Arrhythmias Research Articles

Congenital heart disease and arrhythmia disorders in newborns with congenital diaphragmatic hernia: a 23-year experience at a UK university pediatric surgical centre

PurposeCongenital diaphragmatic hernia (CDH) is associated with congenital heart disease (CHD) and index newborns reportedly may experience cardiac arrhythmia disorders [Tella et al.—Pediatric Critical Care Medicine 2022]. This study analyses, details and reports contemporary outcome metrics of CHD and cardiac rhythm disease (CRD) in CDH babies attending a university surgical centre.MethodsRetrospective analysis of medical records of all newborns undergoing Bochdalek CDH repair between 1999 and 2021 at a university paediatric surgical centre. CDH newborns with CHD and neonatal arrythmias were identified from echocardiogram and electrocardiogram (ECG) investigative studies. Operative native diaphragm and / or use of patch repair(s) was documented. Outcome(s) measured—(i) mortality and (ii) cardiopulmonary interventions including ventilatory strategies—ECMO (%), inotropes and anti-arrhythmic therapy(s).ResultsOf 173 CDH neonates, 95 (55%) had CHD of which 9 babies (10%) had cardiac arrhythmias. CDH and co-existing CHD was linked with (a) lower infant birth weights (3130 g vs 3357 g, p = 0.05), (b) increased use of inotrope agents (48.4% vs 39.3%, p = 0.03) and (c) greater use of high-frequency oscillatory ventilation (38.9% vs 23%, p = 0.004). CDH babies experiencing arrythmias were at higher risk (%) of developing pulmonary hypertension (66.7% vs 28.7%, p = 0.01). No significant differences were observed in ECMO utilisation (12% vs 6%, p = 0.46) or patch repair(s) (53% vs 46%, p = 0.06) in CDH patients with and without CHD. CHD was not associated with increased risk(s) of mortality (OR 2.58, 95% CI 0.81–8.24, p = 0.11). Of 9 index CDH patients with arrhythmias—4 babies (44%) required interventional treatments.ConclusionCHD was prevalent in a high percentage (%) of CDH newborns treated at this university centre and associated with increased use (%) of cardiovascular respiratory support including patch repair. A minority of patients (2.3%) had cardiac rhythm disorders requiring treatment(s). In those developing arrhythmias pulmonary hypertension may be a risk-linked event. Optimising outcomes to offset pulmonary hypertension requires further appraisal. Future large-scale population studies may help underscore the ‘real apparent incidence’ of cardiac rhythm disorders in CDH.

Guideline-directed medical therapy for heart failure in arrhythmia-induced cardiomyopathy with improved left ventricular ejection fraction.

No study has analyzed the impact of guideline-directed medical therapy in preventing heart failure (HF) relapse in patients with arrhythmia-induced cardiomyopathy (AiCM) following left ventricular ejection fraction (LVEF) improvement. We analyzed data from a single-center cohort of 200 patients admitted for HF, LVEF <50% and cardiac arrhythmia considered by cardiologists to be the precipitating cause of the episode. The primary endpoint was time-to-HF relapse, defined as the composite of readmission for HF, Emergency Department (ED) visit for HF, or significant decline in LVEF. Changes in medication were recorded and a time-varying multivariate Cox regression was performed. After a median follow-up period of 6.14 years, diagnostic confirmation was achieved in 188 out of the initial 200 patients with suspected AiCM. A total of 89 patients (47.3%) met the primary endpoint. RAS inhibitors (adjusted hazard ratio (HR) 0.50 [0.31-0.81]; p = 0.005) and beta-blockers (adjusted HR 0.48 [0.28-0.81]; p = 0.006) were associated with a lower incidence of relapse. Mineralocorticoid receptor antagonists were associated with a significantly lower incidence of ED visits for HF (adjusted HR 0.38 [0.15-0.95]; p = 0.038), but did not achieve statistical significance for the combined primary endpoint. Antiarrhythmic drugs did not show a significant impact on the primary endpoint. Maintaining RAS inhibitors and beta-blockers was associated with a significantly lower incidence of relapse in the setting of AiCM with improved LVEF.

Evolution of Theories on Doxorubicin-Induced Late Cardiotoxicity-Role of Topoisomerase

Doxorubicin (DOX) has been widely used as a cytotoxic chemotherapeutic. However, DOX has a number of side effects, such as myelotoxicity or gonadotoxicity, the most dangerous of which is cardiotoxicity. Cardiotoxicity can manifest as cardiac arrhythmias, myocarditis, and pericarditis; life-threatening late cardiotoxicity can result in heart failure months or years after the completion of chemotherapy. The development of late cardiomyopathy is not yet fully understood. The most important question is how DOX reprograms the cardiomyocyte, after which DOX is excreted from the body, initially without symptoms. However, clinically overt cardiomyopathy develops over the following months and years. Since the 1980s, DOX-induced disorders in cardiomyocytes have been thought to be related to oxidative stress and dependent on the Fe/reactive oxygen species (ROS) mechanism. That line of evidence was supported by dexrazoxane (DEX) protection, the only Food and Drug Administration (FDA)-approved drug for preventing DOX-induced cardiomyopathy, which complexes iron. Thus, the hypothesis related to Fe/ROS provides a plausible explanation for the induction of the development of late cardiomyopathy via DOX. However, in subsequent studies, DEX was used to identify another important mechanism in DOX-induced cardiomyopathy that is related to topoisomerase 2β (Top2β). Does the Top2β hypothesis explain the mechanisms of the development of DOX-dependent late heart failure? Several of these mechanisms have been identified to date, proving the involvement of Top2β in the regulation of the redox balance, including oxidative stress. Thus, the development of late cardiomyopathy can be explained based on mechanisms related to Top2β. In this review, we highlight free radical theory, iron imbalance, calcium overload, and finally, a theory based on Top2β.

Modeling Magneto-Active Soft Robots in Vessels Based on Discrete Differential Geometry of Framed Curves

Abstract Cardiac arrhythmias, such as atrial fibrillation, pose significant health risks and are often treated using minimally invasive cardiac ablation. However, the limited maneuverability of mechanically driven catheters can undermine both the success and efficiency of the procedure. In contrast, magnetic soft continuum robots (MSCRs) offer a promising alternative by utilizing external magnetic fields to directly steer the catheter tip. This approach allows for precise control, simplifying navigation through intricate vascular systems, ensuring stable contact with lesions, and minimizing manual manipulation. To optimize the use of MSCRs in magnetically assisted cardiac ablation, it is crucial to model their behavior, focusing on contact with the vascular environment. This article establishes a theoretical model of MSCRs based on Cosserat beam theory and discrete differential geometry (DDG). The model is validated and subsequently used to simulate three scenarios: partially magnetized MSCRs, MSCRs with point contacts, and MSCRs with line contacts. The results reveal significant nonlinear behavior upon contact. By applying our model, we demonstrate how adjustments of the magnetic field's direction, magnitude, and MSCR length can guide navigation through bifurcated vessels and achieve precise contact with a lesion. These findings provide valuable insights into the design and control of MSCRs, enabling more efficient, simulation-driven guidance for minimally invasive procedures and advancing digital health care in endovascular applications.

Transcriptome-wide RNA 5-methylcytosine profiles of human iPSCs and iPSC-derived cardiomyocytes

Cardiac regenerative therapy has recently progressed by reprogramming somatic cells into induced pluripotent stem cells (iPSCs) and advanced by large-scale differentiation-derived cardiomyocytes (hiPSC-CMs). However, repairing damaged cardiac tissues with hiPSC-CMs remains limited due to immune rejection, cardiac arrhythmias, and concerns over tumor formation after hiPSC-CM transplantation. Despite efforts in profiling epigenomic changes during cardiac differentiation, regulatory mechanisms underlying 5-methylcytosine (m5C) deposition in RNA m5C epitranscriptomic landscape during hiPSC-to-cardiomyocyte differentiation remain unclear. Herein, bisulfite RNA-sequencing analysis was conducted in human pluripotent stem cells (hPSCs) from three independent cellular origins, and their derived cardiomyocytes (hPSC-CM), metabolic-maturation of derived cardiomyocytes (hPSC-CM-lac) and biochemical-enhanced derived cardiomyocytes (hPSC-CM-TDI). Integrated analysis of differentially methylated RNA m5C profiles and transcriptome-wide expression facilitated the identification of m5C sites coupled to the cardiomyocyte differentiation and RNA-dependent regulatory mechanisms of stem cell pluripotency. The RNA m5C profiles in this dataset allow the evaluations of the m5C level and distribution of specific m5C loci and facilitate understanding of the m5C epitranscriptomic landscape in biological functions of hPSC-CM beyond in vivo transplantation barriers.

Enhancing stroke risk stratification in atrial fibrillation through non-Newtonian blood modelling and Gaussian process emulation.

Atrial fibrillation (AF) is the most common heart arrhythmia, linked to a five-fold increase in stroke risk. The left atrial appendage (LAA), prone to blood stasis, is a common thrombus formation site in AF patients. The LAA can be classified into four morphologies: broccoli, cactus, chicken wing and windsock. Stroke risk prediction in AF typically relies on demographic characteristics and comorbidities, often overlooking blood flow dynamics. We developed patient-specific non-Newtonian models of blood flow, dependent on fibrinogen and haematocrit, to predict changes in LAA viscosity, aiming to predict stroke in AF patients. We conducted 480 computational fluid dynamics (CFD) simulations using the non-Newtonian model across the four LAA morphologies for four virtual patient cohorts: AF + Covid-19, AF + pathological fibrinogen, AF + normal fibrinogen, and healthy controls. Gaussian process emulators (GPEs) were trained on this in silico cohort to predict average LAA viscosity at near-zero computational cost. GPEs demonstrated high accuracy in AF cohorts but lower accuracy when the chicken wing GPE was applied to other morphologies. Global sensitivity analysis showed fibrinogen significantly influenced blood viscosity in all AF cohorts. The chicken wing morphology exhibited the highest viscosity, while the AF + Covid-19 cohort had the highest viscosity. Our non-Newtonian model in CFD simulations confirmed fibrinogen's substantial impact on blood viscosity at low shear rates in the LAA, suggesting that combining blood values and geometric parameters of the LAA into GPE training could enhance stroke risk stratification accuracy. KEY POINTS: Fibrinogen has a significant effect on blood viscosity in the left atrial appendage (LAA) at low shear rates. Gaussian process emulators (GPEs) can predict the viscosity of blood in the LAA at near-zero computational cost. Out of all LAA morphologies, the chicken wing morphology exhibited the highest average blood viscosity. High average blood viscosity in the LAA of atrial fibrilation + Covid-19 patients was observed due to high fibrinogen levels in this cohort. Combining blood values and geometric parameters of the LAA into GPE training could enhance stroke risk stratification accuracy.

Endurance Sports and Atrial Fibrillation: A Puzzling Conundrum

The confirmed benefits of regular moderate exercise on cardiovascular health have positioned athletes as an illustration of well-being. However, concerns have arisen regarding the potential predisposition to arrhythmias in individuals engaged in prolonged strenuous exercise. Atrial fibrillation (AF), the most common heart arrhythmia, is typically associated with age-related risks but has been documented in otherwise healthy young and middle-aged endurance athletes. The mechanism responsible for AF involves atrial remodeling, fibrosis, inflammation, and alterations in autonomic tone, all of which intersect with the demands of endurance sports, cumulative training hours, and competitive participation. This unique lifestyle requires a tailored therapeutic approach, often favoring radiofrequency ablation as the preferred treatment. As the number of professional and non-professional athletes engaging in high-level daily sports activities rises, awareness of AF within this demographic becomes imperative. This review delivers the etiology, pathophysiology, and therapeutic considerations surrounding AF in endurance sports.

A clinical challenge of cardiomyopathies: Beyond the heart

Introduction: The relation between the cancer and the heart is diverse. It can be affected all parts of the heart directly or indirectly caused by the systemic manifestation of the cancer or by cancer therapy. Paraneoplastic dermatomyositis and tumor lysis syndrome (TLS) are two examples of systemic manifestations of cancer. Being systemic, the cardiovascular system can be affected. Heart failure and arrhythmias are the main cardiac manifestations. Case Report: A 68-year-old man with a recent diagnosis of diffuse large B-cell lymphoma waiting to begin chemotherapy, and paraneoplastic dermatomyositis, presented at the emergency department (ED) with palpitations and dyspnea with a week of evolution. At the physical examination, he presented with pulmonary edema and the novo rapid atrial fibrillation. Also, an Nt-pro BNP of 8957 pg/mL, and echocardiography with severe dilated left ventricle, with a severe reduced ejection fraction. Already in the ward, the patient developed a spontaneous TLS. The etiological interpretation was that paraneoplastic dermatomyositis and TLS were the triggers of atrial fibrillation (AF). Then, the combination of them was responsible for development of the dilated cardiomyopathy (tachymyocardiopathy). The chemotherapy regimen was changed to R-CEOP (Rituximab, cyclophosphamide, etoposide, vincristine sulfate, and prednisone). Conclusion: This clinical case perfectly shows how the world of cardiomyopathies can be challenging and hard to understand all the complexity of the patients.

Mechanisms and Therapeutic Strategies for Myocardial Ischemia-Reperfusion Injury in Diabetic States.

In patients with myocardial infarction, one of the complications that may occur after revascularization is myocardial ischemia-reperfusion injury (IRI), characterized by a depleted myocardial oxygen supply and absence of blood flow recovery after reperfusion, leading to expansion of myocardial infarction, poor healing of myocardial infarction and reversal of left ventricular remodeling, and an increase in the risk for major adverse cardiovascular events such as heart failure, arrhythmia, and cardiac cell death. As a risk factor for cardiovascular disease, diabetes mellitus increases myocardial susceptibility to myocardial IRI through various mechanisms, increases acute myocardial infarction and myocardial IRI incidence, decreases myocardial responsiveness to protective strategies and efficacy of myocardial IRI protective methods, and increases diabetes mellitus mortality through myocardial infarction. This Review summarizes the mechanisms, existing therapeutic strategies, and potential therapeutic targets of myocardial IRI in diabetic states, which has very compelling clinical significance.

Inositol 1,4,5-Trisphosphate Receptor 1 Gain-of-Function Increases the Risk for Cardiac Arrhythmias in Mice and Humans.

Ca2+ mishandling in cardiac Purkinje cells is a well-known cause of cardiac arrhythmias. The Purkinje cell resident inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is believed to play an important role in Ca2+ handling, and ITPR1 gain-of-function (GOF) has been implicated in cardiac arrhythmias. However, nearly all known disease-associated ITPR1 variants are loss-of-function and are primarily linked to neurological disorders. Whether ITPR1 GOF has pathological consequences, such as cardiac arrhythmias, is unclear. This study aimed to identify human ITPR1 GOF variants and determine the impact of ITPR1 GOF on Ca2+ handling and arrhythmia susceptibility. There are a large number of rare ITPR1 missense variants reported in open data repositories. Based on their locations in the ITPR1 channel structure, we selected and characterized 33 human ITPR1 missense variants from open databases and identified 21 human ITPR1 GOF variants. We generated a mouse model carrying a human ITPR1 GOF variant, ITPR1-W1457G (W1447G in mice). We showed that the ITPR1-W1447G± and recently reported ITPR1-D2594K± GOF mutant mice were susceptible to stress-induced ventricular arrhythmias. Confocal Ca2+ and voltage imaging in situ in heart slices and Ca2+ imaging and patch-clamp recordings of isolated Purkinje cells showed that ITPR1-W1447G± and ITPR1-D2594K± variants increased the occurrence of stress-induced spontaneous Ca2+ release, delayed afterdepolarization, and triggered activity in Purkinje cells. To assess the potential role of ITPR1 variants in arrhythmia susceptibility in humans, we looked up a gene-based association study in the UK Biobank data set and identified 7 rare ITPR1 missense variants showing potential association with cardiac arrhythmias. Remarkably, in vitro functional characterization revealed that all these 7 ITPR1 variants resulted in GOF. Our studies in mice and humans reveal that enhanced function of ITPR1, a well-known movement disorder gene, increases the risk for cardiac arrhythmias.

Advantages of using T1-mapping in cardiac magnetic resonance imaging in patients with acromegaly

Aim. To determine the incidence of interstitial myocardial fibrosis (MF) in acromegaly, which leads to the development of cardiac arrhythmias and conduction disorders. Materials and methods. A single-center study was conducted, including 70 patients with acromegaly. All patients underwent standard medical examinations, including hormonal blood tests, electrocardiograms, echocardiography, Holter monitoring electrocardiograms and magnetic resonance imaging (MRI) of the heart with gadolinium contrast, additionally 48 patients underwent T1-mapping, which is an MRI method that allows the detection of diffuse changes by measuring the values of myocardial relaxation time – T1. Results. The study revealed a high incidence of MF – 53 (75.7%) cases (21 women, 32 men). The duration of the disease was found to be critical for myocardial remodeling (p=0.006). Compliance criteria for the T1-mapping technique were determined, with reduced T1-mapping values observed in 85.2% of cases. The ROC analysis (Receiver Operator Characteristic) determined the diagnostic value of post-contrast T1-mapping: AUC (Area Under the Curve)=0.906 (95% confidence interval 0.789–1.000), a sensitivity of 90%, and a specificity of 76.5%, indicating high diagnostic efficiency. According to the Youden index, a cut-off point of 372.5 ms was selected. Conclusion. Myocardial T1-mapping is a novel MRI method that allows to assess the degree of MF without the need for myocardial biopsy. The obtained information is crucial for the diagnosis and prognostic assessment of heart diseases, particularly in cases of hypertrophic cardiomyopathy or infiltrative diseases. The T1-mapping method, which is actively developing, can serve as a marker for early diffuse myocardial fibrosis and help determine the prognosis for patients with acromegalic cardiomyopathy.

Chloride channels and transporters – role in the electrical activity of pacemaker and working myocardium

Chlorine anions have a significant influence on the electrophysiological properties of excitable tissues, including myocardium. Chlorine anions and transmembrane chloride currents (ICl) determine the configuration of action potentials (AP) in various regions of hearts. Disruption of transmembrane chloride transport leads to alterations in normal electrical activity, resulting in cardiac pathologies and arrhythmias. Currently, chloride conductivity and expression in the heart and a functional role have been confirmed for several types of macromolecules. These channels include CFTR, ClC-2, CaCC (TMEM16), and VRAC (LRRC8x). Additionally, chloride cotransporters (KCC, NKCC) and chloride-bicarbonate exchangers make a significant contribution to the regulation of intracellular chlorid ion concentration ([Cl-]i) and, consequently, the equilibrium potential for chloride ions (ECl). The review covers the mechanisms by which chloride transmembrane transport influences the bioelectrical activity of cardiomyocytes and the potential functions of chloride and chloride currents in specialized regions of the heart.

Pulmonary adverse events associated with amiodarone: a real-world pharmacovigilance study based on the FDA adverse event reporting system

ABSTRACT Background: Amiodarone is used to treat cardiac arrhythmias but carries a risk of pulmonary toxicity. Despite this well-known side effect, there is currently no large descriptive case series studying amiodarone-induced pulmonary toxicity. Methods: The reporting odds ratio (ROR) was utilized to quantify signals of amiodarone-related pulmonary adverse events (AEs) from 2004 to 2023. Severity comparisons between serious and non-serious cases were conducted using the Mann-Whitney U test or chi-square (χ2) test, and signal prioritization was achieved through rating scales. Results: A total of 4896 cases of amiodarone-related pulmonary AEs were found, and 56 signals were detected. 27 AEs were classified as serious adverse reactions, and 21 AEs were identified as new and unexpected signals. Even when stratified by age, weight, sex, and reporter type, the association between amiodarone and pulmonary diseases persisted. Seven strong clinical priority signals were defined. The median time to onset (TTO) for strong, moderate, and weak clinical priority signals was 221, 126, and 227 days, respectively. All disproportional signals exhibited an early failure-type pattern. Conclusion: Our study offers a deeper and broader understanding of the pulmonary safety profile of amiodarone, which will aid healthcare professionals in mitigating the risk of pulmonary adverse events in clinical practice.

Environmental Factors, Occupational Hazards, and Seasonal Changes: Unveiling the Triggers of Atrial Fibrillation.

Atrial Fibrillation (AF) is the most common cardiac arrhythmia in the world, with a lifetime risk of 26% for men and 23% for women. Atrial fibrillation is a prevalent cardiac arrhythmia that is more common with increasing age. Globally, around 33.5 million people are estimated to have AF, which is anticipated to rise as the population ages. Although effective therapeutic methods exist, they are costly for the healthcare system. The search was conducted across multiple databases, including Medline, PubMed, and Google Scholar, as well as through manual searches of recognized publications and their bibliographies. Identifying modifiable risk factors for AF and implementing appropriate preventative measures may significantly improve public health and reduce healthcare costs. The development of AF has been reported to be associated with various causes, including electrical and structural changes in the atrial tissue. This article has reviewed how environmental factors, occupational hazards, and seasonal variability can affect AF. The incidence and prevalence of AF have been increasing, leading to a high lifetime risk for individuals. The available evidence indicates that seasonal variation, environmental factors, such as noise and air pollution, type of job, and altitude are all associated with an increased risk of developing AF. Although the exact mechanisms underlying these associations remain unclear, it is likely that a combination of factors, including changes in autonomic tone, inflammation, and oxidative stress, play a role. This review has highlighted the significance of assuming the role of environmental and occupational factors in the development of AF.

Monitoring individualized glucose levels predicts risk for bradycardia in type 2 diabetes patients with chronic kidney disease: a pilot study

Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) exhibit an elevated risk for cardiac arrhythmias, such as bradycardia, which may potentially lead to sudden cardiac death (SCD). While hypoglycemia, defined as a critical drop in glucose levels below the normal range, has long been associated with adverse cardiovascular events, recent studies have highlighted the need for a comprehensive reevaluation of its direct impact on cardiovascular outcomes, particularly in high-risk populations such as those with DM and CKD. In this study, we investigated the association between glucose levels and bradycardia by simultaneously monitoring interstitial glucose (IG) and ECG for 7 days in insulin-treated patients with DM and CKD. We identified bradycardia episodes in 19 of 85 patients (22%) and associated these episodes with personalized low, medium, and high relative glucose levels. Our analysis revealed a significant increase in bradycardia frequency during periods of lowest relative glucose, particularly between 06:00-09:00 and 12:00-15:00. Furthermore, leveraging a Random Forests classifier, we achieved a promising area under the curve (AUC) of 0.94 for predicting bradyarrhythmias using glucose levels and heart rate variability features. Contrary to previous findings, only 4% of bradycardia episodes in our study population occurred at glucose levels of 70 mg/dL or lower, with 28% observed at levels exceeding 180 mg/dL. Our findings not only highlight the strong correlation between relative glucose levels, heart rate parameters, and bradycardia onset but also emphasize the need for a more personalized definition of hypoglycemia to understand its relationship with bradyarrhythmias in high-risk DM and CKD patient populations.

QTc interval prolongation and its associated factors among HIV infected patients on ART in Mettu Town

QTc interval prolongation, which is linked to cardiac arrhythmia and sudden cardiac death, is common in HIV-infected patients. This prolongation can be attributed to the side effects of antiretroviral medications, the direct impact of HIV on the heart, and chronic inflammatory responses that disrupt cardiac electrical activity. This study aimed at assessing QTc interval prolongation and associated factors among HIV-infected adults on ART. A cross-sectional study was conducted among consecutively selected 298 HIV-infected patients at Mettu Karl Specialized Hospital, southwest Ethiopia. A face-to-face interview with a structured and pretested questionnaire was employed to collect socio-demographic and behavioural characteristics data. Electrocardiography was done using a 12-lead electrocardiograph, and interpreted by a cardiologist. Data were entered into Epi-data version 4.6 and analyzed using SPSS version 25. Multivariable logistic regression analyses were done at a significance level of P < 0.05. QTc prolongation was prevalent in 12.4% of participants. Being on PIs containing HAART regimen (AOR = 5.7, 95%CI 2.54–12.8), having recent CD4 count of < 350 cells/mm3 (AOR = 4.8, 95%CI 2.19–10.5), and recent viral load of ≥ 1000coppies/ml (AOR = 2.8, 95%CI 1.24–6.42) were significantly associated with QTc prolongation. According to this study, one of the ten HIV-infected patients on ART had QTc prolongation. Therefore, we suggest that HIV-positive patients receiving treatment should undergo screening for QTc interval prolongation.

Atypical presentation of Andersen-Tawil syndrome: heart failure with reduced ejection without periodic paralysis or dysmorphic features

Background: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder caused by variants in the KCNJ2 gene. It is associated with periodic paralysis, dysmorphic features and cardiac arrhythmias. The syndrome exhibits incomplete penetrance, leading to a broad spectrum of clinical manifestations, making diagnosis challenging. Case description: A male in his mid-20s with class 3 obesity presented to the emergency department with a week-long history of worsening chest pain, orthopnoea and fatigue. His family history was significant for sudden cardiac death affecting both his mother and brother, with his father having died from complications of Wolff-Parkinson-White syndrome. Cardiovascular examination revealed an S3 heart sound and elevated brain natriuretic peptide levels at 875 pg/ml, with undetectable troponins; potassium level on admission was 3.6 mEq/l. An electrocardiogram showed normal sinus rhythm, first-degree heart block, left atrial enlargement, left bundle branch block and a prolonged QTc of 486 ms. A transthoracic echocardiogram demonstrated a 15-20% reduction in ejection fraction with global left ventricular hypokinesis and left atrial enlargement. Ultimately, he was diagnosed with non-ischaemic dilated cardiomyopathy and referred for genetic testing, which revealed a KCNJ2 variant. Shortly after discharge, he experienced a 55-second run of ventricular tachycardia, necessitating the placement of a single-chamber ICD. Currently, the patient remains on guideline-directed medical therapy and is listed for a heart transplant. Conclusions: Dilated cardiomyopathy, although a rare manifestation in ATS, can profoundly increase the risk of fatal arrythmias, necessitating the need for a low threshold of suspicion, to ensure timely diagnosis and management.

Puerarin reduces susceptibility to ventricular arrhythmias and inhibits ferroptosis via Sirt1/Nrf2 signaling in high-fat-diet rats.

Obesity is a significant risk factor for cardiac arrhythmias, and the ferroptosis is closely related to cardiac arrhythmias. This study aimed to investigate whether puerarin (Pue), a natural isoflavone, could reduce the susceptibility to ventricular arrhythmias (VAs) associated with obesity and inhibit ferroptosis, with a particular focus on the Sirt1/Nrf2 signaling pathway. Male rats were randomly divided into three groups: normal chow diet (NC), high-fat diet (HFD), and HFD with Pue treatment (100 mg/kg, HFD+Pue). After 16 weeks, electrophysiological, structural, and molecular analysis were performed. Compared to the NC group, HFD rats exhibited prolonged QT interval and Tpeak-Tend interval, amplified transmural dispersion of ventricular repolarization, and increased susceptibility to VAs. Pue treatment significantly ameliorated these electrophysiological abnormalities and reduced VAs susceptibility. HFD rats showed cardiac hypertrophy, fibrosis, and inflammation, which were alleviated by Pue application. Cardiac lipid peroxidation, iron deposition, mitochondrial abnormality, and ferroptosis marker induction were observed in HFD rats. Further, treatment with Pue improved these alterations. Additionally, molecular docking analysis confirmed the interaction of Pue with Sirt1 and Nrf2. Furthermore, Pue treatment upregulated Sirt1 and Nrf2 expression in HFD rats, thereby reducing reactive oxygen species (ROS) generation and ferroptosis. Moreover, Pue protected cardiomyocytes against palmitic acid (PA)-induced injury by inhibiting ferroptosis via the Sirt1/Nrf2 pathway in H9c2 cells. Overall, our study shows for the first time that Pue reduces susceptibility to VAs and inhibits ferroptosis in HFD rats by modulating the Sirt1/Nrf2 signaling pathway, offering a potential therapeutic strategy for obesity-related cardiac arrhythmias.

Long-term therapeutic efficacy and safety profiles of hpCas13d RNA editing in treating early-onset hypertrophic cardiomyopathy

AimsThrough evolving a precise RNA nuclease, hpCas13d, we have successfully inhibited hypertrophic cardiomyopathy in a compound heterozygous model. However, further investigation is needed to assess the long-term therapeutic effects and safety profiles of hpCas13d treatment. Materials and methodsAAV-hpCas13d[RQ] was subcutaneously injected into neonatal Myh6RH/RQ mice. Sequential echocardiography analyses were conducted at 4 months and 12 months to evaluate the sustained therapeutic effects of hpCas13d. Electrocardiography was employed to assess cardiac arrhythmias, and mice were euthanized at 12 months. Quantification of Myh6RQ degradation induced by hpCas13d[RQ] was performed using digital droplet PCR and cDNA sequencing. Histological analysis, RNA sequencing, and proteomic analyses were utilized to examine the inhibitory effects on pathological phenotypes and downstream signaling pathways. Biodistribution, tissue damage, and host immune response to AAV-hpCas13d[RQ] were assessed to evaluate long-term safety profiles. Key findingsThe allele-specific RNA degradation persisted for 12 months in AAV-hpCas13d[RQ]-treated Myh6RH/RQ mice. Partial degradation of pathogenic Myh6RQ transcripts proved adequate for the long-term inhibition of cardiac hypertrophy, arrhythmias, fibrosis, and cellular apoptosis in Myh6RH/RQ mice. RNA sequencing and proteomic analyses revealed that hpCas13d[RQ] treatment impeded hypertrophy and fibrosis, mitochondrial dysfunction, and abnormalities in ion channels downstream of mutant Myh6. Prolonged treatment with AAV-hpCas13d from the neonatal stage did not induce significant tissue damage, liver toxicity, humoral responses, or cellular immune reactions against the AAV9 capsid and bacterial hpCas13d. SignificanceThese results underscore the promising translational potential of AAV-hpCas13d in treating cardiovascular diseases and advancing in vivo gene therapy.

Comparison between the ECG Outcomes of Metoprolol and Bisoprolol.

Beta-blockers are essential agents in the management of cardiovascular diseases, such as heart failure, acute myocardial infarction (MI), and cardiac arrhythmias. However, there are diurnal variations in the cardioprotective effects of the subgroups as a result of their different pharmacokinetic, pharmacodynamic, and pharmacogenetic profiles. We aimed to compare metoprolol and bisoprolol in terms of electrocardiogram (ECG) outcomes. A retrospective cross-sectional study was conducted at Prince Sultan Cardiac Center. The trial included 404 patients who met the inclusion criteria (204 in the metoprolol arm and 200 in the bisoprolol arm). Using case record forms that had already been created, information, such as patient demographics, medical histories, and treatment histories, was taken from their medical files. The most recent ECG records were also gathered. The ethical approval for this study was obtained from Qassim ethical committee (approval number: 45-44-902). There was no significant difference found between the patients in both arms in terms of baseline characteristics, age, or sex. In this retrospective cross-sectional study, we have compared the effects of metoprolol and bisoprolol beta blockers on ECG changes. The findings have indicated no difference between metoprolol and bisoprolol groups in terms of all ECG readings, particularly PR/ms, QTC-ms, and ventricular rate. Further studies are required to confirm these findings.