Dataset Information

Comparison of Electrocardiographic Biomarkers for Differentiating Drug-Induced Single vs. Multiple Cardiac Ion Channel Block.

ABSTRACT: Since introduction of the International Conference on Harmonization proarrhythmia guidelines in 2005, no new marketed drugs have been associated with unacceptable risk of Torsade de Pointes. Although cardiac safety improved, these guidelines had the unintended consequence of eliminating potentially beneficial drugs from pipelines early in development. More recently, it has been shown that a corrected QT (QTc) prolonging drug may be safe if it impacts multiple ion channels vs. only human ether-a-go-go related gene (hERG) and that this effect can be discriminated using QT subintervals. We compared the predictive power of four electrocardiogram (ECG) repolarization metrics to discriminate single vs. multichannel block: (i) traditional 10-second signal averaged triplicates, and (ii) three metrics that used increasing density of automatically measured beat-to-beat (btb) intervals. Predictive power was evaluated using logistic regression and quantified with receiver operating characteristic (ROC) area under the curve (AUC). Compared with the traditional 10-second signal averaged triplicates, the reduction in classification error ranged from 2-6 with increasing density of btb measurements.

SUBMITTER: Brockway M

PROVIDER: S-EPMC6510380 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Comparison of Electrocardiographic Biomarkers for Differentiating Drug-Induced Single vs. Multiple Cardiac Ion Channel Block.

Brockway Marina M Mason Jay W JW Brockway Brian P BP

Clinical and translational science 20190128 3

Since introduction of the International Conference on Harmonization proarrhythmia guidelines in 2005, no new marketed drugs have been associated with unacceptable risk of Torsade de Pointes. Although cardiac safety improved, these guidelines had the unintended consequence of eliminating potentially beneficial drugs from pipelines early in development. More recently, it has been shown that a corrected QT (QTc) prolonging drug may be safe if it impacts multiple ion channels vs. only human ether-a- ...[more]

PMID: 30414356

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Project description:Study hypothesis:We sought to investigate the association between echocardiographic optimisation and ventricular activation time in cardiac resynchronisation therapy (CRT) patients, obtained through the use of electrocardiographic mapping (ECM). We hypothesised that echocardiographic optimisation of the pacing delay between the atrial and ventricular leads-atrioventricular delay (AVD)-and the delay between ventricular leads-interventricular pacing interval (VVD)-would correlate with reductions in ventricular activation time. Background:Optimisation of AVD and VVD may improve CRT patient outcome. Optimal delays are currently set based on echocardiographic indices; however, acute studies have found that reductions in bulk ventricular activation time correlate with improvements in acute haemodynamic performance. Materials and methods:Twenty-one patients with established CRT criteria were recruited. After implantation, patients underwent echo-guided optimisation of the AVD and VVD. During this procedure, the participants also underwent noninvasive ECM. ECM maps were constructed for each AVD and VVD. ECM maps were analysed offline. Total ventricular activation time (TVaT) and a ventricular activation time index (VaT10-90) were calculated to identify the optimal AVD and VVD timings that gave the minimal TVaT and VaT10-90 values. We correlated cardiac output with these electrical timings. Results:Echocardiographic programming optimisation was not associated with the greatest reductions in biventricular activation time (VaT10-90 and TVaT). Instead, bulk activation times were reduced by a further 20% when optimised with ECM. A significant inverse correlation was identified between reductions in bulk ventricular activation time and improvements in LVOT VTI (p < 0.001), suggesting that improved ventricular haemodynamics are a sequelae of more rapid ventricular activation. Conclusions:EAM-guided programming optimisation may achieve superior fusion of activation wave fronts leading to improvements in CRT response.

Dataset Information

Comparison of Electrocardiographic Biomarkers for Differentiating Drug-Induced Single vs. Multiple Cardiac Ion Channel Block.

Publications

Comparison of Electrocardiographic Biomarkers for Differentiating Drug-Induced Single vs. Multiple Cardiac Ion Channel Block.

Similar Datasets

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