Design and Rationale for the Endothelin-1 Receptor Antagonism in the Prevention of Microvascular Injury in Patients with non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (ENDORA-PCI) Trial.

PURPOSE: Peri-procedural myocardial infarction (PMI) occurs in a small but significant portion of patients undergoing percutaneous intervention (PCI). The underlying mechanisms are complex and may include neurohormonal activation and release of vasoactive substances resulting in disruption of the coronary microcirculation. Endothelin in particular has been found in abundance in atherosclerotic plaques and in systemic circulation following PCI, and may be a potential culprit for PMI through its action on microvascular vasoconstriction, and platelet and neutrophil activation. In this study we aim to characterize the behavior of the coronary microcirculation during a PCI with the index of microvascular resistance (IMR) and the effect of peri-procedural endothelin antagonism. METHODS: The ENDORA-PCI trial is a randomized, double-blind, placebo-controlled, single-center clinical trial designed to evaluate the efficacy of endothelin antagonism in attenuating the peri-procedural rise in IMR as a surrogate marker for PMI. The patients of interest are those with non-ST elevation acute coronary syndrome (NSTEACS) undergoing PCI, and we aim to recruit 52 patients overall to give the study a power of 80 % at an α level of 5 %. Patients will be randomized in a 1:1 fashion to either Ambrisentan, an endothelin antagonist, or placebo, prior to their PCI. IMR will be measured before and after PCI. The primary endpoint is the difference in peri-procedural changes in patients' IMR between the two groups. CONCLUSION: The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri-procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI.

A review of valve surgery for rheumatic heart disease in Australia.

BACKGROUND: Globally, rheumatic heart disease (RHD) remains an important cause of heart disease. In Australia it particularly affects older non-Indigenous Australians and Aboriginal Australians and/or Torres Strait Islander peoples. Factors associated with the choice of treatment for advanced RHD remain variable and poorly understood. METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database was analysed. Demographics, co-morbidities, pre-operative status and valve(s) affected were collated and associations with management assessed. RESULTS: Surgical management of 1384 RHD and 15843 non-RHD valve procedures was analysed. RHD patients were younger, more likely to be female and Indigenous Australian, to have atrial fibrillation (AF) and previous percutaneous balloon valvuloplasty (PBV). Surgery was performed on one valve in 64.5%, two valves in 30.0% and three valves in 5.5%. Factors associated with receipt of mechanical valves in RHD were AF (OR 2.69) and previous PBV (OR 1.98) and valve surgery (OR 3.12). Predictors of valve repair included being Indigenous (OR 3.84) and having fewer valves requiring surgery (OR 0.10). Overall there was a significant increase in the use of mitral bioprosthetic valves over time. CONCLUSIONS: RHD valve surgery is more common in young, female and Indigenous patients. The use of bioprosthetic valves in RHD is increasing. Given many patients are female and younger, the choice of valve surgery and need for anticoagulation has implications for future management of RHD and related morbidity, pregnancy and lifestyle plans.