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Physical justification of an increase in the efficacy of radiofrequency systems for myocardial ablation A.V. Evtushenko,1,3 V.V. Evtushenko,1,3 A.N. Bykov,1 V.S. Sergeev,1 V.I. Syryamkin,1 Yu.V. Kistenev,1 Y. Anfinogenova2,3 1 2 3 National Research Tomsk State University, Tomsk, Russian Federation National Research Tomsk Polytechnic University, Tomsk, Russian Federation Federal State Budgetary Scientific Institution “Research Institute for Cardiology” E-mail: [email protected] Key words: conductivity, impedance, temperature, radiofrequency energy, myocardium Introduction Increasing the efficacy of the radiofrequency (RF) system impact on the myocardium remains one of the most important problems of current cardiovascular surgery. Alternating current in a diapason from 100 to 1000 kHz is damaging for the cardiomyocytes though the cell structure and the continuity of the cardiac cavities remain undisturbed [1]. Radiofrequency energy-induced damage of the cardiomyocytes along particular lines blocks conduction of the pathological impulses and prevents life-threatening heart rhythm abnormalities. Essential condition for achieving such blockage is a damage of the wall of a cardiac cavity throughout from the epicardium to the endocardium [1, 3-5]. Various modifications of RF systems are used to achieve this. They are based on the same principle, but they employ different operation schemes or different algorithms. For example, a unipolar impact on the myocardium is achieved when an active electrode is placed directly at a site of RF application whereas a passive electrode is placed under a patient’s back. Bipolar RF application occurs when both electrodes are placed in the area of the impact: one is placed on the epicardium; the other one is located on the endocardium [2]. Nevertheless, the question on which characteristics of the external environment provide maximum effect remains open. Materials and Methods. To answer this question, we studied impedance of the myocardium at different temperatures by applying RF energy to cadaveric hearts under normothermic (36.6 °C) and hypothermic conditions. The experiment was made in conditions of perfusion with Ringer solution at a predetermined temperature. The studies were performed at the electrophysiology bench with changing tissue temperature and impedance. The experimental series of observations were divided into two groups. The first group of observations was performed in the following conditions: the hearts were placed on the electrophysiology bench heated to 36.6 °C; impedance between the epicardium and endocardium was measured; then, RF energy was applied to the cardiac wall for 10 s according to a unipolar method where the passive and active electrodes were placed under the heart and on the opposite surface of the epicardium, respectivley; after that, the measurements of impedance and temperature on a surface of the epicardium were repeated at a point of RF energy application, in the depth of the exposure area (at mid-distance between epicardium and endocardium), and on a surface of the endocardium. In group 2, the hearts were cooled to 20 °C; impedance between the epicardium and endocardium was measured; and RF energy was applied to intact area again according to a unipolar scheme for 10 s with following measurements of temperature and impedance according to the above-mentioned scheme (Figure 1). After that, the myocardium was cross-sectioned through the centers of the points of RF energy application; visible depth of RFinduced damage was measured macroscopically. Overall, 20 experimental series were studied. No visible pathology and scars were present in the walls of the hearts. Mean thickness of the left ventricular wall was 9.8 ± 1.2 mm. Figure 1. The scheme of the experiment. 1: temperature and impedance probes; 2: myocardium; 3: active unipolar electrode; 4: passive electrode; 5: temperature probe between epicardium and endocardium. Statistical processing of data was performed by using software package Statistica 10 for Windows (StatSoft). The Shapiro–Wilk test was used to test normality of distribution of the variables. Data are presented as mean and standard deviation (M ± StD). Student’s t-test was used to evaluate intergroup differences. Paired Student’s t-test was used to evaluate significance of intragroup differences (changes in parameters after RF energy application within one group). Values were considered statistically significant when P was < 0.05. Results Mean values of the myocardial impedance at temperature of 36.6 °C were 3.57 ± 2.12 МΩ and 4.84 ± 2.47 МΩ before and after RF application, respectively. Mean temperatures of the epicardium were 98.9 ± 0.9°C at a place of RF application, 49.4 ± 4.5°C in the depth of the exposure area, and 40.3 ± 3.5°C on a surface of the endocardium. Mean macroscopically visible depth of the myocardial damage was 4.5 ± 0.7 mm. When the heart was cooled to 20 °C, myocardial impedance drastically decreased and was 0.65 ± 0.43 МΩ before RF application. After RF application, impedance in the perifocal zone increased and was 0.97 ± 0.81 МΩ. Mean temperatures of the epicardium were 90.4 ± 0.8°С at the site of RF application, 67.2 ± 3.1°С in the depth of exposure area; and 40.1 ± 3.8°С on the endocardium. Mean depth of RF damage in this series of observations was 6.7 ± 0.3 mm. The values of tissue impedance for each experimental temperature before and after RF application significantly differed (p < 0.05). The intergroup values of impedance and temperature before and after RF application as well as the depths of RF damage also significantly differed before and after RF exposure (p < 0.01). Discussion The study demonstrated that the efficacy of RF application on cardiac muscle directly depends on a temperature of the surrounding tissues. Initially low temperature ensures a slow increase in the temperature in the area of RF application; it prevents rapid elevation of electric impedance and enables RF energy spreading deep into the tissues causing their effective destruction. The problem of RF system efficacy augmentation has existed for a long time. Indeed, the studies of S. Nath (1993, 1995) concerning the temperature-dependent cardiomyocyte membrane potentials demonstrated that heating of the cardiomyocytes to 48°С results in reversible alterations. Therefore, insufficient heating in the depth of RF application can lead to recovery of the membrane potentials and, therefore, to inefficacy of the procedure [8, 9]. Also, these works demonstrated that, in case of the use of irrigated electrodes, the point of maximum impedance and heating shifts deep into the cardiac muscle causing deeper damage in contrast to non-irrigated systems where the point of maximum heating is situated directly in the area of contact of the electrode with the tissue and causes coagulation and drastic increase in the impedance preventing RF spreading deep into tissues [7]. Our data suggest that the efficacy of RF destruction under normothermic conditions is lower than the efficacy of destruction performed in the presence of local or general hypothermia. Several works demonstrated that optimal destruction temperature is 50–70°С [1, 8] because irreversible cell death occurs in these conditions. Therefore, initially higher tissue impedance induces an increased heating of the subepicardial layers of the myocardium which increases impedance in even higher degree and prevents spreading of RF energy deep into the myocardium. As a consequence, insufficient heating of the subendocardial layers and the absence of RF damage throughout the entire thickness of the heart wall results in inefficacy of the procedure. In turn, RF-induced destruction in the presence of hypothermia allows for achieving the temperature sufficient for irreversible cell damage at a predetermined depth of the myocardium. However, implementation of this method in clinical settings is significantly limited because maintenance of deep myocardial hypothermia requires working with “dry” heart which is not always possible, especially in the context of minimally invasive and endovascular techniques for treatment of cardiac arrhythmias without cardioplegia and without opening of the heart cavities [6]. New principles of RF energy delivery deep into the myocardium may become an alternative to RF energy application in the presence of deep hypothermia. These methods should ideally provide heating of all layers of the myocardium to equal temperature ranging from 50°С to 70°С with minimization of time and area of RF energy application. Conclusion The efficacy of RF energy application on the myocardium directly depends on tissue temperature. The higher the temperature is, the higher impedance that increases heating of the subepicardial layers preventing spreading of RF energy deep into the myocardium and hence attenuating the efficacy of the procedure is. Development and implementation of new principles of RF application will increase the efficacy of RF destruction under normothermic conditions. Conflict of interests The authors declare no conflict of interests. References 1. Swanson DK, Smith WJ, Ibrahim T, et al. Tissue temperature feedback control of power: the key to successful ablation. Innovations (Phila). 2011;6(4):276-282. doi: 10.1097/IMI.0b013e31822b4d22. 2. La Meir M, Gelsomino S, Lucà F, et al. Minimally invasive thoracoscopic hybrid treatment of lone atrial fibrillation: early results of monopolar versus bipolar radiofrequency source. Interact Cardiovasc Thorac Surg. 2012;14(4):445-450. doi: 10.1093/icvts/ivr142. 3. Chang D, Zhang S, Yang D, et al. Effect of epicardial fat pad ablation on acute atrial electrical remodeling and inducibility of atrial fibrillation. Circ J. 2010;74(5):885-894. 4. Saliba W, Wazni OM. Sinus rhythm restoration and treatment success: insight from recent clinical trials. Clin Cardiol. 2011;34(1):12-22. doi: 10.1002/clc.20826. 5. Wenning C, Lange PS, Schülke C, et al. Pulmonary vein isolation in patients with paroxysmal atrial fibrillation is associated with regional cardiac sympathetic denervation. EJNMMI Res. 2013;3(1):81. doi: 10.1186/2191-219X-3-81.. 6. Nasso G, Bonifazi R, Del Prete A, et al. Long-term results of ablation for isolated atrial fibrillation through a right minithoracotomy: toward a rational revision of treatment protocols. J Thorac Cardiovasc Surg. 2011;142(2):e41-e46. doi: 10.1016/j.jtcvs.2011.04.009. 7. Nath S, Haines DE. Biophysics and pathology of catheter energy delivery systems. Prog Cardiovasc Dis. 1995;37(4):185-204. 8. Nath S, Lynch C 3rd, Whayne JG, et al. Cellular electrophysiological effects of hyperthermia on isolated guinea pig papillary muscle. Implications for catheter ablation. Circulation. 1993;88(4 Pt 1):1826-1831. 9. Nath S, Whayne JG, Kaul S, et al. Effects of radiofrequency catheter ablation on regional myocardial blood flow. Possible mechanism for late electrophysiological outcome. Circulation. 1994;89(6):2667-2672.