Endo-Aortic Balloon Occlusion versus Transthoracic Clamping in Minimally Invasive Mitral Valve Surgery.

Objectives: The present study compared the clinical outcome between endo-aortic balloon occlusion (EABO) and transthoracic clamping (TTC) in patients undergoing minimally invasive mitral valve surgery (MIMVS).

Methods: All patients from the Mini-Mitral International Registry undergoing MIMVS were primarily considered for study inclusion. One-to-one nearest neighbour propensity score matching considering clinically relevant baseline covariates. The matched cohort was investigated regarding the clinical outcome between EABO and TTC according to the end-point definitions of the Mitral Valve Academic Research Consortium.

Results: From 2015 to 2021, a total of 6884 patients were primarily included in the study. Propensity score matching resulted in a population of 733 matched pairs. Patients treated with EABO showed significantly lower rates of conversion to sternotomy (13 [1.8%] vs 34 [4. 6%]; P = .001), longer cardiopulmonary bypass time (124 min [105-147] vs 120 min [90-148]; P = .001), and a longer intubation time (11.8 h [7.9-22.2] vs 10.8 h [6.4-20.0]; P < .001). No statistically significant differences were observed regarding postoperative mortality, stroke, bleeding requiring revision, vascular complications, intensive care unit stay, or hospital length of stay.

Conclusions: In patients undergoing MIMVS, EABO and TTC are excellent options for aortic clamping. EABO showed benefits over TTC with lower rates of conversion to full sternotomy.

Keywords: Mini-Mitral International Registry; clinical outcome; endo-aortic balloon occlusion; minimally invasive surgery; mitral valve; transthoracic clamping.

Transcriptional, proteomic and metabolic drivers of cardiac regeneration

Following injury, many organs are capable of rapid regeneration of necrotic tissue to regain normal function. In contrast, the damaged heart typically replaces tissue with a collagen-rich scar, due to the limited regenerative capacity of its functional contractile cardiomyocytes (CMs). However, this regenerative capacity varies dramatically during development and between species. Furthermore, studies have shown that cardiac regeneration can be enhanced to return contractile function to the damaged heart following myocardial infarction (MI). In this review, we outline the proliferative capacity of CMs in utero, postnatally and in adulthood. We also describe the regenerative capacity of the heart following MI injury. Finally, we focus on the various therapeutic strategies that aim to augment cardiac regeneration in preclinical animal models. These include altering transcripts, microRNAs, extracellular matrix proteins and inducing metabolic rewiring. Together, these therapies aim to return function to the damaged heart and potentially improve the lives of the millions of heart failure patients currently suffering worldwide.

Keywords: Cardiovascular Diseases; Heart Failure; Heart Failure, Systolic; Myocardial Infarction.

Left ventricular myocardial molecular profile of human diabetic ischaemic cardiomyopathy

Ischaemic cardiomyopathy is the most common cause of heart failure and often coexists with diabetes mellitus, which worsens patient symptom burden and outcomes. Yet, their combined effects are seldom investigated and are poorly understood. To uncover the influencing molecular signature defining ischaemic cardiomyopathy with diabetes, we performed multi-omic analyses of ischaemic and non-ischaemic cardiomyopathy with and without diabetes against healthy age-matched donors. Tissue was sourced from pre-mortem human left ventricular myocardium. Fatty acid transport and oxidation proteins were most downregulated in ischaemic cardiomyopathy with diabetes relative to donors. However, the downregulation of acylcarnitines, perilipin, and ketone body, amino acid, and glucose metabolising proteins indicated lipid metabolism may not be entirely impaired. Oxidative phosphorylation, oxidative stress, myofibrosis, and cardiomyocyte cytoarchitecture also appeared exacerbated principally in ischaemic cardiomyopathy with diabetes. These findings indicate that diabetes confounds the pathological phenotype in heart failure, and the need for a paradigm shift regarding lipid metabolism.

Keywords: Confocal Microscopy; Diabetes; Human Myocardium; Ischaemic Cardiomyopathy; Multi-omics.

Sheep femoral artery occlusion is well tolerated and does not result in ischemia

Objective: Sheep are commonly used as large animal pre-clinical models for investigating cardiovascular therapies, interventions, anatomy and physiology. Further, novel small diameter vascular grafts are frequently tested via implantation into sheep carotid arteries (CAs). This is because, unlike humans, acute occlusion of one or both sheep CAs is not associated with morbidity or mortality and thus provides safer experimental testing, with reduced ethical constraints, animal numbers and costs. However, to date there has been no evidence regarding sheep tolerance of femoral artery (FA) occlusion.

Methods: In this study, seven sheep underwent CA graft surgery, with digital subtraction angiography (DSA) of the CAs performed every 2 months via femoral access, for a total of 8 months. Four months into the study, the left FA of two sheep became inaccessible due to a suspected FA occlusion. Thus, femoral angiography was performed, followed by FA dissection, FA histology and retrospective analysis of both veterinarian animal monitoring and pain scores.

Results: FA angiography and histology confirmed complete left FA occlusion in two sheep. Retrospective animal monitoring demonstrated sheep with occluded FAs did not display increased pain scores or deleterious effects on their gait or wellbeing.

Conclusion: Our data shows that sheep tolerate FA occlusion with no symptoms, similar to their cerebral circulation, making them an appropriate model for assessing small diameter femoral graft interposition studies and testing other cardiovascular interventions.

Second crossclamp in less invasive mitral valve repair for degenerative mitral regurgitation: predictors and outcomes

Objective: To evaluate the incidence, echocardiographic patterns, operative strategies and results of patients receiving second cross clamp in the large population of the Mini-Mitral-International-Registry.

Methods: We examined 4577 patients with degenerative mitral regurgitation (MR) who underwent less invasive mitral repair. Patients with non-degenerative disease, planned valve replacement, and surgery without cross-clamping were excluded. Multivariable logistic regression model was applied to investigate predictors of second cross-clamp and the relationship between second cross-clamp and outcomes.

Results: Second cross clamp was used in 128 cases (2.8%). Causes of re-crossclamp included residual pathology in 71.9% (n=92) of patients and systolic anterior motion (SAM) in 28.1% (n=36). Re-repair was performed in 104 (81.3%) patients and replacement in 24 (18.7%). After re-repair, 92 patients (94.9%) had no or mild MR, 4 patients (4.1%) had moderate MR and 1 patient (1%) had severe MR. A residual SAM was observed in 2 cases (2.3%). Bileaflet prolapse (OR2.21) and predicted risk of SAM (OR 3.04) were identified as risk factors for second cross-clamp. No association between second cross clamp and mortality or major postoperative complications was found. However, second cross clamp was associated with an increased risk of respiratory insufficiency (OR 4.6) and longer ICU stay (β 0.35).

Conclusions: Second cross-clamping after less invasive mitral repair is infrequent, but may be required particularly in patients with bileafelt pathology or increased risk of SAM. Most re-repairs were successful, with less than 20% of patients requiring replacement. Second cross-clamp was associated with higher risk of respiratory insufficiency and prolonged ICU stay.

Surgical decision-making for concomitant tricuspid valve repair in minimally invasive mitral valve surgery

Objectives: To identify factors influencing the decision to omit tricuspid valve repair in patients who meet guideline criteria for tricuspid valve repair undergoing minimally invasive mitral valve surgery (MIMVS).

Methods: A retrospective analysis was conducted using the MIMVS International Registry, covering 7513 patients from 17 centres in Europe USA, Asia and Australia. Of these, 1077 had an indication for tricuspid valve repair. Patients were stratified into two groups: those who underwent tricuspid valve repair (n = 910) and those who did not (n = 167). Multivariate logistic regression analysis was conducted to identify the factors associated with the decision to perform tricuspid valve repair.

Results: Patients who received tricuspid valve repair were older (72 vs 67 years, P < 0.001), more often female (53.8% vs 39.8%, P < 0.001) and had higher rates of atrial fibrillation (70.1% vs 54%, P < 0.001). Tricuspid valve repair was associated with longer ICU (48 vs 23 hours, P < 0.001) and hospital stays (11 vs 8 days, P < 0.001), but 30-day mortality was similar between groups (4.3% for tricuspid valve repair vs 1.8% for no tricuspid valve repair, P = 0.2). Patients undergoing tricuspid valve repair had higher EuroSCORE II (2.9 vs 1.6, P < 0.001). Key factors for omitting tricuspid valve repair included absence of severe tricuspid regurgitation (odds ratio [OR] 3.31 for moderate tricuspid regurgitation; OR 4.06 for mild tricuspid regurgitation), lower NYHA class (OR 0.61 for NYHA III-IV), and mitral valve disease type (OR 0.38) and institutional practices (SD 0.28).

Conclusions: Prophylactic indications for concomitant tricuspid valve repair in MIMVS are generally followed. Clinical and institutional factors strongly influence the decision to omit the tricuspid procedure despite guideline recommendations. Adhering to guidelines may improve outcomes by standardizing treatment choices.

Mechanical unloading is accompanied by reverse metabolic remodelling in the failing heart: Identification of a novel citraconate-mediated pathway.

Aims: Although functional recovery of the failing heart with left ventricular assist device (LVAD) unloading can occur, the underpinning mechanism is unclear. We aimed to characterize the effect of myocardial biochemical effect of LVAD support in vivo and in vitro.

Methods and results: We performed targeted metabolomics and lipidomics on transcardiac (arterial and coronary sinus) blood samples collected from healthy volunteers (n = 13), patients with end-stage heart failure with reduced ejection fraction (HFrEF, n = 20), and LVAD-supported HFrEF patients (n = 18). Complementary biochemical studies in myocardial tissue samples from healthy donor, HFrEF and LVAD patients, and cardiomyoblasts were performed. Myocardial uptake of intermediates in purine, nucleotide, and tricarboxylic acid (TCA) cycle pathways was depressed in HFrEF patients, with recovery in LVAD patients. Glucose uptake was suppressed in HFrEF but restored in LVAD. Metabolite changes suggestive of impaired fatty acid oxidation were present in HFrEF but not in LVAD. We found that the metabolite citraconate was significantly released by HFrEF hearts compared to controls and this was corroborated, in separate patients, by increased levels of citraconate in HFrEF myocardium but not in LVAD. Whilst citraconate increased succinate deydrogenase (SDH) activity in cardiomyoblasts, its isomer itaconate suppressed SDH activity. SDH activity was maintained in HFrEF myocardium but was diminished in LVAD myocardium.

Conclusions: We report, for the first time, the in-vivo biochemical effects of LVAD unloading in the human heart. Our data identify citraconate as a potentially important regulator of the TCA cycle in the failing heart.

The Historical Evolution of Academic Surgery at Royal Prince Alfred Hospital.

Surgical teaching and research at Royal Prince Alfred Hospital has evolved substantially since the hospital was opened in 1882. Economic constraints, World Wars, developments in technology, changes to healthcare policy and society’s expectations have all presented opportunities and obstacles, and ultimately shaped the current practice of academic surgery at the Hospital. This article aims to trace the historical evolution of academic surgery at Royal Prince Alfred Hospital (RPAH) and discuss the internal and external factors which drove these changes.

Head-to-head comparison of V-A ECMO, Impella and ECPELLA in normal ovine hearts.

Temporary mechanical circulatory support (MCS), including veno-arterial extracorporeal membrane oxygenation (ECMO) and micro-axial pumps (Impella), is increasingly used in clinical practice for refractory circulatory failure. Complex physiological responses to each technique or their combination (ECPELLA) remain debated and are often specific to cardiovascular pathology. A paucity of data on physiological responses to MCS in normal subjects makes comprehensive understanding of such responses in variable disease states difficult, as well as during weaning MCS in recovering hearts. This translational investigation compared three MCS techniques with variable pump flows in healthy sheep (n = 7) to establish baseline for future studies in cardiomyopathic models. All MCS techniques increased arterial elastance, but reduced LV myocardial work, coronary arterial flow and LV myocardial oxygen consumption. ECPELLA was more effective in increasing total systemic blood flow and MAP. The overall similarity between the MCS techniques suggests that the more invasive and complex combination of devices (ECPELLA) can only be justified for management of the severe failing heart as the means for decompressing LV. A study investigating the comparative impacts of different regimes and MCS techniques in a cardiomyopathic model is warranted.

Longitudinal outcomes following international multicentre experience with robotic aortic valve replacement

Objectives: In an effort to maintain the technical aspects of traditional prosthetic surgical aortic valve replacement (AVR) while reducing invasiveness and facilitate options for concomitant operations, transaxillary lateral mini-thoracotomy endoscopic robotic-assisted aortic valve replacement (RAVR) has been introduced. The present data highlight the contemporary international collaborative experience.

Methods: All consecutive patients undergoing standardized RAVR across 10 international sites (1/2020-7/2024) were evaluated using a central database with 1 year follow-up.

Results: A total of 300 patients were analysed with a median predicted risk of 1.6% with aortic stenosis in 85.7%, nearly half with bicuspid valves. Biological prostheses were implanted in 220 (73.3%) with a median valve size 23 mm, 10% receiving aortic root enlargement, with 17% of all patients undergoing concomitant procedures. Median cross-clamp 120 min with no conversions to sternotomy. Median length of stay was 5 days, 4.3% with prolonged ventilation, 1.7% renal failure, 1.0% stroke and 8.3% required re-thoracotomy for evacuation of haemothorax. There were two 30-day operative mortalities (0.7%). The new permanent pacemaker rate for the full cohort was 2.6%. Of 163 patients with complete 1-year clinical and echocardiographic follow-up, mean aortic valve gradient was 10 mmHg and all but 2 patients (1.2%) had trace to no prosthetic or paravalvular insufficiency.

Conclusions: RAVR is safe and effective, providing the reproducible benefits of surgical AVR while affording a less invasive approach that permits the opportunity for concomitant procedures. For low and intermediate risk patients with aortic valve disease, RAVR is a potential reproducible alternative for patients and heart teams.

Keywords: Robotic valve surgery; Robotic-assisted aortic valve replacement.

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