Early results of the Resilia Inspiris aortic valve in the old age patients - a retrospective comparison with the Carpentier Edwards Magna Ease

Introduction: The Inspiris Resilia aortic valve® (INSPIRIS) is a pericardial bio-prosthesis with a new sterilization procedure that shows promising results in terms of reduced calcification. Methods: The 30-day mortality and morbidity were analyzed, comparing the INSPIRIS implanted between May 2017 and the end of January 2019, with its "predecessor", the Carpentier-Edwards Perimound Magna Ease (ME). Echocardiography was performed one-week after surgery. 125consecutively operated patients were included (59 INSPIRIS, 66 ME). Results: One patient in the ME group died and one patient in the INSPIRIS group had a complicated postoperative course due to right heart failure. Two patients (one INSPIRIS, one ME patient) suffered a perioperative stroke. The hemodynamic evaluation shows an effective reduction of mean transvalvular pressure gradients after surgery in both groups. INSPIRIS tended to have lower trans-prosthetic pressure gradients (9 mm Hg, Interquartile range [IQR] 11-7 mm Hg versus 12 mm Hg, IQR 15-9 mmHg; P = 0.001), reduced trans-prosthetic blood flow acceleration (209 cm/s, IQR 220-190 cm/s versus227 cm/s, IQR 263-191 cm/s; P = 0.003) and increased permeability indices (57%, IQR 67%- 47% versus42%, IQR 48%-38%; P8%; P < 0.001). Conclusion: There are only few clinical data available from INSPIRIS, and the present analysis confirms good results initial postoperatively with a tendency towards possibly improved hemodynamics compared to ME.


Introduction
Surgical aortic valve replacement (SAVR) as an isolated or combined procedure remains a treatment option for degenerative valve disease. Current research focuses on new preservation technologies for xeno-pericardial prostheses with the aim of improving long-term durability, lowering the age threshold for bio-prosthetic valve implantation and thus reducing the side effects of long-lasting anticoagulation. 1 The increasing shift of an indicated age threshold for bio-prosthetic valve implantation towards younger patients may also lead to new long-term complementary treatment concepts, especially in times of success of the trans-catheter aortic valve implantation (TAVI).
The Inspiris Resilia aortic valve® (INSPIRIS) (Edwards Lifesciences LLC, Irvine, USA) is a new bovine pericardial prosthesis for SAVR. The functional group capping of aldehydes (glutaraldehyde-fixed tissue) to prevent oxidation and calcification, glycerolization to reduce the amount of residual chemicals and the new sterilization process in which the water of the pericardial tissue is displaced and replaced by glycerol (which allows dry storage) are the key innovations that promise lasting tissue integrity. In vivo animal models confirmed significantly reduced calcifications and initial clinical studies showed promising follow-up results. [2][3][4] The use of INSPIRIS for SAVR, especially in younger patients, can combine the advantages of a durable bioprosthesis with the potential future option of a simplified valve-in-valve procedure for late structural valve deterioration by incorporating an extendable stent for smaller sized annular diameters. The INSPIRIS has been available on the European market since the spring of 2017 after receiving the CE mark. Post-operative clinical data are therefore rare.
We present a small series of early postoperative results (morbidity and mortality) of the INSPIRIS and compare them with those of its "predecessor", the Carpentier-Edwards Perimound Magna Ease (ME) (Edwards Lifesciences LLC, Irvine, USA) aortic bio-prosthesis, with a special emphasis on a comparative evaluation of their postoperative hemodynamic performance.

Materials and Methods
A single database of two surgeons was reviewed, retrospectively searching for either isolated or combined aortic valve replacement with INSPIRIS. The data collection started in February 2019 and covered the period from the beginning of the INSPIRIS implantation in May 2017 until the end of January 2019. According to these 21 months of observation, a comparison group was formed. This control group consisted of patients who had been operated on by the same team during the 21 preceding months (August 2015 to April 2017) and who had thus received the predecessor model, the ME.
Included were elective and urgent, isolated or in combination with coronary artery bypass graft (CABG) performed aortic valve replacements. Patients with concomitant mitral valve or aortic root surgery as well as patients with severe pre-existing left ventricular (LV) dysfunction were excluded with the aim of at least partially reducing possible factors that might influence the postoperative hemodynamic performance of the prostheses to allow for better comparability of the groups.
All patients had a postoperative echocardiography after one week. In addition to the left ventricular ejection fraction (LVEF), the mean pressure gradients (mm Hg), blood flow accelerations (cm/s) and permeability indices (%) of the bio-prostheses were analyzed. Clinical followup after 30 days was completed for all patients and early postoperative mortality and morbidity were documented. The latter was classified into major complications, i.e. non-fatal myocardial infarction, early re-operation (pericardial tamponade, deep sternal wound infection, etc), endocarditis and stroke, or into minor complications including new postoperative arrhythmias requiring permanent pacemaker implantation (PPM), acute renal failure and blood transfusions. All-cause mortality, postoperative morbidity and postoperative hemodynamic parameters of the two different prostheses were compared. The primary endpoint was to demonstrate the noninferiority of the INSPIRIS.

Statistical analysis
The SPSS 22.0 software package for Windows (SPSS Inc. Chicago, Illinois, USA) was used. Categorical variables are presented as numbers and proportions (%). Continuous normally distributed variables are summarized as mean ± one standard deviation (SD), while non-normally distributed variables (according to the Kolmogorov-Smirnov and the Shapiro-Wilk test) are described by their median and interquartile range (IQR). Accordingly, either the t test or the Mann-Whitney U test was used to compare the results. A P value <0.05 was considered significant. The authors had full access to the data and take responsibility for its integrity.

Results
Demographics, risk and operative data 125 patients, 59 in the INSPIRIS group and 66 in the ME group, were identified. All were operated on during the observation period and met the inclusion criteria. The main demographic parameters (age, gender, etc), risk factors and existing comorbidities as well as the logistic EuroSCORE 2 risk calculations were comparable (Table 1, section A). The indications for surgery and the number of single versus combined procedures were similar, except for an increased number of bicuspid valves in the ME group (Table 1, section B). More ME patients were anticoagulated after surgery. This is mainly due to the different observation period in which the operations were performed. Systematic postoperative anticoagulation was only gradually abandoned in favor of the recommended platelet anti-aggregation in recent years (Table 1, section B).

Mortality and Morbidity
One ME patient died, probably due to an annular disruption that led to massive right ventricular intramural bleeding. After initial stabilization, successful hemostasis and admission to the intensive care unit (ICU), the patient had a cardiac arrest a few hours later, probably due to a severe right ventricular dysfunction ( Table 1, section C).
One INSPIRIS patient also had a complicated postoperative course. After surgery (aortic valve replacement and CABG), he developed severe right ventricular (RV) dysfunction requiring urgent reopening of the sternum. A coronary angiography confirmed patent grafts. The patient remained unstable and started bleeding again from the sternum due to a beginning disseminated intravascular coagulation. After blood transfusions and sternal wound revisions with a "chest packing", the patient gradually stabilized and improved his RV function. The sternum was closed 10 days later and the patient left the hospital after one-month. 17 months later he was still alive (as he was admitted to hospital for other non-cardiac complaints).
In two patients from the INSPIRIS and one from the ME group, epicardial PPMs were implanted simultaneously during surgery, which were indicated due to pre-operative rhythmic disorders. Nobody required PPM implantation due to new, procedure-related conduction disorders. Deep sternal wound infections requiring reopening of the sternum with subsequent vacuum-assisted closure and rewiring occurred in two patients from the INSPIRIS group and one patient from the ME group. No postoperative endocarditis (infection of the valve prosthesis) was observed.
The comparison of the postoperative hemodynamic results of the two prostheses regarding their different sizes (for preoperative stenotic valves) showed significantly lower mean gradients in favor of 21 and 25, reduced flow acceleration in favor of 25 and increased permeability indices in favor of all small and medium INSPIRIS compared to ME (