Multicenter, propensity-weighted comparison of stented, rapid-deployment and new-generation aortic valves.

Background: Conventional stented, rapid deployment and new-generation stented valves are now available for surgical aortic valve replacement (SAVR). New-generation devices feature advanced tissue treatment for theoretical prolonged durability and a new stent design able to expand in case of future transcatheter Valve-in-Valve. Aim of this retrospective, multicenter, propensity-weighted study was to compare early clinical and hemodynamic outcomes of these three different bioprostheses. Methods: We analyzed data of 2589 patients from two national multicenter registries and one Institutional database. Study devices were Magna Ease, Intuity/Intuity Elite and Inspiris Resilia (Edwards Lifesciences, Irvine, CA, USA) and were implanted in 296 (11.4 %), 1688 (65.2 %) and 605 (23.4 %) patients, respectively. A propensity score weighting approach was employed. Results: In isolated SAVR, aortic cross clamp (ACC) time was shorter for Intuity (Magna Ease: 87, Intuity: 55, Inspiris: 70 min; Magna Ease vs. Intuity: p < 0.001; Inspiris vs. Intuity: p < 0.001). Overall mortality was 2 %, 1.7 % and 0.5 % in Magna Ease, Intuity and Inspiris groups, respectively (Magna Ease vs. Intuity: p = 0.476; Inspiris vs. Intuity: p = 0.395); permanent pace-maker implantation rate was lower for Inspiris (Magna Ease: 6 %, Intuity: 6 %, Inspiris: 2 %; Magna Ease vs. Intuity: p = 0.679; Inspiris vs. Intuity: p < 0.001). Median mean gradients were 13, 10 and 10 mmHg for Magna Ease, Intuity and Inspiris, respectively (Magna Ease vs. Intuity: p < 0.001; Inspiris vs. Intuity: p = 0.13). Conclusions: All study devices provide excellent early clinical and hemodynamic outcomes. Inspiris shows low rates of permanent pace-maker implantation and its transaortic gradients are similar to rapid-deployment valves and lower than Magna Ease.

Cerebrovascular Events in Patients Undergoing Transfemoral Transcatheter Aortic Valve Implantation: A Pooled Patient-Level Study.

BACKGROUND: Cerebrovascular events remain one of the most devastating complications of transcatheter aortic valve implantation (TAVI). Data from real-world contemporary cohorts on longitudinal trends and outcomes remain limited. The aim of this study was to assess incidence, temporal trends, predictors, and outcomes of cerebrovascular events following transfemoral TAVI. METHODS AND RESULTS: The CENTER2 (Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Implantation With Balloon-Expandable Valves Versus Self-Expandable Valves 2) study includes patients undergoing TAVI between 2007 and 2022. The database contains pooled patient-level data from 10 clinical studies. A total of 24 305 patients underwent transfemoral TAVI (mean age 81.5±6.7 years, 56% women, median Society of Thoracic Surgeon Predicted Risk of Mortality 4.9% [3.1%-8.5%]). Of these patients, 2.2% (n=534) experienced stroke in the first 30 days after TAVI, and 40 (0.4%) had a transient ischemic attack. Stroke rates remained stable during the treatment period (2007-2010: 2.1%, 2011-2014: 2.5%, 2015-2018: 2.1%, 2019-2022: 2.1%; Ptrend=0.28). Moreover, 30-day cerebrovascular event rates were similar across Society of Thoracic Surgeon Predicted Risk of Mortality risk categories: 2.1% in low-risk, 2.6% in intermediate-risk, and 2.5% in high-risk patients (P=0.21). Mortality was higher in patients with 30-day stroke than without at 30 days (20.3% versus 4.7%; odds ratio, 5.1 [95% CI, 4.1-6.5]; P<0.001) and at 1 year (44.1% versus 15.0%; hazard ratio, 3.5 [95% CI, 3.0-4.2]; P<0.001). One-year mortality rates for stroke did not decline over time (2007-2010: 46.9%, 2011-2014: 46.0%, 2015-2018: 43.0%, 2019-2022: 39.1%; Ptrend=0.32). At 1 year, 7.0% of patients undergoing TAVI had a stroke. CONCLUSIONS: In 24 305 patients who underwent transfemoral TAVI, 30-day cerebrovascular event incidence remained ≈ 2.2% between 2007 and 2022. Thirty-day stroke rates were similar throughout Society of Thoracic Surgeon Predicted Risk of Mortality risk categories. Mortality rates after stroke remain high. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03588247.

Six-year clinical and computed tomography angiography follow-up after Nexus implantation.

Endovascular aortic arch repair (Ar-TEVAR) with single-branch, off-the-shelf Nexus aortic arch system has shown promising early and 3-year outcomes. There is lack of data regarding long-term results of this specific device, particularly regarding patency of supra-aortic bypasses and stability of the connection between the 2 modules. This case report describes 6-year clinical and imaging follow-up of a 74-year-old patient who underwent Ar-TEVAR with Nexus. Over 6 years, the patient experienced minor complications unrelated to the device. The patency of supra-aortic bypasses and integrity of the device's connection were confirmed. Computed tomography angiography constantly showed exclusion of the aneurysm and reduction of the aneurysmal sac. In conclusion, although extended research and broader data are needed, this case provides encouraging evidence of long-term results of Ar-TEVAR with Nexus.

Endovascular aortic arch repair under monitored anaesthesia care: maximizing microinvasiveness.

Patients with aortic arch pathologies after surgery for type-A acute aortic dissection represent a challenging population since open surgery is associated with a non-negligible rate of mortality and complications. Microinvasive endovascular aortic arch repair Arch-Thoracic EndoVascular Aortic Repair (Ar-TEVAR) has shown promising results in high-risk patients. Ar-TEVAR is usually performed under general anaesthesia. We report the case of an 83-year-old man with a history of ascending aorta replacement for type-A acute aortic dissection who was referred for an anastomotic pseudoaneurysm. Ar-TEVAR using an off-the-shelf single-branch aortic arch stent graft was chosen. In order to further minimize procedural invasiveness, monitored anaesthesia care (local anaesthesia with sedation and analgesia) was performed since it provides less stress on the cardiovascular and respiratory systems and overall leads to a faster recovery especially in elderly patients.

A cardiac intimal sarcoma mimicking infective endocarditis.

Primary malignant cardiac tumors are rare and usually misdiagnosed because they can mimic more common intracardiac lesions, therefore, in clinical practice it is important to always consider even uncommon diseases in order to avoid delayed diagnosis and to plan the most appropriate therapeutic strategy in a timely fashion. We report a case of a 73-year-old man with clinical signs and imaging findings (echocardiography) suggesting infective bacterial endocarditis of the mitral valve. However, intraoperative evaluation raised suspicion that the mitral lesions had a different nature. Surgical removal of the mass was performed, and the final correct diagnosis was made through pathologic examination, revealing a mitral valve sarcoma thus allowing for the beginning of specific oncological treatment.

Bleeding in Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement: Incidence, Trends, Clinical Outcomes, and Predictors.

BACKGROUND: Bleeding is one of the most frequent complications in patients undergoing transcatheter aortic valve replacement (TAVR). Importantly, major bleeding is associated with poor clinical outcomes after TAVR. However, large studies on bleeding complications in the contemporary TAVR population are limited. OBJECTIVES: The aim of this study was to assess the incidence, temporal trends, clinical outcomes, and predictors of bleeding in patients undergoing transfemoral TAVR. METHODS: The CENTER2 study is a pooled patient-level database from 10 clinical studies including patients who underwent TAVR between 2007 and 2022. RESULTS: A total of 23,562 patients underwent transfemoral TAVR. The mean age was 81.5 ± 6.7 years, and 56% were women. Major bleeding within the first 30 days was observed in 1,545 patients (6.6%). Minor bleeding was reported in 1,143 patients (4.7%). Rates of major bleeding decreased from 11.5% in 2007-2010 to 5.5% in 2019-2022 (Ptrend < 0.001). Dual antiplatelet therapy was associated with higher major bleeding rates compared with single antiplatelet therapy (12.2% vs 9.1%; OR: 1.40; 95% CI: 1.13-1.72; P = 0.002). Patients with major bleeding had increased mortality risk during the first 30 days (14.1% vs 4.3%; OR: 3.66; 95% CI: 3.11-4.31; P < 0.001) and during 1-year follow-up (27.8% vs 14.5%; HR: 1.50; 95% CI: 1.41-1.59; P < 0.001). Minor bleeding did not affect 1-year mortality risk (16.7% vs 14.5%; HR: 1.11; 95% CI: 0.93-1.32; P = 0.27). Predictors of major bleeding were female sex and peripheral vascular disease. CONCLUSIONS: Bleeding complications remain frequent and important in patients undergoing transfemoral TAVR. Increased mortality risk in major bleeding persists after the initial 30 days. (Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Implantation With Balloon-Expandable Valves Versus Self-Expandable Valves [CENTER]; NCT03588247).

Microinvasive mitral valve repair with transapical mitral neochordae implantation.

Microinvasive cardiac surgery includes procedures performed off-pump, on the beating heart, with limited or absent skin incision, and those that rely on live imaging techniques. Transapical off-pump beating heart neochordae implantation allows the repair of severe mitral valve regurgitation due to leaflet prolapse or flail with live three-dimensional echo guidance. This procedure has shown good results for up to 5 years and can be considered as a valid alternative to conventional surgery in selected patients with high prediction of success based on clinical and anatomical considerations. The aim of this review is to describe the devices, indications, patient screening process, clinical and echocardiographic results, and future perspectives of this procedure.

Impact of Previous Cardiac Operations in Patients Undergoing Surgery for Type A Acute Aortic Dissection. Long-Term Follow Up.

Aim of this multicenter study was to evaluate the impact of reoperative cardiac surgery for type A acute aortic dissection (TAAAD) on early and long-term outcomes. Patients with history of previous cardiac surgery were included in group R while those undergoing first operation where included in group F. Kaplan-Meier analysis was used to evaluate long-term survival in the 2 groups. A total of 1472 patients were included in the analysis. Of these, 85 (5.8%) and 1387 (94.2%) were included in group R and F, respectively. Thirty-day mortality was 24% (20 patients) and 18% (249 patients) in groups R and F, respectively(P = 0.8). Kaplan-Meier survival at 10 and at 20-year was 51.5% and 30.2% in group R and 48% and 32% in group F (P = 0.368). Patients with a history of previous cardiac operations who develop TAAAD can undergo surgery with similar early and long-term outcomes compared to those at their first operation.

First in human neochordae retensioning for recurrence of mitral regurgitation after neochord procedure.

The Neochord procedure is a viable option to treat degenerative mitral valve regurgitation in selected patients. Left ventricle reverse remodeling can cause neochord-relative elongation and reprolapse of the treated leaflet, leading to failure. We present a clinical case of extensive ventricle reverse remodeling after neochord implantation and the first-in-man off-pump surgical retensioning of the previously implanted artificial chords.

Sternal-Sparing Transapical, Beating Heart Mitral Valve Repair in an Adult With Repaired Tetralogy of Fallot.

We present the case of a 60-year-old male patient who underwent tetralogy of Fallot repair at 7 years of age and then developed severe degenerative mitral regurgitation during adulthood. Given the increased surgical risk (obesity, obstructive sleep apnea syndrome, and reoperation), the patient underwent a successful microinvasive mitral valve repair with neochordae implantation. (Level of Difficulty: Advanced.).

Transapical TAVI: Survival, Hemodynamics, Devices and Machine Learning. Lessons Learned After 10-Year Experience.

Aim of this single-center, retrospective study was to assess early and long-term clinical and hemodynamic results of transapical aortic valve implantation (TA-TAVI), and to identify predictors of survival at follow-up. All patients undergoing TA-TAVI for severe aortic valve stenosis at our institution were reviewed. A hybrid approach based on machine-learning techniques was employed to identify survival predictors, using a bagging-decision-tree algorithm and a Random-Forest algorithm, respectively. Two-hundred-thirty-four consecutive patients underwent TA-TAVI (March 2009-May 2019). All cause 30-day mortality was 5.1%. Device success was 95.7%. Median follow-up time was 35.2 months. Kaplan-Meier overall survival rates at 2, 5, and 8 years were 75%, 44%, and 15%, respectively. Structural-valve-deterioration occurred in 25 patients (11.3%) overall. The strongest predictors of survival at follow-up were age, body-mass-index, and ejection fraction. TA-TAVI provided valid early and long-term outcomes. These data support its choice as an optimal alternative access whenever the transfemoral route is not feasible.

Technical tips and clinical experience with the Nexus Endospan arch branch stent-graft.

Aortic arch pathologies are commonly treated by open surgery which is still the gold standard. Patients that are unfit for surgery can be effectively treated mini-invasively with novel endovascular endograft specifically designed for the arch. Endovascular technology has remarkably improved in recent years and is a valid alternative option for the treatment of aortic arch. Available endografts on the market include fenestrated and branched (single, double, or triple). Most endograft designed for the aortic arch are custom-made and production time could be limiting. The aim of this study is to report our experience with the only single branch bi-modular off-the shelf device available on the market specifically designed for aortic arch aneurysms and dissections. We perform endovascular treatment of the arch in a multidisciplinary team together with dedicated anesthesiologist team, interventional cardiologists, and cardiac surgeons. Prior to the implantation of the endograft, a debranching procedure must be made to redirect the blood from brachiocephalic trunk (BCT) to the left common carotid artery and left subclavian artery. A through and through system from the right axillary artery to the femoral artery is required to deploy the main module. The ascending module is delivered over an extra stiff guidewire placed in the left ventricle. Molding of the endografts is performed with kissing balloon in rapid pacing. We performed 8 cases. Six of them came to our attention for residual dissection and has already been treated with ascending aorta replacement. Mean aortic diameter was 63 mm. All patients required complete debranching of the supra-aortic vessel and received a right common carotid -left subclavian artery bypass with reimplantation of the left common carotid artery on the graft. Timing of the debranching was a few days before the endovascular procedure in 76% of cases. Technical success of the endovascular intervention occurred in 100% of cases. In 2 cases the target supra-aortic trunk for the deployment of the main module BCT branch was the left subclavian artery with no adverse event related to this variation. No intraoperative adjunctive maneuvers have been registered, left subclavian artery have been embolized during the procedure in 5 cases. No access complications have been reported. We experienced 1 case of major stroke with permanent neurological impairments that lead to worsening of clinical condition and death at 6 months. No cardiological adverse event have been registered. Two cases of type 2 endoleak have been reported and required reintervention with embolization of the LSA. At 1 year follow-up no aorta-related adverse event has been reported. The use of this off-the-shelf device for the treatment of aortic arch pathologies requiring total debranching of the supra-aortic vessels seems to be safe and effective. Preliminary results are promising despite available data are insufficient and further data collection is mandatory.

A journey from resect to respect to restore: aiming at optimal physiological surgical mitral valve repair.

The concept of 'repairing' a degenerated mitral valve in order to restore the native competence means achieving the best physiological result coupled with the least invasive approach: this represents an interesting challenge for cardiac surgeons. The evolution of cardiac surgery through the years has involved techniques and technologies in every field of interest. From 'resect', to 'respect', to 'restore': the micro-invasive approach based on Neochord implant implies a transapical beating heart surgery which is based on the concept of implanting artificial chordae, preserving the physiological dynamics of the mitral annulus and avoiding the disadvantages of cardiopulmonary bypass and cardioplegic arrest of the heart.

Propensity-Weighted Comparison of Conventional Stented and Rapid-Deployment Aortic Bioprostheses.

Aim of this study was to compare early clinical and hemodynamic outcomes of Intuity and ME bioprostheses. A propensity score weighting approach was performed. Preoperative variables were defined according to EuroSCORE criteria and postoperative complications according to VARC-2 definitions. We evaluated 375 patients who underwent SAVR with the 2 study devices. Intuity and ME were implanted in 252 (67.2%) and in 123 (32.8%) patients, respectively. There were no differences in terms of postoperative complications, including mortality (1% in each group; OR 0.46[0.05;4.21]). The incidence of pace-maker implantation was 6% and 5% in Intuity and ME groups, respectively (OR 0.53[0.27;1.07]). Intuity showed significantly lower gradients (Median mean gradients: 9mmHg vs 14mmHg, P<0.001), larger effective orifice area index (1.13cm2/m2 vs 1cm2/m2, P=0.007) and lower incidence of patient-prosthesis mismatch (7.1% vs 22.8%, P=0.006). The RD Intuity provides similar early clinical outcomes but shows significantly better hemodynamic performance compared to the ME valve.

Outcomes of transapical mitral valve repair with neochordae implantation.

OBJECTIVE: Transapical off-pump beating-heart neochord implantation (NC) has shown encouraging early results in patients with degenerative mitral regurgitation. The aim of this study was to evaluate clinical and echocardiographic 5-year outcomes of patients who underwent NC. METHODS: All patients who underwent NC at our institution from November 2013 to March 2016 were included. Indications were severe symptomatic degenerative mitral regurgitation due to leaflet prolapse/flail. Patients were classified as having favorable anatomy (FA) and unfavorable anatomy (UA) on the basis of the extent and severity of mitral valve disease. All patients underwent clinical and echocardiographic follow-up at 1, 3, 6, and 12 months, and annually thereafter. Data were prospectively collected and retrospectively analyzed. Outcomes were on the basis of the Mitral Valve Academic Research Consortium guidelines. RESULTS: One hundred consecutive patients were included in the analysis (FA: 81%; UA: 19%). Median age was 66 years (interquartile range, 58-76) and median European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was 1.4% (interquartile range, 0.7-2.3). Technical and procedural success were 98% and 94%, respectively. Thirty-day mortality was 2%. Device success was 94%, 92%, and 78%, at 30 days, 1-year, and 5 years, respectively. Patient success at 1 year was 92%. Median follow-up was 5.1 years. At 5 years, overall survival was 83% with no difference between FA and UA patients. Cumulative incidence of severe mitral regurgitation recurrence at 5 years was 14% (95% CI, 6.5%-22.8%) in FA patients and 63% (95% CI, 39.7%-86.2%) in UA patients, respectively (P < .001). Patients with FA compared with UA had a lower incidence of reintervention (14.7% vs 43.4%; P < .001). CONCLUSIONS: Transapical off-pump beating heart NC might represent an acceptable option in patients with degenerative mitral valve disease and FA.

NEXUS Arch: A Multicenter Study Evaluating the Initial Experience With a Novel Aortic Arch Stent Graft System.

OBJECTIVE: To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. SUMMARY BACKGROUND DATA: The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. METHODS: Patients underwent transcatheter aortic arch repair with a single branch, 2 stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the 2 stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk, and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid-carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through 1 year. Survival analysis used the Kaplan-Meier method. RESULTS: Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients, while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5 (17.8%) had combined or other pathologies. At 1 month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all nondisabling), and combined mortality/stroke rate was 10.7%. One-year mortality was 10.7%, without device or aneurysm-related death. Two patients (7.1%) reported stroke or transient ischemic attack at 1 year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were 3 patients (10.7%) that had device-related unplanned reinterventions through 1 year. CONCLUSIONS: The NEXUS Aortic Arch Stent Graft System, a novel single branch, 2 stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent 1 year safety and performance.

Three-year follow-up of aortic arch endovascular stent grafting with the Nexus device: results from a prospective multicentre study.

OBJECTIVES: Endovascular aortic arch stent grafting with branched devices has shown initial promising results. The aim of this prospective, multicentre study was to evaluate 3-year outcomes of aortic arch stent grafting with NEXUS® Aortic Arch Stent Graft System (Nexus), a single-branch, bi-modular, off-the-shelf aortic arch stent graft system in high-risk patients. METHODS: Patients treated with Nexus, either under the feasibility clinical study or as compassionate use procedures in 5 centres, were included in this study. The primary end point was overall survival. The secondary end points included the incidence of procedure-related unplanned intervention, stroke, paraplegia and endoleak. Clinical and radiologic follow-up was performed at each study site at 30 days, 6 months and on a yearly basis thereafter up to 3 years postoperatively. RESULTS: We analysed data from a total of 28 patients. The overall median follow-up was 1132 (interquartile range: 809-1537). There were no device or procedure-related deaths between 1 and 3 years. Overall survival at 1 and 3 years was 89% and 71%, respectively. The cumulative incidence of unplanned reintervention at 1 and 3 years was 11% and 29%, respectively. There were no reports of stroke, paraplegia, aneurysm rupture, myocardial infarction or new aortic valve insufficiency. In this study's 1-3 year follow-up period, 1 type Ib (4%), 1 type II (4%) and 2 type III (8%; between Nexus' distal end and Thoracic endovascular aortic repair (TEVAR) extensions) endoleak were detected. CONCLUSIONS: Endovascular aortic arch exclusion with the single-branch, off-the-shelf Nexus system provides promising clinical and radiologic results at 3-year follow-up in a high-risk patient cohort.

Diabetes mellitus in transfemoral transcatheter aortic valve implantation: a propensity matched analysis.

BACKGROUND: Diabetes Mellitus (DM) affects a third of patients with symptomatic severe aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI). DM is a well-known risk factor for cardiac surgery, but its prognostic impact in TAVI patients remains controversial. This study aimed to evaluate outcomes in diabetic patients undergoing TAVI. METHODS: This multicentre registry includes data of > 12,000 patients undergoing transfemoral TAVI. We assessed baseline patient characteristics and clinical outcomes in patients with DM and without DM. Clinical outcomes were defined by the second valve academic research consortium. Propensity score matching was applied to minimize potential confounding. RESULTS: Of the 11,440 patients included, 31% (n = 3550) had DM and 69% (n = 7890) did not have DM. Diabetic patients were younger but had an overall worse cardiovascular risk profile than non-diabetic patients. All-cause mortality rates were comparable at 30 days (4.5% vs. 4.9%, RR 0.9, 95%CI 0.8-1.1, p = 0.43) and at one year (17.5% vs. 17.4%, RR 1.0, 95%CI 0.9-1.1, p = 0.86) in the unmatched population. Propensity score matching obtained 3281 patient-pairs. Also in the matched population, mortality rates were comparable at 30 days (4.7% vs. 4.3%, RR 1.1, 95%CI 0.9-1.4, p = 0.38) and one year (17.3% vs. 16.2%, RR 1.1, 95%CI 0.9-1.2, p = 0.37). Other clinical outcomes including stroke, major bleeding, myocardial infarction and permanent pacemaker implantation, were comparable between patients with DM and without DM. Insulin treated diabetics (n = 314) showed a trend to higher mortality compared with non-insulin treated diabetics (n = 701, Hazard Ratio 1.5, 95%CI 0.9-2.3, p = 0.08). EuroSCORE II was the most accurate risk score and underestimated 30-day mortality with an observed-expected ratio of 1.15 in DM patients, STS-PROM overestimated actual mortality with a ratio of 0.77 and Logistic EuroSCORE with 0.35. CONCLUSION: DM was not associated with mortality during the first year after TAVI. DM patients undergoing TAVI had low rates of mortality and other adverse clinical outcomes, comparable to non-DM TAVI patients. Our results underscore the safety of TAVI treatment in DM patients. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov (NCT03588247).