Increased Beat-to-Beat Variability of T-Wave Heterogeneity Measured From Standard 12-Lead Electrocardiogram Is Associated With Sudden Cardiac Death: A Case–Control Study

Abstract

Introduction The prognostic significance of beat-to-beat variability of spatial heterogeneity of repolarization measured from standard 12-lead ECG is not well-understood. Methods We measured the short-term variability of repolarization parameters, such as T-wave heterogeneity in leads V4–V6 (TWH) and QT interval (QT), from five consecutive beats of previously recorded standard 12-lead ECG in 200 victims of unexpected sudden cardiac death (SCD) confirmed to be due to complicated atherosclerotic coronary artery disease (CAD) in medico-legal autopsy and 200 age- and sex-matched controls with angiographically confirmed CAD. The short-term variability of repolarization heterogeneity was defined as the standard deviation (SD) of the measured repolarization parameters. All ECGs were in sinus rhythm, and no premature ventricular contractions were included in the measured segment. Results TWH-SD and QT-SD were significantly higher in SCD victims than in subjects with CAD (6.9 ± 5.6 μV vs. 3.8 ± 2.6 μV, p = 1.8E-11; 8.3 ± 13.1 ms vs. 3.8 ± 7.1 ms, p = 0.00003, respectively). After adjusting in the multivariate clinical model with factors, such as diabetes, RR interval, and beta blocker medication, TWH-SD and QT-SD retained their significant power in discriminating between the victims of SCD and the patients with CAD ( p = 0.00003, p = 0.006, respectively). TWH-SD outperformed QT-SD in identifying the SCD victims among the study subjects (area under the curve in the receiver operating characteristics curve 0.730 vs. 0.679, respectively). Conclusion Increased short-term variability of repolarization heterogeneity measured from standard 12-lead ECG is associated with SCD.

Spleen contraction elevates hemoglobin concentration at high altitude during rest and exercise

“…It was however recently found that spleen baseline volume was greater in experienced mountaineers going to climb Mt Everest, than in Mt Everest Base Camp trekkers (Schagatay et al 2020 ), suggesting that spleen function is important for successful climbing at high altitude. It was also recently reported that larger spleens and more powerful contractions were present in the Sherpa population of high altitude origin, compared to Nepali lowlanders (Holmström et al 2020 ). A difference between Sherpas currently residing high and low, respectively, was also observed, suggesting that not only genetic factors but also exposure to hypoxia may determine spleen size (Holmström et al 2020 ).…”

“…It was also recently reported that larger spleens and more powerful contractions were present in the Sherpa population of high altitude origin, compared to Nepali lowlanders (Holmström et al 2020 ). A difference between Sherpas currently residing high and low, respectively, was also observed, suggesting that not only genetic factors but also exposure to hypoxia may determine spleen size (Holmström et al 2020 ).…”

Electrophysiological Mechanisms Underlying T-Wave Alternans and Their Role in Arrhythmogenesis

“…Clinically, T-wave alternans (TWA) is the most common form of cardiac electrical alternans. It is associated with the dispersion of repolarization and can be used as a biomarker to predict malignant arrhythmias and sudden cardiac death (SCD; Hekkanen et al, 2020 ). At the cellular level, TWA is measured as every-other-beat variations in action potential morphology (AP alternans) and/or in the cytosolic calcium transient (CaT alternans) at a constant stimulation frequency.…”

Commentary: Increased Beat-to-Beat Variability of T-Wave Heterogeneity Measured From Standard 12-Lead Electrocardiogram Is Associated With Sudden Cardiac Death: A Case-Control Study

“…In the contemporary era of dynamic surface electrocardiography, a formidable challenge is quantifying spatiotemporal repolarization heterogeneity with sufficient fidelity to image the arrhythmogenic myocardial substrate and thereby provide indices for a patient's risk of arrhythmic death (Laguna et al, 2016). Hekkanen et al (2020) performed a large case-control study of 200 victims of sudden cardiac death (SCD) due to autopsy-proven coronary artery disease, who were age-, and sex-matched to controls with angiographically-confirmed coronary artery disease from the ARTEMIS database. A comprehensive analysis of their 12-lead ECGs within a mean of 1.8 months from SCD was performed to evaluate several measures of spatial repolarization heterogeneity, including an assessment of their temporal variability based on the standard deviation (SD) of each measure over 5 consecutive beats.…”

“…In a 5600 subject cohort study with 12-lead ECGs, TWH in the left precordial leads (V4-V6) independently predicted SCD [adjusted Hazard ratio 1.4 (95th confidence interval 1.2-1.8) per increment of one standard deviation] (Kenttä et al, 2016). In contrast, Hekkanen et al (2020) computed TWH from a single beat in order to derive TWH-SD from 5 consecutive beats. This approach necessitates high quality beat-to-beat ECG recordings and there was no assessment of noise or reproducibility by the authors.…”