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Molecular ablation of ventricular tachycardia after myocardial infarction

Abstract

Ventricular tachycardia is a common and lethal complication after myocardial infarction. Here we show that focal transfer of a gene encoding a dominant-negative version of the KCNH2 potassium channel (KCNH2-G628S) to the infarct scar border eliminated all ventricular arrhythmias in a porcine model. No proarrhythmia or other negative effects were discernable. Our results demonstrate the potential viability of gene therapy for ablation of ventricular arrhythmias.

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Figure 1: Ventricular tachycardia after myocardial infarction in a porcine model.
Figure 2: KCNH2-G628S gene transfer in the myocardial infection–ventricular tachycardia model.

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Acknowledgements

This work was funded by grants from the US National Institutes of Health. ICD equipment was donated by St. Jude Inc. Basket catheters and electrogram mapping system were donated by Boston Scientific Corp.

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Authors and Affiliations

Authors

Contributions

T.S. designed the study, carried out experiments, performed analyses and assisted in writing the paper; A.D.M. assisted with performing and troubleshooting the experiments; K.K. assisted with design of the model and performing experiments; and J.K.D. conceived and designed the study, performed analyses and took the primary role in writing the paper.

Corresponding author

Correspondence to J Kevin Donahue.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

EP study before and after gene transfer. (PDF 23 kb)

Supplementary Fig. 2

Validation of quantitative RT-PCR. (PDF 491 kb)

Supplementary Fig. 3

Dofetilide infusion in the post-MI VT model. (PDF 23 kb)

Supplementary Table 1

Echocardiography data (PDF 7 kb)

Supplementary Table 2

ECG and EP study data (PDF 10 kb)

Supplementary Methods (PDF 74 kb)

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Sasano, T., McDonald, A., Kikuchi, K. et al. Molecular ablation of ventricular tachycardia after myocardial infarction. Nat Med 12, 1256–1258 (2006). https://doi.org/10.1038/nm1503

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