Characteristics of culprit lesion and changes in plaque composition during follow-up in NSTEMI patients. A dual energy cardiac CT study

Introduction:
Identifying coronary artery plaques that are responsible for future myocardial infarction, is still a challenge in cardiology and is considered as the “holy grail” in the investigation of coronary artery disease (CAD). Several modalities are used in the investigation of coronary artery plaques in patients suspected to have ischaemic heart disease (IHD). One of these modalities is coronary computed tomography angiography (CCTA), a non-invasive method with a high negative predictive value to exclude ischaemic cardiovascular disease. However, CCTA still has several limitations when it comes to diagnostic accuracy in patients with intermediate or high-risk plaques, and improvement of the diagnostic accuracy is needed. Dual energy computed tomography (DECT) is a recent advance in computed tomography (CT) technology. It has spurred a great interest, because it has the ability to use X-ray spectra consisting of high- and low-energy levels to describe the tissue composition in the scanned area expressed by effective-Z value, which enables a better differentiation between different tissue components.

Aims:
Paper 1:To use DECT in clinical setting to describe the effective-Z value in culprit plaques, to identify the difference in effective-Z between culprit plaques and non-culprit plaques, and to investigate the diagnostic accuracy of detecting high-risk plaques in patients with non-ST-elevation myocardial infarction (NSTEMI).

Paper 2:To use DECT to identify the similarities between culprit plaques in NSTEMI patients in clinical setting and thin-cap fibroatheroma (TCFA) in a post mortem model.

Paper 3:By using effective-Z values obtained from culprit plaques, we identified a group of plaques with similar effective-Z values, and we defined these as high-risk plaques. We aimed to describe the changes in the tissue composition in these high-risk plaques in NSTEMI patients during 2- and 12-month follow-up.

Paper 4:To investigate the capability of DECT to detect ischaemic areas in the myocardium in NSTEMI patients using effective-Z values in the myocardium where we used post-systolic strain (PSS) echocardiography as a reference.

Methods:
In a prospective observational study we included sixty-one patients who were admitted to the Department of Cardiology, OUH Svendborg Hospital, with the diagnosis type-1 NSTEMI. The patients were recruited and underwent contrast-enhanced coronary DECT and echocardiography before conventional invasive coronary angiography (CAG). Guided by CAG and two-observer agreement the culprit plaques were identified. The characteristics of each coronary plaque, such as effective-Z, Hounsfield Units (HU), spotty calcification, remodelling index (RI), and plaque type (characterisation as non-calcified, predominantly non-calcified, predominantly calcified or calcified) were determined from baseline DECT. The baseline characteristics of culprit and non-culprit plaques were compared, and changes in tissue composition in non-culprit plaques were observed at 2-month and 12-month follow-up. In addition, the effective-Z values were measured in each segment of the left ventricle according to the 18-segment model in the longitudinal plan. Using two-dimensional (2D) strain echocardiography, and guided by PSS echocardiography, we defined myocardial segments as ischaemic in the case of a post-systolic strain index (PSI) ≥ 0.25%, which present myocardial segments where ≥ 0.25% of the myocardial contraction took place after the aortic valve closure. The effective-Z values in ischaemic myocardial segments were compared to effective-Z values in non-ischaemic myocardial segments.In the post mortem model, three hearts were prepared with iodine contrast, inserted in a Kyoto phantom and scanned by DECT. Six TCFA were identified using histopathological analysis (cap thickness <65 μm and necrotic core > 10% of the plaque area), and the same DECT plaque characteristics as in NSTEMI patients were determined.

Results:
Paper 1:The culprit plaques had significantly lower effective-Z and HU values, with a higher frequency of non-calcified plaques, and had a greater presence of napkin-ring signs in comparison with non-culprit plaques. The diagnostic accuracy detecting culprit plaques was improved by using effective-Z values, and the highest diagnostic accuracy was obtained by effective-Z value 9.855 as a cut-off value (area under the curve (AUC) 0.770).
Paper 2:In comparison with TCFA, the culprit plaques had significantly lower effective-Z, lower mean HU values, and were more non-calcified.Paper 3:Using the measured effective-Z in culprit plaques as a reference, we separated non-culprit plaques in two groups defined as “high-risk” plaques (effective-Z < 9.855) and “low-risk” plaques (effective-Z ≥ 9.855). We examined the change in tissue composition at 2-month and 12-month follow-up. In the “high-risk” plaques, we observed a significant change in effective-Z from baseline until 2-month follow-up, whereas we did not observe any changes from 2-month to 12-month follow-up. In comparison, we did not observe any changes in the “low-risk” plaques.
Paper 4:Measurements of effective-Z values obtained from each segment of the left ventricle at baseline scan demonstrated that the mean effective-Z values were significantly lower in the ischaemic myocardial segments in comparison with the non-ischaemic myocardial segments.

Conclusion:We have demonstrated that the use of DECT and the use of effective-Z values identifies new differences between culprit and non-culprit plaques in NSTEMI patients and improves the diagnostic accuracy in diagnosing culprit plaques. Surprisingly, we found differences between characteristics and effective-Z between culprit plaques and TCFA, which may indicate that not all TCFA may be considered as vulnerable, but can be explained by the different scan settings. We Hussam Mahmoud Sheta8identified plaques with effective-Z similar to the effective-Z in culprit plaques, and we defined these plaques as “high-risk” plaques and demonstrated that these plaques have the ability to rapid changes in tissue composition short time after the myocardial infarction. These plaques may be considered as potentially vulnerable, but further follow-up studies on this type of plaques are needed to assess the risk for causing myocardial infarction.In addition, we demonstrated that DECT have the potential to identify ischaemic myocardial segments and thereby increase the predictive power of CCTA detecting IHD.