Roles of Atrial Arrhythmias in Triggering Torsade de Pointes in Patients With Acquired Long-QT Syndrome.

BACKGROUND: Little is known about the role of atrial arrhythmias (AAs) in triggering Torsade de Pointes (TdP) in patients with long-QT syndrome (LQTS). The aim of this study was to examine the contribution of AAs to the development of TdP in acquired LQTS patients. METHODS: The initiation patterns of 81 episodes of TdP obtained from 34 consecutive acute acquired LQTS patients (14 men, median age, 69 years; median QTc, 645.5 ms) with documented TdP were analyzed. The initiation mode of TdP was divided into 3 categories: (1) preceding short-long sequence (SLS); (2) sudden R-on-T phenomenon without preceding SLS; and (3) increased atrial rate. The patients were divided into 2 groups based on the presence or absence of AAs-induced TdP; AAs-induced (n=18) and non-AAs-induced (n=16) groups. The association of clinical/ECG characteristics and TdP frequency after initiating conventional therapy with AAs-induced TdP was evaluated. The groups were compared using the Mann-Whitney U test or Fisher exact test. RESULTS: AAs-induced group comprised 52.9% (18/34) of the patients studied. TdP was preceded by AAs-initiated SLSs in 41.2% (14/34) of the patients and was directly induced by R-on-T AAs (AAs coincidentally encountered a vulnerable repolarizing region during the T wave) in 23.5% (8/34). AAs triggered 48 (59.3%) of the 81 TdP episodes. AAs-initiated SLSs in 67.8% (40/59) of the SLS-induced TdP episodes. R-on-T AAs accounted for 23.5% (19/81) of the TdP episodes. AAs-induced group experienced TdP after initiating therapy more frequently than non-AAs-induced group (2.5 versus 1 event, P=0.008). AAs-induced group exhibited macroscopic T-wave alternans more frequently than non-AAs-induced group (6 versus 0, P=0.02). CONCLUSIONS: AAs play a key role in triggering TdP in more than half of patients with acute acquired LQTS and can increase TdP frequency after initiating therapy. Thus, AAs are not benign but rather can be life-threatening in patients with acute acquired LQTS.

Prediction of sudden cardiac death using artificial intelligence: Current status and future directions.

Sudden cardiac death (SCD) remains a pressing health issue, affecting hundreds of thousands each year globally. The heterogeneity among SCD victims, ranging from individuals with severe heart failure to seemingly healthy individuals, poses a significant challenge for effective risk assessment. Conventional risk stratification, which primarily relies on left ventricular ejection fraction, has resulted in only modest efficacy of implantable cardioverter-defibrillators (ICD) for SCD prevention. In response, artificial intelligence (AI) holds promise for personalised SCD risk prediction and tailoring preventive strategies to the unique profiles of individual patients. Machine and deep learning algorithms have the capability to learn intricate non-linear patterns between complex data and defined endpoints, and leverage these to identify subtle indicators and predictors of SCD that may not be apparent through traditional statistical analysis. However, despite the potential of AI to improve SCD risk stratification, there are important limitations that need to be addressed. We aim to provide an overview of the current state-of-the-art of AI prediction models for SCD, highlight the opportunities for these models in clinical practice, and identify the key challenges hindering widespread adoption.

Mitochondria-targeted sonodynamic modulation of neuroinflammation to protect against myocardial ischemia‒reperfusion injury.

Sympathetic hyperactivation and inflammatory responses are the main causes of myocardial ischemia‒reperfusion (I/R) injury and myocardial I/R-related ventricular arrhythmias (VAs). Previous studies have demonstrated that light-emitting diodes (LEDs) could modulate post-I/R neuroinflammation, thus providing protection against myocardial I/R injury. Nevertheless, further applications of LEDs are constrained due to the low penetration depth (<1 cm) and potential phototoxicity. Low-intensity focused ultrasound (LIFU), an emerging noninvasive neuromodulation strategy with deeper penetration depth (∼10 cm), has been confirmed to modulate sympathetic nerve activity and inflammatory responses. Sonodynamic therapy (SDT), which combines LIFU with sonosensitizers, confers additional advantages, including superior therapeutic efficacy, precise localization of neuronal modulation and negligible side effects. Herein, LIFU and SDT were introduced to modulate post-myocardial I/R neuroinflammation to protect against myocardial I/R injury. The results indicated that LIFU and SDT inhibited sympathetic neural activity, suppressed the activation of astrocytes and microglia, and promoted microglial polarization towards the M2 phenotype, thereby attenuating myocardial I/R injury and preventing I/R-related malignant VAs. These insights suggest that LIFU and SDT inspire a noninvasive and efficient neuroinflammatory modulation strategy with great clinical translation potential thus benefiting more patients with myocardial I/R in the future. STATEMENT OF SIGNIFICANCE: Myocardial ischemia-reperfusion (I/R) may cause I/R injury and I/R-induced ventricular arrhythmias. Sympathetic hyperactivation and inflammatory response play an adverse effect in myocardial I/R injury. Previous studies have shown that light emitting diode (LED) can regulate I/R-induced neuroinflammation, thus playing a myocardial protective role. However, due to the low penetration depth and potential phototoxicity of LED, it is difficult to achieve clinical translation. Herein, we introduced sonodynamic modulation of neuroinflammation to protect against myocardial I/R injury, based on mitochondria-targeted nanosonosensitizers (CCNU980 NPs). We demonstrated that sonodynamic modulation could promote microglial autophagy, thereby preventing myocardial I/R injury and I/R-induced ventricular arrhythmias. This is the first example of sonodynamic modulation of myocardial I/R-induced neuroinflammation, providing a novel strategy for clinical translation.

Arrhythmogenic Mitral Valve Prolapse: Can We Risk Stratify and Prevent Sudden Cardiac Death?

Ventricular arrhythmias associated with mitral valve prolapse (MVP) and the capacity to cause sudden cardiac death (SCD), referred to as 'malignant MVP', are an increasingly recognised, albeit rare, phenomenon. SCD can occur without significant mitral regurgitation, implying an interaction between mechanical derangements affecting the mitral valve apparatus and left ventricle. Risk stratification of these arrhythmias is an important clinical and public health issue to provide precise and targeted management. Evaluation requires patient and family history, physical examination and electrophysiological and imaging-based modalities. We provide a review of arrhythmogenic MVP, exploring its epidemiology, demographics, clinical presentation, mechanisms linking MVP to SCD, markers of disease severity, testing modalities and management, and discuss the importance of risk stratification. Even with recently improved understanding, it remains challenging how best to weight the prognostic importance of clinical, imaging and electrophysiological data to determine a clear high-risk arrhythmogenic profile in which an ICD should be used for the primary prevention of SCD.

Association Between Right Bundle Branch Block and Ventricular Arrhythmia in Patients With Cardiac Sarcoidosis.

Background: Ventricular arrhythmia (VA) is a life-threatening condition associated with cardiac sarcoidosis (CS). Right bundle branch block (RBBB) is a common conduction disorder in CS; however, its association with VA remains unknown. Objectives: This study aimed to investigate the relationship between RBBB and VA in patients with CS. Methods: This was a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients with Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of CS. Eligible patients were divided into two groups based on the presence or absence of RBBB at the time of diagnosis. The primary outcome was serious ventricular arrhythmia events (SVAEs), defined as a combination of sudden cardiac death and documented ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Results: Overall, 312 patients were studied, with 155 (49.7%) patients presenting with RBBB (RBBB group). Patients in the RBBB group had a higher prevalence of basal interventricular septum (IVS) thinning and prominent late gadolinium enhancement in the basal IVS on cardiac magnetic resonance imaging than those in the non-RBBB group. During a median follow-up of 3.0 years (IQR: 1.6-6.0 years), 66 patients experienced SVAE. In multivariable Cox regression analysis, the RBBB group was independently associated with a higher incidence of SVAEs (HR: 1.93 [95% CI: 1.14-3.28]; P = 0.015). Conclusions: In patients with CS, RBBB was an independent predictor of SVAEs, which might reflect the specific scar distribution that is predominant in the IVS.

Genetic and clinical characteristics of catecholaminergic polymorphic ventricular tachycardia in a Taiwanese nationwide cohort.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and lethal arrhythmia. Ryanodine receptor 2 (RYR2) mutation accounts for ∼60% of CPVT patients which is inherited in an autosomal dominant pattern. OBJECTIVE: This study aimed to identify CPVT-related mutations and clinical characteristics among Taiwanese CPVT patients and compare to other cohorts worldwide. METHODS: Clinical and genetic data were obtained from the Sudden Arrhythmia Death Syndrome Registry in Taiwan (SADS-TW). Forty clinically diagnosed Taiwanese CPVT patients were included. RESULTS: This is the first nationwide CPVT cohort in Taiwan. Among the 29 Taiwanese patients with CPVT-related gene mutations, 55% had RYR2 mutations, a rate similar to other ethnicities. Three out of 12 RYR2 variants were unreported. Exercise-induced symptoms including syncope and cardiac arrest were more frequent in East Asian cohorts (Taiwanese 79%, Japanese 91%), compared to Caucasian cohorts (59%) (p = 0.002). CONCLUSION: The discovery of diverse RYR2 mutations in the Taiwanese CVPT population demonstrates the importance of genetic testing in different ethnicities.

Zero-fluoroscopy catheter ablation of premature ventricular contractions: comparative outcomes from the right ventricular outflow tract and other ventricular sites.

BACKGROUND: The three-dimensional electroanatomic mapping (EAM) system allows performing catheter ablation (CA) without fluoroscopy in patients with premature ventricular contractions (PVCs). The right ventricle outflow tract (RVOT) location is favorable for performing zero-fluoroscopy CA. Non-RVOT zero-fluoroscopy CA is a challenging procedure. The study aimed to evaluate the efficacy and safety of zero-fluoroscopy CA using the EAM in patients with PVCs from RVOT and non-RVOT. METHODS: Completely zero-fluoroscopy CA of PVCs guided by EAM was performed in 107 patients with PVCs. 54 patients underwent zero-fluoroscopy RVOT CA. The remaining 53 patients underwent zero-fluoroscopy non-RVOT CA. Demographic and clinical baseline characteristics, procedure parameters, and follow-up were obtained from medical records. Primary outcomes were the acute and the permanent success rate (12-month follow-up), complications, and procedure time. RESULTS: There were no significant differences between groups regarding baseline characteristics. Acute procedural success was achieved in 52 patients (94,44%) in the RVOT zero-fluoroscopy CA group and in 45 patients (86,54%) in the non-RVOT zero-fluoroscopy CA group (ns). A long-term success rate was achieved in 50 patients (90,74%) in the RVOT zero-fluoroscopy CA group and in 44 patients (84,62%) in the non-RVOT zero-fluoroscopy CA group (ns). The median procedure time was 80.5 minutes in the RVOT group and 90 minutes in the non-RVOT group (ns). There were two complications in the non-RVOT group (ns). CONCLUSIONS: There were no differences in procedure time efficacy and safety zero-fluoroscopy ablation between RVOT and non-RVOT locations. Non-fluoroscopy CA of PVCs is a feasible, safe, and efficient procedure.

Opioid Use and the Risk of Ventricular Arrhythmias: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between opioid use and the risk of ventricular arrhythmias (VA) is poorly understood. AIMS: The objective of this study was to synthesize the evidence on the risk of VA associated with opioid use. MATERIALS & METHODS: We systematically searched the Cochrane Library, Embase, MEDLINE, and CINAHL databases in July 2022. Risk of bias was assessed using the Cochrane risk for bias tool for randomized controlled trials (RCTs) and ROBINS-I for observational studies. Certainty of evidence was assessed using GRADE. RESULTS: We included 15 studies (12 observational, 2 post hoc analyses of RCTs, 1 RCT). Most studies focused on opioid use for maintenance therapy (n = 9), comparing methadone to buprenorphine (n = 13), and reported QTc prolongation (n = 13). Six observational studies had a critical risk of bias, and one RCT was at high risk of bias. Two studies could not be included in the meta-analysis as they reported a different outcome and studied an opioid antagonist. Meta-analysis of 13 studies indicated that the use of methadone was associated with an increased risk of VA compared to the use of buprenorphine, morphine, placebo, or levacetylmethadol (risk ratio [RR], 2.39; 95% CI, 1.31-4.35; I2 = 60%). The pooled estimate varied greatly between observational studies (RR, 2.12; 95% CI, 1.15-3.91; I2 = 62%) and RCTs (RR, 14.09; 95% CI, 1.52-130.61; I2 = 0%), but both indicated an increased risk. CONCLUSION: In this systematic review and meta-analysis, we found that methadone use is associated with more than twice the risk of VA compared to comparators. However, our findings should be interpreted cautiously given the limited quality of the available evidence.

Natural Course of Electrocardiographic Features in Arrhythmogenic Right Ventricular Cardiomyopathy and Their Relation to Ventricular Arrhythmic Events.

BACKGROUND: Electrocardiographic abnormalities are common in arrhythmogenic right ventricular cardiomyopathy and are included in the 2010 Task Force Criteria. Their time course, however, remains uncertain. In this retrospective observational study, we aimed to assess the long-term evolution of electrocardiographic characteristics and their relation to ventricular arrhythmias. METHODS AND RESULTS: Three hundred fifty-three patients with arrhythmogenic right ventricular cardiomyopathy as per the 2010 Task Force Criteria with 6871 automatically processed 12-lead digital ECGs were included. The relationship between the electrocardiographic parameters and the risk of ventricular arrhythmias was assessed at 10 years from the first ECG. Electrocardiographic parameters were compared between the first contact ECG, the ECG at diagnosis, and the most recent ECG. Median time between the first and the latest ECG was 6 [interquartile range, 1-14] years. Reductions of QRS voltage, R- and T-wave amplitudes between the first, diagnostic, and the latest ECGs were observed across precordial and extremity leads. Mean QRS duration increased from 96 to 102 ms (P<0.001), terminal activation duration (V1) from 47 to 52 ms (P<0.001), and QTc from 419 to 432 ms (P<0.001). T-wave inversions in leads V3 to V6 and aVF at first ECG were associated with ventricular arrhythmias (adjusted hazard ratio [HRadj][V3], 2.03 [95% CI, 1.23-3.34] and HRadj[aVF], 1.87 [95% CI, 1.13-3.08]). CONCLUSIONS: Depolarization and repolarization parameters evolved over time in patients with arrhythmogenic right ventricular cardiomyopathy, supporting the progressive nature of arrhythmogenic right ventricular cardiomyopathy. Electrocardiographic abnormalities may be detected before diagnosis and might, although not fulfilling the 2010 Task Force Criteria, be markers of early disease. T-wave inversion in leads V3 or aVF before diagnosis was associated with ventricular arrhythmias during follow-up.

Impact of Catheter Ablation of Electrical Storm on Survival: A Propensity Score-Matched Analysis.

BACKGROUND: Electrical storm (ES) is a life-threatening condition, associated with substantial early and subacute mortality. Catheter ablation (CA) is a well-established therapy for ES. However, data regarding the impact of CA on the short-term and midterm survival of patients admitted for ES remain unclear. OBJECTIVES: This multicenter study aimed to investigate the impact of CA of ES on survival outcomes, while accounting for key patient characteristics associated with treatment selection. METHODS: A propensity score-matching (PSM) analysis was performed on 780 consecutive patients admitted for ES in 4 tertiary centers. PSM (1:1) based on the main characteristics associated with the use of CA or medical therapy alone was performed, resulting in 2 groups of 288 patients. RESULTS: After PSM, patients who underwent CA (n = 288) and those treated with medical therapy alone (n = 288) did not present any significant differences in the main demographic characteristics, ES presentation, and management. Compared with medical therapy alone, CA was associated with a significantly lower rate of ES recurrence at 1 year (5% vs 26%; P < 0.001). Similarly, CA was associated with a higher 1-year (91% vs 81%; P < 0.001) and 3-year (78% vs 71%; P = 0.017) survival after discharge. In subgroup analyses, effect of ablation therapy remained consistent in patients older than 70 years of age (HR: 0.39; 95% CI: 0.24-0.66), with substantial efficacy in patients with a LVEF <35% (HR: 0.39; 95% CI: 0.27-0.59). CONCLUSIONS: In propensity-matched analyses, this large study shows that CA-based management of patients admitted for ES is associated with a reduction in mortality compared with medical treatment, particularly in patients with a low ejection fraction.

Case report: arrhythmic mitral valve prolapse syndrome-are risk factors underdiagnosed?

Background: Arrhythmic mitral valve prolapse syndrome (ARMV) is a recognized but underdiagnosed disease pattern. Risk factors for ARMV are established but not very well known, and the association of the structural abnormality with ventricular arrhythmias is incompletely understood. Case summary: Here, we present the case of a young man who presented at our hospital for radiofrequency catheter ablation and mitral valve surgery after two episodes of survived sudden cardiac arrest. We discuss the diagnostic and therapeutic strategies that were used. We shine light on the risk factors for ARMV and why early identification is crucial. We address the topic of primary prevention and its limitations. Finally, we discuss different treatment modalities for patients with ARMV. Discussion: More awareness for ARMV is crucial. A consensus statement on clinical management exists, but scientific gaps in prospective data for primary prevention need to be filled and there is a need for a better understanding of the pathogenesis of ARMV.

Can the QRS morphology of outflow tract ventricular arrhythmia change when right bundle branch block emerges during sinus rhythm?

BACKGROUND: QRS morphology can change during ventricular arrhythmias (VAs) with the appearance of bundle branch block (BBB). METHODS: We retrospectively investigated 195 consecutive patients who underwent an initial ablation of VA. The study inclusion criteria were VAs that were successfully ablated in the outflow tract (OT) and in whom right bundle branch block (RBBB) was induced by catheter manipulation close to the His bundle area during sinus rhythm, before any radiofrequency application. We analyzed the QRS morphology of the VAs with and without RBBB during sinus beats. RESULTS: Twenty-four patients (age 59 ± 17 years, female 14) developed RBBB at some point during their procedure. The successful ablation sites of the VAs were the right ventricular outflow tract (RVOT) in 12 patients, pulmonary artery in one, left coronary cusp in five, right coronary cusp in three, right-left cusp junction in two, and great cardiac vein in two. QRS-morphology change was observed in five (20%) cases. The successful ablation sites in that group were the left coronary cusp in three cases, right coronary cusp in one, and RVOT septum in one. The QRS duration of the VAs increased during RBBB. CONCLUSIONS: There are some cases of OT-VAs in which the QRS waveform changes with the appearance of catheter induced RBBB. We need to be aware that when QRS morphology changes during an OT-VA ablation, it does not necessarily mean that the origin or exit of the VA has changed.

Arrhythmogenic Potential of Myocardial Edema: The Interstitial Osmolality Induces Spiral Waves and Multiple Excitation Wavelets.

Myocardial edema is a common symptom of pathological processes in the heart, causing aggravation of cardiovascular diseases and leading to irreversible myocardial remodeling. Patient-based studies show that myocardial edema is associated with arrhythmias. Currently, there are no studies that have examined how edema may influence changes in calcium dynamics in the functional syncytium. We performed optical mapping of calcium dynamics on a monolayer of neonatal rat cardiomyocytes with Fluo-4. The osmolality of the solutions was adjusted using the NaCl content. The initial Tyrode solution contained 140 mM NaCl (1T) and the hypoosmotic solutions contained 105 (0.75T) and 70 mM NaCl (0.5T). This study demonstrated a sharp decrease in the calcium wave propagation speed with a decrease in the solution osmolality. The successive decrease in osmolality also showed a transition from a normal wavefront to spiral wave and multiple wavelets of excitation with wave break. Our study demonstrated that, in a cellular model, hypoosmolality and, as a consequence, myocardial edema, could potentially lead to fatal ventricular arrhythmias, which to our knowledge has not been studied before. At 0.75T spiral waves appeared, whereas multiple wavelets of excitation occurred in 0.5T, which had not been recorded previously in a two-dimensional monolayer under conditions of cell edema without changes in the pacing protocol.

Arrhythmic Prognosis According to Left Ventricular Systolic Dysfunction Severity in Cardiac Sarcoidosis.

BACKGROUND: Current guidelines present varying classes of recommendations for implantable cardioverter-defibrillator (ICD) utilization in patients with cardiac sarcoidosis (CS) and left ventricular ejection fraction (LVEF) <50%. OBJECTIVE: To investigate the ventricular arrhythmia risk in CS patients with ICDs and varying degrees of LV systolic dysfunction. METHODS: We included CS patients with an ICD and LVEF <50% at index evaluation. The primary outcome was survival free of sustained ventricular tachycardia/fibrillation (VT/VF) after ICD implantation and was assessed comparatively for LVEF ≤35 vs 36-49% and for primary vs secondary prevention ICD indication. RESULTS: We included 61 patients (median age 57 years, 61% male) with LVEF 36-49% (n=23) or LVEF ≤35% (n=38). An ICD was implanted for secondary prevention in 24% and 44% of the LVEF ≤35% and 36-49% groups, respectively (p=0.11). The primary outcome did not differ between the two groups in univariable analysis (LVEF ≤35% vs 36-49% HR 0.85 [95% CI 0.39, 1.82], p=0.67). In multivariable analysis, secondary prevention ICD indication was the only significant predictor of incident sustained VT/VF (HR 2.86 [95% CI 1.23, 6.67], p=0.015). The mean sustained VT/VF event burden was higher in the secondary as compared with the primary prevention ICD patients (0.47 vs 0.11 events/patient-year, p=0.005) but did not differ significantly between LVEF ≤35% and 36-49% patients. CONCLUSIONS: CS patients with ICD indications and LVEF 36-49% carry similarly high arrhythmic risk as those with LVEF ≤35%. Patients with secondary prevention ICDs have the highest overall risk.

Role of subpulmonary right ventricle in sudden cardiac death in adults with congenital heart disease.

Despite improved childhood survival of congenital heart disease (CHD) as a result of advances in management, late-onset sudden cardiac death (SCD) from malignant ventricular arrhythmias remains a leading cause of mortality in adults with CHD. Preventing SCD in these patients requires an understanding of the underlying pathophysiological mechanisms. Many CHD patients experience significant hemodynamic stress on the subpulmonary right ventricle (RV), leading to pathologic remodeling. Unlike acquired heart disease in which left ventricular pathology is prevalent, RV pathologies are crucial in the SCD pathogenesis in CHD patients. This review examines the mechanisms and management of SCD related to subpulmonary RV pathologies in CHD patients.

Incidence and risk factors for first and recurrent ICD shock therapy in patients with an implantable cardioverter defibrillator.

BACKGROUND: Advances in medical treatment and outcomes in implantable cardioverter-defibrillator (ICD) recipients incentivize a need for improved candidate selection and identification of risk factors for ICD therapy. We examined contemporary rates of and risk factors for ICD therapy. METHODS: Patients with ICD for primary (PP) or secondary prevention (SP), implanted between January 2010 and December 2020, were followed for appropriate and inappropriate incident and recurrent shock. RESULTS: Overall, 2998 patients (mean age 61.8 ± 12.7 years, 20% female, 73% ICD carriers, and 47.1% SP) were analyzed with a median follow-up of 4.3 (interquartile range (IQR) 2.1-7.4) years. A total of 426/2998 (14.2%) patients had shock; 364/2998 (12.1%) had appropriate and 82/2998 (2.7%) inappropriate shock, with annualized event rates of 2.34 (2.11-2.59) and 0.49 (0.39-0.61) per 100 person-years, respectively. Of those with shock, 133/364 (36.5%) experienced recurrent appropriate shock and 8/364 (2.2%) received recurrent inappropriate shock, with event rates of 10.57 (8.85-12.53) and 0.46 (0.20-0.92), respectively. In multivariable analyses, female sex was associated with a reduced risk of incident appropriate shock (hazard ratio 0.69 [95% confidence interval 0.52; 0.91]). Of other variables, only revascularization status was associated with recurrent appropriate shock in PP, and CRT-D with recurrent appropriate shock in the overall cohort. CONCLUSION: One in eight ICD recipients received appropriate shock 2-7 years after guideline-directed implantation. More than one-third of patients with a first shock experienced recurrent shock. Few clinical variables showed potential in predicting shocks, illustrating a need for more advanced tools to select candidates for implantation.

The Diagnostic Utility of Holter Monitoring in Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Holter monitoring may raise suspicion of an underlying catecholaminergic polymorphic ventricular tachycardia (CPVT) diagnosis. Although not a primary investigation for CPVT, Holter monitoring is ubiquitously used as a diagnostic tool in the heart rhythm clinic. OBJECTIVES: The objective of this study was to explore Holter monitoring in CPVT diagnosis. METHODS: This retrospective cohort study analyzed off-therapy Holter monitoring from 13 ryanodine receptor 2-positive CPVT and 34 healthy patients from the Canadian Hearts in Rhythm Organization national registry. Using the Edwards method, the ratio of ambient-maximum heart rate during Holter monitoring was correlated with exertion level to separate premature ventricular contractions (PVCs) during periods of adrenergic and nonadrenergic stress. A receiver operating characteristic curve analysis determined the optimal threshold for isolating CPVT-induced PVCs during adrenergic states. RESULTS: PVC burden differed between groups (P = 0.001) but was within population norm, suggesting ambient PVCs are uncommon in CPVT. CPVT patients had higher PVC counts than healthy controls (P = 0.002), with a different distribution based on adrenergic state. The optimal threshold for separating PVCs into periods of adrenergic and nonadrenergic stress in CPVT patients was 76% of the maximum heart rate during the monitoring period. Compared with healthy controls, CPVT patients had a higher PVC count, limited to periods of adrenergic stress, defined by >76% maximum heart rate threshold (P = 0.002; area under the receiver operating characteristic curve: 0.84). Below this threshold, there was no significant PVC difference (P = 0.604). CONCLUSIONS: Holter monitor PVC counts alone are inadequate for CPVT diagnosis, owing to the adrenergic nature of the disease. Quantifying PVC prevalence at a heart rate threshold >76% identified CPVT with moderate sensitivity (69%) and high specificity (94%).

A Patch Wearable Cardioverter-Defibrillator for Patients at Risk of Sudden Cardiac Arrest.

BACKGROUND: For many patients, sudden cardiac arrest (SCA) risk is elevated temporarily. Wearable cardioverter-defibrillators (WCDs) can monitor and treat SCA during these temporary periods. Traditional WCDs can be uncomfortable, require frequent maintenance, and cannot be used when showering, resulting in poor compliance and avoidable SCA deaths. The Jewel is a novel, water-resistant patch-wearable cardioverter-defibrillator (P-WCD) with a machine learning detection algorithm designed to improve compliance and protection against SCA. OBJECTIVES: This study aims to demonstrate the safety and clinical effectiveness of a novel P-WCD. METHODS: The Jewel IDE Study, a prospective, single-arm study conducted at 30 U.S. sites, enrolled patients at SCA risk due to ventricular tachycardia/ventricular fibrillation who were not candidates for or refused an implantable defibrillator. The primary safety endpoint was <15% patients with clinically significant cutaneous adverse device effects and the primary effectiveness endpoint was <2 inappropriate shocks/100 patient-months. Secondary endpoints were ≥1 successful ventricular tachycardia/ventricular fibrillation conversion and wear time compliance of >14.1 h/d. RESULTS: A total of 305 patients (mean age: 57.9 years; 30.2% female, 27.9% non-White) were enrolled, of which 290 had available device data. The clinically significant cutaneous adverse device effect rate was 2.30% (upper 1-sided 98% CI: 4.80); none were severe. No device-related deaths or serious adverse events were reported. The inappropriate shock rate was 0.36/100 patient-months (upper 1-sided 98% CI: 1.53). Of 11 shocks in 9 patients, 9 shocks were adjudicated to be appropriate. Eight of 9 shocks were successful with a single shock. Median wear time compliance was 23.5 (20.7-23.9) h/d. CONCLUSIONS: The novel P-WCD is a safe and effective WCD with high patient compliance. There were no deaths due to noncompliance and a high number of successful conversions (Jewel IDE study [A Clinical Evaluation of the Jewel P-WCD in Subjects at High Risk for Sudden Cardiac Arrest]; NCT05201495).

First human safety and effectiveness study of defibrillation with a novel patch wearable cardioverter-defibrillator.

AIMS: Wearable cardioverter-defibrillators (WCDs) are indicated in patients at risk of sudden cardiac arrest who are not immediate candidates for implantable defibrillator therapy. Limitations of existing WCDs include poor compliance and high false alarm rates. The Jewel is a novel patch-WCD (P-WCD) that addresses these limitations with an adhesive-based design for near-continuous wear and a machine learning algorithm designed to minimize inappropriate detections. This was a first-in-human study of the Jewel P-WCD conducted in an electrophysiology (EP) lab to determine the safety and effectiveness of the device in terminating ventricular tachycardia/ventricular fibrillation (VT/VF) with a single shock. The aim was to evaluate the safety and effectiveness of terminating VT/VF with a single shock using the Jewel P-WCD. METHODS AND RESULTS: This was a first-in-human, prospective, single-arm, single-centre study in patients scheduled for an EP procedure in which VT/VF was expected to either spontaneously occur or be induced. The Jewel P-WCD was placed on consented patients; upon confirmation of VT/VF, a single shock (150 J) was delivered via the device. A group sequential design and Pocock alpha spending function was used to measure the observed proportion of successful VT/VF single-shock terminations. The endpoint was achieved if the lower confidence limit exceeded the performance goal of 62%, using a one-sided lower 97.4% exact confidence bound. Of 18 eligible subjects, 16 (88.9%, 97.4% confidence bound: 65.4%) were successfully defibrillated with a single shock, exceeding the primary endpoint performance goal with no adverse events. CONCLUSION: This first-in-human evaluation of the Jewel P-WCD demonstrated the safety and effectiveness of terminating VT/VF. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT05490459.