Implantable cardioverter defibrillator therapy in paediatric patients for primary vs. secondary prevention.

AIMS: The decisions about placing an ICD in a child are more difficult than in an adult due to longer expected lifespan and the complication risk. Young patients gain the most years from ICDs, despite higher risk of device-related complications. The secondary prevention ICD indication is clear, and device is implanted regardless of potential complications. For primary prevention, risk of sudden cardiac death and complications need to be evaluated. We aimed to compare outcomes for primary and secondary prevention ICDs. METHODS AND RESULTS: Retrospective nationwide cohort study including paediatric patients identified from the Danish ICD registry with ICD implanted at an age ≤ 15 from 1982-21. Demographics, complications (composite of device-related infections or lead-failure requiring re-operation, mortality because of arrhythmia, or unknown cause), and mortality were retrieved from medical charts. Endpoint was appropriate therapy (shock or anti-tachycardia pacing for ventricular tachycardia or fibrillation). Of 72 receiving an ICD, the majority had channelopathies (n = 34) or structural heart diseases (n = 28). ICDs were implanted in 23 patients for primary prevention and 49 for secondary prevention, at median ages of 13.8 and 11.6 years (P-value 0.01), respectively. Median follow-up was 9.0 (interquartile ranges: 4.7-13.5) years. The 10-year cumulative incidence of first appropriate therapy was 70%, with complication and inappropriate therapy rates at 41% and 15%, respectively. No difference was observed between prevention groups for all outcomes. Six patients died during follow-up. CONCLUSION: In children, two-thirds are secondary prevention ICDs. Children have higher appropriate therapy and complication rates than adults, while the inappropriate therapy rate was low.

Defibrillation strategies for patients with refractory ventricular fibrillation: A systematic review and meta-analysis.

AIM: The aim of this study was to summarize the existing evidence about the effectiveness of double defibrillation (DD) in comparison to standard defibrillation for patients with refractory ventricular fibrillation (RVF). DD encompasses double "sequential" external defibrillation (DSeq-D) and double "simultaneous" defibrillation (DSim-D), with the study also shedding light on the respective effects of DSeq-D and DSim-D. METHODS: Investigators systematically searched PubMed, EMBASE and Cochrane Central databases for randomized controlled trials (RCTs) and cohort studies from their inception until June 06, 2024. The rate of survival to hospital discharge was the primary outcome, while the incidence of return of spontaneous circulation (ROSC), termination of ventricular fibrillation (VF), survival to hospital admission and good neurologic outcome were secondary outcomes. Relative ratios (RR) and 95% confidence intervals (CIs) were calculated for each outcome. Heterogeneity was assessed using I square value. RESULTS: A total of 6 trials, comprising 1360 patients, were included. One was an RCT, and five were observational cohort studies. The RCT showed that, compared to standard defibrillation, DSeq-D was associated with higher incidences of survival to hospital discharge, termination of VF, ROSC and good neurologic outcome. However, the pooled results of cohort studies found no benefit of DD over standard defibrillation in survival to hospital discharge (RR, 0.91; 95% CI, 0.46-1.78), nor in secondary outcomes. Furthermore, subgroup analysis suggested DSim-D was linked with lower ROSC rate compared to standard defibrillation (RR, 0.65; 95% CI, 0.49-0.86), while there was no significance between DSeq-D and standard defibrillation (RR, 1.00; 95% CI, 0.70-1.42). CONCLUSIONS: The benefit of DSeq-D in survival to hospital discharge for RVF patients was found in the RCT, but not in cohort studies. Additionally, DSim-D should be applied with greater caution for RVF patients. Further validation is needed through larger-scale and higher-quality trials. TRIAL REGISTRY: INPLASY; Registration number: INPLASY202340015; URL: https://inplasy.com/.

Digoxin and Risk of Ventricular Tachyarrhythmia and Death in ICD Recipients.

BACKGROUND: Some studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in heart failure patients with an implantable cardioverter-defibrillator (ICD). OBJECTIVES: This study sought to assess whether digoxin use is associated with increased risk of VT/VF in patients with heart failure with reduced ejection fraction with a primary prevention ICD in landmark clinical trials. METHODS: The study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in 4 landmark MADIT trials (Multicenter Automatic Defibrillator Implantation Trials). We employed propensity score quintile stratification for treatment with digoxin as well as additional multivariable adjustment to assess the risk of digoxin vs no-digoxin therapy for the endpoints of first and recurrent VT/VF and all-cause mortality. The proportional hazards regression models for arrhythmia-specific endpoints incorporated adjustments for the competing risk of death. RESULTS: At baseline, 1,155 of 4,499 patients were on digoxin (26%). After propensity score quintile stratification, patients prescribed digoxin were shown to exhibit a statistically significant 48% increased risk of VT/VF (P < 0.001), 42% increased risk of the composite of VT/VF or death (P < 0.001), and a 37% increased risk of all-cause mortality (P = 0.006). Digoxin use was also associated with increased risk of appropriate ICD shocks (HR: 1.91; P < 0.001) and with increased burden of VT/VF events (HR: 1.46; P = 0.001). CONCLUSIONS: Our findings suggests that digoxin use is associated with ventricular tachyarrhythmia and death in heart failure with reduced ejection fraction patients with an ICD.

Ventricular Arrhythmias After Primary Percutaneous Coronary Intervention for STEMI.

Importance: Currently, mortality risk for patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) with an uncomplicated postprocedure course is low. Less is known regarding the risk of in-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF). Objective: To evaluate the risk of late VT and VF after primary PCI for STEMI. Design, Setting, and Participants: This cohort study included adults aged 18 years or older with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, identified in the US National Cardiovascular Data Registry Chest Pain-MI Registry. Data were analyzed from April to December 2020. Main Outcomes and Measures: Multivariable logistic regression was used to evaluate the risk of late VT (≥7 beat run of VT during STEMI hospitalization ≥1 day after PCI) or VF (any episode of VF≥1 day after PCI) associated with cardiac arrest and associations between late VT or VF and in-hospital mortality in the overall cohort and a cohort with uncomplicated STEMI without prior myocardial infarction or heart failure, systolic blood pressure less than 90 mm Hg, cardiogenic shock, cardiac arrest, reinfarction, or left ventricular ejection fraction (LVEF) less than 40%. Results: A total of 174 126 eligible patients with STEMI were treated with primary PCI at 814 sites in the study; 15 460 (8.9%) had VT or VF after primary PCI, and 4156 (2.4%) had late VT or VF. Among the eligible patients, 99 905 (57.4%) at 807 sites had uncomplicated STEMI. The median age for patients with late VT or VF overall was 63 years (IQR, 55-73 years), and 75.5% were men; the median age for patients with late VT or VF with uncomplicated STEMI was 60 years (IQR, 53-69 years), and 77.7% were men. The median length of stay was 3 days (IQR, 2-7 days) for the overall cohort with late VT or VF and 3 days (IQR, 2-4 days) for the cohort with uncomplicated STEMI with late VT or VF. The risk of late VT or VF was 2.4% (overall) and 1.7% (uncomplicated STEMI). Late VT or VF with cardiac arrest occurred in 674 patients overall (0.4%) and in 117 with uncomplicated STEMI (0.1%). LVEF was the most significant factor associated with late VT or VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54-1.85). Late VT or VF events were associated with increased odds of in-hospital mortality in the overall cohort (AOR, 6.40; 95% CI, 5.63-7.29) and the cohort with uncomplicated STEMI (AOR, 8.74; 95% CI, 6.53-11.70). Conclusions and Relevance: In this study, a small proportion of patients with STEMI treated with primary PCI had late VT or VF. However, late VT or VF with cardiac arrest was rare, particularly in the cohort with uncomplicated STEMI. This information may be useful when determining the optimal timing for hospital discharge after STEMI.

Bleeding and Thrombosis in Patients With Out-of-Hospital Ventricular Tachycardia/Ventricular Fibrillation Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation improves outcomes after out-of-hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in-hospital mortality. METHODS AND RESULTS: Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96-0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P<0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03]). CONCLUSIONS: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.

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.

Association between survival and number of shocks for pulseless ventricular arrhythmias during pediatric in-hospital cardiac arrest in a national registry.

BACKGROUND: Annually 15,200 children suffer an in-hospital cardiac arrest (IHCA) in the US. Ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) is the initial rhythm in 10-15% of these arrests. We sought to evaluate the association of number of shocks and early dose escalation with survival for initial VF/pVT in pediatric IHCA. METHODS: Using 2000-2020 data from the American Heart Association's (AHA) Get with the Guidelines®-Resuscitation (GWTG-R) registry, we identified children >48 hours of life and ≤18 years who had an IHCA from initial VF/pVT and received defibrillation. RESULTS: There were 251 subjects (37.7%) who received a single shock and 415 subjects (62.3%) who received multiple shocks. Baseline and cardiac arrest characteristics did not differ between those who received a single shock versus multiple shocks except for duration of arrest and calendar year. The median first shock dose was consistent with AHA dosing recommendations and not different between those who received a single shock versus multiple shocks. Survival was improved for those who received a single shock compared to multiple shocks. However, no difference in survival was noted between those who received 2, 3, or ≥4 shocks. Of those receiving multiple shocks, no difference was observed with early dose escalation. CONCLUSIONS: In pediatric IHCA, most patients with initial VF/pVT require more than one shock. No distinctions in patient or pre-arrest characteristics were identified between those who received a single shock versus multiple shocks. Subjects who received a single shock were more likely to survive to hospital discharge even after adjusting for duration of resuscitation.

Trends in ventricular fibrillation/flutter mortality in US population, 1999 to 2019.

BACKGROUND: The Ventricular fibrillation and flutter (VF/VFL)-related mortality trends in the United States (US) population have not yet been investigated. We aimed to assess the trends of VT/VFL-related mortality from 1999 to 2019 among subjects aged more than 15 years old in the US. METHODS: Data derived from the Centers for Disease Control and Prevention's (CDC) WONDER were analyzed between 1999 and 2019 for VF/VFL-related mortality in subjects aged more than 15 years of age. Adjusted mortality rates (AAMRs) per 100,000 people by year, sex, race and urban-rural status with relative confidence intervals (CIs) were determined. Both the average annual percent change (AAPC) and the annual percent change (APC) with 95% Cis were calculated. RESULTS: Between 1999 and 2019, 242,125 VT/VFL-related deaths occurred in the US. The overall AAMR steadily declined [AAPC -4.4% (95% CI: -4.7 to -4.0, p < .0001)]. Women showed a more pronounced AAMRs decline [AAPC: -4.8% (95% CI: -5.3 to -4.3, p < .0001). AAMR steadily declined in white subjects and in those of other races [AAPC: -4.5 (95% CI: -4.7 to -4.2, p < .0001) and AAPC: -4.3 (95% CI: -5.1 to -3.5, p < .001), respectively]. Conversely, African Americans showed a steadily AMMR decline between 1999 and 2007 [APC: -8.3 (95% CI: -9.2 to -7.3, p < .0001)], followed by a period of stability from 2007 to 2019 (p = .73). A similar decline was observed for the AAMR among subjects living in urban and rural areas. CONCLUSIONS: VT/VFL-related mortality steadily decreased between 1999 and 2019 in US. Despite the encouraging results, further efforts are needed to prevent VF/VFL-related mortality in US subjects.

Defibrillation Strategies for Refractory Ventricular Fibrillation.

BACKGROUND: Despite advances in defibrillation technology, shock-refractory ventricular fibrillation remains common during out-of-hospital cardiac arrest. Double sequential external defibrillation (DSED; rapid sequential shocks from two defibrillators) and vector-change (VC) defibrillation (switching defibrillation pads to an anterior-posterior position) have been proposed as defibrillation strategies to improve outcomes in patients with refractory ventricular fibrillation. METHODS: We conducted a cluster-randomized trial with crossover among six Canadian paramedic services to evaluate DSED and VC defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest. Patients were treated with one of these three techniques according to the strategy that was randomly assigned to the paramedic service. The primary outcome was survival to hospital discharge. Secondary outcomes included termination of ventricular fibrillation, return of spontaneous circulation, and a good neurologic outcome, defined as a modified Rankin scale score of 2 or lower (indicating no symptoms to slight disability) at hospital discharge. RESULTS: A total of 405 patients were enrolled before the data and safety monitoring board stopped the trial because of the coronavirus disease 2019 pandemic. A total of 136 patients (33.6%) were assigned to receive standard defibrillation, 144 (35.6%) to receive VC defibrillation, and 125 (30.9%) to receive DSED. Survival to hospital discharge was more common in the DSED group than in the standard group (30.4% vs. 13.3%; relative risk, 2.21; 95% confidence interval [CI], 1.33 to 3.67) and more common in the VC group than in the standard group (21.7% vs. 13.3%; relative risk, 1.71; 95% CI, 1.01 to 2.88). DSED but not VC defibrillation was associated with a higher percentage of patients having a good neurologic outcome than standard defibrillation (relative risk, 2.21 [95% CI, 1.26 to 3.88] and 1.48 [95% CI, 0.81 to 2.71], respectively). CONCLUSIONS: Among patients with refractory ventricular fibrillation, survival to hospital discharge occurred more frequently among those who received DSED or VC defibrillation than among those who received standard defibrillation. (Funded by the Heart and Stroke Foundation of Canada; DOSE VF ClinicalTrials.gov number, NCT04080986.).

Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation.

BACKGROUND: Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias. OBJECTIVES: The purpose of this study was to determine whether presence of myocardial fibrosis on visual assessment (MFVA) and gray zone fibrosis (GZF) mass predicts sudden cardiac death (SCD) and ventricular fibrillation/sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation. METHODS: In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of SCD and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation. RESULTS: Among 700 patients (age 68.0 ± 12.0 years), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over median 6.93 years (IQR: 5.82-9.32 years). MFVA predicted SCD (HR: 26.3; 95% CI: 3.7-3,337; negative predictive value: 100%). In competing risk analyses, MFVA also predicted the arrhythmic endpoint (subdistribution HR: 19.9; 95% CI: 6.4-61.9; negative predictive value: 98.6%). Compared with no MFVA, a GZF mass measured with the 5SD method (GZF5SD) >17 g was associated with highest risk of SCD (HR: 44.6; 95% CI: 6.12-5,685) and the arrhythmic endpoint (subdistribution HR: 30.3; 95% CI: 9.6-95.8). Adding GZF5SD mass to MFVA led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint. CONCLUSIONS: In CIED recipients, MFVA excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF5SD mass added predictive value in relation to SCD and the arrhythmic endpoint.

Association of a simple SACAF score with bystander witnessed sudden death due to ventricular tachyarrhythmias in a multicenter cohort.

Out-of-hospital cardiac arrest (OHCA) remains a major threat to public health worldwide. OHCA patients presenting initial shockable ventricular tachycardia/ventricular fibrillation (VT/VF) rhythm have a better survival rate. We sought to develop a simple SACAF score to discriminate VT/VF from non-VT/VF OHCAs based on the Taiwan multicenter hospital-based registry database. We analyzed the in- and pre-hospital data, including demographics, baseline comorbidities, response times, automated external defibrillator information, and the 12-lead ECG recording closest to the OHCA event in bystander-witnessed OHCA patients. Among the 461 study patients, male sex (OR 2.54, 95% CI = 1.32-4.88, P = 0.005), age ≤ 65 years (OR 2.78, 95% CI = 1.64-4.70, P < 0.001), cardiovascular diseases (OR 2.97, 95% CI = 1.73-5.11, P < 0.001), and atrial fibrillation (AF) (OR 2.36, 95% CI = 1.17-4.76, P = 0.017) were independent risk factors for VT/VF OHCA (n = 81) compared with non-VT/VF OHCA (n = 380). A composite SACAF score was developed (male Sex, Age ≤ 65 years, Cardiovascular diseases, and AF) and compared with the performance of a modified CHA2DS2-VASc score (Cardiovascular diseases, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke, Vascular disease, Age 65-74 years, female Sex category). The area under the receiver operating characteristic curve (AUC) of the SACAF was 0.739 (95% CI = 0.681-0.797, P < 0.001), whereas the AUC of the modified CHA2DS2-VASc was 0.474 (95% CI = 0.408-0.541, P = 0.464). A SACAF score of ≥ 2 was useful in discriminating VT/VF from non-VT/VF OHCAs with a sensitivity of 0.75 and a specificity of 0.60. In conclusion, the simple SACAF score appears to be useful in discriminating VT/VF from non-VT/VF bystander-witnessed OHCAs and the findings may also shed light on future mechanistic evaluation.

Atrial fibrillation is associated with increased risk of lethal ventricular arrhythmias.

Atrial fibrillation (AF) is associated with various major adverse cardiac events such as ischemic stroke, heart failure, and increased overall mortality. However, its association with lethal ventricular arrhythmias such as ventricular tachycardia (VT), ventricular flutter (VFL), and ventricular fibrillation (VF) is controversial. We conducted this study to determine whether AF can increase the risk of VT, VFL, and VF. We utilized the Korean National Health Insurance Service database for this nationwide population-based study. This study enrolled people who underwent a nationwide health screen in 2009 for whom clinical follow-up data were available until December 2018. Primary outcome endpoint was the occurrence of VT, VFL, or VF in people who were and were not diagnosed with new-onset AF in 2009. We analyzed a total of 9,751,705 people. In 2009, 12,689 people were diagnosed with new-onset AF (AF group). The incidence (events per 1000 person-years of follow-up) of VT, VFL, and VF was 2.472 and 0.282 in the AF and non-AF groups, respectively. After adjustment for covariates, new-onset AF was associated with 4.6-fold increased risk (p < 0.001) of VT, VFL, and VF over 10 years of follow-up. The risk of VT, VFL, and VF was even higher if identification of AF was based on intensified criteria (≥ 2 outpatient records or ≥ 1 inpatient record; hazard ratio = 5.221; p < 0.001). In conclusion, the incidence of VT, VFL, and VF was significantly increased in people with new-onset AF. The potential risk of suffering lethal ventricular arrhythmia in people with AF should be considered in clinical practice.

Electrical storm: Prognosis and management.

Electrical storm is present when a cluster of ventricular arrhythmias (VAs) occurs within a short time frame. The most widely accepted definition is 3 or more episodes of VA within a 24-h period, although prognostic risk begins to rise when 2 or more events occur within 3months. Electrical storm often presents as a medical emergency in the form of recurrent implantable cardiac defibrillator (ICD) shocks, recurrent syncope in patients with no ICD or low cardiac output symptoms. Management often requires a multimodality approach including ICD management, pharmacologic therapy, catheter ablation and modulations of the autonomic nervous system. In this article, we review the definition, prognosis and management of electrical storm.

Atrial fibrillation increases the risk of recurrent ventricular tachyarrhythmias in implantable cardioverter defibrillator recipients.

BACKGROUND: Data regarding recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients according to atrial fibrillation is limited. OBJECTIVE: To assess the prognostic impact of atrial fibrillation on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator recipients. METHODS: A large retrospective registry was used, including all ICD recipients with episodes of ventricular tachycardia or fibrillation from 2002 to 2016. Patients with atrial fibrillation were compared to those without atrial fibrillation. The primary endpoint was first recurrence of ventricular tachyarrhythmias at 5 years. Secondary endpoints comprised recurrences of ICD-related therapies, first cardiac rehospitalization and all-cause mortality at 5 years. Cox regression, Kaplan-Meier and propensity score-matching analyses were applied. RESULTS: A total of 592 consecutive ICD recipients were included (33% with atrial fibrillation). Atrial fibrillation was associated with reduced freedom from recurrent ventricular tachyarrhythmias (42% vs. 50%, log-rank P=0.004; hazard ratio 1.445, 95% confidence interval 1.124-1.858), mainly attributable to recurrent ventricular fibrillation in secondary-preventive ICD recipients. Accordingly, atrial fibrillation was associated with reduced freedom from first appropriate ICD therapies (31% vs. 42%, log-rank P=0.001; hazard ratio 1.598, 95% confidence interval 1.206-2.118). Notably, the primary endpoint of freedom from first episode of recurrent ventricular tachyarrhythmias was still reduced in those with atrial fibrillation compared to those without atrial fibrillation after propensity score matching. Regarding secondary endpoints, patients with atrial fibrillation still showed a trend towards reduced freedom from appropriate ICD therapies. CONCLUSIONS: Atrial fibrillation was associated with increased rates of recurrent ventricular tachyarrhythmias and appropriate device therapies in ICD recipients with ventricular tachyarrhythmias.

Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study.

[Figure: see text].

Prognostic value of admission serum magnesium in acute myocardial infarction complicated by malignant ventricular arrhythmias.

OBJECTIVES: Although electrolyte abnormalities are related to worse clinical outcomes in patients with acute myocardial infarction (AMI), little is known about the association between admission serum magnesium level and adverse events in AMI patients complicated by out-of-hospital cardiac arrest presenting with malignant ventricular arrhythmias (OHCA-MVA). We investigated the prognostic value of serum magnesium level on admission in these patients. METHODS: We retrospectively analyzed the data of 165 consecutive reperfused AMI patients complicated with OHCA-MVA between April 2007 and February 2020 in our university hospital. Serum magnesium concentration was measured on admission. The primary outcome was in-hospital death. RESULTS: Fifty-four patients (33%) died during hospitalization. Higher serum magnesium level was significantly related to in-hospital death (Fine & Gray's test; p < 0.001). In multivariable logistic regression analyses, serum magnesium level on admission was independently associated with in-hospital death (hazard ratio 2.68, 95% confidence interval 1.24-5.80) even after adjustment for covariates. Furthermore, the incidences of cardiogenic shock necessitating an intra-aortic balloon pump (p = 0.005) or extracorporeal membrane oxygenation (p < 0.001), tracheal intubation (p < 0.001) and persistent vegetative state (p = 0.002) were significantly higher in patients with higher serum magnesium level than in those with lower serum magnesium level. CONCLUSIONS: In reperfused AMI patients complicated by OHCA-MVA, admission serum magnesium level might be a potential surrogate marker for predicting in-hospital death.

Left intraventricular pressure gradient in hypertrophic cardiomyopathy patients receiving implantable cardioverter-defibrillators for primary prevention.

BACKGROUND: Conventional risk factors for sudden cardiac death (SCD) justify primary prevention through implantable cardioverter-defibrillator (ICD) implantation in hypertrophic cardiomyopathy (HCM) patients. However, the positive predictive values for these conventional SCD risk factors are low. Left ventricular outflow tract obstruction (LVOTO) and midventricular obstruction (MVO) are potential risk modifiers for SCD. The aims of this study were to evaluate whether an elevated intraventricular pressure gradient (IVPG), including LVOTO or MVO, is a potential risk modifier for SCD and ventricular arrhythmias requiring ICD interventions in addition to the conventional risk factors among HCM patients receiving ICDs for primary prevention. METHODS: We retrospectively studied 60 HCM patients who received ICDs for primary prevention. An elevated IVPG was defined as a peak instantaneous gradient ≥ 30 mmHg at rest, as detected by continuous-wave Doppler echocardiography. The main outcome was a composite of SCD and appropriate ICD interventions, which were defined as an antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation. The Cox proportional hazards model was used to assess the relationships between risk factors and the occurrence of SCD and appropriate ICD interventions. RESULTS: Thirty patients met the criteria of elevated IVPG (50%). During the median follow-up period of 66 months, 2 patients experienced SCD, and 10 patients received appropriate ICD interventions. Kaplan-Meier curves showed that the incidence of the main outcome was higher in patients with an IVPG ≥ 30 mmHg than in those without an IVPG ≥ 30 mmHg (log-rank P = 0.03). There were no differences in the main outcome between patients with LVOTO and patients with MVO. The combination of nonsustained ventricular tachycardia (NSVT) and IVPG ≥ 30 mmHg was found to significantly increase the risk of the main outcome (HR 6.31, 95% CI 1.36-29.25, P = 0.02). Five patients experienced ICD implant-related complications. CONCLUSIONS: Our findings showed that a baseline IVPG ≥ 30 mmHg was associated with an increased risk of experiencing SCD or appropriate ICD interventions among HCM patients who received ICDs for primary prevention. Combined with NSVT, which is a conventional risk factor, a baseline IVPG ≥ 30 mmHg may be a potential modifier of SCD risk in HCM patients.

FLNC and MYLK2 Gene Mutations in a Chinese Family with Different Phenotypes of Cardiomyopathy.

Mutations in the sarcomeric protein filamin C (FLNC) gene have been linked to hypertrophic cardiomyopathy (HCM), as they have been determined to increase the risk of ventricular arrhythmia and sudden death. Thus, in this study, we identified a novel missense mutation of FLNC in a Chinese family with HCM, and, interestingly, a second novel truncating mutation of MYLK2 was discobered in one family member with different phenotype.We performed whole-exome sequencing in a Chinese family with HCM of unknown cause. To determine and confirm the function of a novel mutation of FLNC, we introduced the mutant and wild-type gene into AC16 cells (human cardiomyocytes): we then used western blotting to analyze the expression of FLNC in subcellular fractions, and confocal microscope to observe the subcellular distribution of the protein.As per our findings, we were able to identify a novel missense single nucleotide variant (FLNC c.G5935A [p.A1979T]) in the family, which segregates with the disease. FLNC expression levels were observed to be equivalent in both wild-type and p.A1979T cardiomyocytes. However, the expression of the mutant protein has resulted in cytoplasmic protein aggregations, in contrast to wild-type FLNC, which was distributed in the cytoplasm and did not form aggregates. Unexpectedly, a second truncating mutation, NM_033118:exon8:c.G1138T:p.E380X of the MYLK2 gene, was identified in the mother of the proband with dilated cardiomyopathy, which was not found in other subjects.We then identified the FLNC A1979T mutation as a novel pathogenic variant associated with HCM in a Chinese family as well as a second causal mutation in a family member with a distinct phenotype. The possibility that there is more than one causal mutation in cardiomyopathy warrants clinical attention, especially for patients with atypical clinical features.

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.