Prediction of Shock-Refractory Ventricular Fibrillation During Resuscitation of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Out-of-hospital cardiac arrest due to shock-refractory ventricular fibrillation (VF) is associated with relatively poor survival. The ability to predict refractory VF (requiring ≥3 shocks) in advance of repeated shock failure could enable preemptive targeted interventions aimed at improving outcome, such as earlier administration of antiarrhythmics, reconsideration of epinephrine use or dosage, changes in shock delivery strategy, or expedited invasive treatments. METHODS: We conducted a cohort study of VF out-of-hospital cardiac arrest to develop an ECG-based algorithm to predict patients with refractory VF. Patients with available defibrillator recordings were randomized 80%/20% into training/test groups. A random forest classifier applied to 3-s ECG segments immediately before and 1 minute after the initial shock during cardiopulmonary resuscitation was used to predict the need for ≥3 shocks based on singular value decompositions of ECG wavelet transforms. Performance was quantified by area under the receiver operating characteristic curve. RESULTS: Of 1376 patients with VF out-of-hospital cardiac arrest, 311 (23%) were female, 864 (63%) experienced refractory VF, and 591 (43%) achieved functional neurological survival. Total shock count was associated with decreasing likelihood of functional neurological survival, with a relative risk of 0.95 (95% CI, 0.93-0.97) for each successive shock (P<0.001). In the 275 test patients, the area under the receiver operating characteristic curve for predicting refractory VF was 0.85 (95% CI, 0.79-0.89), with specificity of 91%, sensitivity of 63%, and a positive likelihood ratio of 6.7. CONCLUSIONS: A machine learning algorithm using ECGs surrounding the initial shock predicts patients likely to experience refractory VF, and could enable rescuers to preemptively target interventions to potentially improve resuscitation outcome.

Induction of ventricular fibrillation during programmed ventricular stimulation in a patient with CASQ2 heterozygous mutation.

INTRODUCTION: We report the case of a 37-year-old male athlete, who developed during exercise atrial and ventricular arrhythmias. No structural heart disease. RESULTS: Invasive programmed ventricular stimulation induced ventricular fibrillation. A heterozygous mutation in the CASQ2 gene (c.775G>T, p.E259X) was found. CONCLUSIONS: The findings in our patient may suggest some increased ventricular excitability using programmed ventricular stimulation in CASQ2 polymorphic ventricular tachycardia patients.

Late life-threatening arrhythmia in patients with Brugada syndrome: Results from long-term follow-up in a large Japanese cohort.

INTRODUCTION: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS. METHODS: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined. RESULTS: During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. CONCLUSION: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

Evaluation of patients with implantable cardioverter-defibrillator in a Latin American tertiary center.

INTRODUCTION: Despite advancements in implantable cardioverter-defibrillator (ICD) technology, sudden cardiac death (SCD) remains a persistent public health concern. Chagas disease (ChD), prevalent in Brazil, is associated with increased ventricular tachycardia (VT) and ventricular fibrillation (VF) events and SCD compared to other cardiomyopathies. METHODS: This retrospective observational study included patients who received ICDs between October 2007 and December 2018. The study aims to assess whether mortality and VT/VF events decreased in patients who received ICDs during different time periods (2007-2010, 2011-2014, and 2015-2018). Additionally, it seeks to compare the prognosis of ChD patients with non-ChD patients. Time periods were chosen based on the establishment of the Arrhythmia Service in 2011. The primary outcome was overall mortality, assessed across the entire sample and the three periods. Secondary outcomes included VT/VF events and the combined outcome of death or VT/VF. RESULTS: Of the 885 patients included, 31% had ChD. Among them, 28% died, 14% had VT/VF events, and 37% experienced death and/or VT/VF. Analysis revealed that period 3 (2015-2018) was associated with better death-free survival (p = .007). ChD was the only variable associated with a higher rate of VT/VF events (p < .001) and the combined outcome (p = .009). CONCLUSION: Mortality and combined outcome rates decreased gradually for ICD patients during the periods 2011-2014 and 2015-2018 compared to the initial period (2007-2010). ChD was associated with higher VT/VF events in ICD patients, only in the first two periods.

Association of device detected atrial and ventricular tachyarrhythmia with adverse events in patients with an implantable cardioverter-defibrillator.

INTRODUCTION: Heart failure patients with a history of atrial fibrillation (AF) and ventricular tachycardia/ventricular fibrillation (VT/VF) are known to have worse outcomes. However, there are limited data on the temporal relationship between development of these arrhythmias and the risk of subsequent congestive heart failure (CHF) exacerbation and death. METHODS: The study cohort comprised 5511 patients implanted with an implantable cardioverter-defibrillator (ICD) in landmark clinical trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID) who were in sinus rhythm at enrollment. Multivariate cox analysis was performed to evaluate the time-dependent association between development of in-trial device detected AF and VT/VF with subsequent CHF exacerbation and death. RESULTS: Multivariate analysis showed that AF occurrence and VT/VF occurrence were both associated with a similar magnitude of risk for subsequent CHF exacerbation (HR = 1.73 and 1.87 respectively, p < .001 for both). In contrast, only in-trial VT/VF was associated with a significant > two-fold increase in the risk of subsequent mortality (HR = 2.13, p < .001) whereas AF occurrence was not associated with a significant mortality increase after adjustment for in-trial VT/VF (HR = 1.36, p = .096). CONCLUSION: Our findings from a large cohort of ICD recipients enrolled in landmark clinical trials show that device detected AF and VT/VF can be used to identify patients with increased risk for CHF exacerbation and mortality. These findings suggest a need for early intervention in CHF patients who develop device-detected atrial and ventricular tachyarrhythmias.

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.

Competing risks of monomorphic vs. non-monomorphic ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study.

AIMS: Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors for MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. METHODS AND RESULTS: The multicentre retrospective cohort study included 2668 patients (age 63.1 ± 13.0 years; 23% female; 78% white; 43% non-ischaemic cardiomyopathy; left ventricular ejection fraction 28.2 ± 11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and electrocardiogram metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate implantable cardioverter-defibrillator (ICD) therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.01-1.34], larger SVGel (HR 1.17; 95% CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95% CI 0.63-0.86) and SAIQRST (HR 0.84; 95% CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT [time-dependent area under the receiver operating characteristic curve (ROC(t)AUC) 0.728; 95% CI 0.668-0.788] identified high-risk (> 50%) patients with 75% sensitivity and 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95% CI 0.868-0.962), both satisfactory calibration. CONCLUSION: We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future randomized controlled trials of prophylactic ventricular tachycardia ablation. CLINICAL TRIAL REGISTRATION: URL:www.clinicaltrials.gov Unique identifier:NCT03210883.

A case report of ventricular fibrillation following Shockwave intravascular lithotripsy during percutaneous coronary intervention.

BACKGROUND: Shockwave intravascular lithotripsy (S-IVL) is widely used during percutaneous coronary intervention (PCI) of calcified coronary arteries. Ventricular capture beats during S-IVL are common but arrhythmias are rare. CASE PRESENTATION: A 75-year-old woman was scheduled for PCI to a short, heavily calcified chronic total occlusion of the right coronary artery. After wiring of the occlusion, S-IVL was used to predilated the calcified stenosis. During S-IVL, the patient developed ventricular fibrillation twice. CONCLUSION: To our knowledge, this is only the second reported case of VF during S-IVL. Although very rare, it is important to be aware of this potential and serious complication.

A case of early repolarization syndrome in which hyponatremia and coronary vasospasms induced ventricular fibrillation.

A 60-year-old man was referred to our hospital presenting with unconsciousness due to severe hyponatremia. The twelve­lead ECG on admission exhibited prominent J waves in the inferolateral leads. During the treatment for hyponatremia, ventricular fibrillation (VF) occurred and the electrogram (ECG) after the VF incident exhibited marked ST elevation in the inferolateral leads. An Ach provocation test induced vasospasms in the right and left coronary arteries and J wave augmentation, suggesting a high risk for vasospastic angina. Finally, a subcutaneous implantable cardioverter defibrillator was implanted in the patient. We hereby discuss the possible contribution of hyponatremia to VF episodes in early repolarization syndrome based on the present case.

A Case of Ventricular Fibrillation in Masked Long-QT Syndrome Coexisting with Coronary Vasospasm.

Although long-QT syndrome (LQTS) with a normal range QT interval at rest leads to fatal ventricular arrhythmias, it is difficult to diagnose. In this article, we present a rare case of a patient who suffered a cardiac arrest and was recently diagnosed with LQTS and coronary vasospasm. A 62-year-old man with no syncopal episodes had a cardiopulmonary arrest while running. During coronary angiography, vasospasm was induced and we prescribed coronary vasodilators, including calcium channel blockers. An exercise stress test was performed to evaluate the effect of medications and accidentally unveiled exercise-induced QT prolongation. He was diagnosed with LQTS based on diagnostic criteria. Pharmacotherapy and an implantable cardioverter defibrillator were used for his medical management. It is extremely rare for LQTS and coronary vasospasm to coexist. In cases of exercise-induced arrhythmic events, the exercise stress test might be helpful to diagnose underlying disease.

[High risk syncope in a young patient: An uncommon cause]. / Sincope de alto riesgo en paciente joven: Una causa poco frecuente.

Syncope is a frequent consult. It's responsible for 1 to 3% of consults to the emergency room in the United States. The cause is generally benign; however, high-risk cases are potentially deadly and must be identified. We present a case report of a 40-year-old female who presents with syncope, Torsade de Pointes, and ventricular fibrillation. The coronary angiography showed no disease of the coronary arteries. The ventriculography, transthoracic echocardiogram, and cardiac magnetic resonance revealed a mid-ventricular Takotsubo cardiomyopathy. The ECG showed a prolonged QT interval with an inverted T wave. During the first 48 hours, she presented multiple episodes of non-sustained polymorphic ventricular tachycardia. The patient evolved with diminished QTc interval and regression of the wall motion abnormalities. At the 6-month follow-up the patient was asymptomatic, without new episodes.

[Characteristics of electrocardiogram in fulminant myocarditis].

Objective: To investugate the unique electrocardiogram (ECG) characteristics of fulminant myocarditis (FM) patients and provide important clues for the diagnosis of FM. Methods: This was a retrospective study. Patients diagnosed with acute myocarditis at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 2017 to April 2022 were enrolled and divided into fulminant myocarditis group (FM) and non-fulminant myocarditis group (NFM) according to clinical diagnosis. A total of 246 healthy people who underwent physical examination in the Health examination Center of Tongji Hospital at the same period were selected as the control group. The clinical data and ECG characteristics of the above 3 groups were analyzed and compared. Logistic regression model was used to analyze the influence of ECG parameters on left ventricular ejection fraction in FM patients. Receiver operating curves were constructed to evaluate the predictive value of different ECG parameters for FM. Results: A total of 180 patients were included in this study (FM group: n=123; NFM group: n=57), with an age of (35.0±16.2) years and 106 males (58.89%). Compared with NFM group, ECG was significantly abnormal in FM group, with a higher incidence of sinus tachycardia, ventricular tachycardia or ventricular fibrillation, escape rhythm, right bundle branch block, third degree atrioventricular block, ST-segment elevation, low voltage, prolonged QTc interval, and widened QRS wave in the FM group (all P<0.05). The ECG parameters showed that the amplitude of the full lead QRS wave in FM group was lower than that in NFM group (P<0.01). The average heart rate and QTc interval of FM group were significantly higher than those of NFM and control groups (all P<0.05). Although ST-segment elevation had a higher incidence in the FM group, ECG parameters showed that except for leads Ⅲ and aVF, the ST segment levels in all leads in the FM group were lower than those in the control group (all P<0.05). There was a statistically significant difference in some ST segment changes between FM and NFM groups, while there was no statistical difference between the NFM and control groups. Multivariate regression analysis showed that widened QRS wave and increased heart rate were the influencing factors for left ventricular systolic dysfunction in FM patients (OR=16.914, 95%CI: 1.367-209.224, P=0.028; OR=1.026, 95%CI: 1.010-1.042, P=0.001). Receiver operating curve analysis showed that heart rate>86.90 beat/min, QTc>431.50 ms, and RV5+SV1<1.72 mV had certain predictive value for FM diagnosis. Conclusions: FM patients displayed marked and severe ECG abnormalities, and characteristic changes in ECG can provide important first clues for the diagnosis of FM.

Effects of parameters on radiofrequency guidewire ablation: In vitro and in vivo experiments.

BACKGROUND: A novel ablation technique with guidewire has emerged as a promising approach for mapping and ablation of arrhythmias originating from left ventricular summit. However, its biophysical characteristics have not been fully clarified. METHODS AND RESULTS: In the in vitro experiment, guidewire ablation (GA) was performed in vessel models of 1.17 and 2.24 mm to determine the maximum safety power. Then with the maximum safety power, the predictive value of generator impedance (GI) drop on lesion radius was explored. In the in vivo experiment, the feasibility of the maximum safety power and lesion formation was verified in the living swine. It was found that in both groups, the incidence of steam pops increased along with the raise of ablation power, and the maximum safety power was 10 W for the 1.17-mm group and 15 W for the 2.24-mm group. There was a strong linear correlation between GI drop and maximum lesion radius (in 1.17 mm-10-W group: r = .961; in 2.24 mm-15-W group: r = .918). In the in vivo experiment, besides ventricular fibrillation happened once, no other complications were observed, and lesions were found at both 48-h and 8-week groups. CONCLUSIONS: The safety power of GA should be adjusted according to the diameter of the vessel. Besides, the GI drop can predict the lesion radius during GA.

Antitachycardia pacing at the His bundle is safer than conventional right ventricular antitachycardia pacing in a canine myocardial ischemic injury model.

INTRODUCTION: Antitachycardia pacing (ATP) is used to terminate ventricular tachycardia (VT) by delivering rapid, low energy pacing to the right ventricle (RV). Unfortunately, ATP is not effective against all VT episodes and can result in adverse outcomes, such as VT acceleration and degeneration into ventricular fibrillation (VF). Improving ATP is therefore desirable. Our objective was to compare the efficacy and safety of ATP delivered at the His bundle to traditional ATP. METHODS: Six dogs were anesthetized and pacing leads were implanted in the RV and His bundle. The left anterior descending artery was occluded for 2 h to create an ischemic injury. In a study 4-7 days later, a 128-electrode sock was placed snugly around the ventricles and VT was induced using rapid pacing. ATP was delivered from either the His bundle or RV lead, then attempted at the other location if unsuccessful. Success rates and instances of VT acceleration and degeneration into VF were calculated. RESULTS: We induced 83 runs of VT and attempted ATP 128 times. RV ATP was successful in 36% of attempts; His ATP was successful in 38% of attempts. RV ATP resulted in significantly more adverse outcomes. RV and His ATP induced VT acceleration in 9% and 3% of trains, respectively, and induced degeneration into VF in 5% and 1% of trains, respectively. CONCLUSION: His bundle ATP is safer, but not significantly more effective, than RV ATP.

Risk of ventricular arrhythmias following implantable cardioverter-defibrillator generator change in patients with recovered ejection fraction: Implications for shared decision-making.

INTRODUCTION: Guidelines indicate primary-prevention implantable cardioverter-defibrillators (ICDs) for most patients with left ventricular ejection fraction (LVEF) ≤ 35%. Some patients' LVEFs improve during the life of their first ICD. In patients with recovered LVEF who never received appropriate ICD therapy, the utility of generator replacement upon battery depletion remains unclear. Here, we evaluate ICD therapy based on LVEF at the time of generator change, to educate shared decision-making regarding whether to replace the depleted ICD. METHODS: We followed patients with a primary-prevention ICD who underwent generator change. Patients who received appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation (VT/VF) before generator change were excluded. The primary endpoint was appropriate ICD therapy, adjusted for the competing risk of death. RESULTS: Among 951 generator changes, 423 met inclusion criteria. During 3.4 ± 2.2 years follow-up, 78 (18%) received appropriate therapy for VT/VF. Compared to patients with recovered LVEF > 35% (n = 161 [38%]), those with LVEF ≤ 35% (n = 262 [62%]) were more likely to require ICD therapy (p = .002; Fine-Gray adjusted 5-year event rates: 12.7% vs. 25.0%). Receiver operating characteristic analysis revealed the optimal LVEF cutoff for VT/VF prediction to be 45%, the use of which further improved risk stratification (p < .001), with Fine-Gray adjusted 5-year rates 6.2% versus 25.1%. CONCLUSION: Following ICD generator change, patients with primary-prevention ICDs and recovered LVEF have significantly lower risk of subsequent ventricular arrhythmias compared to those with persistent LVEF depression. Risk stratification at LVEF 45% offers significant additional negative predictive value over a 35% cutoff, without a significant loss in sensitivity. These data may be useful during shared decision-making at the time of ICD generator battery depletion.

Machine Learned Cellular Phenotypes in Cardiomyopathy Predict Sudden Death.

RATIONALE: Susceptibility to VT/VF (ventricular tachycardia/fibrillation) is difficult to predict in patients with ischemic cardiomyopathy either by clinical tools or by attempting to translate cellular mechanisms to the bedside. OBJECTIVE: To develop computational phenotypes of patients with ischemic cardiomyopathy, by training then interpreting machine learning of ventricular monophasic action potentials (MAPs) to reveal phenotypes that predict long-term outcomes. METHODS AND RESULTS: We recorded 5706 ventricular MAPs in 42 patients with coronary artery disease and left ventricular ejection fraction ≤40% during steady-state pacing. Patients were randomly allocated to independent training and testing cohorts in a 70:30 ratio, repeated K=10-fold. Support vector machines and convolutional neural networks were trained to 2 end points: (1) sustained VT/VF or (2) mortality at 3 years. Support vector machines provided superior classification. For patient-level predictions, we computed personalized MAP scores as the proportion of MAP beats predicting each end point. Patient-level predictions in independent test cohorts yielded c-statistics of 0.90 for sustained VT/VF (95% CI, 0.76-1.00) and 0.91 for mortality (95% CI, 0.83-1.00) and were the most significant multivariate predictors. Interpreting trained support vector machine revealed MAP morphologies that, using in silico modeling, revealed higher L-type calcium current or sodium-calcium exchanger as predominant phenotypes for VT/VF. CONCLUSIONS: Machine learning of action potential recordings in patients revealed novel phenotypes for long-term outcomes in ischemic cardiomyopathy. Such computational phenotypes provide an approach which may reveal cellular mechanisms for clinical outcomes and could be applied to other conditions.

Successful defibrillation testing in patients undergoing elective subcutaneous implantable cardioverter-defibrillator generator replacement.

AIMS: After implantation of a subcutaneous implantable cardioverter-defibrillator (S-ICD), a defibrillation test (DFT) is performed to ensure that the device can effectively detect and terminate the induced ventricular arrhythmia. Data on DFT efficacy at generator replacement are scarce with a limited number of patients and conflicting results. This study evaluates conversion efficacy during DFT at elective S-ICD generator replacement in a large cohort from our tertiary centre. METHODS AND RESULTS: Retrospective data of patients who underwent an S-ICD generator replacement for battery depletion with subsequent DFT between February 2015 and June 2022 were collected. Defibrillation test data were collected from both implant and replacement procedures. PRAETORIAN scores at implant were calculated. Defibrillation test was defined unsuccessful when two conversions at 65 J failed. A total of 121 patients were included. The defibrillation test was successful in 95% after the first and 98% after two consecutive tests. This was comparable with success rates at implant, despite a significant rise in shock impedance (73 ± 23 vs. 83 ± 24 Ω, P < 0.001). Both patients with an unsuccessful DFT at 65 J successfully converted with 80 J. CONCLUSION: This study shows a high DFT conversion rate at elective S-ICD generator replacement, which is comparable to conversion rates at implant, despite a rise in shock impedance. Evaluating device position before generator replacement may be recommended to optimize defibrillation success at generator replacement.

Repolarization indicates electrical instability in ventricular arrhythmia originating from papillary muscle.

AIMS: Cardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood. METHODS AND RESULTS: Ventricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity. CONCLUSION: RT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.

Outcome and safety of intraoperative defibrillation testing during device replacement: the Simpler trial.

AIMS: Intraoperative defibrillation testing (DT) during implant or replacement of implantable cardioverter-defibrillators (ICDs) has been a matter of debate for many years. This debate was put to rest by the Simple and Nordic ICD trials, and the practice of testing during new implantations has essentially been almost abandoned. Old registries demonstrated an increased incidence of significant findings in DT during replacements. The aim of the present study was to evaluate frequency of significant findings and safety of DT in subjects undergoing device replacement. METHODS AND RESULTS: A prospective observational multi-centre study included consecutive patients undergoing ICD generator replacement. The primary outcome was a failure to terminate induced ventricular fibrillation (VF) with a single shock 10 J below the maximal capacity of the device. Secondary outcomes included complications of DT. Patients were followed-up at 1- and 6-months post-procedure. A total of 92 patients were eligible, and consented to the study, of which 84 underwent DT during battery replacement. The median age was 68 years and 79.8% were males. Induction of VF was successful in 84 patients as was a successful conversion on the first attempt in all. There were no procedure-related complications. During follow up one patient had two appropriate ICD shock events. In four patients, ICD programming was changed. None suffered inappropriate shock. There was no evidence of lead malfunction. Two deaths occurred, none of which was related to arrhythmia. CONCLUSION: The present study found DT was not associated with complications in patients undergoing ICD generator replacement but produced no clinically important information.

The genetic basis of apparently idiopathic ventricular fibrillation: a retrospective overview.

AIMS: During the diagnostic work-up of patients with idiopathic ventricular fibrillation (VF), next-generation sequencing panels can be considered to identify genotypes associated with arrhythmias. However, consensus for gene panel testing is still lacking, and variants of uncertain significance (VUS) are often identified. The aim of this study was to evaluate genetic testing and its results in idiopathic VF patients. METHODS AND RESULTS: We investigated 419 patients with available medical records from the Dutch Idiopathic VF Registry. Genetic testing was performed in 379 (91%) patients [median age at event 39 years (27-51), 60% male]. Single-gene testing was performed in 87 patients (23%) and was initiated more often in patients with idiopathic VF before 2010. Panel testing was performed in 292 patients (77%). The majority of causal (likely) pathogenic variants (LP/P, n = 56, 15%) entailed the DPP6 risk haplotype (n = 39, 70%). Moreover, 10 LP/P variants were found in cardiomyopathy genes (FLNC, MYL2, MYH7, PLN (two), TTN (four), RBM20), and 7 LP/P variants were identified in genes associated with cardiac arrhythmias (KCNQ1, SCN5A (2), RYR2 (four)). For eight patients (2%), identification of an LP/P variant resulted in a change of diagnosis. In 113 patients (30%), a VUS was identified. Broad panel testing resulted in a higher incidence of VUS in comparison to single-gene testing (38% vs. 3%, P < 0.001). CONCLUSION: Almost all patients from the registry underwent, albeit not broad, genetic testing. The genetic yield of causal LP/P variants in idiopathic VF patients is 5%, increasing to 15% when including DPP6. In specific cases, the LP/P variant is the underlying diagnosis. A gene panel specifically for idiopathic VF patients is proposed.