Bueno-Orovio, A;
Hanson, BM;
Gill, JS;
Taggart, P;
Rodriguez, B;
(2012)
In Vivo Human Left-to-Right Ventricular Differences in Rate Adaptation Transiently Increase Pro-Arrhythmic Risk following Rate Acceleration.
PLOS ONE
, 7
(12)
, Article e52234. 10.1371/journal.pone.0052234.
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Abstract
Left-to-right ventricular (LV/RV) differences in repolarization have been implicated in lethal arrhythmias in animal models. Our goal is to quantify LV/RV differences in action potential duration (APD) and APD rate adaptation and their contribution to arrhythmogenic substrates in the in vivo human heart using combined in vivo and in silico studies. Electrograms were acquired from 10 LV and 10 RV endocardial sites in 15 patients with normal ventricles. APD and APD adaptation were measured during an increase in heart rate. Analysis of in vivo electrograms revealed longer APD in LV than RV (207.8±21.5 vs 196.7±20.1 ms; P<0.05), and slower APD adaptation in LV than RV (time constant τs = 47.0±14.3 vs 35.6±6.5 s; P<0.05). Following rate acceleration, LV/RV APD dispersion experienced an increase of up to 91% in 12 patients, showing a strong correlation (r2 = 0.90) with both initial dispersion and LV/RV difference in slow adaptation. Pro-arrhythmic implications of measured LV/RV functional differences were studied using in silico simulations. Results show that LV/RV APD and APD adaptation heterogeneities promote unidirectional block following rate acceleration, albeit being insufficient for establishment of reentry in normal hearts. However, in the presence of an ischemic region at the LV/RV junction, LV/RV heterogeneity in APD and APD rate adaptation promotes reentrant activity and its degeneration into fibrillatory activity. Our results suggest that LV/RV heterogeneities in APD adaptation cause a transient increase in APD dispersion in the human ventricles following rate acceleration, which promotes unidirectional block and wave-break at the LV/RV junction, and may potentiate the arrhythmogenic substrate, particularly in patients with ischemic heart disease.
| Type: | Article |
|---|---|
| Title: | In Vivo Human Left-to-Right Ventricular Differences in Rate Adaptation Transiently Increase Pro-Arrhythmic Risk following Rate Acceleration |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0052234 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0052234 |
| Language: | English |
| Additional information: | © 2012 Bueno-Orovio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This study was financially supported by European Commission preDiCT Grant DG-INFSO-224381; United Kingdom Medical Research Council Career Development award to BR; and Medical Research Council (MRC) grant G0901819 to BH and PT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1369979 |
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