Search

Our earlier work has shown inter‑disease and intra‑disease differences in the cardiac proteome between right (RV) and left (LV) ventricles of patients with aortic valve stenosis (AVS) or coronary artery disease (CAD). Whether disease remodeling also affects acute changes occuring in the proteome during surgical intervention is unknown. This study investigated the effects of cardioplegic arrest on cardiac proteins/phosphoproteins in LV and RV of CAD (n=6) and AVS (n=6) patients undergoing cardiac surgery. LV and RV biopsies were collected during surgery before ischemic cold blood cardioplegic arrest (pre) and 20 min after reperfusion (post). Tissues were snap frozen, proteins extracted, and the extracts were used for proteomic and phosphoproteomic analysis using Tandem Mass Tag (TMT) analysis. The results were analysed using QuickGO and Ingenuity Pathway Analysis softwares. For each comparision, our proteomic analysis identified more than 3,000 proteins which could be detected in both the pre and Post samples. Cardioplegic arrest and reperfusion were associated with significant differential expression of 24 (LV) and 120 (RV) proteins in the CAD patients, which were linked to mitochondrial function, inflammation and cardiac contraction. By contrast, AVS patients showed differential expression of only 3 LV proteins and 2 RV proteins, despite a significantly longer duration of ischaemic cardioplegic arrest. The relative expression of 41 phosphoproteins was significantly altered in CAD patients, with 18 phosphoproteins showing altered expression in AVS patients. Inflammatory pathways were implicated in the changes in phosphoprotein expression in both groups. Inter‑disease comparison for the same ventricular chamber at both timepoints revealed differences relating to inflammation and adrenergic and calcium signalling. In conclusion, the present study found that ischemic arrest and reperfusion trigger different changes in the proteomes and phosphoproteomes of LV and RV of CAD and AVS patients undergoing surgery, with markedly more changes in CAD patients despite a significantly shorter ischaemic period.

Introduction: Despite low mortality, cardiac surgery patients may experience serious life-threatening post-operative complications, often due to extracorporeal circulation and reperfusion. Miniaturised cardiopulmonary bypass (minimally invasive extracorporeal circulation) has been developed aiming to reduce the risk of post-operative complications arising with conventional extracorporeal circulation. Methods: The COMICS trial is a multi-centre, international, two-group parallel randomised controlled trial testing whether type II, III or IV minimally invasive extracorporeal circulation is effective and cost-effective compared to conventional extracorporeal circulation in patients undergoing elective or urgent coronary artery bypass grafting, aortic valve replacement or coronary artery bypass grafting + aortic valve replacement. Randomisation (1:1 ratio) is concealed and stratified by centre and surgical procedure. The primary outcome is a composite of 12 serious complications, objectively defined or adjudicated, 30 days after surgery. Secondary outcomes (at 30 days) include other serious adverse events (primary safety outcome), use of blood products, length of intensive care and hospital stay and generic health status (also at 90 days). Status of the trial: Two centres started recruiting on 08 May 2018; 10 are currently recruiting and 603 patients have been randomised (11 May 2020). The recruitment rate from 01 April 2019 to 31 March 2020 was 40-50 patients/month. About 80% have had coronary artery bypass grafting only. Adherence to allocation is good. Conclusions: The trial is feasible but criteria for progressing to a full trial were not met on time. The Trial Steering and Data Monitoring Committees have recommended that the trial should currently continue.

Right ventricular (RV) remodelling may be an important determinant of clinical outcome in patients undergoing mitral valve surgery for mitral regurgitation. In the present study we hypothesised that, compared to valve replacement, mitral valve repair for degenerative mitral regurgitation may result in better RV remodelling, as assessed by real-time, three-dimensional echocardiography (RT3DE).Forty unselected patients with degenerative mitral valve regurgitation were recruited prospectively. Two-dimensional (2DE) and RT3DE studies were performed prior to surgery and 6 months postoperatively. RV volumes, stroke volume, ejection fraction and mass, as well as RV pressures were calculated. Regression analysis was used to demonstrate the effect of surgical mitral repair and replacement on reverse RV remodelling.Twenty-one patients underwent mitral valve repair and 19 valve replacement. Mean age was 59.5 ± 15.4 years. Five patients who underwent repair (23.8%) developed recurrent MR within 6 months postoperatively. RV systolic pressure was reduced from 39.3 ± 11.9 mmHg, to 25.4 ± 8.3 mmHg after surgery (p=0.027). Compared to preoperative volumes, 6 months after surgery there was a significant reduction in RV diastolic volume and stroke volume (from 106.4 ± 16.3 ml to 80.4 ± 12.1 ml and from 69.2 ± 15.4 ml to 52.2 ± 14.1 ml, respectively, p0.001), and an increase in RV ejection fraction (from 54.5 ± 9.2% to 67.3 ± 8.5%, p0.001). Over a 6-month follow-up period there were no deaths. Overall, the functional class was significantly improved in 39/40 patients (97.5%) but there was no difference between the repair and replacement groups. Using a multivariate regression analysis model including all parameters composing RV remodelling postoperatively, mitral valve repair was the strongest predictor of reverse RV remodelling (reduction of RV end-diastolic volume, p0.01; reduction of RV mass, p0.01; reduction of tricuspid regurgitant velocity, p=0.019).Mitral valve repair leads to more favourable reverse RV remodelling, assessed by RT3DE, compared to valve replacement. This may have important clinical implications.