External stenting for saphenous vein grafts reduces early postoperative graft failure.

OBJECTIVES: Multiple studies have shown that external stenting (ExSt) mitigates the progression of vein graft disease years after coronary artery bypass grafting (CABG). We used computed tomography to evaluate the effect of ExSt on perioperative vein graft patency. METHODS: This study assessed graft patency rates of saphenous vein grafts (SVG) in consecutive patients with isolated coronary artery bypass grafting (CABG) between 2018 and 2021. Logistic regression analyses were conducted to compare the outcomes of supported and non-supported groups at both patient and graft levels, with age, EuroSCORE II, gender, diabetes and arterial grafts as covariates. Subgroup analyses were performed based on different covariates. The goal of the study was to provide valuable insights into the clinical outcomes of SVG in patients having CABG. RESULTS: The study examined a total of 357 patients who met the inclusion criteria and evaluated 572 vein grafts. Of these, 150 patients (205 SVGs) received ExSt, whereas 207 patients (337 SVGs) did not receive ExSt. The study results indicated that the likelihood of overall SVG patency at discharge was higher in the stented group than in the non-stented group, both at the level of the grafts [93.8% vs 87.8%, odds ratio (OR) 2.1; 95% confidence interval (CI) 1.0-4.5; P = 0.05] and at the patient level (90.1% vs 83.5%, OR 1.8; 95% CI 0.9-3.6; P = 0.1). It is worth noting that the difference between the stented and non-stented groups was most significant in the subgroup that received 2 arterial grafts (96.5% vs 89.6%, OR 3.2; 95% CI 1.2-8.4; P = 0.02) and in the subgroup with a higher EuroSCORE II (median >1.1) (98.6% vs 88.6%, OR 8.8; 95% CI 1.1-72.7; P = 0.04). CONCLUSIONS: The ExSt is associated with improved perioperative SVG patency at both the graft and the patient levels. Moreover, SVGs to the right territory and high-risk patients appear to have an advantage using ExSt.

Thirteen Years of Impactful, Minimally Invasive Coronary Surgery: Short- and Long-Term Results for Single and Multi-Vessel Disease.

OBJECTIVES: Minimally invasive coronary surgery (MICS) via lateral thoracotomy is a less invasive alternative to the traditional median full sternotomy approach for coronary surgery. This study investigates its effectiveness for short- and long-term revascularization in cases of single and multi-vessel diseases. METHODS: A thorough examination was performed on the databases of two cardiac surgery programs, focusing on patients who underwent minimally invasive coronary bypass grafting procedures between 2010 and 2023. The study involved patients who underwent either minimally invasive direct coronary artery bypass grafting (MIDCAB) for the revascularization of left anterior descending (LAD) artery stenosis or minimally invasive multi-vessel coronary artery bypass grafting (MICSCABG). Our assessment criteria included in-hospital mortality, long-term mortality, and freedom from reoperations due to failed aortocoronary bypass grafts post-surgery. Additionally, we evaluated significant in-hospital complications as secondary endpoints. RESULTS: A total of 315 consecutive patients were identified between 2010 and 2023 (MIDCAB 271 vs. MICSCABG 44). Conversion to median sternotomy (MS) occurred in eight patients (2.5%). The 30-day all-cause mortality was 1.3% (n = 4). Postoperative AF was the most common complication postoperatively (n = 26, 8.5%). Five patients were reoperated for bleeding (1.6%), and myocardial infarction (MI) happened in four patients (1.3%). The mean follow-up time was six years (±4 years). All-cause mortality was 10.3% (n = 30), with only five (1.7%) patients having a confirmed cardiac cause. The reoperation rate due to graft failure or the progression of aortocoronary disease was 1.4% (n = 4). CONCLUSIONS: Despite the complexity of the MICS approach, the results of our study support the safety and effectiveness of this procedure with low rates of mortality, morbidity, and conversion for both single and multi-vessel bypass surgeries. These results underscore further the necessity to implement such programs to benefit patients.

Beyond Conventional Operations: Embracing the Era of Contemporary Minimally Invasive Cardiac Surgery.

Over the past two decades, minimally invasive cardiac surgery (MICS) has gained a significant place due to the emergence of innovative tools and improvements in surgical techniques, offering comparable efficacy and safety to traditional surgical methods. This review provides an overview of the history of MICS, its current state, and its prospects and highlights its advantages and limitations. Additionally, we highlight the growing trends and potential pathways for the expansion of MICS, underscoring the crucial role of technological advancements in shaping the future of this field. Recognizing the challenges, we strive to pave the way for further breakthroughs in minimally invasive cardiac procedures.

Conversion from off-pump to on-pump coronary artery bypass grafting: impact of surgeon and anaesthetist experience.

OBJECTIVES: Intraoperative conversion from off-pump to on-pump coronary artery bypass grafting (CABG) is associated with increased postoperative morbidity and mortality. The aim of this study is to assess the impact of surgeon and anaesthetist experience on the conversion rate. METHODS: We performed a retrospective analysis of the data of all patients who underwent planned off-pump CABG in a single centre in 2007-2021, some of whom were non-electively converted to on-pump. Surgeon and anaesthetist experience were assessed by the number of off-pump bypass procedures per year. Multivariable logistic regression analysis was used to assess the impact of surgeon and anaesthetist experience on conversion rate. RESULTS: A total of 2742 patients met the inclusion criteria. Ninety-four (3.4%) patients underwent non-elective conversion to on-pump surgery. Converted patients had significantly higher mortality [11 (11.7%) vs 35 (1.3%), P < 0.0001] in comparison to non-converted patients. Anaesthetist experience was found to be a risk factor for conversion (P = 0.011). Surgeon experience did not significantly affect conversion rate (P = 0.51). Other risk factors for conversion were female gender [odds ratio 2.65 (95% confidence interval 1.65-4.26), P = 0.0001] and left ventricular ejection fraction ≤35% [odds ratio 1.91 (95% confidence interval 1.05-3.49), P = 0.040]. CONCLUSIONS: Conversion from off-pump to on-pump CABG is associated with worse postoperative outcomes. Limited experience of anaesthetists in off-pump bypass surgery is associated with a higher conversion rate.

Endothelial damage inhibitor preserves the integrity of venous endothelial cells from patients undergoing coronary bypass surgery.

OBJECTIVES: Despite the success of coronary artery bypass graft (CABG) surgery using autologous saphenous vein grafts (SVGs), nearly 50% of patients experience vein graft disease within 10 years of surgery. One contributing factor to early vein graft disease is endothelial damage during short-term storage of SVGs in inappropriate solutions. Our aim was to evaluate the effects of a novel endothelial damage inhibitor (EDI) on SVGs from patients undergoing elective CABG surgery and on venous endothelial cells (VECs) derived from these SVGs. METHODS: SVGs from 11 patients participating in an ongoing clinical registry (NCT02922088) were included in this study, and incubated with both full electrolyte solution (FES) or EDI for 1 h and then examined histologically. In 8 of 11 patients, VECs were isolated from untreated grafts, incubated with both FES and EDI for 2 h under hypothermic stress conditions and then analysed for activation of an inflammatory phenotype, cell damage and cytotoxicity, as well as endothelial integrity and barrier function. RESULTS: The EDI was superior to FES in protecting the endothelium in SVGs (74 ± 8% versus 56 ± 8%, P < 0.001). Besides confirming that the EDI prevents apoptosis in SVG-derived VECs, we also showed that the EDI temporarily reduces adherens junctions in VECs while protecting focal adhesions compared to FES. CONCLUSIONS: The EDI protects the connectivity and function of the SVG endothelium. Our data suggest that the EDI can preserve focal adhesions in VECs during short-term storage after graft harvesting. This might explain the superiority of the EDI in maintaining most of the endothelium in venous CABG surgery conduits.

Isolated Minimally Invasive Mitral Valve Surgery in Octogenarians: Perioperative Outcome.

INTRODUCTION: Despite the feasibility, safety, and excellent outcomes of mitral valve surgery through a right mini-thoracotomy, there is data paucity about its use in octogenarians. In this study, we assess the outcomes of mitral valve surgery via right mini-thoracotomy in octogenarians. METHODS: We performed a retrospective analysis of the in-hospital perioperative data of 38 octogenarian patients with severe mitral regurgitation undergoing isolated mitral valve surgery via right mini-thoracotomy from 2013 to 2021 in our institution. RESULTS: The median patient age was 82 (81-83) years, and the median EuroSCORE II was 3.1% (2.3-4.9). A total of 19 (50%) patients underwent mitral valve repair. The median cardiopulmonary bypass duration was 78 (54-100) min and the median aortic cross-clamping duration was 57 (40-70) min. Two (5.3%) patients were converted to sternotomy, 1 (2.6%) underwent renal replacement therapy, 5 (13.2%) underwent reexploration for bleeding or tamponade, and 12 (31.6%) underwent permanent pacemaker implantation. The surgical repair success rate was 89.5%, with 2 (10.5%) patients requiring reoperation due to repair failure. No other patients required reoperation on the mitral valve. The median intensive care unit stay was 1 (1-2) day, and the median postoperative stay was 9.5 (8-14) days. There was no perioperative stroke or death. CONCLUSION: Despite a relatively increased risk of pacemaker implantation and reexploration for bleeding, our data support the feasibility of mitral valve surgery via a right mini-thoracotomy in octogenarians, with short ischemic times, low overall in-hospital morbidity, and no mortality. Preferring replacement in mitral diseases with a high risk for repair failure could minimize reoperations in this high-risk subgroup.

Anisotropic topographies restore endothelial monolayer integrity and promote the proliferation of senescent endothelial cells.

Thrombogenicity remains a major issue in cardiovascular implants (CVIs). Complete surficial coverage of CVIs by a monolayer of endothelial cells (ECs) prior to implantation represents a promising strategy but is hampered by the overall logistical complexity and the high number of cells required. Consequently, extensive cell expansion is necessary, which may eventually lead to replicative senescence. Considering that micro-structured surfaces with anisotropic topography may promote endothelialization, we investigated the impact of gratings on the biomechanical properties and the replicative capacity of senescent ECs. After cultivation on gridded surfaces, the cells showed significant improvements in terms of adherens junction integrity, cell elongation, and orientation of the actin filaments, as well as enhanced yes-associated protein nuclear translocation and cell proliferation. Our data therefore suggest that micro-structured surfaces with anisotropic topographies may improve long-term endothelialization of CVIs.

Ex Vivo Lung Perfusion with ß-Nicotinamide Adenine Dinucleotide (NAD+) Improves Ischemic Lung Function.

Ischemia-reperfusion injury compromises short- and long-term outcomes after lung transplantation. The scarce existing data on NAD+ suggest effects on hypoxia-induced vasoconstriction, on reactive oxygen species and on tampering inflammation. We exposed rat lungs to 14 h of cold ischemic storage and perfused them in a rat ex vivo lung perfusion (EVLP) system for 4 h. A control group (n = 6) was compared to groups receiving 100 µM (n = 6) or 200 µM NAD+ (n = 6) in the preservation solution and groups receiving 200 µM (n = 4) or 2000 µM (n = 6) NAD+ every 30 min in the perfusate, starting at 1 h of EVLP. Compared to the control, significant effects were only achieved in the 2000 µM NAD+ group. During the 4 h of EVLP, we monitored higher vascular flow, lower mean pulmonary arterial pressure and increased oxygenation capacity. Tissue inflammation estimated with the myeloperoxidase assay was lower in the 2000 µM NAD+ group. We observed higher levels of anti-inflammatory IL-10, higher anti-inflammatory IL-6/IL-10 ratios and lower levels of pro-inflammatory IL-12 and IL-18 as well as a trend of more anti-inflammatory IFNy in the 2000 µM NAD+ perfusate. In the bronchoalveolar lavage, the pro-inflammatory levels of IL-1α and IL-1ß were lower in the 2000 µM NAD+ group. NAD+ administered during EVLP is a promising agent with both anti-inflammatory properties and the ability to improve ischemic lung function.

Differential Leaflet Remodeling of Bone Marrow Cell Pre-Seeded Versus Nonseeded Bioresorbable Transcatheter Pulmonary Valve Replacements.

This study showed that bone marrow mononuclear cell pre-seeding had detrimental effects on functionality and in situ remodeling of bioresorbable bisurea-modified polycarbonate (PC-BU)-based tissue-engineered heart valves (TEHVs) used as transcatheter pulmonary valve replacement in sheep. We also showed heterogeneous valve and leaflet remodeling, which affects PC-BU TEHV safety, challenging their potential for clinical translation. We suggest that bone marrow mononuclear cell pre-seeding should not be used in combination with PC-BU TEHVs. A better understanding of cell-scaffold interaction and in situ remodeling processes is needed to improve transcatheter valve design and polymer absorption rates for a safe and clinically relevant translation of this approach.

Human cell-derived tissue-engineered heart valve with integrated Valsalva sinuses: towards native-like transcatheter pulmonary valve replacements.

Transcatheter valve replacement indication is currently being extended to younger and lower-risk patients. However, transcatheter prostheses are still based on glutaraldehyde-fixed xenogeneic materials. Hence, they are prone to calcification and long-term structural degeneration, which are particularly accelerated in younger patients. Tissue-engineered heart valves based on decellularized in vitro grown tissue-engineered matrices (TEM) have been suggested as a valid alternative to currently used bioprostheses, showing good performance and remodeling capacity as transcatheter pulmonary valve replacement (TPVR) in sheep. Here, we first describe the in vitro development of human cell-derived TEM (hTEM) and their application as tissue-engineered sinus valves (hTESVs), endowed with Valsalva sinuses for TPVR. The hTEM and hTESVs were systematically characterized in vitro by histology, immunofluorescence, and biochemical analyses, before they were evaluated in a pulse duplicator system under physiological pulmonary pressure conditions. Thereafter, transapical delivery of hTESVs was tested for feasibility and safety in a translational sheep model, achieving good valve performance and early cellular infiltration. This study demonstrates the principal feasibility of clinically relevant hTEM to manufacture hTESVs for TPVR.

Mast cells regulate CD4+ T-cell differentiation in the absence of antigen presentation.

BACKGROUND: Given their unique capacity for antigen uptake, processing, and presentation, antigen-presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD+) in T-cell differentiation independently of the cytokine milieu, whereas the precise mechanisms remained unknown. OBJECTIVE: The objective of this study is to further dissect the mechanism of actions of NAD+ and determine the effect of APCs on NAD+-mediated T-cell activation. METHODS: Isolated dendritic cells and bone marrow-derived mast cells (MCs) were used to characterize the mechanisms of action of NAD+ on CD4+ T-cell fate in vitro. Furthermore, NAD+-mediated CD4+ T-cell differentiation was investigated in vivo by using wild-type C57BL/6, MC-/-, MHC class II-/-, Wiskott-Aldrich syndrome protein (WASP)-/-, 5C.C7 recombination-activating gene 2 (Rag2)-/-, and CD11b-DTR transgenic mice. Finally, we tested the physiologic effect of NAD+ on the systemic immune response in the context of Listeria monocytogenes infection. RESULTS: Our in vivo and in vitro findings indicate that after NAD+ administration, MCs exclusively promote CD4+ T-cell differentiation, both in the absence of antigen and independently of major APCs. Moreover, we found that MCs mediated CD4+ T-cell differentiation independently of MHC II and T-cell receptor signaling machinery. More importantly, although treatment with NAD+ resulted in decreased MHC II expression on CD11c+ cells, MC-mediated CD4+ T-cell differentiation rendered mice resistant to administration of lethal doses of L monocytogenes. CONCLUSIONS: Collectively, our study unravels a novel cellular and molecular pathway that regulates innate and adaptive immunity through MCs exclusively and underscores the therapeutic potential of NAD+ in the context of primary immunodeficiencies and antimicrobial resistance.

Sternal Anomalies in Asymptomatic Patients after Median Sternotomy and Potential Influencing Factors.

BACKGROUND: We aimed to assess asymptomatic patients who had open-heart surgery with median sternotomy for potential sternal anomalies (SA), their related patient-specific risk factors, and treatment options for the prevention of SA. METHODS: Multiplanar CT scans (CTs) from 131 asymptomatic consecutive patients were analyzed retrospectively. Of these, 83 underwent CABG (63.4%), and 48 had aortic valve (AV) procedures via median sternotomy. Sternal bone healing was analyzed for SA and their exact location. RESULTS: In total, 49 SA were identified in 42 (32.1%) patients; 65% SA were found in the manubrium (n = 32). Five hundred thirty-two wires were implanted (4.2 ± 0.5 wires/patient), out of which 96.1% (n = 511) were figure 8 wires. There was no difference between normal and abnormal sterna with regard to the number of wires used for sternal closure (4.2 ± 0.5 vs. 4.3 ± 0.6, p = ns). The distance between wire placement to the proximal edge of the manubrium in normal and abnormal sterna was comparable (11.2 ± 4.2 vs. 10.9 ± 4.8 mm, p = ns). Patients who underwent CABG had a significantly higher risk for SA (OR = 2.4, p ≤ 0.05, 95% CI [1.2-4.9]). The use of BIMA (OR = 4.4, p ≤ 0.05, 95% CI [1.1-17.9]) and body mass index (BMI) > 31 kg/m2 (OR = 3.4, p ≤ 0.01, 95% CI [1.4-8.3]) significantly increased the risk of SA. CONCLUSION: At least 30% of patients were at an increased risk for SA after receiving a median sternotomy. CABG, use of BIMA, and a BMI > 30 kg/m2 were potential risk factors for the development of SA and warrant close clinical follow-up. Sternal plate fixation, particularly in the manubrium, could be beneficial in such patients.

Feasibility and safety of transfemoral sheathless portico aortic valve implantation: Preliminary results in a single center experience.

BACKGROUND: Feasibility of transfemoral (TF) transcathteter aortic valve replacement (TAVR) is limited by the smallest diameter, the calcification and tortuosity of the iliofemoral access vessels. The use of the Portico system without delivery sheath results in significantly lower profile delivery system compared to standard technique. We herein report our single center experience, feasibility and safety of such an approach. METHODS: The Portico valve was implanted sheathless in 81 high-risk patients with severe aortic stenosis utilizing percutaneous femoral access. Mean minimal diameter of the ileo-femoral arterial access was 7.06 ± 1.89 mm. In most cases a multidetector computed tomography was performed before the intervention to assess the feasibility of vascular access and for aortic annulus measurements. The vascular access site was preclosed using two ProGlide suture systems. RESULTS: Device implantation was successful 98.7% of patients. Valve recapturing and repositioning as well as valve-in-valve deployment was performed in only one case (1.2%). There were no infarctions, 2 strokes (2.4%) and 2 acute kidney failure (2.4%), 1 major vascular complication1 (1.2%) 4 major bleedings (4.9%), 11 conductions disturbances and relative pace-maker implantations (14.2%). The mean gradient decreased from 42.3 ± 17 to 6.3 ± 2.78 mm Hg. Paravalvular regurgitation as assessed by TTE at discharge was absent or trivial in 19 patients, mild in 60 and moderate 1. Thirty-day mortality was 2.4%. CONCLUSIONS: Sheathless use of the Portico valve is feasible and appears to be safe, with excellent rates of complications and mortality in the short-term. Such an approach has the potential to further expand feasibility of TF TAVR to patients with severe peripheral arterial disease. Feasibility in patients with smaller femoral access and more challenging anatomy has to be proven in further studies. © 2017 Wiley Periodicals, Inc.

Aspects of Tryptophan and Nicotinamide Adenine Dinucleotide in Immunity: A New Twist in an Old Tale.

Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan's immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play an important role in tryptophan's involvement in immune responses. Interestingly, quinolinic acid, which is a neurotoxic catabolite of the kynurenine pathway, is the major pathway for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that NAD+, a natural coenzyme found in all living cells, regulates immune responses and creates homeostasis via a novel signaling pathway. More importantly, the immunoregulatory properties of NAD+ are strongly related to the overexpression of tryptophan hydroxylase 1 (Tph1). This review provides recent knowledge of tryptophan and NAD+ and their specific and intriguing roles in the immune system. Furthermore, it focuses on the mechanisms by which tryptophan regulates NAD+ synthesis as well as innate and adaptive immune responses.

Percutaneous mitral valve repair and replacement: complementary or competitive techniques?

As transcatheter mitral replacement technologies have recently been applied in early clinical trials, the question as to whether valve implantation would have the potential to become the leading percutaneous mitral valve therapy has been raised. The aim of this report is to give an overview of the different peculiarities of percutaneous replacement and repair techniques, and to predict whether the two approaches will have a complementary rather than a competitive clinical role in the near future.

NAD(+) regulates Treg cell fate and promotes allograft survival via a systemic IL-10 production that is CD4(+) CD25(+) Foxp3(+) T cells independent.

CD4(+) CD25(+) Foxp3(+) Tregs have been shown to play a central role in immune homeostasis while preventing from fatal inflammatory responses, while Th17 cells have traditionally been recognized as pro-inflammatory mediators implicated in a myriad of diseases. Studies have shown the potential of Tregs to convert into Th17 cells, and Th17 cells into Tregs. Increasing evidence have pointed out CD25 as a key molecule during this transdifferentiation process, however molecules that allow such development remain unknown. Here, we investigated the impact of NAD(+) on the fate of CD4(+) CD25(+) Foxp3(+) Tregs in-depth, dissected their transcriptional signature profile and explored mechanisms underlying their conversion into IL-17A producing cells. Our results demonstrate that NAD(+) promotes Treg conversion into Th17 cells in vitro and in vivo via CD25 cell surface marker. Despite the reduced number of Tregs, known to promote homeostasis, and an increased number of pro-inflammatory Th17 cells, NAD(+) was able to promote an impressive allograft survival through a robust systemic IL-10 production that was CD4(+) CD25(+) Foxp3(+) independent. Collectively, our study unravels a novel immunoregulatory mechanism of NAD(+) that regulates Tregs fate while promoting allograft survival that may have clinical applications in alloimmunity and in a wide spectrum of inflammatory conditions.