Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.

BACKGROUND: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). METHODS: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 µmol/L. RESULTS: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. CONCLUSIONS: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.

Smartwatch detection of new-onset monomorphic ventricular tachycardia in pregnancy.

Smartwatches provide health tracking in various ways and there has been a recent rise in reporting cardiac arrhythmias. While original studies focused on atrial fibrillation, fewer reports have been made on other arrhythmias especially in pregnancy. We report a pregnant patient who presented at 34 weeks' gestation with palpitations. An ECG recorded through her Apple Watch showed ventricular tachycardia. Hospital ECG confirmed monomorphic ventricular tachycardia likely caused by increased sympathetic tone from the gravid state. She was admitted to the cardiac intensive care unit for close monitoring with intravenous anti-arrhythmic agents; however, the rhythm persisted. She underwent a caesarean delivery and the arrhythmia resolved post partum. She later underwent a catheter ablation, after which she discontinued all anti-arrhythmic medications with no recurrence. This case highlights the importance of requesting relevant digital health information, if available, from patients in our modern era. Controlled clinical studies are needed to validate such practices.

Insights into adherence to medication and lifestyle recommendations in an international cohort of patients with catecholaminergic polymorphic ventricular tachycardia.

AIMS: In patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), a rare inherited arrhythmia syndrome, arrhythmic events can be prevented by medication and lifestyle recommendations. In patients who experience breakthrough arrhythmic events, non-adherence plays an essential role. We aimed to investigate the incidence and potential reasons for non-adherence to medication and lifestyle recommendations in a large, international cohort of patients with CPVT. METHODS AND RESULTS: An online multilingual survey was shared with CPVT patients worldwide by their cardiologists, through peer-recruitment, and on social media from November 2022 until July 2023. Self-reported non-adherence was measured using the validated Medication Adherence Rating Scale (MARS) and a newly developed questionnaire about lifestyle. Additionally, validated questionnaires were used to assess potential reasons for medication non-adherence. Two-hundred-and-eighteen patients completed the survey, of whom 200 (92%) were prescribed medication [122 (61%) female; median age 33.5 years (interquartile range: 22-50)]. One-hundred-and-three (52%) were prescribed beta-blocker and flecainide, 85 (43%) beta-blocker, and 11 (6%) flecainide. Thirty-four (17%) patients experienced a syncope, aborted cardiac arrest or appropriate implantable cardioverter defibrillator shock after diagnosis. Nineteen (13.4%) patients were exercising more than recommended. Thirty (15%) patients were non-adherent to medication. Female sex [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.3-12.0, P = 0.019], flecainide monotherapy compared to combination therapy (OR 6.8, 95% CI 1.6-31.0, P = 0.010), and a higher agreement with statements regarding concerns about CPVT medication (OR 1.2, 95% CI 1.1-1.3, P < 0.001) were independently associated with non-adherence. CONCLUSION: The significant rate of non-adherence associated with concerns regarding CPVT-related medication, emphasizes the potential for improving therapy adherence by targeted patient education.

Combined modified Valsalva maneuver with adenosine supraventricular tachycardia: A comparative study.

BACKGROUND AND IMPORTANCE: Paroxysmal supraventricular tachycardia (PSVT) is an arrhythmia commonly seen in the emergency department. Both modified Valsalva maneuver (MVM) and intravenous adenosine are the first line treatment, of which the former has e lower success rate while the latter has a higher success rate but some risks and adverse effects. Given both of these reverse rhythms quickly, combining them may achieve a better effect. OBJECTIVE: The objective of this study is to evaluate the success rate and potential risk of combining the use of intravenous adenosine while patients were doing MVM as a treatment for paroxysmal supraventricular tachycardia(pSVT). DESIGN, SETTINGS AND PARTICIPANTS: We recruited patients with pSVT from 2017 to 2022, and randomly assigned them into 3 groups, MVM group, intravenous adenosine group, and combination therapy group, in which MVM was allowed to be performed twice, while intravenous adenosine was given in a titration manner to repeat three times, recorded the success rate and side effects in each group. MAIN RESULTS: The success rate of the MVM group, adenosine group, and combination group are 42.11%, 75.00 and 86.11%, respectively. The success rate of the adenosine group and combination group is significantly higher than the n MVSM group (p < 0.01, p < 0.001), while the success rate of the combination group is higher than the adenosine group, it has no significant difference (p = 0.340). In terms of safety, the longest RR durations (asystole period) are 1.61 s, 1.60s, and 2.27 s, there is a statistical difference among the three groups (p < 0.01) and between the adenosine and combination group (0.018). CONCLUSION: Therefore, we can conclude that combination therapy has a relatively high success rate and good safety profile, but the current study failed to show its superiority to adenosine.

Bloqueo del ganglio estrellado como tratamiento de la tormenta arrítmica: estudio observacional / Stellate ganglion block as a treatment for arrhythmic storm: an observational study

Introducción: La tormenta arrítmica (TA) es una situación de emergencia potencialmente letal, con una elevada tasa de mortalidad. Cuando el tratamiento convencional agudo es inefectivo, el bloqueo del ganglio estrellado puede ayudar a controlar la arritmia, aportando un bloqueo simpático cervicotorácico visceral. El objetivo de este estudio es valorar la efectividad y seguridad de los bloqueos del ganglio estrellado (BGE) para el tratamiento de la TA refractaria. Método: Seguimiento de una cohorte de pacientes con TA refractaria que cumplieron los criterios para la realización de BGE. Dicho bloqueo fue ecoguiado al nivel de C6, utilizando un anestésico y un esteroide, de manera unilateral izquierda en primer lugar, y bilateral de no existir respuesta, realizándose posteriormente ablación mediante radiofrecuencia (RFC) guiada por fluoroscopio en C7 de no existir respuesta favorable, sino recidiva subsiguiente. Resultados: Se incluyeron siete pacientes, con una tasa de mortalidad durante el ingreso de 14,29%. Cuatro pacientes recibieron bloqueos unilaterales del ganglio estrellado, y en tres pacientes se realizaron bloqueos bilaterales. En seis de ellos se aplicó ablación, y uno de ellos tenía implantado un cardioversor-desfibrilador. La TA fue controlada temporalmente, más allá del efecto del anestésico local en todos los pacientes. Tres de ellos recibieron ablación por RFC, y dos simpatectomías torácicas quirúrgicas. El único efecto secundario fue el síndrome de Horner, que se observó en todos los casos tras realizar el bloqueo del ganglio estrellado con anestésico local. Dos pacientes murieron tras recibir el alta, y cuatro siguen en sus casas, tres de ellos sin haber sido ingresados a causa de episodios ventriculares durante más de dos años. Conclusión: El bloqueo ecoguiado del ganglio estrellado es una técnica efectiva y segura para el tratamiento de la TA refractaria, como complemento del tratamiento cardiológico habitual.(AU)

Introduction: Arrhythmic storm is a life-threatening emergency with a high mortality rate. When acute conventional treatment is ineffective, a stellate ganglion block can contribute to the control of the arrhythmia by providing a visceral cervicothoracic sympathetic block. The objective of the study is to assess the effectiveness and safety of stellate ganglion blocks for the treatment of refractory arrhythmic storm. Method: Follow-up of a cohort of patients with refractory arrhythmic storm that met the criteria for performing stellate ganglion blocks. The block was ultrasound-guided at C6-level using local anaesthetic and a steroid, left unilateral first, bilateral if no response, and followed by fluoroscopy-guided radiofrequency ablation at C7 if there was a favourable response but subsequent relapse. Results: Seven patients were included, with a mortality rate during admission of 14.29%. Four patients received unilateral and three bilateral stellate ganglion blocks. Six were ablated and one of them had an implanted cardioverter-defibrillator. Arrhythmic storm was controlled temporarily beyond the effect of the local anaesthetic in all patients. Three underwent radiofrequency ablation and two underwent surgical thoracic sympathectomy. The only side effect was Horner's syndrome, which was observed in all cases after administering a stellate ganglion block with local anaesthetic. Two died after discharge and four are still at home, three of them without further admission due to ventricular events for more than two years. Conclusion: An ultrasound-guided stellate ganglion block is an effective and safe technique in the treatment of refractory arrhythmic storm as a complement to the usual cardiological treatment.(AU)

Clinical and genetic profiles of chinese pediatric patients with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUNDS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China. AIMS AND METHODS: We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT. RESULTS: A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations. CONCLUSION: Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation.

Use of mexiletine in therapy-refractory recurrent ventricular tachycardia storm.

Electrical storm due to recurrent ventricular tachycardias (VTs) is a life-threatening arrhythmic emergency. The authors present a case report of a 69-year-old male patient with VT storm of non-ischemic etiology. Despite optimal medical treatment escalated by amiodarone antiarrhythmic drug therapy, the patient experienced multiple implantable cardioverter defibrillator (ICD) shocks. An electrophysiological study revealed an epicardial substrate; however, considering the patient's extreme obesity and active anticoagulant effect, catheter ablation was deemed to be unfeasible. Subsequently, mexiletine was added to the patient's drug regimen, resulting in successful control of arrhythmias during the following 6 months. Although the most recent European guidelines for the management of patients with ventricular arrhythmias mention mexiletine only for the treatment of LQT3 patients, its use for treatment-refractory VT storm seems to also be an important indication area.

Effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction.

BACKGROUND/INTRODUCTION: Heart failure patients with reduced ejection fraction are at high risk for ventricular arrhythmias and sudden cardiac death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, provides heart rate reduction in sinus rhythm and angina control in chronic coronary syndromes. OBJECTIVE: The effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction patients has not been fully elucidated. The aim of this study was to investigate the effect of ivabradine use on life-threatening arrhythmias and long-term mortality in heart failure patients with reduced ejection fraction patients. METHODS: In this retrospective study, 1,639 patients with heart failure patients with reduced ejection fraction were included. Patients were divided into two groups: ivabradine users and nonusers. Patients presenting with ventricular tachycardia, the presence of ventricular extrasystole, and ventricular tachycardia in 24-h rhythm monitoring, appropriate implantable cardioverter-defibrillator shocks, and long-term mortality outcomes were evaluated according to ivabradine use. RESULTS: After adjustment for all possible variables, admission with ventricular tachycardia was three times higher in ivabradine nonusers (95% confidence interval 1.5-10.2). The presence of premature ventricular contractions and ventricular tachycardias in 24-h rhythm Holter monitoring was notably higher in ivabradine nonusers. According to the adjusted model for all variables, 4.1 times more appropriate implantable cardioverter-defibrillator shocks were observed in the ivabradine nonusers than the users (95%CI 1.8-9.6). Long-term mortality did not differ between these groups after adjustment for all covariates. CONCLUSION: The use of ivabradine reduced the appropriate implantable cardioverter-defibrillator discharge in heart failure patients with reduced ejection fraction patients. Ivabradine has potential in the treatment of ventricular arrhythmias in heart failure patients with reduced ejection fraction patients.

Insights on the mechanism of flecainide in catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by defective cardiac ryanodine receptor (RyR2) calcium release during times of adrenergic stimulation, resulting in bidirectional or polymorphic ventricular tachycardia. Flecainide is a class 1c anti-arrhythmic drug that has demonstrated therapeutic efficacy in treating CPVT. However, its mechanism of action remains disputed. One group proposes a direct effect of flecainide on RyR2-mediated calcium release, while another proposes an indirect effect via sodium channel blockade and modulation of intracellular calcium dynamics. In light of recent studies, this commentary aims to explore and discuss the evidence base for these potential mechanisms.

Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

Ventricular tachycardia and acute heart failure induced by atropine in the treatment of bradycardia: A case report and literature review.

RATIONALE: Despite various advantages of laparoscopic surgical procedures, artificial pneumoperitoneum might lead to hemodynamic fluctuations including severe bradycardia and cardiac arrest. Atropine is usually proposed to treat intraoperative severe bradycardia ( < 40 beats per minute). However, atropine could induce ventricular arrhythmias, which might be life-threatening in severe case. PATIENT CONCERNS: Here, we reported a 41-year-old female who was diagnosed with gallbladder polyps and was scheduled for laparoscopic cholecystectomy under general anesthesia. DIAGNOSES: Bradycardia occurred suddenly during the operation and atropine was injected intravenously. Eventually the patient developed ventricular tachycardia and acute heart failure. INTERVENTIONS: We organized an urgent consultation and the patient was treated immediately. OUTCOMES: Fortunately, the patient experienced no complications after timely diagnosis and treatment. After 6 months of follow-up, her New York Heart Association classification was I with no complications. LESSONS: This case highlighted that the administration of atropine to treat bradycardia may lead to ventricular tachycardia and acute heart failure, and anesthesiologists should remain vigilant to avoid potentially life-threatening consequences.

Personalized medicine in the dish to prevent calcium leak associated with short-coupled polymorphic ventricular tachycardia in patient-derived cardiomyocytes.

BACKGROUND: Polymorphic ventricular tachycardia (PMVT) is a rare genetic disease associated with structurally normal hearts which in 8% of cases can lead to sudden cardiac death, typically exercise-induced. We previously showed a link between the RyR2-H29D mutation and a clinical phenotype of short-coupled PMVT at rest using patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs). In the present study, we evaluated the effects of clinical and experimental anti-arrhythmic drugs on the intracellular Ca2+ handling, contractile and molecular properties in PMVT hiPSC-CMs in order to model a personalized medicine approach in vitro. METHODS: Previously, a blood sample from a patient carrying the RyR2-H29D mutation was collected and reprogrammed into several clones of RyR2-H29D hiPSCs, and in addition we generated an isogenic control by reverting the RyR2-H29D mutation using CRIPSR/Cas9 technology. Here, we tested 4 drugs with anti-arrhythmic properties: propranolol, verapamil, flecainide, and the Rycal S107. We performed fluorescence confocal microscopy, video-image-based analyses and biochemical analyses to investigate the impact of these drugs on the functional and molecular features of the PMVT RyR2-H29D hiPSC-CMs. RESULTS: The voltage-dependent Ca2+ channel inhibitor verapamil did not prevent the aberrant release of sarcoplasmic reticulum (SR) Ca2+ in the RyR2-H29D hiPSC-CMs, whereas it was prevented by S107, flecainide or propranolol. Cardiac tissue comprised of RyR2-H29D hiPSC-CMs exhibited aberrant contractile properties that were largely prevented by S107, flecainide and propranolol. These 3 drugs also recovered synchronous contraction in RyR2-H29D cardiac tissue, while verapamil did not. At the biochemical level, S107 was the only drug able to restore calstabin2 binding to RyR2 as observed in the isogenic control. CONCLUSIONS: By testing 4 drugs on patient-specific PMVT hiPSC-CMs, we concluded that S107 and flecainide are the most potent molecules in terms of preventing the abnormal SR Ca2+ release and contractile properties in RyR2-H29D hiPSC-CMs, whereas the effect of propranolol is partial, and verapamil appears ineffective. In contrast with the 3 other drugs, S107 was able to prevent a major post-translational modification of RyR2-H29D mutant channels, the loss of calstabin2 binding to RyR2. Using patient-specific hiPSC and CRISPR/Cas9 technologies, we showed that S107 is the most efficient in vitro candidate for treating the short-coupled PMVT at rest.

Termination of paroxysmal supraventricular tachycardia by intranasal swab insertion.

Paroxysmal supraventricular tachycardia (SVT) is a common emergency department presentation. Vagal maneuvers are commonly tried to terminate SVT but are often unsuccessful in terminating the dysrhythmia. The use of adenosine, while often successful, is associated with a number of side effects and is often disliked by patients with recurrent episodes of SVT. We report on a 44-year-old woman with a past medical history of SVT who presented to the emergency department (ED) due to a recurrence of her SVT. The patient had no intravenous access and preferred not to receive adenosine. The patient received intranasal stimulation with a nasopharyngeal swab used for COVID-19 testing for 5-10 s. After less than 10 s, the patient converted to a sinus rhythm. She was successfully discharged from the ED after 1 h of observation and no recurrence of her SVT.

Sacubitril/valsartan effects on arrhythmias and left ventricular remodelling in heart failure: An observational study.

AIMS: Conflicting results have been reported in the literature on the potential antiarrhythmic effect of sacubitril/valsartan in heart failure patients with reduced ejection fraction (HFrEF). The objectives of this study were: 1- to evaluate the long term effects of sacubitril/valsartan on arrhythmic burden in HFrEF patients; 2- to evaluate the correlation between the reduction of premature ventricular complexes during f-up and reverse remodelling. METHODS: We identified 255 consecutive HFrEF patients treated with sacubitril/valsartan between March 2017 and May 2020 and followed by the Heart Failure and Cardiac Transplant Unit of IRCCS San Matteo Hospital in Pavia (Italy). Within this subgroup, 153 patients underwent 24 h-Holter-ECG or implantable cardioverter defibrillators (ICD) interrogation at baseline, at 12 months (t1) and at 24 months (t2) and transthoracic echocardiography at baseline and after 12 months after the beginning of sacubitril/valsartan. Cardiac-related hospitalizations were analyzed in the 12 months preceding and during 24 months following the drug starting date. RESULTS: Global burden of 24-h premature ventricular complexes (PVC) was significantly reduced at 12 months (t1) and at 24 months (t2) as compared to the same period before treatment (1043 [304-3360] vs 768 [82-2784] at t1 vs 114 [9-333] at t2, P = 0.000). In the subgroup of patients implanted with biventricular ICD (n = 30), the percentage of biventricular pacing increased significantly (96% [94-99] vs 98% [96-99] at t1 vs 98%[97-100] at t2; P = 0.027). The burden of non-sustained ventricular tachycardia and sustained ventricular tachycardia did not change from baseline to t1 and t2, but a reduction of patients with at least one ICD appropriate shock was reported. The correlations between reduction in 24 h PVC and reduction in LV-ESVi or improvement in LVEF were not statistically significant (respectively R = 0.144, P = 0.197 and R = -0.190, P = 0.074). Heart failure related hospitalizations decreased during follow up (11.1% in the year before treatment vs 4.6% at t1 and 4.6% at t2; P = 0.040). CONCLUSION: Sacubitril/valsartan reduced the number of premature ventricular complexes and increased the percentage of biventricular pacing in a cohort of HFrEF patients already on optimal medical therapy. PVC reduction did not correlate with reverse left ventricular remodelling. Whether sacubitril/valsartan has any direct antiarrhythmic effects is an issue to be better explored in future studies.

Trans-2,3-enoyl-CoA reductase-like-related catecholaminergic polymorphic ventricular tachycardia with regular ventricular tachycardia and response to flecainide.

INTRODUCTION: We describe a unique case of TECRL-CPVT presented with cardiac arrest. METHODS: Post resuscitation, the patient developed regular ventricular tachycardia featuring a left purkinje system morphology. RESULTS: There was clear suppression of arrhythmia with the addition of flecainide and isolated ventricular ectopy causing secondary T-wave changes. CONCLUSION: A high index of suspicion was required to eventually make the diagnosis through whole exome sequencing.

RyR2 inhibition with dantrolene is antiarrhythmic, prevents further pathological remodeling, and improves cardiac function in chronic ischemic heart disease.

Diastolic Ca2+ leak due to cardiac ryanodine receptor (RyR2) hyperactivity has been widely documented in chronic ischemic heart disease (CIHD) and may contribute to ventricular tachycardia (VT) risk and progressive left-ventricular (LV) remodeling. Here we test the hypothesis that targeting RyR2 hyperactivity can suppress VT inducibility and progressive heart failure in CIHD by the RyR2 inhibitor dantrolene. METHODS AND RESULTS: CIHD was induced in C57BL/6 J mice by left coronary artery ligation. Four weeks later, mice were randomized to either acute or chronic (6 weeks via implanted osmotic pump) treatment with dantrolene or vehicle. VT inducibility was assessed by programmed stimulation in vivo and in isolated hearts. Electrical substrate remodeling was assessed by optical mapping. Ca2+ sparks and spontaneous Ca2+ releases were measured in isolated cardiomyocytes. Cardiac remodeling was quantified by histology and qRT-PCR. Cardiac function and contractility were measured using echocardiography. Compared to vehicle, acute dantrolene treatment reduced VT inducibility. Optical mapping demonstrated reentrant VT prevention by dantrolene, which normalized the shortened refractory period (VERP) and prolonged action potential duration (APD), preventing APD alternans. In single CIHD cardiomyocytes, dantrolene normalized RyR2 hyperactivity and prevented spontaneous intracellular Ca2+ release. Chronic dantrolene treatment not only reduced VT inducibility but also reduced peri-infarct fibrosis and prevented further progression of LV dysfunction in CIHD mice. CONCLUSIONS: RyR2 hyperactivity plays a mechanistic role for VT risk, post-infarct remodeling, and contractile dysfunction in CIHD mice. Our data provide proof of concept for the anti-arrhythmic and anti-remodeling efficacy of dantrolene in CIHD.

Ventricular Tachycardia and ICD Therapy Burden With Catheter Ablation Versus Escalated Antiarrhythmic Drug Therapy.

BACKGROUND: Catheter ablation improves ventricular tachycardia (VT) event-free (time to event) survival in patients with antiarrhythmic drug (AAD)-refractory VT and previous myocardial infarction (MI). The effects of ablation on recurrent VT and implantable cardioverter-defibrillator (ICD) therapy (burden) have yet to be investigated. OBJECTIVES: This study sought to compare the VT and ICD therapy burden following treatment with either ablation or escalated AAD therapy among patients with VT and previous MI in the VANISH (Ventricular tachycardia AblatioN versus escalated antiarrhythmic drug therapy in ISchemic Heart disease) trial. METHODS: The VANISH trial randomized patients with previous MI and VT despite initial AAD therapy to either escalated AAD treatment or catheter ablation. VT burden was defined as the total number of VT events treated with ≥1 appropriate ICD therapy. Appropriate ICD therapy burden was defined as the total number of appropriate shocks or antitachycardia pacing therapies (ATPs) delivered. The Anderson-Gill recurrent event model was used to compare burden between the treatment arms. RESULTS: Of the 259 enrolled patients (median age, 69.8 years; 7.0% women), 132 patients were randomized to ablation and 129 patients were randomized to escalated AAD therapy. Over 23.4 months of follow-up, ablation-treated patients had a 40% lower shock-treated VT event burden and a 39% lower appropriate shock burden compared with patients who received escalated AAD therapy (P <0.05 for all). A reduction in VT burden, ATP-treated VT event burden, and appropriate ATP burden among ablation patients was only demonstrated in the stratum of patients with amiodarone-refractory VT (P <0.05 for all). CONCLUSIONS: Among patients with AAD-refractory VT and a previous MI, catheter ablation reduced shock-treated VT event burden and appropriate shock burden compared with escalated AAD therapy. There was also lower VT burden, ATP-treated VT event burden, and appropriate ATP burden among ablation-treated patients; however, the effect was limited to patients with amiodarone-refractory VT.