Non-invasive assessement of coronary flow velocity: Clinical and experimental studies

Abstract

BACKGROUND AND OBJECTIVES Coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) evaluated by transthoracic ultrasound is a promising method to assess ischemic heart disease. CFVR is the ratio between CFV during maximal hyperemia and baseline. A reduced CFVR indicates an increased risk for cardiovascular events. The aims of this thesis were 1. To evaluate the effect of nitroglycerine administration on CFV and CFVR. 2. To investigate if CFVR provides prognostic information about cardiovascular events, in addition to myocardial scintigraphy, in patients with suspected coronary artery disease. 3. To investigate the relationship between CFVR and significant coronary stenosis. 4. To assess the effects of ticagrelor on CFV and dyspnea. METHODS In study I, CFV and CFVR and coronary artery diameter were assessed before and after sublingual nitroglycerine administration in 26 healthy subjects. In study II, CFVR was measured in 371 patients undergoing scintigraphy due to suspected coronary artery disease. CFVR and scintigraphy results were related to cardiovascular events (cardiovascular death, myocardial infarction, acute revascularization) during a mean follow-up of 4.5 years. In study III, CFVR and coronary angiograms were evaluated in 123 patients from study II (n=123). Study IV was a double-blind placebo-controlled cross-over study randomizing 40 healthy subjects to ticagrelor or placebo. CFV and dyspnea were assessed at baseline and during increasing doses of adenosine. RESULTS Nitroglycerine increased CFVR due to a reduction in baseline CFV. Adenosineinduced CFV remained unchanged. A CFVR≤2 was independently associated with cardiovascular event rate (adjusted hazard ratio 3.02 (1.51-6.04, p=0.002) and added prognostic information in addition to scintigraphy. There was a significant association between CFVR and the presence of coronary stenoses. Ticagrelor augmented CFV and dyspnea during adenosine administration. CONCLUSIONS Nitroglycerine increases CFVR which indicates that adenosine alone causes a submaximal hyperemia. The associations between CFVR and cardiovascular events, and between CFVR and significant coronary stenosis supports routine assessment with CFVR in patients with suspected ischemic heart disease. The results indicate that adenosine is involved in the systemic effects of ticagrelor. Keywords: ischemic heart disease, coronary flow velocity, ultrasound