TY - JOUR
T1 - Torsade de pointes arrhythmias arise at the site of maximal heterogeneity of repolarization in the chronic complete atrioventricular block dog
AU - Dunnink, Albert
AU - Stams, Thom R G
AU - Bossu, Alexandre
AU - Meijborg, Veronique M F
AU - Beekman, Jet D.M.
AU - Wijers, Sofieke C.
AU - De Bakker, Jacques M.T.
AU - Vos, Marc A.
N1 - Publisher Copyright:
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016.
PY - 2017
Y1 - 2017
N2 - Aims: The chronic complete atrioventricular block (CAVB) dog is highly sensitive for drug-induced torsade de pointes (TdP) arrhythmias. Focal mechanisms have been suggested as trigger for TdP onset; however, its exact mechanism remains unclear. In this study, detailed mapping of the ventricles was performed to assess intraventricular heterogeneity of repolarization in relation to the initiation of TdP. Methods and results: In 8 CAVB animals, 56 needles, each containing 4 electrodes, were inserted in the ventricles. During right ventricular apex pacing (cycle length: 1000 – 1500 ms), local unipolar electrograms were recorded before and after administration of dofetilide to determine activation and repolarization times (RTs). Maximal RT differences were calculated in the left ventricle (LV) within adjacent electrodes in different orientations (transmural, vertical, and horizontal) and within a square of four needles (cubic dispersion). Dofetilide induced TdP in five out of eight animals. Right ventricle – LV was similar between inducible and non-inducible dogs at baseline (327 + 30 vs. 345 + 17 ms) and after dofetilide administration (525 + 95 vs. 508 + 15 ms). All measurements of intraventricular dispersion were not different at baseline, but this changed for horizontal (206 + 20 vs. 142 + 34 ms) and cubic dispersion (272 + 29 vs. 176 + 48 ms) after dofetilide: significantly higher values in inducible animals. Single ectopic beats and the first TdP beat arose consistently from a subendocardially located electrode terminal with the shortest RT in the region with largest RT differences. Conclusion: Chronic complete atrioventricular block dogs susceptible for TdP demonstrate higher RT differences. Torsade de pointes arises from a region with maximal heterogeneity of repolarization suggesting that a minimal gradient is required in order to initiate TdP.
AB - Aims: The chronic complete atrioventricular block (CAVB) dog is highly sensitive for drug-induced torsade de pointes (TdP) arrhythmias. Focal mechanisms have been suggested as trigger for TdP onset; however, its exact mechanism remains unclear. In this study, detailed mapping of the ventricles was performed to assess intraventricular heterogeneity of repolarization in relation to the initiation of TdP. Methods and results: In 8 CAVB animals, 56 needles, each containing 4 electrodes, were inserted in the ventricles. During right ventricular apex pacing (cycle length: 1000 – 1500 ms), local unipolar electrograms were recorded before and after administration of dofetilide to determine activation and repolarization times (RTs). Maximal RT differences were calculated in the left ventricle (LV) within adjacent electrodes in different orientations (transmural, vertical, and horizontal) and within a square of four needles (cubic dispersion). Dofetilide induced TdP in five out of eight animals. Right ventricle – LV was similar between inducible and non-inducible dogs at baseline (327 + 30 vs. 345 + 17 ms) and after dofetilide administration (525 + 95 vs. 508 + 15 ms). All measurements of intraventricular dispersion were not different at baseline, but this changed for horizontal (206 + 20 vs. 142 + 34 ms) and cubic dispersion (272 + 29 vs. 176 + 48 ms) after dofetilide: significantly higher values in inducible animals. Single ectopic beats and the first TdP beat arose consistently from a subendocardially located electrode terminal with the shortest RT in the region with largest RT differences. Conclusion: Chronic complete atrioventricular block dogs susceptible for TdP demonstrate higher RT differences. Torsade de pointes arises from a region with maximal heterogeneity of repolarization suggesting that a minimal gradient is required in order to initiate TdP.
KW - Torsade de pointes
KW - Ventricular remodelling
KW - Mechanism
KW - Dispersion of repolarization
KW - Triggered activity
UR - http://www.scopus.com/inward/record.url?scp=85020863629&partnerID=8YFLogxK
U2 - 10.1093/europace/euw087
DO - 10.1093/europace/euw087
M3 - Article
C2 - 28525920
SN - 1099-5129
VL - 19
SP - 858
EP - 865
JO - Europace
JF - Europace
IS - 5
M1 - 19(5)
ER -