Determination of lipid-rich plaques by artificial intelligence-enabled quantitative computed tomography using near-infrared spectroscopy as reference.

BACKGROUND AND AIMS: Artificial intelligence quantitative CT (AI-QCT) determines coronary plaque morphology with high efficiency and accuracy. Yet, its performance to quantify lipid-rich plaque remains unclear. This study investigated the performance of AI-QCT for the detection of low-density noncalcified plaque (LD-NCP) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The INVICTUS Registry is a multi-center registry enrolling patients undergoing clinically indicated coronary CT angiography and IVUS, NIRS-IVUS, or optical coherence tomography. We assessed the performance of various Hounsfield unit (HU) and volume thresholds of LD-NCP using maxLCBI4mm ≥ 400 as the reference standard and the correlation of the vessel area, lumen area, plaque burden, and lesion length between AI-QCT and IVUS. RESULTS: This study included 133 atherosclerotic plaques from 47 patients who underwent coronary CT angiography and NIRS-IVUS The area under the curve of LD-NCP<30HU was 0.97 (95% confidence interval [CI]: 0.93-1.00] with an optimal volume threshold of 2.30 mm3. Accuracy, sensitivity, and specificity were 94% (95% CI: 88-96%], 93% (95% CI: 76-98%), and 94% (95% CI: 88-98%), respectively, using <30 HU and 2.3 mm3, versus 42%, 100%, and 27% using <30 HU and >0 mm3 volume of LD-NCP (p < 0.001 for accuracy and specificity). AI-QCT strongly correlated with IVUS measurements; vessel area (r2 = 0.87), lumen area (r2 = 0.87), plaque burden (r2 = 0.78) and lesion length (r2 = 0.88), respectively. CONCLUSIONS: AI-QCT demonstrated excellent diagnostic performance in detecting significant LD-NCP using maxLCBI4mm ≥ 400 as the reference standard. Additionally, vessel area, lumen area, plaque burden, and lesion length derived from AI-QCT strongly correlated with respective IVUS measurements.

Thrombocytopenia as a Bleeding Risk Factor in Atrial Fibrillation and Coronary Artery Disease: Insights From the AFIRE Study.

Background Thrombocytopenia poses a risk of bleeding in patients with chronic coronary syndrome after coronary intervention. However, whether thrombocytopenia also increases the bleeding risk in patients with atrial fibrillation and chronic coronary syndrome remains unclear. Methods and Results This study evaluated the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial. Thrombocytopenia was defined as platelet count <100 000/mm3 level at enrollment. Primary end points included incidence of major bleeding based on the International Society on Thrombosis and Hemostasis criterion and major adverse cardiovascular ischemic events (cardiac death, myocardial infarction, and stroke). A total of 2133 patients were classified into the thrombocytopenia (n=70) and nonthrombocytopenia (n=2063) groups. Major bleeding was significantly higher in the thrombocytopenia group than in the nonthrombocytopenia group (10.0% versus 4.1%, P=0.027). The thrombocytopenia group tended to have a higher risk of major adverse cardiovascular ischemic events (11.4% versus 6.2%, P=0.08). The bleeding incidence was significantly higher in patients with thrombocytopenia receiving combination therapy with rivaroxaban and a single antiplatelet drug (thrombocytopenia group, 14.3%, versus nonthrombocytopenia group, 5.0%; hazard ratio, 3.18 [95% CI, 1.27-7.97], P=0.014). Thrombocytopenia was an independent predictor of major bleeding (hazard ratio, 2.57 [95% CI, 1.19-5.56], P=0.017). Conclusions Among patients with atrial fibrillation and chronic coronary syndrome, thrombocytopenia was significantly associated with increased risk of major bleeding. Selecting drugs for patients with thrombocytopenia continuing antithrombotic therapy should be given special consideration. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419. https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000016612.

Rationale and design of the INVICTUS Registry: (Multicenter Registry of Invasive and Non-Invasive imaging modalities to compare Coronary Computed Tomography Angiography, Intravascular Ultrasound and Optical Coherence Tomography for the determination of Severity, Volume and Type of coronary atherosclerosiS).

BACKGROUND: Coronary CT angiography (CCTA) is a first-line noninvasive imaging modality for evaluating coronary artery disease (CAD). Recent advances in CCTA technology enabled semi-automated detection of coronary arteries and atherosclerosis. However, there have been to date no large-scale validation studies of automated assessment of coronary atherosclerosis phenotype and coronary artery dimensions by artificial intelligence (AI) compared to current standard invasive imaging. METHODS: INVICTUS registry is a multicenter, retrospective, and prospective study designed to evaluate the dimensions of coronary arteries, as well as the characteristic, volume, and phenotype of coronary atherosclerosis by CCTA, compared with the invasive imaging modalities including intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS)-IVUS and optical coherence tomography (OCT). All patients clinically underwent both CCTA and invasive imaging modalities within three months. RESULTS: Patients data are sent to the core-laboratories to analyze for stenosis severity, plaque characteristics and volume. The variables for CCTA are measured using an AI-based automated software and assessed independently with the variables measured at the imaging core laboratories for IVUS, NIRS-IVUS, and OCT in a blind fashion. CONCLUSION: The INVICTUS registry will provide new insights into the diagnostic value of CCTA for determining coronary atherosclerosis phenotype and coronary artery dimensions compared to IVUS, NIRS-IVUS, and OCT. Our findings will potentially shed new light on precision medicine informed by an AI-based coronary CTA assessment of coronary atherosclerosis burden, composition, and severity. (ClinicalTrials.gov: NCT04066062).

Ultrathin, Biodegradable-Polymer Sirolimus-Eluting Stent vs Thin, Durable-Polymer Everolimus-Eluting Stent.

BACKGROUND: Previous trials suggested the superiority of ultrathin- over thin-strut drug-eluting stents (DES) concerning target lesion failure (TLF) at 1 year after index percutaneous coronary intervention. OBJECTIVES: The aim of this randomized comparison study of ultrathin-strut and thin-strut DES (CASTLE [Randomized Comparison All-Comer Study of Ultrathin Strut and Thin Strut Drug-Eluting Stent]; jRCTs032180084) was to examine the impact of differences in strut thickness of DES on clinical outcomes when implanted with angiography and intravascular ultrasound or optical coherence tomographic guidance. METHODS: CASTLE was a multicenter, prospective, noninferiority study conducted at 65 institutions in Japan. Percutaneous coronary intervention patients were assigned (1:1) to an ultrathin, biodegradable-polymer sirolimus-eluting stent (BP-SES) or a thin, durable-polymer everolimus-eluting stent (DP-EES). The primary endpoint was TLF, defined as a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization at 1-year follow-up. RESULTS: Between May 2019 and March 2020, 1,440 patients were randomly assigned to BP-SES (n = 722) or DP-EES (n = 718). TLF occurred in 6.0% and 5.7% of patients, respectively. Noninferiority (P = 0.040) was met because the upper limit (2.67%) of the 1-sided 95% CI between the groups was lower than the prespecified noninferiority margin (3.3%). No significant interactions were observed in the relative rates of TLF between prespecified subgroups. CONCLUSIONS: The BP-SES was noninferior to the DP-EES regarding 1-year TLF. This demonstrates that strut thickness differences among DES have little impact on clinical outcomes when implanted with intravascular imaging guidance.

Clinical Outcomes After Percutaneous Coronary Intervention in East Asian Patients　- 30-Month Results of the PENDULUM Registry.

BACKGROUND: The 12-month results of the PENDULUM registry showed that after implantation of second-generation drug-eluting stents (DES), high P2Y12reaction unit (HPR) were independently associated with ischemic but not bleeding events.Methods and Results: This study analyzed cumulative incidences of major adverse cardiac and cerebrovascular events (MACCE) and major bleeding (Bleeding Academic Research Consortium type 3 and 5) at 30 months after index percutaneous coronary intervention (PCI) (primary endpoints). Of 6,422 patients undergoing PCI with DES, 5,796 completed the 30-month follow up. The continuation rate of dual antiplatelet therapy decreased to 59.3% at 12 months and 26.4% at 30 months. At 30 months, the cumulative incidence of MACCE increased linearly and reached 9.5% (95% confidence interval 8.8-10.2) and that of major bleeding had the inflection point at 12 months and was 4.4% (3.9-5.0). MACCE and bleeding events were higher in HPR patients (unadjusted P value). After covariate adjustment, P2Y12reactivity units measured immediately after index PCI was not an independent risk factor for MACCE or major bleeding at 30 months. CONCLUSIONS: MACCE consistently increased after 12 months post-PCI, whereas the increase in major bleeding events slowed down after 12 months in Japanese PCI patients in a real-world clinical setting. HPR patients had increased MACCE and bleeding complications, but HPR was not an independent risk factor of events at 30 months.

Early P2Y12 Inhibitor Single Antiplatelet Therapy for High-Bleeding Risk Patients After Stenting　- PENDULUM Mono 24-Month Analysis.

BACKGROUND: In PENDULUM mono, Japanese patients with high bleeding risk (HBR) received short-term dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with prasugrel after percutaneous coronary intervention (PCI). One-year data from PENDULUM mono showed better outcomes with prasugrel monotherapy after short-term DAPT compared with matched patients in the PENDULUM registry with longer DAPT durations according to guidelines at that time. This study presents 2-year results.Methods and Results: We compared 24-month data from PENDULUM mono (n=1,107; de-escalation strategy group) and the PENDULUM registry (n=2,273; conventional strategy group); both were multicenter, non-interventional, prospective registry studies, using the inverse probability of treatment weighting (IPTW) method. In the PENDULUM mono group, the cumulative incidence of clinically relevant bleeding (CRB) at 24 months post-PCI (primary endpoint) was 6.8%, and that of major adverse cardiac and cerebrovascular events (MACCE) was 8.9%. After IPTW adjustment, the cumulative incidence of CRB was 5.8% and 7.2% in PENDULUM mono and the PENDULUM registry, respectively (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.57-1.04; P=0.086), and that of MACCE was 8.0% and 9.5%, respectively (HR 0.77; 95% CI 0.59-1.01; P=0.061). CONCLUSIONS: Japanese PCI patients with HBR prescribed prasugrel SAPT after short-term DAPT had a lower ischemic event risk than those prescribed long-term DAPT, and this was particularly relevant for ischemic events after 1 year.

Changes in Antithrombotic Therapy Over Time and Durability of a Prasugrel WOEST-Like Regimen for Percutaneous Coronary Intervention Patients With Atrial Fibrillation　- Post Hoc Analysis of the PENDULUM Mono and PENDULUM Registries.

Background: Previously published randomized atrial fibrillation (AF) percutaneous coronary intervention (PCI) trials have demonstrated the safety and efficacy of a WOEST-like regimen (oral anticoagulant [OAC] plus P2Y12 inhibitor) in patients with AF PCI within 1 year. However, the efficacy of this regimen in real-world practice has not been fully confirmed, especially the efficacy of the WOEST-like regimen using the approved dose of prasugrel in Japan. Methods and Results: This post hoc analysis included 186 and 220 patients from the PENDULUM mono and PENDULUM registries, respectively. Endpoints were the cumulative incidences of clinically relevant bleeding (CRB) and major adverse cardiac and cerebrovascular events (MACCE) at 12 months after PCI. Differences in the enrollment period led to an increase in OAC prescriptions (from 64.7% to 81.2%) and a reduction in the median duration of triple antithrombotic therapy (from 203.0 to 32.0 days) in the PENDULUM vs. PENDULUM mono registries, respectively. After adjustment by the inverse probability of treatment method, in patients with OAC, PENDULUM mono AF significantly reduced CRB without increasing MACCE compared with PENDULUM AF. Conclusions: A WOEST-like regimen with prasugrel may reduce CRB, without increasing MACCE, in Japanese patients with AF and high bleeding risk undergoing PCI.

Impact and safety of balloon pulmonary angioplasty for elderly patients.

Recently, balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) has become an established procedure with stable results. The number of elderly CTEPH/CTEPD patients has also increased due to the widespread recognition of the disease concept. However, the reports of BPA in the elderly are limited. The aim of this study was to evaluate the efficacy and safety of BPA in elderly patients (>80 years). From April 2016 to December 2020, 344 BPA sessions (74 patients) were performed. The safety and efficacy of the BPA procedures were compared in the younger group (<80 years; 278 sessions) and the elderly group (≥80 years; 66 sessions). The hemodynamic parameters were significantly improved in both groups (mean pulmonary arterial pressure: 34.4 ± 9.9 → 21.2 ± 6.2 mmHg, p < 0.001 and 33.2 ± 9.6 → 21.8 ± 8.5 mmHg, p < 0.001; pulmonary vascular resistance: 474.5 ± 248.6 → 201.3 ± 108.7 dyne sec cm-5, p < 0.001 and 496.4 ± 290.9 → 260.5 ± 120.2 dyne sec cm-5, p = 0.002, in younger and elderly group, respectively). The rate of death within 30 days of BPA (0.3% vs. 0%, p = 1.000) and use of positive pressure ventilation (1.4% vs. 3.0%, p = 0.600) were not different between the groups (younger vs. elderly, respectively). BPA significantly improved the hemodynamic parameters of elderly CTEPH/CTEPD patients, and the safety is comparable to that of younger patients.

Evaluation of the effect of nitric oxide inhalation in the patients with chronic thromboembolic pulmonary hypertension or pulmonary disease during balloon pulmonary angioplasty.

Balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary disease (CTEPD) is performed worldwide. High mean pulmonary arterial pressure (mPAP) during BPA is associated with aggravation of procedure-related complications. Inhaled nitric oxide (NO) acts as a pulmonary vasodilator in CTEPH patients. The aim of this retrospective observational study was to evaluate the effects of inhaled NO in CTEPH/CTEPD patients during BPA. We assessed hemodynamic changes and the frequency of procedure-related complications with or without NO inhalation. We performed 338 consecutive BPA in 72 CTEPH/CTEPD patients between April 2016 and November 2020. Since December 2019, all 16 patients (72-BPA sessions) inhaled NO during the procedure as a routine. Inhaled NO significantly reduced mPAP from 31.3 ± 8.5 to 27.2 ± 6.8 mmHg (p < 0.001) without lowering systemic blood pressure (systolic: 139.9 ± 19.9 vs. 135.3 ± 21.8 mmHg; p = 0.247, diastolic: 82.8 ± 13.0 vs. 79.0 ± 9.3 mmHg; p = 0.085, before vs. after NO inhalation, respectively). Procedure-related complications were observed in 46 sessions (13.6%). The incidence of hemoptysis was significantly higher in the NO group than in the non-NO group (20.8% vs. 10.9%; p = 0.031). In contrast, all fatal complications (death and use of positive pressure ventilation) occurred in the non-NO group, but the difference was not statistically significant (0 sessions [0.0%] vs. 7 sessions [2.6%], p = 0.353). Inhaled NO acts as a selective pulmonary vasodilator in CTEPH/CTEPD patients during the BPA procedure.

Preprocedural frailty is strongly associated with symptoms after balloon pulmonary angioplasty.

Balloon pulmonary angioplasty (BPA) has improved the survival rate of patients with chronic thromboembolic pulmonary hypertension (CTEPH). The resolution of symptoms is one of the remaining goals of BPA. Frailty affects the outcome of cardiovascular diseases or treatments. The aim of this study is to assess the association between frailty and outcome of BPA. The resolution of symptoms is evaluated by the post-BPA World Health Organization functional class (WHO-FC). A total of 54 patients with CTEPH were divided into 2 groups by post-BPA WHO-FC (WHO-FC I group; n = 34 vs. WHO-FC ≥ II group; n = 20). Frailty was assessed by physicians using the clinical frailty scale (CFS) at the point of patient admission for their first BPA sessions. Compared to the WHO-FC ≥ II group, the WHO-FC I group was younger (65.6 ± 13.9 years vs. 74.3 ± 8.0 years) and had a lower CFS (3 [3, 4] vs. 4 [4, 6]) (median [25th, 75th percentiles]). The WHO-FC I achievement rates for each CFS score were CFS 3: 82.8%; 4: 53.8%; 5: 25.0%; 6: 33.3%; and 7: 20.0%. Logistic regression analysis showed that CFS was an independent predictor of WHO-FC I achievement (odds ratio 0.50, p = 0.012), but pre-BPA hemodynamic parameters and age were not independent predictors. Whether WHO-FC I can be achieved is predicted by pre-BPA patient frailty but not by pre-BPA hemodynamic parameters and age.

Relationship between platelet aggregation and stroke risk after percutaneous coronary intervention: a PENDULUM analysis.

In patients undergoing percutaneous coronary intervention (PCI) with a stent, high on-treatment platelet reactivity may be associated with an increased risk of stroke. This post hoc analysis of the PENDULUM registry compared the risk of post-PCI stroke according to on-treatment P2Y12 reaction unit (PRU) values. Patients aged ≥ 20 years who underwent PCI were stratified by baseline PRU (at 12 and 48 h post-PCI) as either high (HPR, > 208), optimal (OPR, > 85 to ≤ 208), or low on-treatment platelet reactivity (LPR, ≤ 85). The incidences of non-fatal ischemic and non-ischemic stroke through to 12 months post-PCI were recorded. Almost all enrolled patients (6102/6267 [97.4%]) had a risk factor for ischemic stroke, and most were receiving dual antiplatelet therapy. Of the 5906 patients with PRU data (HPR, n = 2227; OPR, n = 3002; LPR, n = 677), 47 had a non-fatal stroke post-PCI (cumulative incidence: 0.68%, ischemic; 0.18%, non-ischemic stroke). Patients with a non-fatal ischemic stroke event had statistically significantly higher post-PCI PRU values versus those without an event (P = 0.037). The incidence of non-fatal non-ischemic stroke was not related to PRU value. When the patients were stratified by PRU ≤ 153 versus > 153 at 12-48 h post-PCI, a significant difference was observed in the cumulative incidence of non-fatal stroke at 12 months (P = 0.044). We found that patients with ischemic stroke tended to have higher PRU values at 12-48 h after PCI versus those without ischemic stroke.Clinical trial registration: UMIN000020332.

Ischemic and Bleeding Events in PENDULUM Patients With High Bleeding Risk and High Platelet Reactivity.

BACKGROUND: The balance between thrombotic and bleeding risk is of great concern in high bleeding risk (HBR) patients. This study evaluated the relationship between perioperative antiplatelet reactivity and thrombotic and bleeding events in patients at HBR undergoing percutaneous coronary intervention (PCI).Methods and Results: In this post hoc analysis of the PENDULUM (Platelet rEactivity in patieNts with DrUg eLUting stent and balancing risk of bleeding and ischeMic event) registry, patients undergoing PCI were categorized as HBR or non-HBR, and stratified as having high platelet reactivity (HPR; P2Y12reaction unit [PRU] >208) or non-HPR (PRU ≤208). Cumulative incidences of cardiovascular and cerebrovascular events (Journal of the American College of Cardiology expert definitions) and bleeding events (Bleeding Academic Research Consortium criteria) were assessed 12 months after index PCI. The incidence of ischemic and bleeding events was ~3-fold higher in HBR vs. non-HBR patients. Thrombotic/ischemic events were significantly more common in the HPR subgroup in HBR patients (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.11-2.28; P=0.012), but there was no difference in non-HBR patients. After adjustment for covariates, HPR in HBR patients remained an independent factor for thrombotic and ischemic events (HR: 1.69; 95% CI: 1.13-2.54; P=0.011), but not for bleeding events (HR: 1.56; 95% CI: 0.78-3.11; P=0.210). CONCLUSIONS: Maintaining adequate PRU levels during PCI is an important factor in improving clinical outcomes, especially for HBR patients.