Catecholaminergic Polymorphic Ventricular Tachycardia Research Articles

Mitochondrial calcium regulation of cardiac metabolism in health and disease.

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+) in health and disease. In physiological states, Ca2+ enters via the mitochondrial Ca2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca2+ homeostasis is critical: insufficient Ca2+ impairs stress adaptation, while Ca2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca2+ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca2+ regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca2+ exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms, but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na+-Ca2+ exchanger and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca2+ transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca2+ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias.

Management of Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a primary electrical heart disease characterized by the development of polymorphic (including bidirectional) ventricular tachycardia in response to adrenergic stimulation. The leading clinical sign of CPVT is syncope provoked by physical or emotional stress, or adrenergic drugs administration. This disease is characterized by high mortality if not treated. The main treatment approach for CPVT is drug therapy with beta-blockers. Recently, however, there are more and more works stating that beta-blockers have lack of efficacy. Combination therapy with the antiarrhythmic drug of the IC class is one of the approaches before implementing the interventional treatment methods in several patients. Interventional methods include cardioverter defibrillator implantation and left side sympathectomy. This paper presents the modern view on the efficacy, safety, and indications for every management method for patients with CPVT.

Successful resuscitation of catecholaminergic polymorphic ventricular tachycardia: a case report

Successful resuscitation of catecholaminergic polymorphic ventricular tachycardia: a case report

Dexmedetomidine inhibited arrhythmia susceptibility to adrenergic stress in RyR2R2474S mice through regulating the coupling of membrane potential and intracellular calcium

BackgroundDexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, can decrease the incidence of arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the underlying mechanisms by which DEX affects cardiac electrophysiological function remain unclear. MethodsRyanodine receptor (RyR2) heterozygous R2474S mice were used as a model for CPVT. WT and RyR2R2474S/+ mice were treated with isoproterenol (ISO) and DEX, and electrocardiograms were continuously monitored during both in vivo and ex vivo experiments. Dual-dye optical mapping was used to explore the anti-arrhythmic mechanism of DEX. ResultsDEX significantly reduced the occurrence and duration of ISO-induced of VT/VF in RyR2R2474S/+ mice in vivo and ex vivo. DEX remarkably prolonged action potential duration (APD80) and calcium transient duration (CaTD80) in both RyR2R2474S/+ and WT hearts, whereas it reduced APD heterogeneity and CaT alternans in RyR2R2474S/+ hearts. DEX inhibited ectopy and reentry formation, and stabilized voltage-calcium latency. ConclusionDEX exhibited an antiarrhythmic effect through stabilizing membrane voltage and intracellular Ca2+. DEX can be used as a beneficial perioperative anesthetic for patients with CPVT or other tachy-arrhythmias.

Prognosis and clinical management of asymptomatic family members with RYR2-mediated catecholaminergic polymorphic ventricular tachycardia: a review.

Despite its low prevalence, the potential diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) should be at the forefront of a paediatric cardiologists mind in children with syncope during exercise or emotions. Over the years, the number of children with a genetic diagnosis of CPVT due to a (likely) pathogenic RYR2 variant early in life and prior to the onset of symptoms has increased due to cascade screening programmes. Limited guidance for this group of patients is currently available. Therefore, we aimed to summarise currently available literature for asymptomatic patients with a (likely) pathogenic RYR2 variant, particularly the history of CPVT and its genetic architecture, the currently available diagnostic tests and their limitations, and the development of a CPVT phenotype - both electrocardiographically and symptomatic - of affected family members. Their risk of arrhythmic events is presumably low and a phenotype seems to develop in the first two decades of life. Future research should focus on this group in particular, to better understand the development of a phenotype over time, and therefore, to be able to better guide clinical management - including the frequency of diagnostic tests, the timing of the initiation of drug therapy, and lifestyle recommendations.

Discovery and Structure-Activity Relationship of a Ryanodine Receptor 2 Inhibitor.

Ryanodine receptor 2 (RyR2) is a large Ca2+-release channel in the sarcoplasmic reticulum (SR) of cardiac muscle cells. It serves to release Ca2+ from the SR into the cytosol to initiate muscle contraction. RyR2 overactivation is associated with arrhythmogenic cardiac disease, but few specific inhibitors have been reported so far. Here, we identified an RyR2-selective inhibitor 1 from the chemical compound library and synthesized it from glycolic acid. Synthesis of various derivatives to investigate the structure-activity relationship of each substructure afforded another two RyR2-selective inhibitors 6 and 7, among which 6 was the most potent. Notably, compound 6 also inhibited Ca2+ release in cells expressing the RyR2 mutants R2474S, R4497C and K4750Q, which are associated with cardiac arrhythmias such as catecholaminergic polymorphic ventricular tachycardia (CPVT). This inhibitor is expected to be a useful tool for research on the structure and dynamics of RyR2, as well as a lead compound for the development of drug candidates to treat RyR2-related cardiac disease.

Catheter Ablation for Channelopathies: When Is Less More?

Ventricular fibrillation (VF) is a common cause of sudden cardiac death in patients with channelopathies, particularly in the young population. Although pharmacological treatment, cardiac sympathectomy, and implantable cardioverter defibrillators (ICD) have been the mainstay in the management of VF in patients with channelopathies, they are associated with significant adverse effects and complications, leading to poor quality of life. Given these drawbacks, catheter ablation has been proposed as a therapeutic option for patients with channelopathies. Advances in imaging techniques and modern mapping technologies have enabled increased precision in identifying arrhythmia triggers and substrate modification. This has aided our understanding of the underlying pathophysiology of ventricular arrhythmias in channelopathies, highlighting the roles of the Purkinje network and the epicardial right ventricular outflow tract in arrhythmogenesis. This review explores the role of catheter ablation in managing the most common channelopathies (Brugada syndrome, congenital long QT syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). While the initial results for ablation in Brugada syndrome are promising, the long-term efficacy and durability of ablation in different channelopathies require further investigation. Given the genetic and phenotypic heterogeneity of channelopathies, future studies are needed to show whether catheter ablation in patients with channelopathies is associated with a reduction in VF, and psychological distress stemming from recurrent ICD shocks, particularly relative to other available therapeutic options (e.g., quinidine in high-risk Brugada patients).

An international multicenter cohort study on implantable cardioverter-defibrillators for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia

BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there are limited data on the outcomes of ICD use in children. ObjectiveThe purpose of this study was to compare the risk of arrhythmic events in pediatric patients with CPVT with and without ICD. MethodsWe compared the risk of SCD in patients with RYR2 (ryanodine receptor 2) variants and phenotype-positive symptomatic patients with CPVT with and without ICD who were younger than 19 years and had no history of sudden cardiac arrest at phenotype diagnosis. The primary outcome was SCD; secondary outcomes were composite end points of SCD, sudden cardiac arrest, or appropriate ICD shocks with or without arrhythmic syncope. ResultsThe study included 235 patients, 73 with ICD (31.1%) and 162 without ICD (68.9%). Over a median follow-up of 8.0 years (interquartile range 4.3–13.4 years), SCD occurred in 7 patients (3.0%), of whom 4 (57.1%) were noncompliant with medications and none had an ICD. Patients with ICD had a higher risk of both secondary composite outcomes (without syncope: hazard ratio 5.85; 95% confidence interval 3.40–10.09; P < .0001; with syncope: hazard ratio 2.55; 95% confidence interval 1.50–4.34; P = .0005). Thirty-one patients with ICD (42.5%) experienced appropriate shocks, 18 (24.7%) inappropriate shocks, and 21 (28.8%) device-related complications. ConclusionSCD events occurred only in the no ICD group and in those not on optimal medical therapy. Patients with ICD had a high risk of appropriate and inappropriate shocks, which may be reduced with appropriate device programming. Severe ICD complications were common, and risks vs benefits of ICDs need to be considered.

Genetic generalized epilepsy with catecholaminergic polymorphic ventricular tachycardia complicated by ryanodine receptor 2 variant: A case report

Genetic generalized epilepsy with catecholaminergic polymorphic ventricular tachycardia complicated by ryanodine receptor 2 variant: A case report

A novel RyR2 mutation associated with co-morbid catecholaminergic polymorphic ventricular tachycardia (CPVT) and benign epilepsy with centrotemporal spikes (BECTS)

In this case report, we describe a 14-year-old patient with a novel RyR2 gene mutation (c.6577G > T/p.Val2193Leu), identified through a comprehensive review of medical history, examination findings, and follow-up data. The pathogenic potential of this mutation, which results in the loss of some interatomic forces and compromises the closure of the RyR2 protein pore leading to calcium leakage, was analyzed using the I-TASSER Suite to predict the structural changes in the protein. This mutation manifested clinically as co-morbid catecholaminergic polymorphic ventricular tachycardia (CPVT) and benign epilepsy with centrotemporal spikes (BECTS), a combination not previously documented in the same patient. While seizures were successfully managed with levetiracetam, the patient's exercise-induced syncope episodes could not be controlled with metoprolol, highlighting the complexity and challenge in managing CPVT associated with this novel RyR2 variation.

Catecholaminergic Polymorphic Ventricular Tachycardia: Clinical Characteristics, Diagnostic Evaluation and Therapeutic Strategies.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe hereditary arrhythmia syndrome predominantly affecting children and young adults. It manifests through bidirectional or polymorphic ventricular arrhythmia, often culminating in syncope triggered by physical exertion or emotional stress which can lead to sudden cardiac death. Most cases stem from mutations in the gene responsible for encoding the cardiac ryanodine receptor (RyR2), or in the Calsequestrin 2 gene (CASQ2), disrupting the handling of calcium ions within the cardiac myocyte sarcoplasmic reticulum. Diagnosing CPVT typically involves unmasking the arrhythmia through exercise stress testing. This diagnosis emerges in the absence of structural heart disease by cardiac imaging and with a normal baseline electrocardiogram. Traditional first-line treatment primarily involves β-blocker therapy, significantly reducing CPVT-associated mortality. Adjunctive therapies such as moderate exercise training, flecainide, left cardiac sympathetic denervation and implantable cardioverter-defibrillators have been utilized with reasonable success. However, the spectrum of options for managing CPVT has expanded over time, demonstrating decreased rates of arrhythmic events. Furthermore, ongoing research into potential new therapies including gene therapies has the potential to further enhance treatment paradigms. This review aims to succinctly encapsulate the contemporary understanding of the clinical characteristics, diagnostic approach, established therapeutic interventions and the promising future directions in managing CPVT.

Whole-exome sequencing in familial type 2 diabetes identifies an atypical missense variant in the RyR2 gene.

Genome-wide association studies have identified several hundred loci associated with type 2 diabetes mellitus (T2DM). Additionally, pathogenic variants in several genes are known to cause monogenic diabetes that overlaps clinically with T2DM. Whole-exome sequencing of related individuals with T2DM is a powerful approach to identify novel high-penetrance disease variants in coding regions of the genome. We performed whole-exome sequencing on four related individuals with T2DM - including one individual diagnosed at the age of 33 years. The individuals were negative for mutations in monogenic diabetes genes, had a strong family history of T2DM, and presented with several characteristics of metabolic syndrome. A missense variant (p.N2291D) in the type 2 ryanodine receptor (RyR2) gene was one of eight rare coding variants shared by all individuals. The variant was absent in large population databases and affects a highly conserved amino acid located in a mutational hotspot for pathogenic variants in Catecholaminergic polymorphic ventricular tachycardia (CPVT). Electrocardiogram data did not reveal any cardiac abnormalities except a lower-than-normal resting heart rate (< 60 bpm) in two individuals - a phenotype observed in CPVT individuals with RyR2 mutations. RyR2-mediated Ca2+ release contributes to glucose-mediated insulin secretion and pathogenic RyR2 mutations cause glucose intolerance in humans and mice. Analysis of glucose tolerance testing data revealed that missense mutations in a CPVT mutation hotspot region - overlapping the p.N2291D variant - are associated with complete penetrance for glucose intolerance. In conclusion, we have identified an atypical missense variant in the RyR2 gene that co-segregates with diabetes in the absence of overt CPVT.

Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.

Primary electrical heart diseases, often considered channelopathies, are inherited genetic abnormalities of cardiomyocyte electrical behavior carrying the risk of malignant arrhythmias leading to sudden cardiac death (SCD). Approximately 54% of sudden, unexpected deaths in individuals under the age of 35 do not exhibit signs of structural heart disease during autopsy, suggesting the potential significance of channelopathies in this group of age. Channelopathies constitute a highly heterogenous group comprising various diseases such as long QT syndrome (LQTS), short QT syndrome (SQTS), idiopathic ventricular fibrillation (IVF), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndromes (ERS). Although new advances in the diagnostic process of channelopathies have been made, the link between a disease and sudden cardiac death remains not fully explained. Evolving data in electrophysiology and genetic testing suggest previously described diseases as complex with multiple underlying genes and a high variety of factors associated with SCD in channelopathies. This review summarizes available, well-established information about channelopathy pathogenesis, genetic basics, and molecular aspects relative to principles of the pathophysiology of arrhythmia. In addition, general information about diagnostic approaches and management is presented. Analyzing principles of channelopathies and their underlying causes improves the understanding of genetic and molecular basics that may assist general research and improve SCD prevention.

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

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. 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. The significant rate of non-adherence associated with concerns regarding CPVT-related medication, emphasizes the potential for improving therapy adherence by targeted patient education.

Clinical and genetic characterization of patients with catecholaminergic polymorphic ventricular tachycardia: a case series

AIM: of the study was to evaluate the clinical and genetic characteristics, including the development of adverse events and outcomes in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT).&#x0D; MATERIALS AND METHODS: The clinical phenotype of eight patients with CPVT, two of whom were relatives of probands, was observed over 4 years. The clinical and instrumental study included ECG-12, 24-hour Holter ECG monitoring, genealogical history collection and family history of sudden cardiac death (SCD), transthoracic echocardiography and cardiac magnetic resonance imaging to detect structural myocardial changes, electrophysiologic study according to indications, and ICD monitoring. High-throughput sequencing (NGS) was utilized to search for mutations in genes linked to the onset of channelopathies and other inherited rhythm disorders.&#x0D; RESULTS: In 8 patients, nucleotide variants of pathogenicity classes III-V were identified according to the ACMG (2015) criteria in the RYR2 gene associated with CPVT. Pathogenic (IV-V class) and likely pathogenic (IV class) mutations in the RYR2 gene were found in 6 (75%) probands, variants with uncertain clinical significance (VUS, class III) were found in 2 patients. At the time of diagnosis, transient QTc interval prolongation of more than 480 ms was detected in 4 (50%) patients; bradycardia less than 54 beats/min — in 2 (25%) patients, sequences of supraventricular tachycardia and ventricular tachyarrhythmia — in 2 (25%) patients. The most severe form of the disease with marked clinical manifestations and an episode of clinical death with subsequent resuscitation, as well as a transient QTc interval prolongation exceeding 500 ms was observed in patients with mutations c.11814C A (p.Ser3938Arg, rs794728704); c.463G A (p.Gly155Arg) and c.14876G A (p.Arg4959Gln, rs794728811) in the RYR2 gene. Three (37.5%) patients underwent ICD implantation; one for primary SCD prevention and two for secondary prevention.&#x0D; CONCLUSION: In this study, the spectrum of clinical manifestations in patients with genetically confirmed CPVT was examined. The findings highlight transient QTc interval extensions, significant sinus bradycardia, and sequences of supraventricular tachyarrhythmias, which can escalate into life-threatening ventricular tachyarrhythmias in CPVT patients.

A case involving tooth extraction of upper and lower third molars under general anesthesia in a patient with catecholaminergic polymorphic ventricular tachycardia

AbstractBackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT), an inheritable arrhythmia, poses a grave risk of syncope or cardiac arrest.Case PresentationA 23‐year‐old female with CPVT history and implantable cardioverter‐defibrillator (ICD) implantation sought tooth extraction of her third molars. She underwent the procedure under general anesthesia to mitigate VT risk. Defibrillation function was temporarily halted during anesthesia induction, managed with total intravenous anesthesia. The postoperative course remained uneventful, obviating defibrillation intervention.ConclusionsThis case underscores the efficacy of general anesthesia in averting VT onset during oral surgery for CPVT patients, ensuring a safe and uneventful postoperative recovery.

Long-term efficacy and safety of cardiac genome editing for catecholaminergic polymorphic ventricular tachycardia.

Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model. The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for Ryr2 variant p.Arg176Gln (R176Q/+). Guide RNA and SaCas9 were delivered using AAV9 vectors injected subcutaneously in 10-day-old mice. At 6 weeks after injection, R176Q/+ mice had a 100% reduction in ventricular arrhythmias compared to controls. When aged to 12 months, injected R176Q/+ mice maintained a 100% reduction in arrhythmia induction. Deep RNA sequencing revealed the formation of insertions/deletions at the target site with minimal off-target editing on the wild-type allele. Consequently, CRISPR/SaCas9 editing resulted in a 45% reduction of total Ryr2 mRNA and a 38% reduction in RyR2 protein. Genome editing was well tolerated based on serial echocardiography, revealing unaltered cardiac function and structure up to 12 months after AAV9 injection. Taken together, AAV9-mediated CRISPR/Cas9 genome editing could efficiently disrupt the mutant Ryr2 allele, preventing lethal arrhythmias while preserving normal cardiac function in the R176Q/+ mouse model of CPVT.

Inherited Arrhythmias in the Pediatric Population: An Updated Overview.

Pediatric cardiomyopathies (CMs) and electrical diseases constitute a heterogeneous spectrum of disorders distinguished by structural and electrical abnormalities in the heart muscle, attributed to a genetic variant. They rank among the main causes of morbidity and mortality in the pediatric population, with an annual incidence of 1.1-1.5 per 100,000 in children under the age of 18. The most common conditions are dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Despite great enthusiasm for research in this field, studies in this population are still limited, and the management and treatment often follow adult recommendations, which have significantly more data on treatment benefits. Although adult and pediatric cardiac diseases share similar morphological and clinical manifestations, their outcomes significantly differ. This review summarizes the latest evidence on genetics, clinical characteristics, management, and updated outcomes of primary pediatric CMs and electrical diseases, including DCM, HCM, arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), and short QT syndrome (SQTS).

The importance of variant reinterpretation in inherited cardiovascular diseases: Establishing the optimal timeframe.

Inherited cardiovascular diseases are rare diseases that are difficult to diagnose by non-expert professionals. Genetic analyses play a key role in the diagnosis of these diseases, in which the identification of a pathogenic genetic variant is often a diagnostic criterion. Therefore, genetic variant classification and routine reinterpretation as data become available represent one of the main challenges associated with genetic analyses. Using the genetic variants identified in an inherited cardiovascular diseases unit during a 10-year period, the objectives of this study were: 1) to evaluate the impact of genetic variant reinterpretation, 2) to compare the reclassification rates between different cohorts of cardiac channelopathies and cardiomyopathies, and 3) to establish the most appropriate periodicity for genetic variant reinterpretation. All the evaluated cohorts (full cohort of inherited cardiovascular diseases, cardiomyopathies, cardiac channelopathies, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, Brugada syndrome, long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) showed reclassification rates above 25%, showing even higher reclassification rates when there is definitive evidence of the association between the gene and the disease in the cardiac channelopathies. Evaluation of genetic variant reclassification rates based on the year of the initial classification showed that the most appropriate frequency for the reinterpretation would be 2 years, with the possibility of a more frequent reinterpretation if deemed convenient. To keep genetic variant classifications up to date, genetic counsellors play a critical role in the reinterpretation process, providing clinical evidence that genetic diagnostic laboratories often do not have at their disposal and communicating changes in classification and the potential implications of these reclassifications to patients and relatives.

Artificial intelligence for a cardiac drug study

Machine learning that is the vital part of modern artificial intelligence was used to classify the potential effects of two drugs on induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM). Peak data were detected from calcium transient signals of cycling iPSC-CMs first at baseline, second exposed to adrenaline and third exposed with one of the drugs either flecainide or carvedilol. Various machine learning classification tests were executed to evaluate whether a drug did or did not affect signal shape after exposing adrenaline or the drugs. According to our classification results, machine learning can be applied to analyze possible effects of drugs on induced pluripotent stem cell-derived cardiomyocytes derived from the catecholaminergic polymorphic ventricular tachycardia patients’ cell samples.