Objectives. This study aimed to determine characteristics and pattern of a calcified nodule (CN) and/or nodular calcification (NC) detected by intravascular ultrasound (IVUS) on the device-oriented composite endpoint (DoCE) in patients with calcified lesions who underwent rotational atherectomy (RA)-assisted percutaneous coronary intervention (PCI). Background. The characteristics and pattern of a CN and/or NC on clinical outcome remain unknown. Methods. We retrospectively enrolled patients who underwent RA-assisted PCI at Siriraj Hospital during August 2016 to April 2020. Preprocedural IVUS imaging was mandatory. CN/NC was defined as convex shape of luminal surface and luminal side of calcium with protrusion into the coronary artery lumen as assessed by IVUS. The primary outcome was cumulative of DoCE, defined as the composite of cardiovascular death, myocardial infarction, and clinically-driven target lesion revascularization. Results. Two hundred patients were included. Primary outcome occurred in 14%. The cumulative DoCE was significantly higher in the CN/NC group than that in the non-CN/NC group (20.7% vs. 8.8%, p = 0.022). CN/NC (p = 0.023) and MSA ≤ 5.5 mm2 (p = 0.047) were correlated with a significantly higher cumulative DoCE. CN/NC was the independent predictor for the cumulative DoCE (HR = 2.96, 95% CI 1.08–8.11, p = 0.035). Pattern and characteristic of CN/NC have a prognostic value. Patients with an eccentric CN/NC had a significantly higher cumulative DoCE compared to those CN/NC with concentric calcification (p = 0.014). Conclusion. The presence of a CN/NC in patients with heavily calcified lesions who underwent RA-assisted PCI was found to be associated with increased cumulative 5 year DoCE, especially in patients with an eccentric CN/NC. The clinical trial is registered with TCTR20210616001.

Background Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in the kynurenine (Kyn) pathway of tryptophan (Trp) degradation, is modulated by inflammation, and is regarded as a key molecule driving immunotolerance and immunosuppressive mechanisms. Little is known about IDO activity in patients with active coronary artery disease (CAD). Methods We prospectively enrolled patients who were scheduled to undergo coronary angiography. Measurement of IDO, high-sensitivity troponin T (hs-TnT), and high-sensitivity C-reactive protein (hs-CRP) levels was performed at baseline, and IDO activity was monitored at the 6-month follow-up. Results Three hundred and five patients were enrolled. Ninety-eight patients (32.1%) presented with recent acute coronary syndrome (ACS). Significant difference in IDO, kynurenine, and hs-TnT between patients with and without significant CAD was observed. Baseline IDO activity, kynurenine level, and hs-TnT level were all significantly higher in significant CAD patients with 3-vessel, 2-vessel, and 1-vessel involvement than in those with insignificant CAD [(0.17, 0.13, and 0.16 vs. 0.03, respectively; p = 0.003), (5.89, 4.58, and 5.24 vs. 2.74 µM/g, respectively; p = 0.011), and (18.27, 12.22, and 12.86 vs. 10.89 mg/dL, respectively; p < 0.001)]. One-year mortality was 3.9%. When we compared between patients who survived and patients who died, we found a significantly lower prevalence of left main (LM) disease by coronary angiogram (6.1% vs. 33.3%, p = 0.007), and also a trend toward higher baseline kynurenine (5.07 vs. 0.79 µM/g, p = 0.082) and higher IDO (0.15 vs. 0.02, p = 0.081) in patients who survived. Conclusion Immunometabolic response mediated via IDO function was enhanced in patients with CAD, and correlated with the extent and severity of disease. Patients with LM disease had higher 1-year mortality. Lower level of IDO, as suggested by inadequate IDO response, demonstrated a trend toward predicting 1-year mortality. Trial registration TCTR Trial registration number TCTR20200626001. Date of registration 26 June 2020. “Retrospectively registered”.

Background Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in in the kynurenine (Kyn) pathway of tryptophan (Trp) degradation, is modulated by inflammation and regarded as a key molecule driving immunotolerance and immunosuppressive mechanisms. This response accelerates the resolution of inflamed tissues to protect them against collateral damage and facilitate tissue healing. A growing body of evidence indicates that IDO-mediated Trp metabolism is involved directly or indirectly in atherogenesis. Little is known about IDO activity in patients with active coronary artery disease (CAD). Purpose We hypothesized that IDO activity as reflected by Kyn/Trp ratio and Kyn levels correlated with coronary artery disease (CAD) severity and predicted 1-year major adverse cardiac events (MACE). Method We prospectively enrolled the patients whom underwent coronary angiography in our institute. We excluded the patients whom might have other non-cardiac causes of elevated inflammatory biomarkers such as rheumatoid arthritis, allergic asthma, and so on. Measurements of IDO, hs-troponin and hs-CRP levels were performed at baseline and IDO activity was monitored every 6 month at interval. Baseline demographic, coronary angiogram/interventions data were recorded. Significant CAD defined as &gt;70% stenosis in major epicardial vessel. Patients were followed up for 1-year. MACE were pre-specified. Results Three-hundred and five patients were enrolled. Ninety-eight patients (32%) presented with acute coronary syndrome. There was a significant difference in IDO, kynurenine, and hs-troponin between patients with and without significant CAD (Table 1). In addition, baseline IDO activity, kynurenine and hs-troponin levels were significantly higher in significant CAD patients with 3-vessel, 2-vessel and 1-vessel involvements than those with insignificant CAD; (0.17 vs 0.14 vs 0.14 vs 0.04, p&lt;0.01), (5.8 vs 4.5 vs 5.1 vs 2.9 μM/g, p&lt;0.01) and (18.2 vs 12.4 vs 12.7 vs 11.1 mg/dL, p&lt;0.001), respectively. Preliminary data in 287 patients with completion of 1-year follow up showed that 1-year mortality was 2.9%. In comparison between patients who survived and death, it demonstrated markedly higher baseline kynurenine (5.12 vs 0.54 μM/g, p&lt;0.03) and IDO (0.15 vs 0.01, p&lt;0.02) in the patients without 1-year mortality. Conclusion Immunometabolic response mediated through IDO function were enhanced in patients with CAD and correlated with the severity and extent of the disease. Patient with inadequate IDO response had a higher 1-year mortality. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Siriraj grant for research development and medical education of the Faculty of Medicine Siriraj Hospital