Experiments on the efficacy and safety of radiofrequency ablation in the in vitro myocardial phantom and in vivo ovine model

Abstract

Background and aims of the thesis The optimal duration for atrial and ventricular ablations is still debated. We aimed at assessing the atrial lesion growth parameters by means of ablation with the Direct Endoscopic Visual catheter. The intention was to correlate the local electrogram amplitude decrement and impedance decrement with lesion growth. In regards to ventricular ablations the lesion growth dynamics and the potential for complications was planned to be evaluated in our validated myocardial phantom model. The value of high power ablations in atrial ablations has not been tested. We aimed at testing this in our myocardial phantom and the in vivo Ovine model. The stability of ablation catheter in highly mobile areas of heart is a concern. The magnetic navigation catheter is claimed to be highly stable in these areas of the heart. We aimed to test the stability of this catheter in the gel tank model. Regarding the variables, which affect the safety and efficacy of RF ablations, the baseline impedance and the impedance decrement during ablation is very common and hence needs to be evaluated. We aimed at devising a formula to correct the power delivered to account for the changes in impedance so that consistent lesion size is feasible. Methods In vitro ablations A myocardial phantom model tested and validated by Chik et al was used for the in vitro part of the experiments. The phantom comprised of a solidified gel in which a thermochromic sheet was embedded. This acted as an analogue for myocardium and the supernatant fluid provided an analogue for blood. The advantages were the precise and accurate delineation of lesion size and real time visualization of lesion formation. This iteration of the phantom utilized two temperature indicating ranges - a low zone from 50°C to ~75°C, and a high zone from 80°C to ~103°C. This allowed higher temperatures immediately around the catheter tip to be examined. The myocardial phantom was prepared by heating saline with an agar substitute powder, which is then allowed to cool. This formed a solid gel in which the thermochromic sheet was embedded prior to solidification. The supernatant fluid temperature of 370C at flow velocity of 55ml/min simulated the characteristics of blood flow in vivo. The impedance of gel and supernatant fluid was similar to myocardium and blood respectively. The phantom was sensitive to temperatures between 500C and 1000C in two stages as previously described and produced a hue (colour), which changed monotonically with temperature, enabling an isotherm of known temperature to be drawn. Images of the phantom were recorded by a camera (Canon 5DmkII, Canon Inc., Japan and macro lens (USM EF 100 mm, Canon, Japan) giving a sensor image resolution of ~90 pixels per millimeter. Image analysis and hue to temperature assignment were performed using in-house software. In the high power short duration ablations, the ablations were performed using an irrigated Navistar Thermocool catheter with a Stockert EP Shuttle Generator. The settings were 40W power, 30 seconds duration and temperature limit of 500C for the conventional arm and for the high power short duration arm ablations were performed at 40W, 50W, 60W, 70W and 80W for 5 seconds each. Saline irrigation rate for the catheter tip was 30ml/min for both systems. Lesion dimensions (depth and width) and overheated dimensions (depth and width) were measured for all ablations. The volume of individual lesions was calculated using the formula for half- ellipsoid. v=(2 × π × (w/2)^2× d)/3 v, w, d- volume, width and depth of the lesion Images of the lesion during RF ablations were captured every half second for short duration ablations and every 5 seconds for 30 seconds ablations. The 500C isotherm was drawn on the images by the custom image analysis software and the isotherm was used to define lesion dimensions (depth and width), while the 800C isotherm was used to assess dimensions of overheating. Lesion depth was measured from the electrode surface nearest to the ablation zone, to the isotherm of interest. Lesion width was defined as the maximal width of the 530C isotherm parallel to the electrode gel surface. For extended ablations on the myocardial phantom model simulating ventricular ablations, all ablations were performed with a Stockert EP Shuttle Generator, with settings of 20-50W power, 180 seconds duration and a temperature limit of 500C. Catheter irrigation rate was set at 30ml/min for 40W and 50W ablations and 17ml/min for 20W and 30W in accordance with the manufacturer’s guidelines. During RF ablations, images of the Phantom were taken at 10, 20, 30, 40, 50, 60, 90, 120, 150 and 180 seconds. The lesion dimensions and volume was measured as described above. For the experiments on circuit impedance and lesion dimensions, the RF ablations were performed with irrigated Navistar Thermocool catheter with a Stockert EP Shuttle Generator. The settings were 40W power, 30 seconds duration and a temperature limit of 500C. Saline irrigation rate for the catheter tip was 30ml/min for both systems. The circuit impedance of the system was set by altering the extent of contact of the return electrode with fluid in the phantom tank, which allowed for titration of impedance to within 2Ω of the target. Lesion dimensions (depth and width) and overheated dimensions (depth and width) were measured for all ablations and the volume was calculated. In vivo procedural details Sydney West Area Health Service Animal Ethics committee in accordance with the guidelines set by the National Health and Medical Research Council of Australia approved the animal projects. The experiments were performed in Merino Whether sheep. The sheep were pre-medicated with 20 mg of intramuscular xylazine. A 6 Fr vascular sheath was placed in the left internal jugular vein using the Seldinger technique. Anesthesia was induced with 200 mg of intravenous propofol before intubation with 8.5 F endotracheal tube and then ventilated with a dual phase ventilator at the rate of 10 to 16 respirations per minute to maintain end tidal PCO2 of 29-35 mm Hg. General anesthesia was maintained with isoflurane 2-5% in 100% Oxygen. Oxygen saturation was monitored with a probe placed over the buccal mucosa. Intra-arterial blood pressures, oxygen saturation, end- tidal CO2, and sedation depth were documented every 10 minutes. RF ablations were performed with Endosense CF sensing irrigated catheter (St Jude) with Stockert EP Shuttle Generator. The catheter was positioned in the right atrium and adjusted to achieve the desired CF. Achieving the desired CF was of prime priority and the electro-anatomical mapping was used to avoid overlapping the lesions. The ablations settings were 40W power, 30 seconds duration and a temperature limit of 600C for the conventional arm. The high power, short duration ablations were performed at 50W, 60W, 70W and 80W for 5 seconds each. Saline irrigation rate for the catheter tip was 30ml/min for all ablations. Lesion dimensions (depth and width) were measured for all ablations. The longest dimension on the ablation surface was measured as width. A five seconds timer was used to deliver RF energy for short duration ablations. The power was delivered for 5 seconds only after the target power level was reached as measured by the radiofrequency generator. Energy generated during the power “ramp-up” phase, prior to the start of the ablation timer, was shunted to a resistor. Ablation using DEV catheter The Direct Endocardial Visualization (DEV) Catheter in the collapsed state has a diameter of 13.5 Fr and a steerable shaft of 93 cms in length. The distal tip of the catheter is fashioned into a hood of 7 mm diameter with a central aperture of 2.7 mm. It has an internal optical fiber light guide and an illumination port constructed in the same manner as an endoscope. The optical fiber light guide was illuminated by a Stryker L 9000 LED light source. An endoscopic camera, ConMed IM 4000 HD Endoscopic Camera System, captured the video. Saline was admitted under positive pressure into the hood of the DEV catheter, which formed a transparent barrier around the light source and endocardium to displace blood between the aperture and myocardium. In this catheter the metal electrode has been separated from the endocardium by a 7 mm column of saline which acts as a virtual electrode. The virtual saline electrode was used to record unipolar electrograms and to deliver RF current for ablation. The advantage of the virtual electrode is to preserve the field of vision (FOV) to assess catheter contact and lesion formation during ablation. A 14 Fr long sheath (VLA-1, Medical) was inserted in the right femoral vein to facilitate insertion of DEV catheter. Intravenous heparin was administered as a bolus followed by infusion to maintain activated clotting time between 300 and 350 seconds. DEV irrigation rate was 15 ml/min to maintain an unobstructed endoscopic field of view (FOV). During ablations the infusion rate was increased to 25mls/min using a Cool Flow pump. It was shown by Chik et al and Sacher et al that in DEV ablations low power was sufficient to create lesions similar in size to conventional ablations. Ablation powers used were 12W, 14W and 16W for 30 seconds duration. Only one power setting was used in each sheep to avoid confusion in autopsy analysis. Ablation sites were chosen under direct endocardial visualization in the right atrium, atrial septum and left atrium. Left atrium was accessed via the retrograde aortic route. Circuit impedance changes were recorded and the local virtual unipolar electrograms were recorded using the Cardiolab Prucka recording system (GE Health Care, Waukesha, WI) before, during and after ablations. Changes in unipolar electrogram for each ablation were analyzed off line in which the local electrogram amplitude was measured from peak to peak. Standard filter settings were used and the virtual electrode unipolar electrogram was referenced to a quadripolar catheter positioned in the inferior venacava. Full colour visual evolution of lesion creation was captured via the endoscopic camera through the distal hood FOV. Lesion growth was recorded throughout each ablation and was analyzed off-line. Anatomical guidance for ablation Three-dimensional anatomical mapping were obtained with the NavX system St Jude Medical Inc., St Paul, MN, USA). Statistical Analysis Parameters analyzed included lesion depth, width and volume. Statistical Package for Social Sciences (Version 22, SPSS Inc., Chicago, Il, USA) software was used to analyze all descriptive and analytical tests. Analysis of Variance test (ANOVA) and post hoc Bonferroni correction were used to compare the means between the groups. Results In irrigated radiofrequency atrial ablations 30-40 W power for 20-25 seconds duration seemed ideal to deliver optimal lesion dimensions. This was true for ablations on the smooth surface of atrium. Local electrogram and circuit impedance decrement, which are widely used to guide ablation, are not ideal parameters to assess the efficacy of ablation. Significant decrement in local electrogram amplitude and circuit impedance could occur early within the first 10 seconds of initiation of ablation. The significant electrogram amplitude decrement was defined as 80% reduction from the initial value and significant impedance decrement was defined as 20% reduction from the initial value. The lesion continued to grow for another 10-15 seconds in the majority of ablations. This observation was based on the surface dimensions of lesions and not the real time lesion depth in vivo in the Ovine heart using a novel direct endocardial visualization catheter. However, all lesions were shown to be transmural in autopsy analysis. Using higher ablation power could safely reduce the radiofrequency ablation duration in atrial ablations. This was shown in an in vitro myocardial phantom model and validated in vivo in the Ovine model. At 50-60 W power only 5 seconds was necessary to produce transmural lesions when the electrode- tissue contact force was kept constant at 10g. This was safer than irrigated RF ablations of 40W power for 30 seconds duration at 10g contact force. For ventricular ablations 90 seconds appeared to be the optimal duration. This was safer than 180 seconds and more effective compared to 30 seconds. This provided deeper lesions without compromising safety for 40-50W of power, which was observed in an in vitro myocardial phantom model. The potential for complications measured with the overheated dimensions showed that extending the duration beyond 90 seconds did not add to the lesion dimensions and had the potential to cause more complications. Fluctuation in the circuit impedance is common during radiofrequency ablations. We demonstrated in the myocardial phantom model that these variations could affect the ablation efficacy and safety. Lower circuit impedance could cause tissue overheating and higher impedance could reduce lesion size. The could make the ablation either unsafe or ineffective. This could be corrected by using a simple formula, which could help increase ablation power when circuit impedance is high and reduce the power when the impedance is low. This helped to maintain constant current, which determines the lesion dimensions. Magnetic navigation system, which is a new advancement in the field of radiofrequency ablations, has been shown to be both efficacious and safe in clinical studies. We provided the basis for this observation with our experiments in the in vitro myocardial phantom model. We showed that MNS provided stable and consistent ablations irrespective of cardiac motion. In areas of significant lateral movement the magnetic force kept the catheter in a stable position leading to stable lesions. Conclusion The optimal duration for atrial ablations is 20-25 seconds. The local electrogram amplitude change, which is frequently used in clinical practise, is unreliable in determining transmurality. High power, 50-60W irrigated atrial ablation is safer and equally effective as conventional ablation. This has the potential to reduce AF ablation procedural times considerably. The optimal duration for ventricular ablations from our in vitro study is 90 seconds when using 40-50W of irrigated ablation. Ablation duration beyond that increases the chance of complications without much increase in lesion dimensions. Baseline circuit impedance and impedance changes during ablation could affect lesion size and safety. A simple formula to correct the ablation power could even out these changes and deliver a consistent lesion. Finally, if stability of the ablation catheter is a concern then magnetic navigation catheter is a reasonable option.