Endocrinopathies mimicking gene negative long QT syndrome

Ventricular repolarisation can be influenced by hormonal milieu which may mimic long QT syndrome. We describe a series of patients referred for genetic testing for diagnosed long QT syndrome where a detailed clinical workup demonstrated endocrinopathies as the cause of presumed “gene negative” long QT syndrome and QT prolongation.

His resynchronization therapy produces more physiological ventricular repolarisation compared with biventricular pacing

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation BACKGROUND Biventricular pacing (BVP) is known to shorten activation time in patients with heart failure and left bundle branch block (LBBB) but its effects on repolarisation are not well studied. His bundle pacing (HBP) can correct LBBB to deliver cardiac resynchronization therapy (HBP-CRT), producing more physiological ventricular activation time and pattern than BVP. It is not known whether this translates to more physiological repolarisation, and if so whether the effect is mediated through its effects on activation. PURPOSE We measured the effects of HBP-CRT and BVP on left ventricular repolarisation using non-invasive epicardial mapping (ECGI). METHODS Patients were recruited in two groups. 1) Patients scheduled for clinically indicated BVP procedures for heart failure with LBBB, 2) Individuals with narrow QRS, normal ventricular function and intact conduction systems. Using non-invasive electrocardiographic imaging, we identified patients with LBBB in whom HBP shortened ECGI-derived left ventricular (LV) activation time by >10ms. We compared the effects of HBP and BVP on ECGI-derived dispersion of LV repolarisation times and activation-recovery intervals (a surrogate for action potential duration). RESULTS 21 patients in whom HBP shortened LV activation time by >10ms and an equal number of individuals with narrow intrinsic QRS were recruited. LV repolarisation dispersion was reduced by HBP-CRT (-42.0 ms, 95% confidence interval (CI): -52.3 to -31.7 ms, p <0.001) but not by BVP (11.9 ms, 95% CI: -6.24 to 30.1 ms, p = 0.182). The mean within-patient change in LV repolarisation dispersion from BVP to HBP-CRT was -56.5 ms (95% CI: -70.5 to -42.5 ms, p < 0.001). LV repolarisation dispersion with HBP-CRT was not different from individuals with narrow intrinsic QRS (2.75 ms, 95% CI: -16.2 to 21.7 ms, p = 0.981). The magnitude of reduction in LV repolarisation dispersion with HBP-CRT from intrinsic LBBB appeared similar to the magnitude of LV activation time shortening (-54.9 ms, 95% CI: -68.2 to -41.6 ms, p < 0.001). However, LV activation-recovery interval dispersion was also reduced by HBP-CRT (-44.3 ms, 95% CI: -69.2 to -19.3 ms, p < 0.001). Repolarisation mapping demonstrated normalisation of repolarisation pattern by HBP-CRT. CONCLUSIONS HBP-CRT can normalise repolarisation dispersion, producing more physiological repolarisation compared with BVP, which does not resolve the repolarisation abnormality of LBBB. HBP-CRT improves repolarisation through both activation resynchronization and modulation of action-potential duration. If these acute results translate to longer term outcomes, HBP-CRT may reduce the risk of ventricular arrhythmias in heart failure with LBBB to a greater extent than BVP. Abstract Figure. Epicardial Repolarisation Maps

Genetically-Determined Serum Calcium Levels and Markers of Ventricular Repolarisation: A Mendelian Randomization Study in the UK Biobank

Background - Electrocardiographic (ECG) markers of ventricular depolarisation and repolarisation are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian Randomization (MR). Methods - Independent lead variants from a newly performed genome-wide association study (GWAS) for serum calcium in >300,000 European-ancestry participants from UK-Biobank were used as instrumental variables. Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT and QRS intervals using an inverse-weighted method in 76,226 participants not contributing to the serum calcium GWAS. Sensitivity analyses including MR-Egger, weighted-median estimator, and MR-PRESSO were performed to test for the presence of horizontal pleiotropy. Results - 205 independent lead calcium-associated variants were used as instrumental variables for MR. A decrease of 0.1 mmol/L serum calcium was associated with longer QT (3.01ms (95% CI 3.99, -2.03) and JT (2.89ms (-3.87, - 1.91) intervals. A weak association was observed for QRS duration (secondary analyses only). Results were concordant in all sensitivity analyses. Conclusions - These analyses support a causal effect of serum calcium levels on ventricular repolarisation, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may therefore directly influence cardiovascular disease risk.

Does obesity influence ventricular repolarisation in children?

Objective: Ventricular repolarisation changes may lead to sudden cardiac death in obese individuals. We aimed to investigate the relationship between ventricular repolarisation changes, echocardiographic parameters, anthropometric measures, and metabolic syndrome laboratory parameters in obese children. Methods: The study involved 81 obese and 82 normal-weight healthy children with a mean age of 12.3 ± 2.7 years. Anthropometric measurements of participants were evaluated according to nomograms. Obese patients were subdivided into two groups; metabolic syndrome and non-metabolic syndrome obese. Fasting plasma glucose, fasting insulin, and lipid profile were measured. QT/QTc interval, QT/QTc dispersions were measured, and left ventricular systolic and diastolic measurements were performed. Results: Body weight, body mass index, relative body mass index, waist/hip circumference ratio, and systolic and diastolic blood pressures were significantly higher in obese children. QT and QTc dispersions were significantly higher in obese children and also obese children with metabolic syndrome had significantly higher QT and QTc dispersions compared to non-metabolic syndrome obese children (p < 0.001) and normal-weight healthy children (p < 0.001). Waist/hip circumference ratio, body mass index, and relative body mass index were the most important determinant of QT and QTc dispersions. Left ventricular wall thickness (left ventricular posterior wall thickness at end-diastole, left ventricular posterior wall thickness at end-systole, interventricular septal thickness at end-diastole) and left ventricular mass index were significantly higher and ejection fraction was lower in obese children. Left ventricular mass index and interventricular septal thickness at end-diastole were positively correlated with QT and QTc dispersions. Conclusions: Our study demonstrated that QT/ QTc interval prolongation and increase in QT and QTc dispersion on electrocardiogram may be found at an early age in obese children.

Evaluation of electrocardiographic markers of cardiac arrhythmic events and their correlation with cardiac iron overload in patients with β-thalassemia major

Iron overload is associated with an increased risk of atrial and ventricular arrhythmias. Data regarding the relationship between electrocardiographic parameters of atrial depolarisation and ventricular repolarisation with cardiac T2* MRI are scarce. Therefore, we aimed to investigate these electrocardiographic parameters and their relationship with cardiac T2* value in patients with β-thalassemia major. In this prospective study, 52 patients with β-thalassemia major and 52 age- and gender-matched healthy patients were included. Electrocardiographic measurements of QT, T peak to end interval, and P wave intervals were performed by one cardiologist who was blind to patients’ data. All patients underwent MRI for cardiac T2* evaluation. Cardiac T2* scores less than 20 ms were considered as iron overload. P wave dispersion, QTc interval, and the dispersions of QT and QTc were significantly prolonged in β-thalassemia major patients compared to controls. Interestingly, we found prolonged P waves, QT and T peak to end dispersions, T peak to end intervals, and increased T peak to end/QT ratios in patients with T2* greater than 20 ms. No significant correlation was observed between electrocardiographic parameters and cardiac T2* values and plasma ferritin levels. In conclusion, our study demonstrated that atrial depolarisation and ventricular repolarisation parameters are affected in β-thalassemia major patients and that these parameters are not correlated with cardiac iron load.