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22q11.2 Deletion Syndrome (22q11.2DS), the most common chromosomal microdeletion, presents as a heterogeneous phenotype characterized by an array of anatomical, behavioral, and cognitive abnormalities. Individuals with 22q11.2DS exhibit extensive cognitive deficits, both in overall intellectual capacity and focal challenges in executive functioning, attentional control, perceptual abilities, motor skills, verbal processing, as well as socioemotional operations. Heterogeneity is an intrinsic factor of the deletion's clinical manifestation in these cognitive domains. Structural imaging has identified significant changes in volume, thickness, and surface area. These alterations are closely linked and display region-specific variations with an overall increase in abnormalities following a rostral-caudal gradient. Despite the extensive literature developing around the neurocognitive and neuroanatomical profiles associated with 22q11.2DS, comparatively little research has addressed specific structure–function relationships between aberrant morphological features and deficient cognitive processes. The current review attempts to categorize these limited findings alongside comparisons to populations with phenotypic and structural similarities in order to answer to what degree structural findings can explain the characteristic neurocognitive deficits seen in individuals with 22q11.2DS. In integrating findings from structural neuroimaging and cognitive assessments, this review seeks to characterize structural changes associated with the broad neurocognitive challenges faced by individuals with 22q11.2DS. [ABSTRACT FROM AUTHOR]

Kounis syndrome, an allergic hypersensitivity coronary disorder, is a rare but potentially lifethreatening condition triggered by various allergens, including medications. We present the case of a 41-year-old male with no prior cardiac history, who developed Kounis syndrome following vancomycin administration for suspected cellulitis. The patient initially presented with rash, fever, and malaise, which progressed to chest discomfort associated with diaphoresis and elevated troponin levels. Diagnostic evaluations, including electrocardiographic changes and coronary angiography, confirmed a diagnosis of type I Kounis syndrome. This case adds to the limited literature on vancomycin-induced Kounis syndrome, and underscores the importance of considering this diagnosis in patients with myocardial damage following exposure to potential allergens. [ABSTRACT FROM AUTHOR]

Background: The 15q11–q13 region is a genetic locus with genes subject to genomic imprinting, significantly influencing neurodevelopment. Genomic imprinting is an epigenetic phenomenon that causes differential gene expression based on the parent of origin. In most diploid organisms, gene expression typically involves an equal contribution from both maternal and paternal alleles, shaping the phenotype. Nevertheless, in mammals, including humans, mice, and marsupials, the functional equivalence of parental alleles is not universally maintained. Notably, during male and female gametogenesis, parental alleles may undergo differential marking or imprinting, thereby modifying gene expression without altering the underlying DNA sequence. Neurodevelopmental disorders, such as Prader–Willi syndrome (PWS) (resulting from the absence of paternally expressed genes in this region), Angelman syndrome (AS) (associated with the absence of the maternally expressed UBE3A gene), and 15q11–q13 duplication syndrome (resulting from the two common forms of duplications—either an extra isodicentric 15 chromosome or an interstitial 15 duplication), are the outcomes of genetic variations in this imprinting region. Methods: Conducted a genomic study to identify the frequency of pathogenic variants impacting the 15q11–q13 region in an ethnically homogenous population from Bangladesh. Screened all known disorders from the DECIPHER database and identified variant enrichment within this cohort. Using the Horizon analysis platform, performed enrichment analysis, requiring at least >60% overlap between a copy number variation and a disorder breakpoint. Deep clinical phenotyping was carried out through multiple examination sessions to evaluate a range of clinical symptoms. Results: This study included eight individuals with clinically suspected PWS/AS, all previously confirmed through chromosomal microarray analysis, which revealed chromosomal breakpoints within the 15q11–q13 region. Among this cohort, six cases (75%) exhibited variable lengths of deletions, whereas two cases (25%) showed duplications. These included one type 2 duplication, one larger atypical duplication, one shorter type 2 deletion, one larger type 1 deletion, and four cases with atypical deletions. Furthermore, thorough clinical assessments led to the diagnosis of four PWS patients, two AS patients, and two individuals with 15q11–q13 duplication syndrome. Conclusion: Our deep phenotypic observations identified a spectrum of clinical features that overlap and are unique to PWS, AS, and Dup15q syndromes. Our findings establish genotype–phenotype correlation for patients impacted by variable structural variations within the 15q11–q13 region. [ABSTRACT FROM AUTHOR]

Introduction: Arjuna is used for its cardioprotective action while Aloe vera is herbal dietary supplement. Isoproterenol hydrochloride was administered subcutaneously to rats to induce myocardial infarction. Objectives: The given study was conducted to determine any pharmacodynamic interaction between marketed formulations i.e., Arjuna and Aloe vera. Materials and Methods: The varying tissue damage caused by Isoproterenol in different groups was confirmed from electrocardiogram (Heart rate, ST segment elevation time, QRS complex amplitude), levels of serum cardiac markers (creatine kinase, isoform of creatine kinase, Lactate dehydrogenase), blood electrolytes levels, by determining antioxidant enzymes activity (Superoxide dismutase, Catalase, Glutathione) and histopathological results. Results: The interaction group showed increased Heart rate, increased ST segment elevation time, decreased QRS complex; decreased antioxidant enzyme activity and increased levels of cardiac markers when compared to Arjuna group. The results were found to be statistically significant (p<0.05). Conclusion: Detrimental effect was found between two herbal formulations as a result of which the Cardioprotective effect of Arjuna was decreased when administered simultaneously with Aloe vera. [ABSTRACT FROM AUTHOR]

Background Thousands of people suffer from anxiety, depression, and insomnia every day, with benzodiazepines being one of the strategies used to treat these conditions. Withdrawal from its long-term use can lead to potentially life-threatening complications, including Takotsubo syndrome. The authors highlight an atypical case of Takotsubo syndrome secondary to benzodiazepine withdrawal, a rare life-threatening complication of acute substance withdrawal. Case summary A 58-year-old female presented to the emergency department with altered mental status and acute pulmonary oedema after discontinuing her prescribed benzodiazepines 3 days prior to presentation. Electrocardiogram (ECG) demonstrated anterior ST-segment elevation, with Q-wave and T-wave inversion with prolonged QT interval. Troponin I concentration and B-type natriuretic peptide were elevated to 5407 ng/L (normal ≤ 16 ng/L) and to 1627.0 pg/L (normal ≤ 100 pg/mL), respectively. Echocardiogram showed ballooning of the left ventricle (LV) apex with dyskinesia of the mid and apical segments, with LV function of 15%. Coronary angiography was normal, but left ventriculography showed severe LV systolic dysfunction with akinesis of the mid and apical LV segments and hyperdynamic basal segments. A presumptive diagnosis of benzodiazepine withdrawal–induced Takotsubo syndrome was made, and patients' symptoms, ECG findings, and LV dysfunction resolved after benzodiazepine administration. Six months post discharge, the patient remained asymptomatic with a normal biventricular function, and a beta-blocker was successfully introduced as part of a lifelong plan. Discussion A diagnosis of benzodiazepine withdrawal–induced Takotsubo syndrome is an underrecognized and challenging diagnosis, due to its atypical clinical presentation. High degree of clinical suspicion for this syndrome is crucial, since favourable prognosis depends on prompt diagnosis and treatment. [ABSTRACT FROM AUTHOR]

We analyzed the possibility of detecting and predicting ventricular fibrillation (VF), a medical emergency that may put people's lives at risk, as the medical prognosis depends on the time in which medical personnel intervene. Therefore, besides immediate detection of VF, the possibility of predicting VF 40 or even 50 min in advance was analyzed. For testing the proposed algorithm, we used ECG signals taken from the MIT-BIH database, namely, Malignant Ventricular Ectopy Database, Sudden Cardiac Death Holter Database and Normal Sinus Rhythm Database. The presented method is based on features extracted from the ECG signals in the time domain, frequency domain and complexity measures. For VF detection, the possibility of identifying the VF episode in the first 3 s after its occurrence was tested. For this, the first 3 s immediately after the appearance of VF were cut out and the features were computed on these sections. For VF prediction, 3 min of the ECG signal clipped 40 or 50 min before VF onset was used. Then, on these pieces of ECG signal, the specific features were calculated for 1 s segments. For the normal signal situation, 3 min was randomly selected from the database with normal ECGs. For the classification or detection stage, both an MLP-type neural network and the classifiers from the Machine Learning toolbox of the MATLAB® environment were used. The results obtained for both detection and classification are over 94% in both cases. The novelty of our results compared to those previously obtained is the time interval with which the possibility of prediction was analyzed, namely, 50 min in advance of the VF installation date. This means that the patient will be informed that it is possible to suffer a VF and has time to take the necessary measures to overcome a possible medical emergency. [ABSTRACT FROM AUTHOR]

Background; Sickle cell anaemia is the most common monogenic hematologic disorder in Nigeria. Cardiovascular pathology, resulting in electrocardiographic abnormalities are a common finding in adult sickle cell patients. Objective; This study investigated the pattern of electrocardiographic (ECG) abnormalities in steady state adult sickle cell anaemia (HbSS) patients and compared the findings with that of age and sex matched Haemoglobin AA(HbAA) controls. Methodology; Fifty steady state adult HbSS participants were recruited from the haematology clinic at Nnamdi Azikiwe University Teaching Hospital while fifty age and sex matched HbAA controls were recruited from the hospital community. Participants underwent resting 12 lead ECG using a Schiller CARDIOVIT AT-1 ECG machine. Data was analyzed using Statistical Package for Social Sciences version 21. Results; The prevalence of ECG abnormalities amongst the adult sickle cell participants and controls was 70% and 10% respectively. ECG abnormalities were more common amongst male sickle cell participants and left ventricle hypertrophy was the most frequent ECG abnormality detected. Conclusion; There is a high prevalence of ECG abnormalities amongst adult sickle cell anaemia patients. Regular Electrocardiography is recommended for early detection of these abnormalities for early treatment and improved quality of life. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes due to COVID-19 include QT prolongation and ST-T changes; however, there have not been studies on the ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All patients had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24 h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 involved a 76-year-old man with hypertension and diabetes, and Case 3 involved a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. The LP, TWA, HRV, and HRT were positive in all three cases with no significant structural cardiac disease at the initial phase of admission. The further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed. Depending on the accumulation of data, the LP, TWA, HRV, and HRT could be identified as potential risk factors for COVID-19 pneumonia in the early phase of admission. [ABSTRACT FROM AUTHOR]

Risk factors for pacemaker-induced cardiomyopathy (PICM) have been previously reported, including a high burden of right ventricular pacing, lower left ventricular ejection fraction, a wide QRS duration, and left bundle branch block before pacemaker implantation (PMI). However, predicting the development of PICM remains challenging. This study aimed to use a convolutional neural network (CNN) model, based on clinical findings before PMI, to predict the development of PICM. Out of a total of 561 patients with dual-chamber PMI, 165 (mean age 71.6 years, 89 men [53.9%]) who underwent echocardiography both before and after dual-chamber PMI were enrolled. During a mean follow-up period of 1.7 years, 47 patients developed PICM. A CNN algorithm for prediction of the development of PICM was constructed based on a dataset prior to PMI that included 31 variables such as age, sex, body mass index, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, severity of mitral regurgitation, severity of tricuspid regurgitation, ischemic heart disease, diabetes mellitus, hypertension, heart failure, New York Heart Association class, atrial fibrillation, the etiology of bradycardia (sick sinus syndrome or atrioventricular block) , right ventricular (RV) lead tip position (apex, septum, left bundle, His bundle, RV outflow tract), left bundle branch block, QRS duration, white blood cell count, haemoglobin, platelet count, serum total protein, albumin, aspartate transaminase, alanine transaminase, estimated glomerular filtration rate, sodium, potassium, C-reactive protein, and brain natriuretic peptide. The accuracy, sensitivity, specificity, and area under the curve of the CNN model were 75.8%, 55.6%, 83.3% and 0.78 respectively. The CNN model could accurately predict the development of PICM using clinical findings before PMI. This model could be useful for screening patients at risk of developing PICM, ensuring timely upgrades to physiological pacing to avoid missing the optimal intervention window. [ABSTRACT FROM AUTHOR]

Cardiac arrhythmias cause significant morbidity and mortality and pose a major public health problem. They arise from disruptions in the normally orderly propagation of cardiac electrophysiological activation and recovery through successive cardiomyocytes in the heart. They reflect abnormalities in automaticity, initiation, conduction, or recovery in cardiomyocyte excitation. The latter properties are dependent on surface membrane electrophysiological mechanisms underlying the cardiac action potential. Their disruption results from spatial or temporal instabilities and heterogeneities in the generation and propagation of cellular excitation. These arise from abnormal function in their underlying surface membrane, ion channels, and transporters, as well as the interactions between them. The latter, in turn, form common regulatory targets for the hierarchical network of diverse signaling mechanisms reviewed here. In addition to direct molecular-level pharmacological or physiological actions on these surface membrane biomolecules, accessory, adhesion, signal transduction, and cytoskeletal anchoring proteins modify both their properties and localization. At the cellular level of excitation-contraction coupling processes, Ca2+ homeostatic and phosphorylation processes affect channel activity and membrane excitability directly or through intermediate signaling. Systems-level autonomic cellular signaling exerts both acute channel and longer-term actions on channel expression. Further upstream intermediaries from metabolic changes modulate the channels both themselves and through modifying Ca2+ homeostasis. Finally, longer-term organ-level inflammatory and structural changes, such as fibrotic and hypertrophic remodeling, similarly can influence all these physiological processes with potential pro-arrhythmic consequences. These normal physiological processes may target either individual or groups of ionic channel species and alter with particular pathological conditions. They are also potentially alterable by direct pharmacological action, or effects on longerterm targets modifying protein or cofactor structure, expression, or localization. Their participating specific biomolecules, often clarified in experimental genetically modified models, thus constitute potential therapeutic targets. The insights clarified by the physiological and pharmacological framework outlined here provide a basis for a recent modernized drug classification. Together, they offer a translational framework for current drug understanding. This would facilitate future mechanistically directed therapeutic advances, for which a number of examples are considered here. The latter are potentially useful for treating cardiac, in particular arrhythmic, disease. [ABSTRACT FROM AUTHOR]

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe hereditary arrhythmia syndrome predominantly affecting children and young adults. It manifests through bidirectional or polymorphic ventricular arrhythmia, often culminating in syncope triggered by physical exertion or emotional stress which can lead to sudden cardiac death. Most cases stem from mutations in the gene responsible for encoding the cardiac ryanodine receptor (RyR2), or in the Calsequestrin 2 gene (CASQ2), disrupting the handling of calcium ions within the cardiac myocyte sarcoplasmic reticulum. Diagnosing CPVT typically involves unmasking the arrhythmia through exercise stress testing. This diagnosis emerges in the absence of structural heart disease by cardiac imaging and with a normal baseline electrocardiogram. Traditional first-line treatment primarily involves β-blocker therapy, significantly reducing CPVT-associated mortality. Adjunctive therapies such as moderate exercise training, flecainide, left cardiac sympathetic denervation and implantable cardioverter-defibrillators have been utilized with reasonable success. However, the spectrum of options for managing CPVT has expanded over time, demonstrating decreased rates of arrhythmic events. Furthermore, ongoing research into potential new therapies including gene therapies has the potential to further enhance treatment paradigms. This review aims to succinctly encapsulate the contemporary understanding of the clinical characteristics, diagnostic approach, established therapeutic interventions and the promising future directions in managing CPVT. [ABSTRACT FROM AUTHOR]

Voltage-gated sodium channels (Naᵥ) are membrane proteins which open to facilitate the inward flux of sodium ions into excitable cells. In response to stimuli, Naᵥ channels transition from the resting, closed state to an open, conductive state, before rapidly inactivating. Dysregulation of this functional cycle due to mutations causes diseases including epilepsy, pain conditions, and cardiac disorders, making Naᵥ channels a significant pharmacological target. Phosphoinositides are important lipid cofactors for ion channel function. The phosphoinositide PI(4,5)P2 decreases Naᵥ1.4 activity by increasing the difficulty of channel opening, accelerating fast inactivation and slowing recovery from fast inactivation. Using multiscale molecular dynamics simulations, we show that PI(4,5)P2 binds stably to inactivated Naᵥ at a conserved site within the DIV S4-S5 linker, which couples the voltage-sensing domain (VSD) to the pore. As the Naᵥ C-terminal domain is proposed to also bind here during recovery from inactivation, we hypothesize that PI(4,5)P2 prolongs inactivation by competitively binding to this site. In atomistic simulations, PI(4,5)P2 reduces the mobility of both the DIV S4-S5 linker and the DIII-IV linker, responsible for fast inactivation, slowing the conformational changes required for the channel to recover to the resting state. We further show that in a resting state Naᵥ model, phosphoinositides bind to VSD gating charges, which may anchor them and impede VSD activation. Our results provide a mechanism by which phosphoinositides alter the voltage dependence of activation and the rate of recovery from inactivation, an important step for the development of novel therapies to treat Naᵥ-related diseases. [ABSTRACT FROM AUTHOR]

Background: During general anesthesia, patients with Brugada syndrome are at risk of malignant arrhythmias following worsened ST-segment elevation, potentially leading to sudden cardiac death. The protocol for safe anesthetic management of patients with Brugada syndrome has not yet been established. Case presentation: A 63-year-old man, diagnosed with a spontaneous Brugada type 1 pattern, was scheduled for a pleural biopsy using video-assisted thoracoscopic surgery under general anesthesia. We planned general anesthesia using volatile induction and maintenance anesthesia with sevoflurane and remifentanil. We monitored ST-segment morphology and observed sustained mitigation of ST-segment elevation throughout general anesthesia. Conclusion: The present case may indicate that safe anesthetic management of patients with Brugada syndrome depends on whether the anesthetics used can reduce ST-segment elevation. [ABSTRACT FROM AUTHOR]

Background and Aims Electrocardiogram (ECG) abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD), but the potential importance of dynamic ECG remodelling has not been investigated. In this study, the nature and prevalence of dynamic ECG remodelling were studied among individuals who eventually suffered SCD. Methods The study population was drawn from two prospective community-based SCD studies in Oregon (2002, discovery cohort) and California, USA (2015, validation cohort). For this present sub-study, 231 discovery cases (2015–17) and 203 validation cases (2015–21) with ≥2 archived pre-SCD ECGs were ascertained and were matched to 234 discovery and 203 validation controls based on age, sex, and duration between the ECGs. Dynamic ECG remodelling was measured as progression of a previously validated cumulative six-variable ECG electrical risk score. Results Oregon SCD cases displayed greater electrical risk score increase over time vs. controls [+1.06 (95% confidence interval +0.89 to +1.24) vs. −0.05 (−0.21 to +0.11); P <.001]. These findings were successfully replicated in California [+0.87 (+0.7 to +1.04) vs. −0.11 (−0.27 to 0.05); P <.001]. In multivariable models, abnormal dynamic ECG remodelling improved SCD prediction over baseline ECG, demographics, and clinical SCD risk factors in both Oregon [area under the receiver operating characteristic curve 0.770 (95% confidence interval 0.727–0.812) increased to area under the receiver operating characteristic curve 0.869 (95% confidence interval 0.837–0.902)] and California cohorts. Conclusions Dynamic ECG remodelling improved SCD risk prediction beyond clinical factors combined with the static ECG, with successful validation in a geographically distinct population. These findings introduce a novel concept of SCD dynamic risk and warrant further detailed investigation. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is an inherited disease characterized by right precordial ST-segment elevation in the right precordial leads on electrocardiograms (ECG), and high risk of life-threatening ventricular arrhythmia and sudden cardiac death (SCD). Mutations in the responsible genes have not been fully characterized in the BrS patients, except for the SCN5A gene. We identified a new genetic variant, c.1189C>T (p.R397C), in the KCNH2 gene in the asymptomatic male proband diagnosed with BrS and mild QTc shortening. We hypothesize that this variant could alter IKr-current and may be causative for the rare non-SCN5A-related form of BrS. To assess its pathogenicity, we performed patch-clamp analysis on IKr reconstituted with this KCNH2 mutation in the Chinese hamster ovary cells and compared the phenotype with the wild type. It appeared that the R397C mutation does not affect the IKr density, but facilitates activation, hampers inactivation of the hERG channels, and increases magnitude of the window current suggesting that the p.R397C is a gain-of-function mutation. In silico modeling demonstrated that this missense mutation potentially leads to the shortening of action potential in the heart. [ABSTRACT FROM AUTHOR]

Although mitral valve prolapse (MVP) is the most prevalent valvular abnormality in Western countries and generally carries a good prognosis, a small subset of patients is exposed to a significant risk of malignant ventricular arrhythmias (VAs) and sudden cardiac death (SCD), the so-called arrhythmic MVP (AMVP) syndrome. Recent work has emphasized phenotypical risk features of severe AMVP and clarified its pathophysiology. However, the appropriate assessment and risk stratification of patients with suspected AMVP remains a clinical conundrum, with the possibility of both overestimating and underestimating the risk of malignant VAs, with the inappropriate use of advanced imaging and invasive electrophysiology study on one hand, and the catastrophic occurrence of SCD on the other. Furthermore, the sports eligibility assessment of athletes with AMVP remains ill defined, especially in the grey zone of intermediate arrhythmic risk. The definition, epidemiology, pathophysiology, risk stratification, and treatment of AMVP are covered in the present review. Considering recent guidelines and expert consensus statements, we propose a comprehensive pathway to facilitate appropriate counseling concerning the practice of competitive/leisure-time sports, envisioning shared decision making and the multidisciplinary "sports heart team" evaluation of borderline cases. Our final aim is to encourage an active lifestyle without compromising patients' safety. [ABSTRACT FROM AUTHOR]

The slmap gene is alternatively spliced to generate many isoforms that are abundant in developing myocardium. The largest protein isoform SLMAP3 is ubiquitously expressed and has been linked to cardiomyopathy, Brugada syndrome and Hippo signaling. To examine any role in cardiogenesis, mice homozygous for floxed slmap allele were crossed with Nkx2.5-cre mice to nullify its expression in cardiac progenitors. Targeted deletion of the slmap gene resulted in the specific knockout (KO) of the SLMAP3 (~91 KDa) isoform without any changes in the expression of the SLMAP2 (~43 kDa) or the SLMAP1 (~35 kDa) isoforms which continued to accumulate to similar levels as seen in Wt embryonic hearts. The loss of SLMAP3 from cardiac progenitors resulted in decreased size of the developing embryonic hearts evident at E9.5 to E16.5 with four small chambers and significantly thinner left ventricles. The proliferative capacity assessed with the phosphorylation of histone 3 or with Ki67 in E12.5 hearts was not significantly altered due to SLMAP3 deficiency. The size of embryonic cardiomyocytes, marked with anti-Troponin C, revealed significantly smaller cells, but their hypertrophic response (AKT1 and MTOR1) was not significantly affected by the specific loss of SLMAP3 protein. Further, no changes in phosphorylation of MST1/2 or YAP were detected in SLMAP3-KO embryonic myocardium, ruling out any impact on Hippo signaling. Rat embryonic cardiomyocytes express the three SLMAP isoforms and their knockdown (KD) with sh-RNA, resulted in decreased proliferation and enhanced senescence but without any impact on Hippo signaling. Collectively, these data show that SLMAP is critical for normal cardiac development with potential for the various isoforms to serve compensatory roles. Our data imply novel mechanisms for SLMAP action in cardiac growth independent of Hippo signaling. [ABSTRACT FROM AUTHOR]

Cardiac troponin (Tn) plays a central role in the evaluation of patients with angina presenting with acute coronary syndrome. The advent of high-sensitivity assays has improved the analytic sensitivity and precision of serum Tn measurement, but this advancement has come at the cost of poorer specificity. The role of clinical judgment is of heightened importance because, more so than ever, the interpretation of serum Tn elevation hinges on the careful integration of findings from electrocardiographic, echocardiographic, physical exam, interview, and other imaging and laboratory data to formulate a weighted differential diagnosis. A thorough understanding of the epidemiology, mechanisms, and prognostic implications of Tn elevations in each cardiac and non-cardiac etiology allows the clinician to better distinguish between presentations of myocardial ischemia and myocardial injury—an important discernment to make, as the treatment of acute coronary syndrome is vastly different from the workup and management of myocardial injury and should be directed at the underlying cause. [ABSTRACT FROM AUTHOR]

Scn5a heterozygous null (Scn5α+/-) mice have historically been used to investigate arrhythmogenic mechanisms of diseases such as Brugada syndrome (BrS) and Lev's disease. Previously, we demonstrated that reducing ephaptic coupling (EpC) in ex vivo hearts exacerbates pharmacological voltage-gated sodium channel (Nav)1.5 loss of function (LOF). Whether this effect is consistent in a genetic Nav1.5 LOF model is yet to be determined. We hypothesized that loss of EpC would result in greater reduction in conduction velocity (CV) for the Scn5α+/- mouse relative to wild type (WT). In vivo ECGs and ex vivo optical maps were recorded from Langendorff-perfused Scn5α+/- and WT mouse hearts. EpC was reduced with perfusion of a hyponatremic solution, the clinically relevant osmotic agent mannitol, or a combination of the two. Neither in vivo QRS duration nor ex vivo CV during normonatremia was significantly different between the two genotypes. In agreement with our hypothesis, we found that hyponatremia severely slowed CV and disrupted conduction for 4/5 Scn5α+/- mice, but 0/6 WT mice. In addition, treatment with mannitol slowed CV to a greater extent in Scn5α+/- relative to WT hearts. Unexpectedly, treatment with mannitol during hyponatremia did not further slow CV in either genotype, but resolved the disrupted conduction observed in Scn5α+/- hearts. Similar results in guinea pig hearts suggest the effects of mannitol and hyponatremia are not species specific. In conclusion, loss of EpC through either hyponatremia or mannitol alone results in slowed or disrupted conduction in a genetic model of Nav1.5 LOF. However, the combination of these interventions attenuates conduction slowing. [ABSTRACT FROM AUTHOR]

Inherited cardiomyopathies represent a highly heterogeneous group of cardiac diseases. DNA variants in genes expressed in cardiomyocytes cause a diverse spectrum of cardiomyopathies, ultimately leading to heart failure, arrythmias, and sudden cardiac death. We applied massive parallel DNA sequencing using a 72-gene panel for studying inherited cardiomyopathies. We report on variants in 25 families, where pathogenicity was predicted by different computational approaches, databases, and an in-house filtering analysis. All variants were validated using Sanger sequencing. Familial segregation was tested when possible. We identified 41 different variants in 26 genes. Analytically, we identified fifteen variants previously reported in the Human Gene Mutation Database: twelve mentioned as disease-causing mutations (DM) and three as probable disease-causing mutations (DM?). Additionally, we identified 26 novel variants. We classified the forty-one variants as follows: twenty-eight (68.3%) as variants of uncertain significance, eight (19.5%) as likely pathogenic, and five (12.2%) as pathogenic. We genetically characterized families with a cardiac phenotype. The genetic heterogeneity and the multiplicity of candidate variants are making a definite molecular diagnosis challenging, especially when there is a suspicion of incomplete penetrance or digenic-oligogenic inheritance. This is the first systematic study of inherited cardiac conditions in Cyprus, enabling us to develop a genetic baseline and precision cardiology. [ABSTRACT FROM AUTHOR]

The STEMI-DTU pilot study tested the early safety and practical feasibility of left ventricular (LV) unloading with a trans-valvular pump before reperfusion. In the intent-to-treat cohort, no difference was observed for microvascular obstruction (MVO) or infarct size (IS) normalized to either the area at risk (AAR) at 3–5 days or total LV mass (TLVM) at 3–5 days We now report a per protocol analysis of the STEMI-DTU pilot study. In STEMI-DTU STUDY 50 adult patients (25 in each arm) with anterior STEMI [sum of precordial ST-segment elevation (ΣSTE) ≥4 mm] requiring primary percutaneous coronary intervention (PCI) were enrolled. Only patients who met all inclusion and exclusion criteria were included in this analysis. Cardiac magnetic resonance (CMR) imaging 3–5 days after PCI quantified IS/AAR and IS/TLVM and MVO. Group differences were assessed using Student's t -tests and linear regression (SAS Version-9.4). Of the 50 patients enrolled, 2 died before CMR imaging. Of the remaining 48 patients those without CMR at 3–5 days (n = 8), without PCI of a culprit left anterior descending artery lesion (n = 2), with OHCA (n = 1) and with ΣSTE < 4 mm (n = 5) were removed from this analysis leaving 32/50 (64 %) patients meeting all inclusion and exclusion criteria (U-IR, n = 15; U-DR, n = 17) as per protocol. Despite longer symptom-to-balloon times in the U-DR arm (228 ± 80 vs 174 ± 59 min, p < 0.01), IS/AAR was significantly lower with 30 min of delay to reperfusion in the presence of active LV unloading (47 ± 16 % vs 60 ± 15 %, p = 0.02) and remained lower irrespective of the magnitude of precordial ΣSTE. MVO was not significantly different between groups (1.5 ± 2.8 % vs 3.5 ± 4.8 %, p = 0.15). Among patients who received LV unloading within 180 min of symptom onset, IS/AAR was significantly lower in the U-DR group. In this per-protocol analysis of the STEMI-DTU pilot study we observed that LV unloading for 30 min before reperfusion significantly reduced IS/AAR compared to LV unloading and immediate reperfusion, whereas in the ITT cohort no difference was observed between groups. This observation supports the design of the STEMI-DTU pivotal trial and suggests that strict adherence to the study protocol can significantly influence the outcome. • LV unloading plus delayed reperfusion may reduce infarct size. • LV unloading plus delayed reperfusion may reduce microvascular obstruction. • This per protocol analysis supports the design of the ongoing STEMI-DTU pivotal trial. [ABSTRACT FROM AUTHOR]

Alternation of left and right antimeres of segmental structures, generally known as the glide-reflection symmetry, was found to be unexpectedly widespread in deuterostomes. It occurs in both somatic and visceral organs. Its distribution in echinoderms, acorn worms, cephalochordates, ascidians, hagfishes, and chimaeras might suggest its ancestral nature in deuterostomes. It could have been inherited from Precambrian ancestors. There is a lead of the left segments against their right counterparts in all deuterostomes with glide-reflection symmetry, where the leading side is known. This allows us to presume an inherent left-to-left-side and right-to-right-side homology across all deuterostomes, contradicting a hypothesis of the whole-body dorsoventral inversion in chordates. The features of inversion could be alternatively explained by a transformation of the gastrulation process, which has caused an inversion of dorsoventral polarity in some parts of the body, but did not affect the left–right polarity. It is suggested that this process had involved the animal-vegetal extension of the blastopore along embryonic dorsal side in basal deuterostomes that was followed by the shift of the left–right organizer from the dorsal lip of the blastopore to the anterior tip of archenteron in non-chordate deuterostomes, which has caused roof-to-floor relocation of the notochordal area in their archenteron. [ABSTRACT FROM AUTHOR]

This article discusses the role of small quantities of cartilage sodium channels in osteoarthritis (OA). The researchers found that the sodium channel Nav1.7 is present and elevated in human OA chondrocytes, and its deletion or blockade can attenuate the progression of OA and alleviate OA pain. The study also highlights the need for further investigation into the molecular mechanisms underlying the role of Nav1.7 in OA progression. The authors suggest that targeting Nav1.7 could be a potential therapeutic approach for treating OA. [Extracted from the article]

Brugada syndrome (BrS) is an inherited cardiac arrhythmogenic disease that predisposes patients to sudden cardiac death. It is associated with mutations in SCN5A , which encodes the cardiac sodium channel alpha subunit (Na V 1.5). BrS-related mutations have incomplete penetrance and variable expressivity within families. The purpose of this study was to determine the role of patient-specific genetic background on the cellular and clinical phenotype among carriers of Na V 1.5_p.V1525M. We studied sodium currents from patient-specific human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) and heterologously transfected human embryonic kidney (HEK) tsA201 cells using the whole-cell patch-clamp technique. We determined gene and protein expression by quantitative polymerase chain reaction, RNA sequencing, and western blot and performed a genetic panel for arrhythmogenic diseases. Our results showed a large reduction in I Na density in hiPSC-CM derived from 2 V1525M single nucleotide variant (SNV) carriers compared with hiPSC-CM derived from a noncarrier, suggesting a dominant-negative effect of the Na V 1.5_p.V1525M channel. I Na was not affected in hiPSC-CMs derived from a V1525M SNV carrier who also carries the Na V 1.5_p.H558R polymorphism. Heterozygous expression of V1525M in HEK-293T cells produced a loss of I Na function, not observed when this variant was expressed together with H558R. In addition, the antiarrhythmic drug mexiletine rescued I Na function in hiPSC-CM. SCN5A expression was increased in the V1525M carrier who also expresses Na V 1.5_p.H558R. Our results in patient-specific hiPSC-CM point to a dominant-negative effect of Na V 1.5_p.V1525M, which can be reverted by the presence of Na V 1.5_p.H558R. Overall, our data points to a role of patient-specific genetic background as a determinant for incomplete penetrance in BrS. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy is a myocardial disease that may go undetected in the early stages due to peripheral vasodilatation. The aim of the study was to evaluate the electrocardiogram (ECG) and heart rate variability (HRV) after raising blood pressure by phenylephrine injection in rats with liver cirrhosis. Twenty male Sprague–Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 44 days, animals were anesthetized and the right femoral artery and vein catheterized. After a steady-state period, a bolus injection of phenylephrine (PHE, 10 μg/μl/IV, baroreflex maneuver) was followed by a slow injection of PHE (100 μg/ml/5 min/IV, sustained maneuver). Rapid and slow injections of PHE resulted in a greater increase in mean arterial pressure (MAP) and a weaker bradycardia response in the CBDL group than in the Sham group. ECG analysis showed increased QT, QTc, JT, and T peak to T end in the CBDL group, which remained unchanged after PHE injection. On the other hand, the parasympathetic indices of the HF band and RMSSD, and the sympathetic index of the LF band after PHE injection were lower in the CBDL group than in the Sham group. ECG data indicated prolonged ventricular depolarization and repolarization, independent of blood pressure levels in cirrhosis. On the other hand, after PHE injection, the parasympathetic and sympathetic components of HRV decreased, regardless of the duration of elevated blood pressure. We suggest that HRV analysis can provide a useful approach to assess cardiac dysfunction associated with elevated blood pressure in cirrhosis. [ABSTRACT FROM AUTHOR]

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Myocardial involvement was shown to be associated with an unfavorable prognosis in patients with COVID-19, which could lead to fatal outcomes as in myocardial injury-induced arrhythmias and sudden cardiac death. We hypothesized that magnetic resonance imaging (MRI) myocardial strain parameters are sensitive markers for identifying subclinical cardiac dysfunction associated with myocardial involvement in the post-acute sequelae of COVID-19 (PASC). This study evaluated 115 subjects, including 65 consecutive COVID-19 patients, using MRI for the assessment of either post-COVID-19 myocarditis or other cardiomyopathies. Subjects were categorized, based on the results of the MRI exams, as having either 'suspected' or 'excluded' myocarditis. A control group of 50 matched individuals was studied. Along with parameters of global cardiac function, the MRI images were analyzed for measurements of the myocardial T1, T2, extracellular volume (ECV), strain, and strain rate. Based on the MRI late gadolinium enhancement and T1/T2/ECV mappings, myocarditis was suspected in 7 out of 22 patients referred due to concern of myocarditis and in 9 out of 43 patients referred due to concern of cardiomyopathies. The myocardial global longitudinal, circumferential, and radial strains and strain rates in the suspected myocarditis group were significantly smaller than those in the excluded myocarditis group, which in turn were significantly smaller than those in the control group. The results showed significant correlations between the strain, strain rate, and global cardiac function parameters. In conclusion, this study emphasizes the value of multiparametric MRI for differentiating patients with myocardial involvement in the PASC based on changes in the myocardial contractility pattern and tissue structure. [ABSTRACT FROM AUTHOR]

Background: Although using electrocardiogram (ECG) for pulmonary embolism (PE) risk stratification has shown mixed results, it is currently used as supplementary evidence in risk stratification. This cross‐sectional study aimed to assess and compare ECG findings of massive and submassive PE versus segmental PE. Methods: This cross‐sectional study included 250 hospitalized patients with a confirmed diagnosis of acute PE from 2015 to 2020 in Southern Iran. Demographic variables, clinical data, troponin levels, on‐admission ECG findings, echocardiography findings, and ECG findings 24 h after receiving anticoagulants or thrombolytics were extracted. Results: Patients diagnosed with submassive or massive PE exhibited significantly higher rates of right axis deviation (p =.010), abnormal ST segment (p <.0001), S1Q3T3 pattern (p <.0001), inverted T wave in leads V1–V3 (p <.0001), inverted T wave in leads V4–V6 (p <.0001), and inverted T wave in leads V1‐V6 (p <.0001). In a multivariable model, inverted T wave in leads V1–V3, inverted T wave in leads V4–V6, pulse rate, and positive troponin test were the statistically independent variables for predicting submassive or massive PE. Furthermore, inverted T wave in leads V1–V3 (sensitivity: 85%, specificity: 95%, accuracy: 93%, AUC: 0.902) and troponin levels (sensitivity: 72%, specificity: 86%, accuracy: 83%, AUC: 0.792) demonstrated the best diagnostic test performance for discriminating submassive or massive PE from segmental PE. Conclusion: In addition to clinical rules, ECG can serve as an ancillary tool for assessing more invasive testing and earlier aggressive treatments among patients with PE, as it can provide valuable information for the diagnosis and risk stratification of submassive or massive PE. [ABSTRACT FROM AUTHOR]

The electrocardiogram (ECG) is a non-invasive diagnostic tool holding significant clinical importance in the diagnosis and risk stratification of cardiac disease. However, access to large-scale, population-based digital ECG data for research purposes remains limited and challenging. Consequently, we established the Danish Nationwide ECG Cohort to provide data from standard 12-lead digital ECGs in both pre- and in-hospital settings, which can be linked to comprehensive Danish nationwide administrative registers on health and social data with long-term follow-up. The Danish Nationwide ECG Cohort is an open real-world cohort including all patients with at least one digital pre- or in-hospital ECG in Denmark from January 01, 2000, to December 31, 2021. The cohort includes data on standardized and uniform ECG diagnostic statements and ECG measurements including global parameters as well as lead-specific measures of waveform amplitudes, durations, and intervals. Currently, the cohort comprises 2,485,987 unique patients with a median age at the first ECG of 57 years (25th–75th percentiles, 40–71 years; males, 48%), resulting in a total of 11,952,430 ECGs. In conclusion, the Danish Nationwide ECG Cohort represents a novel and extensive population-based digital ECG dataset for cardiovascular research, encompassing both pre- and in-hospital settings. The cohort contains ECG diagnostic statements and ECG measurements that can be linked to various nationwide health and social registers without loss to follow-up. [ABSTRACT FROM AUTHOR]

Brugada Syndrome is an "inherited" channelopathy characterized by a predisposition to syncope and sudden death. It typically presents in young adults but is also known to affect the pediatric population, even if the prevalence is low compared to the adult population. The diagnostic ECG pattern shows coved-type ST-segment elevation in the right precordial leads, occurring spontaneously or after provocative drug tests with IV administration of Class I antiarrhythmic drugs. However, the electrocardiographic findings may vary, and transient or concealed forms of the syndrome further complicate diagnosis, necessitating thorough evaluation and close clinical follow-up. The clinical presentation of Brugada Syndrome may range from asymptomatic individuals to patients who have experienced syncope or sudden cardiac arrest. The syndrome remains underdiagnosed due to its elusive symptoms and the absence of abnormal findings between episodes. Additionally, specific triggers such as fever, certain medications and alcohol consumption may unmask the electrocardiographic changes and provoke arrhythmias in susceptible individuals. Given its elusive nature, early diagnosis and risk stratification are crucial in identifying individuals who may benefit from an implantable cardioverter defibrillator, the mainstay of treatment for high-risk patients, or pharmacological interventions. [ABSTRACT FROM AUTHOR]

BackgroundChronic diseases have a negative impact on quality of life (QOL) and psychological health. There are limited related data regarding this topic in Brugada syndrome (BrS). We evaluated the effects of the diagnosis of BrS on health-related QOL and psychological status among patients and their relatives.MethodsPatients with BrS and their relatives underwent psychological evaluation at diagnosis (T0), 1 and 2 years after diagnosis (T1 and T2) using questionnaires on mental QOL, anxiety, depression, stress, post-traumatic stress, and resilience resources.ResultsSixty-one patients and 39 relatives were enrolled. Compared with controls, patients showed increased physical QOL (54.1 ± 6.5 vs. 50.1 ± 8.0, p = 0.014), reduced mental QOL (43.2 ± 11.8 vs. 49.6 ± 9.1, p = 0.018) and increased anxiety (9.9 ± 6.6 vs. 6.9 ± 7.7, p = 0.024) at T0; reduced resilience scores (3.69 ± 0.40 vs. 3.96 ± 0.55, p = 0.008) at T1; and reduced resilience (3.69 ± 0.35 vs. 3.96 ± 0.55, p = 0.019) and increased anxiety scores (16.4 ± 12.8 vs. 6.9 ± 7.7, p = 0.006) at T2. Relatives presented higher stress (17.63 ± 3.77 vs. 12.90 ± 6.0, p = 0.02) at T0 and higher anxiety scores at T0 (13.5 ± 7.6 vs. 6.9 ± 7.7, p

The development of sensitive and low-cost techniques for identifying valve dysfunction has become inevitable in the context of increasing death due to cardiac diseases. The present work attempts to propose a novel technique for cardiac auscultation based on graph theory. The sixty heart sound signals from normal heart (NMH) and with aortic stenosis (ASH) are subjected to Fast Fourier Transform (FFT) and complex network analyses. The murmur signals, a time-series signal, carry information about the blood flow through the heart, which gets exposed in the graph constructed and its features. The finer details of the murmur signal from the defective aortic valve and the normal aortic valve are reflected as the increased number of frequency components in FFT and as interconnected clusters without uncorrelated nodes in the graph of ASH. The distinction in graph features forms the basis of classification based on machine learning techniques (MLTs). When the unsupervised MLT-principal component analysis gives 86.8% total variance, the supervised MLTs-K nearest neighbor (KNN), support vector machine, and KNN subspace ensemble classifiers give 100%, 95.6%, and 90.9% prediction accuracy, suggesting its potential in remote auscultation in rural health centers. [ABSTRACT FROM AUTHOR]

The article focuses on the use of supplemental oxygen in paediatric intensive care units (PICUs) and compares the effects of higher and lower target oxygen saturation levels on critically ill children. It discusses the findings of a pragmatic, multicentre, open-label, randomised controlled trial conducted in 15 UK PICUs, which showed a slight benefit for the lower target saturation strategy over the higher target saturation strategy.

Allergic reactions to components of cardiac implantable electronic devices are rare and often go undiagnosed, which can lead to a misdiagnosis of device infection. Contact allergy to subcutaneous implantable cardioverter defibrillator (S‐ICD) is extremely rare. In this report, we present a case of cobalt‐related contact allergy in a pediatric patient with Brugada syndrome who underwent S‐ICD implantation. [ABSTRACT FROM AUTHOR]

The article discusses Brugada syndrome (BrS), a heritable disorder that increases the risk of sudden cardiac arrest and death. BrS is characterized by a specific electrocardiogram (ECG) pattern in the right ventricular leads. The only known genetic variation associated with BrS is found in the SCN5A gene. A genome-wide association study (GWAS) has identified common genetic variants associated with BrS, and these findings have been validated in different populations. The study also identified novel genetic loci associated with BrS, including one that may explain the male predominance of the syndrome. The article suggests that a polygenic risk score derived from these genetic variants could potentially improve diagnostic accuracy and risk stratification for BrS. However, further research is needed to confirm these findings and assess their clinical implications. [Extracted from the article]

Brugada Syndrome Type 1 is an arrhythmogenic disorder triggered by various etiologies, including febrile illness, pregnancy, and certain medications. This paper describes the electrocardiographic (ECG) manifestation of the Brugada pattern in a patient who developed ventricular arrhythmia after undergoing general anesthesia for pituitary surgery. [ABSTRACT FROM AUTHOR]

3p deletion syndrome or deletion 3p25-pter syndrome is an exceptionally rare genetic disorder characterized by deletion of the distal segment of the short arm of chromosome 3. There are less than a hundred reported cases worldwide. Clinical characteristics include severe physical and mental retardation, trigonocephaly, micrognathia, and diffuse hypotonia. The common ocular manifestations include congenital ptosis and canthal anomalies. To the best of the authors' knowledge, no lacrimal drainage anomalies have been reported earlier. The present case describes proximal lacrimal drainage anomalies in a patient with 3p deletion syndrome. The patient was successfully managed with membranotomy and punctal and canalicular dilatation, resulting in a complete resolution of epiphora. [ABSTRACT FROM AUTHOR]

This article discusses a case of a patient who presented with a bizarre electrocardiogram (ECG) showing bradycardia and severe conduction disorders. The differential diagnosis included sodium channel blockade, elevated intracranial pressure, or primary structural heart disease. Laboratory tests revealed hyponatremia, and further investigation revealed that the patient had ingested berries and leaves from a yew tree, which can have toxic effects on the heart. Despite the lack of an effective antidote, the patient recovered spontaneously and was discharged for further psychological support. [Extracted from the article]

Abstract Background Inherited Primary Arrhythmias Syndromes (IPAS), especially Brugada syndrome (BrS), have been associated with arrhythmogenic substrates that can be targeted through ablation. This meta‐analysis evaluated the outcomes of catheter ablation (CA) in different types of IPAS based on procedural guidance and location. Methods A systematic search was conducted across multiple databases to identify studies reporting on ventricular arrhythmia (VA) events before and after CA in IPAS, including BrS, Long‐QT syndrome (LQTS), Early repolarization syndrome (ERS), and Idiopathic ventricular fibrillation (IVF). The primary outcomes were VA recurrence and VA burden, evaluated through conditional subgroup analysis. Procedural data were collected as secondary outcomes. Results A total of 21 studies involving 584 IPAS patients who underwent CA were included. Following a mean follow‐up duration of 33.5 months, substrate‐based ablation demonstrated efficacy in reducing VA recurrence across all types of IPAS [RR 0.23; 95% CI (0.13–0.39); p

Brugada syndrome (BrS) is an inheritable cardiac arrhythmogenic disease, associated with an increased risk of sudden cardiac death. It is most common in males around the age of 40 and the prevalence is higher in Asia than in Europe and the United States. The pathophysiology underlying BrS is not completely understood, but several hypotheses have been proposed. So far, the best effective treatment is the implantation of an implantable cardioverter-defibrillator (ICD), but device-related complications are not uncommon. Therefore, there is an urgent need to improve diagnosis and risk stratification and to find new treatment options. To this end, research should further elucidate the genetic basis and pathophysiological mechanisms of BrS. Several experimental models are being used to gain insight into these aspects. The zebrafish (Danio rerio) is a widely used animal model for the study of cardiac arrhythmias, as its cardiac electrophysiology shows interesting similarities to humans. However, zebrafish have only been used in a limited number of studies on BrS, and the potential role of zebrafish in studying the mechanisms of BrS has not been reviewed. Therefore, the present review aims to evaluate zebrafish as an animal model for BrS. We conclude that zebrafish can be considered as a valuable experimental model for BrS research, not only for gene editing technologies, but also for screening potential BrS drugs.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic condition with a prevalence of 1:500-1:3 000. Variants in genes encoding sarcomeric proteins are mainly responsible for the disease. MYH7 gene encoding a myosin heavy chain beta, together with MYPBC3 gene are the two most commonly affected genes. The clinical presentation of this disease varies widely between individuals. This study aims to report a variant of MYH7 responsible for HCM in a five-generation family with a history of cardiac problems. Methods: The diagnosis was established according to the European Society of Cardiology HCM criteria based on two-dimensional Doppler echocardiography or cardiovascular magnetic resonance. Genetic analysis was performed using next-generation-sequencing and Sanger method. Results: Themedical history of the presented family began with a prenatal diagnosis of HCM in the first child of a family with previously healthy parents. Five generations of the family had a long history of sudden cardiac death and cardiac problems. ANM_ 000257.4:c.2342T>A (p.Leu781Gln) variant was detected in the MYH7 gene. It was heterozygous in the proband and in all affected individuals in a large family. The variant was present in 10 affected members of the family, and was absent in 7 members. The clinical course of the disease was severe in several members of the family: three familymembers died of sudden cardiac death, one patient required heart transplantation, three underwent septal myectomy, and three required implantable cardioverter defibrillator (ICD) implantation. Conclusion: Herein, we report a MYH7 variant responsible for HCM. Familial HCM is inherited primarily in autosomal dominant mode, which is in accordance with our study. However, the presented family showed a broad clinical spectrum of HCM. Out of 10 family members with positive genetic testing 8 had severe presentation of the disease and 2 had a mild phenotype. This suggests that the severity of the disease may depend on other factors, most likely genetic. [ABSTRACT FROM AUTHOR]

Background and purpose: Peripherally inserted central catheter (PICC) used in neurosurgical patients requires changes in patients' head positions. However, such changes can worsen pressure on the brain tissue, lead to sudden acute brain herniation and respiratory arrest, resulting in a higher chance of patient death. This paper addresses the aforementioned problems by introducing a new PICC catheterization method. Method: In a retrospective study, the records of patients with PICC from April 2020 to April 2023 were reviewed, and they were divided into three groups based on the methods employed. The first group as the conventional group, involved changing patients' body positions during catheterization. The second group, as the intracavitary electrocardiographic (IECG) group, utilized intracavitary electrocardiographic monitoring and involved changing patients' body positions during catheterization. The third group as the intracavitary electrocardiographic with improved body positioning (IECG-IBP) group, catheterization was performed with guidance from intracavitary electrocardiographs and without changing the patients' body positions. The ECG changes among patients undergoing different catheter delivery methods were then compared, as well as the rate of catheter tip misplacement. Result: The study encompassed a total of 354 cases. Our findings reveal distinct P wave amplitude percentages among the groups: 0% in the conventional group, 88.46% in the IECG group, and 91.78% in the IECG-IBP group. Furthermore, the following catheter tip misplacement rates were recorded: 11.54% for the conventional group, 5.39% for the IECG group, and 5.47% for the IECG-IBP group. Significantly notable differences were observed in these two key indicators between the conventional group and the IECG-IBP group. Notably, the IECG-IBP group demonstrated a more favorable outcome compared to the IECG group. Conclusion: In patients with neurosurgical diseases, especially those with tracheostomy and nuchal stiffness, the IECG-IBP PICC catheter insertion method can effectively reduce the patient's neck resistance, does not increase the patient's headache and dizziness symptoms, and does not reduce the success of one-time catheterization. Rate and does not increase the incidence of jugular venous ectopia. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women impacting their reproductive, mental, and metabolic health. Insulin resistance is a major driver of the pathophysiology of PCOS. There are several challenges with the management of this complex disorder including insufficient treatment options. Over the past 88 years, multiple hormonal and non-hormonal medications have been tried to treat the various components of this syndrome and there is no FDA (Food and Drug Administration)-approved medication specifically for PCOS yet. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have a unique mechanism of inhibiting the coupled reabsorption of sodium and glucose in renal proximal convoluted tubules. This review aims to examine the efficacy and side-effect profile of SGLT-2 inhibitors in patients with PCOS. In a limited number of studies, SGLT-2 inhibitors appear to be effective in improving menstrual frequency, reducing body weight and total fat mass, lowering total testosterone and DHEAS levels, and improving some glycemic indices in women with PCOS. SGLT2 inhibitors are generally well tolerated. With future research, it is possible that SGLT-2 inhibitors could become a key therapeutic option for PCOS. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) applied to cardiovascular disease (CVD) is enjoying great success in the field of scientific research. Electrocardiograms (ECGs) are the cornerstone form of examination in cardiology and are the most widely used diagnostic tool because they are widely available, inexpensive, and fast. Applications of AI to ECGs, especially deep learning (DL) methods using convolutional neural networks (CNNs), have been developed in many fields of cardiology in recent years. Deep learning methods provide valuable support for rapid ECG interpretation, demonstrating a diagnostic capability overlapping with specialists in the diagnosis of CVD by a classical analysis of macroscopic changes in the ECG trace. Through photoplethysmography, wearable devices can obtain single-derivative ECGs for the recognition of AI-diagnosed arrhythmias. In addition, CNNs have been developed that recognize no macroscopic electrocardiographic changes and can predict, from a 12-lead ECG, atrial fibrillation, even from sinus rhythm; left and right ventricular function; hypertrophic cardiomyopathy; acute coronary syndromes; or aortic stenosis. The fields of application are many, but numerous are the limitations, mainly associated with the reliability of the acquired data, an inability to verify black box processes, and medico-legal and ethical problems. The challenge of modern medicine is to recognize the limitations of AI and overcome them. [ABSTRACT FROM AUTHOR]