Hillebrenner, Matthew G., James C. Eason, and Natalia A. Trayanova. Mechanistic inquiry into decrease in probability of defibrillation success with increase in complexity of preshock reentrant activity. Am J Physiol Heart Circ Physiol 286: H909-H917, 2004. First published November 6, 2003 10.1152/ajpheart.00492.2003Energy requirements for successful antiarrhythmia shocks are arrhythmia specific. However, it remains unclear why the probability of shock success decreases with increasing arrhythmia complexity. The goal of this research was to determine whether a diminished probability of shock success results from an increased number of functional reentrant circuits in the myocardium, and if so, to identify the responsible mechanisms. To achieve this goal, we assessed shock efficacy in a bidomain defibrillation model of a 4-mm-thick slice of canine ventricles. Shocks were applied between a right ventricular cathode and a distant anode to terminate either a single scroll wave (SSW) or multiple scroll waves (MSWs). From the 160 simulations conducted, dose-response curves were constructed for shocks given to SSWs and MSWs. The shock strength that yielded a 50% probability of success (ED 50) for SSWs was found to be 13% less than that for MSWs, which indicates that a larger number of functional reentries results in an increased defibrillation threshold. The results also demonstrate that an isoelectric window exists after both failed and successful shocks; however, shocks of strength near the ED 50 value that were given to SSWs resulted in 16.3% longer isoelectric window durations than the same shocks delivered to MSWs. Mechanistic inquiry into these findings reveals that the two main factors underlying the observed relationships are 1) smaller virtual electrode polarizations in the tissue depth, and 2) differences in preshock tissue state. As a result of these factors, intramural excitable pathways leading to delayed breakthrough on the surface were formed earlier after shocks given to MSWs compared with SSWs and thus resulted in a lower defibrillation threshold for shocks given to SSWs. scroll waves; isoelectric window; postshock activation; bidomain model ENERGY REQUIREMENTS FOR SUCCESSFUL antiarrhythmia shocks are arrhythmia specific. Cardioversion of a monomorphic ventricular tachycardia (VT) typically requires less energy than termination of ventricular fibrillation (VF). The American Heart Association recommends using lower currents and energies for termination of VT (1); these recommendations are supported by clinical studies (16,28). The study by Kerber et al. (16) demonstrated that the degree of organization of ventricular tachyarrhythmia determines the energy and current requirements for successful transthoracic cardioversion and defibrillation. Similar were the conclusions by Winkle et al. (28), which were derived from their internal defibrillation studies. However, the mechanisms by which the organization of the arrhythmia affects the probability of success for a given shock strength remain unclear. The...

These results present new evidence regarding the mechanisms underlying failure of defibrillation shocks.

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, Section 903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA's review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.

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