Creating a multivariable model to predict primary graft dysfunction after heart transplantation in the United Kingdom using the 2014 International Society of Heart and Lung Transplantation consensus definition

Heart failure places a global strain on healthcare provision. It has an increasing incidence and represents the endpoint of a variety of cardiovascular diseases. The preceding decades have carved out a clear management algorithm for the use of pharmacotherapies (neurohormonal antagonists), device-based therapies (Implantable Cardioverting Defibrillator (ICD) and Cardiac Resynchronisation Therapy (CRT)) and mechanical therapies including left ventricular assist devices and heart transplantation. While heart transplantation remains the gold standard for the suitable few, the advancement of healthcare systems and improved working conditions and safety regulations have changed the demographics of the typical organ donor which traditionally were young brainstem death donors (DBD) with minimal other comorbidities. Nevertheless, transplantation confers a substantial survival benefit for selected patients with advanced heart failure, achieving a 1-year survival rate of ≥80%. The primary cause for early mortality in recipients remains primary graft dysfunction (PGD). The incidence of PGD throughout the UK and the world are variable due to the lack of a standardised definition until 2014. My research explored the true incidence of PGD throughout the UK using data collected from each of the 6 transplant centres alongside the National Health Service Blood and Transplant database. I then looked at risk factors for PGD which culminated in the largest PGD study recorded at the time of writing. I also looked into the role of mechanical circulatory support to bridge patients in cardiogenic shock post-myocardial infarction in Scotland. I finally developed 2 scoring systems, 1 for Primary Graft Dysfunction (PREDICTA) and 1 using the modified Delphi Method of a consensus agreement (GTS) to factor in elements of frailty which had been garnering increasing interest at conferences I had attended

Learning from Controversy and Revisiting the Randomized Trials of Secondary Mitral Regurgitation

Until recently, conventional mitral valve surgery has been the treatment of choice even in secondary mitral regurgitation. Recent evidence, however, advocates the use of transcatheter edge-to-edge mitral valve repair (TEER) of the mitral valve. This has been reflected by the change in guidelines of the American College of Cardiology/American Heart Association. We reviewed the literature to shed light on the risks and benefits of all interventions, surgical, transcatheter and guideline-directed medical therapy. Secondary mitral regurgitation occurs due to an imbalance between closing forces and tethering forces. Given the pathology extends beyond the valve alone, treatment should be directed at restoring the geometrical shape of the left ventricle alongside the valve. Myocardial revascularization plays a pivotal role in preventing recurrence. The role of papillary muscle approximation in addition to restrictive mitral annuloplasty should be considered in a select group of patients. We also reviewed the current literature on TEERs from the COAPT and Mitra-FR trials while highlighting the concept of proportionate/disproportionate MR which may help identify which patients benefit from mitral valve restoration. Treatment of this condition will require robust randomized trials alongside the use of state-of-the-art imaging technologies available with the full complement of the multidisciplinary team to ensure the best outcomes for each patient

Pathophysiology and outcomes of endothelium function in coronary microvascular diseases: a systematic review of randomized controlled trials and multicenter study

Background: Coronary macrovascular disease is a concept that has been well-studied within the literature and has long been the subject of debates surrounding coronary artery bypass grafting (CABG) vs. Percutaneous Coronary Intervention (PCI). ISCHEMIA trial reported no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management, while in the ORBITA trial PCI did not improve angina frequency score significantly more than placebo, albeit PCI resulted in more patient-reported freedom from angina than placebo. However, these results did not prove the superiority of the PCI against OMT, therefore do not indicate the benefit of PCI vs. the OMT. Please rephrase the sentence. We reviewed the role of different factors responsible for endothelial dysfunction from recent randomized clinical trials (RCTs) and multicentre studies. Methods: A detailed search strategy was performed using a dataset that has previously been published. Data of pooled analysis include research articles (human and animal models), CABG, and PCI randomized controlled trials (RCTs). Details of the search strategy and the methods used for data pooling have been published previously and registered with Open-Source Framework. Results: The roles of nitric oxide (NO), endothelium-derived contracting factors (EDCFs), and vasodilator prostaglandins (e.g., prostacyclin), as well as endothelium-dependent hyperpolarization (EDH) factors, are crucial for the maintenance of vasomotor tone within the coronary vasculature. These homeostatic mechanisms are affected by sheer forces and other several factors that are currently being studied, such as vaping. The role of intracoronary testing is crucial when determining the effects of therapeutic medications with further studies on the horizon. Conclusion: The true impact of coronary microvascular dysfunction (CMD) is perhaps underappreciated, which supports the role of medical therapy in determining outcomes. Ongoing trials are underway to further investigate the role of therapeutic agents in secondary prevention

Host–bacterium interaction mechanisms in Staphylococcus aureus endocarditis: a systematic review

Staphylococci sp. are the most commonly associated pathogens in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations, and the protracted infection courses, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. Thirty-five studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored, giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts’ innate immunity also potentiates its virulence. The goal of this study is to attain a better understanding on the molecular pathways involved in infective endocarditis supported by S. aureus and whether therapeutic avenues for the prevention and treatment of IE can be obtained. The use of antibiotic-treated allogeneic tissues have marked antibacterial action, thereby becoming the ideal substitute in native and prosthetic valvular infections. However, the development of effective vaccines against S. aureus still requires in-depth studies

Heart transplantation: a history lesson of Lazarus

One of the notable advances in modern day medicine is organ transplantation. None more so than the heart. A complex interaction between physiology, surgery and immunology that spanned decades, involving the hard work of many pioneers in their fields. We revisit the contributions of the pioneers as well as marvel at the paradigm shifts in medicine that have made heart transplantation safe and reproducible with in excess of 3000 transplants done yearly today

Heart transplantation: a history lesson of Lazarus

One of the notable advances in modern day medicine is organ transplantation. None more so than the heart. A complex interaction between physiology, surgery and immunology that spanned decades, involving the hard work of many pioneers in their fields. We revisit the contributions of the pioneers as well as marvel at the paradigm shifts in medicine that have made heart transplantation safe and reproducible with in excess of 3000 transplants done yearly today

Primary graft dysfunction after heart transplantation: a thorn amongst the roses

Primary graft dysfunction (PGD) remains the leading cause of early mortality post-heart transplantation. Despite improvements in mechanical circulatory support and critical care measures, the rate of PGD remains significant. A recent consensus statement by the International Society of Heart and Lung Transplantation (ISHLT) has formulated a definition for PGD. Five years on, we look at current concepts and future directions of PGD in the current era of transplantation

A narrative review of the interpretation of guidelines for the treatment of infective endocarditis

The recommendations of the current guidelines and the position papers of professional societies from the European Society of Cardiology/European Society of Cardiothoracic Surgeons (ESC), the American College of Cardiology/American Heart Association/Society of Thoracic Surgeon (ACC/AHA/STS) and American Association of Thoracic Surgeon (AATS) regarding management of patients with valvular heart endocarditis were updated over the past decade. However, some of the recommendations appear to contradict one another. Given the changing paradigms on how the disease manifests, our aim was to review the respective guidelines and highlight these differences whilst drawing attention to the subsequent studies from which they were derived. In particular, concerns regarding antibiotic prophylaxis and therapy, imaging modality for diagnosis and follow-up, cerebrovascular sequalae and timing of surgery are appraised in detail. We also identified the novel techniques used such as transcatheter therapies and advances in imaging modalities used for diagnosis and treatment of this condition. The lack of randomised control trials (RCTs) does raise several issues regarding applicability of findings in day-to-day practice. Therefore, the focus of upcoming studies should be on clearly defined multicenter RCTs to provide more robust evidence for the management and treatment of infective endocarditis as future guidelines will be based on the outcomes of these trials

Pharmacologic approaches against advanced glycation end products (ages) in diabetic cardiovascular disease

Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports

An overview of different methods of myocardial protection currently employed peri-transplantation

Myocardial protection is integral to the functioning of hearts in day to day cardiac surgery. However, due to the longer ischaemic times, it becomes pivotal in the management of organs during transplantation. There are many different strategies employed to ensure diligent and judicious myocardial protection during donor management, transportation of the heart and the post-operative period. Given the limited supply of organs and the increasing waiting lists for heart transplants worldwide, it has become an area of renewed interest with many innovations and inventions using the principles of basic sciences to improve outcomes of transplanted hearts. The heart procurement process encompasses several of the different myocardial protection strategies in tandem to provide the greatest benefit to the recipients. This review looks at the different modalities employed, which include different types of cardioplegia, the role of biomarkers, the cutting-edge novel therapies, hormonal therapies and ischaemic conditioning strategies