Antiarrhythmic Research Articles

Cryoballoon Pulmonary Vein Isolation With Versus Without Additional Right Atrial Linear Ablation for Persistent Atrial Fibrillation: The CRALAL Randomized Clinical Trial.

Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with those with paroxysmal AF. We investigate whether additional linear ablation from the superior vena cava to the right atrial septum and cavotricuspid isthmus ablation improves the rhythm outcome of patients with persistent AF undergoing cryoballoon PVI (Cryo-PVI). In this investigator-initiated, multicenter, randomized clinical trial, 289 patients with persistent AF refractory to antiarrhythmic drug therapy were randomized 1:1 to either Cryo-PVI with additional right atrium (RA) linear ablation or Cryo-PVI alone. The primary end point was any documented atrial arrhythmia lasting ≥30 seconds after a 3-month blanking period after ablation. The secondary end points were atrial arrhythmia recurrence or antiarrhythmic drug use after a 3-month blanking period, complications, and total procedure time. During the median follow-up of 24 months (median age, 63 years; 23.9% women), the atrial arrhythmia recurrence was less frequent in the additional RA ablation group (n=50, 37.5%) than in the Cryo-PVI alone group (n=69, 53.1%; absolute difference, -15.6% [95% CI, -27.9% to -3.4%]; hazard ratio, 0.66 [95% CI, 0.46-0.94]). Antiarrhythmic drugs were prescribed after the 3-month period to 72 (49.3%) patients in the additional RA ablation group and 79 (55.2%) patients in the Cryo-PVI alone group. No difference was found in complication rate between the 2 groups. Total procedure time was longer in the additional RA ablation group (median, 88 versus 72 minutes; P<0.001). Additional RA linear ablation beyond Cryo-PVI improved the ablation outcome compared with that of PVI alone in persistent AF patients.

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

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

Catheter Ablation in Atrial Fibrillation: Recent Advances

Atrial fibrillation (AF) is the leading cause of arrhythmia-related morbidity and mortality. Recurrent symptoms, hospitalizations, and cost burden to patients have necessitated treatments beyond antiarrhythmic drugs (AADs) for patients with AF. Catheter ablation has proven to be effective over medical therapy alone; however the recurrence rates for atrial tachyarrhythmias post-ablation remain significant, particularly in patients with persistent and long-standing persistent AF. Hence, new techniques for catheter ablation have arisen, such as non-thermal energy sources, novel catheters, electroanatomical mapping, and ablation of additional targets. In this review, we discuss the recent advances in the field of catheter ablation, including newer modalities for the prevention of adverse events and future perspectives.

Sacubitril/Valsartan and Dapagliflozin in Patients with a Failing Systemic Right Ventricle: Effects on the Arrhythmic Burden

Background/Objectives: Angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) are essential medications in heart failure (HF) therapy, and their potential antiarrhythmic effects have been reported. Recently, ARNI and SGLT2i use for HF in adult congenital heart disease (ACHD) has been studied. However, whether any beneficial effects may be achieved on the arrhythmic burden in the complex population of ACHD with a systemic right ventricle (sRV) is still to be determined. Methods: We retrospectively collected all significant arrhythmic events from a cohort of patients with a failing sRV attending our tertiary care center on optimal guideline-directed medical therapy (GDMT) with ARNI and/or SGLT2i. Results: A total of 46 patients (mean age 38.2 ± 10.7 years, 58% male) on sacubitril/valsartan were included. Twenty-three (50%) patients were also started on dapagliflozin. After a median follow-up of 36 [Q1–Q3: 34–38] months, arrhythmic events occurred globally in 13 (28%) patients. Survival analysis showed significant reduction of clinically relevant atrial and ventricular arrhythmia at follow-up (p = 0.027). Conclusions: Our findings suggest that GDMT including sacubitril/valsartan and dapagliflozin may also offer an antiarrhythmic effect in ACHD patients with a failing sRV, by reducing the incidence of arrhythmic events at follow-up.

Comparative Efficacy of Amiodarone and Lidocaine in Treating Cardiac Arrest Due to Ventricular Fibrillation and Pulseless Ventricular Tachycardia in Adults. A Literature Review

Introduction:Sudden cardiac arrest (SCA) is a critical emergency, with shockable rhythms like ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT) posing challenges. Amiodarone and lidocaine are key antiarrhythmic drugs used with defibrillation. While both improve hospital admission rates, their effects on survival and neurological outcomes remain unclear. This review examines their comparative efficacy to guide clinical practice.Materials and methods:A thorough literature review was performed using electronic databases. The search was restricted to English-language articles published from 1970 to 2024.Aim of the study:The aim of this study is to systematically review and compare the efficacy of lidocaine and amiodarone in the treatment of cardiac arrest due to ventricular fibrillation and ventricular tachycardia in adults. This review seeks to evaluate the existing literature to determine the effectiveness and clinical outcomes associated with each medication.Conclusions: The comparative analysis of amiodarone and lidocaine highlights their respective strengths and limitations in managing cardiac arrest, offering valuable insights for clinical practice. Amiodarone stands out as the preferred antiarrhythmic agent due to its significant efficacy in improving short-term outcomes, such as return of spontaneous circulation (ROSC) and survival to hospital admission. Overall, amiodarone's efficacy and broader applicability position it as the first-line agent for shock-refractory ventricular fibrillation (VF) and pulseless ventricular tachycardia (pVT). Lidocaine serves as an important alternative in specific scenarios. Future research should aim to optimize antiarrhythmic protocols, improve long-term survival and neurological outcomes, and explore innovative approaches to resuscitation.

Oroxin B Resembles Bisoprolol in Attenuating Beta1-Adrenergic Receptor Autoantibody-Induced Atrial Remodelling via the PTEN/AKT/mTOR Signalling Pathway.

Beta1-adrenergic receptor autoantibodies (β1-AAbs) promote atrial remodelling and ultimately lead to the development of atrial fibrillation (AF). Oroxin B is a natural flavonoid glycoside with a variety of biological activities, including anti-inflammatory and autophagy-promoting effects, and has therapeutic benefits for a variety of diseases. The aim of this study was to investigate the potential therapeutic role of Oroxin B in the development of β1-AAb-induced atrial fibrillation and to elucidate the underlying mechanisms involved. We established a rat model of β1-AAb-induced atrial fibrillation via active immunisation. The first stage was divided into three groups: the control group, the β1-AAb group and the β1-AAb + bisoprolol group. The second stage was divided into three groups: the control group, the β1-AAb group and the β1-AAb + Oroxin B group. Serum levels of β1-AAbs, atrial tissue levels of cyclic monophosphate (cAMP), atrial electrophysiological parameters, cardiac structure and function, mitochondrial structure, autophagy levels, cardiomyocyte apoptosis and myocardial fibrosis were examined. The results showed that bisoprolol, a β1-blocker, improved β1-AAb-induced atrial electrical remodelling, reduced atrial collagen deposition, ameliorated the increase in LAD and regulated the balance of autophagy and apoptosis in atrial myocytes through the PTEN/AKT/mTOR signalling pathway. Oroxin B, a PTEN agonist, can improve the impairment of autophagy homeostasis and apoptosis in atrial tissue by activating the PTEN/AKT/mTOR signalling pathway, thereby improving atrial structure and electrical remodelling. Moreover, Oroxin B may play a therapeutic role in β1AAb-induced atrial fibrillation. In conclusion, our results demonstrate the potential therapeutic role of Oroxin B in β1AAb-induced atrial fibrillation and the underlying mechanisms, suggesting that Oroxin B may be an effective antiarrhythmic medication.

Investigating Sodium-Glucose Cotransporter 2 Inhibitors Versus Other Glucose-Lowering Drugs on Ventricular Arrhythmias or Sudden Cardiac Death Using the US FDA Adverse Event Reporting System.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reported to exhibit antiarrhythmic effects. However, there is conflicting evidence regarding the association between SGLT2 inhibitors and ventricular arrhythmias or sudden cardiac death (SCD). We utilized the US FDA Adverse Event Reporting System (FAERS) database to investigate the reporting frequencies of SGLT2 inhibitors with ventricular arrhythmias and SCD compared to other glucose-lowering drugs (ATC-A10B). We used the web data mining tool AERSMine to mine reports of ventricular arrhythmias and SCD from FAERS to compare SGLT2 inhibitors versus other glucose-lowering drugs. The mining range was from 2004q1 to 2023q3. Disproportionality analysis used the proportional reporting ratio (PRR) with 95% confidence interval (CI) and information component (IC) with 95% credible interval. From 2004q1 to 2023q3, a total of 121,129 adverse events were reported for SGLT2 inhibitors, with a total of 1,127,485 in the ATC-A10B group. Ventricular arrhythmias reporting frequency in the SGLT2 inhibitors group was similar to that of the control group (1.36/1000 reports vs 1.55/1000 reports; p = 0.10), with a PRR of 0.88 (95%CI 0.75-1.03). However, the reporting frequency of SCD in the SGLT2 inhibitors group was significantly lower than that of the control group (1.43 vs 4.70/1000; p < 0.001), with a PRR of 0.30 (95%CI 0.26-0.35), and this trend was observed within individual molecules of SGLT2 inhibitors. During the sensitivity analysis process, the results obtained when restricting the scope of data mining to between 2013q1 and 2023q3 were similar to those obtained when using data from 2004q1 to 2023q3. In this drug pharmacovigilance assessment, the reporting frequency of ventricular arrhythmias associated with SGLT2 inhibitors was similar to that of other antidiabetic medications, while the reporting frequency of SCD related to SGLT2 inhibitors was lower. This real-world study evidence complements existing clinical evidence.

Using computed tomography atrial myocardial thickness maps in cryoballoon pulmonary vein isolation: the UTMOST AF II randomized clinical trial.

Whether adjusting the duration of ablation based on left atrial wall thickness (LAWT) provides extra benefits for pulmonary vein (PV) isolation for atrial fibrillation (AF) is uncertain. We studied the safety and efficacy of tailored cryoballoon PV isolation (CB-PVI) based on LAWT for paroxysmal AF. Two hundred seventy-seven patients with paroxysmal AF refractory to anti-arrhythmic drug were randomized 1:1 to either LAWT-guided CB-PVI (n = 135) and empirical CB-PVI (n = 142). Empirical CB-PVI was performed using a 28 mm cryoballoon with recommended application for 240 s per ablation. Cryoapplication in the LAWT-guided group was titrated (additional application for 120 s at PVs, where >25% of the circumference includes segments with LAWT > 2.5 mm and reduced baseline application to 180 s at PVs where >75% of the circumference includes segments with LAWT < 1.5 mm) according to the computed tomography LAWT colour map. The primary endpoint was freedom from any documented atrial arrhythmia of more than 30 s without antiarrhythmic medication, after a single ablation procedure. During a mean follow-up of 18.7 months, patients in the LAWT-guided CB-PVI group (70.8%) had a higher event-free rate from primary endpoint than those in the empirical CB-PVI group (54.4%; hazard ratio 0.64, 95% confidence interval 0.42-0.99; P = 0.043). No differences were observed between the groups in complication rates (3.0% in LAWT-guided vs. 4.9% in empirical CB-PVI). The total procedure time was extended in the LAWT group than in the empirical group (mean 70.2 vs. 65.2 min, respectively). The LAWT-guided energy titration strategy improved freedom from atrial arrhythmia recurrence, compared with conventional strategy.

Arrhythmogenic Cardiomyopathy: Towards Genotype Based Diagnoses and Management.

Arrhythmogenic cardiomyopathy (ACM) is a genetically heterogeneous inherited cardiomyopathy with an estimated prevalence of 1:5000-10 000 that predisposes patients to life-threatening ventricular arrhythmias (VA) and sudden cardiac death (SCD). ACM diagnostic criteria and risk prediction models, particularly for arrhythmogenic right ventricular cardiomyopathy (ARVC), the most common form of ACM, are typically genotype-agnostic, but numerous studies have established clinically meaningful genotype-phenotype associations. Early signs of ACM onset differ by genotype indicating the need for genotype-specific diagnostic criteria and family screening paradigms. Likewise, risk factors for SCD vary by genetic subtype, indicating that genotype-specific guidelines for management are also warranted. Of particular importance, genotype-specific therapeutic approaches are being developed. Results from a randomized controlled trial for flecainide use in ARVC patients are currently pending. Research in a plakophilin-2-deficient mouse model suggests this antiarrhythmic drug may be particularly useful for patients with likely pathogenic or pathogenic (LP/P) PKP2 variants. Additionally, the first gene therapy clinical trials in ARVC patients harboring LP/P PKP2 variants are currently underway. This review aims to provide clinicians caring for ACM patients with an up-to-date overview of the current literature in genotype-specific natural history of disease and management of ACM patients and describe scientific advances that have led to upcoming clinical trials.

Prescription Medication Use and Expenditure of Atrial Fibrillation in the United States.

To study the national trends of anticoagulants, antiarrhythmic drugs (AAD), and expenditures in civilian non-institutionalized AF population. The Medical Expenditure Panel Survey (MEPS) was queried from January 2016 to December 2021 to identify adults (age ≥ 18 years) with a diagnosis of AF utilizing ICD-10-CM code "I48". Prevalence of anticoagulants, AAD, and its expenditure and AF expenditure across clinical settings in the United States were estimated. The predictors of anticoagulant use were identified utilizing multivariate logistic regression analysis. A total of 17.3 million AF adults were identified, of which 46.5% were female, 89.6% were White, and ∼70% were middle/high-income with prevalent comorbidities of hypertension (75.3%) and coronary heart disease (30%). The mean CHA2DS2 VASc score was 3.2, and 40% had a score of ≥4. In the US, an average of $26,103 (2021 inflation-adjusted) was spent per year per adult with AF for health-related expenditures. The prevalence of direct oral anticoagulants (DOAC) and Class I AAD use has increased; in contrast, vitamin K antagonists (VKA) use has declined. DOAC-related per-person annual expenses increased from $849 in 2016 to $1,929 in 2021. In those with a CHA2DS2 VASc score of ≥2, female sex and the presence of coronary heart disease were associated with a lower likelihood of anticoagulant use. AF is a costly condition in which prescription medication use, like DOACs and class III AADs, are significant contributors.

Atrial Fibrillation Types and Chronic Kidney Disease are Independent Predictors of Atrial Fibrillation Recurrence After Radiofrequency Ablation.

Atrial fibrillation (AF) is classified into paroxysmal, persistent, long-term persistent, and permanent types. It is commonly treated by radiofrequency ablation (RFA), which is more successful than conventional anti-arrhythmic drugs, but it is still largely unknown whether these beneficial effects are equally present for all AF types. Here, we evaluated the impact that AF type has on post-RFA patient conditions and identified underlying factors affecting AF prognoses. Three hundred and twenty-nine AF patients who underwent RFA were retrospectively examined (221 paroxysmal, 56 persistent, 52 long-term persistent), during a post-RFA follow-up period, from 3-months to 2-years. Cardiac functional parameters, such as left atrial (LA), ventricular (LV), and pulmonary artery diameters, as well as ejection fraction (EF) and end-diastolic/systolic diameter ratio, were measured using echocardiography. Additionally, chronic kidney disease (CKD) was diagnosed among these AF patients, using the Modification of Diet in Renal Disease (MDRD) formula, and its impact on post-RFA patient outcomes was examined. Logistic regression analysis identified differences between AF and non-AF recurrence groups. In terms of functional parameters, persistent AF had significantly smaller LA, and larger EF, compared to paroxysmal and long-term persistent groups, while paroxysmal had significantly larger LV versus persistent and long-term persistent after RFA. For post-RFA patient conditions, paroxysmal, compared to persistent and long-term persistent, had significantly lower AF recurrence (18.10% versus 30.36% and 36.54%) and re-hospitalization rates (6.79% versus 14.29% and 19.23%); however, no significant difference was present between the 3 groups in terms of post-operative stroke rates, as well as re-hospitalization duration. Additionally, CKD patients, versus non-CKD, were more prone to AF recurrence and re-hospitalization, being 3.268 times more likely. AF types and CKD were independent factors influencing AF recurrence, serving as highly sensitive predictors to monitor prognoses and guide treatments. Therefore, personalized treatment regimens should be recommended for different AF patients.

Pulsed Field Ablation as First-line Therapy for Atrial Fibrillation: A Substudy of the EU-PORIA Registry.

Recent studies have demonstrated the benefit of early ablation in preventing the progression of atrial fibrillation (AF). Clinical practice has reflected this shift in AF management and no longer requires patients to fail antiarrhythmic drugs (AADs) before receiving ablation. However, there is limited evidence on outcomes with pulsed field ablation (PFA) as a first-line therapy. Examination of real-world data may shed light on clinical practices and the effectiveness of PFA with and without a prior history of AAD usage. EU-PORIA is an all-comer AF registry enrolling consecutive patients treated with the pentaspline PFA catheter at 7 high-volume centers in Europe. This subanalysis evaluates patients with a history of class I/III AAD use versus those with no documented history of class I/III AAD use (first-line patients). Patients with incomplete AAD history, long-standing persistent AF, and those undergoing a repeat ablation procedure were excluded. Patients were treated and followed based on institutional standard of care. Any episode of atrial tachycardia or AF lasting longer than 30 s was considered an arrhythmia recurrence. Of 1233 patients enrolled in EU-PORIA, 1091 met the inclusion criteria (mean age, 66 years; 40% females; and persistent AF, 36%). Pulmonary vein isolation-only was used in 90% of the patients, and 10% received extra-PV ablation. Ablation as the first-line approach was chosen in 589 patients, and 502 patients had prior class I/III AAD use. In the first-line PFA group, paroxysmal AF was more frequent (68% versus 59%; P<0.001), and pulmonary vein isolation-only was more frequent (93% versus 86%; P<0.001). At 1-year follow-up, freedom from AF/atrial tachycardia recurrence was similar in the ablation-first versus the ablation after failed AAD group (78% versus 74%, respectively; P=0.076). In this large real-world PFA registry, freedom from AF/atrial tachycardia recurrence after 1 year was similar in patients undergoing PFA as a first-line treatment and those with prior failed AAD therapy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05823818.

Cost Effectiveness of Catheter Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation: A Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with substantial morbidity and mortality. Current international guidelines recommend antiarrhythmic drugs or catheter ablation (CA) as rhythm-control strategies for AF. This study aimed to comprehensively assess economic evaluations (EEs) of the treatment of AF by country income level. Seven electronic databases were systematically searched for EE literature until March 30, 2024, with no constraints on time or language. Two independent reviewers selected the studies, extracted the data, and assessed the quality of the data. Full EEs comparing CA with antiarrhythmic drugs for rhythm-control treatment were included; surgical or rate-control treatments were excluded. The quality of the included articles was assessed using the ECOBIAS checklist. Costs were converted to purchasing power parity US dollars for 2023. A random-effects meta-analysis was applied to pool incremental net benefit (INB) based on a heterogeneity test and its degree (I2 > 25% or Cochran's Q test < 0.1). We also explored heterogeneity and potential publication bias and conducted sensitivity and subgroup analyses. In total, 27 studies across nine countries were eligible, predominantly from high-income countries (n = 25), with a smaller subset from upper-middle-income countries (n = 2). Because of the heterogeneity among the studies, a random-effects model was selected over a fixed-effects model to pool INBs. Most studies (n = 21) favored CA as the cost-effective intervention, yielding an INB of $US23,796 (95% confidence interval [CI] 15,341-32,251) in high-income countries. However, heterogeneity was substantial (I2 = 99.67%). In upper-middle-income countries, the estimated INB was $US18,330 (95% CI - 11,900-48,526). The publication bias results showed no evidence of asymmetrical funnel plots. In this meta-analysis, CA emerged as a cost-effective rhythm-control treatment for AF when compared with antiarrhythmic drugs, particularly in high-income countries. However, economic evidence for upper-middle-income countries is lacking, and no primary evaluations were found for low-middle-income and low-income countries. Further EEs are necessary to expand the understanding of AF treatment globally.

Changes in Hepatic Density Due to Oral Amiodarone-induced Liver injury Shown by Computed Tomography.

Amiodarone is an antiarrhythmic drug that is widely used for atrial fibrillation and other refractory arrhythmias. Although beneficial, its long-term administration is associated with adverse effects on various organs. One patient presented with amiodarone-induced liver injury, which led to liver failure. Computed tomography revealed a gradual increase in hepatic density over a long period following the initiation of amiodarone. Despite the discontinuation of the drug, the patient developed hepatic encephalopathy and subsequently died. This outcome highlights the drug's extended half-life, which caused persistent end-organ damage even after its withdrawal. Drug titration to the lowest effective dose and careful monitoring of annual liver function tests are important.

Maintenance of Sinus Rhythm Is Associated With Lower Incidence of Stroke in Patients With Drug-Refractory Atrial Fibrillation.

Recent studies have demonstrated that early rhythm control for first-line treatment of atrial fibrillation (AF) improved cardiovascular outcomes. However, there is limited data regarding the long-term outcome of patients who failed antiarrhythmic drugs and who refuse radiofrequency catheter ablation (RFCA). Patients with AF who were refractory to antiarrhythmic drugs and had refused further rhythm control attempts via RFCA were retrospectively identified and propensity-score (PS) matched with thosewho had been treated with RFCA. The primary outcome of interest was all-cause mortality or ischemic stroke. A total of 169 patients who refused rhythm control with RFCA and PS matched 169 patients who had been treated with RFCA were included for analysis. During a mean follow-up of 4.3 (2.3;6.9) years, maintenance of sinus rhythm was more achieved in RFCA group (7 [4.1%] in Refuse group vs. 133 [78.7%] in RFCA group, p < 0.001). The incidence of ischemic stroke was significantly higher in patients who refused RFCA compared with patients who underwent RFCA (2.96 per 100 person-years in the Refused group vs. 0.74 per 100 person-years in the RFCA group, log-rank p < 0.001), but all-cause mortality was not significantly different (log-rank p = 0.8). Refusal of attempted rhythm control via RFCA was an independent risk factor for ischemic stroke on multivariate Cox analysis (hazard ratio [HR] 3.2; 95% confidence interval [CI] 1.2-8.53, p = 0.02). In patients with antiarrhythmic drug-refractory AF, the risk of stroke was significantly higher in patients who refused rhythm control via RFCA compared with that of those treated with RFCA.

Unlocking the Cardiovascular Benefits of Walnuts: Insights on Molecular Mechanism From Animal Studies.

The health-promoting benefits of walnut consumption are substantially ascribed to its fatty acid (FA) profile, which is rich in polyunsaturated FA with an exceptionally high n-3 to n-6 ratio. There are also phytonutrients in walnuts that are linked to health welfare. This review article integrates all studies on the effects of walnuts on the cardiovascular system performed on experimental animals, and thus is a source of data on the mechanisms underlying the observed effects. These studies, which are very diverse in experimental design, indicate that a diet enriched with walnuts or treating animals with walnut extract or chemical constituents of walnuts, has many favorable effects on heart and vascular system function. The cardiovascular effect of walnuts depends on the metabolic status of the organism. Among the cardiovascular effects of walnuts is that they improve the FA profile in the circulation and heart in favor of n-3 polyunsaturated FAs. In addition, a favorable effect on triglyceride and cholesterol status, which reduces cardiovascular disease risk, is observed. Intake of walnuts promotes FA catabolism and has anti-inflammatory, antioxidant, and antiarrhythmic effects. Walnuts also have a beneficial effect on vascular tone, accompanied by a decrease in blood pressure and reduced risk for atherosclerosis. In conclusion, studies on experimental animals encourage the consumption of walnuts as a simple, convenient approach to improve cardiovascular health.

Effects and mechanisms of dexmedetomidine preconditioning on isoproterenol-induced ventricular arrhythmias

Dexmedetomidine (DEX) is commonly used in clinical practice because of its sedative, analgesic, antisympathetic, hemodynamic stabilization and antianxiety effects. Previous clinical studies have demonstrated that DEX plays a role in both the prevention and treatment of perioperative arrhythmias. However, the precise mechanisms underlying the effects of DEX remain unclear. Furthermore, few studies have examined the effect of DEX on cardiac electrophysiology. ECG recording was performed in vivo and ex vivo on C57 mice. Simultaneous recording of membrane voltage (Vm) and [Ca2+]i changes was achieved with dual-dye optical mapping, in which voltage- and Ca2+-sensitive dyes are employed. Simultaneous programmed electrical stimulation was used to pacing and induce arrhythmias. Simulating catecholamine-induced arrhythmias with isoprotereno (ISO) and preconditioning with DEX to investigate the antiarrhythmic effects of DEX. Our findings demonstrated that ISO increased the incidence of ventricular tachycardia or ventricular fibrillation in mice during rapid pacing stimulation. DEX preconditioning reduced the incidence of ISO-induced ventricular arrhythmias. Optical mapping with simultaneous recordings of dual dyes (Vm dye and intracellular Ca2+ dye) revealed that DEX pretreatment attenuated the ISO-induced shortening of action potential duration (APD), calcium transient duration (CaTD), and time-to-peak (TTP) of calcium transients, as well as the ISO-induced increase in repolarization heterogeneity. DEX also slowed the conduction velocity. More importantly, DEX preconditioning significantly reduced the calcium transient alternans ratio at 80-ms, 70-ms, and 60-ms pacing cycles. These findings suggest that DEX preconditioning can reduce the incidence of ventricular arrhythmias induced by acute stress simulated by ISO. Prolongation of action potential duration and calcium transient duration and the maintenance of intracellular calcium homeostasis may be the electrophysiological mechanisms involved.

Automaticity of the Pulmonary Vein Myocardium and the Effect of Class I Antiarrhythmic Drugs.

The pulmonary vein wall contains a myocardial layer whose ectopic automaticity is the major cause of atrial fibrillation. This review summarizes the results obtained in isolated pulmonary vein myocardium from small experimental animals, focusing on the studies with the guinea pig. The diversity in the action potential waveform reflects the difference in the repolarizing potassium channel currents involved. The diastolic depolarization, the trigger of automatic action potentials, is caused by multiple membrane currents, including the Na+-Ca2+ exchanger current and late INa. The action potential waveform and automaticity are affected differentially by α- and β-adrenoceptor stimulation. Class I antiarrhythmic drugs block the propagation of ectopic electrical activity of the pulmonary vein myocardium through blockade of the peak INa. Some of the class I antiarrhythmic drugs block the late INa and inhibit pulmonary vein automaticity. The negative inotropic and chronotropic effects of class I antiarrhythmic drugs could be largely attributed to their blocking effect on the Ca2+ channel rather than the Na+ channel. Such a comprehensive understanding of pulmonary vein automaticity and class I antiarrhythmic drugs would lead to an improvement in pharmacotherapy and the development of novel therapeutic agents for atrial fibrillation.

Pulmonary Vein Isolation With Optimized Linear Ablation vs Pulmonary Vein Isolation Alone for Persistent AF

Success rates of pulmonary vein isolation (PVI) are modest for persistent atrial fibrillation (AF). Additional linear ablation beyond PVI has not been proved superior to PVI alone in randomized trials. Ethanol infusion of the vein of Marshall (EIVOM) facilitates ablation at the mitral isthmus and may lead to improved effectiveness of a linear ablation strategy. To determine whether linear ablation with radiofrequency energy combined with EIVOM added to PVI improves sinus rhythm maintenance compared with PVI alone in patients with persistent AF. The PROMPT-AF trial is an investigator-initiated, multicenter, open-label, randomized trial involving 12 tertiary hospitals in China. A total of 498 patients aged 18 to 80 years, with AF persisting for more than 3 months, undergoing first-time AF ablation, were enrolled and randomized from August 27, 2021, to July 16, 2023. Patients were randomized to undergo PVI alone or PVI plus EIVOM and linear ablation (intervention). The latter group first underwent EIVOM, followed by PVI and linear ablation of the left atrial roof, mitral isthmus, and cavotricuspid isthmus. The primary end point was freedom from any documented atrial arrhythmias lasting more than 30 seconds, without the use of antiarrhythmic drugs within 12 months. Secondary outcomes included freedom from atrial arrhythmia recurrence, AF, atrial arrhythmia recurrence after multiple procedures, and documented atrial tachycardia or atrial flutter with or without antiarrhythmic drugs; AF burden; and improvement in quality of life. Patients were monitored with wearable single-lead electrocardiographic (ECG) patches, worn for 24 hours a week, supplemented by symptom-triggered ECGs and Holter monitoring. Among 498 randomized patients, 495 (99.4%) were included in the primary analysis (mean age, 61.1 years [SD, 9.7] years, 361 male [72.9%]). After 12 months, 174 of 246 patients (70.7%) assigned to undergo PVI plus EIVOM and linear ablation and 153 of 249 patients (61.5%) assigned to undergo PVI alone remained free from atrial arrhythmias without taking antiarrhythmic drugs (hazard ratio, 0.73; 95% CI, 0.54-0.99, P = .045). The intervention effect was consistent across all prespecified subgroups. The comparison of secondary outcomes did not demonstrate significant results. Among patients with persistent AF, linear ablation combined with EIVOM in addition to PVI significantly improved freedom from atrial arrhythmias within 12 months compared with PVI alone. ClinicalTrials.gov Identifier: NCT04497376.

Bioelectronic block of stellate ganglia mitigates pacing-induced heterogeneous release of catecholamine and neuropeptide Y in the infarcted pig heart.

The sympathetic nervous system modulates cardiac contractile and electrophysiological function and contributes to adverse remodelling following myocardial infarction (MI). Axonal modulation therapy (AMT), directed at the sympathetic chain, blocks efferent sympathetic outflow to the heart and is a strategy to transiently and controllably mitigate chronic MI-associated sympatho-excitation. In porcine models, we evaluated scalable AMT, directed at the paravertebral chain, in blocking reflex-mediated pacing-induced sympatho-excitation post-MI. The level of sympatho-excitation was assessed by dynamic interstitial measurement of noradrenaline (NA) and neuropeptide Y (NPY). In anaesthetized normal (n=5) and age-matched pigs 6weeks post-MI induction (n=10), we electrically stimulated the right sympathetic chain and determined levels of direct current block applied at the T1-T2 level sufficient to reduce the evoked changes in heart rate and/or contractility by 25-75%. Reflex-mediated neural release of NA and NPY into the interstitial space during programmed pacing (PP) was assessed using fast-scanning cyclic voltammetry and capacitive immunoprobes. Normal animals demonstrated homogeneous NA and NPY release profiles during PP. In contrast, for MI animals PP evoked differential NA and NPY release in remote and MI border zones of the left ventricle. Right-sided AMT mitigated NA and NPY pacing-induced release in the remote left ventricle with a positive correlation to increasing AMT levels. Pacing-induced NA and NPY release in the MI border zone was not mitigated by AMT. Differential effects of AMT on NA and NPY may underlie the anti-arrhythmic effects of partial stellate ganglion block in the setting of chronic MI. KEY POINTS: Programmed cardiac pacing evokes homogeneous noradrenaline (NA) and neuropeptide Y (NPY) release in equivalent areas (e.g. medial and lateral aspects) of the normal left ventricle. Programmed cardiac pacing evokes differential NA and NPY release in remote and border zones of the infarcted left ventricle. Axonal modulation therapy (AMT), using a graded direct current block applied to the stellate ganglia, can proportionally modulate cardiac sympathetic reflexes. Unilateral AMT mitigates NA and NPY release in remote left ventricular tissue, with release negativelycorrelated to increasing AMT levels. Heterogeneities in NA and NPY between the border and remote tissues are reduced by progressive AMT.