Incidence and assessment of delirium following open cardiac surgery; A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis sought i) to provide an overview of the incidence of delirium following open cardiac surgery and ii) to investigate how incidences of delirium are associated with different assessment tools. METHODS AND RESULTS: A systematic search of studies investigating delirium following open cardiac surgery were conducted in Medline (Ovid), EMBASE, PsycINFO, CiNAHL and the Cochrane Database. Only studies with patients diagnosed or screened with a validated tool were included. Studies published from 2005 to 2021 were included in the meta-analysis.Of 7,126 individual studies retrieved, 106 met the inclusion criteria for the meta-analysis, hereof 31% of high quality. The weighted pooled incidence of delirium following open cardiac surgery across all studies was 23% (95% CI 20-26%), however we found a considerable heterogeneity (I2 = 99%), which could not be explained by subgroups or further sensitivity analyses. The most commonly applied screening tool for delirium is CAM/CAM-ICU. The lowest estimates of delirium were found by applying the Delirium Observation Scale (incidence 14%, 95% CI 8-20%), and the highest estimates in studies using "other" screening tools (Organic Brain Symptom Scale, Delirium Symptom Interview) pooled incidence of 43%, (95% CI 19 - 66%), however, only two studies applied these. CONCLUSION: Delirium following open cardiac surgery remains a complication with a high incidence of overall 23%, when applying a validated tool for screening or diagnosis. Nevertheless, this systematic review and meta-analyses highlight the significant inconsistency in current evidence regarding assessment tools and regimens. REGISTRATION: Prospero CRD42020215519.

How to harvest the left internal mammary artery-a randomised controlled trial.

OBJECTIVES: It is uncertain whether Thunderbeat has a place in harvesting the left internal mammary artery and whether skeletonisation is superior to pedicle harvested LIMA. Some investigations have shown improved flowrates in the skeletonised graft. The aim of this study was to compare three groups of harvesting techniques: Pedicled, surgical skeletonised and skeletonised with Thunderbeat in terms of flow rates in the left internal mammary artery and postoperative in-hospital outcomes. METHODS: Patients undergoing coronary artery bypass grafting with the left internal mammary artery to the anterior descending artery were randomized to pedicled (n = 56), surgical skeletonised (n = 55), and skeletonised with Thunderbeat (n = 54). Main outcomes were blood flow and pulsatility index in the graft. RESULTS: No statistical difference between groups regarding flow in LIMA or pulsatility index. Similarly, no difference in postoperative bleeding or days of hospitalisation. The duration of harvesting was faster for the pedicled technique compared with surgical skeletonised and skeletonised with Thunderbeat (mean total min: pedicled 20.2 min SD ± 5.4; surgical skeletonised 28.6 min SD ± 8.7; skeletonised with Thunderbeat 28.3 min SD ± 9.11, p < 0.001). No grafts discarded due to faulty harvesting and there was no graft failure within hospital stay. CONCLUSIONS: We found no difference between the harvesting methods except for a significantly faster harvesting time with the pedicled technique. However, non-touch skeletonised left internal mammary artery harvesting with Thunderbeat seems to be an effective alternative to traditional surgical skeletonised LIMA. The future will reveal whether patency is harvesting dependent.

Right ventricular myocardial edema leading to severe heart failure after open heart surgery - possible effect of high-dose corticosteroid therapy.

BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory response and alterations in fluid homeostasis, resulting in generalized tissue edema. Additionally, ischemia-reperfusion injury following cardioplegic arrest presumably prompts organ-specific myocardial edema. CASE PRESENTATION: The case report presents a 75-year-old Caucasian male diagnosed with aortic dissection, Stanford type A, who underwent complicated open-heart surgery. Postoperatively, the patient developed excessive myocardial edema, particularly affecting the right ventricle myocardium to an extent where the right ventricle surpassed the sternal rim, making it impossible to close the sternum. Ischemia was ruled out by performing coronary angiography, demonstrating well-calibrated coronary arteries. Transoesophageal echocardiography showed a restrictive right ventricle with free-wall thickness of 30 mm, severely reduced right ventricle systolic function and a volume-depleted left ventricle consistent with right ventricular heart failure due to right ventricular edema. The patient presented with unstable haemodynamics despite use of inotropes and continuation of open sternotomy. In an attempt to reduce myocardial edema, the patient was started on corticosteroid treatment despite of ongoing mediastinitis. Corticosteroid treatment reduced myocardial edema and enabled the closure of sternum on the 44th postoperative day. CONCLUSIONS: The case report addresses the clinical relevance of corticosteroid treatment in selective cases of intractable haemodynamically significant postoperative myocardial edema.

Experimental comparative study of a novel drug-eluting arteriovenous graft in a sheep model.

Background: Arteriovenous (AV) grafts often develop severe complications of stenosis due to neointimal proliferation that occurs either at the venous anastomosis site or at the outflow receiving vein. This study compares primary patency during 12 months of follow up for a new experimental Biomodics© interpenetrating polymer network (IPN) drug-eluting graft prototype with state-of-the-art GORE® ACUSEAL (ACUSEAL) in an AV graft model in sheep. Methods and results: An end-to-end bypass from the common carotid artery to the jugularis vein was performed bilaterally in 12 sheep. The usage of ACUSEAL or the IPN, both 6.0 mm in diameter, was determined via randomization. The sheep were followed up every 4 weeks with ultrasonic duplex scanning to determine patency; the experienced observer was blinded to the randomization. One sheep died after 11 days, and the final sample accordingly consisted of 11 animals. When comparing neointimal hyperplasia after 12 months in the two grafts, Fisher's exact test showed a significant difference with none out of 11 in the IPN grafts and 9 out of 11 in the ACUSEAL graft (p < 0.001). However, the Biomodics© IPN exhibited severe deterioration over time. Conclusions: Almost all of the grafts occluded during the 12 months of follow up. Although the zwitterion-bounded interpenetrating drug eluting polymer network showed signs to impair neointimal hyperplasia and thrombosis, age-related degeneration hindered demonstrating a potential improvement in patency.

Pericardial delta like non-canonical NOTCH ligand 1 (Dlk1) augments fibrosis in the heart through epithelial to mesenchymal transition.

BACKGROUND: Heart failure due to myocardial infarction (MI) involves fibrosis driven by epicardium-derived cells (EPDCs) and cardiac fibroblasts, but strategies to inhibit and provide cardio-protection remains poor. The imprinted gene, non-canonical NOTCH ligand 1 (Dlk1), has previously been shown to mediate fibrosis in the skin, lung and liver, but very little is known on its effect in the heart. METHODS: Herein, human pericardial fluid/plasma and tissue biopsies were assessed for DLK1, whereas the spatiotemporal expression of Dlk1 was determined in mouse hearts. The Dlk1 heart phenotype in normal and MI hearts was assessed in transgenic mice either lacking or overexpressing Dlk1. Finally, in/ex vivo cell studies provided knowledge on the molecular mechanism. RESULTS: Dlk1 was demonstrated in non-myocytes of the developing human myocardium but exhibited a restricted pericardial expression in adulthood. Soluble DLK1 was twofold higher in pericardial fluid (median 45.7 [34.7 (IQR)) µg/L] from cardiovascular patients (n = 127) than in plasma (median 26.1 µg/L [11.1 (IQR)]. The spatial and temporal expression pattern of Dlk1 was recapitulated in mouse and rat hearts. Similar to humans lacking Dlk1, adult Dlk1-/- mice exhibited a relatively mild developmental, although consistent cardiac phenotype with some abnormalities in heart size, shape, thorax orientation and non-myocyte number, but were functionally normal. However, after MI, scar size was substantially reduced in Dlk1-/- hearts as compared with Dlk1+/+ littermates. In line, high levels of Dlk1 in transgenic mice Dlk1fl/fl xWT1GFPCre and Dlk1fl/fl xαMHCCre/+Tam increased scar size following MI. Further mechanistic and cellular insight demonstrated that pericardial Dlk1 mediates cardiac fibrosis through epithelial to mesenchymal transition (EMT) of the EPDC lineage by maintaining Integrin ß8 (Itgb8), a major activator of transforming growth factor ß and EMT. CONCLUSIONS: Our results suggest that pericardial Dlk1 embraces a, so far, unnoticed role in the heart augmenting cardiac fibrosis through EMT. Monitoring DLK1 levels as well as targeting pericardial DLK1 may thus offer new venues for cardio-protection.

Impact of mandatory preoperative dental screening on post-procedural risk of infective endocarditis in patients undergoing transcatheter aortic valve implantation: a nationwide retrospective observational study.

Background: Guidelines recommend preoperative dental screening (PDS) prior to cardiac valve surgery, to reduce the incidence of prosthetic valve infective endocarditis (IE). However, limited data support these recommendations, particular in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to investigate the effect of mandatory PDS on risk of IE in patients undergoing TAVI. Methods: In this observational study, a total of 1133 patients undergoing TAVI in Western-Denmark from 2020 to 2022 were included. Patients were categorized based on two implemented PDS practices: mandatory PDS (MPDS group), and no referral for PDS (NPDS group). Outcome data were retrieved from Danish registries and confirmed using medical records. The primary outcome was incidence of IE. Secondary outcomes were all-cause mortality and composite outcome of all-cause mortality and IE. Findings: Of 568 patients in the MPDS group 126 (22.2%) underwent subsequent oral dental surgery, compared to 8 (1.4%) among 565 patients in the NPDS group. During a median follow-up of 1.9 years (interquartile range 1.4-2.5 years), 31 (2.7%) developed IE. The yearly incidence IE rate was 1.4% (0.8-2.3) and 1.5% (0.8-2.4) in MPDS and NPDS, respectively, p = 0.86. All-cause mortality rates were similar between groups (estimated 2-year overall mortality of 6.7% (4.8-9.2) vs. 4.7% (3.2-6.9), MPDS and NPDS, respectively, p = 0.15). Consistent findings were found in 712 propensity score-matched patients. Interpretation: Mandatory PDS did not demonstrate reduced risk of IE or all-cause mortality compared to targeted PDS in patients undergoing TAVI. Funding: The funder had no role in the study design, data management, or writing.

An Antibiotic-Loaded Silicone-Hydrogel Interpenetrating Polymer Network for the Prevention of Surgical Site Infections.

Surgical site infections (SSIs) are among the most frequent healthcare-associated infections, resulting in high morbidity, mortality, and cost. While correct hygiene measures and prophylactic antibiotics are effective in preventing SSIs, even in modern healthcare settings where recommended guidelines are strictly followed, SSIs persist as a considerable problem that has proven hard to solve. Surgical procedures involving the implantation of foreign bodies are particularly problematic due to the ability of microorganisms to adhere to and colonize the implanted material and form resilient biofilms. In these cases, SSIs may develop even months after implantation and can be difficult to treat once established. Locally applied antibiotics or specifically engineered implant materials with built-in antibiotic-release properties may prevent these complications and, ultimately, require fewer antibiotics compared to those that are systemically administered. In this study, we demonstrated an antimicrobial material concept with intended use in artificial vascular grafts. The material is a silicone-hydrogel interpenetrating polymer network developed earlier for drug-release catheters. In this study, we designed the material for permanent implantation and tested the drug-loading and drug-release properties of the material to prevent the growth of a typical causative pathogen of SSIs, Staphylococcus aureus. The novelty of this study is demonstrated through the antimicrobial properties of the material in vitro after loading it with an advantageous combination, minocycline and rifampicin, which subsequently showed superiority over the state-of-the-art (Propaten) artificial graft material in a large-animal study, using a novel porcine tissue-implantation model.

Atorvastatin and the influence on postoperative atrial fibrillation after surgical aortic valve replacement (STARC) in adults at Odense University Hospital, Denmark: study protocol for a randomised controlled trial.

INTRODUCTION: Atrial fibrillation (AF) is the most common postoperative complication after surgical aortic valve replacement (SAVR) and occurs in up to 50% of the patients. Development of postoperative AF (POAF) is associated with a 2-3 fold increased risk of adverse events, including stroke, myocardial infarction and death.Several studies have implied that prophylactic Atorvastatin therapy could prevent POAF in patients undergoing coronary artery bypass graft. These studies suggest that Atorvastatin has rapid and significant pleiotropic actions that reduce the risk of POAF. However, prophylactic treatment with statins has yet to be understood in SAVR. The aim of this study is to investigate whether prophylactic administration of torvastatin reduces POAF in patients undergoing SAVR. METHODS AND ANALYSIS: In this investigator-initiated, prospective, parallel-group, randomised, double-blind, placebo-controlled single-centre trial, 266 patients undergoing elective solitary SAVR with bioprosthetic valve, with no prior history of AF, and statin-naïve will be randomised (1:1) to treatment with Atorvastatin (80 mg once daily) or matching placebo for 1-2 weeks prior to and 30 days after surgery. The primary endpoint is POAF defined as an episode of irregular RR-intervals without a traceable p-wave of at least 30 s duration. After discharge and until day 30 after surgery, POAF will be documented by either rhythm strip or 12-lead ECG. ETHICS AND DISSEMINATION: Protocol approval has been obtained from the Regional Scientific Ethical Committee for Southern Denmark (S-20210159), The Danish Medicines Agency (2021103821) and the Data Protection Agency (21/65621).The trial is conducted in accordance with the Declaration of Helsinki, the ICH-GCP (International Conference on Harmonisation Good Clinical Practice) guidelines and the legal regulations of Denmark. Study findings will be shared via peer-reviewed journal publication and conference presentations. TRIAL REGISTRATION NUMBER: NCT05076019.

A targeted multiplex mass spectrometry method for quantitation of abundant matrix and cellular proteins in formalin-fixed paraffin embedded arterial tissue.

Assessment of proteins in formalin-fixed paraffin-embedded (FFPE) tissue traditionally hinges on immunohistochemistry and immunoblotting. These methods are far from optimal for quantitative studies and not suitable for large-scale testing of multiple protein panels. In this study, we developed and optimised a novel targeted isotope dilution mass spectrometry (MS)-based method for FFPE samples, designed to quantitate 17 matrix and cytosolic proteins abundantly present in arterial tissue. Our new method was developed on FFPE human tissue samples of the internal thoracic artery obtained from coronary artery bypass graft (CABG) operations. The workflow has a limit of 60 samples per day. Assay precision improved by normalisation to both beta-actin and smooth muscle actin with inter-assay coefficients of variation (CV) ranging from 5.3% to 31.9%. To demonstrate clinical utility of the assay we analysed 40 FFPE artery specimens from two groups of patients with or without type 2 diabetes. We observed increased levels of collagen type IV α1 and α2 in patients with diabetes. The assay is scalable for larger cohorts and advantageous for pathophysiological studies in diabetes and the method is easily convertible to analysis of other proteins in FFPE artery samples. SIGNIFICANCE: This article presents a novel robust and precise targeted mass spectrometry assay for relative quantitation of a panel of abundant matrix and cellular arterial proteins in archived formalin-fixed paraffin-embedded arterial samples. We demonstrate its utility in pathophysiological studies of cardiovascular disease in diabetes.

Selection of patients for mechanical circulatory support for refractory out-of-hospital cardiac arrest.

OBJECTIVE: To describe characteristics of patients admitted with refractory cardiac arrest for possible extracorporeal cardiopulmonary resuscitation (ECPR) and gain insight into the reasons for refraining from treatment in some. METHODS: Nationwide retrospective cohort study involving all tertiary centres providing ECPR in Denmark. Consecutive patients admitted with ongoing chest compression for evaluation for ECPR treatment were enrolled. Presenting characteristics, duration of no-flow and low-flow time, end-tidal carbon dioxide (ETCO2), lactate and pH, and recording of reasons for refraining from ECPR documented by the treating team were recorded. Outcomes were survival to intensive care unit admission and survival to hospital discharge. RESULTS: Of 579 patients admitted with refractory cardiac arrest for possible ECPR, 221 patients (38%) proceeded to ECPR and 358 patients (62%) were not considered candidates. Median prehospital low-flow time was 70 min (IQR 56 to 85) in ECPR patients and 62 min (48 to 81) in no-ECPR patients, p<0.001. Intra-arrest transport was more than 50 km in 92 (42%) ECPR patients and 135 in no-ECPR patients (38%), p=0.25. The leading causes for not initiating ECPR stated by the treating team were duration of low-flow time in 39%, severe metabolic derangement in 35%, and in 31% low ETCO2. The prevailing combination of contributing factors were non-shockable rhythm, low ETCO2, and metabolic derangement or prehospital low-flow time combined with low ETCO2. Survival to discharge was only achieved in six patients (1.7%) in the no-ECPR group. CONCLUSIONS: In this large nationwide study of patients admitted for possible ECPR, two-thirds of patients were not treated with ECPR. The most frequent reasons to abstain from ECPR were long duration of prehospital low-flow time, metabolic derangement and low ETCO2.

Factors associated with deep sternal wound infection after open-heart surgery in a Danish registry.

Objective: To conduct a comprehensive multivariate analysis of variables associated with deep sternal wound infection, after open-heart surgery via median sternotomy. Method: A retrospective cohort of all adult patients, who underwent open-heart surgery at Odense University Hospital between 01-01-2000 and 31-12-2020 was extracted from the West Danish Heart Registry. Data were analyzed using maximum likelihood logistic regression. Results: A total of 15,424 patients underwent open-heart surgery and 244 developed a deep sternal wound infection, equivalent to 1,58 %. After data review 11,182 entries were included in the final analysis, of which 189 developed DSWI, equivalent to 1,69 %. Multivariate analysis found the following variables to be associated with the development of deep sternal wound infection (odds ratios and 95%confidens intervals in parentheses): Known arrhythmia (1.70; 1.16-2.44), Left Ventricular Ejection Fraction (1.66; 1.02-2.58), Body Mass Index 25-30 (1.66; 1.12-2.52), Body Mass Index 30-35 (2.35; 1.50-3.71), Body Mass Index 35-40 (3.61; 2.01-6.33), Body Mass Index 40+ (3.70; 1.03-10.20), Age 60-69 (1.64; 1.04-2.67), Age 70-79 (1.95; 1.23-3.19), Chronic Obstructive Pulmonary Disease (1.77; 1.21-2.54), Reoperation (1.63; 1.06-2.45), Blood transfusion in surgery (1.09; 1.01-1.17), Blood transfusion in intensive care unit (1.03; 1.01-1.06), Known peripheral atherosclerosis (1.82; 1.25-2.61), Current smoking (1.69; 1.20-2.35), Duration of intubation (1.33; 1.12-1.57). Conclusion: Increased risk of deep sternal wound infection after open-heart surgery is a multifactorial problem, while some variables are unchangeable others are not. Focus should be on optimizing the condition of the patient prior to surgery e.g. weight loss and smoking. But also factors surrounding the patient e.g. preventing blood loss and minimizing intubation time.

Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury.

AIMS: In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. METHODS AND RESULTS: This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1-2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden's index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time <81 min, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favourable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (P = 0.001) after hospital admission. CONCLUSION: Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Stone heart syndrome after prolonged cardioplegia induced cardiac arrest in open-heart surgery - a pilot study on pigs.

OBJECTIVES: To investigate Stone Heart Syndrome (SHS) as consequence of prolonged ischemic arrest in an experimental study on pigs in regards to onset of SHS and pathological changes. Outcomes defined as aortic cross clamp (ACC) time until onset of SHS and cellular changes characterized by SHS. METHODS: Eight pigs were included to undergo normothermic cardioplegia induced cardiac arrest ranging from 80 to 240 minutes of ACC. Duration of ACC was defined as time from initiation of aortic cross clamping until cessation. Normothermic, cardioplegic solution administered directly into the arterial system, though in a reduced dose compared to clinical practice. Myocardial contracture evaluated by palpation of the myocardium. Biopsies were collected from the left ventricle just after the induction of cardiac arrest and after reperfusion. Biopsies were evaluated for pathological changes indicative of SHS by electron microscopy. RESULTS: Six pigs completed the full trial, while two were lost to bleeding. Pigs undergoing 80 to 120 minutes of ACC regained heart rhythm either spontaneously or after defibrillation. Pigs undergoing more than 180 minutes of ACC had contracted hearts with no electrocardiographic response indicating the development of SHS. Electron microscopy findings after ACC of 80 to 120 minutes showed no or low degrees of cellular changes, whereas pig hearts with more than 180 minutes of ACC showed severe mitochondrial changes, endothelial damage, and shortening of sarcomeres consistent with SHS. CONCLUSION: Development of SHS in pigs was ACC time dependent and solely avoided when ACC was limited to a maximum of 120 minutes.

Occurrence and predictors of pericardial effusion requiring invasive treatment following heart valve surgery.

OBJECTIVES: To describe the occurrence of significant pericardial effusion, and to investigate characteristics associated with pericardial effusion within three months following heart valve surgery. METHODS: A retrospective, observational cohort study including adult patients undergoing heart valve surgery at Odense University Hospital from August 2013 to November 2017. Data were gathered from The Western Denmark Heart Registry and electronic patient records.Cox proportional hazard models were used to investigate the associations between characteristics associated with significant pericardial effusion during index admission and within 3 months. Results are presented as HR with 95% CI. RESULTS: In total, 1460 patients were included (70% men, median age 71 years (IQR 63-76)) and of those, n=230 patients (16%) developed significant pericardial effusion.EuroScore II was significantly associated with an increased risk of pericardial effusion during index admission and associated with a lower risk following discharge (index admission HR 1.05, 95% CI 1.02 to 1.08, after discharge HR 0.80, 95% CI 0.69 to 0.92). Increasing age (HR 0.97, 95% CI 0.95 to 0.98 per year) and concomitant coronary artery bypass grafting versus isolated valve surgery (HR 0.58, 95% CI 0.35 to 0.97) were significantly associated with a reduced risk of pericardial effusions in both periods. Being a man (HR 2.30, 95% CI 1.32 to 4.01) and aortic valve disease versus mitral valve disease (HR 2.16, 95% CI 1.20 to 3.90) were significantly associated with an increased risk after discharge. CONCLUSION: Significant pericardial effusions requiring drainage were present in 16% of cases following heart valve surgery, and different clinical characteristics were associated with the development of effusion.

Influence of fractional flow reserve on grafts patency: Systematic review and patient-level meta-analysis.

OBJECTIVE: To investigate the impact of invasive functional guidance for coronary artery bypass graft surgery (CABG) on graft failure. BACKGROUND: Data on the impact of fractional flow reserve (FFR) in guiding CABG are still limited. METHODS: Systematic review and individual patient data meta-analysis were performed. Primary objective was the risk of graft failure, stratified by FFR. Risk estimates are reported as odds ratios (ORs) derived from the aggregated data using random-effects models. Individual patient data were analyzed using mixed effect model to assess relationship between FFR and graft failure. This meta-analysis is registered in PROSPERO (CRD42020180444). RESULTS: Four prospective studies comprising 503 patients referred for CABG, with 1471 coronaries, assessed by FFR were included. Graft status was available for 1039 conduits at median of 12.0 [IQR 6.6; 12.0] months. Risk of graft failure was higher in vessels with preserved FFR (OR 5.74, 95% CI 1.71-19.29). Every 0.10 FFR units decrease in the coronaries was associated with 56% risk reduction of graft failure (OR 0.44, 95% CI 0.34 to 0.59). FFR cut-off to predict graft failure was 0.79. CONCLUSION: Surgical grafting of coronaries with functionally nonsignificant stenoses was associated with higher risk of graft failure.

Basement membrane proteins in various arterial beds from individuals with and without type 2 diabetes mellitus: a proteome study.

BACKGROUND: Basement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome. METHODS: Human arterial samples collected during heart and vascular surgery from well-characterized patients and stored in the Odense Artery Biobank were analysed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We included ascending thoracic aortas (ATA) (n = 10 (type 2 DM, T2DM) and n = 10 (non-DM)); laser capture micro-dissected plaque- and media compartments from carotid plaques (n = 10 (T2DM) and n = 9 (non-DM)); and media- and adventitia compartments from ITAs (n = 9 (T2DM) and n = 7 (non-DM)). RESULTS: We first extended our previous finding of BM accumulation in arteries from T2DM patients, as 7 of 12 pre-defined BM proteins were significantly upregulated in bulk ATAs consisting of > 90% media. Although less pronounced, BM components tended to be upregulated in the media of ITAs from T2DM patients, but not in the neighbouring adventitia. Overall, we did not detect effects on BM proteins in carotid plaques or in the plaque-associated media. Instead, complement factors, an RNA-binding protein and fibrinogens appeared to be regulated in these tissues from T2DM patients. CONCLUSION: Our results suggest that accumulation of BM proteins is a general phenomenon in the medial layer of non-atherosclerotic arteries in patients with T2DM. Moreover, we identify additional T2DM-associated effects on the arterial proteome, which requires validation in future studies.

Health-Related Quality of Life and Angina in Fractional Flow Reserve- Versus Angiography-Guided Coronary Artery Bypass Grafting: FARGO Trial (Fractional Flow Reserve Versus Angiography Randomization for Graft Optimization).

BACKGROUND: In coronary artery bypass grafting (CABG), the use of fractional flow reserve (FFR) is insufficiently investigated. Stenosis assessment usually relies on visual estimates of lesion severity. This study evaluated health-related quality of life (HRQoL) and angina after FFR- versus angiography-guided CABG. METHODS: One hundred patients referred for CABG were randomized to FFR- or angiography-guided CABG. In the FFR group, lesions with FFR>0.80 were deferred, while the surgeon was blinded to the FFR values in the angiography group. Before and 6 months after CABG, HRQoL was assessed by the health state classifier EQ-5D of the EuroQoL 5-level instrument and angina status based on the Canadian Cardiovascular Society classification system were registered. RESULTS: Six-month angiography included FFR evaluations of deferred lesions. In total, completed EQ-5D of the EuroQoL 5-level instrument questionnaires were available in 86 patients (43 in the FFR versus 43 in the angiography-guided group). HRQoL was significantly improved and angina significantly decreased from baseline to 6 months after CABG with no difference between the randomization groups. Graft failure rates and clinical outcomes were similar in both groups. Patients with graft failure or FFR<0.80 of the previous deferred lesions had significantly lower visual analogue scale scores (78.7±14.2 versus 86.8±14.7, P=0.004) and more angina compared with patients without graft failure or FFR≥0.80 at 6-month follow-up. CONCLUSIONS: FFR- versus angiography-guided CABG demonstrated similar improvements in HRQoL and angina 6 months after CABG. Graft failure or low FFR in deferred lesions were associated with low HRQoL and angina. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02477371.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study.

BACKGROUND: Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. METHODS: This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan-Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. RESULTS: A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow-Pittsburgh Cerebral Performance Categories 1-2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18-1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03-1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12-1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16-1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52-0.76). CONCLUSIONS: A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

Small diameter polycaprolactone vascular grafts are patent in sheep carotid bypass but require antithrombotic therapy.

Background: Polycaprolactone (PCL) scaffolds exhibit high biocompatibility and are attractive as vascular conduits. Materials & methods: PCL tubes were cultivated in bioreactor with human adipose regenerative cells to assess ex vivo cytocompatibility, whereas in vivo PCL tube patency was evaluated in sheep carotid bypass with and without antithrombotic treatment. Results:Ex vivo results revealed increasing adipose regenerative cells on PCL using dynamic bioreactor culturing. In vivo data showed that 67% (2/3) of grafts in the antithrombotic group were patent at day 28, while 100% (3/3) of control grafts were occluded already during the first week due to thrombosis. Histology showed that patent PCL grafts were recellularized by host cells. Conclusion: PCL tubes may work as small diameter vascular scaffolds under antithrombotic treatment.