Heritability of ECG Biomarkers in the Netherlands Twin Registry Measured from Holter ECGs.

INTRODUCTION: The resting ECG is the most commonly used tool to assess cardiac electrophysiology. Previous studies have estimated heritability of ECG parameters based on these snapshots of the cardiac electrical activity. In this study we set out to determine whether analysis of heart rate specific data from Holter ECGs allows more complete assessment of the heritability of ECG parameters. METHODS AND RESULTS: Holter ECGs were recorded from 221 twin pairs and analyzed using a multi-parameter beat binning approach. Heart rate dependent estimates of heritability for QRS duration, QT interval, Tpeak-Tend and Theight were calculated using structural equation modeling. QRS duration is largely determined by environmental factors whereas repolarization is primarily genetically determined. Heritability estimates of both QT interval and Theight were significantly higher when measured from Holter compared to resting ECGs and the heritability estimate of each was heart rate dependent. Analysis of the genetic contribution to correlation between repolarization parameters demonstrated that covariance of individual ECG parameters at different heart rates overlap but at each specific heart rate there was relatively little overlap in the genetic determinants of the different repolarization parameters. CONCLUSIONS: Here we present the first study of heritability of repolarization parameters measured from Holter ECGs. Our data demonstrate that higher heritability can be estimated from the Holter than the resting ECG and reveals rate dependence in the genetic-environmental determinants of the ECG that has not previously been tractable. Future applications include deeper dissection of the ECG of participants with inherited cardiac electrical disease.

Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2.

The heart rhythm disorder long QT syndrome (LQTS) can result in sudden death in the young or remain asymptomatic into adulthood. The features of the surface electrocardiogram (ECG), a measure of the electrical activity of the heart, can be equally variable in LQTS patients, posing well-described diagnostic dilemmas. Here we report a correlation between QT interval prolongation and T-wave notching in LQTS2 patients and use a novel computational framework to investigate how individual ionic currents, as well as cellular and tissue level factors, contribute to notched T waves. Furthermore, we show that variable expressivity of ECG features observed in LQTS2 patients can be explained by as little as 20% variation in the levels of ionic conductances that contribute to repolarization reserve. This has significant implications for interpretation of whole-genome sequencing data and underlies the importance of interpreting the entire molecular signature of disease in any given individual.

Fluoroscopic and electrical assessment of implantable cardioverter defibrillator leads: a prospective observational study.

BACKGROUND: Insulation defects resulting in conductor externalization (CE) have been reported in the Riata family of implantable cardioverter defibrillator (ICD) leads (St. Jude Medical, Sylmar, CA, USA). The aim of this study was to identify, prospectively, the rate of CE and outcomes following this, within a group of patients with a Riata ICD lead. METHODS: Patients with a Riata ICD lead attended for fluoroscopic screening and electrical assessment of the lead at yearly intervals between 2010 and 2012. RESULTS: One hundred and forty patients had no or borderline evidence of CE on initial assessment in 2010. These patients were prospectively followed for 3 years (304.6 patient-years). During this time, 11 patients developed definite CE, equating to an event rate of 3.6 (95% confidence intervals: 1.8-6.5) per 100 patient-years of follow-up. Of those patients developing definite CE, one patient had the ICD lead explanted (for reasons unrelated to CE) and no patients died. CE was not associated with any electrical abnormalities of the ICD lead. CONCLUSIONS: CE was observed at a rate of 3.6 per 100 patient-years of follow-up, in 140 individuals with a Riata ICD lead and no definite evidence of CE at baseline.

An audit of outcomes after same-day discharge post-PCI in acute coronary syndrome and elective patients.

OBJECTIVES: To investigate the outcomes of a cohort of acute and elective percutaneous coronary intervention (PCI) patients who were discharged home 6 hours postprocedure. BACKGROUND: Contemporary PCI is safe with a low rate of acute complications. It is well established as a day procedure in elective cases; however, data are lacking in acute cases. METHODS: We describe a prospective observational audit of routine clinical practice in the 3 PCI centers in Northern Ireland. Patients were selected for same-day discharge after 6 hours of post-PCI observation. Both elective and acute coronary syndrome (ACS) cases were included. Criteria for same-day discharge were based on the technical result of the procedure rather than lesion complexity or clinical presentation. Radial access was preferred but not mandatory. Patients were contacted directly to assess for 30-day major adverse cardiovascular events (MACE). Reported events were corroborated with the general practitioner or hospital notes. RESULTS: A total of 1,059 patients were selected for same-day discharge with 30-day follow-up available for all cases. Of these, 766 (72.3%) were elective and 293 (27.7%) were ACS patients. Radial access was almost universal (98%). A total of 1,224 lesions were stented, of which 432 (40.8%) were high risk (highest risk lesion in each case by AHA/ACC classification). MACE rate at 30 days was 0.85% with a sub-acute stent thrombosis rate of 0.4%. There were no MACE events from discharge to 24 hours. CONCLUSIONS: Selected acute and elective patients with a range of lesion complexity and risk can be discharged safely home early after PCI.

Fluoroscopic and electrical assessment of a series of defibrillation leads: prevalence of externalized conductors.

INTRODUCTION: Insulation defects with externalized conductors have been reported in the St. Jude Riata(®) family of defibrillation leads (St. Jude Medical, Sylmar, CA, USA). The objective of the Northern Ireland Riata(®) lead screening program was to identify insulation defects and externalized conductors by systematic fluoroscopic and electrical assessment in a prospectively defined cohort of patients. We sought to estimate the prevalence, identify risk factors, and determine the natural history of this abnormality. METHODS: All patients with a Riata(®) lead under follow-up at the Royal Victoria Hospital were invited for fluoroscopic imaging and implantable cardioverter-defibrillator lead parameter checks. Fluoroscopic images were read independently by two cardiologists and the presence of externalized conductors was classified as positive, negative, or borderline. RESULTS: One hundred and sixty-five of 212 patients with a Riata lead were evaluated by fluoroscopy and lead parameter measurements. The mean duration after implantation was 3.98+/-1.43 years. After screening 25 (15%) patients were classified as positive, 137 (83%) negative, and three (1.8%) borderline. Time since implantation (P = 0.001), presence of a single coil lead (P = 0.042), and patient age (P = 0.034) were significantly associated with externalized conductors. The observed rate of externalized conductors was 26.9% for 8-French and 4.7% for 7-French leads. No leads that were identified prospectively with externalized conductors had electrical abnormalities. Seven of 25 (28%) patients had a defective lead extracted by the end of this screening period. CONCLUSION: A significant proportion (15%) of patients with a Riata lead had an insulation breach 4 years after implantation. High-resolution fluoroscopic imaging in at least two orthogonal views is required to identify this abnormality.