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.

Outcomes after surgical revascularization in diabetic patients.

OBJECTIVES: Patients with diabetes mellitus (DM) undergoing coronary artery bypass grafting (CABG) have been repeatedly demonstrated to have worse clinical outcomes compared to patients without DM. The objective of this study was to evaluate the impact of DM on 1-year clinical outcomes after isolated CABG. METHODS: The European DuraGraft registry included 1130 patients (44.6%) with and 1402 (55.4%) patients without DM undergoing isolated CABG. Intra-operatively, all free venous and arterial grafts were treated with an endothelial damage inhibitor. Primary end point in this analysis was the incidence of a major adverse cardiac event (MACE), a composite of all-cause death, repeat revascularization or myocardial infarction at 1 year post-CABG. To balance between differences in baseline characteristics (n = 1072 patients in each group), propensity score matching was used. Multivariable Cox proportional hazards regression was performed to identify independent predictors of MACE. RESULTS: Diabetic patients had a higher cardiovascular risk profile and EuroSCORE II with overall more comorbidities. Patients were comparable in regard to surgical techniques and completeness of revascularization. At 1 year, diabetics had a higher MACE rate {7.9% vs 5.5%, hazard ratio (HR) 1.43 [95% confidence interval (CI) 1.05-1.95], P = 0.02}, driven by increased rates of death [5.6% vs 3.5%, HR 1.61 (95% CI 1.10-2.36), P = 0.01] and myocardial infarction [2.8% vs 1.4%, HR 1.99 (95% CI 1.12-3.53) P = 0.02]. Following propensity matching, no statistically significant difference was found for MACE [7.1% vs 5.7%, HR 1.23 (95% CI 0.87-1.74) P = 0.23] or its components. Age, critical operative state, extracardiac arteriopathy, ejection fraction ≤50% and left main disease but not DM were identified as independent predictors for MACE. CONCLUSIONS: In this study, 1-year outcomes in diabetics undergoing isolated CABG were comparable to patients without DM.

Surgical ablation of long-standing persistent atrial fibrillation: 1-year outcomes from the CArdioSurgEry Atrial Fibrillation (CASE-AF) registry.

OBJECTIVES: The CArdioSurgEry Atrial Fibrillation (CASE-AF) registry is a prospective, multicentre study for collecting and analysing real-world data of surgical atrial fibrillation (AF) treatment. This study aimed to evaluate outcomes of surgery for long-standing persistent AF at 1 year. METHODS: In total, 17 centres consecutively include all eligible patients with continuous AF lasting for ≥1 year. Exclusion criteria are missing informed consent or age <18 years. For patient-reported outcomes measures, the European Heart Rhythm Association score was used. No presence of AF (based on ECG findings including Holter ECG and/or implanted devices), no re-ablation, no further cardioversion and no rehospitalization due to AF after a 3-month blanking period defined no AF recurrence at 1 year. RESULTS: From January 2017 to January 2020, a total of 1115 patients were enrolled in CASE-AF. Of them, 202 patients (mean age 69.7 ± 7.8 years, 27.2% female) underwent surgical ablation of long-standing persistent AF (study cohort), mostly accompanied by left atrial appendage closure (n = 180 [89%], resection n = 75 [42%]) and predominantly performed as concomitant (n = 174 [86%]) and left atrial only procedure (n = 144 [71%]). Early mortality (30 days) was 2.0% and morbidity was low. At follow-up (median 14.4 months, interquartile range, 12.7-17.6 months, 100% complete), 106 patients (56%) had no AF recurrence and 93% of them were asymptomatic. AF recurrence was accompanied by AF-related rehospitalization (n = 12, P = 0.003), direct current shock cardioversion (n = 23, P < 0.001), AF ablation (n = 7, P = 0.003) and stroke (n = 3, P = 0.059). Multivariable analysis identified cryoablation, predominantly performed endocardially including additional left atrial (74%) and biatrial (42%) lesions, as a significant factor for freedom from AF recurrence (odds ratio 2.7, 95% confidence interval 1.07-6.79, P = 0.035). CONCLUSIONS: According to CASE-AF, surgical ablation of long-standing persistent AF is most effective when concomitantly performed using endocardial cryoablation. Ongoing follow-up allows further elucidation of efficacious treatment strategies.

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.

Clinical outcomes and quality of life after contemporary isolated coronary bypass grafting: a prospective cohort study.

OBJECTIVES: The objective of the European Multicenter Registry to Assess Outcomes in coronary artery bypass grafting (CABG) patients (DuraGraft Registry) was to determine clinical outcomes and quality of life (QoL) after contemporary CABG that included isolated CABG and combined CABG/valve procedures, using an endothelial damage inhibitor (DuraGraft) intraoperatively for conduit preservation. Here, we report outcomes in the patient cohort undergoing isolated CABG. METHODS: The primary outcome was the composite of all-cause death, myocardial infarction (MI), or repeat revascularization (RR) [major adverse cardiac events (MACE)] at 1 year. Secondary outcomes included the composite of all-cause death, MI, RR, or stroke [major adverse cardiac and cerebrovascular events (MACCE)], and QoL. QoL was assessed with the EuroQol-5 Dimension questionnaire. Independent risk factors for MACE at 1 year were determined using Cox regression analysis. RESULTS: A total of 2532 patients (mean age, 67.4±9.2 years; 82.5% male) underwent isolated CABG. The median EuroScore II was 1.4 [interquartile range (IQR), 0.9-2.3]. MACE and MACCE rates at 1 year were 6.6% and 7.8%, respectively. The rates of all-cause death, MI, RR, and stroke were 4.4, 2.0, 2.2, and 1.9%, respectively. The 30-day mortality rate was 2.3%. Age, extracardiac arteriopathy, left ventricular ejection fraction less than 50%, critical operative state, and left main disease were independent risk factors for MACE. QoL index values improved from 0.84 [IQR, 0.72-0.92] at baseline to 0.92 [IQR, 0.82-1.00] at 1 year ( P <0.0001). CONCLUSION: Contemporary European patients undergoing isolated CABG have a low 1-year clinical event rate and an improved QoL.

Clinical event rate in patients with and without left main disease undergoing isolated coronary artery bypass grafting: results from the European DuraGraft Registry.

OBJECTIVES: Left main coronary artery disease (LMCAD) is considered an independent risk factor for clinical events after coronary artery bypass grafting (CABG). We have conducted a subgroup analysis of the multicentre European DuraGraft Registry to investigate clinical event rates at 1 year in patients with and without LMCAD undergoing isolated CABG in contemporary practice. METHODS: Patients undergoing isolated CABG were selected. The primary end point was the incidence of a major adverse cardiac event (MACE) defined as the composite of death, myocardial infarction (MI) or repeat revascularization (RR) at 1 year. The secondary end point was major adverse cardiac and cerebrovascular events (MACCE) defined as MACE plus stroke. Propensity score matching was performed to balance for differences in baseline characteristics. RESULTS: LMCAD was present in 1033 (41.2%) and absent in 1477 (58.8%) patients. At 1 year, the MACE rate was higher for LMCAD patients (8.2% vs 5.1%, P = 0.002) driven by higher rates of death (5.4% vs 3.4%, P = 0.016), MI (3.0% vs 1.3%, P = 0.002) and numerically higher rates of RR (2.8% vs 1.8%, P = 0.13). The incidence of MACCE was 8.8% vs 6.6%, P = 0.043, with a stroke rate of 1.0% and 2.4%, P = 0.011, for the LMCAD and non-LMCAD groups, respectively. After propensity score matching, the MACE rate was 8.0% vs 5.2%, P = 0.015. The incidence of death was 5.1% vs 3.7%, P = 0.10, MI 3.0% vs 1.4%, P = 0.020, and RR was 2.7% vs 1.6%, P = 0.090, for the LMCAD and non-LMCAD groups, respectively. Less strokes occurred in LMCAD patients (1.0% vs 2.4%, P = 0.017). The MACCE rate was not different, 8.5% vs 6.7%, P = 0.12. CONCLUSIONS: In this large registry, LMCAD was demonstrated to be an independent risk factor for MACE after isolated CABG. Conversely, the risk of stroke was lower in LMCAD patients. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02922088.

Does Preoperative Sinus Rhythm Influence Surgical Ablation's Perioperative Safety in Patients with Atrial Fibrillation?

BACKGROUND: Despite excellent data on lowering long-term stroke and all-cause mortality rates, currently, only 25-40% of atrial fibrillation (AF) patients undergo simultaneous surgical ablation therapy (SA) during cardiac surgery. Surgeon's fear exposing their patients to an additional, unjustified, and disproportionate risk when performing SA in AF patients presenting with sinus rhythm (SR) before surgery. To clarify the influence of preoperative SR before SA for AF, we conducted a subgroup analysis of the German Cardiosurgical Atrial Fibrillation (CASE-AF) register. METHODS: Between September 2016 and August 2020, 964 AF patients with an underlying cardiac disease were scheduled for surgery with SA and enrolled in the CASE-AF register. Data prospectively were collected and analyzed retrospectively. We divided the entire cohort into an SR-group (38.2%, N = 368) and an AF-group (61.8%, N = 596), based on preoperative heart rhythm. RESULTS: Over half of the patients were moderately affected by their AF, with no difference between the groups (European Heart Rhythm Association class ≥IIb: SR-group 54.2% versus AF-group 58.5%, P = .238). The AF-group had a higher preoperative EuroSCORE II (4.8 ± 8.0% versus 4.2 ± 6.3%, P = .014). In-hospital mortality (SR-group 0.8% versus AF-group 1.7%, P = .261), major perioperative adverse cardiac and cerebrovascular events (SR-group 2.7% versus AF-group 3.5%, P = .500), and the new pacemaker implantation rate (SR-group 6.0% versus AF-group 5.9%, P = .939) were low and showed and no group difference. Logistic regression analysis showed a protective effect for preoperative SR to perioperative complications in AF patients undergoing SA (odds ratio (OR) 0.72 (95% CI 0.52 - 0.998); P = .0485). CONCLUSIONS: Concomitant SA in AF patients presenting in SR before cardiac surgery is safe, has a low perioperative risk profile, and should be carried out with almost no exceptions.

Endothelial damage inhibitors for improvement of saphenous vein graft patency in coronary artery bypass grafting.

The saphenous vein graft (SVG) remains the most commonly used conduit in coronary artery bypass grafting (CABG). In light of this further research must be aimed at the development of strategies to optimize SVG patency and thereby improve both short- and long-term outcomes of CABG surgery. SVG patency in large part depends on the protection of the structural and functional integrity of the vascular endothelium at the time of conduit harvesting, including optimal storage conditions to prevent endothelial damage. This review provides an overview of currently available storage and preservation solutions, including novel endothelial damage inhibitors, and their role in mitigating endothelial damage and vein graft failure.

Epicardial left atrial appendage occlusion with a new medical device: assessment of procedural feasibility, safety and efficacy in a large animal model.

BACKGROUND: Left atrial appendage occlusion (LAAO) represents a treatment alternative to anticoagulation in patients with atrial fibrillation. We evaluate a novel device for epicardial LAAO in a translational canine model. METHODS: Nine hounds (n = 9) were used to assess usability, safety, and efficacy of the TigerPaw Pro (TPP) device for epicardial LAAO. Following baseline imaging (intra-cardiac echocardiography (ICE) and angiography) and intraoperative visual inspection, usability was tested via a ``closure/re-opening`` maneuver followed by deployment of a total of twenty TPP devices (n = 20) on the left and right atrial appendages respectively. Procedural safety was evaluated by assessing for adverse-events via direct Epicardial inspection and endocardial imaging. Efficacy evaluation included assessment of device positioning, presence of residual stumps and completeness of closure. Post-mortem evaluation was performed to confirm safety and efficacy. RESULTS: Usability testing of all TPP devices was successful (n = 20;100%, delivery-time range 22-120 s) without any procedural adverse-events (tissue damage or tears, bleeding, vessel-impingement, structural impact). All devices fully traversed the ostium (n = 18) or appendage body (n = 2), and conformed smoothly to adjacent cardiac anatomy. In nineteen deployments (n = 19;95%), all device connector pairs were fully engaged, while in one TPP device the most distal pair remained unengaged. ICE and post-mortem inspections revealed complete closure of all appendage ostia (n = 18;100%) and only in one case a small residual stump was detected. Intraoperative safety findings were further confirmed post-mortem. Devices created a nearly smooth line of closure via symmetric endocardial tissue-coaptation. CONCLUSIONS: In this preclinical model, the TPP demonstrated good ease of use for ostial access, ability to re-position (after engagement) and rapid deployment, while achieving safe and effective LAAO.

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.

Saphenous vein grafts in contemporary coronary artery bypass graft surgery.

Myocardial ischaemia resulting from obstructive coronary artery disease is a major cause of morbidity and mortality in the developed world. Coronary artery bypass graft (CABG) surgery is the gold-standard treatment in many patients with complex multivessel coronary artery disease or left main disease. Despite substantial improvements in the outcome of patients undergoing CABG surgery in the past decade, graft patency remains the 'Achilles' heel' of this procedure. Whereas the use of the left internal mammary artery as a conduit is associated with the highest 10-year patency rate (>90%), saphenous vein grafts - the most commonly used conduit in CABG surgery - fail in 40-50% of treated patients by 10 years after surgery. Vein graft disease (VGD) and failure result from complex pathophysiological processes that can lead to complete occlusion of the graft, affecting long-term clinical outcomes. Optimal harvesting techniques, intraoperative preservation strategies and intraoperative patency control have important roles in the prevention of VGD. In addition, several studies published in the past decade have reported similar mid-term patency rates between vein grafts and arterial grafts when veins are used as a composite graft based on the internal mammary artery. In this Review, we present the latest evidence on the utilization of saphenous vein grafts for CABG surgery and provide an overview of the current practices for the prevention of VGD and vein graft failure.

A novel endothelial damage inhibitor for the treatment of vascular conduits in coronary artery bypass grafting: protocol and rationale for the European, multicentre, prospective, observational DuraGraft registry.

BACKGROUND: Vein graft disease (VGD) impairs graft patency rates and long-term outcomes after coronary artery bypass grafting (CABG). DuraGraft is a novel endothelial-damage inhibitor developed to efficiently protect the structural and functional integrity of the vascular endothelium. The DuraGraft registry will evaluate the long-term clinical outcomes of DuraGraft in patients undergoing CABG procedures. METHODS: This ongoing multicentre, prospective observational registry will enrol 3000 patients undergoing an isolated CABG procedure or a combined procedure (ie, CABG plus valve surgery or other surgery) with at least one saphenous vein grafts or one free arterial graft (ie, radial artery or mammary artery). If a patient is enrolled, all free grafts (SVG and arterial will be treated with DuraGraft. Data on baseline, clinical, and angiographic characteristics as well as procedural and clinical events will be collected. The primary outcome measure is the occurrence of a major adverse cardiac event (MACE; defined as death, non-fatal myocardial-infarction, or need for repeat-revascularisation). Secondary outcome measures are the occurrence of major adverse cardiac and cerebrovascular events (MACCE; defined as death, non-fatal myocardial-infarction, repeat-revascularisation, or stroke), patient-reported quality of life, and health-economic data. Patient assessments will be performed during hospitalisation, at 1-month, 1-year, and annually thereafter to 5 years post-CABG. Events will be adjudicated by an independent clinical events committee. This European, multi-institutional registry will provide detailed insights into clinical outcome associated with DuraGraft. DISCUSSION: This European, multi-institutional registry will provide detailed insights into clinical outcome associated with the use of DuraGraft. Beyond that, and given the comprehensive data sets comprising of patient, procedural, and graft parameters that are being collected, the registry will enable for multiple subgroup analyses targeting focus groups or specific clinical questions. These may include analysis of subpopulations such as patients with diabetes or multimorbid high-risk patients (patient level), evaluation of relevance of harvesting technique including endoscopic versus open conduit harvesting (procedural level), or particular graft-specific aspects (conduit level). TRIAL REGISTRATION: ClinicalTrials.gov NCT02922088 . Registered October 3, 2016. ETHICS AND DISSEMINATION: The regional ethics committees have approved the registry. Results will be submitted for publication.

Incidence and characteristics of left atrial appendage stumps after device-enabled epicardial closure.

OBJECTIVES: High success rates for left atrial appendage (LAA) exclusion with the AtriClip (Atricure, USA) device have been reported in the literature. This study evaluated the presence and characteristics of residual LAA stumps after AtriClip LAA exclusion using postoperative short- and long-term computed tomography angiography (CTA). METHODS: In this retrospective analysis, 43 of 291 consecutive patients undergoing cardiac surgery with concomitant LAA occlusion using the AtriClip device were identified with available postoperative short- and long-term follow-up by CTA. LAA patency and the absence or the size of a present residual LAA stump were assessed on 2-dimensional multiplanar reconstructions, on maximum intensity projection images and on volume-rendered 3-dimensional computed tomography reconstructions. Based on current recommendations, the threshold for a significant LAA stump length was defined <10 mm. RESULTS: The LAA was successfully occluded in all 43 patients (100%) as confirmed by intraoperative transoesophageal echocardiography and CTA imaging with a mean follow-up duration of 7.1 ± 0.8 years post-implant. The absence of blood flow in the excluded LAA was confirmed in all cases. In 31 of 43 patients (72%), no residual stump (0 mm) was observed creating a smooth endocardial surface, CTA revealed residual LAA stumps in 11/43 patients (26%) with a length <10 mm and a significant residual stump with a depth of >10 mm (12 mm) in 1 patient (2%). The mean length, width and depth of the residual stumps were 5.8 ± 2.1, 4.4 ± 1.2 and 7.3 ± 2.3 mm, respectively. CONCLUSIONS: This study investigated the incidence of residual stump formation (>10 mm) after LAA closure with the AtriClip device based on CTA imaging data obtained during short- and long-term follow-up. While no LAA stump was detectable in the majority of patients, a non-significant LAA stump (<10 mm) was present in 26% of cases, indicating a favourable LAA occlusion profile for the AtriClip device. However, although a LAA stump length <10 mm is currently considered clinically safe, this definition needs further attention in future studies with regards to its potential clinical implications.

What will surgical coronary revascularization look like in 25 years?

PURPOSE OF REVIEW: Coronary artery bypass grafting evolved in incremental but significant steps since its introduction. Here, we provide an update on operative techniques, choice of conduits, patient selection/decision-making and primary and secondary prevention measures with potential of influencing the future of coronary artery bypass grafting (CABG) surgery. RECENT FINDINGS: Associated mortality of off-pump CABG (OPCAB) procedures performed in high-volume OPCAB centers (≥164 cases per year) and by experienced surgeons (≥48 cases per year) was reduced compared with on-pump CABG with two or more grafts suggesting a volume-based dependency of outcomes in CABG procedures with high-technical complexity. Ten-year results from the recent Arterial Revascularization Trial showed no significant between-group difference for the primary and secondary outcome. Total arterial revascularization using composite bilateral internal mammary artery-Y-conduits through a limited access mini-thoracotomy was not only shown to be feasible but a safe and reproducible procedure with excellent midterm outcomes. The most recent Randomized Trial of Endoscopic or Open Vein-Graft Harvesting for Coronary-Artery Bypass (REGROUP) trial demonstrated no significant difference between open vein-graft harvesting and endoscopic vein-graft harvesting in the occurrence of major adverse cardiac events. SUMMARY: Adherence to the most recent guidelines on myocardial revascularization is a key component for providing state-of the CABG surgery. Trends to lesser invasiveness in surgical coronary revascularization will gain momentum and is expected - with further improvements - to be the mainstay of future surgical coronary revascularization strategies.

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.