Theodor Lav - Institutionen för kliniska vetenskaper, Lund

Title: Evaluation of ischemic heart disease using cardiovascular magnetic resonance with aspects on diabetes

Main supervisor: Henrik Engblom

Reviewers: Peder Sörensson, Hannes Holm, Abdulla Ahmed

Abstract

Background

Ischemic heart disease is the leading cause of death worldwide. Coronary artery disease (CAD), defined by flow-limiting atherosclerotic plaques, is a common cause for myocardial ischemia. A common and increasing risk factor for CAD is diabetes. The effect of diabetes on ischemic heart disease is not fully understood. Cardiovascular magnetic resonance (CMR) is used to evaluate cardiac pathology such as myocardial ischemia. It is not known whether CMR could be used for differentiating and prognosing patients with comorbidities such as diabetes which (1) have developed acute coronary syndrome (ACS), (2) have developed ischemia with no obstructive coronary arteries (INOCA) and (3) are asymptomatic.

Research questions

Paper 1: Can non-contrast CMR by native T1-mapping be used to assess myocardium at risk in an experimental porcine model and in patients during the first week after ST-elevation myocardial infarction (STEMI)?

Paper 2: Does non-invasive pressure-volume (PV) loop variables by CMR have an incremental prognostic value to conventional measurements for clinical outcome in post-STEMI patients independent of  diabetes?

Paper 3: Is myocardial perfusion by CMR associated with endothelial dysfunction assessed by circulating endothelial progenitor cells in patients with diabetes without known cardiovascular disease? 

Paper 4:  What is the long-term cardiovascular prognosis of patients with diabetes and chest pain who have INOCA identified by non-invasive ischemia testing and coronary angiography? 

Preliminary results

Paper 1: Non-contrast native T1-mapping agreed with myocardium at risk assessed by CE-SSFP post-STEMI in a porcine model (bias: 0.9±18%) and in patients (bias: 0.8±7.5%).

Paper 2: Non-invasive PV loop variables were associated with all-cause mortality and heart failure hospitalizations independent of age, sex, infarct size, and diabetes (Potential energy: HR 2.8, p=0.03; Ventriculoarterial coupling: HR 1.6, p=0.03) in 619 post-STEMI patients, whereas ejection fraction was not (HR 0.97, p=0.1).

Paper 4: Patients with INOCA had an increased risk of heart failure hospitalizations compared with non-ischemic controls independent of risk factors such as diabetes.

Significance

Imaging biomarkers by CMR can be used to assess clinical prognosis and pathophysiological characteristics in patients with ischemic heart disease as presented by ACS or INOCA despite presence of comorbidities such as diabetes. 

Published studies

Paper 1: Lav T, Nordlund D, Xanthis C, Berg J, Bidhult S, Aletras AH, et al. Native T1-mapping using cardiovascular magnetic resonance detects myocardium at risk during the first week following myocardial infarction in a swine model and in patients - comparison to contrast-enhanced cine steady-state free precession. BMC Cardiovasc Disord. 2026;26(1):86.

Paper 2: Lav T, Kyhl K, Nordlund D, Kelbæk H, Køber L, Høfsten D, et al. Non-invasive pressure-volume loops by cardiovascular magnetic resonance and outcome in ST-elevation myocardial infarction. European Heart Journal - Imaging Methods and Practice. 2026:qyag055.

Paper 4: Accepted abstract for presentation at the Young Investigator Award Session at European Society of Cardiology Sessions 2026 in Munich. The paper is under preparation.

Additional works (not included in the thesis)

Nordlund D, Lav T, Jablonowski R, Khoshnood A, Ekelund U, Atar D, et al. Contractility, ventriculoarterial coupling, and stroke work after acute myocardial infarction using CMR-derived pressure-volume loop data. Clinical Cardiology. 2024;47(1):e24216.

Lav T, Engstrøm T, Kyhl K, Nordlund D, Lønborg J, Engblom H, et al. Non-invasive pressure volume loops provide incremental value to age, sex, and infarct size for predicting adverse cardiac remodeling after ST-elevation myocardial infarction. European Heart Journal - Imaging Methods and Practice. 2025:qyaf008.