Adipocyte size and lipid content in perivascular adipose tissue are inversely associated with coronary inflammation and atherosclerotic plaque burden in human patients.

Perfusion cardiovascular magnetic resonance (CMR) performed with inadequate adenosine stress leads to false-negative results and suboptimal clinical management. The recently proposed marker of adequate stress, the “splenic switch-off” sign, detects splenic blood flow attenuation during stress perfusion (spleen appears dark), but can only be assessed after gadolinium first-pass, when it is too late to optimize the stress response. Reduction in splenic blood volume during adenosine stress is expected to shorten native splenic T1, which may predict splenic switch-off without the need for gadolinium. Two-hundred and twelve subjects underwent adenosine stress CMR: 1.5 T (n = 104; 75 patients, 29 healthy controls); 3 T (n = 108; 86 patients, 22 healthy controls). Native T1spleen was assessed using heart-rate-independent ShMOLLI prototype sequence at rest and during adenosine stress (140 μg/kg/min, 4 min, IV) in 3 short-axis slices (basal, mid-ventricular, apical). This was compared with changes in peak splenic perfusion signal intensity (ΔSIspleen) and the “splenic switch-off” sign on conventional stress/rest gadolinium perfusion imaging. T1spleen values were obtained blinded to perfusion ΔSIspleen, both were derived using regions of interest carefully placed to avoid artefacts and partial-volume effects. Normal resting splenic T1 values were 1102 ± 66 ms (1.5 T) and 1352 ± 114 ms (3 T), slightly higher than in patients (1083 ± 59 ms, p = 0.04; 1295 ± 105 ms, p = 0.01, respectively). T1spleen decreased significantly during adenosine stress (mean ΔT1spleen ~ −40 ms), independent of field strength, age, gender, and cardiovascular diseases. While ΔT1spleen correlated strongly with ΔSIspleen (rho = 0.70, p < 0.0001); neither indices showed significant correlations with conventional hemodynamic markers (rate pressure product) during stress. By ROC analysis, a ΔT1spleen threshold of ≥ −30 ms during stress predicted the “splenic switch-off” sign (AUC 0.90, p < 0.0001) with sensitivity (90%), specificity (88%), accuracy (90%), PPV (98%), NPV (42%). Adenosine stress and rest splenic T1-mapping is a novel method for assessing stress responses, independent of conventional hemodynamic parameters. It enables prediction of the visual “splenic switch-off” sign without the need for gadolinium, and correlates well to changes in splenic signal intensity during stress/rest perfusion imaging. ΔT1spleen holds promise to facilitate optimization of stress responses before gadolinium first-pass perfusion CMR.

Recent clinical trials indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in heart failure patients, but the underlying mechanisms remain unknown. We explored the direct effects of canagliflozin, an SGLT2 inhibitor with mild SGLT1 inhibitory effects, on myocardial redox signalling in humans. Study 1 included 364 patients undergoing cardiac surgery. Right atrial appendage biopsies were harvested to quantify superoxide (⁠ $O2.−$⁠) sources and the expression of inflammation, fibrosis, and myocardial stretch genes. In Study 2, atrial tissue from 51 patients was used ex vivo to study the direct effects of canagliflozin on NADPH oxidase activity and nitric oxide synthase (NOS) uncoupling. Differentiated H9C2 and primary human cardiomyocytes (hCM) were used to further characterize the underlying mechanisms (Study 3). SGLT1 was abundantly expressed in human atrial tissue and hCM, contrary to SGLT2. Myocardial SGLT1 expression was positively associated with $O2.−$ production and pro-fibrotic, pro-inflammatory, and wall stretch gene expression. Canagliflozin reduced NADPH oxidase activity via AMP kinase (AMPK)/Rac1signalling and improved NOS coupling via increased tetrahydrobiopterin bioavailability ex vivo and in vitro. These were attenuated by knocking down SGLT1 in hCM. Canagliflozin had striking ex vivo transcriptomic effects on myocardial redox signalling, suppressing apoptotic and inflammatory pathways in hCM. We demonstrate for the first time that canagliflozin suppresses myocardial NADPH oxidase activity and improves NOS coupling via SGLT1/AMPK/Rac1 signalling, leading to global anti-inflammatory and anti-apoptotic effects in the human myocardium. These findings reveal a novel mechanism contributing to the beneficial cardiac effects of canagliflozin. Proposed mechanism of canagliflozin-induced improvement of myocardial redox state. Canagliflozin increases intracellular AMP/ATP ratio through inhibition of SGLT1, which can activate AMPK/NOS signalling and increase NO that suppresses pro-inflammatory signalling. AMPK activation also inhibits activation of Rac1 and membrane translocation of Rac1 and p47^phox, which decrease NADPH oxidase activity and superoxide (⁠ $O2.−$⁠) production, attenuates inflammatory and apoptotic pathways and increasing the bioavailability of tetrahydrobiopterin (BH4), a key factor for NOS coupling.

Adipose-secreted WNT5A triggers vascular disease in obesity, activating vascular smooth muscle cell migration by an NADPH oxidase–dependent mechanism.

Operability of type A acute aortic dissections (TAAAD) is currently based on non-standardized decision-making process, and it lacks a disease-specific risk evaluation model that can predict mortality. We investigated patient, intraoperative data, surgeon, and centre-related variables for patients who underwent TAAAD in the UK. We identified 4203 patients undergoing TAAAD surgery in the UK (2009–18), who were enrolled into the UK National Adult Cardiac Surgical Audit dataset. The primary outcome was operative mortality. A multivariable logistic regression analysis was performed with fast backward elimination of variables and the bootstrap-based optimism-correction was adopted to assess model performance. Variation related to hospital or surgeon effects were quantified by a generalized mixed linear model and risk-adjusted funnel plots by displaying the individual standardized mortality ratio against expected deaths. Final variables retained in the model were: age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.02–1.03; P < 0.001]; malperfusion (OR 1.79, 95% CI 1.51–2.12; P < 0.001); left ventricular ejection fraction (moderate: OR 1.40, 95% CI 1.14–1.71; P = 0.001; poor: OR 2.83, 95% CI 1.90–4.21; P < 0.001); previous cardiac surgery (OR 2.29, 95% CI 1.71–3.07; P < 0.001); preoperative mechanical ventilation (OR 2.76, 95% CI 2.00–3.80; P < 0.001); preoperative resuscitation (OR 3.36, 95% CI 1.14–9.87; P = 0.028); and concomitant coronary artery bypass grafting (OR 2.29, 95% CI 1.86–2.83; P < 0.001). We found a significant inverse relationship between surgeons but not centre annual volume with outcomes. Patient characteristics, intraoperative factors, cardiac centre, and high-volume surgeons are strong determinants of outcomes following TAAAD surgery. These findings may help refining clinical decision-making, supporting patient counselling and be used by policy makers for quality assurance and service provision improvement.

No uniform consensus in the UK or Europe exists, for glycaemic management of patients with Diabetes or pre-diabetes undergoing cardiac surgery. [i] Determine the relationship between glycaemic control and cardiac surgical outcomes; [ii] Compare current vs gold standard management of patients with Diabetes or pre-diabetes undergoing cardiac surgery. Searches of MEDLINE, NHS Evidence and Web of Science databases were completed. Articles were limited to those in English, German and French. No date limit was enforced.13,232 articles were identified on initial literature review, and 50 relevant papers included in this review. No national standards for glycaemic control prior to cardiac surgery were identified. Upto 30% of cardiac surgical patients have undiagnosed Diabetes. Cardiac surgical patients without Diabetes with pre-operative hyperglycaemia have a 1 year mortality double that of patients with normoglyacemia, and equivalent to patients already diagnosed with Diabetes. Pre- and peri-operative hyperglycaemia is associated with worse outcomes. Evidence regarding tight glycaemic control vs moderate glycaemic control is conflicting. Tight control may be more effective in patients without Diabetes with pre−/peri-operative hyperglycaemia, and moderate control appears more effective in patients with pre-existing Diabetes. Patients with well controlled Diabetes may achieve comparable outcomes to patients without Diabetes with similar glycaemic control. Pre / peri-operative hyperglycaemia is associated with worse outcomes in both patients with, and without Diabetes undergoing CABG. This review supports the pre-operative screening, and optimisation of glycaemic control in patients undergoing cardiac surgery. Optimal glycaemic management remains unclear and clear guidelines are needed.