Management of Rapid Atrial Fibrillation Using Stellate Ganglion Blockade.

Background: Stellate ganglion blockade has been demonstrated as an efficacious treatment for refractory ventricular tachyarrhythmias. There are no published reports of the use of this technique in management of rapid atrial arrhythmia. Case Summary: A 73-year-old woman presented to our institution in rapid atrial fibrillation and cardiogenic shock. She was intubated for airway protection and underwent successful electrical cardioversion. However, atrial fibrillation returned multiple times with weaning of sedation for extubation. Stellate ganglion infusion catheter was placed with infusion of ropivacaine and subsequent maintenance of sinus rhythm, with successful extubation, ablation of atrial fibrillation, improvement of left ventricular ejection fraction, and discharge. Take-Home Message: For selected patients, stellate ganglion blockade can be used as a technique to aid in the management of rapid atrial fibrillation.

Best practices in robotic magnetic navigation-guided catheter ablation of cardiac arrhythmias, a position paper of the Society for Cardiac Robotic Navigation.

Preamble: Robotic magnetic navigation (RMN)-guided catheter ablation (CA) technology has been used for the treatment of cardiac arrhythmias for almost 20 years. Various studies reported that RMN allows for high catheter stability, improved lesion formation and a superior safety profile. So far, no guidelines or recommendations on RMN-guided CA have been published. Purpose: The aim of this consensus paper was to summarize knowledge and provide recommendations on management of arrhythmias using RMN-guided CA as treatment of atrial fibrillation (AF) and ventricular arrhythmias (VA). Methodology: An expert writing group, performed a detailed review of available literature, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Recommendations on RMN-guided CA are presented in a guideline format with three levels of recommendations to serve as a reference for best practices in RMN procedures. Each recommendation is accompanied by supportive text and references. The various sections cover the practical spectrum from system and patient set-up, EP laboratory staffing, combination of RMN with fluoroscopy and mapping systems, use of automation features and ablation settings and targets, for different cardiac arrhythmias. Conclusion: This manuscript, presenting the combined experience of expert robotic users and knowledge from the available literature, offers a unique resource for providers interested in the use of RMN in the treatment of cardiac arrhythmias.

Sex Disparities in the Management, Outcomes, and Transfer of Patients Hospitalized for Cardiogenic Shock.

Background: Previous studies have shown that women have worse outcomes for cardiogenic shock (CS) than men. Patients who receive care in CS "hubs" have also been shown to have improved outcomes when compared to those treated at "spokes." This study aimed to examine the presence of sex disparities in the outcomes of CS in relation to hospital type. Methods: Hospitalizations of adults with a diagnosis of CS were identified using data from the 2016-2019 Nationwide Readmissions Database. CS "hubs" were defined as any centers receiving at least 1 interhospital transfer with CS, while those without such transfers were classified as "spokes." Data were combined across years and multivariable logistic regression modeling was used to evaluate the association of sex with in-hospital mortality, invasive procedures, and transfer to hubs. Results: There were a total of 618,411 CS hospitalizations (62.2% men) with CS related to acute myocardial infarction comprising 15.3 to 17.3% of women hospitalizations and 17.8 to 20.3% of men hospitalizations. In-hospital mortality was lower at hubs (34.5% for direct admissions, 31.6% for transfers) than at spokes (40.3%, all P < .01). Women underwent fewer invasive procedures (right heart catheterization, percutaneous coronary intervention, mechanical circulatory support) and had higher mortality than men. Female sex was independently associated with decreased transfers to hubs (odds ratio, 0.93; 95% CI, 0.89-0.96) and increased mortality (odds ratio, 1.09; 95% CI, 1.05-1.12). Conclusions: Women with CS were less likely to be treated at a hub or transferred to a hub, had higher in-hospital mortality, and had a lower likelihood of receiving CS-related procedures than men. Further research is needed to understand sex-specific gaps in CS outcomes.

Association between COVID-19 vaccination and atrial arrhythmias in individuals with cardiac implantable electronic devices.

INTRODUCTION: The impact of mRNA-based coronavirus disease-2019 (COVID-19) vaccines on atrial arrhythmias (AA) and ventricular arrhythmias incidence is unknown. METHODS: BIOTRONIK Home Monitoring data and Medicare Claims data were utilized to identify individuals implanted with a cardiac implantable electronic device (CIED) between 2010 and 2020 who received one or more doses of COVID-19 vaccine in 2021. The burden of AA (%) in the 3 months postvaccination was compared to those noted in the preceding 3 months using the Wilcoxon signed rank test. Sub-analyses comparing the effects of the influenza vaccine against the COVID-19 vaccine were also evaluated for individuals who received the influenza vaccine in 2020. A 1:1 propensity score match comparison between COVID-19 vaccine and non-vaccinated patients was also performed. RESULTS: First and second doses of the COVID-19 vaccine were administered to 7757 and 6579 individuals with a CIED (age 76.2 ± 9.0 years, 49% males), respectively. While a small but statistically significant increase in the burden of AA was noted in the 3 months postvaccination compared to the preceding 3 months after the first dose of the COVID-19 vaccine (0.43 ± 9.04%, p = .028) a similar rise in AA was found following the influenza vaccine and for matched patients who did not receive the COVID-19 vaccine. No significant difference in device therapies was seen pre- and postvaccination. CONCLUSIONS: Though we report a small but significant increase in the number of CIED-detected AAs following vaccination for COVID-19 over a 3-month window, we believe these results correlate more with time and the progressive nature of AF rather than the vaccine itself. While these data should not dissuade from the use of these vaccines, increased vigilance and prompt treatment of AF is required for high-risk groups, specifically males over 70 years of age, following vaccination.

Electrophysiologic and cardiovascular manifestations of Duchenne and Becker muscular dystrophies.

There have been significant advances in the diagnosis and management of the hereditary muscular disorders Duchenne and Becker muscular dystrophy (DMD and BMD). Cardiac electrophysiologic and cardiovascular involvement has long been important in the surveillance, care, and prognosis of patients with both BMD and DMD and is the leading cause of mortality in patients with DMD. With improved long-term prognosis, rhythm disorders and progressive cardiomyopathy with resultant heart failure are increasingly common. This review aimed to provide an overview to electrophysiologists and cardiologists of the cardiac electrophysiologic phenotypes and genetics of BMD and DMD and to highlight the recent discoveries that have advanced clinical course and management. A systematic review was performed of the diagnosis and management of DMD and BMD. The Cochrane Library, PubMed, MEDLINE, Europe PubMed Central, AMED, and Embase databases were accessed for available evidence. The research reported in this paper adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Evidence from randomized controlled trials and studies cited in expert consensus and practice guidelines are examined. Advanced imaging techniques and a spectrum of rhythm disorders associated with the progressive cardiomyopathy are presented. Early initiation of heart failure therapies, the role of cardiac implantable devices, and novel gene therapies approved for use with the potential to alter the disease course are discussed. When profound cardiac and cardiac electrophysiologic involvement is diagnosed and treated earlier, outcomes for DMD and BMD patients may be improved.

Predictors of Shock-Reduction Programming and Its Impact on Implantable Cardioverter-Defibrillator Therapies and Mortality: The CERTITUDE Registry.

BACKGROUND: Shock-reduction implantable cardioverter-defibrillator programming (SRP) was associated with fewer therapies and improved survival in randomized controlled trials, but real-world studies investigating SRP and associated outcomes are limited. METHODS AND RESULTS: The BIOTRONIK CERTITUDE registry was linked with the Medicare database. We included all patients with an implantable cardioverter-defibrillator implanted between August 22, 2012 and September 30, 2021 in the United States. SRP was defined as programming to either a therapy rate cutoff ≥188 beats per minute or number of intervals to detection ≥30/40 for treatment. Among 6781 patients (mean 74±9 years; 27% women), 3393 (50%) had SRP. Older age, secondary prevention indication, and device implantation in the southern or western United States were associated with lower use of SRP. The cumulative incidence rate of implantable cardioverter-defibrillator shocks was lower in the SRP group (5.1% shocks/patient year) compared with the non-SRP group (7.2% shocks/patient year) (adjusted hazard ratio [HR], 0.83 [95% CI, 0.73-0.96]; P=0.005). Over a median follow-up of 2.9 years, 739 deaths occurred in the SRP group and 822 deaths occurred in the non-SRP group (adjusted HR, 0.97 [95% CI, 0.88-1.07]; P=0.569). SRP was associated with a lower all-cause mortality among patients without ischemic heart disease compared with patients with ischemic heart disease (adjusted HR, 0.64 [95% CI, 0.48-0.87] versus adjusted HR, 1.02 [95% CI, 0.92-1.14]; Pinteraction=0.004). CONCLUSIONS: Adoption of SRP is low in real-world clinical practice. Age, clinical variables, and geographic factors are associated with use of SRP. In this study, SRP-associated decrease in mortality was limited to patients without ischemic heart disease.

Management of anesthesia for procedures in the cardiac electrophysiology laboratory.

The complexity of cardiac electrophysiology procedures has increased significantly during the past 3 decades. Anesthesia requirements of these procedures can differ on the basis of patient- and procedure-specific factors. This manuscript outlines various anesthesia strategies for cardiac implantable electronic devices and electrophysiology procedures, including preprocedural, procedural, and postprocedural management. A team-based approach with collaboration between cardiac electrophysiologists and anesthesiologists is required with careful preprocedural and intraprocedural planning. Given the recent advances in electrophysiology, there is a need for specialized cardiac electrophysiology anesthesia care to improve the efficacy and safety of the procedures.

Contemporary Management of Cardiac Implantable Electronic Device Infection: The American College of Cardiology COGNITO Survey.

Background: Cardiac implantable electronic devices (CIEDs) infection remains a serious complication, causing increased morbidity and mortality. Early recognition and escalation to definitive therapy including extraction of the infected device often pose challenges. Objectives: The purpose of this study was to assess U.S.-based physicians current practices in diagnosing and managing CIED infections and explore potential extraction barriers. Methods: An observational survey was performed by the American College of Cardiology including U.S. physicians managing CIEDs from February to March 2022. Sampling techniques and screener questions determined eligibility. The survey featured questions on knowledge and experience with CIED infection patients and case scenarios. Results: Of 387 physicians completing the survey (20% response rate), 49% indicated familiarity with current guidelines regarding CIED infection. Electrophysiologists (EPs) (91%) were more familiar with these guidelines, compared to non-EP cardiologists (29%) and primary care physicians (23%). Only 30% of physicians specified that their institution had guideline-based protocols in place for managing patients with CIED infection. When presented with pocket infection cases, approximately 89% of EPs and 50% of non-EP cardiologists would follow guideline recommendation to do complete CIED system removal, while 70% of primary care physicians did not recommend guideline-directed treatment. Conclusions: There are gaps in familiarity of guidelines as well as the knowledge in practical management of CIED infection with non-extracting physicians. Most institutions lack a definite pathway. Addressing discrepancies, including guideline education and streamlining care or referral pathways, will be a key factor to bridging the gap and improving CIED infection patient outcomes.

Rates of pulmonary vein reconnection at repeat ablation for recurrent atrial fibrillation and its impact on outcomes among females and males.

BACKGROUND: Several studies have demonstrated that females have a higher risk of arrhythmia recurrence after pulmonary vein (PV) isolation for atrial fibrillation (AF). There are limited data on sex-based differences in PV reconnection rates at repeat ablation. We aimed to investigate sex-based differences in electrophysiological findings and atrial arrhythmia recurrence after repeat AF ablation METHODS: We conducted a retrospective study of 161 consecutive patients (32% female, age 65 ± 10 years) who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Demographics, procedural characteristics and follow-up data were collected. Recurrent atrial tachycardia (AT)/AF was defined as any atrial arrhythmia ≥30 s in duration. RESULTS: Compared to males, females tended to be older and had a significantly higher prevalence of prior valve surgery (10 vs. 2%; P = .03). At repeat ablation, PV reconnection was found in 119 (74%) patients. Males were more likely to have PV reconnection at repeat ablation compared to females (81 vs. 59%; P = .004). Excluding repeat PV isolation, there were no significant differences in adjunctive ablation strategies performed at repeat ablation between females and males. During follow-up, there were no significant differences in freedom from AT/AF recurrence between females and males after repeat ablation (63 vs. 59% at 2 years, respectively; P = .48). CONCLUSIONS: After initial PV isolation, significantly fewer females have evidence of PV reconnection at the time of repeat ablation for recurrent AF. Despite this difference, long-term freedom from AT/AF was similar between females and males after repeat ablation.

Impact of Advanced Therapy Centers on Characteristics and Outcomes of Heart Failure Admissions.

BACKGROUND: Although much attention has been paid to admission and transfer patterns for cardiogenic shock, contemporary data are lacking on decompensated heart failure (HF) admissions and transfers and the impact of advanced therapy centers (ATCs) on outcomes. METHODS: HF hospitalizations were obtained from the Nationwide Readmissions Database 2016 to 2019. Centers performing at least 1 heart transplant or left ventricular assist device were classified as ATCs. Patient characteristics, outcomes, and procedural volume were compared among 3 cohorts: admissions to non-ATCs, admissions to ATCs, and transfers to ATCs. A secondary analysis evaluated outcomes for severe HF hospitalizations (cardiogenic shock, cardiac arrest, and mechanical ventilation). Multivariable logistic regression was performed to adjust for the presence of HF decompensations and significant clinical variables during univariate analysis. RESULTS: A total of 2 331 690 hospitalizations (81.2%) were admissions to non-ATCs (94.5% of centers), 525 037 (18.3%) were admissions to ATCs (5.5% of centers), and 15 541 (0.5%) were transferred to ATCs. Patients treated at ATCs (especially those transferred) had higher rates of HF decompensations, procedural frequency, lengths of stay, and costs. Unadjusted mortality was 2.6% at non-ATCs and was higher at ATCs, both for directly admitted (2.9%, P<0.001) and transferred (11.2%, P<0.001) patients. However, multivariable-adjusted mortality was significantly lower at ATCs, both for directly admitted (odds ratio, 0.82 [95% CI, 0.78-0.87]; P<0.001) and transferred (odds ratio, 0.66 [95% CI, 0.57-0.78]; P<0.001) patients. For severe HF admissions, unadjusted mortality was 37.2% at non-ATCs and was lower at ATCs, both for directly admitted (25.3%, P<0.001) and transferred (25.2%, P<0.001) patients, with similarly lower multivariable-adjusted mortality. CONCLUSIONS: Patients with HF treated at ATCs were sicker but associated with higher procedural volume and lower adjusted mortality.

Implantable cardiac monitors: artificial intelligence and signal processing reduce remote ECG review workload and preserve arrhythmia detection sensitivity.

Introduction: Implantable cardiac monitors (ICMs) provide long-term arrhythmia monitoring, but high rates of false detections increase the review burden. The new "SmartECG" algorithm filters false detections. Using large real-world data sets, we aimed to quantify the reduction in workload and any loss in sensitivity from this new algorithm. Methods: Patients with a BioMonitor IIIm and any device indication were included from three clinical projects. All subcutaneous ECGs (sECGs) transmitted via remote monitoring were classified by the algorithm as "true" or "false." We quantified the relative reduction in workload assuming "false" sECGs were ignored. The remote monitoring workload from five hospitals with established remote monitoring routines was evaluated. Loss in sensitivity was estimated by testing a sample of 2000 sECGs against a clinical board of three physicians. Results: Of our population of 368 patients, 42% had an indication for syncope or pre-syncope and 31% for cryptogenic stroke. Within 418.5 patient-years of follow-up, 143,096 remote monitoring transmissions contained 61,517 sECGs. SmartECG filtered 42.8% of all sECGs as "false," reducing the number per patient-year from 147 to 84. In five hospitals, nine trained reviewers inspected on average 105 sECGs per working hour. This results in an annual working time per patient of 83 min without SmartECG, and 48 min with SmartECG. The loss of sensitivity is estimated as 2.6%. In the majority of cases where true arrhythmias were rejected, SmartECG classified the same type of arrhythmia as "true" before or within 3 days of the falsely rejected sECG. Conclusion: SmartECG increases efficiency in long-term arrhythmia monitoring using ICMs. The reduction of workload by SmartECG is meaningful and the risk of missing a relevant arrhythmia due to incorrect filtering by the algorithm is limited.

Antithrombotic Therapy for Patients Undergoing Cardiac Electrophysiological and Interventional Procedures: JACC State-of-the-Art Review.

Electrophysiological and interventional procedures have been increasingly used to reduce morbidity and mortality in patients experiencing cardiovascular diseases. Although antithrombotic therapies are critical to reduce the risk of stroke or other thromboembolic events, they can nonetheless increase the bleeding hazard. This is even more true in an aging population undergoing cardiac procedures in which the combination of oral anticoagulants and antiplatelet therapies would further increase the hemorrhagic risk. Hence, the timing, dose, and combination of antithrombotic therapies should be carefully chosen in each case. However, the maze of society guidelines and consensus documents published so far have progressively led to a hazier scenario in this setting. Aim of this review is to provide-in a single document-a quick, evidenced-based practical summary of the antithrombotic approaches used in different cardiac electrophysiology and interventional procedures to guide the busy clinician and the cardiac proceduralist in their everyday practice.

Impella Versus Intra-Aortic Balloon Pump in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: An Observational Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with cardiogenic shock. Although Impella or intra-aortic balloon pump (IABP) is frequently used for left ventricular unloading (LVU) during VA-ECMO treatment, there are limited data on comparative outcomes. We compared outcomes of Impella and IABP for LVU during VA-ECMO. METHODS AND RESULTS: Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes in 3 groups of patients with cardiogenic shock requiring VA-ECMO based on LVU strategies: extracorporeal membrane oxygenation (ECMO) only, ECMO with IABP, and ECMO with Impella. Of 15 980 patients on VA-ECMO, IABP and Impella were used in 19.4% and 16.4%, respectively. The proportion of patients receiving Impella significantly increased from 2016 to 2020 (6.5% versus 25.8%; P-trend<0.001). In-hospital mortality was higher with ECMO with Impella (54.8%) compared with ECMO only (50.4%) and ECMO with IABP (48.4%). After adjustment, ECMO with IABP versus ECMO only was associated with lower in-hospital mortality (adjusted odds ratio [aOR], 0.83; P=0.02). ECMO with Impella versus ECMO only had similar in-hospital mortality (aOR, 1.09; P=0.695) but was associated with more bleeding (aOR, 1.21; P=0.007) and more acute kidney injury requiring hemodialysis (aOR, 1.42; P<0.001). ECMO with Impella versus ECMO with IABP was associated with greater risk of acute kidney injury requiring hemodialysis (aOR, 1.49; P=0.002), higher in-hospital mortality (aOR, 1.32; P=0.001), and higher 40-day mortality (hazard ratio, 1.25; P<0.001). CONCLUSIONS: In patients with cardiogenic shock on VA-ECMO, LVU with Impella, particularly with 2.5/CP, was not associated with improved survival at 40 days but was associated with increased adverse events compared with IABP. More data are needed to assess Impella platform-specific comparative outcomes of LVU.

Localized Re-Entry Is a Frequent Mechanism of De Novo Atypical Flutter.

BACKGROUND: Limited data exist about the origins and mechanisms of atypical atrial flutter that occurs in the absence of prior ablation or surgery. OBJECTIVES: The aims of this study were to report a large cohort of patients who presented for catheter ablation of de novo atypical flutters, to identify the most common locations and mechanisms of arrhythmia, and to describe outcomes after ablation. METHODS: Demographic, electrophysiological, and outcome data were collected for patients who underwent ablation of de novo atypical flutter. RESULTS: The mechanisms of 85 atypical flutters were identified in 62 patients and localized to the left atrium (LA) in 58 and right atrium (RA) in 27. In the LA, mechanisms were classified as macro-re-entry in 29 (50%) and localized re-entry in 29 (50%), whereas in the RA, mechanisms were macro-re-entry in 8 (30%) and localized re-entry in 19 (70%) (proportion of localized re-entry in the LA vs. RA, P = 0.08). Nine patients had both localized and macro-re-entrant atypical flutters. In the LA, localized re-entry was commonly found in the anterior LA, followed by the pulmonary veins and septum. In the RA, localized re-entry was found at various sites, including the lateral or posterior RA, septum, and coronary sinus ostium. During 39.4 months (Q1-Q3: 18.2-65.8 months) of follow-up, atrial arrhythmias occurred in 66% of patients after a single ablation and in 50% after >1 ablation. Among patients who underwent repeat ablation, compared with the index arrhythmia, different tachycardia circuits or arrhythmias were documented in 13 of 18 cases (72%). CONCLUSIONS: Atypical atrial flutters in patients without prior surgery or complex ablation are often due to localized re-entry (approximately 50% in the LA and a higher frequency in the RA). Other atrial tachycardias commonly occur during long-term follow-up following ablation, suggesting progressive atrial myopathy in these patients.

Ventricular Tachycardia Due to Triggered Activity: Role of Early and Delayed Afterdepolarizations.

Most forms of sustained ventricular tachycardia (VT) are caused by re-entry, resulting from altered myocardial conduction and refractoriness secondary to underlying structural heart disease. In contrast, VT caused by triggered activity (TA) is unrelated to an abnormal structural substrate and is often caused by molecular defects affecting ion channel function or regulation of intracellular calcium cycling. This review summarizes the cellular and molecular bases underlying TA and exemplifies their clinical relevance with selective representative scenarios. The underlying basis of TA caused by delayed afterdepolarizations is related to sarcoplasmic reticulum calcium overload, calcium waves, and diastolic sarcoplasmic reticulum calcium leak. Clinical examples of TA caused by delayed afterdepolarizations include sustained right and left ventricular outflow tract tachycardia and catecholaminergic polymorphic VT. The other form of afterpotentials, early afterdepolarizations, are systolic events and inscribe early afterdepolarizations during phase 2 or phase 3 of the action potential. The fundamental defect is a decrease in repolarization reserve with associated increases in late plateau inward currents. Malignant ventricular arrhythmias in the long QT syndromes are initiated by early afterdepolarization-mediated TA. An understanding of the molecular and cellular bases of these arrhythmias has resulted in generally effective pharmacologic-based therapies, but these are nonspecific agents that have off-target effects. Therapeutic efficacy may need to be augmented with an implantable defibrillator. Next-generation therapies will include novel agents that rescue arrhythmogenic abnormalities in cellular signaling pathways and gene therapy approaches that transfer or edit pathogenic gene variants or silence mutant messenger ribonucleic acid.

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.