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Background Observational studies suggest that electrocardiogram (ECG) indices might be influenced by obesity and other anthropometric measures, though it is difficult to infer causal relationships based on observational data due to risk of residual confounding. We utilized mendelian randomization (MR) to explore causal relevance of multiple anthropometric measures on P-wave duration (PWD), PR interval, QRS duration, and corrected QT interval (QTc). Methods and findings Uncorrelated (r.sup.2 < 0.001) genome-wide significant (p < 5 x 10.sup.-8) single nucleotide polymorphisms (SNPs) were extracted from genome-wide association studies (GWAS) on body mass index (BMI, n = 806,834), waist:hip ratio adjusted for BMI (aWHR, n = 697,734), height (n = 709,594), weight (n = 360,116), fat mass (n = 354,224), and fat-free mass (n = 354,808). Genetic association estimates for the outcomes were extracted from GWAS on PR interval and QRS duration (n = 180,574), PWD (n = 44,456), and QTc (n = 84,630). Data source GWAS studies were performed between 2018 and 2022 in predominantly European ancestry individuals. Inverse-variance weighted MR was used for primary analysis; weighted median MR and MR-Egger were used as sensitivity analyses. Higher genetically predicted BMI was associated with longer PWD ([beta] 5.58; 95%CI [3.66,7.50]; p = < 0.001), as was higher fat mass ([beta] 6.62; 95%CI [4.63,8.62]; p < 0.001), fat-free mass ([beta] 9.16; 95%CI [6.85,11.47]; p < 0.001) height ([beta] 4.23; 95%CI [3.16, 5.31]; p < 0.001), and weight ([beta] 8.08; 95%CI [6.19,9.96]; p < 0.001). Finally, genetically predicted BMI was associated with longer QTc ([beta] 3.53; 95%CI [2.63,4.43]; p < 0.001), driven by both fat mass ([beta] 3.65; 95%CI [2.73,4.57]; p < 0.001) and fat-free mass ([beta] 2.08; 95%CI [0.85,3.31]; p = 0.001). Additionally, genetically predicted height ([beta] 0.98; 95%CI [0.46,1.50]; p < 0.001), weight ([beta] 3.45; 95%CI [2.54,4.36]; p < 0.001), and aWHR ([beta] 1.92; 95%CI [0.87,2.97]; p = < 0.001) were all associated with longer QTc. The key limitation is that due to insufficient power, we were not able to explore whether a single anthropometric measure is the primary driver of the associations observed. Conclusions The results of this study support a causal role of BMI on multiple ECG indices that have previously been associated with atrial and ventricular arrhythmic risk. Importantly, the results identify a role of both fat mass, fat-free mass, and height in this association., Author(s): Maddalena Ardissino 1,2, Kiran Haresh Kumar Patel 1, Bilal Rayes 1, Rohin K. Reddy 1, Greg J. Mellor 2, Fu Siong Ng 1,* Introduction Obesity is a growing global [...]

Aims Although electrical activity of the normal human heart is well characterized by the electrocardiogram, detailed insights into within-subject and between-subject variations of ventricular activation and recovery by noninvasive electroanatomic mapping are lacking. We characterized human epicardial activation and recovery within and between normal subjects using non-invasive electrocardiographic imaging (ECGI) as a basis to better understand pathology. Methods and results Epicardial activation and recovery were assessed by ECGI in 22 normal subjects, 4 subjects with bundle branch block (BBB) and 4 with long-QT syndrome (LQTS). We compared characteristics between the ventricles [left ventricle (LV) and right ventricle (RV)], sexes, and age groups (<50/≥50years). Pearson's correlation coefficient (CC) was used for within-subject and between-subject comparisons. Age of normal subjects averaged 49 ± 14 years, 6/22 were male, and no structural/electrical heart disease was present. The average activation time was longer in LV than in RV, but not different by sex or age. Electrical recovery was similar for the ventricles, but started earlier and was on average shorter in males. Median CCs of between-subject comparisons of the ECG signals, activation, and recovery patterns were 0.61, 0.32, and 0.19, respectively. Within-subject beat-to-beat comparisons yielded higher CCs (0.98, 0.89, and 0.82, respectively). Activation and/or recovery patterns of patients with BBB or LQTS contrasted significantly with those found in the normal population. Conclusion Activation and recovery patterns vary profoundly between normal subjects, but are stable individually beat to beat, with a male preponderance to shorter recovery. Individual characterization by ECGI at baseline serves as reference to better understand the emergence, progression, and treatment of electrical heart disease. [ABSTRACT FROM AUTHOR]

Aims: Although electrical activity of the normal human heart is well characterized by the electrocardiogram, detailed insights into within-subject and between-subject variations of ventricular activation and recovery by noninvasive electroanatomic mapping are lacking. We characterized human epicardial activation and recovery within and between normal subjects using non-invasive electrocardiographic imaging (ECGI) as a basis to better understand pathology., Methods and Results: Epicardial activation and recovery were assessed by ECGI in 22 normal subjects, 4 subjects with bundle branch block (BBB) and 4 with long-QT syndrome (LQTS). We compared characteristics between the ventricles [left ventricle (LV) and right ventricle (RV)], sexes, and age groups (<50/≥50years). Pearson's correlation coefficient (CC) was used for within-subject and between-subject comparisons. Age of normal subjects averaged 49 ± 14 years, 6/22 were male, and no structural/electrical heart disease was present. The average activation time was longer in LV than in RV, but not different by sex or age. Electrical recovery was similar for the ventricles, but started earlier and was on average shorter in males. Median CCs of between-subject comparisons of the ECG signals, activation, and recovery patterns were 0.61, 0.32, and 0.19, respectively. Within-subject beat-to-beat comparisons yielded higher CCs (0.98, 0.89, and 0.82, respectively). Activation and/or recovery patterns of patients with BBB or LQTS contrasted significantly with those found in the normal population., Conclusion: Activation and recovery patterns vary profoundly between normal subjects, but are stable individually beat to beat, with a male preponderance to shorter recovery. Individual characterization by ECGI at baseline serves as reference to better understand the emergence, progression, and treatment of electrical heart disease., Competing Interests: Conflict of interest: M.J.M.C. is part-time employed by Philips Research. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Obesity is associated with higher risks of cardiac arrhythmias. Although this may be partly explained by concurrent cardiometabolic ill-health, growing evidence suggests that increasing adiposity independently confers risk for arrhythmias. Among fat depots, epicardial adipose tissue (EAT) exhibits a proinflammatory secretome and, given the lack of fascial separation, has been implicated as a transducer of inflammation to the underlying myocardium. The present review explores the mechanisms underpinning adverse electrophysiological remodeling as a consequence of EAT accumulation and the consequent inflammation. We first describe the physiological and pathophysiological function of EAT and its unique secretome and subsequently discuss the evidence for ionic channel and connexin expression modulation as well as fibrotic remodeling induced by cytokines and free fatty acids that are secreted by EAT. Finally, we highlight how weight reduction and regression of EAT volume may cause reverse remodeling to ameliorate arrhythmic risk.

Chronic inflammatory disorders, including rheumatoid arthritis (RA), are associated with a twofold increase in the incidence of sudden cardiac death (SCD) compared with the healthy population. Although this is partly explained by an increased prevalence of coronary artery disease, growing evidence suggests that ischemia alone cannot completely account for the increased risk. The present review explores the mechanisms of cardiac electrophysiological remodeling in response to chronic inflammation in RA. In particular, it focuses on the roles of nonischemic structural remodeling, altered cardiac ionic currents, and autonomic nervous system dysfunction in ventricular arrhythmogenesis and SCD. It also explores whether common genetic elements predispose to both RA and SCD. Finally, it evaluates the potential dual effects of disease-modifying therapy in both diminishing and promoting the risk of ventricular arrhythmias and SCD.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) represents an exciting development in ICD technology. It has relative advantages over traditional transvenous systems, particularly for young patients in whom the lifetime risk of device-related complications may be deemed to be unacceptably high. While data relating to device longevity and long term safety profile is yet to be accrued, several recent studies have demonstrated good clinical efficacy comparable to transvenous ICDs. Indeed, new techniques have also been developed to simplify the S-ICD implantation procedure and attempts have been made to address challenges pertaining to T-wave oversensing to reduce the delivery of inappropriate shocks. The impact of inappropriate shocks and lack of anti-tachycardia pacing (ATP) function are not only contentious matters, but also have important implications for patients in whom the S-ICD would be suitable. It is envisaged that subsequent models of this device will be less cumbersome, with the possibility that an entirely leadless pacemaker-defibrillator will one day be possible. Although the S-ICD may not completely replace transvenous devices in its current form, evidence suggests that it is a viable alternative particularly in preventing sudden cardiac death in non-pacing dependent patients.