Risk Stratification Of Ventricular Arrhythmias Research Articles

Serial Cardiac Magnetic Resonance Imaging in Patients with Mitral Valve Prolapse-A Single-Center Retrospective Registry.

Background: Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac magnetic resonance imaging (CMR) has a key role in risk stratification of VA, including assessment of late gadolinium enhancement (LGE). Methods: Single-center retrospective analysis of patients with MVP or MAD who had >1 CMR and >1 24 h Holter registration available. Data are presented in detail, including evolution of VA and presence of LGE over time. Results: A total of twelve patients had repeated CMR and Holter registrations available, of which in four (33%) patients, it was conducted before and after minimal invasive mitral valve repair (MVR). After a median of 4.7 years, four out of eight (50%) patients without surgical intervention had new areas of LGE. New LGE was observed in the papillary muscles and the mid to basal inferolateral wall. In four patients, presenting with syncope or high-risk non-sustained ventricular tachycardia (VT), programmed ventricular stimulation was performed and in two (50%), sustained monomorphic VT was easily inducible. In two patients who underwent MVR, new LGE was observed in the basal inferolateral wall of which one presented with an increased burden of VA. Conclusions: In patients with MVP and MAD, repeat CMR may show new LGE in a small subset of patients, even shortly after MVR. A subgroup of patients who presented with an increase in VA burden showed new LGE upon repeat CMR. VA in patients with MVP and MAD are part of a heterogeneous spectrum that requires further investigation to establish risk stratification strategies.

Ultra-High-Frequency ECG in Cardiac Pacing and Cardiac Resynchronization Therapy: From Technical Concept to Clinical Application.

Identifying electrical dyssynchrony is crucial for cardiac pacing and cardiac resynchronization therapy (CRT). The ultra-high-frequency electrocardiography (UHF-ECG) technique allows instantaneous dyssynchrony analyses with real-time visualization. This review explores the physiological background of higher frequencies in ventricular conduction and the translational evolution of UHF-ECG in cardiac pacing and CRT. Although high-frequency components were studied half a century ago, their exploration in the dyssynchrony context is rare. UHF-ECG records ECG signals from eight precordial leads over multiple beats in time. After initial conceptual studies, the implementation of an instant visualization of ventricular activation led to clinical implementation with minimal patient burden. UHF-ECG aids patient selection in biventricular CRT and evaluates ventricular activation during various forms of conduction system pacing (CSP). UHF-ECG ventricular electrical dyssynchrony has been associated with clinical outcomes in a large retrospective CRT cohort and has been used to study the electrophysiological differences between CSP methods, including His bundle pacing, left bundle branch (area) pacing, left ventricular septal pacing and conventional biventricular pacing. UHF-ECG can potentially be used to determine a tailored resynchronization approach (CRT through biventricular pacing or CSP) based on the electrical substrate (true LBBB vs. non-specified intraventricular conduction delay with more distal left ventricular conduction disease), for the optimization of CRT and holds promise beyond CRT for the risk stratification of ventricular arrhythmias.

Right Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: Potential Value of Strain Echocardiography

Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy, characterized by abnormal cell adhesions, disrupted intercellular signaling, and fibrofatty replacement of the myocardium. These changes serve as a substrate for ventricular arrhythmias, placing patients at risk of sudden cardiac death, even in the early stages of the disease. Current echocardiographic criteria for diagnosing arrhythmogenic right ventricular cardiomyopathy lack sensitivity, but novel markers of cardiac deformation are not subject to the same technical limitations as current guideline-recommended measures. Measuring cardiac deformation using speckle tracking allows for meticulous quantification of global systolic function, regional function, and dyssynchronous contraction. Consequently, speckle tracking to quantify myocardial strain could potentially be useful in the diagnostic process for the determination of disease progression and to assist risk stratification for ventricular arrhythmias and sudden cardiac death. This narrative review provides an overview of the potential use of different myocardial right ventricular strain measures for characterizing right ventricular dysfunction in arrhythmogenic right ventricular cardiomyopathy and its utility in assessing the risk of ventricular arrhythmias.

Dynamic prediction of malignant ventricular arrhythmias using neural networks in patients with an implantable cardioverter-defibrillator

Risk stratification for ventricular arrhythmias currently relies on static measurements that fail to adequately capture dynamic interactions between arrhythmic substrate and triggers over time. We trained and internally validated a dynamic machine learning (ML) model and neural network that extracted features from longitudinally collected electrocardiograms (ECG), and used these to predict the risk of malignant ventricular arrhythmias. A multicentre study in patients implanted with an implantable cardioverter-defibrillator (ICD) between 2007 and 2021 in two academic hospitals was performed. Variational autoencoders (VAEs), which combine neural networks with variational inference principles, and can learn patterns and structure in data without explicit labelling, were trained to encode the mean ECG waveforms from the limb leads into 16 variables. Supervised dynamic ML models using these latent ECG representations and clinical baseline information were trained to predict malignant ventricular arrhythmias treated by the ICD. Model performance was evaluated on a hold-out set, using time-dependent receiver operating characteristic (ROC) and calibration curves. 2942 patients (61.7±13.9 years, 25.5% female) were included, with a total of 32,129 ECG recordings during a mean follow-up of 43.9±35.9 months. The mean time-varying area under the ROC curve for the dynamic model was 0.738±0.07, compared to 0.639±0.03 for a static (i.e. baseline-only model). Feature analyses indicated dynamic changes in latent ECG representations, particularly those affecting the T-wave morphology, were of highest importance for model predictions. Dynamic ML models and neural networks effectively leverage routinely collected longitudinal ECG recordings for personalised and updated predictions of malignant ventricular arrhythmias, outperforming static models. This publication is part of the project DEEP RISK ICD (with project number 452019308) of the research programme Rubicon which is (partly) financed by the Dutch Research Council (NWO). This research is partly funded by the Amsterdam Cardiovascular Sciences (personal grant F.V.Y.T).

The application of radiology for dilated cardiomyopathy diagnosis, treatment, and prognosis prediction: a bibliometric analysis.

Radiology plays a highly crucial role in the diagnosis, treatment, and prognosis prediction of dilated cardiomyopathy (DCM). Related research has increased rapidly over the past few years, but systematic analyses are lacking. This study thus aimed to provide a reference for further research by analyzing the knowledge field, development trends, and research hotspots of radiology in DCM using bibliometric methods. Articles on the radiology of DCM published between 2002 and 2021 in the Web of Science Core Collection database (WoSCCd) were searched and analyzed. Data were retrieved and analyzed using CiteSpace V, VOSviewer, and Scimago Graphic software, and included the name, research institution, and nationality of authors; journals of publication; and the number of citations. A total of 4,257 articles were identified on radiology of DCM from WoSCCd. The number of articles published in this field has grown steadily from 2002 to 2021 and is expected to reach 392 annually by 2024. According to subfields, the number of papers published in cardiac magnetic resonance field increased steadily. The authors from the United States published the most (1,364 articles, 32.04%) articles. The author with the most articles published was Bax JJ (54 articles, 1.27%) from Leiden University Medical Center. The most cited article was titled "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure", with 138 citations. Citation-based clustering showed that arrhythmogenic cardiomyopathy, T1 mapping, and endomyocardial biopsy are the current hots pots for research in DCM radiology. The most frequently occurring keyword was "dilated cardiomyopathy". The keyword-based clusters mainly included "late gadolinium enhancement", "congestive heart failure", "cardiovascular magnetic resonance", "sudden cardiac death", "ventricular arrhythmia", and "cardiac resynchronization therapy". The United States and Northern Europe are the most influential countries in research on DCM radiology, with many leading distinguished research institutions. The current research hots pots are myocardial fibrosis, risk stratification of ventricular arrhythmia, the prognosis of cardiac resynchronization therapy (CRT) treatment, and subtype classification of DCM.

Non-sustained ventricular arrhythmias at exercise ECG predict severe ventricular arrhythmias in arrhythmic mitral valve prolapse

Abstract Background A subset of patients with mitral valve prolapse experience ventricular arrhythmias (VA) and even sudden cardiac death, defined as arrhythmic mitral valve prolapse (AMVP). Risk stratification of VA is challenging in this relatively young population. The predictive role of exercise testing has not been investigated. Purpose We aimed to explore if VA burden on exercise ECG can predict severe ventricular arrhythmic events in AMVP patients. Methods We included consecutive AMVP patients without prior severe VA referred to our tertiary center. Exercise bicycle ECG test by standard protocol was performed at inclusion. Non-sustained VT (nsVT) during exercise testing was defined as ≥3 consecutive ventricular beats with a rate ≥100/min lasting <30 seconds. Our endpoint of severe VA during follow-up was defined as aborted cardiac arrest, sustained ventricular tachycardia, nsVT with syncope or appropriate ICD shock therapy detected by either ECG, Holter monitoring, implantable loop recorder or primary preventive ICD. Results We included 91 AMVP patients without prior severe VA (51±16 years of age, 63% women) with exercise test at baseline. NsVT occurred in 5 patients during exercise testing. During 67±7 months of follow-up, 5 (5.5%) patients experienced severe VA. In all, 3 of the 5 (60%) with nsVT at exercise test experienced severe VA during follow-up, compared to only 2 of 86 (2%) without nsVT at exercise testing (age adjusted hazard ratio [HR] 35 [95% CI 5–249], p<0.001). Survival free from severe VA was worse in those with nsVT at exercise test (log rank p<0.001) (Figure 1). Conclusions Non-sustained VT occurring during exercise ECG testing was a strong marker of subsequent severe VA in AMVP patients without previous severe VA. These novel findings indicate that exercise testing may improve risk stratification in AMVP patients. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The Research Council of Norway.

Predictors of ventricular arrhythmias in arrhythmic mitral valve syndrome – a study using implantable loop recorders

Abstract Background Arrhythmic mitral valve syndrome is linked to life-threatening ventricular arrhythmias, but the incidence and methods for risk stratification of ventricular arrhythmias are not well known. Purpose In this prospective study, we aimed to describe the incidence of ventricular arrhythmias by use of continuous rhythm monitoring and propose risk stratification in patients with arrhythmic mitral valve syndrome. Methods We included consecutive patients with arrhythmic mitral valve prolapse, defined as mitral valve prolapse and/or mitral annulus disjunction (MAD) with arrhythmic symptoms or documented complex premature ventricular complexes (PVC). We implanted loop recorders (ILR) in patients with arrhythmic mitral valve syndrome with no previous severe ventricular arrhythmias and all were followed by remote monitoring. We monitored for non-sustained ventricular tachycardias (NSVT) and severe ventricular arrhythmia, defined as aborted cardiac arrest, sustained ventricular tachycardia and NSVT with syncope/presyncope. At baseline, patients underwent echocardiography, 24-hour Holter monitoring, stress ECG and cardiac magnetic resonance imaging. Results We included 60 patients (73% female, 49 years [interquartile range [IQR] 37–60]). At baseline, median PVC burden was 232 per 24-hours (IQR 33–1329), and 8 (13%) patients had NSVT by Holter monitoring or stress ECG. During 3.0±0.5 years of follow-up, severe ventricular arrhythmia occurred in 7 (12%) patients (1 aborted cardiac arrest, 6 NSVT with syncope/pre-syncope). Annual incidence rate of severe events was 4% per person-year (95% confidence interval [CI] 2–9)). Predictors of severe ventricular arrhythmia were frequent PVCs (6683 PVCs per 24h [IQR 612–10861] vs. 154 PVCs per 24h [IQR 25–562], p=0.01), more NSVTs by ILR (4 NSVTs [IQR 2–7] vs. 0 NSVTs [0–1], p<0.001), greater left ventricular diameter (57±6 mm vs. 51±6 mm, p=0.01) and greater posterolateral MAD distance (9 mm [IQR 8–12] vs. 4 mm [IQR 0–6], p=0.02). Adjustment for age and sex did not change significant risk markers (all p<0.02). During follow-up 102 NSVTs were recorded in 24 (40%) patients. In multivariate Poisson regression adjusting for age, mitral regurgitation grade and bileaflet prolapse, predictors of high NSVT burden were frequent PVCs (incidence rate ratio [IRR] 1.14 [95% CI 1.04–1.27], p=0.01), PVCs from inferior left ventricle (IRR 5.19 [95% CI 2.80–9.63], p<0.001) and late gadolinium enhancement (IRR 3.16 [95% CI 1.68–5.97], p<0.001). Conclusion Yearly incidence of first severe ventricular arrhythmia was 4% in patients with arrhythmic mitral valve syndrome, emphasizing the high risk of life-threatening events in these patients. Frequent PVCs, NSVTs, greater left ventricular diameter and greater posterolateral MAD distance were predictors of first severe ventricular arrhythmia and should be used in risk stratification. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by a public grant from the Norwegian Research Council (#288438 and #309762), Precision Health Center for optimized cardiac care (ProCardio).

Advanced imaging for risk stratification for ventricular arrhythmias and sudden cardiac death.

Sudden cardiac death (SCD) is a leading cause of mortality, comprising approximately half of all deaths from cardiovascular disease. In the US, the majority of SCD (85%) occurs in patients with ischemic cardiomyopathy (ICM) and a subset in patients with non-ischemic cardiomyopathy (NICM), who tend to be younger and whose risk of mortality is less clearly delineated than in ischemic cardiomyopathies. The conventional means of SCD risk stratification has been the determination of the ejection fraction (EF), typically via echocardiography, which is currently a means of determining candidacy for primary prevention in the form of implantable cardiac defibrillators (ICDs). Advanced cardiac imaging methods such as cardiac magnetic resonance imaging (CMR), single-photon emission computerized tomography (SPECT) and positron emission tomography (PET), and computed tomography (CT) have emerged as promising and non-invasive means of risk stratification for sudden death through their characterization of the underlying myocardial substrate that predisposes to SCD. Late gadolinium enhancement (LGE) on CMR detects myocardial scar, which can inform ICD decision-making. Overall scar burden, region-specific scar burden, and scar heterogeneity have all been studied in risk stratification. PET and SPECT are nuclear methods that determine myocardial viability and innervation, as well as inflammation. CT can be used for assessment of myocardial fat and its association with reentrant circuits. Emerging methodologies include the development of “virtual hearts” using complex electrophysiologic modeling derived from CMR to attempt to predict arrhythmic susceptibility. Recent developments have paired novel machine learning (ML) algorithms with established imaging techniques to improve predictive performance. The use of advanced imaging to augment risk stratification for sudden death is increasingly well-established and may soon have an expanded role in clinical decision-making. ML could help shift this paradigm further by advancing variable discovery and data analysis.

C - reactive protein is a promising indicator of ventricular arrhythmias in pacemaker patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Ventricular tachyarrhythmias are the main reason for sudden cardiac death to date. Accordingly, tools for risk stratification for ventricular arrhythmias are paramount. Non-sustained ventricular tachycardia (nsVT) represents a predictor of malignant rhythm disorders. Recently, low grade chronic inflammation was shown to predict ventricular arrhythmic events in high risk patients. This study aims to investigate, if inflammatory markers may predict higher arrhythmia burden in a low risk population. Methods We prospectively analyzed ventricular arrhythmia burden in pacemaker records of 166 patients (age 79.2 9.3; male 60.2%, 38 with coronary artery disease (CAD)) with preserved ejection fraction (left ventricular ejection fraction≥50%) during a annually pacemaker follow up in a single center. To evaluate potential predictive factors, associations of laboratory values including inflammatory markers (CRP and interleukin 6) with occurrence of nsVT was evaluated using logistic regression. Sensitivity analysis in patients with and without established CAD was performed. Results The cumulative incidence of nsVT was 12.7%. Concentrations of BNP (OR 1.00 95%CI 0.99-1.01; p=0.46), troponin (OR 0.98 95%CI 0.95-1.02; p=0.43) or interleukin-6 (OR 1.03 95%CI 0.99-1.07; p=0.16) were not associated with the occurrence of nsVTs. However, the concentration of CRP was associated with increased odds of nsVT (OR 1.26 95%CI 0.97-1.64; p=0.09) in trend. In sensitivity analysis in CAD patients, CRP was associated with increased likelihood of nsVT (OR 3.89 95%CI 1.14-13.29; p=0.03), whereas in patients without CAD there was no association between CRP and rates of nsVTs (OR 1.16 95%CI 0.88-1.54; p=0.30). Conclusion Our study shows that inflammatory markers like CRP may be promising predictors of rhythm disorders CAD patients. While CRP was associated with increased odds for nsVTs in pacemaker patients with CAD, IL-6 did not show a significant correlation. This might be based on a more volatile expression of IL-6 while CRP represents a more stable parameter for inflammation.

Electrical markers and arrhythmic risk associated with myocardial fibrosis in mitral valve prolapse.

AimsWe aimed to characterize the substrate of T-wave inversion (TWI) using cardiac magnetic resonance (CMR) and the association between diffuse fibrosis and ventricular arrhythmias (VA) in patients with mitral valve prolapse (MVP).Methods and resultsTWI was defined as negative T-wave ≥0.1 mV in ≥2 adjacent ECG leads. Diffuse myocardial fibrosis was assessed by T1 relaxation time and extracellular volume (ECV) fraction by T1-mapping CMR. We included 162 patients with MVP (58% females, age 50 ± 16 years), of which 16 (10%) patients had severe VA (aborted cardiac arrest or sustained ventricular tachycardia). TWI was found in 34 (21%) patients. Risk of severe VA increased with increasing number of ECG leads displaying TWI [OR 1.91, 95% CI (1.04–3.52), P = 0.04]. The number of ECG leads displaying TWI increased with increasing lateral ECV (26 ± 3% for TWI 0-1leads, 28 ± 4% for TWI 2leads, 29 ± 5% for TWI ≥3leads, P = 0.04). Patients with VA (sustained and non-sustained ventricular tachycardia) had increased lateral T1 (P = 0.004), also in the absence of late gadolinium enhancement (LGE) (P = 0.008).ConclusionsGreater number of ECG leads with TWI reflected a higher arrhythmic risk and higher degree of lateral diffuse fibrosis by CMR. Lateral diffuse fibrosis was associated with VA, also in the absence of LGE. These results suggest that TWI may reflect diffuse myocardial fibrosis associated with VA in patients with MVP. T1-mapping CMR may help risk stratification for VA.

Sex-specific differences in outcome and risk stratification of ventricular arrhythmias in implantable cardioverter defibrillator patients.

AimsRisk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women.Methods and resultsWe performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow‐up was 4.6 (inter‐quartile range: 4.4–4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P < 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P < 0.01) was associated with ADT, whereas higher age (HR 1.20, P < 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P < 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex‐specific pattern in ADT.ConclusionsMale ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non‐ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex‐specific relation to ventricular arrhythmias. As a consequence, sex‐specific risk stratification models of SCD using commonly available clinical parameters could not be derived.

Risk stratification of ventricular arrhythmias in repaired tetralogy of Fallot

Introduction and objectivesRisk stratification of ventricular arrhythmias in patients with repaired tetralogy of Fallot (rTOF) remains unresolved. We aimed to identify right ventricular (RV) electrophysiological parameters potentially associated with a higher risk of ventricular arrhythmias in patients with rTOF. MethodsWe included all consecutive patients with rTOF who underwent RV electroanatomical mapping at a single tertiary center. We used logistic regression modeling to identify those variables associated with an increased risk of clinical or induced ventricular tachycardia (VT), or clinical VT exclusively. ResultsTwenty-one of the 56 patients included had clinical or induced VT. A high-frequency of premature ventricular contractions/nonsustained VT (OR, 11.34; 95%CI, 1.50-85.97; P=.019), an HV interval > 55 ms (OR, 21.20; 95%CI, 3.12-144.14; P=.002), and RV activation time (ms) (OR [per 10ms intervals], 1.34; 95%CI, 1.02-1.75; P=.035) proved to be associated with clinical or induced VT. The model including this information had good discrimination ability, with an area under the curve of 0.884 (95%CI, 0.79-0.97; P <.001). When considering only clinical VT as the outcome of interest, only an HV interval > 55ms (OR, 9.65; 95%CI, 1.41-66.14; P=.021) and high-frequency of premature ventricular contractions/nonsustained VT (OR, 13.14; 95%CI, 1.95-88.54; P=.008) were independently associated (area under the curve of 0.836 [95%CI, 0.663-1.000; P=.002]). ConclusionsHigh-frequency of premature ventricular contractions/nonsustained VT, an HV interval> 55ms and RV activation time are factors associated with an increased risk of ventricular arrhythmias in patients with rTOF.

Sex-specific differences in risk stratification of ventricular arrhythmias among implantable cardioverter defibrillator patients: do women differ from men?

Abstract Background Implantable cardioverter defibrillator (ICD) guidelines and risk stratification models of sudden cardiac death (SCD) are applied without differentiation between men and women, based on the assumption that the incidence of ventricular arrhythmias and risk factors of SCD are similar in both sexes. Sex-specific risk factors of SCD may influence studies evaluating the benefit of ICD therapy, for both men and women. Purpose Aim of the study is to assess sex-specific differences in occurrence and predictors of appropriate device therapy (ADT) for ventricular arrhythmias. Methods A multicenter retrospective cohort of 2300 consecutive patients was evaluated, including patients referred for ICD implantation between the years 2009–2018 (age 62±13 years, LVEF 32±12%, 53% ischemic cardiomyopathy [CMP], 28% resynchronization therapy, 65% primary prevention). Exclusion criteria were: (1) patients with hypertrophic CMP, arrhythmogenic right ventricular CMP, systemic infiltrative cardiac disease or channelopathy; (2) lost to follow-up immediately after ICD implantation. Primary endpoint was ADT, defined as anti-tachycardia pacing or shock for ventricular tachyarrhythmia. Secondary endpoints were mortality and inappropriate ICD therapy. Univariable and multivariable Cox regression analyses, stratified by sex, were performed to assess predictors of ADT. Results The cohort primarily consisted of men (75%). After a mean follow-up of 4.8±3.0 years, men experienced more ADT compared to women (25% versus 16%, HR 1.71, p&amp;lt;0.001) and men displayed a higher mortality compared to women (25% versus 19%, HR 1.37, p&amp;lt;0.01). No difference in inappropriate ICD therapy was observed (9% versus 10%, HR 1.01, p=0.94). In the total study cohort, male sex (HR 1.55, p&amp;lt;0.001), higher age (HR 1.15 per 10 years, p&amp;lt;0.0019), left bundle branch block (LBBB, HR 0.74, p=0.01) and secondary prevention indication (HR 1.89, p&amp;lt;0.001) were independently associated with ADT. In male patients, independent predictors of ADT were comparable with the total study cohort: higher age (HR 1.20 per 10 years, p&amp;lt;0.001), LBBB (HR 0.72, p=0.01) and secondary prevention therapy (HR 1.80, p&amp;lt;0.001). In contrast, age (p=0.54) or LBBB (p=0.29) were not associated with ADT in women. In women, only paroxysmal atrial fibrillation (HR 1.76, p=0.03) and secondary prevention therapy (HR 1.78, p&amp;lt;0.01) were independently associated with ADT. Conclusion This study showed that men were at higher risk of ADT compared to women and that risk factors associated with SCD differ between both sexes. The results strongly suggests that SCD risk stratification models are primarily driven by male patients and sex-specific risk models of SCD are needed to identify those women at high risk of SCD. Figure 1 Funding Acknowledgement Type of funding source: None

Ventricular arrhythmias in heart failure with reduced ejection fraction.

To provide a framework for approaching ventricular arrhythmias in the setting of cardiomyopathy, outline the latest evidence-based recommendations for catheter ablation and device therapy, and discuss novel treatment strategies. Risk stratification of ventricular arrhythmias in systolic heart failure has evolved, with an increasing role for cardiac magnetic resonance imaging to identify underlying substrate and scar burden. Medical therapy for heart failure has greatly improved, and the role of primary prevention defibrillators in nonischemic cardiomyopathy has become more ambiguous. Catheter ablation is superior to medical therapy for arrhythmia control and should be considered early, particularly for premature ventricular complex mediated cardiomyopathy. Novel technologies to deliver energy to previously inaccessible sites include high-impedance catheter irrigants, multicatheter bipolar ablation, specialized catheters with extendable needles, transcoronary ethanol infusion, and stereotactic body radiation therapy. Assessment and management of ventricular arrhythmias in systolic heart failure requires a systematic, multimodality approach aimed at identifying the underlying cause and reversible causes, optimizing medical therapy, assessing need for an implantable cardioverter defibrillator, and considering catheter ablation. Further research will focus on prevention of disease progression, improved risk stratification, and ablation technologies that minimize procedure duration and enable delivery of durable lesions.

P5976Prediction of ventricular arrhythmias with mechanical dispersion assessed by strain echocardiography: a systematic review and meta-analysis

Abstract Background Recent studies have demonstrated that left ventricular mechanical dispersion (LVMD) assessed by speckle tracking might be a powerful marker in risk stratification for ventricular arrhythmias (VA). We sought to perform a systematic review and meta-analysis to i) assess the prognostic value of this parameter (previous studies were predominantly single-center), ii) define the value relative to other parameters, iii) identify the most appropriate cutoff for designating risk. Purpose To assess the association between LVMD and the incidence of VA. Methods A systemic review of studies reporting the predictive value of LVMD for VA was undertaken from a search of Medline and Embase. LVMD was defined as the standard deviation of time from Q/R on ECG to peak negative strain from each LV segment. VA events were defined as sudden cardiac death, cardiac arrest, documented ventricular tachyarrhythmia, and appropriate implantable cardioverter defibrillator therapy. Hazard ratios (HRs) were extracted from univariable and multivariable models reporting on the association of LVMD and VA and described as pooled estimates with 95% confidence intervals (CIs). In a meta-analysis, the predictive value of LVMD was compared to that of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Results Among 3198 patients (weighted mean, 63 years, 30% female; 82% ischemic heart disease) in 12 published articles, 387 (12%) had VA events over a follow-up (17–70 months). Patients with VA events had a significantly greater mechanical dispersion compared with those without VA events (weighted mean difference, −20.3 ms; 95% CI, −27.3 to −13.2; p&lt;0.01); 60 ms was found to be the optimal cutoff LVMD value for predicting VA events. Each 10 ms increment of LVMD was significantly and independently associated with VA events (HR, 1.19; 95% CI, 1.09 to 1.29; p&lt;0.01). The predictive value of LVMD was superior to that of LVEF or GLS (Figure). Figure 1 Conclusion LVMD assessed by speckle tracking provides important predictive value for VA in patients with a number of cardiac diseases and appears to have superior predictive value to LVEF and GLS for risk stratification.

Prediction of Ventricular Arrhythmias With Left Ventricular Mechanical Dispersion: A Systematic Review and Meta-Analysis

ObjectivesThe aim of this study was to assess the association between left ventricular mechanical dispersion (LVMD) and the incidence of ventricular arrhythmias (VAs). BackgroundRecent, mainly single-center, studies have demonstrated that LVMD assessed using speckle tracking might be a powerful marker in risk stratification for VA. A systematic review and meta-analysis provides a means of understanding the prognostic value of this parameter, relative to other parameters, the most appropriate cutoff for designating risk. MethodsA systemic review of studies reporting the predictive value of LVMD for VA was undertaken from a search of MEDLINE and Embase. VA events were defined as sudden cardiac death, cardiac arrest, documented ventricular tachyarrhythmia, and appropriate implantable cardioverter-defibrillator (ICD) therapy. Hazard ratios were extracted from univariate and multivariate models reporting on the association of LVMD and VA and described as pooled estimates with 95% confidence intervals. In a meta-analysis, the predictive value of LVMD was compared with that of left ventricular ejection fraction and global longitudinal strain. ResultsAmong 3,198 patients in 12 published studies, 387 (12%) had VA events over follow-up ranging from 17 to 70 months. Patients with VAs had greater LVMD than those without (weighted mean difference −20.3 ms; 95% confidence interval: −27.3 to −13.2; p < 0.01). Each 10 ms increment of LVMD was significantly and independently associated with VA events (hazard ratio: 1.19; 95% confidence interval: 1.09 to 1.29; p < 0.01). The predictive value of LVMD was superior to that of left ventricular ejection fraction or global longitudinal strain. ConclusionsLVMD assessed using speckle tracking provides important predictive value for VA in patients with a number of cardiac diseases and appears to have superior predictive value over left ventricular ejection fraction and global longitudinal strain for risk stratification.

Mean entropy predicts implantable cardioverter-defibrillator therapy using cardiac magnetic resonance texture analysis of scar heterogeneity

Risk stratification of ventricular arrhythmia remains complex in patients with ischemic and nonischemic cardiomyopathy. The purpose of this study was to determine whether scar heterogeneity, quantified by mean entropy, predicts appropriate implantable cardioverter-defibrillator (ICD) therapy. We hypothesized that higher mean entropy calculated from cardiac magnetic resonance texture analysis (CMR-TA) will predict appropriate ICD therapy. Consecutive patients underwent CMR imaging before ICD implantation. Short-axis left ventricular scar was manually segmented. CMR-TA was performed using a Laplacian filter to extract and augment image features to create a scar texture from which histogram analysis of pixel intensity was used to calculate mean entropy. The primary end point was appropriate ICD therapy. A total of 114 patients underwent CMR-TA (ischemic cardiomyopathy [ICM]: n = 70; nonischemic cardiomyopathy [NICM]: n = 44) with a median follow-up of 955 days (interquartile range 691-1185 days). Mean entropy was significantly higher in the ICM group (5.7 ± 0.7 vs 5.5 ± 0.7; P= .045). Overall, 33 patients received appropriate ICD therapy. Using optimized cutoff values from receiver operating characteristic curves, Kaplan-Meier survival analysis demonstrated time until first appropriate therapy was significantly shorter in the high mean entropy group (P = .003). Multivariable analysis showed that mean entropy was the sole predictor of appropriate ICD therapy (hazard ratio 1.882; 95% confidence interval 1.083-3.271; P = .025). In the ICM group, mean entropy remained an independent predictor of appropriate ICD therapy, whereas in the NICM group, precontrast T1 values were the sole predictor. Scar heterogeneity, quantified by mean entropy using CMR-TA, was an independent predictor of appropriate ICD therapy in the mixed cardiomyopathy cohort and ICM-only group, suggesting a potential role for CMR-TA in predicting ventricular arrhythmia and risk-stratifying patients for ICD implantation.

Global Longitudinal Strain as a Predictor of First and Subsequent Arrhythmic Events in Remotely Monitored ICD Patients With Structural Heart Disease

ObjectivesThis study sought to assess speckle-tracking–derived parameters as predictors of first and subsequent ventricular events in patients with structural heart disease and implantable cardioverter-defibrillators (ICD). BackgroundLeft ventricular ejection fraction (LVEF), the current primary parameter of risk stratification for ventricular arrhythmias (VAs) in structural heart diseases is burdened by many limitations. MethodsIn this retrospective, observational study, all consecutive patients with structural heart disease were admitted for ICD implantation. Patients not followed by a home-monitoring system were excluded. Two-dimensional (2D) speckle-tracking analysis was used to derive global longitudinal strain (GLS), mechanical dispersion (MD), and delta contraction duration (DCD) of all patients at enrollment. Home monitoring was checked weekly to detect all VAs and ICD therapies. A recurrent event statistical approach (Prentice, Williams, and Peterson model) was applied to evaluate subsequent events after the first ones. ResultsA total of 203 patients were consecutively enrolled and followed for a median of 2.2 years. Kaplan-Meier curves showed an increased risk of antitachycardia pacing or shock (log-rank p = 0.003) and VAs (log-rank p = 0.001) associated with lower quartiles of GLS. An impaired GLS was independently associated with an increased risk for the first ICD therapy (hazard ratio [HR]: 1.94; 95% confidence interval [CI]: 1.30 to 2.91; p = 0.001) and (HR: 1.42; 95% CI: 1.01 to 1.98; p = 0.04) for the first VA. GLS impairment was not significantly associated with an increased risk of recurrent ICD therapies or VAs. LVEF, MD, and DCD were not associated with an increased risk of first, second, and third ICD therapies or VA. ConclusionsImpaired GLS is associated with an increased risk of VAs and appropriate ICD therapies in a consecutive “real-world,” unselected population of remotely monitored patients with structural heart disease, although it does not seem reliable in predicting further arrhythmic events after the first one. MD and DCD do not predict first or subsequent arrhythmic events in ICD patients with structural heart disease.

Abstract 17194: Incremental Value of JTc Interval in Improving Risk Stratification for Life-Threatening Ventricular Arrhythmias in Patients Considered Low Risk by LVEF

Introduction: ICD implantation is recommended in patients with LVEF&lt;35%, while those with LVEF between 35 to 40% are not considered at high risk for primary prevention ICD implantation. A subset of these patients develops life threatening ventricular arrhythmias (VA) and improvement in risk stratification may help identify and implement life-saving intervention. Hypothesis: Prolonged repolarization is a marker of electrical instability and JTc interval on ECG could provide prognostic information in patients with LVEF 35-40% incremental to that from LVEF. Methods: Patients ≥18 yr with no history of VA and an ECG and echocardiogram obtained at initial encounter between 11/2011 to 12/2016 with long-term follow-up were identified. The incremental predictive ability of JTc interval on improvement in risk stratification for VA was determined by receiver operating characteristics (ROC) curve, integrated discrimination improvement (IDA) and net reclassification improvement (NRI) analysis. All tests were performed at a 5% level of significance. Results: Out of 29,700 pts that met inclusion criteria, 1,102 (3.7%) had LVEF 35-40% (mean age 70.5±14.6 yrs, 49% males, CAD 67%) and 24,894 (84%) LVEF &gt;40% (65.9±16.3 yrs , 61.8% M). Over the mean follow-up of 4.6±4.2 years, the incidence of VT/VF/cardiac arrest was 16.1% in patients with LVEF 35-40% compared to 4.1% with LVEF &gt;40%. For every 50 ms increase in JTc interval above 300 ms, the risk for arrhythmic event in LVEF 35-40% increased two-fold (Odds Ratio=1.83 (95 % CI 1.72-1.94, P=0.013). Incorporation of JTc to LVEF improved the C statistics (95% Confidence Limit) in the model with only LVEF from 0.56 (0.54-0.57) to 0.72 (0.70-0.73) for the model combining LVEF and JTc. In addition, NRI was estimated at 0.57, which was statistically significant with p values &lt;0.001 while IDI was estimated as 0.015 with p values &lt;0.001 for the model incorporating JTc to LVEF. Conclusions: In patients with LVEF 35-40% considered low risk for life threatening VA by EF, incorporating JTc interval information improved risk stratification and identified those who subsequently developed VT/VF or cardiac arrest and thus identifies a subgroup that can benefit from prophylactic ICD implantation.

Isolated Late Activation Detected by Magnetocardiography Predicts Future Lethal Ventricular Arrhythmic Events in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Risk stratification of ventricular arrhythmias is vital to the optimal management in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect isolated late activation (ILA) by overcoming the limitations of conventional noninvasive predictors of ventricular tachyarrhythmias, including epsilon waves, late potential (LP), and right ventricular ejection fraction (RVEF), in ARVC patients.Methods and Results:We evaluated ILA on MCG, defined as discrete activations re-emerging after the decay of main RV activation (%magnitude >5%), and conventional noninvasive predictors of ventricular tachyarrhythmias (epsilon waves, LP, and RVEF) in 40 patients with ARVC. ILA was noted in 24 (60%) patients. Most ILAs were found in RV lateral or inferior areas (17/24, 71%). We defined "delayed ILA" as ILA in which the conduction delay exceeded its median (50 ms). During a median follow-up of 42.5 months, major arrhythmic events (MAEs: 1 sudden cardiac death, 3 sustained ventricular tachycardias, and 4 appropriate implantable cardioverter defibrillator discharges) occurred more frequently in patients with delayed ILA (6/12) than in those without (2/28; log-rank: P=0.004). Cox regression analysis identified delayed ILA as the only independent predictor of MAEs (hazard ratio 7.63, 95% confidence interval 1.72-52.6, P=0.007), and other noninvasive parameters were not significant predictors. MCG is useful to identify ARVC patients at high risk of future lethal ventricular arrhythmias.