Aims The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. Methods and results COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99–10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12–12.34; P < 0.001). Conclusions Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

The dynamic interaction between subendocardial and subepicardial fibre helices in the left ventricle (LV) leads to a twisting deformation, which has an important role in LV function. This study sought to assess the influence of cardiac shape on LV twist in the normal and dilated human heart. The study comprised 45 dilated cardiomyopathy (DCM) patients and 60 for age- and gender-matched healthy volunteers. Speckle tracking echocardiography was used to determine basal and apical LV peak systolic rotation (Rot(max)) and instantaneous LV peak systolic twist (Twist(max)). LV sphericity index was calculated by dividing the LV maximal long-axis internal dimension by the maximal short-axis internal dimension at end-diastole. A parabolic relation between the sphericity index and apical Rot(max) or Twist(max) was identified in the total study population (R(2) = 0.56 and R(2) = 0.54, respectively; both P < 0.001) and healthy volunteers (R(2) = 0.39 and R(2) = 0.25, respectively; both P < 0.001), whereas these relations were linear in DCM patients (R(2) = 0.40 and R(2) = 0.43, respectively; both P < 0.001). In a multivariate analysis, LV sphericity index was the strongest independent predictor of apical Rot(max) and Twist(max). In conclusion, LV apical rotation and twist are significantly influenced by LV configuration. Taking the important function of LV twist into account, this finding highlights the vital influence of cardiac shape on LV systolic function.

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The most robust method to assess LV rotation with QLAB software is from the mid-myocardium. This method is feasible in approximately two-thirds of subjects and has good intra-observer, inter-observer, and temporal reproducibility, allowing to study changes over time in LV rotation in an individual patient.

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