The Role of Telocytes and Telocyte-Derived Exosomes in the Development of Thoracic Aortic Aneurysm.

A hallmark of thoracic aortic aneurysms (TAA) is the degenerative remodeling of aortic wall, which leads to progressive aortic dilatation and resulting in an increased risk for aortic dissection or rupture. Telocytes (TCs), a distinct type of interstitial cells described in many tissues and organs, were recently observed in the aortic wall, and studies showed the potential regulation of smooth muscle cell (SMC) homeostasis by TC-released shed vesicles. The purpose of the present work was to study the functions of TCs in medial degeneration of TAA. During aneurysmal formation an increase of aortic TCs was identified in human surgical specimens of TAA-patients, compared to healthy thoracic aortic (HTA)-tissue. We found the presence of epithelial progenitor cells in the adventitial layer, which showed increased infiltration in TAA samples. For functional analysis, HTA- and TAA-telocytes were isolated, characterized, and compared by their protein levels, mRNA- and miRNA-expression profiles. We detected TC and TC-released exosomes near SMCs. TAA-TC-exosomes showed a significant increase of the SMC-related dedifferentiation markers KLF-4-, VEGF-A-, and PDGF-A-protein levels, as well as miRNA-expression levels of miR-146a, miR-221 and miR-222. SMCs treated with TAA-TC-exosomes developed a dedifferentiation-phenotype. In conclusion, the study shows for the first time that TCs are involved in development of TAA and could play a crucial role in SMC phenotype switching by release of extracellular vesicles.

Impacts of Telomeric Length, Chronic Hypoxia, Senescence, and Senescence-Associated Secretory Phenotype on the Development of Thoracic Aortic Aneurysm.

Thoracic aortic aneurysm (TAA) is an age-related and life-threatening vascular disease. Telomere shortening is a predictor of age-related diseases, and its progression is associated with premature vascular disease. The aim of the present work was to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of TAA. We analyzed healthy and aortic aneurysm specimens (215 samples) for telomere length (TL), chronic DNA damage, and resulting changes in cellular homeostasis, focusing on senescence and apoptosis. Compared with healthy thoracic aorta (HTA), patients with tricuspid aortic valve (TAV) showed telomere shortening with increasing TAA size, in contrast to genetically predisposed bicuspid aortic valve (BAV). In addition, TL was associated with chronic hypoxia and telomeric DNA damage and with the induction of senescence-associated secretory phenotype (SASP). TAA-TAV specimens showed a significant difference in SASP-marker expression of IL-6, NF-κB, mTOR, and cell-cycle regulators (γH2AX, Rb, p53, p21), compared to HTA and TAA-BAV. Furthermore, we observed an increase in CD163+ macrophages and a correlation between hypoxic DNA damage and the number of aortic telocytes. We conclude that chronic hypoxia is associated with telomeric DNA damage and the induction of SASP in a diseased aortic wall, promising a new therapeutic target.

The Iliofemoral tortuosity score predicts access and bleeding complications during transfemoral transcatheter aortic valve replacement: DataData from the VIenna Cardio Thoracic aOrtic valve registrY (VICTORY).

BACKGROUND: Arterial tortuosity is linked to a higher risk of adverse clinical events after transfemoral transcatheter aortic valve replacement (TF-TAVR). Currently, there are no assessment tools that can quantify this variable in three-dimensional space. This study investigated the impact of novel scoring methods of iliofemoral tortuosity on access and bleeding complications after TF-TAVR. METHODS: The main access vessel was assessed between the aortoiliacal and femoral bifurcation in preoperative multislice computed tomography scans of 240 consecutive patients undergoing TF-TAVR. Tortuosity was assessed by three methods: largest single angle, sum of all angles, and iliofemoral tortuosity (IFT) score [((true vessel length/ideal vessel length)-1)*100]. The primary study endpoint was a composite of access and bleeding complications. The secondary study endpoints were 30-day mortality and long-term survival. RESULTS: Among 240 patients, only the IFT score demonstrated a good positive correlation with the composite primary endpoint of access and bleeding complications (P = 0.031). A higher incidence of access and bleeding complications was found in patients with a higher IFT score (56 [36.8%] vs 17 [19.3%]; P = 0.003). In a multivariate logistic regression analysis, only the IFT score was a significant predictor of the primary endpoint (OR: 2.11; 95% CI: 1.09-4.05; P = 0.026). CONCLUSION: Vascular tortuosity is an underestimated risk factor during TF-TAVR. The IFT score is a valuable tool in risk stratification before TF-TAVR, predicting periprocedural access and bleeding complications.

The impact of antiplatelet and antithrombotic regimen after TAVI: Data from the VIenna CardioThOracic Aortic Valve RegistrY (VICTORY).

BACKGROUND: We compared the outcomes and adverse events of TAVI patients based on the discharge and long-term antiplatelet or anticoagulant treatment regimens (single antiplatelet [SAPT] vs. dual antiplatelet [DAPT] vs. anticoagulation [OAC] vs. no treatment [NT]). METHODS: The outcome of 532 consecutive patients treated with TAVI was evaluated. As the main study endpoint, the 1-year all-cause mortality was chosen to compare the different discharge treatment regimens and the 3-year all-cause mortality to compare the different long-term treatment regimens. The secondary endpoints were adverse events as defined by the Valve Academic Research Consortium-II. RESULTS: One-year survival after TAVI was highest amongst patients treated with DAPT compared to SAPT (P < .001) and OAC (P = .003), and patients under OAC demonstrated improved 1-year survival over patients treated with SAPT (P = .006). Furthermore, there was a strong trend towards improved 3-year survival for patients in the OAC cohort treated with non-vitamin K antagonists compared to vitamin K antagonists (N-VKAs vs. VKA; log-rank P = .056). CONCLUSION: The lower all-cause mortality for DAPT within the first year and N-VKAs over VKA within the first 3 years warrant considerable attention in further recommendations of antithrombotic and anticoagulation regimens after TAVI.

The use of semi-compliant versus non-compliant balloon systems for predilatation during the implantation of self-expandable transcatheter aortic valves: Data from the VIenna CardioThOracic Aortic Valve RegistrY (VICTORY).

BACKGROUND: This study aimed to evaluate the differences in outcome arising from the use of semi-compliant (SCB) versus non-compliant balloon (NCB) systems for predilatation during self-expanding transcatheter aortic valve replacement (TAVR). METHODS: 251 TAVR procedures with the implantation of self-expanding valves after predilatation were analyzed. SCB systems were used in 166 and NCB systems in 85 patients. The primary endpoint was defined as device success, a composite endpoint comprising the absence of procedural mortality, correct valve positioning, adequate valve performance and the absence of more than a mild paravalvular leak. The secondary endpoints were chosen in accordance with the valve academic research consortium (VARC-2) endpoint definitions. RESULTS: No significant differences were observed with regard to procedural device success between the SCB- and NCB cohort (SCB: 142 [85.5%%] vs. NCB: 77 [90.6%]; P = .257). There was a notable difference between the rates of conversion to open surgery and the postdilatation rate, both of which were higher for the NCB group (SCB: 1 [0.6%] vs. NCB: 4 [5.1%]; P = .042; SCB: 30 [18.1%] vs. NCB: 34 [40%]; P < .001). In a multivariate logistic regression analysis, the use of semi-compliant balloon systems for predilatation was associated with a lower risk for postdilatation (OR: 0.296; 95% CI: 0.149-0.588) and conversion to open surgery (OR: 0.205; 95% CI: 0.085-0.493; P = .001) but not for device success. CONCLUSION: While the balloon compliance did not affect the procedural mortality, device success or the rate of paravalvular leakage, the use of semi-compliant balloons for predilatation during TAVR should be investigated in larger randomized trials in the light of the lower rates of postdilatation and conversion to open surgery compared to their non-compliant counterparts.

The impact of subclinical congestion on the outcome of patients undergoing transcatheter aortic valve implantation.

BACKGROUND: We investigated the impact of an elevated plasma volume status (PVS) in patients undergoing TAVI on early clinical safety and mortality and assessed the prognostic utility of PVS for outcome prediction. MATERIALS AND METHODS: We retrospectively calculated the PVS in 652 patients undergoing TAVI between 2009 and 2018 at two centres. They were then categorized into two groups depending on their preoperative PVS (PVS ≤-4; n = 257 vs PVS>-4; n = 379). Relative PVS was derived by subtracting calculated ideal (iPVS = c × weight) from actual plasma volume (aPVS = (1 - haematocrit) × (a + (b × weight in kg)). RESULTS: The need for renal replacement therapy (1 (0.4%) vs 17 (4.5%); P = .001), re-operation for noncardiac reasons (9 (3.5%) vs 32 (8.4%); P = .003), re-operation for bleeding (9 (3.5%) vs 27 (7.1%); P = .037) and major bleeding (14 (5.4%) vs 37 (9.8%); P = .033) were significantly higher in patients with a PVS>-4. The composite 30-day early safety endpoint (234 (91.1%) vs 314 (82.8%); P = .002) confirms that an increased preoperative PVS is associated with a worse overall outcome after TAVI. CONCLUSIONS: An elevated PVS (>-4) as a marker for congestion is associated with significantly worse outcome after TAVI and therefore should be incorporated in preprocedural risk stratification.

Impact of COPD on Outcome in Patients Undergoing Transfemoral versus Transapical TAVI.

OBJECTIVE: The purpose of this study was to evaluate the impact of chronic obstructive pulmonary disease (COPD) on clinical outcomes in patients referred for transfemoral (TF) as well as transapical (TA) aortic valve implantation and furthermore to delineate possible advantages of the TF access. METHODS: One thousand eight hundred forty-two patients undergoing transcatheter aortic valve implantation (TAVI) at two study centers were included in the present analysis. The outcome was measured and classified according to Valve Academic Research Consortium-II criteria. Kaplan-Meier estimate was used to assess long-term survival. RESULTS: The present analysis suggests that COPD has limited influence on post-procedural outcome after TAVI. Comparing the TF to TA approach, no significant difference on the impact of COPD on clinical outcomes has been found, except for longer post-procedural ventilation times in COPD patients treated via TA access (p < 0.001). CONCLUSIONS: COPD in patients referred for TAVI procedure was associated with poorer overall long-term survival, thus characterizing a high-risk population for futile treatment; however, the selection of access did not result in a significant difference in most Valve Academic Research Consortium-II-defined clinical outcomes in COPD patients.

A Smart Solution for Solving Acute Angulations during Frozen Elephant Trunk Implantation.

Acute angulations of native thoracic aortic segments affect treatment strategies for acute and chronic thoracic aortic pathology. These angulations might present an issue not only in segments where thoracic endovascular aortic repair is planned but also in segments where open repair is intended. Consequently, clinical scenarios arise where there is need for adapting strategies in frozen elephant trunk implantation. In this conceptual report, we do describe a technical modification to solve this issue.

E-vita OPEN NEO in the treatment of acute or chronic aortic pathologies: first interim results of the NEOS study.

OBJECTIVES: The aim of this multicentre study was to demonstrate the safety and clinical performance of E-vita OPEN NEO Stent Graft System (Artivion, Inc.) in the treatment of aneurysm or dissection, both acute and chronic, in the ascending aorta, aortic arch and descending thoracic aorta. METHODS: In this observational study of 12 centres performed in Europe and in Asia patients were enrolled between December 2020 and March 2022. All patients underwent frozen elephant trunk using E-vita OPEN NEO Stent Graft System. Primary end point was the rate of all-cause mortality at 30 days and secondary end points included further clinical and safety data are reported up to 3-6 months postoperatively. RESULTS: A total of 100 patients (66.7% male; mean age, 57.7 years) were enrolled at 12 sites. A total of 99 patients underwent surgery using the E-vita OPEN NEO for acute or subacute type A aortic dissection (n = 37), chronic type A aortic dissection (n = 33) or thoracic aortic aneurysm (n = 29), while 1 patient did not undergo surgery. Device technical success at 24 h was achieved in 97.0%. At discharge, new disabling stroke occurred in 4.4%, while new paraplegia and new paraparesis was reported in 2.2% and 2.2%, respectively. Renal failure requiring permanent (>90 days) dialysis or hemofiltration at discharge was observed in 3.3% of patients. Between discharge and the 3-6 months visit, no patients experienced new disabling stroke, new paraplegia or new paraparesis. The 30-day mortality was 5.1% and the estimated 6-month survival rate was 91.6% (standard deviation: 2.9). CONCLUSIONS: Total arch replacement with the E-vita OPEN NEO can be performed with excellent results in both the acute and chronic setting. This indicates that E-vita OPEN NEO can be used safely, including in the setting of acute type A aortic dissection.

Consensus statement-graft treatment in cardiovascular bypass graft surgery.

Coronary artery bypass grafting (CABG) is and continues to be the preferred revascularization strategy in patients with multivessel disease. Graft selection has been shown to influence the outcomes following CABG. During the last almost 60 years saphenous vein grafts (SVG) together with the internal mammary artery have become the standard of care for patients undergoing CABG surgery. While there is little doubt about the benefits, the patency rates are constantly under debate. Despite its acknowledged limitations in terms of long-term patency due to intimal hyperplasia, the saphenous vein is still the most often used graft. Although reendothelialization occurs early postoperatively, the process of intimal hyperplasia remains irreversible. This is due in part to the persistence of high shear forces, the chronic localized inflammatory response, and the partial dysfunctionality of the regenerated endothelium. "No-Touch" harvesting techniques, specific storage solutions, pressure controlled graft flushing and external stenting are important and established methods aiming to overcome the process of intimal hyperplasia at different time levels. Still despite the known evidence these methods are not standard everywhere. The use of arterial grafts is another strategy to address the inferior SVG patency rates and to perform CABG with total arterial revascularization. Composite grafting, pharmacological agents as well as latest minimal invasive techniques aim in the same direction. To give guide and set standards all graft related topics for CABG are presented in this expert opinion document on graft treatment.

Global and local stiffening of ex vivo-perfused stented human thoracic aortas: A mock circulation study.

The effects of thoracic endovascular repair (TEVAR) on the biomechanical properties of aortic tissue have not been adequately studied. Understanding these features is important for the management of endograft-triggered complications of a biomechanical nature. This study aims to examine how stent-graft implantation affects the elastomechanical behavior of the aorta. Non-pathological human thoracic aortas (n=10) were subjected to long-standing perfusion (8h) within a mock circulation loop under physiological conditions. To quantify compliance and its mismatch in the test periods without and with a stent, the aortic pressure and the proximal cyclic circumferential displacement were measured. After perfusion, biaxial tension tests (stress-stretch) were carried out to examine the stiffness profiles between non-stented and stented tissue, followed by a histological assessment. Experimental evidence shows: (i) a significant reduction in aortic distensibility after TEVAR, indicating aortic stiffening and compliance mismatch, (ii) a stiffer behavior of the stented samples compared to the non-stented samples with an earlier entry into the nonlinear part of the stress-stretch curve and (iii) strut-induced histological remodeling of the aortic wall. The biomechanical and histological comparison of the non-stented and stented aortas provides new insights into the interaction between the stent-graft and the aortic wall. The knowledge gained could refine the stent-graft design to minimize the stent-induced impacts on the aortic wall and the resulting complications. STATEMENT OF SIGNIFICANCE: Stent-related cardiovascular complications occur the moment the stent-graft expands on the human aortic wall. Clinicians base their diagnosis on the anatomical morphology of CT scans while neglecting the endograft-triggered biomechanical events that compromise aortic compliance and wall mechanotransduction. Experimental replication of endovascular repair in cadaver aortas within a mock circulation loop may have a catalytic effect on biomechanical and histological findings without an ethical barrier. Demonstrating interactions between the stent and the wall can help clinicians make a broader diagnosis such as ECG-triggered oversizing and stent-graft characteristics based on patient-specific anatomical location and age. In addition, the results can be used to optimize towards more aortophilic stent grafts.

Impact of CytoSorb® on interleukin-6 in cardiac surgery.

Objective: Cardiac surgery is known to activate a cascade of inflammatory mediators leading to a systemic inflammatory response. Hemadsorption (HA) devices such as CytoSorb® have been postulated to mitigate an overshooting immune response, which is associated with increased morbidity and mortality, and thus improve outcome. We aimed to investigate the effect of CytoSorb® on interleukin (IL)-6 levels in patients undergoing complex cardiac surgery in comparison to a control group. Methods: A total of 56 patients (28 CytoSorb®, 28 control) undergoing acute and elective cardiac surgery between January 2020 and February 2021 at the Department of Cardiac and Vascular Surgery, Clinic Floridsdorf, Vienna, were retrospectively analyzed. The primary endpoint was the difference in IL-6 levels between the CytoSorb® and control group. Secondary endpoint was periprocedural mortality. Results: CytoSorb®, installed in the bypass circuit, had no significant effect on IL-6 levels. IL-6 peaked on the first postoperative day (HA: 775.3 ± 838.4 vs. control: 855.5 ± 1,052.9 pg/ml, p = 0.856). In total, three patients died in the HA group, none in the control (logistic regression model, p = 0.996). Patients with an increased Euroscore II of 7 or more showed a reduced IL-6 response compared to patients with an Euroscore II below 7 (178.3 ± 63.1 pg/ml vs. 908.6 ± 972.6 pg/ml, p-value = 0.00306). Conclusions: No significant reduction of IL-6 levels or periprocedural mortality through intraoperative HA with CytoSorb® in patients undergoing cardiac surgery was observed. However, this study was able to show a reduced immunologic response in patients with a high Euroscore II. The routine application of CytoSorb® in cardiac surgery to reduce inflammatory mediators has to be scrutinized in future prospective randomized studies.

Long-Term Results with 187 Frozen Elephant Trunk Procedures.

The frozen elephant trunk (FET) technique is an established therapeutic option in the treatment of complex aortic diseases. We report our long-term clinical outcomes after FET repair. A total of 187 consecutive patients underwent FET repair at our department between 8/2005 and 3/2023. Indications included acute and chronic aortic dissections and thoracic aneurysms. Endpoints included operative morbidity and mortality, long-term survival, and the need for reinterventions. Operative mortality, spinal cord injury and permanent stroke rates were: 9.6%, 2.7% and 10.2%, respectively. At five years, overall survival was 69.9 ± 3.9% and freedom from aortic-related death was 82.5 ± 3.0%, whereas at ten years, overall survival was 53.0 ± 5.5% and freedom from aortic-related death was 75.8 ± 4.8%. Sixty-one reinterventions on the thoracic aorta were necessary. Freedom from secondary interventions at ten years was 44.7 ± 6.4% overall (63.1 ± 10.0% for acute dissections, 40.8 ± 10.3% for chronic dissections and 28.9 ± 13.1% for aneurysms, respectively). The high reintervention rate for chronic dissections and for aneurysms is related to the pre-existing aortic pathology. Late aortic growth of untreated segments with potentially fatal outcome occurs even after ten years, so careful annual follow-up is mandatory in this patient cohort.

Durability of bioprosthetic aortic valve replacement in patients under the age of 60 years - 1-year follow-up from the prospective INDURE registry.

OBJECTIVES: We report 1-year safety and clinical outcomes in patients <60 years undergoing bioprosthetic surgical aortic valve intervention. METHODS: The INSPIRIS RESILIA Durability Registry is a prospective, multicentre registry to assess clinical outcomes of patients <60 years. Patients with planned SAVR with or without concomitant replacement of the ascending aorta and/or coronary bypass surgery were included. Time-related valve safety, haemodynamic performance and quality of life (QoL) at 1 year were assessed. RESULTS: A total of 421 patients were documented with a mean age of 53.5 years, 76.5% being male and 27.2% in NYHA class III/IV. Outcomes within 30 days included cardiovascular-related mortality (0.7%), time-related valve safety (VARC-2; 5.8%), thromboembolic events (1.7%), valve-related life-threatening bleeding (VARC-2; 4.3%) and permanent pacemaker implantation (3.8%). QoL was significantly increased at 6 months and sustained at 1 year. Freedom from all-cause mortality at 1 year was 98.3% (95% confidence interval 97.1; 99.6) and 81.8% were NYHA I versus 21.9% at baseline. No patient developed structural valve deterioration stage 3 (VARC-3). The mean aortic pressure gradient was 12.6 mmHg at 1 year and the effective orifice area was 1.9 cm2. CONCLUSIONS: The 1-year data from the INSPIRIS RESILIA valve demonstrate good safety and excellent haemodynamic performance as well as an early QoL improvement. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03666741.

Graft preservation confers myocardial protection during coronary artery bypass grafting.

Background: During on-pump coronary artery bypass grafting (ONCAB), graft flushing for distal anastomoses testing also perfuses the downstream myocardium. This single-center retrospective study evaluated the impact of specific preservation solutions on myocardial protection during ONCAB. Materials and methods: Between July 2019 and March 2020 either DuraGraft (DG) or 0.9% Saline/Biseko (SB) was applied to 272 ONCAB. Overall, 166 patients were propensity-matched into two groups. Cardiac enzymes [high-sensitive Troponin I (hs-TnI) and creatine kinase (CK)] were evaluated 7 days post-surgery. Results: Post-surgery, hs-TnI values were significantly lower from 3 to 6 h (h) up to 4 days in the DG group: 3-6 h: 4,034 ng/L [IQR 1,853-8,654] vs. 5,532 ng/L [IQR 3,633-8,862], p = 0.05; 12-24 h: 2,420 ng/L [IQR 1,408-5,782] vs. 4,166 [IQR 2,052-8,624], p < 0.01; 2 days: 1,095 ng/L [IQR 479-2,311] vs. 1,564 ng/L [IQR 659-5,057], p = 0.02 and at 4 days: 488 ng/L [IQR 232-1,061] vs. 745 ng/L [IQR 319-1,820], p = 0.03. The maximum value: 4,151 ng/L [IQR 2,056-8,621] vs. 6,349 ng/L [IQR 4,061-12,664], p < 0.01 and the median area under the curve (AUC): 6,146 ng/L/24 h [IQR 3,121-13,248] vs. 10,735 ng/L/24 h [IQR 4,859-21,484], p = 0.02 were lower in the DG group. CK values were not significantly different between groups: maximum value 690 [IQR 417-947] vs. 631 [464-979], p = 0.61 and AUC 1,986 [1,226-2,899] vs. 2,081 [1,311-3,063], p = 0.37. Conclusion: Repeated graft flushing with DG resulted in lower Troponin values post-surgery suggesting enhanced myocardial protection compared to SB. Additional studies are warranted to further assess the myocardial protection properties of DG.

The Technological Basis of a Balloon-Expandable TAVR System: Non-occlusive Deployment, Anchorage in the Absence of Calcification and Polymer Leaflets.

Leaflet durability and costs restrict contemporary trans-catheter aortic valve replacement (TAVR) largely to elderly patients in affluent countries. TAVR that are easily deployable, avoid secondary procedures and are also suitable for younger patients and non-calcific aortic regurgitation (AR) would significantly expand their global reach. Recognizing the reduced need for post-implantation pacemakers in balloon-expandable (BE) TAVR and the recent advances with potentially superior leaflet materials, a trans-catheter BE-system was developed that allows tactile, non-occlusive deployment without rapid pacing, direct attachment of both bioprosthetic and polymer leaflets onto a shape-stabilized scallop and anchorage achieved by plastic deformation even in the absence of calcification. Three sizes were developed from nickel-cobalt-chromium MP35N alloy tubes: Small/23 mm, Medium/26 mm and Large/29 mm. Crimp-diameters of valves with both bioprosthetic (sandwich-crosslinked decellularized pericardium) and polymer leaflets (triblock polyurethane combining siloxane and carbonate segments) match those of modern clinically used BE TAVR. Balloon expansion favors the wing-structures of the stent thereby creating supra-annular anchors whose diameter exceeds the outer diameter at the waist level by a quarter. In the pulse duplicator, polymer and bioprosthetic TAVR showed equivalent fluid dynamics with excellent EOA, pressure gradients and regurgitation volumes. Post-deployment fatigue resistance surpassed ISO requirements. The radial force of the helical deployment balloon at different filling pressures resulted in a fully developed anchorage profile of the valves from two thirds of their maximum deployment diameter onwards. By combining a unique balloon-expandable TAVR system that also caters for non-calcific AR with polymer leaflets, a powerful, potentially disruptive technology for heart valve disease has been incorporated into a TAVR that addresses global needs. While fulfilling key prerequisites for expanding the scope of TAVR to the vast number of patients of low- to middle income countries living with rheumatic heart disease the system may eventually also bring hope to patients of high-income countries presently excluded from TAVR for being too young.

Minimally Invasive and Robotic Mitral Valve Surgery: Methods and Outcomes in a 20-Year Review.

In the mid- to late-1990s the cardiac surgery community began to apply limited incisions in mitral valve surgery. Ministernotomies and right-sided minithoracotomies were placed instead of the classic midline sternotomy. Adjunct technology such as videoscopy, advanced peripheral cannulation techniques, procedure specific long shafted surgical instruments, as well as surgical robots became available, and the procedures were refined in a stepwise fashion. In 2021, minimally invasive mitral valve repair is routine at many centers around the globe. We reviewed a total of 50 consecutive patient series published on the topic between 1999 and 2019. Three main versions of minimally invasive mitral valve surgery were applied in 20,539 patients. The surgical methods, their specific results, and the cumulative outcome of less invasive mitral valve surgery published over more than 20 years are reported and an integrated view on what less invasive mitral valve surgery can offer is presented.