrhythmias (VTA). METHODS: The present longitudinal, observational, registry-based, monocentric cohort study includes all consecutive patients 45 years old or younger presenting with VTA at admission from 2002 to 2016. Rates of coronary angiography, coronary artery disease (CAD) and need for percutaneous coronary intervention (PCI), cardiac diseases associated with VTA, and differences in long-term prognostic endpoints for young adults (20-34 years old) were analyzed and compared to those of adults (35-45 years old), for whom multivariable risk prediction models were developed. Kaplan-Meier analyses were performed according to age and type of VTA. RESULTS: A total of 259 consecutive patients were included in the study (36% young adults and 64% adults). At admission, 38% of young adults had VTA due to CAD that required PCI. Furthermore, VTA in young adults was commonly idiopathic (27%), or had underlying channelopathies (18%), primary cardiomyopathies (13%) or acute myocardial infarction (AMI, 11%). In adults, VTA was mostly associated with AMI (28%), though the rate of idiopathy was still high (20%). A total 41% of all patients received cardiopulmonary resuscitation (CPR), for whom AMI (STEMI 17%, NSTEMI 24%) was most frequently observed. Irrespective of the type of VTA, all-cause mortality was similar for young adults and adults. In young adults, left ventricular ejection fraction (LVEF) < 35% (HR = 33.590) was associated with increased long-term all-cause mortality. CONCLUSION: Despite high rates of idiopathic ventricular tachyarrhythmias, CAD and AMI are common causes of VTA and CPR in adults 45 years old and younger. Young adults and adults had comparable survival at index hospitalization and after 2.5 years irrespective of the type of VTA. Clinical trial registration clinicaltrials.gov identifier: NCT02982473.

Adverse events and stroke prevention by interventional left atrial appendage occlusion in patients with low CHA2 DS2 -VASc score-results from the multicenter German LAARGE registry.

BACKGROUND: Interventional left atrial appendage occlusion (LAAO) is routinely performed in patients with nonvalvular atrial fibrillation and contraindications to standard anticoagulation. AIMS: We investigated its role in patients at low stroke risk, and compared the effectiveness and safety in patients with low versus high risk. METHODS: LAARGE is a prospective registry depicting the clinical reality of LAAO. LAAO was conducted with different standard commercial devices, and follow-up period was 1 year. Patients with started procedure and documented CHA2 DS2 -VASc score were selected from the whole database. RESULTS: A total of 638 patients from 38 centers were divided into CHA2 DS2 -VASc score ≤2, i.e., low-risk group (10.2%), and >2, i.e., high-risk group (89.8%). The latter had a pronounced cardiovascular risk profile and preceding strokes (0% vs. 23.9%; p < 0.001). Implantation success was consistently high (97.6%), frequencies of intrahospital major adverse cardiac and cerebrovascular events (0% vs. 0.5%) and other major complications (4.6% vs. 4.0%) were low (each p = not significant [NS]). Numerous moderate complications were also observed in the low-risk patients (12.3% vs. 9.4%; p = NS). Frequencies of nonfatal strokes (0% vs. 0.7%) and severe bleedings (0% vs. 0.7%) were low (each p = NS). In a specific analysis, patients at very high risk of stroke (i.e., CHA2 DS2 -VASc score >4) did not have increased rates of complications or nonfatal strokes in the first year after the procedure. CONCLUSIONS: Low-risk patients had no nonfatal strokes and major bleedings within 1 year after hospital discharge but had unexpectedly high rates of moderate procedural complications. The indication in these patients should be strictly defined based on an individual benefit-risk assessment.

A Case Series of Concomitant Cardiac Electrical Disease among Takotsubo Syndrome Patients and Literature Review.

The pathophysiology of Takotsubo Syndrome (TTS) is not completely understood and the trigger of sudden cardiac death (SCD) in TTS is not clear either. We therefore sought to find an association between TTS and primary electrical diseases. A total of 148 TTS patients were analyzed between 2003 and 2017 in a bi-centric manner. Additionally, a literature review was performed. The patients were included in an ongoing retrospective cohort database. The coexistence of TTS and primary electrical diseases was confirmed in five cases as the following: catecholaminergic polymorphic ventricular tachycardia (CPVT, 18-year-old female) (n = 1), LQTS 1 (72-year-old female and 65-year-old female) (n = 2), LQTS 2 (17-year-old female) (n = 1), and LQTS in the absence of mutations (22-year-old female). Four patients suffered from malignant tachyarrhythmia and recurrent syncope after TTS. Except for the CPVT patient and one LQTS 1 patient, all other cases underwent subcutaneous ICD implantation. An event recorder of the CPVT patient after starting beta-blocker did not detect arrhythmias. The diagnosis of primary electrical disease was in 80% of cases unmasked on a TTS event. This diagnosis triggered a family clinical and genetic screening confirming the diagnosis of primary electrical disease. A subsequent literature review identified five cases as the following: a congenital atrioventricular block (n = 1), a Jervell and Lange-Nielsen Syndrome (n = 1), and a family LQTS in the absence of a mutation (n = 2), LQTS 2 (n = 1). A primary electrical disease should be suspected in young and old TTS patients with a family history of sudden cardiac death. In suspected cases, e.g., ongoing QT interval prolongation, despite recovery of left ventricular ejection fraction a family screening is recommended.

Distribution and prognostic impact of coronary artery disease and nonischemic cardiomyopathies in patients with electrical storm.

BACKGROUND: he distribution and prognostic impact of coronary artery disease (CAD) in ES are still under debate. METHODS: Consecutive ES patients with implantable cardioverter-defibrillator (ICD) were included retrospectively from 2002 to 2016. Three analyses were applied to characterize ES patients: (a) ES patients without CAD (non-CAD), (b) ES patients with CAD (CAD), and (c) diagnostic findings assessed by coronary angiography (CA) at the time of ES (immediate CA). CAD was compared with non-CAD ES patients, and progressive CAD was compared with stable CAD ES patients. The primary endpoint was all-cause mortality at 2.5 years. Secondary endpoints were the composite endpoint of first recurrent ventricular tachyarrhythmias and appropriate ICD therapies, and recurrence of ES (ES-R) at 2.5 years. RESULTS: Within a total of 87 consecutive ES patients. CAD was present in more than two-thirds (67%). However, only 52% patients underwent immediate CA at the time of ES. Here, 84% had CAD, of which 39% revealed progressive CAD with the need of target vessel revascularization (TVR) or cardiac transplantation ( n = 1). At long-term follow-up, neither the presence (or absence) of CAD (41% vs. 34%; log rank P = 0.708) nor of progressive CAD (33% vs. 26%; log rank P = 0.372) was associated with all-cause mortality at 2.5 years, and further secondary endpoints including the composite of recurrent ventricular tachyarrhythmias plus appropriate ICD therapies, or ES-R. CONCLUSION: In ES patients, CAD was more common than non-CAD-related cardiac diseases, accompanied by an underinvestigated rate of CA despite increasing rates of progressive CAD. CAD had no prognostic impact in ES.