Antiarrhythmic Research Articles

New Perspectives in The Management of Paroxysmal Atrial Fibrillation: Dual AntiArrhythmic Medications.

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice projected to affect 12.1 million individuals by the year 2030. Patients who are diagnosed with AF have an increased risk of morbidity and mortality. Although catheter ablation is a class I treatment recommendation in patients with symptomatic paroxysmal AF, antiarrhythmic medications (AAM) continue to be the mainstay of treatment in limited resource settings not offering ablation procedures. Currently, the most used AAMs are those which block either the sodium or potassium channels. We hypothesized that the use of selective dual AAM (sodium and potassium channel blockers) (DAAM) improves the chance of maintaining sinus rhythm and decreases the need for catheter ablation when compared with single AAM (SAAM). This retrospective observational study was conducted in 150 patients with paroxysmal AF over 5 years at Richmond University Medical Center in Staten Island, New York. The following data were collected: age, sex, comorbidities, electrocardiogram findings, ejection fraction by echocardiography, classes of AAM, duration, and response to treatments. The primary endpoint included the absence of symptoms and maintenance of sinus rhythm. The secondary endpoint included the requirement of electrical cardioversion or catheter ablation. A total of 86 patients met the inclusion criteria in our analysis. The average age of the patients was 71.06 years (SD = 7.66). About 45 patients were given DAAM of either amiodarone + flecainide or dronedarone + flecainide and were treated for an average of 15.4 months, followed by catheter ablation, if needed. Also, 41 patients received a SAAM followed by catheter ablation, if needed. A Mann-Whitney test indicated that electrical cardioversion and catheter ablation were greater for the SAAM group (Md = 1) than for the DAAM group (Md = 0) (U = 294.00, P value <0.001; U = 507.00, P value <0.001, respectively). No pro-arrhythmic side effects or death were encountered in either group. Treatment of paroxysmal AF with DAAM is effective compared with SAAM and is less likely to need catheter ablation or electrical cardioversion. Well-designed prospective studies are needed to further explore the use of DAAM in the management of paroxysmal AF and its clinical impact in limited resource settings.

Percutaneous left stellate ganglion block for refractory ventricular tachycardia in structural heart disease: our single-centre experience.

When electrical storm (ES) is amenable to neither antiarrhythmic drugs, nor deep sedation or catheter ablation, autonomic modulation may be considered. We report our experience with percutaneous left stellate ganglion block (PSGB) to temporarily suppress refractory ventricular arrhythmia (VA) in patients with structural heart disease. Aretrospective analysis was performed at our institution of patients with structural heart disease and an implantable cardioverter defibrillator (ICD) who had undergone PSGB for refractory VA between January 2018 and October 2021. The number of times antitachycardia pacing (ATP) was delivered and the number of ICD shocks/external cardioversions performed in the week before and after PSGB were evaluated. Charts were checked for potential complications. Twelve patients were identified who underwent acombined total of 15PSGB and 5surgical left cardiac sympathetic denervation procedures. Mean age was 73 ± 5.8years and all patients were male. Nine of 12 (75%) had ischaemic cardiomyopathy, with the remainder having non-ischaemic dilated cardiomyopathy. Mean left ventricular ejection fraction was 35% (± 12.2%). Eight of 12 (66.7%) patients were already being treated with both amiodarone and beta-blockers. The reduction in ATP did not reach statistical significance (p = 0.066); however, ICD shocks (p = 0.028) and ATP/shocks combined were significantly reduced (p = 0.04). At our follow-up electrophysiology meetings PSGB was deemed ineffective in 4of 12patients (33%). Temporary anisocoria was seen in 2 of12 (17%) patients, and temporary hypotension and hoarseness were reported in asingle patient. In this limited series, PSGB showed promise as amethod for temporarily stabilising refractory VA and ES in acohort of male patients with structural heart disease. The side effects observed were mild and temporary.

DNA Framework-Enabled 3D Organization of Antiarrhythmic Drugs for Radiofrequency Catheter Ablation.

Preorganizing molecular drugs within a microenvironment is crucial for the development of efficient and controllable therapeutic systems. Here, the use of tetrahedral DNA framework (TDF) is reported to preorganize antiarrhythmic drugs (herein doxorubicin, Dox) in 3D for catheter ablation, a minimally invasive treatment for fast heartbeats, aiming to address potential complications linked to collateral tissue damage and the post-ablation atrial fibrillation (AF) recurrence resulting from incomplete ablation. Dox preorganization within TDF transforms its random distribution into a confined, regular spatial arrangement governed by DNA. This, combined with the high affinity between Dox and DNA, significantly increases local Dox concentration. The exceptional capacity of TDF for cellular internalization leads to a 5.5-fold increase in intracellular Dox amount within cardiomyocytes, effectively promoting cellular apoptosis. In vivo investigations demonstrate that administering TDF-Dox reduces the recurrence rate of electrical conduction after radiofrequency catheter ablation (RFCA) to 37.5%, compared with the 77.8% recurrence rate in the free Dox-treated group. Notably, the employed Dox dosage exhibits negligible adverse effects in vivo. This study presents a promising treatment paradigm that strengthens the efficacy of catheter ablation and opens a new avenue for reconciling the paradox of ablation efficacy and collateral damage.

A rare variant of the development of the proarrhythmogenic effect of etacizine in a child with chronic kidney disease (clinical case)

This article describes a rare clinical case of the development of severe ventricular tachycardia while taking etacizine in a 3-year-8-month-old patient with chronic kidney disease. A clinical case demonstrates the pharmacodynamics and pharmacokinetics of class 1C antiarrhythmic drugs in pediatric patients with kidney pathology.

Repositioning of antiarrhythmics for prostate cancer treatment: a novel strategy to reprogram cancer-associated fibroblasts towards a tumor-suppressive phenotype

BackgroundCancer-associated fibroblasts (CAFs) play a significant role in fueling prostate cancer (PCa) progression by interacting with tumor cells. A previous gene expression analysis revealed that CAFs up-regulate genes coding for voltage-gated cation channels, as compared to normal prostate fibroblasts (NPFs). In this study, we explored the impact of antiarrhythmic drugs, known cation channel inhibitors, on the activated state of CAFs and their interaction with PCa cells.MethodsThe effect of antiarrhythmic treatment on CAF activated phenotype was assessed in terms of cell morphology and fibroblast activation markers. CAF contractility and migration were evaluated by 3D gel collagen contraction and scratch assays, respectively. The ability of antiarrhythmics to impair CAF-PCa cell interplay was investigated in CAF-PCa cell co-cultures by assessing tumor cell growth and expression of epithelial-to-mesenchymal transition (EMT) markers. The effect on in vivo tumor growth was assessed by subcutaneously injecting PCa cells in SCID mice and intratumorally administering the medium of antiarrhythmic-treated CAFs or in co-injection experiments, where antiarrhythmic-treated CAFs were co-injected with PCa cells.ResultsActivated fibroblasts show increased membrane conductance for potassium, sodium and calcium, consistently with the mRNA and protein content analysis. Antiarrhythmics modulate the expression of fibroblast activation markers. Although to a variable extent, these drugs also reduce CAF motility and hinder their ability to remodel the extracellular matrix, for example by reducing MMP-2 release. Furthermore, conditioned medium and co-culture experiments showed that antiarrhythmics can, at least in part, reverse the protumor effects exerted by CAFs on PCa cell growth and plasticity, both in androgen-sensitive and castration-resistant cell lines. Consistently, the transcriptome of antiarrhythmic-treated CAFs resembles that of tumor-suppressive NPFs. In vivo experiments confirmed that the conditioned medium or the direct coinjection of antiarrhythmic-treated CAFs reduced the tumor growth rate of PCa xenografts.ConclusionsCollectively, such data suggest a new therapeutic strategy for PCa based on the repositioning of antiarrhythmic drugs with the aim of normalizing CAF phenotype and creating a less permissive tumor microenvironment.

Toxicologic analysis of 35 drugs in post mortem human blood samples with focus on antihypertensive and antiarrhythmic drugs

Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS).Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.

Folate as a potential treatment for lethal ventricular arrhythmias in TANGO2-deficiency disorder.

TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac arrhythmias are recalcitrant to standard antiarrhythmic medications and constitute the leading cause of death. Disease modeling for TDD has been primarily carried out using human dermal fibroblast and, more recently, in Drosophila by multiple research groups. No human cardiomyocyte system has been reported, which greatly hinders the investigation and understanding of TDD-associated arrhythmias. Here, we established potentially novel patient-derived induced pluripotent stem cell differentiated cardiomyocyte (iPSC-CM) models that recapitulate key electrophysiological abnormalities in TDD. These electrophysiological abnormalities were rescued in iPSC-CMs with either adenoviral expression of WT-TANGO2 or correction of the pathogenic variant using CRISPR editing. Our natural history study in patients with TDD suggests that the intake of multivitamin/B complex greatly diminished the risk of cardiac crises in patients with TDD. In agreement with the clinical findings, we demonstrated that high-dose folate (vitamin B9) virtually abolishes arrhythmias in TDD iPSC-CMs and that folate's effect was blocked by the dihydrofolate reductase inhibitor methotrexate, supporting the need for intracellular folate to mediate antiarrhythmic effects. In summary, data from TDD iPSC-CM models together with clinical observations support the use of B vitamins to mitigate cardiac crises in patients with TDD, providing potentially life-saving treatment strategies during life-threatening events.

A meta-analysis and cost-minimization analysis of cryoballoon ablation versus radiofrequency ablation for paroxysmal atrial fibrillation.

Previous studies have shown inconsistent results in clinical effectiveness between cryoballoon ablation (CBA) and radiofrequency ablation (RFA), and cost assessment between the procedures is important. The aim of this study was to evaluate the clinical effectiveness and cost-effectiveness between the procedures in patients with paroxysmal atrial fibrillation (AF) refractory to antiarrhythmic drug therapy. A systematic review and meta-analysis were performed. The primary outcome for the meta-analysis was long-term AF recurrence. Following the results of the meta-analysis, the cost-effectiveness of CBA versus RFA in Japan was assessed. The meta-analysis included 12 randomized controlled trials and six propensity-score matching cohort studies. AF recurrence was slightly lower in patients referred for CBA than for RFA, with an integrated risk ratio of 0.93 (95% confidence interval: 0.81-1.07) and an integrated hazard ratio of 0.96 (95% confidence interval: 0.77-1.19), but no significant difference was found. A cost-minimization analysis was conducted to compare the medical costs of CBA versus RFA because there was no significant difference in the risk of AF recurrence between the procedures. The estimated costs for CBA and RFA were JPY 4 858 544 (USD 32 390) and JPY 4 505 255 (USD 30 035), respectively, with cost savings for RFA of JPY 353 289 (USD 2355). Our meta-analysis suggests that CBA provides comparable benefits with regard to AF recurrence compared with RFA, as shown in previous studies. Although the choice of treatment should be based on patient and treatment characteristics, RFA was shown that it might be cost saving as compared to CBA.

Novel Antiarrhythmic and Cardioprotective Effects of Brilliant Blue G

In this study, we investigated the effects of the purinergic P2X7 receptor antagonist brilliant blue G (BBG) on cardiac arrhythmia and myocardial injury induced by intravenously (i.v.) administered epinephrine in anesthetized rats. We also examined the possible involvement of beta-adrenergic receptors or cholinergic mechanisms in the effects of BBG. Sprague-Dawley rats were treated with epinephrine (10 μg/kg, i.v.). Brilliant blue G (100 mg/kg) was intraperitoneally (i.p.) administered thirty minutes prior to i.v. epinephrine. The effects of pretreatment with propranolol (2 mg/kg, i.p.) or atropine (2 mg/kg, i.v.) given prior to BBG and epinephrine were examined. The control group received saline. Moreover, the effects of only BBG on electrocardiogram (ECG) parameters were investigated. Results showed that compared with the saline control, BBG caused significant bradycardia (from 405.8 ± 1.18 to 239.4 ± 6.69 beats/min), increased RR interval (from 0.149 ± 0.002 to 0.254± 0.007 sec) and PR interval (from 0.051 ± 0.0008 to 0.059 ± 0.0004 sec), increased R wave amplitude (from 0.238 ± 0.019 to 0.548 ± 0.009 mv), and shortened QTc interval (from 0.169 ± 0.006 to 0.141 ± 0.003 sec) over 15 minutes after of BBG administration. BBG did not cause cardiac arrhythmia. Meanwhile, epinephrine produced significant bradycardia (209.8 ± 28.78 vs. 405.8 ± 1.18 beats/min), increased PR interval, prolonged the QRS complex, shortened QTc interval, decreased R wave amplitude and induced ventricular tachycardia. Brilliant blue G given prior to epinephrine increased heart rate and completely suppressed the epinephrine-induced ventricular arrhythmia. The inhibitory effect of BBG on the arrhythmia caused by epinephrine was prevented by atropine. In contrast the epinephrine induced arrhythmia was completely suppressed with propranolol and BBG. The histopathological study showed that epinephrine caused necrosis and apoptosis of cardiac muscle cells, degeneration of cardiac muscle fibers, and interstitial haemorrhages. These changes were markedly prevented by BBG alone, propranolol/BBG and to a less extent by atropine/BBG pretreatment. The study provided the first evidence for a cardioprotective and anti-arrhythmogenic actions for BBG against epinephrine-induced arrhythmia and myocardial damage, and suggested that cholinergic mechanisms are involved in its anti-arrhythmogenic action.

Clinical outcomes of catheter ablation for atrial fibrillation, atrial flutter, and atrial tachycardia in wild-type transthyretin amyloid cardiomyopathy: a proposed treatment strategy for catheter ablation in each arrhythmia.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA. A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA. The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.

Tachyarrhythmias in congenital heart disease.

The prevalence of congenital heart disease (CHD) in adult patients has risen with advances in diagnostic and surgical techniques. Surgical modifications and hemodynamic changes increase the susceptibility to arrhythmias, impacting morbidity and mortality rates, with arrhythmias being the leading cause of hospitalizations and sudden deaths. Patients with CHD commonly experience both supraventricular and ventricular arrhythmias, with each CHD type associated with different arrhythmia patterns. Macroreentrant atrial tachycardias, particularly cavotricuspid isthmus-dependent flutter, are frequently reported. Ventricular arrhythmias, including monomorphic ventricular tachycardia, are prevalent, especially in patients with surgical scars. Pharmacological therapy involves antiarrhythmic and anticoagulant drugs, though data are limited with potential adverse effects. Catheter ablation is preferred, demanding meticulous procedural planning due to anatomical complexity and vascular access challenges. Combining imaging techniques with electroanatomic navigation enhances outcomes. However, risk stratification for sudden death remains challenging due to anatomical variability. This article practically reviews the most common tachyarrhythmias, treatment options, and clinical management strategies for these patients.

In Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: the i-STRATIFICATION study.

Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials. A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient's ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant. In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool.

Real-World Outcomes of a Rhythm Control Strategy for Atrial Fibrillation Patients with Reduced Left Ventricular Ejection Fraction (

Background/Objectives: The effectiveness of a rhythm control strategy in patients with atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF < 50%) in real-world practice remains uncertain. Our objective was to evaluate the real-world outcomes of a rhythm control strategy in patients with AF and reduced LVEF, focusing on changes in LV systolic function and brain natriuretic peptide (BNP) levels. Methods: The study retrospectively reviewed the medical records of 80 patients with concurrent AF and reduced LVEF who underwent rhythm control therapy between March 2015 and December 2021. Results: The patients had an average age of 63.6 years and an initial LVEF of 34.3%. Sinus rhythm was restored using anti-arrhythmic drugs (38, 47.5%) or electrical cardioversion (42, 52.5%). Over a follow-up period of 53.0 months, AF recurred in 65% of patients, with 57.7% undergoing catheter ablation. Significant improvements were noted in LVEF (from 34.3% to 55.1%, p < 0.001) and BNP levels (from 752 pg/mL to 72 pg/mL, p < 0.001) at the last follow-up. Nearly all patients (97.5%) continued with the rhythm control strategy during the follow-up period. Conclusions: In real-world settings, a rhythm control strategy proves to be feasible and effective for improving LVEF and reducing BNP levels in AF patients with reduced LVEF.

Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology

BackgroundPromising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood. ObjectiveWe hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression. MethodsAfter exposure to 20 Gy of x-rays in a single fraction, neonatal rat ventricular cardiomyocytes were analyzed 24 and 96 hours postradiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration in both monolayers and single cells. In addition, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and messenger RNA levels. ResultsAfter irradiation with 20 Gy, neonatal rat ventricular cardiomyocytes exhibited increased beat rate and conduction velocity 24 and 96 hours after treatment. Messenger RNA and protein levels of ion channels were altered, with the most significant changes observed at the 96-hour mark. Upregulation of Cacna1c (Cav1.2), Kcnd3 (Kv4.3), Kcnh2 (Kv11.1), Kcnq1 (Kv7.1), Kcnk2 (K2P2.1), Kcnj2 (Kir2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 ryanodin-rezeptor 2 and Slc8a1 Na+/Ca2+ exchanger expression and altered properties 96 hours posttreatment. Fibroblast and myofibroblast levels remained unchanged. ConclusioncSBRT modulates the expression of various ion channels, calcium handling proteins, and gap junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed after cSBRT.

Randomized Study Comparing Radiofrequency Ablation with the PVAC Gold System vs. Antiarrhythmic Drugs in Elderly Patients with Symptomatic Atrial Fibrillation.

There are no randomized studies comparing the maintenance of sinus rhythm after catheter ablation (CA) concerning treatment with antiarrhythmic drugs (AA) in elderly patients with paroxysmal atrial fibrillation (AF). To compare the clinical results of pulmonary vein (PV) isolation with the second-generation PVAC Gold catheter against AA treatment in elderly people with recurrent symptomatic paroxysmal AF, refractory to at least one AA, and without structural heart disease. Sixty patients with paroxysmal AF ≥ 65 years old were randomized to two forms of treatment: group 1: CA and group 2: AA drugs. The primary outcome was the AF recurrence-free rate after at least one year of follow-up. Secondary outcomes were: progression to persistent forms of AF, impact on quality of life (QOLF), and complications. The significance level adopted in the statistical analysis was 5% (p<0.05). The AF recurrence-free rate was 80% (10% with amiodarone) in the CA group, after 1.3 procedures per patient and 65% in the AA group (60% with amiodarone), (p = 0.119) in an average follow-up of 719 days (Q1: 566; Q3: 730). The persistent AF free rate was 83.4% in the AC group and 67.7% in the AA group (p = 0.073) Both strategies showed an improvement in the AFQoL score during follow-up (p < 0.001), with no difference between the groups. Although without clinical repercussions or impact on the intellectual assessment test, 25% of patients in the CA group showed signs of cerebral embolization on brain MRI. Both strategies for maintaining sinus rhythm promoted an improvement in the quality of life of elderly patients with symptomatic AF, with no statistical difference in the clinical outcomes. Additional studies using technologies with a better safety profile are needed to evaluate the benefits of CA in elderly patients with AF.

Overcoming patient reluctance to statin intolerance.

Statin therapy is a cornerstone in the management of dyslipidemia, both in primary and secondary prevention of cardiovascular events. Despite strong guidelines supporting statin use, concerns regarding side effects, particularly musculoskeletal symptoms, contribute to statin intolerance and patient reluctance. While statin intolerance is reported in 5% to 30% of patients, its true prevalence may be overestimated due to the influence of the nocebo effect. Factors associated with higher incidence of statin intolerance include older age, female sex, comorbidities such as diabetes and chronic kidney disease, and concurrent use of medications such as antiarrhythmic agents or calcium channel blockers. Clinical characterization of statin intolerance requires thorough evaluation and exclusion of alternative causes of musculoskeletal symptoms. Strategies to address statin intolerance include reassessing cardiovascular risk, engaging in shared decision-making, statin rechallenge after appropriate washout periods, dosage titration for tolerability, and consideration of alternative therapies when low-density lipoprotein goals cannot be achieved with statins. This review provides an overview of the spectrum of statin intolerance, its clinical assessment, and a systematic approach to caring for a patient with statin intolerance.

Verapamil increases susceptibility of colistin-resistant Acinetobacter baumannii to colistin

Acinetobacter baumannii, which is predominantly responsible for hospital-acquired infections, presents a tremendous clinical challenge due to its increasing antibiotic resistance to colistin (COL), a last-line antibiotic. As a result, the combination of antimicrobial and non-antimicrobial agents is emerging as a more popular treatment approach against infections caused by COL-resistant A. baumannii. This study administered COL and verapamil (VER), that is an antihypertensive and antiarrhythmic agent. We found that the susceptibility of A. baumannii to COL was restored both in vitro and in vivo. Scanning electron microscope and Crystal violet staining showed inhibition of the VER/COL combination on bacterial biofilm formation. Cytotoxicity assay and haemolysis test were used to confirm in vitro safety evaluation. Further experiments using propidium iodide staining revealed that the VER/COL combination improved the therapeutic efficacy of COL by modifying the permeability of bacterial membranes. As demonstrated by reactive oxygen species experiments, the drug combination caused the accumulation of bacterial reactive oxygen species and their eventual death. Additionally, VER/COL treatment significantly reduced the efflux of Rhodamine 123 (Rh123). For the first time, this study identifies the anti-hypertensive drug VER as a COL potentiator against A. baumannii, providing a potential treatment approach against A. baumannii infections and improving patient outcomes.

Ventricular arrhythmias in a child with Marfan syndrome: case report

We present a severe disease progression observed in a 13-year-old patient diagnosed with Marfan syndrome and associated cardiac rhythm disorders, including polymorphic ventricular premature contractions and persistent ventricular tachycardia resistant to a wide range of antiarrhythmic medications. We conducted an analysis of contemporary perspectives on the etiology of ventricular tachyarrhythmias and their impact on the prognosis of patients with Marfan syndrome. Conclusions were drawn regarding the selection of treatment strategies for this specific patient population.

Propafenone-induced connexin-43 protein accumulation and intracellular dynamics

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): China Scholarship Council Background Connexin-43 (Cx43) plays a pivotal role in intercellular communication through gap junctions. It is instrumental in propagating electrical signals and allowing ions to flow between neighboring cardiomyocytes. This synchronized electrical activity allows the heart to work as a functional syncytium. Any disruption or malfunction of Cx43 can lead to arrhythmias and other cardiac issues. Understanding the functions and regulation of Cx43 is vital in both basic research and clinical contexts. Propafenone, a class Ic antiarrhythmic drug, has shown promise in rhythm control; however, its precise impact on cardiac cellular physiology, particularly regarding Cx43, remains incompletely understood. Purpose To investigate propafenone’s effect on Cx43 expression, physiology, and underlying mechanisms in cell systems. Methods Used cell lines include human embryonic kidney HEK293 cells transfected with Cx43; differentiated murine embryonic carcinoma EPI7 cells with an epithelioid morphology and visceral endoderm-like END2 cells, endogenously expressing high amounts of functional Cx43. Cx43 protein expression levels were determined by Western blot analysis, whereas immunofluorescence (IF) imaged by a Total Internal Reflection Fluorescence (TIRF) microscope was used to assess the subcellular localization of Cx43 proteins. Dye injections were used to gain insight into the effects of propafenone on Cx43 metabolic coupling. Results and Conclusion Full length Cx43 protein levels were increased after treatment with propafenone and IF microscopy showed an intracellular accumulation of Cx43 protein, both on ectopically and endogenously expressed Cx43. Propafenone did not alter Cx43 half-life, in contrast to the lysosomal inhibitor chloroquine. Finally, gap-junctional coupling was decreased by chronic propafenone treatment. We conclude that the class 1c antiarrhythmic drug propanone increases Cx43 protein expression, resulting in its intracellular accumulation, as a side effect.

Arrhythmogenic Right Ventricular Dysplasia: A Comprehensive Review of Pathophysiology, Diagnosis, and Management Strategies

Arrhythmogenic Right Ventricular Dysplasia (ARVD) is a rare inherited heart disorder characterized by fibrofatty replacement of the right ventricular myocardium, leading to ventricular arrhythmias and an increased risk of sudden cardiac death. This review aims to provide a comprehensive overview of ARVD, including its pathophysiology, clinical manifestations, diagnostic criteria, and management strategies. The pathogenesis of ARVD involves genetic mutations affecting proteins of the cardiac desmosome, leading to myocardial cell death and fibrofatty replacement. Clinical presentation varies widely, ranging from asymptomatic individuals to those with palpitations, syncope, or sudden cardiac arrest. Diagnosis is challenging and relies on a combination of clinical, electrocardiographic, imaging, and histopathologic findings. Management involves risk stratification for sudden cardiac death, lifestyle modifications, antiarrhythmic medications, and, in select cases, implantable cardioverter-defibrillator placement or catheter ablation.