Risk Of Major Arrhythmic Events Research Articles

SCN5A gene variants and arrhythmic risk in Brugada syndrome: An updated systematic review and meta-analysis

BackgroundA rare gene variant in SCN5A can be found in approximately 20%–25% of patients with Brugada syndrome (BrS). ObjectiveThe aim of this systematic review and meta-analysis was to evaluate the differences in clinical characteristics of BrS patients with and without SCN5A rare variants and the prognostic role of SCN5A for ventricular arrhythmias in BrS. MethodsPubMed and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 2024 to identify all relevant studies. Studies were analyzed if they included patients diagnosed with BrS in whom genetic testing for SCN5A variants was performed and arrhythmic outcomes were reported. ResultsA total of 17 studies with 3568 BrS patients, of whom 3030 underwent genetic testing for SCN5A variants, fulfilled the eligibility criteria and were included. Compared with SCN5A− patients, SCN5A+ BrS patients more frequently had spontaneous type 1 electrocardiogram, history of syncope, and documented arrhythmias. Furthermore, higher PQ and QRS intervals in SCN5A+ BrS patients compared with SCN5A− have been found. The pooled analysis demonstrated a significant association between the presence of SCN5A rare variants in BrS patients and the risk of major arrhythmic events, with a pooled odds ratio of 2.14 (95% confidence interval, 1.53–2.99; I2 = 29%). ConclusionSCN5A+ BrS patients showed a worse clinical phenotype compared with SCN5A−. The pooled analysis demonstrated a significant association between SCN5A+ mutation status and the risk of major arrhythmic events in BrS patients.

Relation between non-sustained ventricular tachycardia and major arrhythmic events in patients with dilated cardiomyopathy caused by titin truncating variants

Abstract Background Truncating titin variants (TTNtv) are the most frequent monogenetic cause of dilated cardiomyopathy (DCM). Current data suggest that nonsustained ventricular arrhythmia is common in patients with TTVtv but its relation to the risk of major arrhythmic events (MAE) is uncertain. Purpose To investigated the relationship between NSVT recorded on Holter ECG or implanted device and MAE in patients with DCM. Methods We retrospectively studied consecutively evaluated patients with DCM (left ventricle ejection fraction (LVEF) below 50%) on echocardiography and a pathogenic TTNtv. Patients with obstructive coronary artery disease, valvular disease, ventricular tachycardia ablation during follow-up time and follow-up less than one month were excluded. Survival was modelled from the initial Holter or device implantation. NSVT was defined as ≥3 consecutive ventricular beats at a rate >120 beats per minute, lasting for <30 s. MAE was defined as sustained ventricular tachycardia (VT), ventricular fibrillation (VF), sudden cardiac death, implantable cardioverter defibrillator (ICD) treated ventricular arrhythmias (appropriate shock and ATP). The clinical endpoint was MAE (sustained VT, VF, sudden cardiac death, ICD shocks and ATP) and multivariable analysis was performed using Cox proportional hazards models. Event-free survival probabilities were estimated using the Kaplan-Meier method, and comparisons of Kaplan-Meier curves were made using log-rank tests. Results The cohort comprised 58 men and 30 women [mean age 49 ± 15 years; mean follow-up 3.5 ± 1.8 years]. Symptoms were NYHA class I in 56 patients, class II in 25 patients, class III in 7 patients and class IV in none. Holter ECGs were performed in 77 patients, 41 of whom had NSVT. Twenty five patients had pacemaker/ICD in situ; 14 had NSVT. Six patients had MAE; 4 with NSVT. Univariate analysis association between MAE and LVEF ≤35% (hazard ratio (HR), 9.03; 95% confidence interval (CI), 1.49-54.71; P=0.017), prolonged (>8 beats) NSVT (HR, 6.71; 95% CI, 1.22-36.98; P=0.029) and fast (>200 bpm) NSVT (HR, 5.09; 95% CI, 1.02-25.47; P=0.048). Kaplan-Meier showed similar differences in freedom from MAE (LVEF ≤35%; P=0.004, long NSVT; P=0.025, fast NSVT; P=0.031). Conclusion Fast and prolonged NSVT is associated with a higher risk of MAE in patients with TTNtv.Characteristics at the beginningSurvival probability for freedom

Abstract 17912: Late Potential and the Risk of Major Arrhythmic Events in Brugada Syndrome Patients: A Systematic Review and Meta-Analysis

Introduction: Brugada syndrome is an inherited arrhythmic disease associated with fatal ventricular arrhythmias. However, ventricular arrhythmia risk stratification remains challenging and controversial. Hypothesis: The late potential may be useful as a predictor of major arrhythmic events in Brugada syndrome patients. Aims: We aimed to assess the association between late potential and risk of major arrhythmic events by a systematic review and meta-analysis. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to January 2023. The included studies were cohort and case-control studies that reported the relationship between late potential and major arrhythmic events. The included studies were selected to yield a maximum total number of sample sizes without population duplications across the studies. Data from each study were combined using the random-effects model to calculate pooled odds ratio and 95% confidence intervals. The late potential was defined as RMS40 <20 μV and/or LAS40 >38 ms on signal-averaged ECG. Results: Five studies were included in this meta-analysis involving 743 Brugada syndrome patients (438 with late potential and 743 without late potential). The mean age was 47.3 ± 14.1 years. The patients were predominately men (61.6%). The late potential was not associated with major arrhythmic events (pooled odds ratio 1.17, 95% confidence intervals: 0.62-2.21, p=0.63, I 2 =21.3%). Conclusions: Our study demonstrated that late potential is not associated with a higher risk of major arrhythmic events in Brugada syndrome populations. To our knowledge, our study is the first meta-analysis of late potential in Brugada syndrome patients.

Advanced 3D analysis of fibrotic ring-like pattern in non-ischemic cardiomyopathy predicts major arrhythmic events

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ Trust and King’s College, the Centre of Excellence in Medical Engineering funded by the Wellcome Trust and Engineering and Physical Sciences Research Council (EPSRC; WT088641/Z/09/Z). M.J.B. is supported by a Medical Research Council New Investigator Grant (MR/N011007/1) and British Heart Foundation (Project grant PG/18/74/34077). This work was supported by EPSRC 2018/19 DTP - EP/R513064/1 grant. This work was supported by a National Heart and Lung Institute Foundation grant awarded to Professor Sanjay Prasad and Dr Richard Jones. This work was supported by a National Heart and Lung Institute Foundation grant awarded to SKP, DJH, REJ, UT and BPH. Additionally, the study was supported by an Intermediate Clinical Research Fellowship awarded to BPH (FS/ICRF/21/26019). Background The presence of ring-like patterns of mid-wall fibrosis identified on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is associated with an increased risk of major arrhythmic events (MAE) in non-ischemic cardiomyopathy (NICM). Analysis of tissue bordering core fibrosis and healthy myocardium (Gray Zone [GZ]) has been suggested as an important pro-arrhythmic substrate in this population. Purpose To investigate refined anatomical definitions of the fibrotic ring pattern, including the importance of GZ inclusion in the association with MAE in NICM. Methods LGE CMR data from 292 NICM patients were analysed to delineate both core and GZ fibrosis. Fibrosis quantification masks for each 2D image slice were used, along with AHA 17-segment maps, to identify fibrotic ring patterns: defined by fibrosis extending by 3 or more continuous AHA-segments for any individually-contiguous fibrotic component within each slice (Fig 1A). Ring patterns were assessed separately for core fibrosis and core + GZ, as well as individually in basal, mid-basal and mid-apical regions. In separate analysis, LGE contours were aligned, interpolated, and used to generate 3D computational volumetric models (Fig 1B). Individually-connected scar components were extracted and the 3D circumferential angular variation (3DCAV) of each separate fibrotic structure quantified as a continuous variable (Fig 1C). Association of the presence of ring patterns and 3DCAV with a composite MAE were investigated. Results Of 292 patients, 67(23%) had core fibrotic ring patterns (54 basal, 28 mid-cavity level, 6 apical). Over a median(IQR) of 6(4) years, 16(24%) patients experienced MAE. On univariate Cox analysis, ring pattern core fibrosis was a strong predictor of MAE (Hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.13-4.31, p=0.021). Apical-basal region analysis showed that basal ring pattern was associated with MAE (HR 2.25, 95%CI, 1.13-4.51, p=0.022). Multivariate Cox analysis including raised NYHA Class and severely reduced LVEF, overall ring (HR 2.14, 95%CI, 1.05-4.33, p=0.035) and basal ring pattern (HR 2.9, 95%CI 1.39-6.02, P=0.004) continued to show independent association with the MAE. Analysis of the full 3D geometry of the individual scar components also showed that our novel 3DCAV metric was associated with the MAE on both univariate (HR 1.31, 95%CI 1.08-1.59, P=0.007) and multivariate (HR 1.3, 95%CI, 1.06-1.60, P=0.013). Analysis of core ring patterns outperformed analysis of core+GZ patterns in all cases. Conclusions Our study confirms that ring-like patterns of fibrosis in NICM are strongly associated with MAE in NICM, with patterns predominantly at the basal regions conferring enhanced risk relative to mid-basal and mid-apical regions. Inclusion of GZ quantification in ring-pattern analysis did not enhance risk prediction. Our novel 3D analysis of circumferential fibrosis patterns may provide a more robust quantitative metric for stratification.

Pathogenesis and Management of Brugada Syndrome: Recent Advances and Protocol for Umbrella Reviews of Meta-Analyses in Major Arrhythmic Events Risk Stratification.

Brugada syndrome (BrS) is a primary electrical disease associated with life-threatening arrhythmias. It is estimated to cause at least 20% of sudden cardiac deaths (SCDs) in patients with normal cardiac anatomy. In this review paper, we discuss recent advances in complex BrS pathogenesis, diagnostics, and current standard approaches to major arrhythmic events (MAEs) risk stratification. Additionally, we describe a protocol for umbrella reviews to systematically investigate clinical, electrocardiographic, electrophysiological study, programmed ventricular stimulation, and genetic factors associated with BrS, and the risk of MAEs. Our evaluation will include MAEs such as sustained ventricular tachycardia, ventricular fibrillation, appropriate implantable cardioverter–defibrillator therapy, sudden cardiac arrest, and SCDs from previous meta-analytical studies. The protocol was written following the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidelines. We plan to extensively search PubMed, Embase, and Scopus databases for meta-analyses concerning risk-stratification in BrS. Data will be synthesized integratively with transparency and accuracy. Heterogeneity patterns across studies will be reported. The Joanna Briggs Institute (JBI) methodology, A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) are planned to be applied for design and execution of our evidence-based research. To the best of our knowledge, these will be the first umbrella reviews to critically evaluate the current state of knowledge in BrS risk stratification for life-threatening ventricular arrhythmias, and will potentially contribute towards evidence-based guidance to enhance clinical decisions.

Impact of the number of comorbidities on cardiac sympathetic derangement in patients with reduced ejection fraction heart failure

IntroductionHeart failure (HF) is frequently associated with comorbidities. 123I-metaiodobenzylguanidine (123I-mIBG) imaging constitutes an effective tool to measure cardiac adrenergic innervation and to improve prognostic stratification in HF patients, including the risk of major arrhythmic events. Although comorbidities have been individually associated with reduced cardiac adrenergic innervation, thus suggesting increased arrhythmic risk, very comorbid HF patients seem to be less likely to experience fatal arrhythmias. We evaluated the impact of the number of comorbidities on cardiac adrenergic innervation, assessed through 123I-mIBG imaging, in patients with systolic HF. MethodsPatients with systolic HF underwent clinical examination, transthoracic echocardiography and cardiac 123I-mIBG scintigraphy. The presence of 7 comorbidities/conditions (smoking, chronic obstructive pulmonary disease, diabetes mellitus, peripheral artery disease, atrial fibrillation, chronic ischemic heart disease and chronic kidney disease) was documented in the overall study population. ResultsThe study population consisted of 269 HF patients with a mean age of 66±11 years, a left ventricular ejection fraction (LVEF) of 31±7%, and 153 (57%) patients presented ≥3 comorbidities. Highly comorbid patients presented a reduced late heart to mediastinum (H/M) ratio, while no significant differences emerged in terms of early H/M ratio and washout rate. Multiple regression analysis revealed that the number of comorbidities was not associated with mIBG parameters of cardiac denervation, which were correlated with age, body mass index and LVEF. ConclusionIn systolic HF patients, the number of comorbidities is not associated with alterations in cardiac adrenergic innervation. These results are consistent with the observation that very comorbid HF patients suffer lower risk of sudden cardiac death.

Late-Gadolinium Enhancement Interface Area and Electrophysiological Simulations Predict Arrhythmic Events in Patients With Nonischemic Dilated Cardiomyopathy.

ObjectivesThis study sought to investigate whether shape-based late gadolinium enhancement (LGE) metrics and simulations of re-entrant electrical activity are associated with arrhythmic events in patients with nonischemic dilated cardiomyopathy (NIDCM).BackgroundThe presence of LGE predicts life-threatening ventricular arrhythmias in NIDCM; however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.MethodsCardiac magnetic resonance (CMR)-LGE shape metrics were computed for a cohort of 156 patients with NIDCM and visible LGE and tested retrospectively for an association with an arrhythmic composite endpoint of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for re-entry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations.ResultsDuring a median follow-up of 1,611 (interquartile range: 881 to 2,341) days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE–myocardial interface area (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.24 to 2.47; p = 0.001), number of simulated re-entries (HR: 1.40; 95% CI: 1.23 to 1.59; p < 0.01) and LGE volume (HR: 1.44; 95% CI: 1.07 to 1.94; p = 0.02) were associated with arrhythmic events. Computational modeling revealed repolarization heterogeneity and rate-dependent block of electrical wavefronts at the LGE–myocardial interface as putative arrhythmogenic mechanisms directly related to the LGE interface area.ConclusionsThe area of interface between scar and surviving myocardium, as well as simulated re-entrant activity, are associated with an elevated risk of major arrhythmic events in patients with NIDCM and LGE and represent novel risk predictors.

Wide QRS complex and the risk of major arrhythmic events in Brugada syndrome patients: A systematic review and meta-analysis.

BackgroundBrugada syndrome (BrS) is an inherited arrhythmic disease associated with an increased risk of major arrhythmic events (MAE). Previous studies reported that a wide QRS complex may be useful as a predictor of MAE in BrS patients. We aimed to assess the correlation of wide QRS complex with MAE by a systematic review and meta‐analysis.MethodsWe comprehensively searched the databases of MEDLINE and EMBASE from inception to June 2019. Included studies were cohort and case control studies that reported QRS duration and the relationship between wide QRS complex (>120 milliseconds) and MAE (sudden cardiac death, sudden cardiac arrest, ventricular fibrillation, sustained ventricular tachycardia, or appropriate shock). Data from each study were combined using the random‐effects model.ResultsTwenty‐two studies from 2007 to 2018 were included in this meta‐analysis involving 4,814 BrS patients. The mean age was 46.1 ± 12.8 years. The patients were predominately men (77.6%). Wide QRS duration was an independent predictor of MAE (pooled risk ratio 1.55, 95% confidence interval: 1.04‐2.30, P = .30, I 2 = 38.4%). QRS duration was wider in BrS who had history of MAE (weight mean difference = 8.12 milliseconds, 95% confidence interval: 5.75‐10.51 milliseconds).ConclusionsOur study demonstrated that QRS duration is wider in BrS who had history of MAE, and a wide QRS complex is associated with 1.55 times higher risk of MAE in BrS populations. Wide QRS complex can be considered for risk stratification in prediction of MAE in patients with BrS, especially when considering implantable cardioverter‐defibrillator placement in asymptomatic patients.

Atrial fibrillation and risk of major arrhythmic events in Brugada syndrome: A meta-analysis.

Brugada syndrome (BrS) is a common cause of sudden cardiac death (SCD). There is recent evidence that atrial fibrillation (AF) is associated with increased risk of SCD in general population. However, whether AF increases a risk of major arrhythmic events (MAE) in patients with BrS is still unclear. We performed a systematic review and meta-analysis to explore the effect of AF on MAE in BrS population. We searched the databases of MEDLINE and EMBASE from inception to March 2019. Included studies were published cohort studies reporting rates of MAE (ventricular fibrillation, sustained ventricular tachycardia, SCD, or sudden cardiac arrest) in BrS patients, with and without previous documented AF. Data from each study were combined using the random-effects model. Six studies from 1,703 patients were included. There was a significant association between AF and an increased risk of MAE in patients with BrS (pooled OR=2.37, 95% CI=1.36-4.13, p-value=.002, I2 =40.3%). Our meta-analysis demonstrated that AF is associated with an increased risk of MAE in patients with BrS.

A Retrospective Analysis Of VPBs In Trained Bicuspid Aortic Valve Athletes.

PURPOSE: Bicuspid aortic valve (BAV) represents a common congenital cardiac disease (1-2%) normally compatible with sports activity. In case of competitive sports, the eligibility can be otherwise limited by the presence of symptoms, aortic valve dysfunction or arrhythmias. The investigation aims to verify, in a large cohort of BAV athletes, the prevalence of ventricular arrhythmic events (VPBs) found at the maximal exercise test (ET) at the first sports medicine clinical evaluation. METHODS: A sample of 356 BAV athletes, regularly followed at Sports Medicine Center of the University of Florence, since 10 years, was retrospectively evaluated for arrhythmic events found at the first check-up. The athletes (321 M and 35 F) were in the range of 8-50 years old (medium 24.00 ± 14.14) and practiced sports at high cardiovascular impact (predominantly soccer, basketball and track and field). Inclusion criteria were to undergo a 2D echocardiography and ET conducted at 85% of their maximal effort. VPBs were reported if they were ≥ 3 at rest and/or during the test. Exclusion criteria were age > 50 years and the presence of any other cardiac or systemic structural disease. They were matched with a control group of 400 athletes (age 19.70±9,7) without BAV and similarly trained. RESULTS: Only 25 (7,02%) showed VPBs at the ET. The total amount was 403 single VPBs and 4 monomorphic couples; a polymorphic pattern was present in only 3 athletes and only 5 had induced-exercise VPBs at peak. None of them showed acute events or had major arrhythmias. The difference of the VPBs prevalence in BAV athletes versus control (VPBs in 6,25%) was not significant (p >0.05). CONCLUSIONS: Prevalence of VPBs is low in BAV athletes and it seems to be not different from athletes without BAV. In case of sports eligibility, BAV should not be considered as a cause of risk of major arrhythmic events. More data in this field could optimize the cost/effective ratio for the eventual ECG holter indications.

Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta-analysis.

Whether the presence of SCN5A mutation is a predictor of BrS risk remains controversial, and patient selection bias may have weakened previous findings. Therefore, we performed this study to clarify the clinical characteristics and outcomes of BrS probands with SCN5A mutations. We systematically retrieved eligible studies published through October 2018. A total of 17 studies enrolling 1780 BrS patients were included. Overall, our results found that compared with BrS patients without SCN5A mutations, patients with SCN5A mutations exhibited a younger age at the onset of symptoms and higher rate of the spontaneous type-1 electrocardiogram pattern, more pronounced conduction or repolarization abnormalities, and increased atrial vulnerability. In addition, the presence of SCN5A mutations was associated with an elevated risk of major arrhythmic events in both Asian (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.07-3.11; P = .03) and Caucasian (OR = 2.24, 95% CI 1.02-4.90; P = .04) populations. In conclusions, patients with SCN5A mutations exhibit more pronounced electrophysiological defects and more severe prognosis. Clinicians should be cautious when utilizing genetic testing for risk stratification or treatment guidance before determining whether the causal relationship regarding SCN5A mutation status is an independent predictor of risk.

A novel prediction model for risk stratification in patients with a type 1 Brugada ECG pattern

BackgroundRisk stratification in Brugada syndrome remains a controversial and unresolved clinical problem, especially in asymptomatic patients with a type 1 ECG pattern. The purpose of this study is to derive and validate a prediction model based on clinical and ECG parameters to effectively identify patients with a type 1 ECG pattern who are at high risk of major arrhythmic events (MAE) during follow-up. MethodsThis study analysed data from 103 consecutive patients with Brugada Type 1 ECG pattern and no history of previous cardiac arrest. The prediction model was derived using logistic regression with MAE as the primary outcome, and patient demographic and electrocardiographic parameters as potential predictor variables. The model was externally validated in an independent cohort of 42 patients. ResultsThe final model (Brugada Risk Stratification [BRS] score) consisted of 4 independent predictors (1 point each) of MAE during follow-up (median 85.3 months): spontaneous type 1 pattern, QRS fragments in inferior leads≥3,S wave upslope duration ratio ≥ 0.8, and T peak – T end ≥ 100 ms. The BRS score (AUC = 0.95,95% CI 0.0.92–0.98) stratifies patients with a type 1 ECG pattern into low (BRS score ≤ 2) and high (BRS score ≥ 3) risk classes, with a class specific risk of MAE of 0–1.1% and 92.3–100% across the derivation and validation cohorts, respectively. ConclusionsThe BRS score is a simple bed-side tool with high predictive accuracy, for risk stratification of patients with a Brugada Type 1 ECG pattern. Prospective validation of the prediction model is necessary before this score can be implemented in clinical practice.

SCN5A mutation status increases the risk of major arrhythmic events in Asian populations with Brugada syndrome: systematic review and meta-analysis.

Brugada syndrome (BrS) is an inherited arrhythmic disease linked to SCN5A mutations. It is controversial whether SCN5A mutation carriers possess a greater risk of major arrhythmic events (MAE). We examined the association of SCN5A mutations and MAE in BrS patients. We comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Included studies were published cohort and case-control studies that compared MAE in BrS patients with and without SCN5A mutations. Data from each study were combined using the random-effects model. Generic inverse variance method of DerSimonian and Laird was employed to calculate the risk ratios (RR) and 95% confidence intervals (CI). Seven studies from March 2002 to October 2017 were included (1,049 BrS subjects). SCN5A mutations were associated with MAE in Asian populations (RR=2.03, 95% CI: 1.37-3.00, p=0.0004, I2 =0.0%), patients who were symptomatic (RR=2.66, 95% CI: 1.62-4.36, p=0.0001, I2 =23.0%), and individuals with spontaneous type-1 Brugada pattern (RR=1.84, 95% CI: 1.05-3.23, p=0.03, I2 =0.0%). SCN5A mutations in BrS increase the risk of MAE in Asian populations, symptomatic BrS patients, and individuals with spontaneous type-1 Brugada pattern. Our study suggests that SCN5A mutation status should be an important tool for risk assessment in BrS patients.

Baseline fragmented QRS increases the risk of major arrhythmic events in hypertrophic cardiomyopathy: Systematic review and meta-analysis.

Fragmented QRS reflects disturbances in the myocardium predisposing the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented QRS (fQRS) is associated with worse major arrhythmic events in hypertrophic cardiomyopathy (HCM). However, a systematic review and meta-analysis of the literature has not been done. We assessed the association between fQRS and major arrhythmic events in hypertrophic cardiomyopathy by a systematic review of the literature and a meta-analysis. We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2017. Included studies were published prospective or retrospective cohort studies that compared major arrhythmic events (sustained ventricular tachycardia, sudden cardiac arrest, or sudden cardiac death) in HCM with fQRS versus non-fQRS. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. Five studies from January 2013 to May 2017 were included in this meta-analysis involving 673 subjects with HCM (205 fQRS and 468 non-fQRS). Fragmented QRS was associated with major arrhythmic events (pooled risk ratio=7.29, 95% confidence interval: 4.00-13.29, p<.01, I2 =0%). Baseline fQRS increased major arrhythmic events up to sevenfold. Our study suggests that fQRS could be an important tool for risk assessment in patients with HCM.

Baseline fragmented QRS increases the risk of major arrhythmic events in Brugada syndrome: Systematic review and meta-analysis.

Fragmented QRS reflects disturbances in the myocardium predisposing the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented QRS (fQRS) is associated with major arrhythmic events in Brugada syndrome. However, a systematic review and meta-analysis of the literature has not been done. We assessed the association between fQRS and major arrhythmic events in Brugada syndrome by a systematic review of the literature and a meta-analysis. We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2017. Included studies were published prospective or retrospective cohort studies that compared major arrhythmic events (ventricular fibrillation, sustained ventricular tachycardia, sudden cardiac arrest, or sudden cardiac death) in Brugada syndrome with fQRS versus normal QRS. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate risk ratios and 95% confidence intervals. Nine studies from January 2012 to May 2017 were included in this meta-analysis involving 2,360 subjects with Brugada syndrome (550 fQRS and 1,810 non-fQRS). Fragmented QRS was associated with major arrhythmic events (pooled risk ratio =3.36, 95% confidence interval: 2.09-5.38, p<.001, I2 =50.9%) as well as fatal arrhythmia (pooled risk ratio =3.09, 95% confidence interval: 1.40-6.86, p=.005, I2 =69.7%). Baseline fQRS increased major arrhythmic events up to 3-fold. Our study suggests that fQRS could be an important tool for risk assessment in patients with Brugada syndrome.

Early Arrhythmic Events in IdiopathicDilated Cardiomyopathy.

The study sought to provide an insight into the prevalence, characterization and possible reliable indicators of early sudden cardiac death/malignant ventricular arrhythmias (SCD/MVAs) in a large cohort of dilated cardiomyopathy (DCM). DCM generally affects young individuals and is characterized by an unpredictable prognosis with a non-negligible risk of SCD/MVAs, particularly in early stages of disease. From 1988 to 2014, 952 patients with DCM were consecutively included in the Heart Muscle Disease Registry of Trieste. Globally, 20 patients (2.1% of the overall population) experienced SCD/MVAs within the first 6 months after enrollment (primary endpoint). At baseline they showed a worse functional class (New York Heart Association functional class III to IV 42% vs. 22%, p= 0.038), a longer QRS complex duration (127 ± 41 ms vs. 108 ± 33 ms; p= 0.013) andalarger indexed left ventricular end-systolic volume (LVESVI) (82 ± 49 ml/m2 vs. 67 ± 34 ml/m2; p= 0.049), as compared to patients without early SCD/MVAs. Beta-blockers were less tolerated (59% vs. 83% in patients with no early SCD/MVAs; p= 0.008), mostly due to hemodynamic intolerance. At multivariate analysis, LVESVI (odds ratio [OR]: 1.012; 95% confidence interval [CI]: 1.000 to 1.024; p= 0.043) and QRS complex duration (OR: 1.017; 95% CI: 1.003 to 1.030; p= 0.015) were independently associated with the primary endpoint, whereas beta-blockers demonstrated a protective effect (OR: 0.169, CI: 0.048 to 0.593; p= 0.006). Patients with DCM present a significant risk of major arrhythmic events in the first phase of the disease. Baseline LVESVI, QRS duration, and intolerance to beta-blocker therapy might be useful tools in the arrhythmic early risk assessment.

Genetics can contribute to the prognosis of Brugada syndrome: a pilot model for risk stratification

Brugada syndrome is an inherited arrhythmogenic disorder leading to sudden death predominantly in the 3-4 decade. To date the only reliable treatment is the implantation of a cardioverter defibrillator; however, better criteria for risk stratification are needed, especially for asymptomatic subjects. Brugada syndrome genetic bases have been only partially understood, accounting for <30% of patients, and have been poorly correlated with prognosis, preventing inclusion of genetic data in current guidelines. We designed an observational study to identify genetic markers for risk stratification of Brugada patients by exploratory statistical analysis. The presence of genetic variants, identified by SCN5A gene analysis and genotyping of 73 candidate polymorphisms, was correlated with the occurrence of major arrhythmic events in a cohort of 92 Brugada patients by allelic association and survival analysis. In all, 18 mutations were identified in the SCN5A gene, including 5 novel, and statistical analysis indicated that mutation carriers had a significantly increased risk of major arrhythmic events (P=0.024). In addition, we established association of five polymorphisms with major arrhythmic events occurrence and consequently elaborated a pilot risk stratification algorithm by calculating a weighted genetic risk score, including the associated polymorphisms and the presence of SCN5A mutation as function of their odds ratio. This study correlates for the first time the presence of genetic variants with increased arrhythmic risk in Brugada patients, representing a first step towards the design of a new risk stratification model.

Association of Heart Rate Variability With Arrhythmic Events in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is associated with an increased risk of sudden cardiac death (SCD). Risk stratification of ARVC/D patients, however, remains an unresolved issue. In this study we investigated whether heart rate variability (HRV) can be helpful in identifying ARVC/D patients with increased risk of arrhythmic events. We studied 30 consecutive patients (17 males; 45.4 ± 18 years) with ARVC/D, diagnosed according to guideline criteria; 15 patients (50%) had received an implantable cardioverter defibrillator (ICD) for primary SCD prevention. HRV was assessed on 24-h ECG Holter monitoring. The primary endpoint was the occurrence of major arrhythmic events (SCD, sustained ventricular tachycardia (VT), ICD therapy for sustained VT or ventricular fibrillation (VF)). During the follow-up period (19 ± 7 months), no deaths occurred, but 5 patients (17%) experienced arrhythmic events (4 VTs and 1 VF, all in the ICD group). All HRV parameters were significantly lower in patients with, compared with those without, arrhythmic events. Low-frequency amplitude was the most significant HRV variable associated with arrhythmic events in univariate Cox regression analysis (P=0.017), and was the only significant predictor of arrhythmic events in multivariable regression analysis (hazard ratio 0.88, P=0.047), together with unexplained syncope (hazard ratio 16.1, P=0.039). Our data show that among ARVC/D patients HRV analysis might be helpful in identifying those with increased risk of major arrhythmic events.

Long Runs of Non‐Sustained Ventricular Tachycardia on 24‐Hour Ambulatory Electrocardiogram Predict Major Arrhythmic Events in Patients with Idiopathic Dilated Cardiomyopathy

This study examined the prognostic significance of the rate and length of non-sustained (NS) ventricular tachycardia (VT) on 24-hour ambulatory electrocardiograms (ECG) recorded in 343 patients with idiopathic dilated cardiomyopathy (IDC) in the prospective Marburg Cardiomyopathy study. NSVT was defined as >/=3 consecutive ventricular premature beats at >120 bpm. During 52 +/- 21 months of follow-up, major arrhythmic events defined as sustained VT, VF, or sudden cardiac death occurred in 46 of 343 patients (13%). Patients with 3-4 beat runs of NSVT had a similar arrhythmia-free survival as patients without NSVT on baseline 24-hour ambulatory ECG. The incidence of major arrhythmic events during follow-up increased significantly from 2% per year in patients without NSVT, to 5% per year in patients with 5-9 beat runs of NSVT, to 10% per year in patients with >/=10 beat runs of NSVT (P < 0.05). Unlike the length, the rate of NSVT was similar in patients with versus without subsequent major arrhythmic events (163 +/- 23 vs 160 +/- 24 bpm). Thus, the length but not the rate of NSVT on 24-hour ambulatory ECG was a predictor of major arrhythmic events in patients with IDC. The presence of NSVT with >/=10 beat runs on ambulatory ECG was associated with a particularly high risk of major arrhythmic events.

Utility of current risk stratification tests for predicting major arrhythmic events after myocardial infarction

OBJECTIVESWe surveyed the literature to estimate prediction values for five common tests for risk of major arrhythmic events (MAEs) after myocardial infarction. We then determined feasibility of a staged risk stratification using combinations of noninvasive tests, reserving an electrophysiologic study (EPS) as the final test.BACKGROUNDImproved approaches are needed for identifying those patients at highest risk for subsequent MAE and candidates for implantable cardioverter-defibrillators.METHODSWe located 44 reports for which values of MAE incidence and predictive accuracy could be inferred: signal-averaged electrocardiography; heart rate variability; severe ventricular arrhythmia on ambulatory electrocardiography; left ventricular ejection fraction; and EPS. A meta-analysis of reports used receiver-operating characteristic curves to estimate mean values for sensitivity and specificity for each test and 95% confidence limits. We then simulated a clinical situation in which risk was estimated by combining tests in three stages.RESULTSTest sensitivities ranged from 42.8% to 62.4%; specificities from 77.4% to 85.8%. A three-stage stratification yielded a low-risk group (80.0% with a two-year MAE risk of 2.9%), a high-risk group (11.8% with a 41.4% risk) and an unstratified group (8.2% with an 8.9% risk equivalent to a two-year incidence of 7.9%).CONCLUSIONSSensitivities and specificities for the five tests were relatively similar. No one test was satisfactory alone for predicting risk. Combinations of tests in stages allowed us to stratify 91.8% of patients as either high-risk or low-risk. These data suggest that a large prospective study to develop a robust prediction model is feasible and desirable.