Non-invasive cardiac imaging and the risk of coronary atherosclerosis

In this thesis we describe how non-invasive cardiac imaging such as MDCT and dobutamine stress MRI (DSMR) have opened the way to screening cardiac asymptomatic high risk patients. We present the rationale and design of the GROUND study, a prospective, multi-center, randomized clinical trial. Patients with peripheral artery disease (PAD), but without symptomatic cardiac disease were randomized to undergo either CT calcium scoring only or to undergo a non-invasive cardiac imaging algorithm consisting of CT calcium scoring, coronary CT angiography and DSMR testing. Patients with a left main (or equivalent) coronary artery stenosis of >50% on CT did not undergo DSMR testing, but were referred to a cardiologist. Also patients with a positive DSMR were referred to a cardiologist. These referred patients were candidates for conventional coronary artery angiography and cardiac interventions. All participants entered a 5 year follow up period for the occurrence of cardiovascular events. The aim of the study was to evaluate whether a modern imaging algorithm consisting of CT and DSMR can help to reduce cardiac morbidity and mortality in a cardiac asymptomatic high risk population. We present baseline results of 231 participants of the GROUND study. We demonstrate that one fifth of cardiac asymptomatic patients with PAD have a significant stenosis in the left main coronary artery or its equivalent on cardiac CT angiography. A stenosis in this area is considered a class I indication for revascularization. Only 2 out of 76 participants who underwent DSMR had a positive test result. This finding may have major implications for the management of patients with cardiac asymptomatic PAD. More than 90% of the participants show coronary atherosclerosis and half of the patients has a significant stenosis in their coronary arteries. Also half of the patients showed soft plaque in their coronary arteries. With the use of CT calcium scoring, we show a considerable amount of calcium in the coronary arteries of the GROUND study population. We found a 6 times increase in the risk of having a class I revascularization indication for diabetics and a more than 12 times increase of this risk in patients with an Agatston calcium score of more than 400. Diabetic status and the use of calcium scoring may help in selecting PAD patients at highest risk of suffering a cardiac event. In the second half of the thesis we focus on the role of epicardial adipose tissue (EAT) as a potential risk factor for the development of coronary atherosclerosis. EAT is a source of bioactive molecules in the direct surrounding of the coronary artery vessel wall. With the use of cardiac CT the amount of EAT around the heart can be quantified in a reliable way. We demonstrated that EAT was related to multiple known cardiovascular risk factors. Peri-coronary EAT was also related to calcium scoring as a sign of coronary atherosclerosis. Furthermore, we found that EAT is related to the metabolic syndrome and that there was a graded relation between the number of metabolic syndrome factors and peri-coronary EAT.