Database Open Access

ECG Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine

Published: July 26, 2016. Version: 1.0.0


When using this resource, please cite the original publication:

Johannesen L, Vicente J, Mason JW, Sanabria C, Waite-Labott K, Hong M, Guo P, Lin J, Sørensen JS, Galeotti L, Florian J, Ugander M, Stockbridge N, Strauss DG. Differentiating Drug-Induced Multichannel Block on the Electrocardiogram: Randomized Study of Dofetilide, Quinidine, Ranolazine, and Verapamil. Clin Pharmacol Ther. 2014 Jul 23. doi: 10.1038/clpt.2014.155.

Please include the standard citation for PhysioNet: (show more options)
Goldberger, A., Amaral, L., Glass, L., Hausdorff, J., Ivanov, P. C., Mark, R., ... & Stanley, H. E. (2000). PhysioBank, PhysioToolkit, and PhysioNet: Components of a new research resource for complex physiologic signals. Circulation [Online]. 101 (23), pp. e215–e220.

Abstract

The ECGRDVQ database contains multi-channel ECG recordings of 22 healthy subjects partaking in a randomized, double‐blind, 5‐period crossover clinical trial aimed at comparing the effects of four known QT prolonging drugs versus placebo on electrophysiological and other clinical parameters.

Experimental Method

In the morning of each period of the five 24-hour periods, each subject received a single dose of 500 μg dofetilide (Tikosyn, Pfizer, New York, NY), 400 mg quinidine sulfate (Watson Pharma, Corona, CA), 1500 mg ranolazine (Ranexa, Gilead, Foster City, CA), 120 mg verapamil hydrochloride (Heritage Pharmaceuticals, Edison, NJ) or placebo under fasting conditions. There was a 7-day washout period between each 24‐hour treatment period.

During each period, continuous ECGs were recorded at 500 Hz with an amplitude resolution of 2.5 μV. From the continuous recording, triplicate 10‐second ECGs were extracted at 16 predefined time-points: 1 point pre-dose (-0.5 h) and 15 points post-dose (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 14, and 24 h), during which the subjects were resting in a supine position for 10 minutes.

At each of the 16 time-points, 3 optimal 10-second 12-lead ECGs were extracted with stable heart rates and maximum signal quality using Antares software (AMPS-LLC, New York City, NY). The resulting 5232 ECGs were up-sampled from 500 to 1000 Hz.

Files

The raw directory contains the 5232 original extracted 10-second standard 12 lead ECG segments organized in subdirectories named after the subject number or randomization number RANDID in the second column of the SCR-002.Clinical.Data.csv file. The ECGs are stored in standard MIT format, with a signal .dat file and corresponding header .hea file for each segment

The medians directory contains derived representative median beats for 5223 of the 5232 raw ECG segments. Median beats were obtained as follows: the median PQRST waveform (median cardiac beat) for each lead was calculated by sample-by-sample synchronization of the QRS complex, and beats of a nonsinus origin were excluded based on a cross-correlation coefficient and RR interval history [1].

There are also semi-automatic annotations of each median beat based on the vector magnitude lead, containing P onset, QRS onset, QRS offset, T peak, secondary T peak (if present) and T offset. The annotations are stored in standard MIT annotation format, with annotator extension .atr.

The SCR-002.Clinical.Data.csv file contains demographic information about the subjects, and important metadata about each ECG recording including their time-point, dosing period, associated drug, various beat intervals, and morphology measurements as described in Vicente et al. JAHA 2015. The spreadsheet column headings are described in the SCR-002.Clinical.Data.Description.txt file.

References

  1. Improving the assessment of heart toxicity for all new drugs through translational regulatory science

Additional Information

This data set, its source, and the methods used to generate it, are described in:

Johannesen L, Vicente J, Mason JW, Sanabria C, Waite-Labott K, Hong M, Guo P, Lin J, Sørensen JS, Galeotti L, Florian J, Ugander M, Stockbridge N, Strauss DG. Differentiating Drug-Induced Multichannel Block on the Electrocardiogram: Randomized Study of Dofetilide, Quinidine, Ranolazine, and Verapamil. Clin Pharmacol Ther. 2014 Jul 23. doi: 10.1038/clpt.2014.155.

The data set is also used in:

Vicente J, Johannesen L, Mason JW, Crumb WJ, Pueyo E, Stockbridge N, Strauss DG. Comprehensive T wave morphology assessment in a randomized clinical study of dofetilide, quinidine, ranolazine, and verapamil.doi: 10.1161/JAHA.114.001615.

ClinicalTrials.gov identifier: NCT01873950


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Anyone can access the files, as long as they conform to the terms of the specified license.

License (for files):
Open Data Commons Attribution License v1.0

Corresponding Author
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Files

Total uncompressed size: 1.4 GB.

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ffab8700-d707-45b8-95f2-f4dee6c537c5.hea (download) 1.3 KB 2016-07-13