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Introduction: In patients with acute myocardial infarction (AMI) and multivessel coronary disease, revascularization of non-culprit lesions guided by proof of ischemia usually requires staged ischemia testing. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in AMI patients is unknown. In this study, we tested the diagnostic value of QFR based on acute angiograms (aQFR) during AMI to assess the hemodynamic relevance of non-culprit lesions., Methods: We retrospectively assessed the diagnostic efficiency of aQFR in 280 vessels from 220 patients, comparing it with staged ischemia testing using elective coronary angiography with FFR (n = 47), stress cardiac MRI (n = 200) or SPECT (n = 33)., Results: aQFR showed a very good diagnostic efficiency (AUC = 0.887, 95% CI 0.832-0.943, p < 0.001) in predicting ischemia of non-culprit lesions, significantly superior to coronary lesion's geometry as assessed by quantitative coronary angiography. The optimal cut-off for aQFR to predict ischemia was 0.80 (sensitivity = 83.7%, specificity = 86.1%). Maintaining a predefined level of 95% sensitivity and specificity, we created a decision model based on aQFR: lesions with aQFR ≤ 0.75 should be treated, lesions with aQFR ≥ 0.92 do not yield any hemodynamic relevance, and lesions in the "grey zone" (aQFR 0.75-0.92) benefit from further ischemia testings. This model would allow to reduce staged ischemia tests by 46.8% without a relevant loss in diagnostic efficiency., Conclusion: Our data demonstrate that aQFR allows an effective assessment of hemodynamic relevance of non-culprit lesions in AMI and may guide interventions of non-culprit coronary lesions., (© 2021. The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased cardiovascular risk related at least in part to a more vulnerable plaque phenotype. However, patients with T2DM exhibit also an increased risk following percutaneous coronary intervention (PCI). It is unknown if plaque vulnerability of a treated lesion influences cardiovascular outcomes in patients with T2DM. In this study, we aimed to assess the association of plaque morphology as determined by optical coherence tomography (OCT) with cardiovascular outcome following PCI in high-risk patients with T2DM., Methods: 81 patients with T2DM and OCT-guided PCI were recruited. Pre-interventional OCT and systematic follow-up of median 66.0 (IQR = 8.0) months were performed., Results: During follow-up, 24 patients (29.6%) died. The clinical parameters age (HR 1.16 per year, 95% CI 1.07-1.26, p < 0.001), diabetic polyneuropathy (HR 3.58, 95% CI 1.44-8.93, p = 0.006) and insulin therapy (HR 3.25, 95% CI 1.21-8.70, p = 0.019) predicted mortality in T2DM patients independently. Among OCT parameters only calcium-volume-index (HR 1.71 per 1000°*mm, 95% CI 1.21-2.41, p = 0.002) and lesion length (HR 1.93 per 10 mm, 95% CI 1.02-3.67, p = 0.044) as parameters describing atherosclerosis extent were significant independent predictors of mortality. However, classical features of plaque vulnerability, such as thickness of the fibrous cap, the extent of the necrotic lipid core and the presence of macrophages had no significant predictive value (all p = ns)., Conclusion: Clinical parameters including those describing diabetes severity as well as OCT-parameters characterizing atherosclerotic extent but not classical features of plaque vulnerability predict mortality in T2DM patients following PCI. These data suggest that PCI may provide effective plaque sealing resulting in limited importance of local target lesion vulnerability for future cardiovascular events in high-risk patients with T2DM.

Background: Coronary calcification is associated with high risk for cardiovascular events. However, its impact on plaque vulnerability is incompletely understood. In the present study we defined the intrinsic calcification angle (ICA) as the angle externally projected by a vascular calcification and analyzed its role as novel feature of coronary plaque vulnerability in patients with type 2 diabetes., Methods: Optical coherence tomography was used to determine ICA in 219 calcifications from 56 patients with stable coronary artery disease (CAD) and 143 calcifications from 36 patients with acute coronary syndrome (ACS). We then used finite elements analysis to gain mechanistic insight into the effects of ICA., Results: Minimal (139.8 ± 32.8° vs. 165.6 ± 21.6°, p < 0.001) and mean ICA (164.1 ± 14.3° vs. 176.0 ± 8.4°, p < 0.001) were lower in ACS vs. stable CAD patients. Mean ICA predicted ACS with very good diagnostic efficiency (AUC = 0.840, 95% CI 0.797-0.882, p < 0.001, optimal cut-off 175.9°); younger age (OR 0.95 per year, 95% CI 0.92-0.98, p = 0.002), male sex (OR 2.18, 95% CI 1.41-3.38, p < 0.001), lower HDL-cholesterol (OR 0.82 per 10 mg/dl, 95% CI 0.68-0.98, p = 0.029) and ACS (OR 14.71, 95% CI 8.47-25.64, p < 0.001) were determinants of ICA < 175.9°. A lower ICA predicted ACS (OR for 10°-variation 0.25, 95% CI 0.13-0.52, p < 0.001) independently from fibrous cap thickness, presence of macrophages or extension of lipid core. In finite elements analysis we confirmed that lower ICA causes increased stress on a lesion's fibrous cap; this effect was potentiated in more superficial calcifications and adds to the destabilizing role of smaller calcifications., Conclusion: Our clinical and mechanistic data for the first time identify ICA as a novel feature of coronary plaque vulnerability.

Background: The minimal fibrous cap thickness overlying the necrotic lipid core as well as the presence of macrophages are established characteristics of coronary plaque vulnerability. Recently, the presence of microcalcifications has emerged as a novel feature of vulnerable lesions. However, clinical and plaque morphological predictors of microcalcifications are unknown., Methods: In patients with stable coronary artery disease, analysis of plaque morphology (n = 112) was performed using optical coherence tomography prior to coronary intervention to assess predictors of microcalcifications., Results: Microcalcifications were present in 21/112 (18.7%) lesions. Segments with microcalcifications showed a higher total number of calcifications per lesion (6.7 ± 3.0 vs. 3.2 ± 2.5, p < 0.001), a lower percent area stenosis (70.9 ± 11.1 vs. 76.2 ± 9.7%, p = 0.028), and a higher frequency of macrophage infiltration (66.7 vs. 37.4%, p = 0.014). In lesions with vs. without microcalcifications, macrophage infiltration was characterized by a wider macrophage angle (31.1° ± 34.4° vs. 13.7° ± 20.6°, p = 0.003), a higher macrophage index (105.6 ± 269.0 vs. 31.6 ± 66.5° mm, p = 0.020), and an increased frequency of calcium-macrophage co-localization (47.6 vs. 15.6%, p = 0.001). In multivariable logistic regression analysis, the total number of calcifications per lesion (OR 1.53, 95% CI 1.23-1.91, p < 0.001), average macrophage angle (OR 1.28 for 10°-variation, 95% CI 1.03-1.60, p = 0.024), and percent area stenosis (OR 0.59 for 10% increase, 95% CI 0.34-1.04, p = 0.070) were independent predictors for the presence of microcalcifications, whereas the latter did not reach statistical significance., Conclusion: Microcalcifications are related to a less advanced stenosis severity and to extensive plaque inflammation, but not to clinical parameters. Our data may add to the understanding and role of microcalcifications in coronary artery lesions.

Background: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events, which usually arise from the rupture of a vulnerable coronary plaque. The minimal fibrous cap thickness (FCT) overlying a necrotic lipid core is an established predictor for plaque rupture. Recently, coronary calcification has emerged as a relevant feature of plaque vulnerability. However, the impact of T2DM on these morphological plaque parameters is largely unexplored. Therefore, this study aimed to compare differences of coronary plaque morphology in patients with and without T2DM with a particular focus on coronary calcification., Methods: In 91 patients (T2DM = 56, non-T2DM = 35) with 105 coronary de novo lesions (T2DM = 56, non-T2DM = 49) plaque morphology and calcification were analyzed using optical coherence tomography (OCT) prior to coronary intervention., Results: Patients with T2DM had a lower minimal FCT (80.4 ± 27.0 µm vs. 106.8 ± 27.8 µm, p < 0.001) and a higher percent area stenosis (77.9 ± 8.1% vs. 71.7 ± 11.2%, p = 0.001) compared to non-diabetic subjects. However, patients with and without T2DM had a similar total number of calcifications (4.0 ± 2.6 vs. 4.2 ± 3.1, p = ns) and no significant difference was detected in the number of micro- (0.34 ± 0.79 vs. 0.31 ± 0.71), spotty (2.11 ± 1.77 vs. 2.37 ± 1.89) or macro-calcifications (1.55 ± 1.13 vs. 1.53 ± 0.71, all p = ns). The mean calcium arc (82.3 ± 44.8° vs. 73.7 ± 31.6), the mean thickness of calcification (0.54 ± 0.13 mm vs. 0.51 ± 0.15 mm), the mean calcified area (0.99 ± 0.72 mm 2 vs. 0.78 ± 0.49 mm 2 ), the mean depth of calcification (172 ± 192 μm vs. 160 ± 76 μm) and the cap thickness overlying the calcification (50 ± 71 μm vs. 62 ± 61 μm) did not differ between the diabetic and non-diabetic groups (all p = ns)., Conclusion: T2DM has an impact on the minimal FCT of the coronary target lesion, but not on localization, size, shape or extent of calcification. Thus, the minimal FCT overlying the necrotic lipid core but not calcification is likely to contribute to the increased plaque vulnerability observed in patients with T2DM.

Background: Fractional flow reserve (FFR) measurements accurately assess functional relevance in intermediate grade coronary lesions. A significant relationship between hemodynamic stenosis severity and optical coherence tomography (OCT)-derived intraluminal dimensions has recently been demonstrated. However, morphologic thresholds to identify significant stenoses are variable and exploration of this correlation in patients with diabetes mellitus (DM) remains currently incomplete. This study aimed at comparing the diagnostic value of intraluminal parameters as determined by OCT to predict FFR ≤0.8 in lesions of patients with versus without DM., Methods: In 100 patients (DM = 56, non-DM = 44) with 142 coronary de novo lesions (DM = 80, non-DM = 62) of intermediate grade as determined by quantitative coronary angiography, we performed OCT and FFR. Stenoses were defined functionally relevant if FFR was ≤0.8., Results: FFR measurements in the overall study cohort, the DM and the non-DM group correlated significantly with minimal lumen area (MLA) [overall: r (2) = 0.339, DM: r (2) = 0.341, non-DM: r (2) = 0.355 (all p < 0.001)], percent area stenosis [overall: r (2) = 0.352, DM: r (2) = 0.376, non-DM: r (2) = 0.351 (all p < 0.001)] and minimal lumen diameter [overall: r (2) = 0.333, DM: r (2) = 0.277, non-DM: r (2) = 0.417 (all p < 0.001)] without differing statistically between diabetic and non-diabetic patients (p = ns). Receiver operating characteristic analysis demonstrated that among OCT-derived parameters, MLA predicted FFR ≤0.8 with the best diagnostic efficiency and with similar cut-off values for all patients [area under the curve (AUC) = 0.836, 95% confidence interval (CI) = 0.772-0.901, cut-off value = 1.64 mm(2)] as well as for diabetic (AUC = 0.840, 95% CI = 0.754-0.927, cut-off value = 1.59 mm(2)) and non-diabetic subjects (AUC = 0.833, 95% CI = 0.734-0.932, cut-off value = 1.64 mm(2))., Conclusion: In both, diabetic and non-diabetic patients, FFR and OCT-derived intraluminal measurements are significantly correlated and OCT predicts hemodynamically relevant coronary stenosis with moderate diagnostic efficiency.

Patients with type 2 diabetes are at increased risk for post-PCI complications including stent thrombosis and restenosis. Stent edge dissections (SEDs) have been associated with these complications. This study assessed incidence and predictors of SEDs in patients with type 2 diabetes using optical coherence tomography (OCT). Intravascular lesion parameters and plaque morphology were investigated pre- and post-PCI using OCT in 73 type 2 diabetic patients with 90 lesions and 166 visible stent edges. We detected 42 (25.3 %) SEDs in 166 stent edges and 37 (41.1 %) SEDs in 90 lesions. More SEDs occurred if the border of the stent had been placed within diseased vessel segments with predominantly fibrous (42.9 %) and fibrocalcific (40.5 %) plaques compared to healthy vessel wall morphology (p < 0.001). Furthermore, the lumen eccentricity of the stent at its edges (SAE) (16.00 ± 6.07 vs. 13.11 ± 5.22 %, p < 0.003) and the stent-edge-to-lumen-area-ratio (1.26 ± 0.27 vs. 0.99 ± 0.20, p < 0.001) were both significantly larger in the presence of SEDs. All of the above parameters were significant predictors for SEDs on uni- and multivariate logistic regression analysis (all p < 0.01), suggesting that the lumen eccentricity of the SAE, the stent-edge-to-lumen-area-ratio and diseased vessel wall morphology of the reference segment adjacent to the stent edge are independent risk factors for the presence of SEDs. These results suggest that diseased vessel wall morphology at the stent edges may promote the occurrence of SEDs and that avoidance of longitudinal and transverse mismatch between stent and vessel could be important to reduce SEDs in cardiovascular high-risk patients with type 2 diabetes.

Objective: Transcatheter coil embolization of coronary artery fistulas (CAFs) has emerged as an alternative to surgical closure despite limited data in the current literature. The aim of this study was to show the efficacy of CAF closure and the benefit of the combined preinterventional use of cardiac computed tomography and coronary angiography to evaluate the feasibility and enhance the safety of this procedure by obtaining precise information about the CAF anatomy., Patients and Methods: Five consecutive patients (three men, two women, age 51-68 years) with symptomatic angiographically proven CAFs were screened for transcatheter treatment and underwent preinterventional cardiac multidetector computed tomography (MDCT)., Results: On the basis of CAF-associated clinical symptoms, exercise-induced ischemia, coronary angiography, and cardiac MDCT, four of five patients with a CAF draining into the pulmonary artery system were considered eligible for transcatheter coil embolization, whereas in MDCT the fifth patient had multiple draining sites of the CAF and a relevant drainage into the right ventricular myocardium and was thus excluded from the procedure. Coil embolization was successfully performed in the remaining four cases without any complications. There was no residual flow through the CAF after the procedure. Clinical symptoms resolved almost completely in all four patients during a median 15.6-month follow-up., Conclusion: Transcatheter coil embolization is a feasible and effective method for the treatment of symptomatic CAFs in selected cases. The adjunctive preinterventional use of cardiac MDCT with conventional angiography can identify vessels that are anatomically applicable for transcatheter closure, defer therapy in morphologically unsuitable complex cases, and thus optimize the safety of the procedure.

Background: Patients with type 2 diabetes are at increased risk for both, left ventricular (LV)-dilatation and myocardial infarction (MI) following the rupture of a vulnerable plaque. This study investigated the to date incompletely understood relationship between plaque vulnerability and LV-dilatation using optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) in patients with type 2 diabetes and stable coronary artery disease., Methods: CMR was performed in 58 patients with type 2 diabetes, in which 81 coronary lesions were investigated using OCT., Results: A decreased minimal fibrous cap thickness (FCT) of coronary lesions was associated with an increase of several CMR-derived parameters including LV-end diastolic volume (LVEDV, r = 0.521, p < 0.001), LV-end diastolic diameter (r = 0.502, p < 0.001) and LV-end systolic volume (r = 0.467, p = 0.001). Similar results were obtained for mean FCT., Conclusion: These data suggest that vulnerability of coronary lesions is associated with LV-dilatation in high risk patients with type 2 diabetes. CMR may be a useful adjunct to the risk-stratification in this population. Future studies are warranted to investigate potential mechanisms linking plaque vulnerability and LV-dilatation.

Background: The relationship between functional relevance and optical coherence tomography (OCT)-derived measurements of coronary lesions is incompletely understood and of critical importance, particularly in cardiovascular high-risk patients with type 2 diabetes., Objective: To investigate the association between functional relevance of intermediate grade coronary stenoses as assessed by fractional flow reserve (FFR) and OCT-derived lesion parameters in patients with diabetes., Methods: In 46 diabetic patients with stable coronary artery disease, FFR and OCT were performed in 62 coronary lesions with intermediate severity as determined by quantitative coronary angiography. Among lesions haemodynamic relevance was defined as FFR≤0.8., Results: There was a significant association between FFR and OCT-derived minimal lumen area (r(2)=0.379) and minimal lumen diameter (r(2)=0.268), all p<0.001. Receiver operating curve (ROC)-analysis demonstrated an OCT-derived minimal lumen area <1.59 mm(2) and minimal lumen diameter <1.31 mm to be optimal cut-off values to predict FFR≤0.8. Furthermore, in lipid-rich plaques FFR was significantly associated with minimal fibrous cap thickness (FCT, r(2)=0.399). Minimal FCT in lesions with FFR≤0.8 was significantly smaller (60.7±15.0 µm) compared with those lesions with FFR>0.8 (106.0±13.0 µm, p<0.001). ROC-analysis revealed that 0.81 is the ideal FFR cut-off to identify lesions with a minimal FCT≤80 µm (accuracy 97.3%, sensitivity 100%, specificity 93.8%, area under the curve 0.943 (95% CI 0.836 to 1.000))., Conclusions: Haemodynamic relevance of intermediate grade lesions in patients with type 2 diabetes is closely related to (1) intraluminal measurements, which are smaller than previously described in non-diabetic cohorts and to (2) minimal FCT. Furthermore, FFR may be useful to identify vulnerable (minimal FCT≤80 µm) lesions among those with intermediate severity in lipid-rich plaques.