Antiarrhythmic Research Articles

The incidence and risk factors of atrial high‐rate episodes in patients with a dual‐chamber pacemaker

AbstractBackground and ObjectivesCardiovascular implantable electronic devices can detect atrial high‐rate episodes (AHREs). However, the predictors of clinically relevant AHREs have not been well identified.MethodsThis prospective study included 145 patients (median age 64.5 ± 16.4 years, 53.1% females) without atrial fibrillation (AF) from December 2020 to January 2022. AHREs were defined as a programmed atrial detection rate >190 beats per minute. Cox regression analysis was used to identify the risk factors of AHREs.ResultsDuring 6 months of follow‐up, AHREs occurred in 30.3% of patients. Multivariable Cox regression analysis showed factors related to development of AHREs including using anti‐arrhythmic drugs (AAD) before implantation (Hazard ratio (HR) 7.71; 95% confidence interval [95% CI], 2.58–23.02, p < .001), history of paroxysmal supraventricular tachycardia (PSVT; HR 2.45; [95% CI], 1.18–5.09, p = .016), the percentage of premature atrial contraction (PAC) on 24‐h Holter electrocardiogram (ECG) monitoring (HR 1.008; [95% CI], 1.003–1.014, p = .003), and left ventricular global longitudinal strain (GLS‐LV; HR 0.92;[95% CI], 0.84–0.99, p = .049).ConclusionsThis study showed that a history of PSVT and using AAD, the percentage of PAC on 24‐h Holter ECG monitoring, and GLS‐LV were the independent predictors of new‐onset AHREs.

Cardiac arrhythmias in adults with congenital heart disease

In patients with congenital heart disease, cardiac arrhythmias are complex and require athorough understanding of the anatomy, past surgical and interventional procedures, and the specific electric processes. Supraventricular tachycardias commonly present as emergency situations and should be treated immediately, particularly when there is an underlying complex malformation. Establishing sinus rhythm is usually superior to pure frequency control for hemodynamic reasons. Catheter ablation should be preferred over medical treatment, even though several procedures are often necessary. In addition, bradycardia is seen more frequently in congenital heart defects; this could be aggravated by antiarrhythmic drugs. There are significant differences between the indications and techniques used for pacemaker implantation in patients with congenital heart defects and those without. Patients with complex congenital heart diseases have an increased risk of thromboembolism; therefore, an individual and early indication for low-threshold oral anticoagulation is necessary; direct oral anticoagulants can also be used for this purpose. In risk stratification for sudden cardiac death, the principles of general guidelines are often not applicable, and individualized decisions are required. Recently, anew general risk score for congenital heart disease has been developed. The treatment of cardiac arrhythmias in patients with congenital heart disease should always be performed in close cooperation with specialized centers.

β-Adrenergic receptor signalling pathway mediated antiarrhythmic activity of s-limonene in the rat heart.

S-Limonene (s-Lim) is a monocyclic monoterpene found in a variety of plants and has been shown to present antioxidant and cardioprotective activity in experimental models of myocardial infarction. The aim of this study was to evaluate the potential mechanism by which s-Lim exerts its antiarrhythmic effect, focusing on the blockade of β-adrenoceptor (β-AR) and its effects on various in vivo and in vitro parameters, including electrocardiogram (ECG) measurements, left ventricular developed pressure (LVDP), the β-adrenergic pathway, sarcomeric shortening and L-type calcium current (ICa,L). In isolated hearts, 10 μM of s-Lim did not alter the ECG profile or LVPD. s-Lim increased the heart rate corrected QT interval (QTc) (10.8%) at 50 μM and reduced heart rate at the concentrations of 30 (12.4%) and 50 μM (16.6%). s-Lim (10 μM) also inhibited the adrenergic response evoked by isoproterenol (ISO) (1 μM) reducing the increased of heart rate, LVDP and ECG changes. In ventricular cardiomyocyte, s-Lim antagonized the effect of dobutamine by preventing the increase of sarcomeric shortening, demonstrating a similar effect to atenolol (blocker β1-AR). In vivo, s-Lim antagonized the effect of ISO (agonists β1-AR), presenting a similar effect to propranolol (a non-selective blocker β-AR). In ventricular cardiomyocyte, s-Lim did not alter the voltage dependence for ICa,L activation or the ICa,L density. In addition, s-Lim did not affect changes in the ECG effect mediated by 5 μM forskolin (an activator of adenylate cyclase). In an in vivo caffeine/ISO-induced arrhythmia model, s-Lim (1 mg/kg) presented antiarrhythmic action verified by a reduced arrhythmia score, heart rate, and occurrence of ventricular premature beats and inappropriate sinus tachycardia. These findings indicate that the antiarrhythmic activity of s-Lim is related to blockade of β-AR in the heart.

Clinical and economic impact of first-line or drug-naïve catheter ablation and delayed second-line catheter ablation for atrial fibrillation using a patient-level simulation model

Aims To determine the clinical and economic implications of first-line or drug-naïve catheter ablation compared to antiarrhythmic drugs (AADs), or shorter AADs-to-Ablation time (AAT) in atrial fibrillation (AF) patients in France and Italy, using a patient level-simulation model. Materials and methods A patient-level simulation model was used to simulate clinical pathways for AF patients using published data and expert opinion. The probabilities of adverse events (AEs) were dependent on treatment and/or disease status. Analysis 1 compared scenarios of treating 0%, 25%, 50%, 75% or 100% of patients with first-line ablation and the remainder with AADs. In Analysis 2, scenarios compared the impact of delaying transition to second-line ablation by 1 or 2 years. Results Over 10 years, increasing first-line ablation from 0% to 100% (versus AAD treatment) decreased stroke by 12%, HF hospitalization by 29%, and cardioversions by 45% in both countries. As the rate of first-line ablation increased from 0% to 100%, the overall 10-year per-patient costs increased from €13,034 to €14,450 in Italy and from €11,944 to €16,942 in France. For both countries, the scenario with no delay in second-line ablation had fewer AEs compared to the scenarios where ablation was delayed after AAD failure. Increasing rates of first-line or drug-naïve catheter ablation, and shorter AAT, resulted in higher cumulative controlled patient years on rhythm control therapy. Limitations The model includes assumptions based on the best available clinical data, which may differ from real-world results, however, sensitivity analyses were included to combat parameter ambiguity. Additionally, the model represents a payer perspective and does not include societal costs, providing a conservative approach. Conclusion Increased first-line or drug-naïve catheter ablation, and shorter AAT, could increase the proportion of patients with controlled AF and reduce AEs, offsetting the small investment required in total AF costs over 10 years in Italy and France.

Evaluation of Amiodarone Administration in Patients with New-Onset Atrial Fibrillation in Septic Shock.

Background and Objective: New-onset atrial fibrillation (NOAF) is a common cardiac condition often observed in intensive care units. When amiodarone is used to treat this condition, either to maintain sinus rhythm after electrical cardioversion or to control heart rate, complications can arise when a systemic pathology is present. Systemic pathology can result in a decrease in cardiac output and blood pressure, making the management of NOAF and septic shock challenging. Limited international research exists on the coexistence of NOAF and septic shock, making it difficult to determine the optimal course of treatment. While amiodarone is not the primary choice of antiarrhythmic drug for patients in septic shock, it may be considered for those with underlying cardiac issues. This paper aims to investigate the safety of administering amiodarone to patients with septic shock and explore whether another antiarrhythmic drug may be more effective, especially considering the cardiac conditions that patients may have. Materials and Methods: To write this article, we searched electronic databases for studies where authors used amiodarone and other medications for heart rate control or sinus rhythm restoration. Results: The studies reviewed in this work have shown that for the patients with septic shock and NOAF along with a pre-existing cardiac condition like a dilated left atrium, the use of amiodarone may provide greater benefits compared to other antiarrhythmic drugs. For patients with NOAF and septic shock without underlying heart disease, the initial use of propafenone has been found to be advantageous. However, a challenge arises when deciding between rhythm or heart rate control using various drug classes. Unfortunately, there is limited literature available on this specific scenario. Conclusions: NOAF is a frequent and potentially life-threatening complication occurring in one out of seven patients with sepsis, and its incidence is rising among patients with septic shock.

Long-term health-related quality of life and rhythm outcomes of catheter ablation versus antiarrhythmic drugs in patients with atrial fibrillation

BackgroundData on long-term effects of catheter ablation vs antiarrhythmic drugs (AADs) on health-related quality of life (HRQoL) and atrial fibrillation (AF) burden are limited. ObjectiveThe study aimed to assess long-term HRQoL and rhythm data in patients with symptomatic AF. MethodsThe 75 patients who underwent ablation and 74 receiving AAD in the Catheter Ablation compared with Pharmacological Therapy for Atrial Fibrillation trial were followed for 48 months. The General Health subscale of the 36-Item Short-Form Health Survey, time to first AF episode ≥1 hour, and AF burden, recorded by implantable cardiac monitors, were compared. ResultsOne hundred forty-seven patients completed follow-up, with 7 crossovers in the ablation group and 34 crossovers in the AAD group. General Health improved by ablation from a median of 62 points at baseline to 79.2 points at follow-up (P < .001) and by AAD from a median of 67 to 77 points (P < .001), without treatment differences (P = .77). Time to first AF episode ≥1 hour was longer (median 257 days in the ablation group vs 180 days in the AAD group; P = .025). The cumulative AF burden during follow-up was lower in the ablation group (median 0.3%; interquartile range [IQR] 0%–1.4%) than in the AAD group (1.6%; IQR 0.1%–11.0%) (P = .01). The cumulative reduction in AF burden compared with baseline was greater in the ablation group (median −89.5%; IQR −98.4% to −51.3%) than in the AAD group (−52.7%; IQR −92.6% to 263.6%); P < .001). ConclusionHRQoL improvement at long-term did not differ between ablation and AAD groups despite a larger reduction in AF burden after ablation. The results should be interpreted in the light of a high crossover rate in the AAD group.

The European Society of Cardiology quality indicators in atrial fibrillation in centers of excellence in Spain: the SEC-EXCELENTE FA registry

Introduction and objectivesBy 2022, 9 centers had been accredited by the Spanish Society of Cardiology for the atrial fibrillation (AF) process. Our objective was to evaluate the performance of these centers based on the quality indicators (QIs) proposed by the European Society of Cardiology (ESC) in 2020. MethodsAdults with AF who were attended in the cardiology departments of participating centers during the second week of May 2019 were included in a retrospective registry (n=797, age 72±11 years, 60% male). Key ESC QIs were assessed. ResultsCHA2DS2-VASc, HAS-BLED scores, and serum creatinine levels were documented in 24.9%, 6.1%, and 96.2% of patients, respectively. Anticoagulation was appropriately prescribed in 90.6% of high-risk patients according to the CHA2DS2-VASc score, but was inappropriately prescribed in 57.8% of low-risk patients. Among all patients, 84.1% received high-quality anticoagulation. Inappropriate antiarrhythmic drugs were prescribed in 7.2% of patients with permanent AF, 2.9% of those with structural heart disease, and 0.0% of those with end-stage kidney disease. Catheter ablation was offered to 70% of patients with symptomatic paroxysmal or persistent AF after the failure or intolerance of 1 antiarrhythmic drug. All modifiable risk factors were documented in 59.3% of patients. Rates of all-cause mortality, ischemic stroke or transient ischemic attack, and major bleeding were 8.1, 0.8, and 2.56 per 100 patients/y, respectively. QIs for anticoagulation and outcomes were similar between general cardiology and tertiary referral centers. ConclusionsAlthough accredited centers in Spain demonstrated good performance in many of the ESC QIs for AF, there remains room for improvement. These data could serve as a starting point for enhancing the quality of care in this population.

Early Cryoablation After First Diagnosis of Atrial Fibrillation Reduces Arrhythmia Recurrence in Heart Failure Patients

BackgroundAtrial fibrillation (AF) and heart failure (HF) often coexist, leading to increased mortality. A cryoballoon-based approach is a potential treatment for patients with HF because of its safety and efficacy. ObjectivesThe authors sought to evaluate the optimal timing of cryoballoon ablation after the first clinical diagnosis of AF and its prognosis for patients with HF. MethodsThis large-scale multicenter study retrospectively collected data of patients with HF who underwent cryoballoon ablation for AF from 17 Japanese institutions. Patients were divided into 2 groups depending on the duration between the first diagnosis and ablation using a median time of 0.5 year (IQR: 0.3-2.0 years). Clinical endpoints of recurrence, mortality, and HF hospitalization were compared between the 2 groups. ResultsAmong 3,655 patients, 543 with HF were included for analysis. During a median follow-up period of 21.3 months (IQR: 12.0-36.8 months), 151 of 520 patients (29%) had a recurrence. The AF recurrence rate was significantly lower in the early-ablation group (≤0.5 year) than in the delayed-ablation group (>0.5 year) (24% [65/266] vs 34% [86/254], respectively; P = 0.018). In the multivariable analysis, early ablation ≤ 0.5 year was independently associated with an absence of recurrence (HR: 0.581; 95% CI: 0.401-0.842; P = 0.004). Delayed time for cryoballoon ablation incrementally increased the risk of postablation recurrence. Antiarrhythmic drug use was independently associated with delayed ablation. No significant differences in mortality or HF hospitalization were observed between the 2 groups. ConclusionsEarly cryoablation reduced the risk of recurrence in patients with HF, which may help improve clinical management.

Efficacy and safety of early postoperative ablation in patients with congenital heart disease

BackgroundPostoperative arrhythmias are most often transient and medically treated, but some patients may require electrophysiology study (EPS) and ablation. ObjectiveThe purpose of this study was to describe the efficacy and safety of early postoperative ablation. MethodsThis study presents a retrospective series of patients who underwent EPS within 12 months of surgery for congenital heart disease between 2000 and 2021. The procedural outcome included complete or partial success, empirical ablation or failure, and complications. The long-term outcome included arrhythmia recurrence and burden according to a 12-point clinical arrhythmia severity score (documented arrhythmia, arrhythmia severity, cardioversion, and antiarrhythmic medication). ResultsAmong 28,902 operations during the study period, 24 patients (0.1%) underwent EPS within 3 months of surgery and 26 (0.1%) 3–12 months after surgery. Most patients had great (n = 27 [50%]) or moderate (n = 21 [42%]) congenital heart disease complexity. Mechanisms of arrhythmias included intra-atrial reentrant tachycardia (n = 23 [46%]), ectopic atrial tachycardia (n = 13 [26%]), accessory pathway (n = 6 [12%]), atrioventricular nodal reentrant tachycardia (n = 7 [14%]), twin atrioventricular node (n = 1 [2%]), atrial fibrillation (n = 1 [2%]), junctional ectopic tachycardia (n = 1 [2%]), and ventricular tachycardia (n = 2 [4%]). The procedure was acutely successful in 41 patients (82%), empirical in 5 (10%), and unsuccessful in 4 (8%). Complications occurred in 4 (8%) patients (major in 1, moderate in 1, and minor in 2). The recurrence of arrhythmia was documented in 27 patients (54%), although the burden of arrhythmia was significantly reduced. ConclusionA minority of patients require early postoperative EPS and ablation. For those, the procedure can be performed with reasonable acute success and manageable morbidity even in critically ill patients with complex surgical anatomy.

Multi-faceted potential of sophoridine compound's anti-arrhythmic and antioxidant effects through ROS/CaMKII pathway

Cardiac arrhythmias remain a significant cause of mortality and morbidity, for novel antiarrhythmic therapies. This study states that the first report of sophoridine (SPN), a quinolizidine alkaloid derived from traditional Chinese herbs, shows promise as a potential candidate due to its anti-arrhythmic and antioxidant properties. The study found that cell viability in H9C2 rat cardiomyocytes remained stable even when treated with SPN at a higher dosage of 100 μg/ml. This phenomenon was accompanied by increases in mitochondria-derived reactive oxygen species (ROS) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling, at 50 and 100 μg/ml. Glucose fluctuations regulate ventricular arrhythmias caused by SPN by activating the ROS/CaMKII pathway. Experimental models using zebrafish provided additional evidence supporting the regulatory effects of SPN on heart rate. In addition, the administration of SPN resulted in substantial deregulation of crucial genes involved in heart development (nppa, nppb, tnnt2a) at the transcriptional level in zebrafish. These findings provide insight into the various pharmacological properties of SPN and this opens up new possibilities for anti-arrhythmic treatment strategies.

RETRACTION: Wound incidence and outcomes in atrial fibrillation: Comparing catheter ablation and anti-arrhythmic drug therapy.

Retraction: Z. Xinyu , X. Sheng , "Wound incidence and outcomes in atrial fibrillation: Comparing catheter ablation and anti-arrhythmic drug therapy," Int Wound J 21, no. 4 (2023): e14612, https://doi.org/10.1111/iwj.14612. The above article, published online on 21 December 2023, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the authors; the journal Editor-in-Chief, Professor Keith Harding; and John Wiley & Sons, Ltd. The authors submitted a request for retraction, reporting that the conclusions in the published article were partially inaccurate. Following an investigation by the publisher and Editor-in-Chief, they concluded that the peer review and publishing process were found to have been manipulated. The retraction has been agreed on because the findings reported in the article are not considered reliable. The authors did not respond to our notice of retraction.

P164 SOLUBLE GUANYLATE CYCLASE STIMULATORS: AN EMERGING OPTION IN THE TREATMENT OF PRESSURE AND VOLUME OVERLOAD INDUCED CHRONIC HEART FAILURE

Pressure and volume overload-induced chronic heart failure (HF) is associated with characteristic cardiac remodeling and ventricular myocardial proteomic alterations, that can lead to the formation of a substrate for arrhythmias. Antiarrhythmic drug therapy is still suboptimal and current therapies are not efficacious enough. The purpose of the current study was therefore to examine the efficiency of nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) stimulator. We used as an experimental model male hypertensive Ren-2 transgenic rats (TGR) (n = 16), normotensive Hannover Sprague–Dawley rats (HSD, n = 17), and a volume-overload HF rat model induced by creating the aortocaval fistula (ACF) in rats of both strains (n = 27). Rats were after the induction of ACF treated by sGC stimulator BAY41-8543 (3 mg/kg/day for 30 weeks) alone or combined with angiotensin-converting enzyme inhibitor (ACEi) Trandolapril (0.25 mg/kg/day for 30 weeks). The age of the animals at the end of the experiment was 40 weeks. Left ventricle tissue and plasma samples were used for further analyses. Blood pressure (BP) was measured by telemetry. Combined treatment with sGC stimulator and ACEi was the most potent in lowering BP. Moreover, supplementation by sGC stimulator alone significantly decreased mortality and increased levels of the antioxidant enzyme superoxide dismutase 1, matrix metalloproteinase 2, total and phosphorylated connexin 43 as well as protein kinase C epsilon, implicated in remodeling of extracellular matrix and intercellular communication, in the left ventricle of TGR rats. Application of the sGC stimulator also slightly normalized elevated collagen deposition and hydroxyproline content in the left ventricular tissue of TGR rats. Unfortunately, we did not observe any effect of the sGC stimulator in the TGR ACF group. These results support the hypothesis that sGC stimulators might represent a class of drugs suitable for the prevention and treatment of related disorders in HF. This work was supported by APVV-21-0410, VEGA 2/0006/23, and EXCELES LX22NPO5104. Supported by APVV-21-0410, VEGA 2/0006/23, and EXCELES LX22NPO5104.

Thyroïdites : pathologies les plus courantes

AbstractThyroiditis are common conditions, mostly benign and accompanied by a biological disruption in the thyroid function. In fact, their resolution can sometimes be spontaneous. The term ‘thyroiditis’ encompasses several diseases characterized by inflammation of the thyroid gland. Patients often describe a neck pain that may be associated with the presence of a goiter. The causes are multiple. The most common condition is Hashimoto’s thyroiditis, characterized by hypothyroidism. Conversely, Basedow’s thyroiditis is characterized by hyperthyroidism. These are two autoimmune diseases whose diagnosis, in addition to the measurement of thyrotropin and thyroid hormones T4 and T3, relies on the measurement of specific antibodies. There are also iatrogenic thyroiditis: amiodarone, an antiarrhythmic drug prescribed by cardiologists, can cause thyroid dysfunction and requires close monitoring. Postpartum thyroiditis is a transient, sometimes persistent thyroiditis that occurs within a year following a pregnancy or miscarriage. Finally, some thyroiditis have infectious origins, such as De Quervain’s subacute thyroiditis, which is of viral origin. The treatment implemented will be tailored to the aetiology of the thyroiditis and monitored by an endocrinologist.

ER stress modulates Kv1.5 channels via PERK branch in HL-1 atrial myocytes: Relevance to atrial arrhythmogenesis and the effect of tetramethylpyrazine

Endoplasmic reticulum (ER) stress is implicated in cardiac arrhythmia whereas the associated mechanisms remain inadequately understood. Kv1.5 channels are essential for atrial repolarization. Whether ER stress affects Kv1.5 channels is unknown. This study aimed to elucidate the response of Kv1.5 channels to ER stress by clarifying the unfolded protein response (UPR) branch responsible for the channel modulation. In addition, the effect of tetramethylpyrazine (TMP) on Kv1.5 channels was studied. Patch clamp and western-blot results revealed that exposure of HL-1 atrial myocytes to ER stress inducer tunicamycin upregulates Kv1.5 expression, increases Kv1.5 channel current (IKur) (14.91 ± 1.11 vs. 6.11 ± 1.31 pA/pF, P < 0.001), and shortened action potential duration (APD) (APD90: 82.79 ± 5.25 vs.121.11 ± 6.72 ms, P < 0.01), which could be reverted by ER stress inhibitors. Blockade of the PERK branch while not IRE1 and ATF6 branches of UPR downregulated Kv1.5 expression, accompanied by a decreased IKur (9.03 ± 0.99 pA/pF) and a prolonged APD90 (113.69 ± 4.41 ms) (P < 0.01). PERK-mediated increases of Kv1.5 expression and IKur were also observed in HL-1 cells incubated with thapsigargin. TMP suppressed the enhancement of IKur (10.52 ± 0.97 vs. 17.52 ± 2.25 pA/pF, P < 0.05), prevented the shortening of APD (APD90: 110.16 ± 5.36 vs. 84.84 ± 4.58 ms, P < 0.05), and inhibited the upregulation of Kv1.5 triggered by ER stress. Our study suggests that ER stress induces upregulation and activation of Kv1.5 channels in atrial myocytes through the PERK branch of UPR. TMP prevents Kv1.5 upregulation/activation and the resultant APD shortening by inhibiting ER stress. These results may shed light on the mechanisms of atrial arrhythmogenesis and the antiarrhythmic effect of the traditional Chinese herb TMP.

NBQX mediates ventricular fibrillation susceptibility in rat models of anxiety via the Nrf2/HO-1 pathway

ObjectiveAnxiety disorder (AD) is a common mental disorder related to cardiovascular disease morbidity. Oxidative stress plays a crucial role in the anxiety state and can lead to cardiac remodeling. Over-activation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in cardiomyocytes and neurons can cause oxidative stress. Additionally, the AMPAR inhibitor—2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline-2,3-dione (NBQX) plays an important role in ameliorating oxidative stress. This study aimed to explore the anti-arrhythmic effects of NBQX in a rat model of anxiety. MethodsThe AD model was induced using empty bottle stimulation. Male Sprague Dawley rats were randomly divided into four groups: control + saline, control + NBQX, AD + saline, and AD + NBQX. Open field test was conducted to measure anxiety-like behavior. Electrophysiological experiments, histological analysis, biochemical detection and molecular biology were performed to verify the effects of NBQX on the amelioration of electrical remodeling and structural remodeling. Furthermore, the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) was used in vitro to demonstrate the signaling pathway. ResultsOxidative stress levels increased with AMPAR over-activation in AD rats, leading to heightened vulnerability to ventricular fibrillation (VF). NBQX reverses anxiety and VF susceptibility. Our results showed that NBQX activated the Nrf2/heme oxygenase-1 (HO-1) pathway, leading to a decline in oxidative stress levels. Connexin 43 and ion channel expression was upregulated. NBQX treatment attenuated fibrosis and apoptosis. This effect was diminished by ML385 treatment in vitro. ConclusionNBQX can alleviate VF susceptibility in rat models of anxiety by alleviating electrical remodeling, structural remodeling via regulating the Nrf2/HO-1 pathway to some extent.

3-N-Butylphthalide Confers Antiarrhythmic Features in Ischemia/Reperfusion Injury of Diabetic Heart by Targeting Mitochondria-Endoplasmic Reticulum Network and Inhibiting Oxidative Stress and Inflammation

While 3-N-butylphthalide (NBP) has demonstrated notable cardioprotective effects, its precise role in mitigating myocardial arrhythmia following ischemia/reperfusion (IR) injury in diabetes remains unclear. This study aimed to explore the potential mechanisms through which NBP mitigates reperfusion-induced myocardial arrhythmia in diabetic rats, with a particular focus on mitochondrial function and biogenesis, endoplasmic reticulum (ER) stress, and oxidative/inflammatory responses. Sixty Sprague-Dawley rats were divided into non-diabetic and diabetic groups, subjected to in-vivo myocardial IR injury, and treated with NBP (100 mg/kg, intraperitoneally) through different modalities: preconditioning, postconditioning, or a combination of both. Electrocardiography (ECG) was employed to assess the incidence and severity of arrhythmia. Fluorometric, Western blotting and ELISA analyses were utilized to measure the mitochondrial, ER stress, and cellular outcomes. Treatment of non-diabetic rats with NBP in preconditioned, postconditioned, and combined approaches significantly reduced cardiotroponin-I and the frequency and severity of arrhythmias induced by IR injury. However, only the combined preconditioning plus postconditioning approach of NBP had protective and antiarrhythmic effects in diabetic rats, in an additive manner. Moreover, the NBP combined approach improved mitochondrial function and upregulated the expression of PGC-1α, Sirt1, and glutathione while concurrently downregulating ER stress and oxidative and pro-inflammatory-related proteins in diabetic rats. In conclusion, the combined approach of NBP treatment was effective in mitigating myocardial arrhythmia in diabetic rats. This approach coordinates interactions within the mitochondria-endoplasmic reticulum network and inhibits oxidative and inflammatory mediators, offering a promising strategy for managing myocardial arrhythmia in diabetic patients.

Comparing simultaneous hybrid ablation with stand-alone thoracoscopic surgical ablation for the treatment of non-paroxysmal atrial fibrillation: a prospective randomized controlled trial.

Advanced atrial fibrillation (AF) is currently a dilemma for electrophysiologists when choosing a minimally invasive treatment strategy. Previous studies have demonstrated the outcome of either catheter ablation or thoracoscopic surgical ablation (SA) is unsatisfactory in these patients. Whether hybrid ablation (HA) could improve outcomes in these patients is unknown. The purpose of this study was to evaluate the clinical efficacy of HA for the treatment of advanced AF. A randomized controlled trial was designed to enrol patients with persistent AF (PerAF) and enlarged left atrium or long-standing persistent AF (LSPAF) who were randomized to HA or thoracoscopic SA at a 1:1 ratio. The primary endpoint was freedom from any recurrence of AF off antiarrhythmic drugs (AADs) 12 months after operation. The primary endpoint was monitored by 7-day electrocardiogram monitoring devices. One hundred patients were enrolled. The mean age was 58.5 ± 7.6 years, and the mean left atrial diameter (LAD) was 50.1 ± 6.1 mm. At 12 months, freedom from AF off AADs was recorded in 71.4% (35/49) of patients in HA group and 45.8% (22/48) in SA group [odds ratio 2.955, 95% confidence interval (1.275-6.848), P = 0.014]. HA significantly reduced patients' AF burden (30.2% in SA group and 14.8% in HA group, P = 0.048) and the LAD (mean differences: -5.53 ± 4.97 mm in HA group and -3.27 ± 5.20 mm in SA group, P = 0.037) at 12 months after operation. In patients with PerAF and enlarged left atrium or LSPAF, HA achieved better freedom from AF after 1 year of follow-up compared with thoracoscopic SA.

Impact of Physical Activity in Patients With Atrial Fibrillation Undergoing Catheter Ablation: The Multicenter Randomized BE-ACTION Trial.

Arrhythmia recurrence after pulmonary vein isolation (PVI) is common. We conducted a multicenter, randomized trial to determine the impact of increased physical activity on atrial fibrillation recurrence after PVI. From 2018 to 2020, we randomly assigned 200 patients with atrial fibrillation to the ACTION or NO-ACTION group in 4 different centers in the local country of Brandenburg, Germany. Patients were eligible if they were scheduled to undergo PVI, aged ≥50 to ≤77 years, body mass index ≥23 to ≤35 kg/m2, and accepted wearing an activity tracker allowing 24-hour activity monitoring via mobile app. Patients in the ACTION group were actively remote-controlled via transmitted activity data by a physiotherapist, and individual motivational interviewing call sessions were scheduled with each ACTION patient every 2 weeks. The primary end point was the composite of recurrence of any atrial arrhythmia >30 seconds, additional ablation procedure, cardioversion, and new onset of antiarrhythmic drugs earliest after 90 days after index PVI over 12 months. Overall, the median age of patients was 66 (interquartile range, 61-71) years, 33.5% were women, and 52% had persistent atrial fibrillation. The number of steps per day increased in both groups of patients from baseline to 12 months (P<0.001). The absolute increase in steps per day did not differ between patients in the ACTION group with +3205 steps (597-4944) compared with those in the NO-ACTION group +2423 steps (17-4284), P=0.325. Unadjusted intention-to-treat analysis showed no difference in the primary composite end point in the ACTION group (27.3%) versus the NO-ACTION group (32.7%), P=0.405. Physical activity improved in patients after PVI. The present randomized controlled trial shows that activity tracker and motivational calls to increase physical activity versus activity tracker alone did not reduce the occurrence of the primary composite end point of atrial fibrillation recurrence or the absolute increase in steps per day. URL: https://www.cochranelibrary.com; Unique identifier: DRKS00012914.

Safety of adenosine for pediatric tachyarrhythmia treatment in the emergency department: a multi-hospital 10-year cross-sectional study

BackgroundSupraventricular tachycardia is the most common dysrhythmia in children. Initial vagal maneuvers are successful less than half of the time. Adenosine, a potent AV nodal blocker with a short half-life, is recommended as first line pharmacotherapy. Minor side effects from adenosine are common, but report of serious side effects such as sustained ventricular tachycardia, torsades de pointes, syncope or hypotension are confined to small case series or studies greater than 20 years old. We aimed to specifically identify the incidence of serious side effects of adenosine in children in the emergency department.MethodsBetween 2002 and 2022, all children less than 18 years old who received adenosine for tachyarrhythmia treatment in two emergency departments were included. The electronic record was reviewed for demographic information, patient history, treatments given, and side effects or complications were observed. Electrocardiograms before, during and after adenosine administration were reviewed.Results77 patients met inclusion criteria. There were 74 patients with an initial rhythm of typical SVT. The other three patients included one with a junctional rhythm, one with atrial fibrillation, and one with an undetermined narrow complex tachycardia. 49 patients had cardiac rhythm monitoring during adenosine administration. 17 of these patients had three or more consecutive ventricular beats following adenosine, however no patients required treatment. No patients had syncope. One patient had brief hypotension after adenosine that normalized without intervention. Four patients were electrically cardioverted after adenosine, all for persistent dysrhythmias: two for persistent SVT with hypotension, one for atrial fibrillation and one for an undetermined rhythm. Twelve patients were placed on continuous antiarrhythmic medication for persistent SVT. Age, gender, prior SVT history, initial adenosine dose, and need for additional doses were not significant risk factors for a prolonged sinus pause or greater than two ventricular beats.ConclusionsAdenosine treatment in typical supraventricular tachycardia in pediatric patients is safe.

Patient selection, ventricular tachycardia substrate delineation and data transfer for stereotactic arrhythmia radioablation. A Clinical Consensus Statement of the European Heart Rhythm Association (EHRA) of the ESC and the Heart Rhythm Society (HRS).

Stereotactic arrythmia radioablation (STAR) is a novel, non-invasive and promising treatment option for ventricular arrythmias (VA). It has been applied in highly selected patients mainly as bail-out procedure, when (multiple) catheter-ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including etiology specific aspects, and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.