VItamin D as a Novel Determinant of Injurious Cardiac Remodelling After acuTE Myocardial Infarction

Participants Patients who have recently (<72 hours) suffered an acute myocardial infarction will be invited to participate. The immediate post-infarction period is one of particular anxiety for patients and their carers and the project has been designed following advice from Patient-Public-Involvement advisers and also after discussion of the project at the Cardiovascular Clinical Research Facility PPI group meeting. Patient attendance will be kept to a minimum and dovetail with clinical investigations wherever possible. In view of the exploratory nature of the project, and the primary endpoint: left ventricular remodelling, exclusion and inclusion criteria have been limited, preferring instead to capture a real-world pragmatic view of changes in cardiac function following myocardial infarction. This is also important when viewed in context of the long-term plan to investigate the effects of vitamin D in ameliorating these adverse changes following a heart attack.

Data collection, administration and imaging protocol Demographic and clinical variables will be recorded on a bespoke database, which will also store biochemical information including vitamin D, PTH and vitamin D binding protein levels measured in routine blood samples. EDTA blood we will also be stored for analysis of vitamin D binding protein haplotypes. It is thought that vitamin D does not exhibit an acute phase response so levels are stable following a myocardial infarction. Each participant will undergo full bedside echocardiography within 72 hours of an acute ST elevation myocardial infarction, the results of which will be available for clinical use. European and American guidelines recommend echocardiography prior to discharge for patients admitted with a STEMI, so this scan will not be an extra procedure. The consent process will describe that the scan is clinically indicated but will also be used for research purposes. As such this proposed study will provide support for the clinical service.

VINDICATE (vitamin D replenishment in patients with chronic heart failure) examined remodelling and vitamin D over 12 months. Remodelling is expected to be accelerated in patients experiencing an acute STEMI (a recent study of acute iron supplementation compared scans at baseline and at three months) and indeed previous work describing the outcomes and predictors of remodelling in 284 STEMI patients did so using repeat echocardiography at 6 months.

Full conventional echocardiography will be carried out with grey-scale and tissue Doppler images recorded in the two and four chamber views using harmonics to improve border definition if necessary. All images will be stored in the 'echopac' digital imaging system and analysed offline. This analysis will include a calculation of LV end diastolic and end systolic volumes using the real-time three dimensional data and two-dimensional biplane discs (modified Simpson's) method by tracing the endocardial border excluding the papillary muscles. An average of three measurements will be used in the final analysis. The frame at the R-wave will be taken as end diastole, and the frame with the smallest LV cavity, as end systole. The LV end-systolic volume index (LVESVi) will be calculated as LVESV/body surface area.

Statistical considerations Study design and analysis plan have been developed with the help of Dr David Cairns, Principal Statistician at the Leeds Clinical Trials Research Unit.