Development Of New Devices For Endovascular Treatment Of Ascending Aortic Dilation Combined With Valvular Disease

BackgroundWith the aging of our population,the prevalence of ascending aortic dilation(AAD)combined with valvular disease,which is mainly caused by degenerative diseases,is increasing in the population.The interaction of AAD and valvular disease aggravates the disease and leads to decompensation of cardiac function,rupture of dissecting aneurysm and death eventually.With further research and application of endovascular technique,thoracic endovascular aortic repair(TEVAR)and transcatheter aortic valve replacement(TAVR)have become the main method of minimally invasive treatment for aortic and aortic valve(AV)diseases and also provide new options for surgical high-risk patients.However,the research data of integrated endovascular treatment for AAD combined with valvular diseases is still insufficient.Therefore,the demand of endovascular treatment for this complex disease is particularly urgent owing to the aging process of population.How to use endovascular strategy to treat AAD with AV disease,even multiple valve disease,needs exploratory research.Objective(1)To obtain the clinical characteristics and treatment results of patients with AAD combined with valvular disease.(2)To explore the hemodynamic characteristics of AAD combined with AV disease.(3)To analyze the imaging morphological characteristics of patients with AAD combined with AV disease,and to propose the design of a new endograft and a delivery system.(4)To explore the early feasibility and safety of aortic valved-fenestrated endograft system through in vitro and in vivo experiments.(5)To explore the feasibility of simultaneous treatment of ascending thoracic aortic aneurysm(ATAA)with aortic regurgitation(AR)and mitral regurgitation(MR)in vitro experiment.Methods(1)Clinical study:This study retrospectively analyzed the treatment of patients with AAD who were admitted to our center for surgery from January 2015 to December 2018.The distribution of the pathologies and prognosis after surgery were analyzed.(2)Based on the CTA(Computed tomography angiography)data,the 3D AAD model was established.Through numerical simulation of fluid-structure interaction,the related parameters were analyzed to explore the hemodynamic characteristics between different pathologies.(3)Endograft designing:38 patients with AAD combined with AV disease were compared with those with normal ascending aorta morphology according to age and gender.According to the anatomic data,the endograft was designed.(4)In vitro and in vivo experiments:A new aortic valved-fenestrated endograft system was introduced into 20 pig heart-aortas through the transapical access to explore the optimal operation process and evaluate the efficiency and feasiblity.The new endograft system was deployed in six healthy adult pigs.The early safety and feasibility of the new graft system were evaluated by CTA,echocardiography,electrocardiogram,general anatomy and pathological examination.(5)In vitro study of simultaneous endovascular repair of ATAA with AR and MR:The model of ATAA+AR+MR was established in ten pig heart-aorta models.Aortic valved-fenestrated endograft and mitral valved endograft system were deployed through the transapical access to explore the preliminary feasibility of simultaneous treatment of ATAA with AR and MR.Results(1)Among the 342 patients,degenerative disease(162/342,48.8%)were still the main causes of AAD.The proportion of pure AAD was the smallest(12/342,3.5%).AAD with AV disease accounted for the highest proportion(129/342,37.7%),and AR was the most common type(51/342,14.9%).AR combined with MR accounted for the highest proportion(67/342,19.6%)in AAD combined with double valve disease.The operative mortality was2.1%(7/342).Univariate analysis showed that operative death was associated with coronary atherosclerotic heart disease(CHD)(P=0.012),preoperative ejection fraction(EF)<40%(P=0.007)and surgery(P=0.040).Multivariate logistic regression analysis showed that CHD and preoperative EF<40%were independent risk factors for operative death[CHD,(OR=8.657,95CI=1.73-43.09,P=0.008);EF<40%(OR=0.075,95CI=0.01-0.04,P=0.002)].Postoperative complications were relatively common(115/342,33.6%).There were17 late deaths.The 2-,4-,and 6-year survival rates were 93.9%,93.0%,and 93.0%,respectively.There were 40 cases of complications during the follow-up period.The incidence of no adverse events in 2-,4-and 6-years after operation was 58.8%,58.2%and58.2%,respectively.(2)In terms of hemodynamic parameters,the EOA(Effective orifice area)of AV in the normal,AAD+AS+AR and ATAA+AR group were 2.67 cm~2,2.17 cm~2 and 4.31 cm~2.The maximum pressure difference of the three groups were 14.65 mm Hg,18.63 mm Hg and 13.82mm Hg,respectively.The peak velocity of normal and AAD+AS+AR group appeared at AV.In the ATAA+AR group,the peak velocity appeared at the end of the ascending aorta.In terms of diastolic flow distribution,there was a small high velocity area at the AV in the AAD+AS+AR group,indicating mild-moderate AR.A large area of high flow velocity was found at the AV in the ATAA+AR group,indicating severe AR.For the morphology of AV,the opening edge in normal group was approximately circular in systole.The aortic valve closed well without regurgitation in diastolic phase.In the AAD+AS+AR group,the opening edge was triangular in systole with a smaller EOA.It showed obvious regurgitation in diastole phase.For the ATAA+AR group,the opening edge was triangular with a larger EOA in systole.Diastolic aortic valve indicated severe regurgitation.The peak stress of the three models appeared in the diastole phase.The areas of high stress in the three models were concentrated on the commissure edge(normal),calcified area and commissure edge(AAD+AS+AR)and nocoronary valve(ATAA+AR),respectively.(3)Compared with the normal group,diameter of the aortic annulus,sinus of Valsalva,sinus junction plane(STJ),middle ascending aorta,distal ascending aorta,proximal left common carotid artery(LCCA)and proximal left subclavian artery(LSA)were significantly enlarged in the AAD group(P<0.05).There was no significant difference in the diameter of bilateral coronary artery origins(P=0.239;P=0.066).The circumferential angle of bilateral coronary openings in the AAD group was larger than that in the normal group(127.3±26.8°vs 115.8±13.5°,P=0.031).There was no significant difference between the three groups(12.8±4.5 mm vs 13.4±3.1 mm,P=0.663;20.0±4.2 mm vs 19.5±2.0 mm,P=0.501;26.9±5.0 mm vs 27.8±3.3 mm,P=0.492)in the measurement of the central line distance from the left coronal artery(LCA),right coronal artery(RCA)and STJ to the aortic annulus,respectively.The length of the ascending aorta in the AAD group were greater than the normal group(P<0.05).According to the results of anatomical measurement,we have completed the development of an aortic valved-fenestrated endograft and adaptive delivery system,as well as the standardization of graft compression method.(4)The in vitro release of the novel aortic valved-fenestrated endograft was deployed through the transapical access in 20 pig heart-aortas.The technical success rate was 100%,and the average release time was 37.3±8.2 min(25-59 min).When the fenestration height and diameter were both 1.25cm,the flow of bilateral coronary arteries decreased at different degrees,and the flow of RCA decreased significantly(P=0.014).In fenestration height of1.25 cm with 1.5 cm diameter,height of 1.5 cm with 1.25cm diameter and height of 1.5 cm with 1.5 cm diameter groups,there was no significant decrease in the flow of bilateral coronary arteries.Endoscopic observation showed that the AVs function were normal without affecting the anterior mitral valves'(MVs)activity.The results of general anatomy showed that the endografts were in good shape.Bilateral fenestrations were well aligned with coronary artery origins.Aortic valved-fenestrated endografts were successfully implanted in six animals.Intraoperative angiography showed that the bilateral coronary arteries were in good alignment and the function of artificial AVs were good.The optimal parameters of fenestration in vitro were further verified by animal experiments.Five animals survived during the follow-up period,and one died on the 12th day after operation due to infection.The echocardiography showed that the valves function were normal,and there was no obvious stenosis,regurgitation and perivalvular leakage(PVL).The results of CTA and ECG showed no abnormality.The results of gross anatomy showed that the endografts were in good position and there was no coronary artery obstruction or tissue infarction.(5)The ATAA+AR+MR model was successfully established in ten pig heart-aortas.Aortic valved-fenestrated endograft and mitral valved endografts were successfully deployed through the transapical access in all cases(100%).Postoperative angiography showed that the sacs were completely excluded and the endografts were in good position and shape.There was no significant decrease in the flow of bilateral coronaries after endografts implantation(LCA:289.4±10.2 ml/min vs 330.4±12.1 ml/min,P<0.001;RCA:350.0±14.5 ml/min vs 376.8±10.5 ml/min,P<0.001).Endoscopy showed that the function of artificial valves were normal.No obvious regurgitation and PVL were found in echocardiography.There was no significant difference in trans-AV and trans-MV gradient pressure before and after operation(aortic valve,6.0±0.6 mm Hg vs 5.5±0.9 mm Hg,P=0.076;mitral valve,5.4±1.0 mm Hg vs 4.9±1.0 mm Hg,P=0.094).The gradient pressure of left ventricular outflow tract(LVOT)also did not increase significantly(2.0±0.5 mmhg vs 1.9±0.5 mmhg,P=0.154).The results of gross anatomy showed that the endografts were in good position,and the coronary artery openings were accurate without obstruction.ConclusionAAD with valvular disease was the main group of patients with AAD.The feasibility and safety of the new aortic valved-fenestrated endograft system were verified in vitro and in vivo experiments.The feasibility of transcatheter treatment of ATAA with AR and MR was also studied in vitro.The above research will provide new clues for endovascular treatment for AAD combined with multiple valvular diseases and relevant scientific data.