Cardiovascular Risk in Cancer Patients Treated with Immune Checkpoint Inhibitors: Challenges and Future Directions.

Cardiovascular disease is the leading cause of non-cancer related mortality and morbidity among people living with or cured from cancer. Immune checkpoint inhibitors (ICIs) are systemic anti-cancer therapies that have revolutionised the treatment of numerous cancers, even achieving durable long-term responses among patients with metastatic disease. However, the pro-inflammatory effects of ICIs have been postulated to increase the risk of atherosclerotic cardiovascular disease (ASCVD) in cancer survivorship. Standard modifiable cardiovascular risk factors can further contribute to ASCVD risk during cancer survivorship but are not routinely screened and are often untreated in patients with cancer. With the expanding use of ICIs leading to improved cancer survivorship, cardiovascular risk identification and prevention will be paramount in the care of patients with cancer. This review highlights the practical challenges associated with ASCVD prevention among the growing number of patients treated with ICIs for cancer, including balancing competing mortality risks from cancer and ASCVD, the lack of ICI-specific cardiovascular risk stratification tools, potential interactions between cardiovascular and oncological therapies, and barriers to implementation of cardiovascular screening and prevention within existing healthcare systems.

Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis.

BACKGROUND: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation. METHODS: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity. RESULTS: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I2 â€‹= â€‹93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates. CONCLUSION: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.

Asymptomatic coronary artery disease in ischaemic stroke survivors: A systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke and coronary artery disease share risk factors and stroke survivors experience a high rate of cardiac events. Recent work suggests a high burden of asymptomatic coronary artery disease (CAD) in ischaemic stroke survivors. Thus, we performed this systematic review and meta-analysis to A) estimate the prevalence of CAD in ischaemic stroke survivors without known CAD and B) evaluate the association between coronary atherosclerosis and future major adverse cardiovascular events (MACE) in stroke survivors. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis according to the PRISMA statement. We included studies investigating acute ischaemic stroke or transient ischaemic attack where participants underwent anatomical assessment of all coronary arteries. For objective B) we included studies that reported an association between coronary atherosclerosis and MACE. Two reviewers used the Newcastle-Ottawa Scale to assess risk of bias. We used random-effects modelling for our analyses. RESULTS: We identified 2983 studies of which 17 were included. These studies had a total of 6862 participants between 2008 and 2022. The pooled prevalence of any coronary atherosclerosis was 66.8% (95% CI 57.2%-75.1%) with substantial heterogeneity (I2 = 95.2%). The pooled prevalence of obstructive (>50%) stenosis was 29.3% with substantial heterogeneity (I2 = 91%). High-risk coronary anatomy (triple vessel disease or left main stenosis) was found in 7.0% (95% CI 4%-12%) with high heterogeneity I2 = 72%. One study examined high-risk plaques and found a prevalence of 5.9%. Five studies reported the association of coronary atherosclerosis with future MACE. The presence of obstructive CAD confers a HR of 8.0 (95% CI 1.7-37.1, p = 0.007) for future MACE. DISCUSSION AND CONCLUSIONS: Asymptomatic CAD is common in ischaemic stroke survivors. The presence and severity of asymptomatic CAD strongly associates with the risk of future MACE. Further evaluation of the benefits of routine coronary assessment in ischaemic stroke is warranted.

Asia-Pacific Investigators and Asian Enrollment in Cardiometabolic Trials: Insights From Publications Between 2011 and 2020.

Background: A lack of geographic and racial diversity in clinical trial populations may arise from a disproportionate focus on the United States and Europe for trial leadership and conduct. Inadequate diversity may compromise the external validity to the Asia-Pacific (APAC) region, where 60% of global cardiometabolic disease exists. Objectives: This study aimed to assess the proportion and trends of Asian race participants and APAC authorship in cardiometabolic trials. Methods: We performed a systematic review of all cardiovascular, diabetes and obesity-related randomized controlled trials (phase ≥2, n = ≥100) published in these major medical journals: the New England Journal of Medicine, the Lancet, and the Journal of the American Medical Association between January 1, 2011, and December 31, 2020. Trial leadership was defined by first authorship, and any listed author was considered a trial collaborator. Temporal trends were evaluated using the Jonckheere-Terpstra proportion test and correlations using Pearson's correlation coefficient. Participant-to-prevalence ratios (PPR) were determined using Global Health Data Exchange registry data. Results: A total of 8.3% (218,613 of 2,619,710) participants identified as being of Asian race and 7.7% of total enrollment occurred in APAC. APAC lead authorship occurred in 52 of 656 (7.9%) trials and collaboration in 10.1% (1312 of 13,000 of authors), which correlated with Asian enrollment (r = 0.63 and r = 0.76, respectively). A marginal increase in the proportion of Asian race (Δ1.40% ± 6.95%/year, P = 0.003) and APAC regional (Δ1.46% ± 8.67%/year, P = 0.003) enrollment was observed; however, severe regional underrepresentation persisted (PPR <0.30). Conclusions: Despite a favorable trend over the past decade, Asian participants and authors from APAC remain significantly underrepresented in seminal cardiometabolic trials; barriers to trial conduct and leadership in this region must be addressed.

Incessant myopericarditis after mRNA vaccination requiring IL-1 receptor antagonist therapy and pericardiectomy: case report.

Background: During the COVID-19 pandemic, there has been global administration of novel mRNA vaccines that are effective in reducing the burden of COVID-19. In tandem with this administration, mRNA vaccine-associated complications have been identified. One such complication is mRNA vaccine-associated pericarditis. Case summary: This is a case of a 40-year old male who developed clinical pericarditis 3 days after his first dose of the Pfizer-BioNtech mRNA COVID-19 vaccination. The diagnosis of mRNA vaccine-induced pericarditis was confirmed on cardiac magnetic imaging and was resistant to numerous lines of medical therapy. These included substantial simple and opioid-based analgaesia, colchicine, prednisolone, interleukin-1 receptor antagonist therapy (anakinra), and a ketamine infusion that were all titrated over the course of eight hospital admissions. Ultimately, surgical pericardiectomy was performed that resulted in a favourable outcome. Discussion: This case depicts an example of incessant mRNA vaccine-associated pericarditis, a known complication of the Pfizer-BioNtech mRNA COVID-19 vaccination. There is limited evidence guiding the therapy of mRNA-induced pericarditis especially when recurrent and resistant to simple analgaesia, colchicine, and steroids. Thus, this case represents a potential framework to help future cases of incessant mRNA vaccine-induced pericarditis.

Inter-software and inter-scan variability in measurement of epicardial adipose tissue: a three-way comparison of a research-specific, a freeware and a coronary application software platform.

OBJECTIVES: Epicardial adipose tissue (EAT) is a proposed marker of cardiovascular risk; however, clinical application may be limited by variability in post-processing software platforms. We assessed inter-vendor agreement of EAT volume (EATv) and attenuation on both contrast-enhanced (CE) and non-contrast CT (NCT) using a standard coronary CT reporting software (Vitrea), an EAT research-specific software (QFAT) and a freeware imaging software (OsiriX). METHODS: Seventy-six consecutive patients undergoing simultaneous CE and NCT had complete volumetric EAT measurement. Between-software, within-software NCT vs. CE, and inter- and intra-observer agreement were evaluated with analysis by ANOVA (with post hoc adjustment), Bland-Altman with 95% levels of agreement (LoA) and intraclass correlation coefficient (ICC). RESULTS: Mean EATv (freeware 53 ± 31 mL vs. research 93 ± 43 mL vs. coronary 157 ± 64 mL) and attenuation (freeware - 72 ± 25 HU vs. research - 75 ± 3 HU vs. coronary - 61 ± 10 HU) were significantly different between all vendors (ANOVA p < 0.001). EATv was consistently higher in NCT vs. CE for all software packages, with most reproducibility found in research software (bias 26 mL, 95% LoA: 2 to 56 mL), compared to freeware (bias 11 mL 95% LoA: - 46 mL to 69 mL) and coronary software (bias 10 mL 95% LoA: - 127 to 147 mL). Research software had more comparable NCT vs. CE attenuation (- 75 vs. - 72 HU) compared to freeware (- 72 vs. - 57 HU) and coronary (- 61 vs. - 39 HU). Excellent inter-observer agreement was seen with research (ICC 0.98) compared to freeware (ICC 0.73) and coronary software (ICC 0.75) with narrow LoA on Bland-Altman analysis. CONCLUSION: There are significant inter-vendor differences in EAT assessment. Our study suggests that research-specific software has better agreement and reproducibility compared to freeware or coronary software platforms. KEY POINTS: • There are significant differences between EAT volume and attenuation values between software platforms, regardless of scan type. • Non-contrast scans routinely have higher mean EAT volume and attenuation; however, this finding is only consistently seen with research-specific software. • Of the three analyzed packages, research-specific software demonstrates the highest reproducibility, agreement, and reliability for both inter-scan and inter-observer agreement.

Socioeconomic determinants of health, traditional risk factors and cardiovascular outcomes in Australia.

Background: Cardiovascular disease burden is decreasing, but these reductions have not been distributed equally amongst socioeconomic groups. Objectives: The aim of this study was to define the relationships between different domains of socioeconomic health, traditional cardiovascular risk factors and cardiovascular events. Methods: This was a cross-sectional study of local government areas (LGAs) in Victoria, Australia. We used data from a population health survey combined with cardiovascular event data derived from hospital and government data. Four socioeconomic domains: educational attainment, financial wellbeing, remoteness, and psychosocial health, were generated from 22 variables. The primary outcome was a composite of non-STEMI, STEMI, heart failure and cardiovascular deaths per 10,000 persons. Linear regression and cluster analysis were used to assess the relationships between risk factors and events. Results: Across 79 LGAs there were 33,654 interviews conducted. All socioeconomic domains were associated with burden of traditional risk factors, including hypertension, smoking, poor diet, diabetes, and obesity. Financial wellbeing, educational attainment and remoteness were all correlated with cardiovascular events on univariate analysis. After multivariate adjustment for age and sex, financial wellbeing, psychosocial wellbeing, and remoteness were associated with cardiovascular events, while educational attainment was not. After including traditional risk factors only financial wellbeing and remoteness remained correlated with cardiovascular events. Conclusions: Financial wellbeing and remoteness independently be associated with cardiovascular events, while educational attainment and psychosocial wellbeing are attenuated by traditional cardiovascular risk factors. Poor socioeconomic health is clustered in certain areas, which have high cardiovascular event rates.

Quantitative plaque characterisation and association with acute coronary syndrome on medium to long term follow up: insights from computed tomography coronary angiography.

Background: Computed tomography coronary angiography (CTCA) is an established imaging modality widely used for diagnosing coronary artery stenosis with expanding potential for comprehensive assessment of coronary artery disease (CAD). Lesion-based analyses of high-risk plaques (HRP) on CTCA may aid further in prognostication presenting with stable chest pain. We conduct qualitative and quantitative assessments to identify HRPs that are associated with acute coronary syndrome (ACS) on a medium to long term follow-up. Methods: Retrospective cohort study of patients who underwent CTCA for suspected CAD. Obstructive stenosis (OS) is defined as ≥50% and the presence of HRP and its constituents: positive-remodelling (PR), low-attenuation-plaque (LAP; <56 HU), very-low-attenuation-plaque (vLAP; <30 HU) and spotty-calcification (SC) were recorded. A cross-sectional quantitative analysis of HRP was performed at the site of minimum-luminal-area (MLA). The primary endpoint was fatal or non-fatal ACS on follow-up. Results: A total of 1,257 patients were included (mean age 61±14 years old and 51% male) with a median follow-up of 7.24 years (interquartile range 5.5 to 7.7 years). The occurrence of ACS was significantly higher in HRP (+) patients compared to HRP (-) patients and patients with no plaques (20.5% vs. 1.6% vs. 0.4%, log-rank test P<0.001). ACS was more frequent in HRP (+)/OS (+) patients (20.7%) compared to HRP (+)/OS (-) patients (8.6%), HRP (-)/OS (+) patients (1.8%) and HRP (-)/OS (-) patients (1.0%). OS, cross-sectional plaque area (PA) and the presence of vLAP identified those HRP lesions that were more likely to cause future ACS. Cross-sectional LAP area (<56 HU) in HRP lesions added incremental prognostic value to OS in predicting ACS (P=0.008). Conclusions: The presence of OS and the LAP area at the site of MLA identify the HRP lesions that have the greatest association with development of future ACS.

Applications of Machine Learning in Cardiac Electrophysiology.

Artificial intelligence through machine learning (ML) methods is becoming prevalent throughout the world, with increasing adoption in healthcare. Improvements in technology have allowed early applications of machine learning to assist physician efficiency and diagnostic accuracy. In electrophysiology, ML has applications for use in every stage of patient care. However, its use is still in infancy. This article will introduce the potential of ML, before discussing the concept of big data and its pitfalls. The authors review some common ML methods including supervised and unsupervised learning, then examine applications in cardiac electrophysiology. This will focus on surface electrocardiography, intracardiac mapping and cardiac implantable electronic devices. Finally, the article concludes with an overview of how ML may impact on electrophysiology in the future.

The Natural history of Epicardial Adipose Tissue Volume and Attenuation: A long-term prospective cohort follow-up study.

Epicardial adipose tissue (EAT) is associated with cardiovascular risk. The longitudinal change in EAT volume (EATv) and density (EATd), and potential modulators of these parameters, has not been described. We prospectively recruited 90 patients with non-obstructive coronary atherosclerosis on baseline computed tomography coronary angiography (CTCA) performed for suspected coronary artery disease to undergo a repeat research CTCA. EATv in millilitres (mL) and EATd in Hounsfield units (HU) were analysed and multivariable regression analysis controlling for traditional cardiovascular risk factors (CVRF) performed to assess for any predictors of change. Secondary analysis was performed based on statin therapy. The median duration between CTCA was 4.3years. Mean EATv increased at follow-up (72 ± 33 mL to 89 ± 43 mL, p < 0.001) and mean EATd decreased (baseline -76 ± 6 HU vs. -86 ± 5 HU, p < 0.001). There were no associations between baseline variables of body mass index, age, sex, hypertension, hyperlipidaemia, diabetes or smoking on change in EATv or EATd. No difference in baseline, follow-up or delta EATv or EATd was seen in patients with (60%) or without baseline statin therapy. In this select group of patients, EATv consistently increased and EATd consistently decreased at long-term follow-up and these changes were independent of CVRF, age and statin use. Together with the knowledge of strong associations between EAT and cardiac disease, these findings may suggest that EAT is an independent parameter rather than a surrogate for cardiovascular risk.

Off- vs. On-Pump Coronary Artery Bypass Grafting Long-Term Survival is Driven by Incompleteness of Revascularisation.

BACKGROUND: Off-pump coronary artery bypass grafting (CABG) negates the requirement for extracorporeal circulation used with the traditional on-pump approach. However, off-pump CABG is technically more challenging and may theoretically lead to less complete revascularisation. Recent data suggests a prognostic benefit for traditional on-pump CABG, but the mechanism for this remains unclear. We hypothesised that the inferior outcomes with off-pump CABG could be driven by the need for repeat revascularisation, with this benefit only becoming clear at long-term follow-up. We therefore evaluated short, medium and long-term outcomes of patients undergoing revascularisation with on vs. off-pump CABG. METHODS: Electronic databases were searched to identify suitable randomised controlled trials enrolling ≥100 patients in each arm. Clinical outcomes were extracted at 30-days, 12-months or >4years. The primary outcome was long-term all-cause death, while secondary outcomes included 30-day, 12-month and >4-year cardiac death, stroke, myocardial infarction or revascularisation. RESULTS: Thirteen (13) studies comprising 13,234 patients were included. Off-pump CABG was associated with an increased risk of all-cause death (Odds Ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.32, p=0.01) and repeat bypass surgery (OR 2.57, 95%CI 1.23-5.39, p=0.01) at long-term follow-up. A significant, increased requirement for revascularisation in off-pump was seen at 12-month follow-up (OR 1.59, 95%CI 1.09-2.33, p=0.02). No differences were noted between groups at 30-days, 12-months and >4years for myocardial infarction or stroke. CONCLUSIONS: Off-pump CABG is associated with significantly higher rates of all-cause mortality rate at long-term follow-up. These outcomes demonstrate a temporal relationship that may be driven by a greater requirement for repeat revascularisation at 1- and 5-year follow-up. STUDY REGISTRATION: CRD42018102019 (PROSPERO).

Characteristics of myocardial tissue staining and lesion creation with an infusion-needle ablation catheter for the treatment of ventricular tachycardia in humans.

BACKGROUND: Intramural substrate causing ventricular tachycardia can be targeted by radiofrequency (RF) infusion-needle catheter ablation. OBJECTIVE: The purpose of the study was to assess fluid distribution within the myocardium after needle-ablation catheter infusion and its evidence to RF lesion creation. METHODS: In 25 patients (21 (84%) male; 67 ± 9 years; 8 (32%) with ischemic cardiomyopathy) intramural ablation of ventricular tachycardia was performed with a needle catheter. Fluoroscopic images of myocardial staining patterns produced by pre-RF saline/contrast infusion were analyzed. Lesion creation was defined as tissue inexcitability to high-output needle pacing. RESULTS: Data from 155 sites were eligible for analysis. Tissue staining was evident in 111 (72%) and absent in 44 (28%). The stain shapes were variable, with average dimensions of 20 ± 10 × 8 ± 4 mm with an area of 68 ± 58 mm2. Round/oval-shaped stains were most common (62 [56%]), while multisegmented (36 [32%]) and long flat (13 [12%]) configurations were less frequent. Evidence of staining was associated with evidence of lesion creation (92/111 (83%) vs 17/44 (39%); P ≤ .0001). Contrast staining around the needle was present in 50%, usually had blurred margins, and was associated with lesion creation. When staining extended well beyond the needle, the margins were often sharp, suggesting dissection through tissue planes, and lesion creation tended to be less effective. CONCLUSION: With infusion-needle ablation, preablation injection of contrast can help confirm an intramural position and predict lesion creation. Tissue diffusion patterns vary markedly, and studies to assess its relation to tissue architecture and ablation lesion geometry warrants further investigation. The findings also have implications for the injection of therapeutic agents into the regions of scar.

Catheter ablation of polymorphic ventricular tachycardia/fibrillation in patients with and without structural heart disease.

BACKGROUND: Catheter ablation for polymorphic ventricular tachycardia and ventricular fibrillation (PMVT/VF) may target triggering premature ventricular contractions (PVCs). Targeting ventricular scar has also been suggested, but data are limited. OBJECTIVE: The purpose of this study was to characterize the electrophysiological findings and ablation outcomes for patients with PMVT/VF and structural heart disease (SHD) compared to those with idiopathic VF. METHODS: Data from 32 consecutive patients (13 idiopathic VF, 19 SHD) with recurrent PMVT/VF who underwent catheter ablation were reviewed. RESULTS: A low-voltage area of myocardial scar was present in 15 of 19 patients with SHD. Sustained monomorphic ventricular tachycardia (SMVT) associated with scar was inducible and targeted in 8, 3 of whom had previous SMVT episodes separate from PMVT/VF episodes and 5 had no history of SMVT. Triggering PVCs were identified in 11 patients and arose from an area of endocardial scar in 6. Only scar ablation was performed in 8 patients who did not have triggering PVCs. All idiopathic VF patients underwent PVC ablation only. During a median of 540 days, 74% of SHD patients and 77% of idiopathic VF patients were free of recurrence, including 75% of those with only PVC ablation, 86% of those with scar plus PVC ablation, and 63% of those with only scar ablation. CONCLUSION: Patients with recurrent PMVT/VF and SHD often have a low-voltage scar associated with PVCs or inducible SMVT, which may also be the substrate for PMVT/VF. When present, substrate ablation targeting scar is a reasonable option for treatment of PMVT/VF even if PVCs are absent.

Endpoints for Successful Slow Pathway Catheter Ablation in Typical and Atypical Atrioventricular Nodal Re-Entrant Tachycardia: A Contemporary, Multicenter Study.

OBJECTIVES: This study sought to investigate markers of success following slow pathway ablation for atrioventricular nodal re-entrant tachycardia (AVNRT). BACKGROUND: Published data are conflicting. METHODS: The authors studied 1,007 patients with typical AVNRT and 77 patients with atypical AVNRT. RESULTS: Following ablation, tachycardia was rendered not inducible in all patients. One case of transient (0.09%) and 1 of permanent (0.09%) atrioventricular (AV) block were encountered. At a 3-month follow-up, arrhythmia recurrence was noted in 21 (2.10%) patients in the typical and 3 (3.90%) patients in the atypical group (odds ratio: 0.525; 95% confidence interval [CI]: 0.153 to 1.802; p = 0.298). To predict absence of recurrence in 3 months, the induction of junctional rhythm (95.70% in typical and 96.10% in atypical groups) had sensitivity of 95.9% (95% CI: 94.6% to 97.0%) and specificity of 4.20% (95% CI: 0.11% to 21.10%), while the absence of dual AV nodal conduction post-ablation had sensitivity of 65.2% (95% CI: 62.2% to 68.1%) and specificity of 33.30% (95% CI: 15.60% to 55.30%). Neither junctional rhythm nor residual dual AV nodal pathway conduction were predictive of arrhythmia recurrence by univariate analysis. In long-term follow-up data available for 239 patients, arrhythmia-free survival was not associated with the induction of junctional rhythm or the absence of residual dual AV nodal conduction (log-rank test, p = 0.819 and p = 0.226, respectively). CONCLUSIONS: Induction of a junctional rhythm during ablation is a sensitive but not a specific marker of success. Residual dual AV nodal conduction is not predictive of recurrence. Noninducibility of the arrhythmia, usually after ablation-induced junctional rhythm, and despite isoproterenol challenge, is the most credible endpoint for success.

Left Ventricular Entropy Is a Novel Predictor of Arrhythmic Events in Patients With Dilated Cardiomyopathy Receiving Defibrillators for Primary Prevention.

OBJECTIVES: The aim of this study was to assess the utility of left ventricular (LV) entropy, a novel measure of myocardial heterogeneity, for predicting cardiovascular events in patients with dilated cardiomyopathy (DCM). BACKGROUND: Current risk stratification for ventricular arrhythmia in patients with DCM is imprecise. LV entropy is a measure of myocardial heterogeneity derived from cardiac magnetic resonance imaging that assesses the probability distribution of pixel signal intensities in the LV myocardium. METHODS: A registry-based cohort of primary prevention implantable cardioverter-defibrillator patients with DCM had their LV entropy, late gadolinium enhancement (LGE) presence, and LGE mass measured on cardiac magnetic resonance imaging. Patients were followed from implantable cardioverter-defibrillator placement for arrhythmic events (appropriate implantable cardioverter-defibrillator therapy, ventricular arrhythmia, or sudden cardiac death), end-stage heart failure events (cardiac death, transplantation, or ventricular assist device placement), and all-cause mortality. RESULTS: One hundred thirty patients (mean age 55 years, 83% men, LV ejection fraction 29%, mean LV entropy 5.58 ± 0.72, LGE present in 57%) were followed for a median of 3.2 years. Eighteen (14.0%) experienced arrhythmic events, 17 (13.1%) experienced end-stage heart failure events, and 7 (5.4%) died. LV entropy provided substantial improvement of predictive ability when added to a model containing clinical variables and LGE mass (hazard ratio: 3.5; 95% confidence interval: 1.42 to 8.82; p = 0.007; net reclassification index = 0.345, p = 0.04). For end-stage heart failure events, LV entropy did not improve the model containing clinical variables and LGE mass (hazard ratio: 2.03; 95% confidence interval: 0.78 to 5.28; p = 0.14). Automated LV entropy measurement has excellent intraobserver (mean difference 0.04) and interobserver (mean difference 0.03) agreement. CONCLUSIONS: Automated LV entropy measurement is a novel marker for risk stratification toward ventricular arrhythmia in patients with DCM.