Jannike Nickander

Patients with a suspected acute non-ST-elevation myocardial infarctions (NSTEMI) currently undergo invasive coronary angiography (ICA) to identify a potential infarct-related artery (IRA) that become the target for revascularization. However, 25% of patients have no IRA and an identified coronary stenosis may be an en passant finding in a patient with non-ischemic chest pain, i.e. myocarditis or Tako-Tsubo. Cardiac magnetic resonance (CMR) offers non-invasive myocardial tissue characterization and can identify both ischaemic- and non-ischaemic aetiologies for the acute event. Therefore we are performing the Karolinska pilot study for cardiac MRI prior to invasive coronary angiography in patients with suspected NSTEMI (KAPSICA-CMR). This prospective clinical trial tests the hypothesis that implementing novel high-resolution CMR techniques in suspected NSTEMI patients will lead to more accurate diagnosis and the ability to safely rule out the need for an ICA. Patients (n=150) with suspected NSTEMI undergo a CMR before ICA. The CMR is analysed without any clinical or ICA information and is not used to guide ICA or clinical decision making. The CMR is compared with the ICA results and clinical outcome and the health-economic consequences of a CMR first approach will be evaluated. The results of this pilot study will inform a randomized clinical multi-center trial testing the approach of CMR-guided management of patients with suspected NSTEMI.

Bakgrund: Coronary microvascular dysfunction (CMD) is a debilitating syndrome causing significant mortality and morbidity. Despite a high reported prevalence, basic pathophysiological knowledge is still missing, leaving a large patient group without tailored treatment. By targeting the lack of molecular studies in the coronary microcirculation in a controlled fashion in combination with temporal trends and prognostic value, this project will link molecule to imaging to outcome. Målsättning: This project will provide a paradigm for CMD from molecular pathways to diagnostic imaging, by unraveling mechanistic knowledge through RNA sequencing combined with biological trends and prognostic value of myocardial perfusion linking molecule to imaging to outcome. Specific aims include: 1. Identify molecular pathways for the development of CMD through RNA sequencing in endomyocardial biopsies from heart transplanted patients with reduced quantitative perfusion. 2. Investigate the diagnostic yield of CMD in myocardial infarction with normal coronary arteries and uncover biological trends in perfusion over time using quantitative perfusion. 3. Establish the prognostic value of quantitative perfusion as an imaging biomarker across various cardiovascular pathologies. Arbetsplan: Combining in vivo myocardial perfusion mapping with in vitro cardiac biopsies through RNA sequencing to improve mechanistic insight into molecular pathways govering CMD. We will also uncover unkown biological trends in myocardial perfusion over time, and establish the prognostic value of myocardial perfusion as an imaging biomarker in relation to modern cardiovascular therapies. Betydelse: This project will provide a paradigm from molecular pathways to diagnostic imaging which will uncover much needed mechanistic knowledge, but also provide new targets for tailored therapy. Identified molecules may also be used in the future for tailored molecular imaging in the future.