Risk Of Sudden Arrhythmic Death Research Articles

Primary Atriopathy in Mitral Valve Prolapse: Echocardiographic Evidence and Clinical Implications.

Prominent multi-scallop systolic leaflet displacement toward the left atrium (atrialization) is typically observed in bileaflet mitral valve prolapse (MVP) with mitral annular disjunction. We hypothesized that mitral leaflet atrialization is associated with an underlying left atrial (LA) myopathy characterized by progressive structural and functional abnormalities, irrespective of mitral regurgitation (MR) severity. We identified 334 consecutive patients with MVP, no prior atrial fibrillation, and comprehensive clinical and echocardiographic data. LA function was assessed by LA reservoir strain, LA function index, and LA emptying fraction. We also classified the stage of LA remodeling based on LA enlargement and LA reservoir strain (stage 1: no remodeling; stage 2: mild remodeling; stage 3: moderate remodeling; and stage 4: severe remodeling). The primary end point was the composite risk of sudden arrhythmic death, heart failure hospitalization, or the new onset of atrial fibrillation. Bileaflet MVP with no or mild MR had a lower LA reservoir strain (P=0.04) and LA function index (P<0.001) compared with other MVP subtypes. In multivariable linear regression adjusted for cardiovascular risk factors and MR ≥moderate, bileaflet MVP remained significantly associated with lower LA function parameters (all P<0.05). There was a significant increase in the risk of events as the LA reservoir strain and LA remodeling stage increased (P<0.001). In multivariable analysis, stage 4 of LA remodeling remained significantly associated with a higher risk of events compared with stage 1 (hazard ratio, 6.09 [95% CI, 1.69-21.9]; P=0.006). In a large MVP registry, bileaflet involvement is associated with reduced LA function regardless of MR severity, suggesting a primary atriopathy in this MVP subtype. Abnormal LA function, particularly when assessed through a multiparametric approach, is linked to a higher risk of cardiovascular events and may improve risk stratification in MVP, even in those without significant MR.

History of clinical electrophysiology in diagnosing and treatment monitoring of high ventricular vulnerability

The paper presents the history of hope from 1980-1995 to predict the risk of sudden arrhythmic death using electrophysiologic techniques in individual patients. Even if this prediction seems possible in selected highly risk cohorts, many more patients will die in ventricular arrhythmia without fulfilling the criteria. Ultimately, high risk of sudden cardiac death can be predicted in selected patient groups, but not in the majority of patients at risk. It is ahistory of dashed hope.

Rationale and study protocol for the BRITISH randomized trial (Using cardiovascular magnetic resonance identified scar as the benchmark risk indication tool for implantable cardioverter defibrillators in patients with nonischemic cardiomyopathy and severe systolic heart failure)

BackgroundFor patients with nonischemic cardiomyopathy (NICM), current guidelines recommend implantable cardioverter defibrillators (ICD) when left ventricular ejection fraction (LVEF) is ≤35%, but the DANISH trial failed to confirm that ICDs reduced all-cause mortality for such patients. Circumstantial evidence suggests that scar on CMR is predictive of sudden and arrhythmic death in this population. The presence of myocardial scar identified by cardiac magnetic resonance imaging (CMR) in patients with NICM and an LVEF ≤35% might identify patients at higher risk of sudden arrhythmic death, for whom an ICD is more likely to reduce all-cause mortality. Methods/DesignThe BRITISH trial is a prospective, multicenter, randomized controlled trial aiming to enrol 1,252 patients with NICM and an LVEF ≤35%. Patients with a nonischemic scar on CMR will be randomized to either: (1) ICD, with or without cardiac resynchronization (CRT-D), or (2) implantable loop recorder (ILR) or cardiac resynchronization (CRT-P). Patients who are screened for the trial but are found not to be eligible, predominantly due to an absence of scar or those who decline to be randomized will be enrolled in an observational registry. The primary endpoint is all-cause mortality, which we plan to assess at 3 years after the last participant is randomized. Secondary endpoints include clinical outcomes, appropriate and inappropriate device therapies, symptom severity and well-being, device-related complications, and analysis of the primary endpoint by subgroups with other risk markers. ConclusionThe BRITISH trial will assess whether the use of CMR-defined scar to direct ICD implantation in patients with NICM and an LVEF ≤35% is associated with a reduction in mortality.

Idiopathic left fascicular ventricular tachycardia in children and adolescents.

Idiopathic ventricular tachycardia (VT) in children with structurally normal hearts is generally unrelated to the risk of sudden arrhythmic death. Still, it may be associated with deterioration in the quality of life. VT involving the fascicular conduction system is the most typical form of idiopathic left VT. In this retrospective study, we describe the experience of the clinical presentation, catheter ablation, and long-term follow-up of left fascicular VT in children. An electrophysiological study was performed on consecutive children at a single tertiary center. Clinical fascicular left VT was induced by programmed stimulation, and catheter ablation was guided searching for Purkinje potentials. We included 18 patients (0.8 patients/year): 14 (77.8%) males and four females. The mean age of the first VT episode was 8.5 ± 5 years. Intravenous verapamil administration was effective for paroxysmal fascicular VT but not for prevention of recurrences. The mean age at the time of catheter ablation was 11.1 ± 3.8 years (8 months-16 years). The mean weight was 36.8 ± 16.4 kg (8.7-58 kg). A 100% success rate was observed with catheter ablation after repeated procedures without major complications. Mean follow-up was 2.0 ± 1.2 years (1.0-4.0 years, median 1.5), with permanent success in all patients and no antiarrhythmic drug administration. Fascicular VT has an adverse clinical course in children. In most cases, this condition is drug refractory. Catheter ablation is successful and safe treatment and should represent the first-line approach in symptomatic children.

P24 WEAREBLE CARDIOVERTER – DEFIBRILLATOR : UTILITY AND USER FRIENDLINESS

Abstract Background Worldwide, cardiovascular disease are still a major mode of death, being sudden arrhythmic death (SCD)25 % of total death. Implantable cardioverter defibrillator (ICD) is an effective weapon for SCD prevention in high risk patients with reasonable expectation of survival with good functional status for &amp;gt;1 year. However sometimes the risk of SCD can be transient, so the use of a wearable cardioverter defibrillator (WCD) is considered. Methods We considered consecutively 40 patients discharged from our cardiology department of Piacenza and Castel san Giovanni that, for potentially transient high risk of SCD, weared a WCD from August 2017 to September 2021, after a systematic education session lasting 30 – 45 minutes. They are followed through remote monitoring. Results Out of 40 patients, with average age 66 years old and average left ventricular ejection fraction (LVEF) 29%, 88% were males, 70 % suffered from arterial hypertension, 32% diabetes mellitus, 17,5 % peripheral vascular disease, 35 % chronic renal failure, 55% heart failure, 7,5% previous stroke. 56% of these patients weared WCD for severe systolic disfunction in ischemic cardiac disease after recent myocardial infarction, after percutaneous coronary intervention or coronary artery bypass graft, 7% after removal of an infected ICD, 9 % whilst awaiting completion of diagnostic tests (chanalopathies/right arrhythmogenic ventricular cardiomyopathy), 34% after newly diagnosed cardiomyopathy.The patients were discharged in high risk mode of SCD with WCD protection.The average wearing time of WCD was 51 days and 22,98 hours daily. We received 953 trasmissions, with 21 events: 7 ventricular tachicardia, 4 Sopraventricular tachicardia and 5 T wave oversensing .Neither inappropriate shock and neither death were detected .After wearing time and after clinical evaluation, only 52% of patients were subjected to ICD implantation. Conclusions In our experience we may consider that WCD use is effective, safe and with a good adherence in all patients, considering wearing time. The WCD allows saving resources with less hospitalization time.

A new algorithm to reduce T-wave over-sensing based on phase space reconstruction in S-ICD system

The subcutaneous implantable cardioverter defibrillator (S-ICD) reduces mortality in individuals at high risk of sudden arrhythmic death, by rapid defibrillation of life-threatening arrhythmia. Unfortunately, S-ICD recipients are also at risk of inappropriate shock therapies, which themselves are associated with increased rates of mortality and morbidity. The commonest cause of inappropriate shock therapies is T wave oversensing (TWOS), where T waves are incorrectly counted as R waves leading to an overestimation of heart rate. It is important to develop a method to reduce TWOS and improve the accuracy of R-peak detection in S-ICD system. This paper introduces a novel algorithm to reduce TWOS based on phase space reconstruction (PSR); a common method used to analyse the chaotic characteristics of non-linear signals. The algorithm was evaluated against 34 records from University Hospital Southampton (UHS) and all 48 records from the MIT-BIH arrhythmia database. In the UHS analysis we demonstrated a sensitivity of 99.88%, a positive predictive value of 99.99% and an accuracy of 99.88% with reductions in TWOS episodes (from 166 to 0). Whilst in the MIT-BIH analysis we demonstrated a sensitivity of 99.87%, a positive predictive value of 99.99% and an accuracy of 99.91% for R wave detection. The average processing time for 1min ECG signals from all records is 2.9s. Our algorithm is sensitive for R-wave detection and can effectively reduce the TWOS with low computational complexity, and it would therefore have the potential to reduce inappropriate shock therapies in S-ICD recipients, which would significantly reduce shock related morbidity and mortality, and undoubtedly improving patient's quality of life.

ECG markers of malignant arrhythmias risk in patients with arterial hypertension hospitalized for COVID-19 pneumonia

Funding AcknowledgementsType of funding sources: None.Introduction.Changes in the myocardium in patients with arterial hypertension (AH) can cause fatal arrhythmias. The effects of inflammation and drugs on the heart in COVID-19 pneumonia can also increase the risk of sudden arrhythmic death.The aim of the paper is to study interrelationship of ECG markers of malignant arrhythmias and clinical and laboratory findings in patients with AH and COVID-19 pneumonia.Methods.48 patients with AH hospitalized for COVID-19 pneumonia (32 women aged 34 to 83, 16 men aged 48-80) were included in the study in October-November 2020. Exclusion criteria: congestive heart failure, previous myocardial infarction, reduced ejection fraction, valvular disease, life-threatening COVID-19 and other serious diseases. Main clinical characteristics and recommended laboratory findings were taken into account. Corrected QT and Tpeak-Tend were analyzed.Results.The QTc fluctuations were from 353 ms to 494 ms. The QTc values were higher than normal in 28%. The QTc duration correlated with C-reactive protein level (Kendall R = 0.59) and NYHA class (Gamma = 0.48). The Tpeak-Tend value correlated with coronary heart disease (Gamma 0.65), C-reactive protein (Kendall R = 0.57) and taking dexamethasone (Gamma 0.44) and fluoroquinolones (Gamma 0.58). Multivariate analysis has showed that high level of C-reactive protein (Wald = 7.4) and the presence of heart failure (Wald = 5.2) were independent predictors of QTc increase. Coronary heart disease (Wald = 4,8) and taking respiratory fluoroquinolones (Wald= 3.7) were independent predictors of Tpeak-Tend increase. Age, SatO2, taking betablockers and other analyzed indicators were not significantly related to QTc and Tpeak-Tend.Conclusion.Systemic inflammatory response, heart diseases and taking respiratory fluoroquinolones can adversely affect the myocardial repolarization indicators associated with the risk of sudden death in patients with AH hospitalized for COVID-19 pneumonia.

Cardiac Fibroma with Asymptomatic Ventricular Arrhythmia in an Adolescent with Gorlin's Syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS), also referred to as Gorlin's syndrome, is an autosomal dominant inherited condition that predisposes affected individuals to various tumors such as cardiac fibromas. Though technically benign, cardiac fibromas may result in malignant arrhythmias and sudden death. The pertinent literature pertaining to pediatric cases of cardiac fibromas and their clinical features were reviewed. We present the case of an asymptomatic teenage with de novo NBCCS who was diagnosed with both NBCCS and cardiac fibroma later in life. The patient was noted to have clinically significant ventricular arrhythmias that were eliminated with tumor resection. There are no established best practice guidelines for the management of cardiac fibromas in patients with NBCCS. Given the risk of sudden arrhythmic death, the presence of ventricular arrhythmias should prompt strong consideration of tumor resection.

Analysis of the Early Repolarization in Competitive Athletes: Comparison Between the Notch and The Slur

Early repolarization is currently defined by the presence of notch or slur, at the end of QRS complex, greater ≥ than 0.1 mV in two contiguous leads, and the ST-segment elevation is not necessary for diagnosis. Several studies have confirmed that early repolarization on the electrocardiogram has been associated with an increased risk of sudden arrhythmic death either in the general population or in athletes. However, no study has evaluated the prevalence of this anomaly, using the current definition of early repolarization, in the population of Algerian or North African athletes, no study analyzed notches and slurs separately, and no study compared them. The main objective of our study is to determine the prevalence of ER in an Algerian population of competitive athletes. The secondary objective was to compare the end-QRS Notching and Slurring, and to determine the influence on this prevalence of certain clinical and electrocardiographic parameters, to establish an epidemiological profile of this anomaly. Methods: In our study, we used the current definition of early repolarization. The study population is represented by 621 athletes participating in the various sports competitions organized in the region of Sétif, having undergone a cardiological examination, at the level of the cardiology service of Setif university hospital center, as part of the establishment of a medical certificate of no contraindication to the practice of the sport. Athletes also benefited from a clinical examination (weight, height, cardiac auscultation, functional signs (angina, palpitation, loss of awareness and dyspnea), palpation of the pulse, and measurement of the blood pressure). The electrocardiograms were collected at rest and away from any sporting activity. And in addition to the analysis of ER (prevalence, notch, slur, amplitude, and topography), criteria for ventricular hypertrophy (Sokolow-Lyon index and Cornell index), heart rate, and right bundle branch block were sought and analyzed. Results: The ECG was normal in 29.3% of the athletes, while the majority of athletes (66.3%) had adaptative electrocardiographic abnormalities to regular physical training (minimum of 4 h per week) and competition, 4.3% of athletes had abnormal electrocardiographic patterns suggesting underlying heart disease. The prevalence of ER in our athletes according to the new diagnostic criteria is 26.1%, with a clear male predominance. This prevalence increases with age, peaking in the third decade and then declines. The prevalence of ER is higher in bradycardic athletes and those with a Sokolow-Lyon index greater than 35 mm; for the Cornell index, no relationship was found. Moreover, ER is significantly lower in athletes with incomplete right Branch Block. In our series, ER is predominant in the inferior leads (40.7%) than lateral ones (34.6%), and the double location is found in 24.7%. This distribution of topographies is not influenced by age and gender. 31.8% of ER has an amplitude ≥ of 2 mm. 30.9% of ER is associated with ST-segment elevation. Notch is the predominant pattern whatever the topography of ER is (notch, 57.4%; slur, 18.5%; notch+slur, 24.1%); notch predominates in lateral leads (52.3%) while slur is predominant in inferior leads (68.0%).1%); only the notch has a significant relationship with male sex (23.8% vs 5.7%, p&lt;0.001) with bradycardia (41.4% vs 16%, P&lt;0.001) and with physical training. The prevalence of notches and slurs is significantly higher in athletes with a Sokolow-Lyon index greater than 35 mm. Conclusion: The pattern of ER is frequent in athletes; its prevalence is influenced by age, sex, heart rate, left ventricular hypertrophy, and incomplete right bundle branch block, type of sport, and intensity of the dynamic and static component of sports activity. The inferior topography (considered as a criterion of the high risk of ER) is found the most in our athletes; the notch is the most frequent pattern. It has been found that the two patterns "notch" and "slur", which are the basis of the definition of ER, are not influenced in the same way by the other clinical and electrocardiographic parameters.

Protected risk stratification with the wearable cardioverter-defibrillator: results from the WEARIT-II-EUROPE registry

BackgroundThe prospective WEARIT-II-EUROPE registry aimed to assess the value of the wearable cardioverter-defibrillator (WCD) prior to potential ICD implantation in patients with heart failure and reduced ejection fraction considered at risk of sudden arrhythmic death.Methods and results781 patients (77% men; mean age 59.3 ± 13.4 years) with heart failure and reduced left ventricular ejection fraction (LVEF) were consecutively enrolled. All patients received a WCD. Follow-up time for all patients was 12 months. Mean baseline LVEF was 26.9%. Mean WCD wearing time was 75 ± 47.7 days, mean daily WCD use 20.3 ± 4.6 h. WCD shocks terminated 13 VT/VF events in ten patients (1.3%). Two patients died during WCD prescription of non-arrhythmic cause. Mean LVEF increased from 26.9 to 36.3% at the end of WCD prescription (p < 0.01). After WCD use, ICDs were implanted in only 289 patients (37%). Forty patients (5.1%) died during follow-up. Five patients (1.7%) died with ICDs implanted, 33 patients (7%) had no ICD (no information on ICD in two patients). The majority of patients (75%) with the follow-up of 12 months after WCD prescription died from heart failure (15 patients) and non-cardiac death (15 patients). Only three patients (7%) died suddenly. In seven patients, the cause of death remained unknown.ConclusionsMortality after WCD prescription was mainly driven by heart failure and non-cardiovascular death. In patients with HFrEF and a potential risk of sudden arrhythmic death, WCD protected observation of LVEF progression and appraisal of competing risks of potential non-arrhythmic death may enable improved selection for beneficial ICD implantation.Graphic abstract

Exploring the acceptability of implantable defibrillators in patients with cardiac dystrophinopathy and carers

ObjectiveUnlike for patients with other forms of cardiomyopathies, those with severe ventricular dysfunction due to Duchenne muscular dystrophy (DMD) are not offered implantable cardioverter-defibrillator (ICD) therapy routinely. This prospective study...

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death

QT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown. To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death. This prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019. QT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high). Death due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause. A total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P < .001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P = .04) and high (OR, 6.70 [95% CI, 1.47-30.67]; P = .01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P = .02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P = .02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P = .001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group. These findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.

Progressive cardiac arrhythmias and ECG abnormalities in the Huntington's disease BACHD mouse model.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease. There is accumulating evidence that HD patients have increased prevalence of conduction abnormalities and compromised sinoatrial node function which could lead to increased risk for arrhythmia. We used mutant Huntingtin (mHTT) expressing bacterial artificial chromosome Huntington's disease mice to determine if they exhibit electrocardiogram (ECG) abnormalities involving cardiac conduction that are known to increase risk of sudden arrhythmic death in humans. We obtained surface ECGs and analyzed arrhythmia susceptibility; we observed prolonged QRS duration, increases in PVCs as well as PACs. Abnormal histological and structural changes that could lead to cardiac conduction system dysfunction were seen. Finally, we observed decreases in desmosomal proteins, plakophilin-2 and desmoglein-2, which have been reported to cause cardiac arrhythmias and reduced conduction. Our study indicates that mHTT could cause progressive cardiac conduction system pathology that could increase the susceptibility to arrhythmias and sudden cardiac death in HD patients.

Prescribing an automated external defibrillator for children at increased risk of sudden arrhythmic death.

Automated external defibrillators can be life-saving in out-of-hospital cardiac arrest. Our aim was to review our experience of prescribing automated external defibrillators for children at increased risk of sudden arrhythmic death. We reviewed all automated external defibrillators issued by the Scottish Paediatric Cardiac Electrophysiology Service from 2005 to 2015. All parents were given resuscitation training according to the Paediatric Resuscitation Guidelines, including the use of the automated external defibrillator. A total of 36 automated external defibrillators were issued to 36 families for 44 children (27 male). The mean age at issue was 8.8 years. Diagnoses at issue included long QT syndrome (50%), broad complex tachycardia (14%), hypertrophic cardiomyopathy (11%), and catecholaminergic polymorphic ventricular tachycardia (9%). During the study period, the automated external defibrillator was used in four (9%) children, and in all four the automated external defibrillator correctly discriminated between a shockable rhythm - polymorphic ventricular tachycardia/ventricular fibrillation in three patients with one or more shocks delivered - and non-shockable rhythm - sinus rhythm in one patient. Of the three children, two of them who received one or more shocks for ventricular fibrillation/polymorphic ventricular tachycardia survived, but one died as a result of recurrent torsades de pointes. There were no other deaths. Parents can be taught to recognise cardiac arrest, apply resuscitation skills, and use an automated external defibrillator. Prescribing an automated external defibrillator should be considered for children at increased risk of sudden arrhythmic death, especially where the risk/benefit ratio of an implantable defibrillator is unclear or delay to defibrillator implantation is deemed necessary.

Safety of the Wearable Cardioverter Defibrillator (WCD) in Patients with Implanted Pacemakers.

The wearable cardioverter defibrillator (WCD) is an important approach for better risk stratification, applied to patients considered to be at high risk of sudden arrhythmic death. Patients with implanted pacemakers may also become candidates for use of the WCD. However, there is a potential risk that pacemaker signals may mislead the WCD detection algorithm and cause inappropriate WCD shock delivery. The aim of the study was to test the impact of different types of pacing, various right ventricular (RV) lead positions, and pacing modes for potential misleading of the WCD detection algorithm. Sixty patients with implanted pacemakers received the WCD for a short time and each pacing mode (AAI, VVI, and DDD) was tested for at least 30 seconds in unipolar and bipolar pacing configuration. In case of triggering the WCD detection algorithm and starting the sequence of arrhythmia alarms, shock delivery was prevented by pushing of the response buttons. In six of 60 patients (10%), continuous unipolar pacing in DDD mode triggered the WCD detection algorithm. In no patient, triggering occurred with bipolar DDD pacing, unipolar and bipolar AAI, and VVI pacing. Triggering was independent of pacing amplitude, RV pacing lead position, and pulse generator implantation site. Unipolar DDD pacing bears a high risk of false triggering of the WCD detection algorithm. Other types of unipolar pacing and all bipolar pacing modes do not seem to mislead the WCD detection algorithm. Therefore, patients with no reprogrammable unipolar DDD pacing should not become candidates for the WCD.

Incidence and predictors of sudden arrhythmic death or ventricular tachyarrhythmias after acute coronary syndrome: An asian perspective

Current data on the risk of sudden arrhythmic death (SAD) and ventricular tachyarrhythmias (VTs) after acute coronary syndrome (ACS) in the Asian population are limited. The purpose of this study was to investigate the incidence and predictors of SAD or VT after ACS in a contemporary cohort of Chinese patients in the era of early revascularization. Consecutive patients admitted to our unit for ACS from 2010 to 2015 were retrospectively reviewed. A total of 918 patients (74.8% male, mean age 65.9 ± 13.4 years) were included in the study. Of these patients, 864 (94.1%) survived to discharge. After a mean of 34.1 ± 21.8 months, 42 (4.9%) had SAD or VT. The event rate was 0.46% in month 1, 0.26% per month in the months 2 to 6, 0.15% per month in months 6 to 12, and 1.23% per year from the second year onward. In multivariate analysis, early VT (hazard ratio [HR] 5.78, 95% confidence interval [CI] 2.63-12.72, P < .01), left ventricular ejection fraction ≤35% (HR 1.96, 95% CI 1.03-3.73, P = .04), prior coronary artery disease (HR 2.50, 95% CI 1.29-4.82, P < .01), triple-vessel disease (HR 3.69, 95% CI 1.81-7.54, P < .01), and chronic kidney disease (HR 2.43, 95% CI 1.21-4.92, P = .01) independently predicted SAD or VT. This study reports the rate of SAD or VT among Asian patients after ACS in the era of early revascularization and optimal medical therapy. Aggressive preventive measures should be considered for patients with multiple risk factors for SAD or VT, especially in the initial period after ACS.

Improving the appropriateness of sudden arrhythmic death primary prevention by implantable cardioverter-defibrillator therapy in patients with low left ventricular ejection fraction. Point of view.

It is generally accepted that the current guidelines for the primary prevention of sudden arrhythmic death, which are based on ejection fraction, do not allow the optimal selection of patients with low left ventricular ejection fraction of ischemic and nonischemic etiology for implantation of a cardioverter-defibrillator. Ejection fraction alone is limited in both sensitivity and specificity. An analysis of the risk of sudden arrhythmic death with a combination of multiple tests (ejection fraction associated with one or more arrhythmic risk markers) could partially compensate for these limitations. We propose a polyparametric approach for defining the risk of sudden arrhythmic death using ejection fraction in combination with other clinical and arrhythmic risk markers (i.e. late gadolinium enhancement cardiac magnetic resonance, T-wave alternans, programmed ventricular stimulation, autonomic tone, and genetic testing) that have been validated in nonrandomized trials. In this article, we examine these approaches to identify three subsets of patients who cannot be comprehensively assessed by the current guidelines: patients with ejection fraction of 35% or less and a relatively low risk of sudden arrhythmic death despite the ejection fraction value; patients with ejection fraction of 35% or less and high competitive risk of death due to evolution of heart failure or noncardiac causes; and patients with ejection fraction between 35 and 45% with relatively high risk of sudden arrhythmic death despite the ejection fraction value.

Flecainide-induced prolongation of ventricular repolarization contributes to the proarrhythmic profile of action

Flecainide is class Ic Na + channel blocker that is used to restore sinus rhythm and to prevent the arrhythmia recurrence in patients with atrial fibrillation. Antiarrhythmic effect of flecainide is attribut- ed to prolonged atrial effective refractory period and depressed car- diac action potential upstroke. Nevertheless, flecainide has been reported to produce arrhythmogenic responses in ventricular myo- cardium. In this regard, the Cardiac Arrhythmia Suppression Trial (CAST) has shown that flecainide therapy is associated with marked- ly increased risk of sudden arrhythmic death in patients with healed myocardial infarction, an effect possibly accounted for by the drug- induced anisotropic conduction slowing in the peri-infarct zone. Based on these findings, indications for flecainide therapy are cur- rently limited to the atrial fibrillation control in patients with no structural heart disease. Although flecainide-induced conduction abnormalities are unlikely to occur in the absence of myocardial ischemia or fibrosis, there is in- creasing evidence to suggest that flecainide may promote arrhythmo- genic responses in patients with structurally normal hearts. Flecainide administration has been reported to induce torsade de pointes, a poten- tially life-threatening polymorphic ventricular tachycardia, in patients with no coronary artery disease or severe heart failure (1,2). This kind of arrhythmia is thought to be attributed to the prolonged QT interval and increased spatial dispersion of ventricular repolarization. However, the contribution of these factors to flecainide-induced proarrhythmia is often overlooked, because flecainide (along with other class Ic Na + channel blockers) is generally regarded asanagentproducingonly little or no effect on ventricular repolarization.

Sudden death associated with QT interval prolongation and KCNQ1 gene mutation in a family of English Springer Spaniels.

BackgroundA 5‐year‐old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly.HypothesisAbnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family.AnimalsFour remaining dogs from the affected litter and 11 related dogs.MethodsPhysical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs.ResultsThree of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T‐wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure.Conclusions and Clinical ImportanceThis family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current I Ks, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

Evaluation of genes encoding for the transient outward current (Ito) identifies the KCND2 gene as a cause of J-wave syndrome associated with sudden cardiac death.

J-wave ECG patterns are associated with an increased risk of sudden arrhythmic death, and experimental evidence supports a transient outward current (I(to))-mediated mechanism of J-wave formation. This study aimed to determine the frequency of genetic mutations in genes encoding the I(to) in patients with J waves on ECG. Comprehensive mutational analysis was performed on I(to)-encoding KCNA4, KCND2, and KCND3 genes, as well as the previously described J-wave-associated KCNJ8 gene, in 51 unrelated patients with ECG evidence defining a J-wave syndrome. Only patients with a resuscitated cardiac arrest or type 1 Brugada ECG pattern were included for analysis. A rare genetic mutation of the KCND2 gene, p.D612N, was identified in a single patient. Co-expression of mutant and wild-type KCND2 with KChIP2 in HEK293 cells demonstrated a gain-of-function phenotype, including an increase in peak I(to) density of 48% (P<0.05) in the heterozygous state. Using computer modeling, this increase in Ito resulted in loss of the epicardial action potential dome, predicting an increased ventricular transmural Ito gradient. The previously described KCNJ8-S422L mutation was not identified in this cohort of patients with ECG evidence of J-wave syndrome. These findings are the first to implicate the KCND2 gene as a novel cause of J-wave syndrome associated with sudden cardiac arrest. However, genetic defects in I(to)-encoding genes seem to be an uncommon cause of sudden cardiac arrest in patients with apparent J-wave syndromes.