BACKGROUND: The determinants of severe diastolic dysfunction (DD) following myocardial infarction (MI) are not well defined. This study sought to define the determinants of severe DD (restrictive mitral inflow pattern on Doppler echocardiography [RFP]) in patients with a first-ever MI, with particular emphasis on the impact of infarct size. METHODS: Retrospective single-centre study including consecutive patients admitted to a tertiary referral centre with a first-ever non-ST-elevation-MI (NSTEMI) or ST-elevation-MI (STEMI) (n=477). Peak troponin-I (Peak-TnI) was used as the principal measure of infarct size, whilst left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were regarded as surrogate measures. Echocardiography was performed within 24 hours of admission for all patients. RFP was defined as E/A ratio >2.0 or E/A ratio >1.5 and E-wave deceleration time <140 ms. RESULTS: A total of 69 patients (14.5%) had RFP. Peak-TnI levels were higher in the RFP group (32.6±32.7 versus 16.9±25.2 μg/L, p<0.001). In sequential multivariable models incorporating significant clinical, angiographic and left ventricular (LV) size-related variables, Peak-TnI (OR 1.98, p=0.001), WMSI (OR 2.34, p=0.048) and LVEF (OR 0.97, p=0.044) were independent predictors of RFP. Presence of diabetes was also an independent predictor in all the models constructed. When patients were stratified according to an LVEF of 50%, 39% of RFP patients had a preserved LVEF (RFP/preserved EF group), and these patients had lower Peak-TnI levels compared to the RFP/reduced EF group (14.4±18.7 vs 44.5±35.5 μg/L). CONCLUSIONS: Whilst infarct size is a major determinant of severe diastolic dysfunction after MI, a significant subset of patients develop severe diastolic dysfunction despite a small infarct size and preserved LVEF, highlighting that other factors such as pre-existing diastolic dysfunction due to risk factors such as diabetes have an important role in causation.