Impaired Intracellular Calcium Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From Patients With Atrial Fibrillation.

BACKGROUND: Alterations in the buffering of intracellular Ca2+, for which myofilament proteins play a key role, have been shown to promote cardiac arrhythmia. It is interesting that although studies report atrial myofibrillar degradation in patients with persistent atrial fibrillation (persAF), the intracellular Ca2+ buffering profile in persAF remains obscure. Therefore, we aimed to investigate the intracellular buffering of Ca2+ and its potential arrhythmogenic role in persAF. METHODS: Transmembrane Ca2+ fluxes (patch-clamp) and intracellular Ca2+ signaling (fluo-3-acetoxymethyl ester) were recorded simultaneously in myocytes from right atrial biopsies of sinus rhythm (Ctrl) and patients with persAF, alongside human atrial subtype induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). Protein levels were quantified by immunoblotting of human atrial tissue and induced pluripotent stem cell-derived cardiac myocytes. Mouse whole heart and atrial electrophysiology were measured on a Langendorff system. RESULTS: Cytosolic Ca2+ buffering was decreased in atrial myocytes of patients with persAF because of a depleted amount of Ca2+ buffers. In agreement, protein levels of selected Ca2+ binding myofilament proteins, including cTnC (cardiac troponin C), a major cytosolic Ca2+ buffer, were significantly lower in patients with persAF. Small interfering RNA (siRNA)-mediated knockdown of cTnC (si-cTNC) in atrial iPSC-CM phenocopied the reduced cytosolic Ca2+ buffering observed in persAF. Si-cTnC treated atrial iPSC-CM exhibited a higher predisposition to spontaneous Ca2+ release events and developed action potential alternans at low stimulation frequencies. Last, indirect reduction of cytosolic Ca2+ buffering using blebbistatin in an ex vivo mouse whole heart model increased vulnerability to tachypacing-induced atrial arrhythmia, validating the direct mechanistic link between impaired cytosolic Ca2+ buffering and atrial arrhythmogenesis. CONCLUSIONS: Our findings suggest that loss of myofilament proteins, particularly reduced cTnC protein levels, causes diminished cytosolic Ca2+ buffering in persAF, thereby potentiating the occurrence of spontaneous Ca2+ release events and atrial fibrillation susceptibility. Strategies targeting intracellular buffering may represent a promising therapeutic lead in persAF management.

Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNFα (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities in a murine model of KD vasculitis. METHODS: Lactobacillus casei cell wall extract-induced KD vasculitis model was used to investigate the therapeutic efficacy of clinically relevant IL-1Ra (IL-1 receptor antagonist) and TNFα neutralization. Echocardiography, in vivo electrophysiology, whole-heart optical mapping, and imaging were performed. RESULTS: KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity. Since our transcriptomic analysis of human patients showed elevated levels of both IL-1ß and TNFα, we asked whether either cytokine was linked to the development of myocardial dysfunction. Remarkably, only inhibition of IL-1 signaling by IL-1Ra but not TNFα neutralization was able to prevent changes in ejection fraction and arrhythmias, whereas both IL-1Ra and TNFα neutralization significantly improved vasculitis and heart vessel inflammation. The treatment of L casei cell wall extract-injected mice with IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk. In contrast, in mice with gain of function of the IL-1 signaling pathway, L casei cell wall extract induced spontaneous ventricular tachycardia and premature deaths. CONCLUSIONS: Our results characterize the electrophysiological abnormalities associated with L casei cell wall extract-induced KD and show that IL-1Ra is more effective in preventing KD-induced myocardial dysfunction and arrhythmias than anti-TNFα therapy. These findings support the advancement of clinical trials using IL-1Ra in patients with KD.

The electrical restitution of the non-propagated cardiac ventricular action potential.

Sudden changes in pacing cycle length are frequently associated with repolarization abnormalities initiating cardiac arrhythmias, and physiologists have long been interested in measuring the likelihood of these events before their manifestation. A marker of repolarization stability has been found in the electrical restitution (ER), the response of the ventricular action potential duration to a pre- or post-mature stimulation, graphically represented by the so-called ER curve. According to the restitution hypothesis (ERH), the slope of this curve provides a quantitative discrimination between stable repolarization and proneness to arrhythmias. ER has been studied at the body surface, whole organ, and tissue level, and ERH has soon become a key reference point in theoretical, clinical, and pharmacological studies concerning arrhythmia development, and, despite criticisms, it is still widely adopted. The ionic mechanism of ER and cellular applications of ERH are covered in the present review. The main criticism on ERH concerns its dependence from the way ER is measured. Over the years, in fact, several different experimental protocols have been established to measure ER, which are also described in this article. In reviewing the state-of-the art on cardiac cellular ER, I have introduced a notation specifying protocols and graphical representations, with the aim of unifying a sometime confusing nomenclature, and providing a physiological tool, better defined in its scope and limitations, to meet the growing expectations of clinical and pharmacological research.

Burden of cardiac arrhythmias in patients with acute myocardial infarction and their impact on hospitalization outcomes: insights from China acute myocardial infarction (CAMI) registry.

BACKGROUND: The coexistence of cardiac arrhythmias in patients with acute myocardial infarction (AMI) usually exhibits poor prognosis. However, there are few contemporary data available on the burden of cardiac arrhythmias in AMI patients and their impact on in-hospital outcomes. METHODS: The present study analyzed data from the China Acute Myocardial Infarction (CAMI) registry involving 23,825 consecutive AMI patients admitted to 108 hospitals from January 2013 to February 2018. Cardiac arrhythmias were defined as the presence of bradyarrhythmias, sustained atrial tachyarrhythmias, and sustained ventricular tachyarrhythmias that occurred during hospitalization. In-hospital outcome was defined as a composite of all-cause mortality, cardiogenic shock, re-infarction, stroke, or heart failure. RESULTS: Cardiac arrhythmia was presented in 1991 (8.35%) AMI patients, including 3.4% ventricular tachyarrhythmias, 2.44% bradyarrhythmias, 1.78% atrial tachyarrhythmias, and 0.73% ≥2 kinds of arrhythmias. Patients with arrhythmias were more common with ST-segment elevation myocardial infarction (83.3% vs. 75.5%, P < 0.001), fibrinolysis (12.8% vs. 8.0%, P < 0.001), and previous heart failure (3.7% vs. 1.5%, P < 0.001). The incidences of in-hospital outcomes were 77.0%, 50.7%, 43.5%, and 41.4%, respectively, in patients with ≥ 2 kinds of arrhythmias, ventricular tachyarrhythmias, bradyarrhythmias, and atrial tachyarrhythmias, and were significantly higher in all patients with arrhythmias than those without arrhythmias (48.9% vs. 12.5%, P < 0.001). The presence of any kinds of arrhythmia was independently associated with an increased risk of hospitalization outcome (≥ 2 kinds of arrhythmias, OR 26.83, 95%CI 18.51-38.90; ventricular tachyarrhythmias, OR 8.56, 95%CI 7.34-9.98; bradyarrhythmias, OR 5.82, 95%CI 4.87-6.95; atrial tachyarrhythmias, OR4.15, 95%CI 3.38-5.10), and in-hospital mortality (≥ 2 kinds of arrhythmias, OR 24.44, 95%CI 17.03-35.07; ventricular tachyarrhythmias, OR 13.61, 95%CI 10.87-17.05; bradyarrhythmias, OR 7.85, 95%CI 6.0-10.26; atrial tachyarrhythmias, OR 4.28, 95%CI 2.98-6.16). CONCLUSION: Cardiac arrhythmia commonly occurred in patients with AMI might be ventricular tachyarrhythmias, followed by bradyarrhythmias, atrial tachyarrhythmias, and ≥ 2 kinds of arrhythmias. The presence of any arrhythmias could impact poor hospitalization outcomes. REGISTRATION: Clinical Trial Registration: Identifier: NCT01874691.

Continuous cardiac monitoring in epilepsy: an implantable loop manual activation algorithm for improving ECG signal acquisition accuracy.

BACKGROUND: The muscle artifacts, caused by prominent muscle contractions, mimicking cardiac arrhythmias, might compromise the ECG signal quality and the implantable loop recorder memory capacity in patients with epilepsy. We developed an epileptic seizures clinical pattern-based implantable loop recorder manual activation algorithm, presenting its real-world efficacy here. METHODS: One hundred ninety-three patients (18-60 years) with drug-resistant focal epilepsy were consecutively enrolled and underwent a subcutaneous loop recorder implantation. Patients with focal onset-aware seizures and patients with focal impaired awareness seizures /bilateral tonic-clonic seizures without aura were recommended to use the activator once - just after the episode. Patients with focal impaired awareness seizures/bilateral tonic-clonic seizures with aura, the caregivers of patients experiencing status epilepticus, were advised to use the activator twice - during the aura and after the episode/ regaining consciousness. RESULTS: Six thousand four hundred ninety-four ECG traces (4826 - auto-triggered events, 1668 - person-activated events) were recorded and analyzed. The rate of true positive events in the person-activated group was statistically higher than in the autoactivation group (72.5% vs.19.4%, p < 0.0001). Person-activated false-positive events were observed in 30.5% of patients with focal impaired awareness seizures and 27.7% in patients with bilateral tonic-clonic seizures. The highest rate of false-positive events (61.5%) was detected in patients undergoing epileptic status, and the lowest rate (3.8%) - was in patients with focal onset aware seizures. The rate of false-positive events was significantly higher in patients with impaired awareness seizures without aura both in focal impaired awareness (45.5% vs. 19.3%, p < 0.0001) and bilateral tonic-clonic seizure groups (38.8% vs. 5.9%, p < 0.0001). CONCLUSIONS: Arrhythmias with varying clinical outcomes are expected in epilepsy patients and have been monitored continuously. The specified loop recorder external activation algorithm can improve the clinically relevant cardiac arrhythmia detection accuracy in epilepsy patients and the value of future studies.

A dynamic online nomogram predicting post-traumatic arrhythmias: A retrospective cohort study.

BACKGROUND: A nomogram is a visualized clinical prediction models, which offer a scientific basis for clinical decision-making. There is a lack of reports on its use in predicting the risk of arrhythmias in trauma patients. This study aims to develop and validate a straightforward nomogram for predicting the risk of arrhythmias in trauma patients. METHODS: We retrospectively collected clinical data from 1119 acute trauma patients who were admitted to the Advanced Trauma Center of the Affiliated Hospital of Zunyi Medical University between January 2016 and May 2022. Data recorded included intra-hospital arrhythmia, ICU stay, and total hospitalization duration. Patients were classified into arrhythmia and non-arrhythmia groups. Data was summarized according to the occurrence and prognosis of post-traumatic arrhythmias, and randomly allocated into a training and validation sets at a ratio of 7:3. The nomogram was developed according to independent risk factors identified in the training set. Finally, the predictive performance of the nomogram model was validated. RESULTS: Arrhythmias were observed in 326 (29.1%) of the 1119 patients. Compared to the non-arrhythmia group, patients with arrhythmias had longer ICU and hospital stays and higher in-hospital mortality rates. Significant factors associated with post-traumatic arrhythmias included cardiovascular disease, catecholamine use, glasgow coma scale (GCS) score, abdominal abbreviated injury scale (AIS) score, injury severity score (ISS), blood glucose (GLU) levels, and international normalized ratio (INR). The area under the receiver operating characteristic curve (AUC) values for both the training and validation sets exceeded 0.7, indicating strong discriminatory power. The calibration curve showed good alignment between the predicted and actual probabilities of arrhythmias. Decision curve analysis (DCA) indicated a high net benefit for the model in predicting arrhythmias. The Hosmer-Lemeshow goodness-of-fit test confirmed the model's good fit. CONCLUSION: The nomogram developed in this study is a valuable tool for accurately predicting the risk of post-traumatic arrhythmias, offering a novel approach for physicians to tailor risk assessments to individual patients.

Intrathecal Anesthesia Prevents Ventricular Arrhythmias in Rats with Myocardial Ischemia/Reperfusion.

INTRODUCTION: Ventricular arrhythmia is commonly provoked by acute cardiac ischemia through sympathetic exaggeration and is often resistant to anti-arrhythmic therapies. Thoracic epidural anesthesia has been reported to terminate fatal ventricular arrhythmia; however, its underlying mechanism is unknown. METHODS: Rats were randomly divided into four groups: sham, sham plus bupivacaine, ischemia/reperfusion (IR), and IR plus bupivacaine groups. Bupivacaine (1 mg/mL, 0.05 mL/100 g body weight) was injected intrathecally into the L5-L6 intervertebral space prior to establishing a myocardial IR rat model. Thereafter, cardiac arrhythmia, cardiac function, myocardial injury, and electrical activities of the heart and spinal cord were evaluated. RESULTS: Intrathecal bupivacaine inhibited spinal neural activity, improved heart rate variability, reduced ventricular arrhythmia score, and ameliorated cardiac dysfunction in IR rats. Furthermore, intrathecal bupivacaine attenuated cardiac injury and myocardial apoptosis and regulated cardiomyocyte autophagy and connexin-43 distribution during myocardial IR. CONCLUSION: Our results indicate that intrathecal bupivacaine blunts spinal neural activity to prevent cardiac arrhythmia and dysfunction induced by IR and that this anti-arrhythmic activity may be associated with regulation of autonomic balance, myocardial apoptosis and autophagy, and cardiac gap junction function.

Optimizing the management of electrophysiology labs in Chinese hospitals using a discrete event simulation tool.

BACKGROUND: The growing demand for electrophysiology (EP) treatment in China presents a challenge for current EP care delivery systems. This study constructed a discrete event simulation (DES) model of an inpatient EP care delivery process, simulating a generalized inpatient journey of EP patients from admission to discharge in the cardiology department of a tertiary hospital in China. The model shows how many more patients the system can serve under different resource constraints by optimizing various phases of the care delivery process. METHODS: Model inputs were based on and validated using real-world data, simulating the scheduling of limited resources among competing demands from different patient types. The patient stay consists of three stages, namely: the pre-operative stay, the EP procedure, and the post-operative stay. The model outcome was the total number of discharges during the simulation period. The scenario analysis presented in this paper covers two capacity-limiting scenarios (CLS): (1) fully occupied ward beds and (2) fully occupied electrophysiology laboratories (EP labs). Within each CLS, we investigated potential throughput when the length of stay or operative time was reduced by 10%, 20%, and 30%. The reductions were applied to patients with atrial fibrillation, the most common indication accounting for almost 30% of patients. RESULTS: Model validation showed simulation results approximated actual data (137.2 discharges calculated vs. 137 observed). With fully occupied wards, reducing pre- and/or post-operative stay time resulted in a 1-7% increased throughput. With fully occupied EP labs, reduced operative time increased throughput by 3-12%. CONCLUSIONS: Model validation and scenario analyses demonstrated that the DES model reliably reflects the EP care delivery process. Simulations identified which phases of the process should be optimized under different resource constraints, and the expected increases in patients served.

Epilepsy and long-term risk of arrhythmias.

BACKGROUND AND AIMS: Previous evidence has mainly supported transient changes in cardiac function during interictal or peri-ictal phases in people with epilepsy, but the long-term risk of cardiac arrhythmias is poorly described. This study aimed to assess the long-term association of epilepsy with cardiac arrhythmias, considering the potential role of genetic predisposition and antiseizure medications (ASMs) in any associations observed. METHODS: This population-based study evaluated UK Biobank data for individuals recruited between 2006 and 2010. Cox proportional hazards models and competing risk models were used to examine the association of epilepsy history with the long-term incidence risk of cardiac arrhythmias and arrhythmias subtypes. Polygenic risk scores (PRS) were calculated to investigate the effect of genetic susceptibility. The role of ASMs was also evaluated by integrating observational and drug target Mendelian randomization (MR) evidence. RESULTS: The study included 329 432 individuals, including 2699 people with epilepsy. Compared with those without epilepsy, people with epilepsy experienced an increased risk of all cardiac arrhythmias [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.21-1.53], atrial fibrillation (HR 1.26, 95% CI 1.08-1.46), and other cardiac arrhythmias (HR 1.56, 95% CI 1.34-1.81). The associations were not modified by genetic predisposition as indicated by PRS. Competing and sensitivity analyses corroborated these results. Individuals with epilepsy using ASMs, especially carbamazepine and valproic acid, were at a higher risk for cardiac arrhythmias. This observation was further supported by drug target MR results (PSMR < .05 and PHEIDI > .05). CONCLUSION: This study revealed the higher risk of cardiac arrhythmias persists long term in people with epilepsy, especially among those using carbamazepine and valproic acid. These findings highlight the need for regular heart rhythm monitoring and management in people with epilepsy in order to reduce the risk of further cardiovascular complications.

Pathophysiology of Atrial Fibrillation and Approach to Therapy in Subjects Less than 60 Years Old.

Atrial fibrillation (AF) is an arrhythmia that affects the left atrium, cardiac function, and the patients' survival rate. Due to empowered diagnostics, it has become increasingly recognized among young individuals as well, in whom it is influenced by a complex interplay of autoimmune, inflammatory, and electrophysiological mechanisms. Deepening our understanding of these mechanisms could contribute to improving AF management and treatment. Inflammation is a complexly regulated process, with interactions among various immune cell types, signaling molecules, and complement components. Addressing circulating antibodies and designing specific autoantibodies are promising therapeutic options. In cardiomyopathies or channelopathies, the first manifestation could be paroxysmal AF; persistent forms tend not to respond to antiarrhythmic drugs in these conditions. Further research, both in vitro and in vivo, on the use of genomic biotechnology could lead to new therapeutic approaches. Additional triggers that can be encountered in AF patients below 60 years of age are systemic hypertension, overweight, diabetes, and alcohol abuse. The aims of this review are to briefly report evidence from basic science and results of clinical studies that might explain the juvenile burden of the most encountered sustained supraventricular tachyarrhythmias in the general population.

Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension.

While essential hypertension (HTN) is very prevalent, pulmonary arterial hypertension (PAH) is very rare in the general population. However, due to progressive heart failure, prognoses and survival rates are much worse in PAH. Patients with PAH are at a higher risk of developing supraventricular arrhythmias and malignant ventricular arrhythmias. The latter underlie sudden cardiac death regardless of the mechanical cardiac dysfunction. Systemic chronic inflammation and oxidative stress are causal factors that increase the risk of the occurrence of cardiac arrhythmias in hypertension. These stressful factors contribute to endothelial dysfunction and arterial pressure overload, resulting in the development of cardiac pro-arrhythmic conditions, including myocardial structural, ion channel and connexin43 (Cx43) channel remodeling and their dysfunction. Myocardial fibrosis appears to be a crucial proarrhythmic substrate linked with myocardial electrical instability due to the downregulation and abnormal topology of electrical coupling protein Cx43. Furthermore, these conditions promote ventricular mechanical dysfunction and heart failure. The treatment algorithm in HTN is superior to PAH, likely due to the paucity of comprehensive pathomechanisms and causal factors for a multitargeted approach in PAH. The intention of this review is to provide information regarding the role of Cx43 in the development of cardiac arrhythmias in hypertensive heart disease. Furthermore, information on the progress of therapy in terms of its cardioprotective and potentially antiarrhythmic effects is included. Specifically, the benefits of sodium glucose co-transporter inhibitors (SGLT2i), as well as sotatercept, pirfenidone, ranolazine, nintedanib, mirabegron and melatonin are discussed. Discovering novel therapeutic and antiarrhythmic strategies may be challenging for further research. Undoubtedly, such research should include protection of the heart from inflammation and oxidative stress, as these are primary pro-arrhythmic factors that jeopardize cardiac Cx43 homeostasis, the integrity of intercalated disk and extracellular matrix, and, thereby, heart function.

The Role of Cardiovascular Magnetic Resonance Imaging in Patients with Cardiac Arrhythmias.

Cardiac arrhythmias are associated with significant morbidity, mortality and poor quality of life. Cardiovascular magnetic resonance (CMR) imaging, with its unsurpassed capability of non-invasive tissue characterisation, high accuracy, and reproducibility of measurements, plays an integral role in determining the underlying aetiology of cardiac arrhytmias. CMR can reliably diagnose previous myocardial infarction, non-ischemic cardiomyopathy, characterise congenital heart disease and valvular pathologies, and also detect the underlying substrate concealed on conventional investigations in a significant proportion of patients with arrhythmias. Determining the underlying substrate of arrhythmia is of paramount importance for treatment planning and prognosis. However, CMR imaging in patients with irregular heart rates can be problematic. Understanding the different ways to overcome the limitations of CMR in arrhythmia is essential for providing high-quality imaging, comprehensive information, and definitive answers in this diverse group of patients.

Sustained heart rate-corrected QT prolongation during recovery from hypoglycaemia in people with type 1 diabetes, independently of recovery to hyperglycaemia or euglycaemia.

AIM: To investigate changes in cardiac repolarization abnormalities (heart rate-corrected QT [QTc ] [primary endpoint], T-wave abnormalities) and heart-rate variability measures in people with type 1 diabetes during insulin-induced hypoglycaemia followed by recovery hyperglycaemia versus euglycaemia. METHODS: In a randomized crossover study, 24 individuals with type 1 diabetes underwent two experimental clamps with three steady-state phases during electrocardiographic monitoring: (1) a 45-minute euglycaemic phase (5-8 mmol/L), (2) a 60-minute insulin-induced hypoglycaemic phase (2.5 mmol/L), and (3) 60-minute recovery in either hyperglycaemia (20 mmol/L) or euglycaemia (5-8 mmol/L). RESULTS: All measured markers of arrhythmic risk indicated increased risk during hypoglycaemia. These findings were accompanied by a decrease in vagal tone during both hyperglycaemia and euglycaemia clamps. Compared with baseline, the QTc interval increased during hypoglycaemia, and 63% of the participants exhibited a peak QTc of more than 500 ms. The prolonged QTc interval was sustained during both recovery phases with no difference between recovery hyperglycaemia versus euglycaemia. During recovery, no change from baseline was observed in heart-rate variability measures. CONCLUSIONS: In people with type 1 diabetes, insulin-induced hypoglycaemia prolongs cardiac repolarization, which is sustained during a 60-minute recovery period independently of recovery to hyperglycaemia or euglycaemia. Thus, vulnerability to serious cardiac arrhythmias and sudden cardiac death may extend beyond a hypoglycaemic event, regardless of hyperglycaemic or euglycaemic recovery.

Electrocardiographic markers of subclinical atrial fibrillation detected by implantable loop recorder: insights from the LOOP Study.

AIMS: Insights into subclinical atrial fibrillation (AF) development are warranted to inform the strategies of screening and subsequent clinical management upon AF detection. Hence, this study sought to characterize the onset and progression of subclinical AF with respect to 12-lead electrocardiogram (ECG) parameters. METHODS AND RESULTS: We included AF-naïve individuals aged 70-90 years with additional stroke risk factors who underwent implantable loop recorder (ILR) monitoring in the LOOP Study. Using data from daily ILR recordings and the computerized analysis of baseline ECG, we studied empirically selected ECG parameters for AF detection (≥6 min), cumulative AF burden, long-lasting AF (≥24 h), and AF progression. Of 1370 individuals included, 419 (30.6%) developed AF during follow-up, with a mean cumulative AF burden of 1.5% [95% CI: 1.2-1.8]. Several P-wave-related and ventricular ECG parameters were associated with new-onset AF and with cumulative AF burden in AF patients. P-wave duration (PWD), P-wave terminal force in Lead V1, and interatrial block (IAB) further demonstrated significant associations with long-lasting AF. Among AF patients, we observed an overall reduction in cumulative AF burden over time (IRR 0.70 [95% CI: 0.51-0.96]), whereas IAB was related to an increased risk of progression to AF ≥24 h (HR 1.86 [95% CI: 1.02-3.39]). Further spline analysis also revealed longer PWD to be associated with this progression in AF duration. CONCLUSION: We identified several ECG parameters associated with new-onset subclinical AF detected by ILR. Especially PWD and IAB were robustly related to the onset and the burden of AF as well as progression over time.

New insertable cardiac monitors show high diagnostic yield and good safety profile in real-world clinical practice: results from the international prospective observational SMART Registry.

AIMS: Insertable cardiac monitors (ICMs) are indicated for long-term monitoring of unexplained syncope or palpitations, and for detection of bradycardia, ventricular tachycardia, and/or atrial fibrillation (AF). The aim of our study was to evaluate the safety and clinical value associated with a new generation ICM (Confirm Rx™, Abbott, Illinois, USA), featuring a new remote monitoring system based on smartphone patient applications. METHODS AND RESULTS: The SMART Registry is an international prospective observational study. The main endpoints were ICM safety (incidence of serious adverse device and procedure-related events (SADEs) at 1 month), ICM clinical value (incidence of device-detected true arrhythmias and of clinical diagnoses and interventions), and patient-reported experience measurements (PREMs). A total of 1400 subjects were enrolled. ICM indications included syncope (49.1%), AF (18.8%), unexplained palpitations (13.6%), risk of ventricular arrhythmia (6.6%), and cryptogenic stroke (6.0%). Freedom from SADEs at 1 month was 99.4% (95% Confidence Interval: 98.8-99.7%). In the 6-month monitoring period, the ICM detected true cardiac arrhythmias in 45.7% of patients and led to clinical interventions in a relevant proportion of patients; in particular, a pacemaker implant was performed after bradycardia detection in 8.9% of subjects who received an ICM for syncope and oral anticoagulation therapy was indicated after AF detection in 15.7% of subjects with cryptogenic stroke. PREMs showed that 78.2% of subjects were satisfied with the remote monitoring patient app. CONCLUSION: The evaluated ICM is associated with an excellent safety profile and high diagnostic yield. Patients reported positive experiences associated with the use of their smartphone for the device remote monitoring.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Arrhythmogenic mechanism of a novel ryanodine receptor mutation underlying sudden cardiac death.

AIMS: The ryanodine receptor 2 (RyR2) is essential for cardiac muscle excitation-contraction coupling; dysfunctional RyR2 participates in the development of inherited arrhythmogenic cardiac disease. In this study, a novel RyR2 mutation A690E is identified from a patient with family inheritance of sudden cardiac death, and we aimed to investigate the pathogenic basis of the mutation. METHODS AND RESULTS: We generated a mouse model that carried the A690E mutation. Mice were characterized by adrenergic-induced ventricular arrhythmias similar to clinical manifestation of the patient. Optical mapping studies revealed that isolated A690E hearts were prone to arrhythmogenesis and displayed frequency-dependence calcium transient alternans. Upon ß-adrenoceptor challenge, the concordant alternans was shifted towards discordant alternans that favour triggering ectopic beats and Ca2+ re-entry; similar phenomenon was also found in the A690E cardiomyocytes. In addition, we found that A690E cardiomyocytes manifested abnormal Ca2+ release and electrophysiological disorders, including an increased sensitivity to cytosolic Ca2+, an elevated diastolic RyR2-mediated Ca2+ leak, and an imbalance between Ca2+ leak and reuptake. Structural analyses reveal that the mutation directly impacts RyR2-FK506 binding protein interaction. CONCLUSION: In this study, we have identified a novel mutation in RyR2 that is associated with sudden cardiac death. By characterizing the function defects of mutant RyR2 in animal, whole heat, and cardiomyocytes, we demonstrated the pathogenic basis of the disease-causing mutation and provided a deeper mechanistic understanding of a life-threatening cardiac arrhythmia.

Prevalence of different echocardiographic abnormalities in a large Turkish workers population.

OBJECTIVE: We aimed to investigate the echocardiographic characteristics of workers with resting major electrocardiography (ECG) anomalies and risk factors of sudden cardiac death in the large Turkish workers population in different heavy industry sectors. METHODS: Between April 2016 and January 2020, 8668 consecutive ECGs were obtained and interpreted during health examinations of working in Istanbul, Turkey. ECGs were classified as major, minor anomaly, and normal according to the Minnesota code criteria. The workers with major anomaly on ECGs, recurrent syncope attacks, and family history (FH) of sudden or inexplicably death under the age of 50 and with a positive FH of cardiomyopathy were also referred to further transthoracic echocardiographic (TTE) examination. RESULTS: The mean age of the workers was 30.47 ± 9.4 years, most of them were male (97.1%) and under the age of 30 (54.2%). Major ECG changes were detected in 4.6%, and minor anomalies were 28.3%. A total of 663 workers were referred to our cardiology clinic for advanced TTE examination, but only 578 (87.17% of the selected) attended the appointment. Four hundred and sixty-seven (80.7%) echocardiography examinations were within normal limits. Echocardiographic imaging revealed abnormal findings in 98 cases (25.7%) in the ECG abnormalities group, three (4.4%) in the syncope group, and 10 (7.6%) in the positive FH group (p < .001). CONCLUSIONS: This work demonstrated the ECG findings and echocardiographic features of a large sample of Turkish workers from high-risk employment sectors. This is the first study conducted in Turkey on this subject.

Insomnia and Cardiovascular Health: Exploring the Link Between Sleep Disorders and Cardiac Arrhythmias.

Cardiovascular diseases (CVDs), driven by modern lifestyles, have increased, with atrial fibrillation (AF) being a major concern linked to heart failure and stroke. Insomnia affects a large population, especially younger individuals, males, and menopausal women, decreasing the quality of life and potentially causing autonomic disturbances and cardiac arrhythmias. PURPOSE OF REVIEW: This review explores the link between insomnia and cardiac arrhythmias, particularly AF, and its impact on cardiovascular health and emphasizes the need to address insomnia in individuals with cardiac arrhythmias by tailored strategies for sleep management to improve their overall well-being. RECENT FINDINGS: Recent findings emphasize maintaining a regular sleep schedule to lower AF and bradyarrhythmia risks. Better sleep scores correlate with reduced AF and bradyarrhythmia risks, while insomnia increases AF risk, particularly in those under 40 years of age. Studies underscore the potential impact of sleep management in reducing cardiovascular risks and highlight the importance of addressing sleep issues to improve cardiovascular health outcomes. Our review presents compelling evidence connecting insomnia and AF. Improving sleep patterns and addressing sleep issues can reduce AF risk, benefiting cardiovascular health. A comprehensive approach for managing at-risk individuals with cardiac arrhythmias, considering co-existing conditions, can decrease long-term disease burden and expenses. Incorporating sleep assessments and interventions into cardiovascular risk management, especially for those with insomnia, is recommended. Further research is needed to fully comprehend the complex relationship between insomnia and cardiac arrhythmias.

Predictive factors for type A aortic dissection mortality based on electrocardiogram parameters and clinical presentations.

BACKGROUND: Aortic dissection is a rare but potentially lethal disorder and may be associated with electrocardiogram (ECG) changes. In this study, we aim to investigate ECG-related parameters alongside clinical presentations of type A aortic dissection to come up with the predictive factors for the severity of the disease and its mortality rate. METHODS: In this retrospective study, 201 patients with type A aortic dissection were studied between March 2015 and March 2020. Two expert cardiologists blinded to the diagnosis studied former and new patients' ECGs and recorded changes. RESULTS: Two-hundred and one patients, including 143 (71.1%) men and 58 (28.9%) women, presented with acute dissection of the aorta, were studied. Forty-four (21.8%) and 84 (41.7%) patients had ST-segment elevation and depression in ECG, respectively. Bivariate analysis revealed that higher heart rate (p = 0.006), longer QTc (p = 0.044), and ST-segment elevation in aVR lead (p = 0.044) were associated with mortality in the patients. Multivariate regression showed higher heart rate (OR = 1.022, CI = 1.003-1.041, p = 0.012) and ST-segment elevation in aVR (OR = 4.854, CI = 2.255-10.477, p < 0.001) were independently associated with increased odds of mortality in aortic dissection patients. ROC curve analysis showed heart rate equal to or >60 per minute (AUC = 0.625, sensitivity = 86%, specificity = 10%, p = 0.019) and ST-segment elevation in aVR >0.5 mm (AUC = 0.854, sensitivity = 75%, specificity = 92%, p < 0.001) were associated with a higher mortality rate. CONCLUSION: Heart rate equal or >60 and ST-segment elevation >0.5 mm in aVR lead can be used as predictive factors for mortality of patients with type A aortic dissection.