PubMed Posts

Ageing is one of the most significant risk factors for heart disease; however, it is still not clear how the human heart changes with age. Taking advantage of a unique set of pre-mortem, cryopreserved, non-diseased human hearts, we performed omics analyses (transcriptomics, proteomics, metabolomics, and lipidomics), coupled with biologically informed computational modelling in younger (≤ 25 years old) and older hearts (≥ 50 years old) to describe the molecular landscape of human cardiac ageing. In older hearts, we observed a downregulation of proteins involved in calcium signalling and the contractile apparatus. Furthermore, we found a potential dysregulation of central carbon generation of fuel, glycolysis, and fatty acids oxidation, along with an increase in long-chain fatty acids. This study presents and analyses the first molecular data set of normal human cardiac ageing, which has relevant implications for understanding the human cardiac ageing process and the development of age-related heart disease.

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.

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.

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.

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.

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.