An algorithm for synchronization of in vivo electroporation with ECG

The combined treatment of tumours in which delivery of a chemotherapeutic agent is followed by high voltage electroporation pulses has been termed electrochemotherapy. The electrochemotherapy of tumours located relatively close to the heart muscle can lead to fibrillation of the heart, especially if electroporation pulses are delivered in the vulnerable period of the heart or in coincidence with heart arrhythmias. We built an electroporation pulse delivery algorithm that enables safer use of electrochemotherapy. The algorithm is designed to deliver pulses outside the vulnerable period and to prevent pulses from being generated in the presence of heart arrhythmias. We evaluated the algorithm's performance using records of the Long-Term ST Database, thus simulating real-world conditions. The results of the evaluation, a sensitivity of 91.751%, a positive predictivity of 100.000% and a delivery error rate of 8.268% for electroporation pulse delivery (medians), suggest that the algorithm is accurate and appropriate for application in electrochemotherapy of tumours regardless of tumour location.

[1]  Carl J. Wiggers,et al.  VENTRICULAR FIBRILLATION DUE TO SINGLE, LOCALIZED INDUCTION AND CONDENSER SHOCKS APPLIED DURING THE VULNERABLE PHASE OF VENTRICULAR SYSTOLE , 1940 .

[2]  D. Miklavcic,et al.  Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. , 1998, British Journal of Cancer.

[3]  Gregor Serša,et al.  Electrochemotherapy with Bleomycin in the Treatment of Hypernephroma Metastasis: Case Report and Literature Review , 2000, Tumori.

[4]  D Miklavcic,et al.  The effect of pulse repetition frequency on the uptake into electropermeabilized cells in vitro with possible applications in electrochemotherapy. , 2002, Bioelectrochemistry.

[5]  M. Jaroszeski,et al.  Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin , 1998, Cancer.

[6]  G. A. Hofmann,et al.  Instrumentation and electrodes for in vivo electroporation. , 2000, Methods in molecular medicine.

[7]  A. Ruha,et al.  A real-time microprocessor QRS detector system with a 1-ms timing accuracy for the measurement of ambulatory HRV , 1997, IEEE Transactions on Biomedical Engineering.

[8]  A. Taddei,et al.  Long-term ST database: A reference for the development and evaluation of automated ischaemia detectors and for the study of the dynamics of myocardial ischaemia , 2003, Medical and Biological Engineering and Computing.

[9]  Willis J. Tompkins,et al.  A Real-Time QRS Detection Algorithm , 1985, IEEE Transactions on Biomedical Engineering.

[10]  L. Mir,et al.  Mechanisms of in vivo DNA electrotransfer: respective contributions of cell electropermeabilization and DNA electrophoresis. , 2002, Molecular therapy : the journal of the American Society of Gene Therapy.

[11]  Franc Jager.  Feature Extraction and Shape Representation of Ambulatory Electrocardiogram Using the Karhunen-Loève Transform , 2002 .

[12]  D Miklavcic,et al.  Electrochemotherapy with cisplatin: clinical experience in malignant melanoma patients. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  M. Bureau,et al.  Importance of association between permeabilization and electrophoretic forces for intramuscular DNA electrotransfer. , 2000, Biochimica et biophysica acta.

[14]  J. Patrick Reilly,et al.  Applied Bioelectricity: From Electrical Stimulation to Electropathology , 1998 .

[15]  Willis J. Tompkins,et al.  Quantitative Investigation of QRS Detection Rules Using the MIT/BIH Arrhythmia Database , 1986, IEEE Transactions on Biomedical Engineering.

[16]  H. T. Nagle,et al.  A comparison of the noise sensitivity of nine QRS detection algorithms , 1990, IEEE Transactions on Biomedical Engineering.

[17]  S. Orlowski,et al.  Mechanisms of electrochemotherapy. , 1999, Advanced drug delivery reviews.

[18]  P Caminal,et al.  Automatic detection of wave boundaries in multilead ECG signals: validation with the CSE database. , 1994, Computers and biomedical research, an international journal.

[19]  A. Guyton,et al.  Textbook of Medical Physiology , 1961 .

[20]  Richard Heller,et al.  Electrochemotherapy, electrogenetherapy, and transdermal drug delivery : electrically mediated delivery of molecules to cells , 2000 .

[21]  M. Rols,et al.  In vivo electrically mediated protein and gene transfer in murine melanoma , 1998, Nature Biotechnology.

[22]  D.S. Benitez,et al.  A new QRS detection algorithm based on the Hilbert transform , 2000, Computers in Cardiology 2000. Vol.27 (Cat. 00CH37163).

[23]  L A Geddes,et al.  Strength-duration curves for cardiac pacemaking and ventricular fibrillation. , 1977, Cardiovascular Research Center bulletin.

[24]  G. Ayers,et al.  Ventricular proarrhythmic effects of ventricular cycle length and shock strength in a sheep model of transvenous atrial defibrillation. , 1994, Circulation.