超声引导下经皮心肌内室间隔射频消融术减容小尾寒羊室间隔1年期的安全性及有效性评估

Safety and efficacy of trans-right-ventricular echocardiography guided percutaneous intramyocardial septal radiofrequency ablation for interventricular septal reduction:an ovine model with 1-year outcomes

目的:探讨超声引导下经右室行经皮心肌内室间隔射频消融术(PIMSRA)减容小尾寒羊室间隔心肌1年期的安全性及有效性,并观察1年后消融区心肌的病理改变。方法:12只普通种小尾寒羊随机分为PIMSRA组(n=6)及空白对照组(Sham组,n=6),PIMSRA组采用经皮经右室心尖部穿刺进入室间隔基底部进行消融,最大功率80 W,消融时间5 min;Sham组以同样路径将穿刺针插入室间隔基底部并留置5 min,但不进行消融。应用超声心动图、12导联心电图、心肌声学造影(MCE)评估术前及术后即刻、1周、2周、1个月、2个月、3个月、6个月、12个月消融区结构及功能改变,记录室间隔消融区厚度、运动幅度、室壁增厚率、左室流出道压差及左室射血分数(LVEF),二尖瓣舒张早期峰值流速(E)、舒张晚期峰值流速(A),二尖瓣环舒张早期运动速度(E′)、舒张晚期运动速度(A′)。分别于术前及术后3 h、术后2周行血清学心肌损伤三项检查:肌钙蛋白I(Trop I)、肌红蛋白(Myoglobin)及肌酸激酶同工酶质量(CM-MBmass)。HE及Masson染色观察消融区组织病理学改变。结果:围术期两组动物均未出现心包压塞。术后即刻观察到消融区室壁运动不协调,PIMSRA组术后即刻消融区室壁增厚率以及室壁运动幅度显著低于术前(P<0.005),并维持该水平至术后12个月;Sham组术前与术后各时间点手术区室壁增厚率以及室壁运动幅度差异无统计学意义(P>0.05)。PIMSRA组术后即刻消融区厚度显著大于术前(P<0.001),1周后显著下降至接近术前水平(P=0.931),3个月后显著低于术前水平(P<0.001);Sham组术后即刻手术区厚度大于术前(P=0.005),术后1周下降至术前水平(P=0.027)。两组消融前后LVEF、E/A以及E′/A′差异无统计学意义(均P>0.05)。PIMSRA组及Sham组术后3 h血清学检测Trop I显著升高(均P<0.005),术后2周下降至接近术前水平(均P>0.05)。术后随访期间,两组实验动物心电图均显示为正常窦性心律;组织病理学观察显示1年后消融区心肌组织呈纤维化改变,与周围正常组织边界清晰,无碳化形成。结论:经右室行PIMSRA可对小尾寒羊室间隔心肌组织进行精准消融,减容效果显著,左室整体功能得以保留,未并发心包压塞、心律失常等并发症。经右室行PIMSRA可成为一种安全有效的室间隔微创减容方式。

Objective To investigate the safety and efficacy of echocardiography-guided trans-right-ventricular percutaneous intramyocardial septal radiofrequency ablation(PIMSRA)in a healthy sheep model,and to observe the pathological changes of myocardium in ablation area one year later.Methods Twelve sheep were divided into PIMSRA group(n=6)and sham group(n=6).In PIMSRA group,a radiofrequency(RF)electrode was inserted to the interventricular septum(IVS)with maximum power of 80 Watts for 5 minutes.In the sham group,RF electrode tip was positioned in IVS segment but without the RF power delivery.Electrocardiogram(ECG),echocardiography,myocardial contrast echocardiography(MCE)were performed to assess the efficacy of PIMSRA at postoperative immediately,2-week,1-month,2-month,3-month,6-month and 12-month during the follow-up.The following parameters were recorded,including the thickness of ablation area,the systolic wall thickening rate and amplitude of movement of the ablated region,left ventricular outflow tract pressure gradient(LVOT PG),and left ventricular ejection fraction(LVEF),mitral valve early diastolic peak velocity(E),late diastolic peak velocity(A)and the E/A ratio,peak velocity of early diastolic mitral annular motion(E′),peak velocity of late diastolic mitral annular motion(A′),and the E′/A′ratio.For both groups,the myocardial biomarkers of troponin I,myoglobin and isoenzymes of creatine kinase were tested before the ablation and 3 h after the ablation,and again after 2 weeks.Tissue pathology examinations were performed at the end of study.Results None of the animals in both groups was observed to have pericardial tamponade during perioperative period.Immediately after the procedure,septal hypokinesis was seen in all PIMSRA group animals,the systolic wall thickening rate and amplitude of movement of the ablated region were significantly decreased(P<0.001),which was sustained until 12 months.In Sham group,there were no significant differences in the wall thickening rate and amplitude of movement of the operated region(all P>0.05).The thickness of the ablation area in the PIMSRA group was significantly increased immediately after the procedure(P<0.001),decreased to baseline level at 1-week(P=0.931),and significantly increased at 3-month(P<0.001).In the Sham group,the IVS thickness was significantly increased immediately after the procedure(P=0.005),decreased to baseline level at 1-week(P=0.027),then has no further significant changes.There were no significant differences in LVEF,E/A,E′/A′between PIMSRA and Sham group(all P>0.05).MCE showed the thickness of the ablation area was significantly decreased in the PIMSRA group 12 months after the operation.In both groups,troponin I increased significantly 3 h after the operation(all P<0.005),which decreased to baseline level 2 weeks later(all P>0.05).ECG showed that all the sheep had normal sinus rhythm.Pathological examinations revealed the tissue in the ablation area was fibrotic,having clear boundary with the surrounding normal tissue and no carbonization was observed 1 year later.Conclusions Echocardiography-guided trans-right-ventricular PIMSRA produced precisely ablated myocardial tissues,reduced the IVS thickness significantly,preserved the global left ventricular function.All the sheep had normal sinus rhythm and without pericardial tamponade in 1 year follow-ups.Echocardiography-guided trans-right-ventricular PIMSRA is a safe and effective minimally invasive treatment for septal reduction therapy.