聚焦功率超声肾周脂肪改性治疗原发性高血压病的探索性研究

Focused power ultrasound mediated peri-renal fat modifi cation therapy for essential hypertension:a pilot study

目的探索非侵入性体外聚焦功率超声(FPU)肾周脂肪改性治疗原发性高血压病的安全性及有效性。方法(1)安全性研究:拟入选健康家猪分为FPU组及对照组,完成FPU肾周脂肪改性及1周、4周、8周随访,评估治疗安全性及改性后肾周脂肪组织结构变化。(2)临床探索研究:拟入选原发性高血压病患者,完成FPU肾周脂肪改性及1个月、6个月随访,评估安全性事件和血压变化,主要有效终点定义为6个月随访时诊室血压及24 h动态血压变化。结果(1)安全性研究:共入选16只健康家猪,FPU组及对照组各8只,顺利完成FPU肾周脂肪改性及1周、4周、8周随访。随访过程中无动物死亡、器官损伤等严重安全事件发生,血生化等安全性指标未见异常。FPU组家猪术后1周、4周、8周组织病理结果提示,肾周脂肪结构明显破坏伴组织纤维化且以8周变化最明显。(2)临床探索研究:共入选原发性高血压病患者21例,均完成FPU肾周脂肪改性及1个月、6个月随访。研究中未见死亡、器官损伤等严重不良事件发生,血生化等安全性指标未见异常。6个月随访时患者诊室收缩压较基线下降了(18.1±13.7)mmHg(P<0.001),舒张压下降了(13.9±11.3)mmHg(P<0.001),24 h平均动态收缩压下降了(11.3±13.2)mmHg(P=0.003),24 h平均动态舒张压下降了(7.3±8.5)mmHg(P=0.002)。其中诊室收缩压下降>10 mmHg占比为66.7%(14/21)。结论动物实验基础研究和小样本临床研究表明FPU肾周脂肪改性具有良好的安全性且可有效降压。

Objective The aim of this study was to assess the safety and effi cacy of peri-renal fat modifi cation(PRFM)in treating hypertension via a completely noninvasive focused power ultrasound system(FPU).Methods This study was divided into 2 parts,(1)Safety study:Healthy domestic pigs were enrolled and equally assigned to the FPU group and the Sham group.The safety events were evaluated 1 week,4 weeks and 8 weeks post-procedure with the histopathological evaluation of peri-renal fat at each follow-up timepoint.(2)Clinical pilot study:Essential hypertension patients were enrolled and received PRFM via FPU with follow-up visits at 1 month and 6 months post-procedure.Safety events and the blood pressure response would be assessed at each timepoint.The major clinical effi cacy endpoints were defi ned as the changes of offi ce blood pressure and 24h ambulatory blood pressure at 6 months.Results In safety study,16 healthy domestic pigs were enrolled,including 8 in the FPU group and 8 in the Sham group,who were all completed the PRFM therapy and 1 week,4 weeks and 8 weeks follow-up.No major safety event(including all-cause death,severe organ injury,etc.)was observed during or after the procedure.Biological indexes of serum examination showed nothing abnormal.The histopathological results of the peri-renal fat in the FPU group showed the obvious destruction of adipose structure with fibrosis formation over time,which was most obvious at 8 weeks post procedure.In clinical pilot study,21 essential hypertension patients were enrolled and received PRFM therapy with 1 and 6 months follow-up.No major safety event(including all-cause death,severe organ injury,etc.)was observed.The office systolic and diastolic blood pressure were significantly decreased by(18.1±13.7)mmHg(P<0.001)and(13.9±11.3)mmHg(P<0.001)at 6 months compared with baseline.Mean 24 h ambulatory systolic and diastolic blood pressure were significantly decreased by(11.3±13.2)mmHg(P=0.003)and(7.3±8.5)mmHg(P=0.002)at 6 months,respectively.The ratio of patients with over 10 mmHg reduction of office systolic blood pressure was 66.7%(14/21).Conclusions The results of animal and pilot study suggested that FPU mediated PRFM is a safe and eff ective therapy for essential hypertension.