Radiofrequency Ablation Of Ventricular Outflow Tract Septum Animal Experiment In Canine

Background: Hypertrophic cardiomyopathy(HCM)is a kind of cardiomyopathies which is defined as structural and functional abnormalities of ventricular myocardium but can’t be explained by abnormal cardiac load only.HCM is an autosomal dominant genetic disease of heart with a characteristic of familial hereditary.It was reported that worldwide incidence rate of HCM is nealy 1/500.Hypertrophic cardiomyopathy accompanied with left ventricular outflow tract obstruction(LVOTO)is called hypertrophic obstructive cardiomyopathy(HOCM),of which clinical symptoms include exercise intolerance,dyspnea,angina pectoris,dizziness,syncope and sudden death which will haveserious impact on patients’ life quality,threaten their life safety and causeenormous medical burden to our soceity.At present,symptomatic treatment is the main therapeutic strategy of HOCM to relieve symptoms and improve life quality and prevent from sudden death.Drugs such as beta blockers and calcium ion antagonists are the basis medicine for HOCM patients.In addition,dual chamber pacemaker implantation,surgical resection of hypertrophic myocardium,and percutaneous transluminal septal myocardial(PTSMA)ablation are very important supplemental strategy for patients of which symptoms can’t be controlled well by drugs only.However,there were also specific limitations for these treatment.Evidencesshowed that dual chamber pacemaker implantation can help reduce the pressure gradient,but it could not improve patients’ exercise tolerance to bring real benefits.Surgical resection of hypertrophic myocardium could significantly improve the life quality of patients,but the procedures were complicated and,the mortality rate is nearly 1%-5%.PTSMA requires a suitable target vessel and is technically not suitable for children.PTSMA is also not recommended for patients with diffuse thickening of the ventricular septum.The catheter-based radiofrequency ablation has developed rapidly and is mainly used in treatment of arrhythmia.The advantages of this procedure on cadiac ablation is easy to control and positional accurately.There is a study on treatment of HOCM patients with hypertrophic myocardium by catheter-based radiofrequency ablation which has the advantages of a smaller trauma,more accurate location of hypertrophy myocardium,and will not limited by target blood vessels.However,cases are not too much and related study on animals were never been performed to evaluate safety and efficacy systematicly.Therefore,we designed our study to perform catheter-based radiofrequency ablation on outflow tract septum of canines and compare left ventricular structure and function before and after the procedure to evaluate the safety and efficacy,so that we can accumulate more experience and data evidence to carry on this procedure on HOCM patients.Objective: To find suitable condition for radiofrequency ablation of ventricular outflow tract septum in vitro study.Radiofrequency ablation of ventricular outflow tract septum animal experiment in canine to observe left ventricular structure and function change.To investigate the parameters,efficacy and safety of radiofrequency catheter ablation of ventricular outflow tract septumMethods: 1.To find suitable condition for radiofrequency ablation of ventricular outflow tract septum in vitro study:(1)The anesthetized canine’s thigh muscle was exposed,fixed output temperature,radiofrequency current was terminated immediately in the event of an impedance rise >=10 Omega.(2)The ablation depth and maximum damage diameter of the common ablation catheter and the cool-tip ablation catheter can be compared.(3)After explored appropriate conditions for ablation,we exposed the outflow tract septum from isolated canine heart.Then perform ablation around the area below aortic,and observe whether aortic structure is affected.Subsequently,pathological biopsy is processed to verify if endothelial of aorta is damaged.(4)We use left ventricular angiography to find the right location for ablation,we observe whether arrhythmic occurred during ablation.The experimental canines were sacrificed immediately after ablation.The general observation was similar to the experimental results.The pathological sections were observed to find if endothelial of aorta is damaged.2.Radiofrequency ablation of ventricular outflow tract septum animal experiment in canine: we use canine to radiofrequency ablation of ventricular outflow tract septum.(1)Preoperative examination of left ventricular outflow tract width,septum thickness and left ventricular ejection fraction.(2)Ablation catheter was positioned to the left ventricular outflow tract septum guided by ultrasonic echocardiography.Immediately after ablation we check the examination again.(3)Follow-up: While the canines died during the procedure are dissected instantly for gaining experience,other canines are scheduled to follow-up visits at 1,3 months after the procedure,including the general condition,ECG,blood pressure.transthoracic echocardiography,observation of gross specimens and pathological sections,in an attempt to gain preliminary evaluation of radiofrequency ablation of ventricular outflow tract septum safety and efficacy in animal experiments.Results: 1.To find suitable condition for radiofrequency ablation of ventricular outflow tract septum in vitro study:(1)Set ablation time 180 s,fixed output temperature of 55℃,60℃,65℃,we completed set ablation time without impedance rise is equal to or more than 10 Omega when need to stop the ablation caused by coagulation necrosis.Fixed output temperature of 70℃,the impedance is increased more than 10 Omega,occurred during the ablation to 91 seconds.The conventional catheter Lesion dimensions in the depth of 3.2mm,the maximum diameter of 9.2mm.A cooled catheter,fixed output temperature to 80℃,the catheter tip temperature can be maintained at 50℃.The use of saline irrigation system,the lesion dimensions in this experiment can be the most in the depth of 12.1mm,the maximum diameter of 15.1mm.(2)Below 10mm-20 mm of the aortic valve ablation.After ablation we observe whether aortic structure was damaged,pathological biopsy to verify whether the involvement of the aorta.(3)Pre experiment: left ventricular angiography assisted positioning radiofrequency ablation of ventricular outflow tract septum.One of three canines emerges ventricular fibrillation after 11 seconds.The others completed ablation successfully.The canines were dissected instantly,no visible damage on ventricular outflow septum,no involvement of the aorta,the myocardial biopsy damage detection.Myocardial injury,cell disorder and inflammatory cell occur in ablation area.The reason for ventricular fibrillation is lack of experience,during ablation the catheter removed than ventricular fibrillation appered.Radiofrequency ablation of ventricular outflow tract septum animal experiment in canine:(1)Nine of ten canines do radiofrequency ablation successfully.The third experimental canine was died of ventricular fibrillation.Transient atrioventricular block occurred in the fifth canine.The ninth canine was successfully performed radiofrequency ablation,died of postoperative deep anesthesia,respiratory inhibition.The others survived to the scheduled follow-up time point.The success rate of operation is 80%.(2)After ablation survival canines retest ECG and blood pressure,there is no obviously change.(3)The preoperative and postoperative echocardiographic indices were statistically analyzed.Eight successful ablation of canines preoperative left ventricular outflow track width was 10.91±0.66 mm,postoperative 11.4±0.74 mm,p = 0.016;preoperative systolic ventricular septum thickness 11.09±0.88 mm,postoperative 9.39±0.73 mm,p< 0.001;preoperative left ventricular ejection fraction 67.63%±1.30%,postoperative 67.50%±2.00%,p = 0.882.Four successful ablation of canines preoperative left ventricular outflow track width was 11.03±0.29 mm,one month after the operation 12.20±0.42 mm,p = 0.034;preoperative systolic ventricular septum thickness 11.25±1.1mm,one month after the operation 8.38±1.01 mm,p=0.021;preoperative left ventricular ejection fraction 67.75%±0.96%,one month after the operation 68.00%±1.83%,p = 0.761.Four successful ablation of canines preoperative left ventricular outflow track width was 10.08±0.96 mm,three month after the operation 12.05±0.93 mm,p = 0.008;preoperative systolic ventricular septum thickness 10.93±0.70 mm,three month after the operation 8.68±0.46 mm,p=0.03;preoperative left ventricular ejection fraction 67.50%±1.73%,three month after the operation 68.25%±1.71%,p = 0.608.The left ventricular outflow width and systolic ventricular septum thickness were statistically significant difference,but left ventricular ejection fraction change was not statistically significant in immediate postoperative,one month after operation and three month after operation.The reason was the experiment uses the healthy canines which the heart function are normal,radiofrequency ablation does not make further improvement of heart function.(4)When compared with the surrounding normal myocardium,ablation necrosis area showed obvious hyperplasia of fibrous tissue,coagulation necrosis,there were a few inflammatory cells and tissue reactions one month after operation.Compared with the surrounding normal myocardium,ablation necrosis area showed obvious hyperplasia of fibrous tissue,coagulation necrosis,no obvious inflammatory cell infiltration three month after operation.Conclusion: Radiofrequency ablation of ventricular outflow tract septum animal experiment in canine shows it is safe and effective.When we select the appropriate radiofrequency power and cold saline perfusion the damage depth can be more than 10 mm.The rate of complications is similar with surgical resection and PTSMA.NO postoperative complications were found at 1,3months after operation.It is proved that radiofrequency ablation of ventricular outflow tract septum is safety and feasibility.It provides experimental basis fo subsequent animal experiments and clinical trials.