The validity and reliability of the Arabic version of the EQ-5D in atrial fibrillation patients in a conflict country: a study from Syria.

BACKGROUND: The EQ-5D is one of the most commonly used tools to establish health-related quality of life (QoL). EQ-5D data in atrial fibrillation (AF) patients in the Middle East are lacking. OBJECTIVES: This study aims to evaluate the reliability and validity of the Arabic version of the EQ-5D in AF inpatients in Syria. METHODS: The study involved patients admitted to the emergency department of Tishreen's University Hospital in Latakia with AF as the primary diagnosis between the 1st of June 2021 and the 1st of June 2023. Arabic versions of the EQ-5D, EQ-VAS and SF36 questionnaires were administered to patients. Validation was done using convergent, discriminant, and known-groups validity, while reliability was conducted using EQ-5D retesting within 2-4 weeks. RESULTS: 432 participants were included in the study with a mean ± standard deviation of 63 ± 15. Males represented 242 (56%) of the participants. All hypotheses relating EQ-5D responses to external variables were satisfied. All three validation hypotheses demonstrated that the EQ-5D had the convergent, discriminant and known group validity to assess QoL in this cohort. The intraclass correlation coefficient (ICC) for test-retest reliability ranged between 0.74 and 0.88, while Cohen's κ ranged between 0.72 and 0.86. Cronbach's α value for internal consistency was 0.73. CONCLUSION: The Arabic version of EQ-5D was valid and reliable in measuring QoL in AF inpatients in Syria. This validation opens the door for more widespread use of the EQ-5D in Arabic-speaking regions, facilitating better-informed healthcare decisions and improving patient care strategies in Syria and other Middle Eastern countries.

Incidence, outcomes, and predictors of new heart failure in syrian conflict-affected population following hospitalization for atrial fibrillation: A retrospective cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia worldwide. Data regarding readmission for new congestive heart failure (CHF) following index admission for AF in the developing world are poorly described. OBJECTIVES: The study aimed to assess the rate, predictors, and outcomes of 120-day CHF readmission after index admission for AF in Syria. METHODS: This retrospective cohort study collected all adult patients without known CHF who had an index admission with AF to Latakia's tertiary center between June 2021-December 2023. Data were taken from patients' medical notes. The primary outcome included readmission with incident CHF within 120 of index discharge, and secondary outcomes included predictors and outcomes of these CHF readmissions. RESULTS: A total of 660 patients were included in the final analysis, of which 69 (11.7%) were readmitted with new CHF within 120 days of index discharge. Readmitted patients had higher median age (58 vs 70 years, p < .001). Factors that independently increased 120-day CHF incidence were age ≥60 years (HR: 9.8, 95% CI: 4.8-23.6, p < .001), diabetes mellitus (DM) (HR:2.9, 95% CI:1.7-4.9, p < .001), valvular heart disease (VHD) (HR:1.7, 95% CI:1.04-2.78, p = .047), and hypertension (HR:2.5, 95% CI:1.5-4, p < .001). Inpatient mortality occurred in six readmitted patients (9%). LVEF <40% (HR:6.7, 95% CI: 24.31, p = .01) and DM (HR:7.2, 95% CI: 1.9-33, p = .004) were independently associated with inpatient mortality. CONCLUSION: Hospitalization for new CHF was common in Syrian patients discharged with AF. The clinical predictors of incident CHF emphasize the importance of integrated management of lifestyle risk factors and common comorbidities in AF patients to optimize outcomes in resource-depleted communities.

Two Decades of CABG in the UK: A Propensity Matched Analysis of Outcomes by Conduit Choice.

Background/Objectives: Grafting of LIMA to LAD has long been considered the gold-standard conduit choice for patients undergoing CABG. Despite this, the LSV remains the most used conduit by volume and some patients may not receive even a single arterial conduit. However, the outcomes in this group are not frequently explored. This study, therefore, compares in-hospital outcomes of patients who underwent CABG without any arterial conduits to those who received at least one arterial conduit. Methods: Retrospective propensity-matched database analysis of consecutive patients undergoing CABG in the UK between 1996 and 2019 using data from the National Adult Cardiac Surgery Audit. Results: 335,144 patients underwent CABG, with 6% receiving venous conduits only; matched outcomes are reported for 39,812 patients. In both unmatched and matched groups, we found a significant increase in mortality with the use of veins only (matched mortality 5.3% vs. 3.8%, p < 0.001) with estimated treatment effect for mortality OR 1.43, p < 0.001 (95% CI: 1.31-1.57). We also identified greater rates of post-operative dialysis, IABP insertion, and length of hospital stay in this group. Conclusions: We identified a significant increase in in-hospital mortality with the use of veins only compared to using at least one arterial graft to the LAD. While a single arterial graft should be prioritised wherever possible, venous revascularisation retains a critical role for specific patients. We must, therefore, continue to conduct research addressing the mechanisms underlying and propagating vein graft disease in order better to optimise outcomes for this niche patient group after CABG.

Atrial fibrillation inpatient management patterns and clinical outcomes during the conflict in Syria: An observational cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there is no data on AF inpatient management strategies and clinical outcomes in Syria. OBJECTIVES: The study aims were to review the inpatient management of patients with AF and assess cardiovascular (CV) mortality in a tertiary cardiology centre in Latakia, Syria. METHODS: A single-centre retrospective observational cohort study was conducted at Tishreen's University Hospital, Latakia, Syria, from June 2021 to June 2023. Patients ≥16 years of age presenting and being treated for AF as the primary diagnosis with or without a thromboembolic event were included. Medical records were examined for patients' demographics, laboratory results, treatment plans and inpatient details. Studied outcomes include inpatient all-cause and CV mortality, ischemic and bleeding events, and conversion to sinus rhythm (SR). RESULTS: The study included 596 patients. The median age was 58, and 61% were males. 121 patients (20.3%) were known to have AF. A rhythm control strategy was pursued in 39% of patients. Ischemic and bleeding events occurred in 62 (11%) and 12 (2%), respectively. CV and all-cause mortality occurred in 28 (4.7%) and 31 patients (5%), respectively. The presence of valvular heart disease (VHD) (adjusted odds ratio (aOR) = 9.1, 95% confidence interval (CI): 1.7 to 55.1, p < .001), thyroid disease (aOR: 9.7, 95% CI = 1.2 to 91.6, p < .001) and chronic obstructive pulmonary disease (COPD) (aOR: 82, 95% CI: 12.7 to 71, p < .001) were independent risk factors of increased CV inpatient mortality. CONCLUSION: Syrian inpatients admitted with AF in Latakia are relatively younger than those in other countries. Active thyroid disease, COPD and VHD were independent risk factors of inpatient CV mortality with AF.

Transaortic septal myectomy at the time of aortic valve replacement for severe aortic stenosis: a case series of 55 cases.

Introduction: Symptomatic aortic valve stenosis (AS) is associated with asymmetric basal septal hypertrophy (ABSH) in 10% of cases. In this cohort, it has been suggested that rectification of the left ventricular outflow tract obstruction (LVOTO) by concomitant septal myectomy (CSM) can improve the results of aortic valve replacement (AVR). Objective: This study aims to present the technique of AVR with CSM for severe AS with ABSH and to determine the associated early and late post-operative outcomes. Methods: Fifty-five patients were prospectively recruited to undergo AVR with CSM between 2011 and 2021 at two centres. The primary outcomes were mortality within 30 days, incidence of post-operative ventricular septal defects (VSD) and prosthetic valve sizing. The secondary outcomes were in-hospital complications, permanent pacemaker implantation (PPI), survival at 15 months and changes on transthoracic echocardiogram. Results: Post-operative mortality was 1.8% and this figure was unchanged at 15-month follow-up. No patients developed a post-operative VSD. Intra-operatively, it was found that in 94.6% cases the direct valve sizing increased by one, when compared to the measurement made before CSM. The indexed effective orifice area (iEOA) was > 85 cm2/m2 in 96.4% and no patients had an iEOA ≤ 0.75 cm2/m2. Four patients (7.3%) required PPI due to complete atrioventricular block. Conclusion: AVR with CSM is a simple technique that can be utilised in severe AS with ABSH. There does not appear to be an increase in mortality or incidence of iatrogenic VSDs. Importantly, CSM allows for the implantation of a larger aortic valve compared to measurements made before CSM.

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery.

BACKGROUND: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. OBJECTIVES: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. SECONDARY OBJECTIVE: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. SEARCH METHODS: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. SELECTION CRITERIA: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. AUTHORS' CONCLUSIONS: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts.

Effect of on-pump vs. off-pump coronary artery bypass grafting in patients with non-dialysis-dependent severe renal impairment: propensity-matched analysis from the UK registry dataset.

Introduction: On-pump coronary artery bypass (ONCABG) grafting in patients with a pre-existing poor renal reserve is known to carry significant morbidity and mortality. There is limited controversial evidence on the benefit of off-pump coronary artery bypass (OPCABG) grafting in these high-risk groups of patients. We compared early clinical outcomes in propensity-matched cohorts of patients with non-dialysis-dependent pre-operative severe renal impairment undergoing OPCABG vs. ONCABG, captured in a large national registry dataset. Methods: All data for patients with a pre-operative creatinine clearance of less than 50 mL/min who underwent elective or urgent isolated OPCABG or ONCABG from 1996 to 2019 were extracted from the UK National Adult Cardiac Surgery Audit (NACSA) database. Propensity score matching was performed using 1:1 nearest neighbor matching without replacement using several baseline characteristics. We investigated the effect of ONCABG vs. OPCABG in the matched cohort using cluster-robust standard error regression. Results: We identified 8,628 patients with severe renal impairment undergoing isolated CABG, of whom 1,142 (13.23%) underwent OPCABG during the study period. We compared 1,141 propensity-matched pairs of patients undergoing OPCABG vs. ONCABG. The median age of the matched population was 78 years in both groups, with no significant imbalance post-matching in the rest of the variables. There was no difference between OPCABG and ONCABG in in-hospital mortality rates, post-operative dialysis, and stroke rates. However, the return to theatre for bleeding or tamponade was higher in ONCABG vs. OPCABG (P > 0.02); however, OPCABG reduced the total length of stay in the hospital by 1 day (P = 0.008). After double adjustment in the matched population using cluster-robust standard regression, ONCABG did not increase mortality compared to OPCABG (OR, 1.05, P = 0.78), postoperative stroke (OR, 1.7, P = 0.12), and dialysis (OR, 0.7, P = 0.09); however, ONCABG was associated with an increased risk of bleeding (OR, 1.53, P = 0.03). Discussion: In this propensity analysis of a large national registry dataset, we found no difference in early mortality and stroke in patients with pre-operative severe renal impairment undergoing OPCABG or ONCABG surgery; however, ONCABG was associated with an increased risk of return to theatre for bleeding and an increased length of hospital stay.

Osteopontin Activation and Microcalcification in Venous Grafts Can Be Modulated by Dexamethasone.

BACKGROUND: Osteopontin has been implicated in vascular calcification formation and vein graft intimal hyperplasia, and its expression can be triggered by pro-inflammatory activation of cells. The role of osteopontin and the temporal formation of microcalcification in vein grafts is poorly understood with a lack of understanding of the interaction between haemodynamic changes and the activation of osteopontin. METHODS: We used a porcine model of vein interposition grafts, and human long saphenous veins exposed to ex vivo perfusion, to study the activation of osteopontin using polymerase chain reaction, immunostaining, and 18F-sodium fluoride autoradiography. RESULTS: The porcine model showed that osteopontin is active in grafts within 1 week following surgery and demonstrated the presence of microcalcification. A brief pretreatment of long saphenous veins with dexamethasone can suppress osteopontin activation. Prolonged culture of veins after exposure to acute arterial haemodynamics resulted in the formation of microcalcification but this was suppressed by pretreatment with dexamethasone. 18F-sodium fluoride uptake was significantly increased as early as 1 week in both models, and the pretreatment of long saphenous veins with dexamethasone was able to abolish its uptake. CONCLUSIONS: Osteopontin is activated in vein grafts and is associated with microcalcification formation. A brief pretreatment of veins ex vivo with dexamethasone can suppress its activation and associated microcalcification.

Trends and outcomes of concomitant aortic valve replacement and coronary artery bypass grafting in the UK and a survey of practices.

OBJECTIVES: Concomitant revascularization of coronary artery disease at the same time as treatment for aortic valvopathy favourably impacts survival. However, combined surgery may be associated with increased adverse outcomes compared to aortic valve replacement (AVR) or coronary artery bypass grafting in isolation. METHODS: We retrospectively analyzed all patients who underwent AVR with bypass grafting between February 1996 and March 2019 using data from the National Adult Cardiac Surgery Audit. We used a generalized mixed-effects model to assess the effect of the number and type of bypass grafts associated with surgical AVR on in-hospital mortality, postoperative stroke, and the need for renal dialysis. Furthermore, we conducted an international cross-sectional survey of cardiac surgeons to explore their views about concomitant AVR with coronary bypass grafting interventions. RESULTS: Fifty-one thousand two hundred and seventy-two patients were included in the study. Patients receiving 2 or more bypass grafts demonstrated more significant preoperative comorbidity and disease severity. Patients undergoing 2 and >2 grafts in addition to AVR had increased mortality as compared to patients undergoing AVR and only 1 graft [odds ratio (OR) 1.17, 95% confidence interval (CI) [1.05-1.30], P = 0.005 and OR 1.15, 95% CI [1.02-1.30], P = 0.024 respectively]. A single arterial conduit was associated with a reduction in mortality (OR 0.75, 95% CI [0.68-0.82], P < 0.001) and postoperative dialysis (OR 0.87, 95% CI [0.78-0.96], P = 0.006), but this association was lost with >1 arterial conduit. One hundred and three surgeons responded to our survey, with only a small majority believing that the number of bypass grafts can influence short- or long-term postoperative outcomes in these patients, and an almost equal split in responders supporting the use of staged or hybrid interventions for patients with concomitant pathology. CONCLUSIONS: The number of grafts performed during combined AVR and coronary artery bypass grafting is associated with increased morbidity and mortality. The use of an arterial graft was also associated with reduced mortality. Future studies are needed to assess the effect of incomplete revascularization and measure long-term outcomes. Based on our data, current published evidence, and the collective expert opinion we gathered, we endorse future work to investigate the short and long-term efficacy and safety of hybrid intervention for patients with concomitant advanced coronary and aortic valve disease.

The Role of Preservation Solutions upon Saphenous Vein Endothelial Integrity and Function: Systematic Review and UK Practice Survey.

The long saphenous vein is the most used conduit in cardiac surgery, but its long-term patency is limited by vein graft disease (VGD). Endothelial dysfunction is a key driver of VGD; its aetiology is multi-factorial. However emerging evidence identifies vein conduit harvest technique and preservation fluids as causal in their onset and propagation. This study aims to comprehensively review published data on the relationship between preservation solutions, endothelial cell integrity and function, and VGD in human saphenous veins harvested for CABG. The review was registered with PROSPERO (CRD42022358828). Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were undertaken from inception until August 2022. Papers were evaluated in line with registered inclusion and exclusion criteria. Searches identified 13 prospective, controlled studies for inclusion in the analysis. All studies used saline as a control solution. Intervention solutions included heparinised whole blood and saline, DuraGraft, TiProtec, EuroCollins, University of Wisconsin (UoW), buffered, cardioplegic and Pyruvate solutions. Most studies demonstrated that normal saline appears to have negative effects on venous endothelium and the most effective preservation solutions identified in this review were TiProtec and DuraGraft. The most used preservation solutions in the UK are heparinised saline or autologous whole blood. There is substantial heterogeneity both in practice and reporting of trials evaluating vein graft preservation solutions, and the quality of existing evidence is low. There is an unmet need for high quality trials evaluating the potential for these interventions to improve long-term patency in venous bypass grafts.

Large animal model of vein grafts intimal hyperplasia: A systematic review.

Coronary artery bypass grafting remains the treatment of choice for a large cohort of patients with significant coronary disease. Despite the increased use of arterial grafts, the long saphenous vein remains the most commonly used conduit. Long-term graft patency continues to be the Achilles heel of saphenous vein grafts. This is due to the development of intimal hyperplasia, a chronic inflammatory disease that results in the narrowing and occlusion of a significant number of vein grafts. Research models for intimal hyperplasia are essential for a better understanding of pathophysiological processes of this condition. Large animal models resemble human anatomical structures and have been used as a surrogate to study disease development and prevention over the years. In this paper, we systematically review all published studies that utilized large animal models of vein graft disease with a focus on the type of model and any therapeutic intervention, specifically the use of external stents/mesh.

The Role of Endothelial Cells in the Onset, Development and Modulation of Vein Graft Disease.

Endothelial cells comprise the intimal layer of the vasculature, playing a crucial role in facilitating and regulating aspects such nutrient transport, vascular homeostasis, and inflammatory response. Given the importance of these cells in maintaining a healthy haemodynamic environment, dysfunction of the endothelium is central to a host of vascular diseases and is a key predictor of cardiovascular risk. Of note, endothelial dysfunction is believed to be a key driver for vein graft disease-a pathology in which vein grafts utilised in coronary artery bypass graft surgery develop intimal hyperplasia and accelerated atherosclerosis, resulting in poor long-term patency rates. Activation and denudation of the endothelium following surgical trauma and implantation of the graft encourage a host of immune, inflammatory, and cellular differentiation responses that risk driving the graft to failure. This review aims to provide an overview of the current working knowledge regarding the role of endothelial cells in the onset, development, and modulation of vein graft disease, as well as addressing current surgical and medical management approaches which aim to beneficially modulate endothelial function and improve patient outcomes.

Evaluating the Feasibility of Screening Relatives of Patients Affected by Nonsyndromic Thoracic Aortic Diseases: The REST Study.

Background Diseases of the thoracic aorta are characterized by a familial etiology in up to 30% of the cases. Nonsyndromic thoracic aorta diseases (NS-TADs) lack overt clinical signs and systemic features, which hinder early detection and prompt surgical intervention. We hypothesize that tailored genetic testing and imaging of first-degree and second-degree relatives of patients affected by NS-TADs may enable early diagnosis and allow appropriate surveillance or intervention. Methods and Results We conducted a feasibility study involving probands affected by familial or sporadic NS-TADs who had undergone surgery, which also offered screening to their relatives. Each participant underwent a combined imaging (echocardiogram and magnetic resonance imaging) and genetic (whole exome sequencing) evaluation, together with physical examination and psychological assessment. The study population included 16 probands (8 sporadic, 8 familial) and 54 relatives (41 first-degree and 13 second-degree relatives) with median age 48 years (range: 18-85 years). No syndromic physical features were observed. Imaging revealed mild-to-moderate aortic dilation in 24% of relatives. A genetic variant of uncertain significance was identified in 3 families. Imaging, further phenotyping, or a form of secondary prevention was indicated in 68% of the relatives in the familial group and 54% in the sporadic group. No participants fulfilled criteria for aortic surgery. No differences between baseline and 3-month follow-up scores for depression, anxiety, and self-reported quality of life were observed. Conclusions In NS-TADs, imaging tests, genetic counseling, and family screening yielded positive results in up to 1 out of 4 screened relatives, including those in the sporadic NS-TAD group. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03861741.

Next-Generation and Single-Cell Sequencing Approaches to Study Atherosclerosis and Vascular Inflammation Pathophysiology: A Systematic Review.

Background and Aims: Atherosclerosis is a chronic inflammatory disease that remains the leading cause of morbidity and mortality worldwide. Despite decades of research into the development and progression of this disease, current management and treatment approaches remain unsatisfactory and further studies are required to understand the exact pathophysiology. This review aims to provide a comprehensive assessment of currently published data utilizing single-cell and next-generation sequencing techniques to identify key cellular and molecular contributions to atherosclerosis and vascular inflammation. Methods: Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were undertaken from inception until February 2022. A narrative synthesis of all included studies was performed for all included studies. Quality assessment and risk of bias analysis was evaluated using the ARRIVE and SYRCLE checklist tools. Results: Thirty-four studies were eligible for narrative synthesis, with 16 articles utilizing single-cell exclusively, 10 utilizing next-generation sequencing and 8 using a combination of these approaches. Studies investigated numerous targets, ranging from exploratory tissue and plaque analysis, cell phenotype investigation and physiological/hemodynamic contributions to disease progression at both the single-cell and whole genome level. A significant area of focus was placed on smooth muscle cell, macrophage, and stem/progenitor contributions to disease, with little focus placed on contributions of other cell types including lymphocytes and endothelial cells. A significant level of heterogeneity exists in the outcomes from single-cell sequencing of similar samples, leading to inter-sample and inter-study variation. Conclusions: Single-cell and next-generation sequencing methodologies offer novel means of elucidating atherosclerosis with significantly higher resolution than previous methodologies. These approaches also show significant potential for translatability into other vascular disease states, by facilitating cell-specific gene expression profiles between disease states. Implementation of these technologies may offer novel approaches to understanding the disease pathophysiology and improving disease prevention, management, and treatment.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021229960, identifier: CRD42021229960.

Acute shear stress and vein graft disease.

The long saphenous vein is commonly used in cardiac surgery to bypass occluded coronary arteries. Its use is complicated by late stenosis and occlusion due to the development of intimal hyperplasia. It is accepted that intimal hyperplasia is a multifactorial inflammatory process that starts immediately after surgery. The role of acute changes in haemodynamic conditions when the vein is implanted into arterial circulation, especially shear stress, is not fully appreciated. This review provides an overview of intimal hyperplasia and the effect of acute shear stress changes on the activation of pro-inflammatory mediators.

Gene and metabolite expression dependence on body mass index in human myocardium.

We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-six adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28-29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI < 25, 25 ≤ BMI ≤ 32, and BMI > 32. The analysis indicated that protein translation-related pathways were downregulated in 25 ≤ BMI ≤ 32 compared with BMI < 25 patients. Muscle contraction transcripts were upregulated in 25 ≤ BMI ≤ 32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI > 32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI > 32 group and α-ketoglutarate increasing in the BMI < 25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.

Nrf2-Keap-1 imbalance under acute shear stress induces inflammatory response in venous endothelial cells.

Vascular endothelial cell stimulation is associated with the activation of different signalling pathways and transcription factors. Acute shear stress is known to induce different pro-inflammatory mediators such as IL-8. Nrf2 is activated by prolonged high shear stress promoting an antiinflammatory and athero-protective environment. However, little is known about the impact of acute shear stress on Nrf2 and Keap1 function and its role in IL-8 regulation. We aimed to examine Nrf2-Keap1 complex activation in-vitro and its role in regulating IL-8 transcripts under acute arterial shear stress (12 dyn/cm2) in venous endothelial cells (ECs). We note that acute high shear stress caused a significant upregulation of Nrf2 target genes, HO-1 and GCLM and an increased IL-8 upregulation at 90 and 120 minutes. Mechanistically, acute high shear did not affect Nrf2 nuclear translocation but resulted in reduced nuclear Keap1, suggesting that the reduction in nuclear Keap1 may result in increased free nuclear nrf2 to induce transcription. Consistently, the suppression of Keap1 using shRNA (shKeap1) resulted in significant upregulation of IL-8 transcripts in response to acute shear stress. Interestingly; the over expression of Nrf2 using Nrf2-Ad-WT or Sulforaphane was also associated with significant upregulation of IL-8 compared to controls. This study highlights the role of Keap1 in Nrf2 activation under shear stress and indicates that activation of Nrf2 may be deleterious in ECs in the context of acute haemodynamic injury.

The impact of patient-prosthesis mismatch on early and long-term survival after aortic replacement with the Edwards Perimount valve: A propensity score-matched analysis.

BACKGROUND: To investigate the impact of severe patient-prosthesis mismatch (PPM) related to the Edwards Lifesciences Perimount (EP) bioprosthesis in the aortic position on early in-hospital outcomes and long-term survival. METHODS: A total of 5964 consecutive patients underwent aortic valve replacement at the Bristol Heart Institute between 1998 and 2014, 2667 representing the cohort of this study received EP. PPM was defined severe as EOAi < 0.65 cm2 /m2 . To minimize bias, propensity score matching was conducted and two groups A and B (without and with severe PPM) of 320 patients with similar preoperative characteristics were matched. We assessed early in-hospital outcomes including CVA, re-exploration for bleeding, low cardiac output, wound infection, acute renal injury, length of hospital stay, and long-term survival for both groups in unmatched and matched populations. RESULTS: In the unmatched analysis, 18.3% of patients had severe PPM. Severe PPM was not associated with increased in-hospital mortality (4.5% vs. 2.9%, respectively, p = .09) or any other early adverse outcomes except increased length of hospital stay (10.57 ± 8.2 vs. 11.7 ± 9.4, respectively, p = .01). Long-term survival differed significantly between groups at 2 and 8 years (91.8% vs. 91.4% and 60.5% vs. 55.7%, respectively, p = .02). Matched analysis showed no differences between the groups in early health outcomes and overall survival at 2 and 8 years was also similar (89.7% vs. 91% and 57.3% vs. 58%, group A vs. B, respectively p = .9). CONCLUSION: Presence of PPM does not seem to affect early in-hospital outcomes or late survival when using EP in patients undergoing aortic valve replacement.

Benefits of mitral valve repair over replacement in the elderly: a systematic review and meta-analysis.

OBJECTIVES: Mitral valve (MV) repair has demonstrated excellent short- and long-term outcomes, however, its merit in the elderly population is still debated. We conducted a meta-analysis of studies that have compared the MV repair to replacement in the elderly population. METHODS: A systematic literature search was conducted for any study published on MV surgery on elderly patients (≥75 years old). A pooled risk-ratio meta-analysis was done to evaluate short-term mortality, postoperative complications, surgical timings, and long-term survival rates. RESULTS: A total of nine retrospective observational studies were included in the quantitative meta-analysis. Pooled meta-analysis showed a reduced risk of short-term mortality for the MV repair group (risk ratio [RR] = 0.41 [0.24-0.71], p-value = .005). Postoperative neurological complications were in favor of repair, although not significantly (RR = 0.49 [0.21-1.11], p-value = .07). Operative timings (cardiopulmonary bypass and crossclamp time) were not different between the groups although no data were available on the complexity of the repairs. Long-term survival rates were in favor of the repairs (pooled treatment effect of -0.47 [-0.64; -0.29], p = .005). CONCLUSIONS: MV surgery is a safe and effective procedure for the elderly. MV repair demonstrated better short-term outcomes compared to replacement. Long-term survival rates are significantly better after repair.