Major Arrhythmic Events Research Articles

Cardiac magnetic resonance for prophylactic implantable-cardioVerter defibrillator therapy international registry in patients with ischemic cardiomyopathy

Abstract Background Sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) remains a leading cause of death. Current guidelines provide a class I recommendation for implantable cardioverter–defibrillator (ICD) implantation in ICM patients with transthoracic echocardiographic (TTE) left ventricular ejection fraction (LVEF) ≤35%. and NYHA functional class II or III. The current paradigm is suboptimal in identifying patients who are likely to benefit. In fact, only a relatively small proportion of ICD recipients for SCD primary prevention receive appropriate device therapy and instead there is a not negligible percentage of patients who experienced SCD event despite not fulfilling criteria for implantation. Purpose The DERIVATE-ICM registry sought to evaluate the additional prognostic value for the indication of ICD implantation using cardiac magnetic resonance (CMR) as compared to standard of care based on TTE in a large cohort of ICM patients. Methods We enrolled 861 ICM patients (86% male, mean age 65±11 years) with chronic heart failure and TTE-LVEF<50%. Major adverse arrhythmic cardiac events (MAACE), defined as the combination of SCD, aborted SCD event, and sustained ventricular tachycardia. were the primary endpoint. Independent predictors were used to calculate a CMR risk score for each patient. Risk levels were defined as low (quantile 1 [Q1]), medium (Q2 and Q3) and high (Q4). Results During a median follow-up of 1054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR:1.007, 95%CI:1.000-1.011, p=0.05), CMR-LVEF (HR:0.972, 95%CI: 0.945-0.999, p=0.045) and late gadolinium enhancement (LGE) mass (HR:1.010, 95%CI: 1.002–1.018, p=0.015) were independent predictors of MAACE. Based on the multivariate analysis, CMR weighted risk score was developed according to the following equation [0.005 * EDV/BSA (mL/m2) – 0.029 * LVEF (%) + 0.010 * LGE ischemic mass (g)]. A multiparametric CMR weighted predictive derived score effectively identifies subjects at high risk for MAACE as compared to TTE-LVEF cut-off of 35% with a Continuous NRI: 31.7% (95%CI: 8.6%-54.8%, p=0.007) (Figure 1, Figure 2). Conclusions In this large multicenter registry, a multi-parametric CMR predictive model provides additional prognostic stratification for MAACE predictions in a large cohort of ICM patients as compared to standard of care. This model identifies a large number of patients with TTE-LVEF<35% at low risk of SCD event and on the other side it identifies a subset of patients who are at high risk of MAACE despite TTE-LVEF≥35% (i.e. the population currently not fulfilling the guideline-based criteria for ICD implantation). Further randomized trials to test a CMR guided strategy for ICD implantation versus standard of care are now needed.Kaplan-Meier curvesEvent rate redistribution

Arrhythmic risk stratification in patients with left ventricular ring-like scar

Abstract Background Myocardial fibrosis assessment with late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has recently emerged as an independent predictor of major adverse events in patients with non-ischemic cardiomyopathy. Several studies have examined different locations and extension degrees of LGE, and the so called "ring-like pattern" has been related with an increased incidence of ventricular arrhythmias, in patients with dilated cardiomyopathy (DCM), but also in patients with preserved systolic function. Purpose To describe clinical, electrocardiographic, echocardiographic, CMR and genetic features of the left ventricular (LV) ring-like scar phenotype and to evaluate which characteristics may be associated with the risk of sudden cardiac death (SCD). Methods Patients diagnosed with LV ring-like scar were identified at 6 referral Centres. Diagnosis was based on: 1) ring-like LGE LV pattern, defined as at least 3 contiguous segments with subepicardial/midwall LGE in the same slice with or without fatty infiltration; or 2) pathology examination of explanted hearts/autoptic cases suffering from sudden cardiac death (SCD). Moreover, patients must have an additional inclusion criterion: a positive genetic test, or ≥1 patient in the same family with an ascertained cardiomyopathy. Major adverse arrhythmic cardiac events (MAACE), defined as a composite of SCD, aborted SCD, and sustained ventricular tachycardia (SVT), were the primary study endpoint. Results The final cohort comprised 129 patients (male 59.7%, median age at diagnosis 44 years). During a median follow-up of 3.4 years (IQR 1.2 – 64.), MAACE occurred in 31 patients (24%). Nearly 70% of the patients had a likely pathogenic/pathogenic mutation, mostly in desmoplakin (DSP) and filamin-C (FLNC) genes (65% and 19%, respectively). Sex, QRS width, and LGE in LV anterior wall and/or apex, were the only independent predictors of the outcome events (HR: 0.329, 95% CI: 0.119-0.916, P = 0.033; HR: 1.036, 95% CI 1.019-1.053, P < 0.001; HR 4.270, 95% CI 1.337-13.630, P = 0.014, respectively). A significant interaction between sex and LGE in anterior wall/apex was observed, being this regions associated with MAACE only in male patients (p for interaction = 0.033). Although related to the arrhythmic endpoint at the Kaplan-Meier survival curves, neither DCM echocardiographic phenotype, nor LV ejection fraction ≤35% remained statistically associated to MAACE at the multivariate analysis. Age, genetic mutations, right ventricular involvement, proband status, LV-LGE extension (number of segments) were not statistically related to the study endpoint. Conclusions In this selected cohort of patients with LV ring-like scar and either a genetic test or family history, malignant arrhythmic events were predicted by male sex, QRS width and LGE in anterior wall and/or apex.Graphical Abstract

Influence of left ventricular ejection fraction, type of mutation and sex on malignant ventricular arrhythmias in dsp and flnc mutations

Abstract Introduction Pathogenic mutations in FLNC and DSP are a common cause of arrhythmogenic left ventricular cardiomyopathy and "arrhythmic dilated cardiomyopathy". We aimed to study demographic and clinical differences amongst these carriers. Purpose 1. To study the prevalence of malignant ventricular arrhythmias in DSP and FLNC mutation carriers in the studies and reports published in the literature. 2. To analyse the effect of age, left ventricular ejection fraction (LVEF), and sex on ventricular arrhythmias in both groups. Methods A systematic review of the human studies published in Medline and EMBASE until September 2022 was carried out. "Desmoplakin Mutations", "Filamin Mutations", "Arrhythmogenic Cardiomyopathy" and "Dilated Cardiomyopathy" were the keywords included in the search queries. Studies, family reports, and registries reporting on individual data of pathogenic or likely pathogenic mutation carriers were selected for analysis. Results Twenty-four articles published between 2002 and 2020 were selected from a total of 430 entries. 171 DSP carriers (from 16 studies) and 169 FLNC carriers (from 7 studies) were included in the analysis. Mean age was similar in both groups: 39.45±19.23 years in DSP vs 42.02±16.27 in the FLNC group (p:0.201). The proportion of females was higher among DSP carriers than that found among FLNC carriers: 101 (59%) vs 76 (45%), p: 0.012. Non-missense mutations were more frequent in both groups: 98 DSP carriers (57%) and 157 FLNC carriers (97%). LVEF was slightly more depressed amongst FLNC carriers: 47.75±14.94% vs 52.37±14.64%, p:0.014. A total of 81 major arrhythmic events (sudden death, ventricular fibrillation, sustained ventricular tachycardia were reported. The LVEF of the male patients that had suffered a major event was similar in both groups (39.13±18.20% in DSP vs 39.03±12.24% in FLNC, p:0.987). On the contrary, LVEF was significantly lower in female carriers of DSP mutations (32.33±15.65% in DSP vs 47.60±15.88% in FLNC, p:0.050). Male carriers show a worse prognosis than their female counterparts (log-rank 0.005) (Figure). The difference was not significant after adjusting for LVEF and type of mutation (missense vs non-missense). LVEF (HR 0.94 per percentage unit (0.91-0.96), p <0.001) and non-missense mutations (HR 0.21 (0.07-0.66), p:0.008) were inversely associated with adverse outcomes in DSP carriers in a multivariate analysis. LVEF was also associated with a better outcome in FLNC carriers (HR 0.97 (0.95-0.99), p: 0.019. Conclusion Moderate systolic dysfunction is a risk factor for malignant arrhythmias amongst DSP and FLNC mutation carriers. Female FLNC carriers with mild systolic dysfunction are at risk for sustained ventricular arrhythmias. Missense DSP mutations are associated with poor arrhythmic prognosis.Sex differences in survival

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.

Predictors of outcome in a contemporary cardiac sarcoidosis population: Role of brain natriuretic peptide, left ventricular function and myocardial inflammation.

Cardiac sarcoidosis (CS) is a potentially fatal condition that varies in its clinical presentation. Here, we describe baseline characteristics at presentation along with prognosis and predictors of outcome in a sizable and deeply phenotyped contemporary cohort of CS patients. Consecutive CS patients seen at one institution were retrospectively enrolled after undergoing laboratory testing, electrocardiogram, echocardiography, cardiac magnetic resonance (CMR) imaging and 18 F-flourodeoxyglucose positron emission tomography (FDG-PET) at baseline. The composite endpoint consisted of all-cause mortality, aborted sudden cardiac death, major ventricular arrhythmic events, heart failure hospitalization and heart transplantation. A total of 319 CS patients were studied (67% male, 55.4 ± 12 years). During a median follow-up of 2.2 years (range: 1 month-11 years), 8% of patients died, while 33% reached the composite endpoint. The annualized mortality rate was 2.7% and the 5- and 10-year mortality rates were 6.2% and 7.5%, respectively. Multivariate analysis showed serum brain natriuretic peptide (BNP) levels (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.34-4.31, p = 0.003), CMR left ventricular ejection fraction (LVEF) (HR 0.96, 95% CI 0.94-0.98, p < 0.0001) and maximum standardized uptake value of FDG-PET (HR 1.11, 95% CI 1.04-1.19, p = 0.001) to be independent predictors of outcome. These findings remained robust for different patient subgroups. Cardiac sarcoidosis is associated with significant morbidity and mortality, particularly in those with cardiac involvement as the first manifestation. Higher BNP levels, lower LVEF and more active myocardial inflammation were independent predictors of outcomes.

Artificial Intelligence ECG Analysis in Patients with Short QT Syndrome to Predict Life-Threatening Arrhythmic Events

Short QT syndrome (SQTS) is an inherited cardiac ion-channel disease related to an increased risk of sudden cardiac death (SCD) in young and otherwise healthy individuals. SCD is often the first clinical presentation in patients with SQTS. However, arrhythmia risk stratification is presently unsatisfactory in asymptomatic patients. In this context, artificial intelligence-based electrocardiogram (ECG) analysis has never been applied to refine risk stratification in patients with SQTS. The purpose of this study was to analyze ECGs from SQTS patients with the aid of different AI algorithms to evaluate their ability to discriminate between subjects with and without documented life-threatening arrhythmic events. The study group included 104 SQTS patients, 37 of whom had a documented major arrhythmic event at presentation and/or during follow-up. Thirteen ECG features were measured independently by three expert cardiologists; then, the dataset was randomly divided into three subsets (training, validation, and testing). Five shallow neural networks were trained, validated, and tested to predict subject-specific class (non-event/event) using different subsets of ECG features. Additionally, several deep learning and machine learning algorithms, such as Vision Transformer, Swin Transformer, MobileNetV3, EfficientNetV2, ConvNextTiny, Capsule Networks, and logistic regression were trained, validated, and tested directly on the scanned ECG images, without any manual feature extraction. Furthermore, a shallow neural network, a 1-D transformer classifier, and a 1-D CNN were trained, validated, and tested on ECG signals extracted from the aforementioned scanned images. Classification metrics were evaluated by means of sensitivity, specificity, positive and negative predictive values, accuracy, and area under the curve. Results prove that artificial intelligence can help clinicians in better stratifying risk of arrhythmia in patients with SQTS. In particular, shallow neural networks’ processing features showed the best performance in identifying patients that will not suffer from a potentially lethal event. This could pave the way for refined ECG-based risk stratification in this group of patients, potentially helping in saving the lives of young and otherwise healthy individuals.

Twelve-Lead ECG, Holter Monitoring Parameters, and Genetic Testing in Brugada Syndrome: Insights from Analysis of Multigenerational Family with a History of Sudden Cardiac Arrest during Physical Activity.

Brugada syndrome (BrS) is an arrhythmogenic disorder increasing the risk of syncopal episodes and sudden cardiac death. BrS usually runs through families with reduced penetrance and variable expression. We analyzed the multigenerational family of a patient who died after sudden cardiac arrest with post-mortem diagnosis of BrS. We analyzed clinical history, comprehensive arrhythmic risk, genetic findings, and additional tests, including electrocardiogram (ECG), detailed 24-hour Holter ECG results, and standard echocardiography findings, and followed up the patients in the ambulatory clinic. We analyzed a pedigree of 33 members of four generations of the family (19 male and 14 female patients). In this family, we identified 7 patients with BrS (median Modified Shanghai Score and Sieira model: 4.5 (4-6) and 1 (0-4) points, respectively), including both parents of the deceased patient, and 8 relatives with negative sodium channel blocker drug challenge test. Genetic testing revealed a novel mutation in sodium voltage-gated channel alpha subunit 5 (SCN5A) c.941A>G, (p.Tyr314Cys) inherited from the father of the proband. Patients with BrS were characterized by longer P-wave duration (120 (102-155) vs. 92.5 (88-110) ms, p = 0.013) and longer PR intervals (211.3 ±26.3 vs. 161.6 ± 18.9 ms, p = 0.001), along with more frequent positive aVR sign, but did not differ in terms of QRS duration or T-wave characteristics in resting ECGs. BrS patients were characterized by lower mean, minimal, and maximal (for all p ≤ 0.01) heart rates obtained from Holter ECG monitoring, while there was no difference in arrhythmias among investigated patients. Moreover, visual diurnal variability of ST segment changes and fragmented QRS complexes were observed in patients with BrS in Holter ECG monitoring. There were no major arrhythmic events during median follow-up of 68.7 months of alive BrS patients. These results suggest ECG features which may be associated with a diagnosis of BrS and indicate a novel SCN5A variant in BrS patients. Twelve-lead Holter ECG monitoring, with modified precordial leads placement, may be useful in BrS diagnostics and risk stratification in personalized medicine.

Impact of late gadolinium-enhanced cardiac MRI on arrhythmic and mortality outcomes in nonischemic dilated cardiomyopathy: updated systematic review and meta-analysis

Risk stratification based mainly on the impairment of left ventricular ejection fraction has limited performance in patients with nonischemic dilated cardiomyopathy (NIDCM). Evidence is rapidly growing for the impact of myocardial scar identified by late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMR) on cardiovascular events. We aim to assess the prognostic value of LGE on long-term arrhythmic and mortality outcomes in patients with NIDCM. PubMed, Scopus, and Cochrane databases were searched from inception to January 21, 2022. Studies that included disease-specific subpopulations of NIDCM were excluded. Data were independently extracted and combined via random-effects meta-analysis using a generic inverse-variance strategy. Data from 60 studies comprising 15,217 patients were analyzed with a 3-year median follow-up. The presence of LGE was associated with major ventricular arrhythmic events (pooled OR: 3.99; 95% CI 3.08, 5.16), all-cause mortality (pooled OR: 2.14; 95% CI 1.81, 2.52), cardiovascular mortality (pooled OR 2.83; 95% CI 2.23, 3.60), and heart failure hospitalization (pooled OR: 2.53; 95% CI 1.78, 3.59). Real-world evidence suggests that the presence of LGE on CMR was a strong predictor of adverse long-term outcomes in patients with NIDCM. Scar assessment should be incorporated as a primary determinant in the patient selection criteria for primary prophylactic implantable cardioverter-defibrillator placement.

Predicting arrhythmic event score in Brugada syndrome: Worldwide pooled analysis with internal and external validation

Brugada syndrome is an inherited arrhythmic disease associated with major arrhythmic events (MAE). Risk predictive scores were previously developed with various performances. The purpose of this study was to create a novel score-Predicting Arrhythmic evenT (PAT)-with internal and external validation. A systematic review was performed to identify risk factors for MAE. The odds ratios (ORs) of each factor were pooled across studies. The PAT scoring scheme was developed based on pooled ORs. The PAT score was internally validated with published 105 Asian patients (follow-up 8.0 ± 4.1 [SD] years) and externally validated with unpublished 164 multiracial patients (82.3% White, 14.6% Asian, 3.2% Black; mean follow-up 8.0 ± 6.9 years) with Brugada syndrome. Performances were assessed and compared with previous scores using receiver operating characteristic curve (ROC) analysis. Sixty-seven studies published between 2002 and 2022 from 26 countries (7358 patients) were included. Pooled ORs were estimated, indicating that 15 of 23 risk factors were significant. The PAT score was then developed accordingly. The PAT score had significantly better discrimination (ROC 0.9671) than the BRUGADA-RISK score (ROC 0.7210; P = .006), Shanghai Score System (ROC 0.7079; P = .003), and Sieira etal score (ROC 0.8174; P = .026) in an external validation cohort. PAT score ≥ 10 predicted the first MAE with 95.5% sensitivity and 89.1% specificity (ROC 0.9460) and the recurrent MAE (ROC 0.7061) with 15.4% sensitivity and 93.3% specificity. The PAT score was shown to be useful in predicting MAE for primary prevention in patients with Brugada syndrome.

An overview of the electrocardiographic monitoring devices in sports cardiology: Between present and future.

Athletes represent a mainly healthy population, which however could be considered at risk of major arrhythmic events, especially in case of undiagnosed cardiomyopathies. For this reason, the periodical sports medicine examination and the electrocardiography are essential tools in the cardiovascular screening, even though they do not always succeed in identifying rhythm disturbances, particularly when asymptomatic or rarely symptomatic. Prolonged cardiac monitoring often enables clinicians to stratify the arrhythmic risk and reach the diagnosis. The technological progress of the last decades has produced an always-increasing number of heart rhythm monitoring devices, starting from the 24-hourelectrocardiogram Holtermonitoring and ending with the wide world of wearable devices. In the literature, the extreme utility of this equipment in the patients affected by cardiovascular diseases and in the general population is well established. On the contrary, athletes-based randomized trials or large-scale epidemiological studies targeting the frequency of cardiac symptoms and the use of cardiac monitoring are missing, while an ever-growing number of case series and small observational studies are flourishing in recent years. The present review showcases the available electrocardiographic monitoring options, principally in the medical setting, listing their characteristics, their indications, their supporting evidence, and their general pros and cons. The ultimate goal of this review is guiding physicians through the wide variety of heart rhythm monitoring options in the specific subfield of sports cardiology, when an arrhythmia is suspected in an athlete, to tailor the diagnostic process and favor the best diagnostic accuracy.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study in ischemic cardiomyopathy: international DERIVATE-ICM Registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Implantable cardioverter–defibrillator (ICD) therapy is the most effective sudden cardiac death (SCD) event prophylactic-strategy in ischemic cardiomyopathy (ICM) patients with transthoracic echocardiographic (TTE) left ventricular ejection fraction (LVEF) ≤35%. This approach has been recently questioned due to the low rate of ICD interventions in patients who received implantation and the not negligible percentage of patients who experienced SCD event despite not fulfilling criteria for implantation. Purpose The DERIVATE-ICM registry (RCT#NCT03352648) is an international, multicenter and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to standard of care based on TTE in ICM patients. Methods We enrolled 861 ICM patients (mean age 65±11 years, 86% male) with chronic heart failure and TTE-LVEF&amp;lt;50%. Major adverse arrhythmic cardiac events (MAACE), defined as the combination of SCD, aborted SCD event, and sustained ventricular tachycardia were the primary endpoint. Independent predictors were used to calculate a CMR risk score for each patient. Risk levels were defined as low (quantile 1 [Q1]), medium (Q2 and Q3) and high (Q4). Results During a median follow-up of 1054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007, 95%CI:1.000–1.011, p = 0.050), CMR-LVEF (HR: 0.972, 95%CI: 0.945–0.999, p = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010, 95%CI: 1.002–1.018, p = 0.015) were independent predictors of MAACE. Based on the multivariable analysis, CMR weighted risk score was developed according to the following equation [0.005 * EDV/BSA (mL/m²) – 0.029 * LVEF (%) + 0.010 * LGE ischemic mass (g)]. Figure 1 (top) shows the Kaplan-Meier curves according to the guidelines-based TTE-LVEF model and the CMR risk score. Moreover, the table of reclassification of the CMR versus TTE predictive model is reported in Figure 1 (bottom). This multiparametric CMR weighted predictive derived score effectively identifies subjects at high risk for MAACE as compared to TTE-LVEF cut-off of 35% with a NRI of 31.7% (p = 0.007). The distribution of CMR predictive score in patients with TTE-LVEF≤35% (panel A) and with TTE LVEF&amp;gt;35% (panel C) is represented in Figure 2, together with the event rate redistribution according to the CMR risk score (panel B and panel D). Conclusions The DERIVATE-ICM study is the first large multicenter registry testing the additional value of CMR to stratify the risk for MAACE in a large cohort of ICM patients as compared to standard of care. This model identifies a large number of patients with TTE-LVEF&amp;lt;35% at low risk of SCD event and on the other side it identifies a subset of patients who are at high risk of MAACE despite TTE-LVEF≥35%. Further randomized trials to test a CMR guided strategy for ICD implantation versus standard of care are now needed.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international registry: prognostic value of LGE distribution in non-ischemic dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by Italian Ministry of Health, Rome, Italy (RC 2017 R659/17-CCM698). Background/Introduction Tissue characterization obtained by cardiac magnetic resonance (CMR) has emerged as a promising tool for better identification of non ischemic cardiomyopathy patients at high arrhythmic risk and thus worthy of prophylactic ICD therapy. Purpose Current analysis has the scope to assess the prognostic value of fibrosis, as evaluated by late gadolinium enhancement sequences (LGE) specifically regarding its LV wall distribution, and a CMR-derived risk score. The primary endpoint was all-cause mortality. The secondary end-point consisted of major adverse arrhythmic cardiac events (MAACE), defined as combination of SCD, aborted SCD, and sustained ventricular tachycardia Methods DERIVATE Study is an international, multicenter, prospective, observational registry including consecutive patients from 21 sites referred for heart failure (HF) work-up including transthoracic echocardiography (TTE) and CMR without a history of previous major ventricular arrhythmias. Inclusion criteria were: (i) aged 18 or older, (ii) chronic HF, and (iii) LV-EF&amp;lt;50% at initial TTE. All patients underwent TTE and CMR within 3 months. Patients with (i) decompensated within 3 months of enrollment, (ii) recent myocardial infarction (&amp;lt;40 days), (iii) unstable angina, (iv) severe valvular disease, (v) primary or secondary cardiomyopathies other than NICM, (vi) cardiac amyloidosis, and (vii) congenital heart disease were excluded. Results The entire cohort consisted of 1384 subjects [mean age: 56±14 years, male: 948 (68.4%)]. The median follow-up time was 959 days. Mortality and MAACE occurred in 92 (6.6%) and 125 (9%) patients, respectively. SCD, aborted SCD, and sustained VT occurred in 15 (1.1%), 80 (5.8%), and 104 (7.5%), respectively. The sum of events exceeds the overall number of MAACE because several events could occur in the same patients but just the first event was counted. In the multivariate analyses for all-cause mortality, only the number of segments with LGE at the level of the septum was an independent predictor (p = 0.002), while in the analyses for MAACE the only independent predictors were male gender, LVEDVi by CMR, and the number of segments with LGE at the level of septum inferior. Based on the multivariate analysis, the DERIVATE score (including all 1384 patients) ranging from 0 to 8 (Cox regression analysis HR=1.35, 95%CI 1.24–1.46, p&amp;lt; 0.001) was realized. The redistribution of patients according to the CMR composite DERIVATE risk/year MAACE was of 44%, 37% and 32% for the low, intermediate and high risk groups, respectively. Conclusions The arrhythmic risk of patients with NICM is also dependent on the different distribution of fibrosis in the LV. The redistribution of the event rate according to the CMR composite risk score indicates the potential to alter the decision on ICD implantation in a relevant portion of NICM patients. These results warrant further confirmation in prospective randomized controlled trials.

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.

Utility of cardiac magnetic resonance in assessing arrhythmic risk in patients with non ischemic cardiomyopathy undergoing biventricular pacing

Abstract Funding Acknowledgements Type of funding sources: None. Background Non-ischemic cardiomyopathy (NICM) is a common heart muscle disorder, which is responsible for approximately one-third of heart failure and is associated with significant morbidity and mortality. Recent data suggested the lack of mortality reduction from adding a defibrillator to cardiac resynchronization therapy (CRT) in all patients with NICM. Myocardial fibrosis detected by cardiac magnetic resonance late gadolinium enhancement (CMR-LGE) can help risk stratify patients who would benefit from adding a defibrillator to CRT in this patient population. Purpose We aim at assessing the relationship between the presence of myocardial fibrosis detected by CMR-LGE and the rate of major arrhythmic events (MAE) that included sustained VT, appropriate CRT-D intervention, VF, and SCD in patients with NICM undergoing (CRT) and to compare all-cause mortality and heart failure improvement between patients who receiving CRT-P vs those who receiving CRT-D based on the presence of myocardial fibrosis. Methods All consecutive patients with NICM satisfying a guideline directed indication for CRT implantation were included in the study after excluding patients who refused to consent, patients with acute decompensated heart failure and those contraindicated for a CMR. Patients were divided into two groups according to presence of fibrosis in cardiac MRI into (CRT-D/LGE) group and CRT-P/No LGE group and followed along for one year. Results Sixty patients were enrolled. Sixteen patients (26.6%) developed MAE during the study duration. Seven patients had myocardial fibrosis (receiving CRT-D as per protocol), while only nine patients had no myocardial fibrosis (receiving CRT-P as per protocol), (41.2% vs 20.9%, P=0.045). Presence of CMR-LGE, regardless the extent and distribution, predicted MAE with odd ratio 2.6 (CI=1.78-8.9, P=0.04). The presence of ≥7.5 % of myocardial fibrosis by CMR was associated with 54 % sensitivity and 100% specificity for MAE in the study population (Figure 1). However, All-cause mortality was significantly higher in the (CRT-P/No LGE) group vs (CRT-D/LGE) group [15 (34.9%) vs 2 (11.8%), P=0.076]. Comparison between both groups regarding symptoms of heart failure, QoL and ejection fraction is shown in Table 1. Conclusion In patients with NICM candidates for biventricular pacing, the presence of LGE on CMR, irrespective of the extent or segmental pattern, is independently associated with a major arrhythmic event and is associated with worse heart failure outcome. However, the absence of LGE did not rule out MAE and implanting CRT-P based on lack of fibrosis may result in higher all-cause mortality.

Left ventricular shape remodelling predicts major arrhythmic events in stable coronary artery disease

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. Background Arrhythmic risk stratification of patients with stable coronary artery disease (CAD) for defibrillator implantation remains imprecise. Current clinical guidelines center on a basic assessment of adverse cardiac remodelling, an approach with well documented limitations. More advanced analysis of intricate and regional LV remodelling in these patients may shed new insight for enhanced risk prediction of life-threatening arrhythmia in stable CAD. Objective We explored a novel computational 3D LV shape analysis strategy to accurately represent, and quantify, arrhythmogenic LV remodelling patterns in late gadolinium enhancement cardiovascular magnetic resonance images (LGE-CMR) in patients with stable CAD. We assess the utility of our patient-specific 3D LV arrhythmic shape (LVAS) score predicting major arrhythmic event; comparing to the current clinical benchmark of severely reduced LVEF and NYHA functional class. Methods Patients with stable CAD were prospectively recruited into a CMR registry and followed up for a composite endpoint of major arrhythmic events (MAE) consisting of sudden cardiac death (SCD), aborted SCD or haemodynamically unstable VT. Time-to-event data was also recorded. 2D LGE-CMR images were contoured and used as input to an advanced computational shape-analysis approach (Figure 1A). Reconstructed 3D LV shape models were analysed using Principle Component Analysis and Cox-Lasso to characterise the average arrhythmogenic LV shape, which was then used to quantitatively define a patient-specific LV arrhythmic shape (LVAS) score. Results Of 397 patients (mean [SD] LVEF% 45.4 ± 16.0) followed for a median (IQR) of 6 (3) years, 55 (14%) experienced a major arrhythmic event (MAE). The mean (SD) LVEF for patients who experienced MAE was lower than for those that did not (37.1% ± 13.2 vs 46.7% ± 16.0), yet there was no difference in NYHA class. LVAS mean (95% confidence interval [CI]) score was different between event and event-free patients: 2.98 (0.48-6.44) vs 19.83 (10.66-29), P&amp;lt;0.001. On univariate Cox regression analysis both LVAS score (hazard ratio [HR] 2.1, 95% CI 1.6-2.7, P&amp;lt;0.001) and LVEF&amp;lt;35% (HR 2.9, 95% CI 1.6-5.0, P&amp;lt;0.01) were associated with the primary endpoint. NYHA Class &amp;gt;I was not associated with the primary endpoint (HR 1.5, 95% CI 0.8-2.7, P=0.221). In multivariate Cox regression analysis, LVAS remained independently associated with the primary endpoint after adjusting for LVEF&amp;lt;35% and NYHA&amp;gt;Class I: LVAS score HR 2.1, 95% CI 1.5-3.0, P&amp;lt;0.001; LVEF&amp;lt;35% HR 1.0, 95% CI 0.5-2.2, P=0.923; NYHA&amp;gt;Class I HR 1.3, 95% CI 0.7-2.5, P=0.443 (Figure 1 B, C). The addition of the LVAS score increased the C-statistic from 0.6 to 0.75 between models. Conclusion A Left Ventricle Arrhythmic Shape score improved arrhythmic risk stratification compared to guideline-based clinical parameters, highlighting a potentially novel approach to identifying candidates for implantable cardioverter defibrillators in stable CAD.

Ventricular pre-excitation in young patients: long term follow-up and natural history in a contemporary cohort

Abstract Funding Acknowledgements Type of funding sources: None. Background Ventricular preexcitation (VPE) due to atrio-ventricular accessory pathways (AP) has been associated to a higher incidence of sudden cardiac death (1,2). The incidence of major arrhythmic events (MAE) may be higher in children (1,3), but most of the past studies recruited a high proportion of patients with congenital heart disease (CHD), treated with outdated pharmacological therapy (1). Transcatheter ablation (TCA) of the AP is a safe and effective therapy and it is nowadays the standard of care (1,2). However, it may be less effective and more dangerous in smaller and younger children (1,3). It is described that patients may spontaneously lose VPE during childhood (1), but the natural history of VPE is not well understood yet. Purpose To study the natural history of VPE. We focused especially on the likelihood of spontaneous resolution of VPE during growth, the possible associated factors, and the incidence of MAE during a long follow up in a contemporary paediatric cohort. Methods We retrospectively recruited patients diagnosed with VPE at age 0 to 12, referred from 1993 to 2021 to two tertiary care hospitals. Significant CHD and double AP were excluded. The primary outcome was the spontaneous resolution of VPE, defined by the loss of short PR and delta wave seen in at least two consecutive ECG and/or on 24-hour Holter monitoring. The follow up stopped when the patients reached 16 years of age, met the primary outcome or effective TCA was performed. Given the time-to-event dependency of the condition, the survival analysis of VPE considered the left truncation resulted from the recruitment of patients after the first days of life. Results We recruited 153 patients with a median age of diagnosis of 4.9 (0.2 – 8.4). The median follow-up time was 4.9 (1.6 – 8) years. During follow-up, 42 (28%) patients spontaneously loss VPE. The left truncated Kaplan-Meier survival curve of VPE is shown in Picture 1. It estimates that VPE would persist in 53% (40.1-70.2) and 33.8% (23.7-48.4) of patients at the age of 1 and 16, respectively. Symptoms and intermittent preexcitation were the only variables significantly associated with lower (OR 0.2) and higher probability (OR 3.45) of SR of VPE. The vast majority of patients with symptoms was treated with drug therapy before the age of 8, and TCA was safely delayed thereafter. None of the patients experienced a MAE during follow up. Conclusion According to our data, a large proportion of paediatric patients are likely to spontaneously lose VPE within the first year of life, and a spontaneous resolution may occur later during childhood in a non-negligible number of cases. The absence of symptoms and/or intermittent preexcitation are significant predictors of loss of VPE. The results of our study are of the utmost clinical relevance, since they support a wait-and-see strategy, especially in very young children with VPE.

Cardiac Magnetic Resonance for Prophylactic Implantable-Cardioverter Defibrillator Therapy in Ischemic Cardiomyopathy: The DERIVATE–ICM International Registry

BackgroundImplantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. ObjectivesThe DERIVATE (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy)-ICM registry (NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. MethodsA total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. ResultsDuring a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). ConclusionsThe DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.

Surviving critical COVID-19 requiring mechanical ventilation is associated with a high long-term risk of de novo arrhythmic events

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Research Council Swedish Heart- and Lung Foundation Background The long-term risk of de novo arrhythmic events after severe COVID-19 requiring intensive care is largely unknown, especially after adjusting for multiple risk factors such as co-morbidities and socio-economic factors. Objective The primary objective of this study was to investigate the long-term, co-variate adjusted risk of arrhythmic event after discharge from intensive care unit for critical COVID-19. Methods We performed a nationwide case-control study on patients with severe COVID-19 (cases) treated with mechanical ventilation and discharged alive from an intensive care unit. Each case was matched (age, sex, district of residence) with up to 10 population-based control. The study database from the Swedish ICU register was merged with multiple compulsory national registries. The primary outcome was hospitalizations with the following arrhythmias identified: ventricular tachycardia, atrial fibrillation, any other tachy-arrhythmia, or bradycardia/pacemaker implantation. Hazard ratios were adjusted for co-morbidities, socioeconomic status, level of education, region of birth and disposable income. Average follow-up was 12 months. Results We included 3 023 patients with severe COVID-19 that were treated with mechanical ventilation at a Swedish ICU (March 1, 2020 to June 8, 2021) and were discharged alive. Control subjects (n= 28,463 ) were selected based on matching by age, sex and district of residence. The Hazard ratios for the risk of de novo arrhythmic event post ICU discharge for COVID-19 adjusted for age, gender, all comorbidities, level of education, marital status and income were increased between 13.1 – 21.0 in all four types of arrhythmias (Table 1). Conclusions We report increased risks for major arrhythmic events following severe COVID-19 even after adjusting for cardiovascular risk factors and for socio-economic factors. These data suggest that at least patients with inherit risk factors for developing arrhythmias in need of ICU treatment for COVID-19 should be closely followed-up after discharge.

P123 TRANSCATHETER ABLATION OF SUPRAVENTRICULAR ARRHYTHMIAS IN PATIENTS SUFFERING FROM HYPERTROPHIC CARDIOMYOPATHY: A PROPENSITY SCORE–BASED ANALYSIS

Abstract Background To date, the prognostic impact of transcatheter ablation (T–Abl) of supraventricular arrhythmias (SA) in HCM patients has not been satisfactorily elucidated. Objectives To assess the impact of T–Abl on clinical outcomes in a large cohort of HCM patients. Methods In this retrospective multicenter study, 570 consecutive HCM patients with SA were enrolled, 425 receiving medical therapy and 145 undergoing T–Abl. 1:1 propensity score matching (PSM) led to the inclusion of 234 patients (117 intervention group, 117 medical group) in the final analysis for endpoint evaluation. The primary outcome was a composite of all–cause mortality, heart transplantation (HT) and worsening heart failure (HF). Additionally, an inverse probability weighted (IPW) model was elaborated. Results At PSM analysis, after a median follow-up of 57.3 months, the primary endpoint occurred in 31 (26.5%) patients in the intervention group vs 38 (32.5%) in the medical group (p=0.871). Thromboembolic strokes and major arrhythmic events in the intervention vs the medical group were 9.4% vs 9.4% (p=0.367) and 5.1 vs 7.7% (p=0.741), respectively. Fewer patients in the intervention vs medical group experienced SA recurrences (64.1% vs 84.6%, p&amp;lt;0.001) and transition to permanent SA patterns (21.4% vs 37.6%, p=0.007). IPW analysis showed consistent results. Severe complications related to T–Abl were uncommon (0.7%). Conclusions At 5–year follow–up, T–Abl does not improve major clinical outcomes in a large cohort of HCM patients. Nevertheless, T–Abl seems to facilitate the maintenance of sinus rhythm and decelerate the progression to permanent SA. Lastly, T–Abl is usually safe in HCM.

MP-453090-11 HIBERNATING MYOCARDIUM IS ASSOCIATED WITH A LOWER INCIDENCE OF SUSTAINED VENTRICULAR ARRHYTHMIAS IN PATIENTS WITH ISCHEMIC CARDIOMYOPATHY

Prognostic markers for the prediction of major arrhythmic events (MAE) in patients with ischemic cardiomyopathy (ICM) are scarce. Although myocardial scar is associated with ventricular arrhythmias (VA), the role of hibernating myocardium (HM) is unclear. The aim of this study was to identify prognostic markers for MAE using positron emission tomography (PET) in patients with ICM. In this retrospective single-center study, consecutive patients with ICM confirmed by invasive coronary angiography undergoing both 13N-ammonia (NH3) and 18F-fluorodeoxyglucose (FDG) scan for evaluation of myocardial ischemia and HM were assessed for the occurrence of MAE after PET scan of sudden cardiac death (SCD), survived SCD, VA requiring external or ICD shock, antitachycardia pacing (ATP) or sustained VA during follow-up. PET scan was performed in 254 with ICM and they were followed up for a median of 5.4 years (IQR 3.6-9.8). Mean age was 65.6 years (±10.9), mean ejection fraction was 36.2% (±12.1), 69 patients (27%) had an ICD at baseline, 39 (56.5%) for primary prevention. PET scan revealed myocardial ischemia, scar (=NH3-PET resting perfusion defect) and HM in 94 (37%), 229 (90.2%) and 121 (47.6%) patients, respectively. Mean left ventricular (LV) scar size was 23.5% (±13.5) and mean HM size 8.1% (±7.6). MAE after PET scan occurred in 34 patients (13.4%); 18 patients (7%) suffered SCD, 19 patients had sustained VA, 4 (1.6%) an external, 4 (1.6%) an ICD shock and 12 (4.7%) received ATP. Median time to MAE was 2.5 years (IQR 1-3.9). Scar >10% detected by NH3-PET scan was associated with a higher incidence of MAE (HR 1.24, CI 1.21-9.82, p=0.02) compared to ≤10%. HM >10% detected by FDG-PET scan in patients with scars >10% had lower incidence of MAE (HR 0.89, CI 0.18-0.93, p=0.033) compared to HM ≤10% or scar ≤10%, even after adjusting for LVEF ≤35%. This association remained significant when patients (n=49) revascularized within 90 days of PET scan were censored at the time of revascularization. There was no significant association between MAE and myocardial ischemia (HR 0.84, CI 0.42-1.7, p=0.63), independent of any revascularization. Patients with large and non-viable myocardial scars are at increased risk for MAE. Large (>10% of LV), but viable scars carry similar risk of MAE as smaller (≤10% of LV) scars. The combination of cardiac NH3 and FDG PET scans may serve as a prognostic tool for the prediction of clinically important endpoints such as SCD and sustained VA.