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Telocytes (TCs), a novel interstitial cell entity promoting tissue regeneration, have been described in various tissues. Their role in inter‐cellular signalling and tissue remodelling has been reported in almost all human tissues. This study hypothesizes that TC also contributes to tissue remodelling and regeneration of the human thoracic aorta (HTA). The understanding of tissue homeostasis and regenerative potential of the HTA is of high clinical interest as it plays a crucial role in pathogenesis from aortic dilatation to lethal dissection. Therefore, we obtained twenty‐five aortic specimens of heart donors during transplantation. The presence of TCs was detected in different layers of aortic tissue and characterized by immunofluorescence and transmission electron microscopy. Further, we cultivated and isolated TCs in highly differentiated form identified by positive staining for CD34 and c‐kit. Aortic‐derived TC was characterized by the expression of PDGFR‐α, PDGFR‐β, CD29/integrin β‐1 and αSMA and the stem cell markers Nanog and KLF‐4. Moreover, TC exosomes were isolated and characterized for soluble angiogenic factors by Western blot. CD34+/c‐kit+ TCs shed exosomes containing the soluble factors VEGF‐A, KLF‐4 and PDGF‐A. In summary, TC occurs in the aortic wall. Correspondingly, exosomes, derived from aortic TCs, contain vasculogenesis‐relevant proteins. Understanding the regulation of TC‐mediated aortic remodelling may be a crucial step towards designing strategies to promote aortic repair and prevent adverse remodelling.

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.

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.

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.

Introduction: Totally endoscopic coronary artery bypass grafting (TECAB) can only be performed in a reproducible manner using robotic technology. This operation has been developed for more than 20 years seeing three generations of surgical robots. TECAB can be carried out beating heart but also on the arrested heart. Single and multiple grafts can be placed and TECAB can be combined with percutaneous coronary intervention in hybrid procedures.Areas covered: This review outlines indications for the procedure, the surgical technique, and the postoperative care. Intra- and postoperative results as available in the literature are reported. Further areas focus on technological development, training methods, learning curves as well as on cost. Finally, we give an outlook on the potential future of this operation.Expert opinion: Robotic TECAB represents a complex, sophisticated but safe, and over-the-years grown procedure. Even though results seem to be in line with conventional coronary surgery worldwide adoption still has been slow probably due to procedure times, costs and learning curves. Main advantages of TECAB are minimized surgical trauma and subsequent reduction of postoperative healing time. With the current introduction of new robotic devices, a new era of procedure development is on its way.

Endothelial progenitor cells (EPC) may influence the integrity and stability of the vascular endothelium. The association of an altered total EPC number and function with cardiovascular diseases (CVD) and risk factors (CVF) was discussed; however, their role and applicability as biomarkers for clinical purposes have not yet been defined. Endothelial dysfunction is one of the key mechanisms in CVD. The assessment of endothelial dysfunction in vivo remains a major challenge, especially for a clinical evaluation of the need for therapeutic interventions or for primary prevention of CVD. One of the main challenges is the heterogeneity of this particular cell population. Endothelial cells (EC) can become senescent, and the majority of circulating endothelial cells (CEC) show evidence of apoptosis or necrosis. There are a few viable CECs that have properties similar to those of an endothelial progenitor cell. To use EPC levels as a biomarker for vascular function and cumulative cardiovascular risk, a correct definition of their phenotype, as well as an update on the clinical application and practicability of current isolation methods, are an urgent priority.

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

AIMS OF THE STUDY: Minimally invasive extracorporeal circulation (MiECC) is an established alternative to conventional extracorporeal circulation (CECC) in coronary artery bypass graft surgery (CABG), but data on its use in cardiac reoperations are limited. We aimed to analyse perioperative morbidity and mortality in adult patients undergoing reoperations for isolated CABG using either CECC or MiECC circuits at our centre. METHODS AND RESULTS: In a single centre retrospective observational study of all adult patients undergoing cardiac reoperations for isolated CABG between 2004 and 2016, we identified 310 patients, and excluded those who received concomitant cardiac procedures (n = 205). Of the remaining 105 patients, 47 received isolated redo-CABG using MiECC, and 58 received CECC. Propensity score modelling was performed, and inversed probability treatment analysis was used between the treatment groups. Primary endpoint was 30-day all-cause mortality. Secondary endpoints included major adverse cardiac or cerebrovascular events or need for conversion to CECC. Groups were comparable, apart from a higher incidence of NYHA class III or higher in CECC group (33.5% vs 8.6%, p= 0.004). Shorter times for operation, cardiopulmonary bypass and aortic cross-clamp were observed in the MiECC group. The incidence of postoperative atrial fibrillation was significantly lower with MiECC (22.1%, p = 0.012). No significant difference was observed in all-cause 30-day mortality between the MiECC and CECC groups (6.8% vs. 8.3%, p = 0.81). CONCLUSION: We found no difference in overall mortality between CECC and MiECC in patients undergoing reoperation for isolated CABG. Furthermore, we found no indication of differences in most outcomes between extracorporeal circuit types. In the case of redo-CABG, MiECC could provide an alternative strategy.

OBJECTIVES Our goal was to develop a modified frozen elephant trunk (FET) prosthesis with a stented left subclavian artery (LSA) side branch for LSA connection and to perform preclinical testing in a human cadaver model. METHODS We measured aortic diameters, distance between and diameters of supra-aortic vessels and the distance from the LSA offspring to the level of the left vertebral artery offspring in 70 patients. Based on these measurements, a novel FET prosthesis was developed (Cryolife/Jotec, Hechingen, Germany) featuring a stented side branch for an intrathoracic LSA connection. The feasibility and ease of implantation were tested in 2 human cadaver models at the Anatomical Institute of the Medical University Graz. A covered stent graft (Advanta V12™ by Atrium Medical Corp., Hudson, NH, USA) was used for an LSA extension. RESULTS Accurate deployment of the novel FET prosthesis with anatomical orientation of the stented side branch towards the LSA ostium followed by consecutive stent graft deployment was feasible in both cases. Proximalizing the distal anastomosis level from zone 3 to zone 1 not only diminished the complexity of the procedure but substantially facilitated the completion of the distal anastomosis. A 2.5-cm long extension stent graft was sufficient to seal to the LSA and to maintain left vertebral artery patency in both cases. CONCLUSIONS This initial study in human anatomical bodies could demonstrate the feasibility of implanting a newly designed FET prosthesis. This evolution of the FET technique has the potential to substantially ease total aortic arch replacement by proximalization of the distal anastomosis into zone 1 and by shortening spinal and lower body hypothermic circulatory arrest times via a stented side branch to the LSA. This direct connection enables early restoration of systemic perfusion.

Background While transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic valve stenosis, wearable health-monitoring devices are gradually transforming digital patient care. Objective The aim of this study was to develop a simple, efficient, and economical method for preprocedural frailty assessment based on parameters measured by a wearable health-monitoring device. Methods In this prospective study, we analyzed data of 50 consecutive patients with mean (SD) age of 77.5 (5.1) years and a median (IQR) European system for cardiac operative risk evaluation (EuroSCORE) II of 3.3 (4.1) undergoing either transfemoral or transapical TAVR between 2017 and 2018. Every patient was fitted with a wrist-worn health-monitoring device (Garmin Vivosmart 3) for 1 week prior to the procedure. Twenty different parameters were measured, and threshold levels for the 3 most predictive categories (ie, step count, heart rate, and preprocedural stress) were calculated. Patients were assigned 1 point per category for exceeding the cut-off value and were then classified into 4 stages (no, borderline, moderate, and severe frailty). Furthermore, the FItness-tracker assisted Frailty-Assessment Score (FIFA score) was compared with the scores of the preprocedural gait speed category derived from the 6-minute walk test (GSC-6MWT) and the Edmonton Frail Scale classification (EFS-C). The primary study endpoint was hospital mortality. Results The overall preprocedural stress level (P=.02), minutes of high stress per day (P=.02), minutes of rest per day (P=.045), and daily heart rate maximum (P=.048) as single parameters were the strongest predictors of hospital mortality. When comparing the different frailty scores, the FIFA score demonstrated the greatest predictive power for hospital mortality (FIFA area under the curve [AUC] 0.844, CI 0.656-1.000; P=.048; GSC-6MWT AUC 0.671, CI 0.487-0.855; P=.42; EFS-C AUC 0.636, CI 0.254-1.000; P=.44). Conclusions This proof-of-concept study demonstrates the strong predictive performance of the FIFA score compared to that of the conventional frailty assessments.

Background The ideal approach for transfemoral transcatheter aortic valve implantation is still widely debated. The objective of this study was to compare access and bleeding complications of complete percutaneous versus the surgical cut-down approach for transfemoral transcatheter aortic valve implantation. Methods The study included 667 consecutive patients from November 2008 to December 2016, 466 in the percutaneous group and 201 in the cut-down group. There were no significant differences in baseline characteristics between the 2 groups. Primary study endpoints were vascular access site and bleeding complications according to the Valve Academic Research Consortium II criteria. Results Mean procedure time was shorter in the cut-down group: 93.5 ± 22.0 (percutaneous) vs. 69 ± 19 min (cut-down), p Conclusions Surgical cut-down provided controlled access and resulted in fewer access site and bleeding complications. Nonetheless, major access complications were not significantly different between the two cohorts. The two approaches must be seen as complementary techniques. A portfolio containing both techniques is the only way to provide a tailor-made and patient-orientated approach ensuring the safest access based on the individual vessel condition.

The procedure of coronary artery bypass grafting continues to be the "gold standard" for patients with multivessel coronary artery disease and left main stenosis due to favourable long-term and consistent outcomes despite the advent of new generations of stents. But the targeted better long-term outcome of surgical revascularization over percutaneous interventions depends on several variables and aspects; one of them is the choice of conduits used to bypass the stenosed arteries. Coronary artery bypass surgery has been studied and debated for decades and the same applies to the selection of grafts. Current data provide significant benefits for patients who receive full arterial revascularization using both internal thoracic arteries and, if applicable, the radial artery. Unfortunately, the use of multiple arterial grafts is still not performed widely despite the evidence of superiority over multiple saphenous vein grafts that are still the most used grafts in cardiovascular procedures. In this review article, we present current trends and evidences for graft selection and give an overview of controversial data regarding the comparison of the radial artery and saphenous vein. Additionally, few words are spelt on alternative conduits.

Background Simultaneous transapical implantation of transcatheter heart valves in the native mitral and aortic position may be considered as an alternative to surgical valve replacement in high-risk patients presenting with combined valve disease. Case presentation A 59-year-old female with severe aortic stenosis, severe mitral stenosis with mild mitral insufficiency, persistent atrial fibrillation, severe chronic obstructive pulmonary disease and NYHA class of IV was evaluated by our interdisciplinary heart team. Due to the calculated Euroscore II, logistic Euroscore with 10% and 17% a decision was made towards a transapical TAVI approach. The implantation of a Sapien 3 (Edwards Lifesciences) valve in the aortic position was performed and the perioperative TEE showed a good result. The preoperative imaging revealed a narrow LVOT with risk for post interventional left ventricular outflow tract obstruction. Accordingly, it was decided against the use of balloon-expanding valves for the mitral valve position in the interdisciplinary team, as it is not repositionable. Instead, it was decided for the use of a Lotus (Boston Scientific) valve, as it is repositionable and therefore possible to retract in case of LVOT obstruction. In the present case of double valve intervention, the implantation attempt of a fully repositionable transcatheter heart valve into the native mitral annulus resulted in acute LVOT obstruction requiring immediate removal of the device. The patient was extubated and experienced uneventful postoperative recovery. Conclusions The case shows that improved preoperative work-up is necessary for better prediction of significant LVOT obstruction following transcatheter mitral valve implantation. In borderline cases, the use of a fully repositionable device is preferred.

The pathophysiologic side effects of cardiopulmonary bypass have already been identified. Minimally invasive extracorporeal circulation technologies (MiECT) and off-pump coronary artery bypass graft surgery (OPCABG) aim to reduce these problems. This meta-analysis provides a comparison of MiECT and OPCABG in randomized and observational studies. A fully probabilistic, Bayesian approach of primary and secondary endpoints was conducted. MiECT does not give inferior results when compared with OPCABG. However, there is a trend to borderline significantly higher blood loss in this group in randomized controlled trials. The question whether MiECT is equivalent to OPCABG can be answered with the affirmative, but long-term follow-up data are needed to detect any advantage over time.

Performing transcatheter aortic valve implantation in the presence of aneurysmatic aortopathy is widely contraindicated but needs to be taken into account as a bailout strategy in selected patients. Deliberate preoperative assessment of measurements becomes the crucial key element in this context. After meticulous valve selection, retrograde access is obtained through the right subclavian artery additionally serving as a backup arterial cannulation site in case of conversion. Transcatheter aortic valve implantation is then performed through the transapical route. Transcatheter aortic valve implantation in complex aneurysmatic aortic morphology is feasible in highly selected patients after comprehensive preoperative evaluation. The present article describes our initial experience, safeguards, and technical details.

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 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.

Vein grafts are still the most commonly used graft material in cardiovascular surgery and much effort has been spent in recent years on investigating the optimal harvesting technique. One other related topic of similar importance remained more or less an incidental one. The storage solutions of vein grafts following procurement and prior to implantation are, despite their assumed impact, a relatively neglected theme. There is no doubt that the endothelium plays a key role in long-term patency of vein grafts, but the effects of the different storage solutions on the endothelium remain unclear : In a review of the literature, we could find 20 specific papers that addressed the question, of which the currently available preservation solutions are superior, harmless, damaging or ineffective. The focus lies on saline and autologous whole blood. Besides these two storage media, novel or alternative solutions have been investigated with surprising findings. In addition, a few words will be spent on potential alternatives and novel solutions on the market. As there is currently no randomized clinical trial regarding saline versus autologous whole blood available, this review compares all previous studies and methods of analysis to provide a certain level of evidence on this topic. In summary, saline has negative effects on the endothelial layers and therefore may compromise graft patency. Related factors, such as distension pressure, may outbalance the initial benefit of autologous whole blood or storage solutions and intensify the harmful effects of warm saline. In addition, there is no uniform consent on the superiority of autologous whole blood for vein graft storage. This may open the door to alternatives such as the University of Wisconsin solution or one of the specific designed storage solutions like TiProtec™ or Somaluthion™. Whether these preservation solutions are superior or advantageous remains the subject of further studies.

Objective Type A aortic dissection is a life-threatening disease requiring immediate surgical treatment. With emerging catheter-based technologies, endovascular stent-graft implantation to treat aneurysms and dissections has become a standardized procedure. However, endovascular treatment of the ascending aorta remains challenging. Thus we designed an ascending aortic dissection model to allow simulation of endovascular treatment. Methods Five formalin-fixed human aortas were prepared. The ascending aorta was opened semicircularly in the middle portion and the medial layer was separated from the intima. The intimal tube was readapted using running monofilament sutures. The preparations were assessed by 128-slice computed tomography. A bare-metal stent was implanted for thoracic endovascular aortic repair in 4 of the aortic dissection models. Results Separation of the intimal and medial layer of the aorta was considered to be sufficient because computed tomography showed a clear image of the dissection membrane in each aorta. The dissection was located 3.9 ± 1.4 cm proximally from the aortic annulus, with a length of 4.6 ± 0.9 cm. Before stent implantation, the mean distance from the intimal flap to the aortic wall was measured as 0.63 ± 0.163 cm in the ascending aorta. After stent implantation, this distance decreased to 0.26 ± 0.12 cm. Conclusion This model of aortic dissection of the ascending human aorta was reproducible with a comparable pathological and morphological appearance. The technique and model can be used to evaluate new stent-graft technologies to treat type A dissection and facilitate training for surgeons.

BACKGROUND Surgical aortic valve replacement (SAVR) is the treatment of choice in severe symptomatic aortic valve disease. New techniques and prostheses have been recently developed to facilitate the procedure and reduce aortic cross-clamp time (AOx). The aim of this study was to analyse the different procedural steps in order to identify the most time-consuming part during aortic clamping time and to compare impact of experience on procedural aspects. METHODS AOx during SAVR was divided into five consecutive steps. Duration of each step was measured. The first procedural step started with clamping of the aorta and ended with the beginning of the second step starting with the resection of the native aortic valve. The third step started with placement of the first valve anchoring suture, the fourth step started with tying of the first suture and the fifth and final step started after the cut of the last suture and ended with removal of the aortic clamp. Surgeons were divided into two groups based on their experience, which in our analysis was defined as a total SAVR experience of more than 100 procedures. RESULTS From March 2013 to August 2015 57 nonconsecutive patients (33% female; age, median 71.0 years, interquartile range 65.0-76.0) undergoing isolated SAVR for severe aortic valve stenosis in our institution were included in this process analysis. Two different prostheses were implanted. Forty-eight (84%) patients received a tissue valve (Perimount Magna Ease, Edwards Lifesciences, Irvine, USA) and 9 (16%) patients received a mechanical prosthesis (Medtronic AP 360, St-Paul, MN, USA). The mean estimated risk of mortality was 1.1% (0.7-1.6) according to the logistic EUROScore II. Overall duration of AOx was 50.5 ± 13.8 min, with 32.3% (16.4 ± 5.9 min) accounting for placing the sutures into the native annulus and the prosthetic sewing ring and 18.5% (9.2 ± 3.0min) accounting for tying and cutting the sutures. Surgeons with more experience performed 35 operations (61.4%) and needed an average of 44.1 ± 11.5 min versus 60.6 ± 11.0 min (p

OBJECTIVE Coronary artery bypass grafting (CABG) remains the gold standard for complex revascularisation in multivessel disease. The concept of the minimally invasive extracorporeal circulation circuit (MiECC) was introduced to minimise pathophysiological side effects of conventional extracorporeal circulation. This study presents early and long-term outcomes after CABG with use of MiECC in a single-centre consecutive patient cohort. METHODS From 1 January 2005 to 31 December 2010, 2130 patients underwent isolated CABG with MiECC at our centre. We evaluated morbidity and mortality follow-up data with a median follow-up of 3.6 years. Kaplan-Meier curves and estimates of the primary end-point for all-cause mortality were compared with the life expectancy of the general population. RESULTS Mortality in CABG patients was comparable to the general population beginning 1 year after surgery for the whole observation period. All-cause 30-day mortality was 0.8%. The mean estimated logistic EuroSCORE and EuroSCORE II were 5.8 ± 8.6 and 3.0 ± 5.1, respectively. Mean perfusion time was 71.1 ± 23.8 min with a cross-clamp time of 44.9 ± 16.3 min. Mortality was predicted by the presence of diabetes mellitus (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.40-2.46; p

Objectives In this study, the influence of aortic root distensibility on the haemodynamic parameters and valve kinematics of a bioprosthetic aortic valve was investigated in a controlled in vitro experiment. Methods An Edwards INTUITY Elite 21 mm sutureless aortic valve (Edwards Lifesciences, Irvine, CA, USA) was inserted in three transparent aortic root phantoms with different wall thicknesses (0.55, 0.85 and 1.50 mm) mimicking different physiological distensibilities. Haemodynamic measurements were performed in an in vitro flow loop at heart rates of 60, 80 and 100 bpm with corresponding cardiac outputs of 3.5, 4.0 and 5.0 l/min and aortic pressures of 100/60, 120/90 and 145/110 mmHg, respectively. Aortic valve kinematics were assessed using a high-speed camera. The geometric orifice area (GOA) was measured by counting pixels in the lumen of the open aortic valve. The effective orifice area (EOA) was calculated from the root-mean-square value of the systolic aortic valve flow rate and the mean systolic trans-valvular pressure gradient. Results The tested aortic root phantoms reproduce physiological distensibilities of healthy individuals in age groups ranging from 40 to 70 years (±10 years). The haemodynamic results show only minor differences between the aortic root phantoms: the trans-valvular pressure gradient tends to increase for stiffer aortic roots, whereas the systolic aortic valve flow rate remains constant. As a consequence, the EOA decreased slightly for less distensible aortic roots. The GOA and the aortic valve opening and closing velocities increase significantly with reduced distensibility for all haemodynamic measurements. The resulting mean systolic flow velocity in the aortic valve orifice is lower for the stiffer aortic root. Conclusions Aortic root distensibility may influence GOA and aortic valve kinematics, which affects the mechanical load on the aortic valve cusps. Whether these changes have a significant effect on the onset of structural valve deterioration of bioprosthetic heart valves needs to be further investigated.

OBJECTIVES Objective evaluation of the impact of minimized extracorporeal circulation (MECC) on perioperative cognitive brain function in coronary artery bypass grafting (CABG) by electroencephalogram P300 wave event-related potentials and number connection test (NCT) as metrics of cognitive function. METHODS Cognitive brain function was assessed in 31 patients in 2013 with a mean age of 65 years [standard deviation (SD) 10] undergoing CABG by the use of MECC with P300 auditory evoked potentials (peak latencies in milliseconds) directly prior to intervention, 7 days after and 3 months later. Number connection test, serving as method of control, was performed simultaneously in all patients. RESULTS Seven days following CABG, cognitive P300 evoked potentials were comparable with preoperative baseline values [vertex (Cz) 376 (SD 11) ms vs 378 (18) ms, P = 0.39; frontal (Fz) 377 (11) vs 379 (21) ms, P = 0.53]. Cognitive brain function at 3 months was compared with baseline values [(Cz) 376 (11) ms vs 371 (14 ms) P = 0.09; (Fz) 377 (11) ms vs 371 (15) ms, P = 0.04]. Between the first postoperative measurement and 3 months later, significant improvement was observed [(Cz) 378 (18) ms vs 371 (14) ms, P = 0.03; (Fz) 379 (21) vs 371 (15) ms, P = 0.02]. Similar clearly corresponding patterns could be obtained via the number connection test. Results could be confirmed in repeated measures analysis of variance for Cz (P = 0.05) and (Fz) results (P = 0.04). CONCLUSIONS MECC does not adversely affect cognitive brain function after CABG. Additionally, these patients experience a substantial significant cognitive improvement after 3 months, evidentiary proving that the concept of MECC ensures safety and outcome in terms of brain function.

We describe 2 cases of mechanical aortic valve endocarditis and the influence on clinical outcome and prostheses material integrity. One patient required extensive reconstruction due to active endocarditis leading to a “rocking valve”. The second case was caused by late aortic dissection following endocarditis. Both valve prostheses showed remarkable material quality and performance in functional assessment and high resolution scanning electron microscopic evaluation after 27 and 23 years of service.

Current guidelines for the treatment of hypothermic cardiocirculatory arrest recommend extracorporeal life support and rewarming, using cardiopulmonary bypass or extracorporeal membrane oxygenation circuits. Both have design-related shortcomings which may result in prolonged reperfusion time or insufficient oxygen delivery to vital organs. This article describes clear advantages of minimally invasive extracorporeal circulation systems during emergency extracorporeal life support in hypothermic arrest. The technique of minimally invasive extracorporeal circulation for reperfusion and rewarming is represented by the case of a 59-year-old patient in hypothermic cardiocirculatory arrest at 25.3°C core temperature, with multiple trauma. With femoro-femoral cannulation performed under sonographic and echocardiographic guidance, extracorporeal life support was initiated using a minimally invasive extracorporeal circulation system. Perfusing rhythm was restored at 28°C. During rewarming on the mobile circuit, trauma surveys were completed and the treatment initiated. Normothermic weaning was successful on the first attempt, trauma surgery was completed and the patient survived neurologically intact. For extracorporeal resuscitation from hypothermic arrest, minimally invasive extracorporeal circulation offers all the advantages of conventional cardiopulmonary bypass and extracorporeal membrane oxygenation systems without their shortcomings.

Numerous designs of bioprosthetic valves exist. The sutureless surgical valve is a newer design concept which combines elements of the transcatheter valve technology with surgical valves. This design aims at shorter and easier implantation. It was the aim of this study to perform hemodynamic and kinematic measurements for this type of valves to serve as a baseline for following studies which investigate the effect of the aortic root on the valve performance. To this end, the Edwards Intuity aortic valve was investigated in a new in vitro flow loop mimicking the left heart. The valve was implanted in a transparent, compliant aortic root model, and the valve kinematics was investigated using a high speed camera together with synchronized hemodynamic measurements of pressures and flows. The valve closure was asynchronous (one by one leaflet), and the valve started to close before the deceleration of the fluid. The aortic root model showed a dilation of the sinuses which was different to the ascending aorta, and the annulus was found to move towards the left ventricle during diastole and towards the aorta during systole.

OBJECTIVES: Long-term follow-up reports after implantation of the Shelhigh (R) (Shelhigh, Inc., NJ, USA) No-React (R) aortic valved conduit used for aortic root replacement do not exist. METHODS: Between November 1998 and December 2007, the Shelhigh (R) No-React (R) aortic valved conduit was implanted in 291 consecutive patients with a mean age of 69.6 +/- 9.1 years, and 33.7% were female (n = 98). Indications were annulo-aortic ectasia (n = 202), aortic valve stenosis combined with ascending aortic aneurysm (n = 67), acute type A aortic dissection (n = 29), endocarditis (n = 26) and other related pathologies (n = 48) including 62 patients with previous cardiac surgery. Data from two cardiac institutions were analysed retrospectively using SPSS (SPSS Software IBM, Inc., 2014, NY, USA). RESULTS: Operative mortality was 10% (n = 29). Main cause of death was cardiac failure in 15 patients (51.8%), neurological events in 6 patients (20.7%), respiratory failure in 4 patients (13.8%), bleeding complications in 2 patients (6.9%) and gastrointestinal ischaemia in 2 cases (6.9%). There were 262 hospital survivors and all were entered in the follow-up study (100% complete). During the long-term followup (mean 70.3 +/- 53.1 in months), a total of 126/262 patients (44.3%) died. Main causes of death in patients after discharge were cardiac (n = 37, 14.1%), neurological (n = 15, 5.7%) respiratory (n = 12, 4.6%), endocarditis (n = 12, 4.6%) and peripheral vascular disease (n = 5, 1.9%). In 29 (11.1%) patients, the cause of death could not be determined. Reoperation was required in 25 (8.6%) patients due to infection of the conduit (n = 9), aortoventricular disconnection (n = 4), pseudoaneurysm formation (n = 4) and structural valve degeneration (n = 8). Reoperations were performed 5.0 +/- 3.8 (range 0.1-11.7) years after index surgery. CONCLUSIONS: The Shelhigh (R) No-React (R) aortic valved conduit showed satisfactory short-term operative results. However, the long-term follow-up revealed a relatively high rate of deaths, which may be explained by the epidemiology of the patient group, but a substantial proportion of deaths could not be clarified. The overall rate of reoperation (8.6%) during the mid-term follow-up is worrisome and the failures due to aortoventricular disconnection, endocarditis and pseudoaneurysm formation remain unexplained. The redo-procedures were technically demanding. We recommend close follow-up of patients with the Shelhigh (R) No-React (R) aortic valved conduit, because besides classical structural valve degeneration, unexpected findings may be observed

BACKGROUND Definitive fate of the coronary endothelium after implantation of a drug-eluting stent remains unclear, but evidence has accumulated that treatment with rapamycin-eluting stents impairs endothelial function in human coronary arteries. The aim of our study was to demonstrate this phenomenon on functional, morphological and biochemical level in human internal thoracic arteries (ITA) serving as coronary artery model. METHODS After exposure to rapamycin for 20 h, functional activity of ITA rings was investigated using the organ bath technique. Morphological analysis was performed by scanning electron microscopy and evaluated by two independent observers in blinded fashion. For measurement of endothelial nitric oxide synthase (eNOS) release, mammalian target of rapamycin (mTOR) and protein kinase B (PKB) (Akt) activation, Western blotting on human mammary epithelial cells-1 and on ITA homogenates was performed. RESULTS Comparison of the acetylcholine-induced relaxation revealed a significant concentration-dependent decrease to 66 ± 7 % and 36 ± 7 % (mean ± SEM) after 20-h incubation with 1 and 10 μM rapamycin. Electron microscopic evaluation of the endothelial layer showed no differences between controls and samples exposed to 10 μM rapamycin. Western blots after 20-h incubation with rapamycin (10 nM-1 μM) revealed a significant and concentration-dependent reduction of p (Ser 1177)-eNOS (down to 38 ± 8 %) in human mammary epithelial cells (Hmec)-1. Furthermore, 1 μM rapamycin significantly reduced activation of p (Ser2481)-mTOR (58 ± 11 %), p (Ser2481)-mTOR (23 ± 4 %) and p (Ser473)-Akt (38 ± 6 %) in ITA homogenates leaving Akt protein levels unchanged. CONCLUSIONS The present data suggests that 20-h exposure of ITA rings to rapamycin reduces endothelium-mediated relaxation through down-regulation of Akt-phosphorylation via the mTOR signalling axis within the ITA tissue without injuring the endothelial cell layer.

Background Management of deep sternal wound infection (DSWI) in cardiac surgical patients still remains challenging. A variety of treatment strategies has been described. Aim of this cohort study was to analyse two different treatment strategies for DSWI: titanium sternal plating system (TSFS) and muscle flap coverage (MFC). Methods Between January 2007 and December 2011, from 3122 patients undergoing cardiac surgery 42 were identified with DSWI and treated with one of the above mentioned strategies. In-hospital data were collected, follow-up performed by telephone and assessment of Quality of Life (QoL) using the SF-12 Health Survey Questionnaire. Results 20 patients with deep sternal wound infection were stabilized with TSFS and 22 patients treated with MFC. Preoperative demographics and risk factors did not reveal any significant differences. Patients treated with TSFS had a significantly shorter operation time (p

Rationale: Smooth muscle cells (SMCs) are a key component of tissue-engineered vessels. However, the sources by which they can be isolated are limited. Objective: We hypothesized that a large number of SMCs could be obtained by direct reprogramming of fibroblasts, that is, direct differentiation of specific cell lineages before the cells reaching the pluripotent state. Methods and Results: We designed a combined protocol of reprogramming and differentiation of human neonatal lung fibroblasts. Four reprogramming factors (OCT4, SOX2, KLF4, and cMYC) were overexpressed in fibroblasts under reprogramming conditions for 4 days with cells defined as partially-induced pluripotent stem (PiPS) cells. PiPS cells did not form tumors in vivo after subcutaneous transplantation in severe combined immunodeficiency mice and differentiated into SMCs when seeded on collagen IV and maintained in differentiation media. PiPS-SMCs expressed a panel of SMC markers at mRNA and protein levels. Furthermore, the gene dickkopf 3 was found to be involved in the mechanism of PiPS-SMC differentiation. It was revealed that dickkopf 3 transcriptionally regulated SM22 by potentiation of Wnt signaling and interaction with Kremen1. Finally, PiPS-SMCs repopulated decellularized vessel grafts and ultimately gave rise to functional tissue-engineered vessels when combined with previously established PiPS-endothelial cells, leading to increased survival of severe combined immunodeficiency mice after transplantation of the vessel as a vascular graft. Conclusions: We developed a protocol to generate SMCs from PiPS cells through a dickkopf 3 signaling pathway, useful for generating tissue-engineered vessels. These findings provide a new insight into the mechanisms of SMC differentiation with vast therapeutic potential.

The generation of induced pluripotent stem (iPS) cells is an important tool for regenerative medicine. However, the main restriction is the risk of tumor development. In this study we found that during the early stages of somatic cell reprogramming toward a pluripotent state, specific gene expression patterns are altered. Therefore, we developed a method to generate partial-iPS (PiPS) cells by transferring four reprogramming factors (OCT4, SOX2, KLF4, and c-MYC) to human fibroblasts for 4 d. PiPS cells did not form tumors in vivo and clearly displayed the potential to differentiate into endothelial cells (ECs) in response to defined media and culture conditions. To clarify the mechanism of PiPS cell differentiation into ECs, SET translocation (myeloid leukemia-associated) (SET) similar protein (SETSIP) was indentified to be induced during somatic cell reprogramming. Importantly, when PiPS cells were treated with VEGF, SETSIP was translocated to the cell nucleus, directly bound to the VE-cadherin promoter, increasing vascular endothelial-cadherin (VE-cadherin) expression levels and EC differentiation. Functionally, PiPS-ECs improved neovascularization and blood flow recovery in a hindlimb ischemic model. Furthermore, PiPS-ECs displayed good attachment, stabilization, patency, and typical vascular structure when seeded on decellularized vessel scaffolds. These findings indicate that reprogramming of fibroblasts into ECs via SETSIP and VEGF has a potential clinical application.

SummaryTests that enable prediction of adverse outcome after surgical or nonsurgical intervention in cardiac patients are of great importance since they can help guide clinical decision making. The new evolving percutaneous therapeutic techniques combined with the currently available risk scoring systems require improved prediction models. In the context of steadily improving surgical techniques and perioperative care, on the one hand, and the inadequacy of regional patient data sets to provide generally applicable risk prediction base, on the other, there is need for adaption and recalibration of scoring systems some of which are partly outdated but still widely in use. The accuracy of predictive models depends on their proper application as well as the knowledge of their individual strengths and weaknesses. The EuroSCORE and the STS score take into consideration some risk factors associated with mortality, whereas the SYNTAX score relies solely on coronary anatomy and lesion characteristics. A combination of selected score components from the EuroSCORE, assessing the mortality risk, and those from the SYNTAX score, reflecting the coronary artery disease complexity, can be expected to yield more accurate results in estimating risk in individual patients. In this review, the predictive ability of the SYNTAX score, the STS score and the EuroSCORE will be discussed.

Synovial sarcoma metastasis affecting the heart and infiltrating the mitral valve is a very rare pathology. We report the case of a 44-year-old male treated with chemotherapy for atypical synovial sarcoma of the oral mucosa who presented to our clinic after cardiac decompensation with a presumptive diagnosis of myxoma of the left atrium. A large necrotic tumour positive for CK 22, EMA, CD 99 and BCL-2 but negative for translocation in COBRA-FISH analysis by break-apart probe could be excised and revealed a very rare subtype of synovial sarcoma metastasis arising from the endocard of the left atrium. The tumour was resected and the mitral valve reconstructed through ring annuloplasty.

Purpose Established hemostatic devices can injure vessel wall integrity. LeGoo (Pluromed, Woburn, MA), a novel poloxamer gel with reverse thermosensitive properties, is a new device for temporary occlusion of blood vessels. The present study investigated the effects of LeGoo on vascular function and morphology. Description The distal end of the human internal thoracic artery was used to assess vascular function of LeGoo-applied segments in organ bath experiments and by scanning electron microscopy. Evaluation After LeGoo application, both maximal contractile responses to noradrenaline and endothelium-dependent relaxant responses to acetylcholine were significantly reduced. Scanning electron microscopy showed areas of injured endothelium with exposure of subendothelial structures being in line with the functional changes. Conclusions Data suggested that application of LeGoo induced significant endothelial injury and deterioration of the smooth muscle in human internal thoracic arteries.

An increasing number of aortic valve replacements are performed through a ministernotomy. Due to the small incision and partial fixation of the caudal sternum, the traditional wire closure can be complicated and even harmful to the surrounding tissue. In such cases, we recommend the use of nitinol clips for sternal closure. This technique, which we have used in 48 patients, is simple, safe, and fast, and results in excellent outcomes.

Fig. 2. Intra-operative view through the opened right atrium (A) and the aortotomy (B). There is a large defect at the base of the tricuspid septal leaflet (arrow) with vegetations (A). A surgical spatula within the defect (introduced from the right atrial side) demonstrates the communication (dashed arrow) to the left ventricle just below the right coronary to non-coronary commissure (B). RS, right coronary sinus.

Figure 1: A CT scan 2 years (A) and 14 years (B) after the initial aortic repair. It shows the enlarged prosthesis diameter of 42 mm (black dotted arrows), which has remained stable over time. Compared with the original dimension, the cross-sectional area of the prosthesis increased by 96%, and the prosthesis wall tension by 40%. Figure 2: Reconstructed three-dimensional angiography demonstrating the enlarged aortic prosthesis compared with the aortic root and the proximal aortic arch. White arrows mark the proximal and distal anastomosis site.

A 72-year-old woman with a long-standing history of rheumatic heart disease was admitted to our hospital for a severe paravalvular leak (PVL). The patient contracted rheumatic fever in 1953 and received closed mitral commissurotomy in 1965, mechanical aortic valve replacement with open mitral