Temporal trends in coronary intervention strategies and the impact on one-year clinical events: data from a Japanese multi-center real-world cohort study.

Percutaneous coronary intervention (PCI) has significantly advanced over the last 40 years, but it is not clear whether there have been any changes in prognosis in recent years. The Kumamoto Intervention Conference Study Real-World Registry is a multi-center registry that enrolls consecutive patients undergoing PCI in 17 centers in Kyushu, Japan. To elucidate the clinical impact of recent changes in treatment strategies, 8841 consecutive participants (historical PCI: n = 4038, enrolled between January 2013 and December 2014, and current PCI: n = 4803, between January 2015 and March 2017) with 1-year follow-up data were analyzed. The incidences of major adverse cardiovascular and other clinical events were comparable between historical PCI and current PCI, even though complex lesions were more frequent during the more recent period. During this period, the use of radial approaches, drug eluting stents, and coronary imaging was greater. The use of prasugrel was more frequent (P < 0.001) during the time periods. Comparable event rates were associated with the use of clopidogrel (52.7%) and prasugrel (47.3%). In the sub-analysis for acute coronary syndrome (n = 5047), similar clinical event rates were recorded for historical and current PCI. Although the lesions to be treated are becoming more severe and complex, equivalent clinical outcomes have been maintained in recent years, possibly due to advances in the devices and medication used.

Effects of Statin Plus Ezetimibe on Coronary Plaques in Acute Coronary Syndrome Patients with Diabetes Mellitus: Sub-Analysis of PRECISE-IVUS Trial.

AIM: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM. METHODS: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9-12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) ＜70 mg/dL. RESULTS: In DM patients, the monotherapy group (n=13) and the DLLT group (n=12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: -2.77±3.47% vs. -0.77±2.51%, P=0.11; non-DM: -2.01±3.36% vs. -0.08±2.66%, P=0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r=0.52, P=0.008). CONCLUSIONS: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.

Imaging-guided PCI for event suppression in Japanese acute coronary syndrome patients: community-based observational cohort registry.

Although there is accumulating evidence for the usefulness of imaging-guided percutaneous coronary intervention (PCI), there are few studies for acute coronary syndrome (ACS), and the impact of the frequency of use has not been well addressed. From the Kumamoto Intervention Conference Study; a Japanese registry comprising 17 institutions, consecutive patients undergoing successful PCI from April 2008 through March 2014 were enrolled. Subjects were divided into two groups: imaging-guided PCI and angiography-guided PCI. Clinical outcome was a composite of cardiac death, non-fatal myocardial infarction, and stent thrombosis within 1 year. A total of 6025 ACS patients were enrolled: 3613 and 2412 patients with imaging- and angiography-guided PCI, respectively. Adverse cardiac events were significantly lower in the imaging-guided PCI group (long-rank P < 0.001). Even after propensity-score matching, the event rates still showed significant differences between the two groups (log-rank P = 0.004). To assess the effects of frequency of imaging usage, we divided the 17 institutions into six low-, six moderate-, and five high-frequency groups. The event rates decreased depending on the frequency, seemingly driven by stepwise event suppression in angiography-guided PCI. In Japanese ACS patients, the incidence of adverse clinical events in patients treated with imaging-guided PCI were significantly lower than that in patients with angiography-guided PCI. Better clinical result was found in the institutions using intravascular imaging more frequently. University Hospital Medical Information Network (UMIN)-CTR ( http://www.umin.ac.jp/ctr/ ). Identifier: KICS (UMIN000015397).

Impact of hydrostatic pressure on fractional flow reserve: in vivo experimental study of anatomical height difference of coronary arteries.

BACKGROUND: Although pressure equalization of the sensor-tipped guidewire and systemic pressure is mandatory in measuring fractional flow reserve (FFR), pressure in the distal artery (Pd) with wire advancement can be influenced by hydrostatic pressure related to the height difference between the catheter tip and the distal pressure sensor. We therefore analyzed the impact of hydrostatic pressure on FFR in vivo by modification of the height difference. METHODS: To reveal the anatomical height difference in human coronary arteries, measurement was performed during computed tomography angiography (CTA) of five consecutive patients. Utilizing the healthy coronary arteries of female swine, height difference diversity was reproduced by body rotation and vertical inclination. FFR measurements were performed during maximum hyperemia with adenosine. The height difference was calculated fluoroscopically with a contrast medium-filled balloon for reference. RESULTS: In human coronary CTA, height averages from the ostium in the left anterior descending artery (34.6 mm) were significantly higher than in the left circumflex (-15.5 mm, p = 0.008) and right coronary arteries (-2.3 mm, p = 0.008). In our swine model, reproduced height variation ranged from -7.2 cm to +6.5 cm. Mean FFR was significantly lower in positive sensor height and higher in negative sensor height compared to the reference height. Linear regression analyses revealed significant correlations between height difference and FFR, observed among all coronary arteries, as well as between the height difference and Pd-aortic pressure mismatch. Subtracting 0.622 mmHg/cm height difference from Pd could correct the expected hydrostatic pressure influence. CONCLUSION: Hydrostatic pressure variation resulting from sensor height influenced FFR values might affect interpretation during FFR assessment.

A case of repetitive acute coronary syndrome in a patient with familial hypercholesterolemia.

The low-density lipoprotein-cholesterol (LDL-C) level of a 60-year-old woman diagnosed with acute coronary syndrome (ACS) was 212 mg/dL. She was suspected of having familial hypercholesterolemia, therefore, administration of a proprotein convertase subtilisin-kexin type 9 (PCSK9) antibody in addition to atorvastatin plus ezetimibe was initiated, reducing her LDL-C level to 42 mg/dL. Nine months after initial ACS, the PCSK9 antibody was discontinued. Six months after the iturruption, she relapsed with ACS, and neoatherosclerosis progression was confirmed via intravascular ultrasound. Then, the PCSK9 antibody was reintroduced. Disruption of a PCSK9 may be associated with the progression and destabilization of neoatherosclerosis. .

Reduction in thrombogenic activity and thrombocytopenia after transcatheter aortic valve implantation - The ATTRACTIVE-TTAS study.

INTRODUCTION: Bleeding complications after transcatheter aortic valve implantation (TAVI) is a major problem in clinical practice. However, there is few information on thrombogenicity after TAVI. The aim of this study was to establish a monitoring of total thrombogenicity in perioperative TAVI using the Total Thrombus-formation Analysis System (T-TAS), a microchip-based flow chamber system for analysis of thrombus formation under flow condition. METHODS: Twenty-three patients with severe aortic stenosis who underwent TAVI between August 2017 and March 2018 at Kumamoto university hospital were enrolled. After exclusion, data of 21 patients were analyzed. Blood samples were obtained before, 2, 7, and 30 days after TAVI. Thrombogenicity were assessed by the T-TAS to compute the area under the curve (AUC) (AR10-AUC30) in the AR chip. We also measured platelet count, high-molecular-weight von Willebrand factor (HMW-vWF) multimers, and plasma thrombopoietin. Computational fluid dynamics (CFD) analysis was performed to calculate the wall shear stress (WSS). RESULTS: The AR10-AUC30 levels and platelet counts were significantly lower at 2 days post-TAVI, and then increased gradually. HMW-vWF multimers, and plasma thrombopoietin, were significantly higher at 2 days post-TAVI, compared with before TAVI. CFD analysis showed that WSS of the aortic valve and posterior ascending aortic wall were significantly lower after TAVI than before-TAVI. Multivariate analysis identified max velocity measured by echocardiography, platelet count, and D-dimer as significant determinants of AR10-AUC30, representing total thrombogenicity. CONCLUSIONS: Although HMW-vWF multimers improved earlier after TAVI, total thrombogenic activity evaluated by T-TAS remained relatively low followed by improvement in thrombogenic activity at 30 days after TAVI.Clinical Trial Registration: https://clinicaltrials.gov. Unique identifiers: NCT03248232.

Coronary Artery Plaque Regression by a PCSK9 Antibody and Rosuvastatin in Double-heterozygous Familial Hypercholesterolemia with an LDL Receptor Mutation and a PCSK9 V4I Mutation.

The low-density lipoprotein-cholesterol (LDL-C) level of a 38-year-old man diagnosed with acute coronary syndrome was 257 mg/dL. The administration of a proprotein convertase subtilisin-kexin type 9 (PCSK9) antibody in addition to rosuvastatin plus ezetimibe was initiated, reducing his LDL-C level to 37 mg/dL. A genetic analysis revealed both an LDL receptor (LDLR) mutation and a PCSK9 V4I mutation. Nine months after revascularization, intravascular ultrasound revealed plaque regression in the coronary arteries. LDLR/PCSK9 mutation carriers are prone to coronary artery disease. Intensive LDL-C lowering by including PCSK9 antibody was associated with coronary plaque regression, suggesting the expectation of prognosis improvement.

Impact of statin-ezetimibe combination on coronary atheroma plaque in patients with and without chronic kidney disease - Sub-analysis of PRECISE-IVUS trial.

BACKGROUND: Chronic kidney disease (CKD) deteriorates the prognosis of patients undergoing percutaneous coronary intervention (PCI). Because coronary artery disease (CAD) is the major cause of death in CKD patients, cardiovascular risk reduction has been clinically important in CKD. We hypothesized intensive lipid-lowering with statin/ezetimibe attenuated coronary atherosclerotic development even in patients with CKD. METHODS: In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound (IVUS)-guided PCI were randomly assigned to receive atorvastatin/ezetimibe combination or atorvastatin alone (the dosage of atorvastatin was up-titrated to achieve the level of low-density lipoprotein cholesterol < 70 mg/dL). Serial volumetric IVUS findings obtained at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients were compared stratified by the presence or absence of CKD. RESULTS: CKD was observed in 52 patients (26%) among 202 enrolled patients. Compared with the non-CKD group, the CKD group was significantly older (71.5 ±â€¯8.6 years vs. 64.4 ±â€¯9.6 years, P < 0.001) with similar prevalence of comorbid coronary risk factors and lipid profiles. Similar to the non-CKD group (-1.4 [-2.8 to -0.1]% vs. -0.2 [-1.7 to 1.0]%, P = 0.002), the atorvastatin/ezetimibe combination significantly reduced ∆PAV compared with atorvastatin alone even in the CKD group (-2.6 [-5.6 to -0.4]% vs. -0.9 [-2.4 to 0.2]%, P = 0.04). CONCLUSIONS: As with non-CKD, intensive lipid-lowering therapy with atorvastatin/ezetimibe demonstrated stronger coronary plaque regression effect even in patients with CKD compared with atorvastatin monotherapy. TRIAL REGISTRATION: NCT01043380 (ClinicalTrials.gov).

Atherosclerotic Coronary Plaque Development Visualized by In Vivo Coronary Imaging.

In the past decades, coronary imaging has evolved as a valuable adjunct to angiography, providing scientific insights into vascular biology and practical guidance by direct visualization of atherosclerosis and other pathologic conditions within the vessel walls. Especially with intravascular ultrasound (IVUS), the signal is able to penetrate below the luminal surface, so the entire cross-section of an artery, including the complete thickness of the plaque, can be imaged in real-time. On the other hand, optical coherence tomography (OCT) has been offering higher image resolution of both the plaque and the luminal surface. These technologies offer the opportunity to gather diagnostic information about the process of atherosclerosis and to directly observe the effects of various interventions on the plaque and arterial walls. IVUS has proven itself to be a practical and useful tool in the evaluation and optimal guidance of interventional vascular medicine. In this review, we detail the current modalities of coronary imaging and their usefulness in the diagnosis and management of patients with high-risk coronary plaques.

Impact of Chronic Kidney Disease on Outcomes After Percutaneous Coronary Intervention for Chronic Total Occlusions (from the Japanese Multicenter Registry).

The impact of chronic kidney disease (CKD) and potential pharmacologic intervention on clinical outcomes after percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) remains unknown. A total of 1,463 patients underwent successful CTO-PCI between August 2004 and December 2014. Major adverse cardiovascular events (MACE) defined as the composite of all-cause death, myocardial infarction and target lesion revascularization, cardiac death, and stent thrombosis were compared between patients with and without CKD (555 and 908 patients, respectively). The results demonstrated higher risks of MACE (log-rank p = 0.015), all-cause death (log-rank p <0.001), and cardiac death (log-rank p <0.001) in the CKD group compared with the non-CKD group. Multivariable analyses demonstrated that CKD was an independent predictor for MACE (hazard ratio 1.23, 95% confidence interval 1.02 to 1.47, p = 0.03). With regard to pharmacotherapy, statin use was associated with significantly lower rates of MACE in the CKD group (log-rank p = 0.003). In conclusion, the presence of CKD would be an important predictor of long-term clinical outcomes in patients who underwent CTO-PCI, and use of statin may influence in reducing the adverse clinical outcomes.

In Vivo optical coherence tomography visualization of intraplaque neovascularization at the site of coronary vasospasm: a case report.

BACKGROUND: Coronary plaques in patients with coronary vasospastic angina have been characterized by diffuse intima-media thickening with homogeneous fibrous tissue, without confluent necrotic tissue. However, coronary vasospasm can trigger coronary thrombosis, and may play an important role in the pathogenesis of acute coronary syndromes, though the precise morphological mechanisms underlying this process remain unclear. CASE PRESENTATION: A 43-year-old man with a history of multivessel coronary vasospastic angina had been treated with long-acting diltiazem and fluvastatin since 2004. Eleven years later, following 1 month of medication nonadherence, he experienced recurrence of rest angina and myocardial infarction, with elevated high-sensitivity troponin T. An emergency coronary angiogram demonstrated no de novo lesions, and the current episode was diagnosed as intractable sustained coronary spasm-induced anterior myocardial infarction. Optical coherence tomography imaging revealed the coronary plaque with homogeneous high-intensity signal, and a clearly visualized intraplaque neovascular microchannel (NVMC) network. CONCLUSIONS: Neovascularization within a coronary atheroma is known to accelerate coronary atherosclerosis. The current case with coronary vasospastic angina highlights the role of NVMC formation in this process.