Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits ...trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.
Background:Stent thrombosis (ST) is a serious complication after drug-eluting stents (DES) implantation. To identify the risk factors of mortality following ST, we evaluated adverse event reports ...used for safety measures after approval.Methods and Results:Between July 2004 and August 2019, 2,887 ST case reports were submitted to the Pharmaceutical and Medical Device Agency. Reports of probable or possible ST (n=604), with insufficient data regarding in-hospital outcome or duration between procedure and ST occurrence (n=37) or duplicate reports (n=191) were excluded. Accordingly, 2,045 reports with definite ST were analyzed. Among the subjects, there were 286 in-hospital deaths (14.0%). Multivariate logistic regression analysis revealed that left main trunk (LMT) (odds ratio OR: 4.76, 95% confidence interval CI: 3.26–6.96), chronic heart failure (CHF) (OR: 2.88, 95% CI: 1.61–5.14), hemodialysis (OR: 2.69, 95% CI: 1.66–4.36), prior stroke (OR: 2.28, 95% CI: 1.15–4.51), over 70 years old (OR: 1.62, 95% CI: 1.22–2.16), and right coronary artery (OR: 0.41, 95% CI: 0.27–0.63) were independent factors for in-hospital death after DES-ST.Conclusions:LMT, CHF, hemodialysis, prior stroke, and older age were independently associated with higher risk of in-hospital death following DES-ST. If target patients have these factors, maximum preventive strategies against ST occurrence, including adequate dual-antiplatelet therapy duration and optimal DES deployment procedures, are required.
Coronary angioscopy (CAS) is a unique diagnostic device that allows direct visualization of the vascular luminal surface in living patients. CAS contributes to elucidate the pathology of coronary ...artery disease. This consensus document provides a standard for CAS examination and assessment.
In Japan, a robotic-assisted PCI (R-PCI) system, the CorPath GRX System (Corindus Inc.), has been approved for clinical use in 2018, which is the first introduction of R-PCI into Japan. In this ...study, the clinical performance of the R-PCI system in the initial year at Kurume University Hospital was evaluated comparing with conventional manual PCI (M-PCI). A total of 30 R-PCI and 77 M-PCI procedures performed between April 2019 and March 2020, were retrospectively included. The primary outcome was the rate of clinical success defined as < 30% residual stenosis without in-hospital major adverse cardiovascular events (MACE). The secondary outcomes were fluoroscopy time, dose area product (DAP), amount of radiation exposure to operators and assistants, procedural time, and contrast volume. Propensity-matching technique was used to match each R-PCI lesion to the nearest M-PCI lesion without replacement. After propensity score matching, 30 R-PCI procedures in 28 patients and 37 M-PCI procedures in 35 patients were analyzed. Clinical success rate with R-PCI was favorable and comparable to M-PCI (93.3 vs. 94.6%,
p
= 0.97), without any in-hospital MACE. The operator radiation exposure was significantly lower in R-PCI (0 vs. 24.5 µSV,
p
< 0.0001). Radiation exposure to the patients was tended to be reduced by R-PCI (DAP: 77.6 vs. 100.2 Gycm
2
,
p
= 0.07). There were no statistically significant differences in radiation exposure to the assistant, fluoroscopy time, procedural time and contrast volume between the two groups (radiation exposure to the assistant: 10.5 vs. 10.0 µSV,
p
= 0.64, fluoroscopy time: 27.5 vs. 30.1 min,
p
= 0.55, procedural time: 72.4 vs. 61.6 min,
p
= 0.23, and contrast volume: 93.2 vs. 102.0 ml,
p
= 0.36). R-PCI in selected patients demonstrated favorable clinical outcomes with dramatical reduction of radiation exposure to operators.
In 2013, a drug-coated balloon catheter (DCB) (SeQuent Please) for the treatment of coronary in-stent restenosis (ISR) was approved in Japan. The pre-marketing Japan domestic NP001 study demonstrated ...better outcomes of the DCB (
n
= 138) compared to plain balloon angioplasty (
n
= 72). After the introduction to marketing, a post-marketing surveillance (PMS) (
n
= 396) was conducted to evaluate the safety and efficacy of the DCB in Japanese routine clinical practice. The aim of this paper was to assess differences between the pre-marketing NP001 study and the PMS. Compared to the NP001 study, more complex lesions were treated in the PMS (type B2/C: 69.0% vs 20.4%, total occlusion: 11.2% vs 0%,
p
< 0.001, respectively) and target lesion was more frequently ISR related to drug-eluting stent (DES) (79.5% vs 39.4%,
p
< 0.001). Regarding clinical outcomes, the rate of target lesion revascularization (TLR) was higher in the PMS than in the NP001 study (TLR: 12.9% at 7 months and 17.6% at 12 months vs 2.8% at 6 months,
p
= 0.001,
p
< 0.001, respectively). Multivariable logistic regression analysis revealed that DES-ISR was a risk factor of TLR after DCB treatment for ISR (odds ratio: 5.77, 95% CI 1.75–18.95,
p
= 0.004). Among representative published trials using DCB for ISR, clinical outcomes are often worse in DES-ISR trials than those in bare metal stent-ISR trials. The rates of TLR in previous DES-ISR trials are similar to that in the current PMS (TLR at 12 months: 22.1% for ISAR-DESIRE 3, 15.3% for PEPCAD-DES, and 13.0% for RIBS IV). The effectiveness and safety of DCB for coronary ISR have been confirmed in the Japanese real-world survey. PMS would be useful to evaluate the safety and effectiveness of medical products throughout their total life cycles.
Although a domestic trial in Japan revealed that Absorb bioresorbable vascular scaffold (BVS) has no inferiority to everolimus-eluting stent (EES) cohort in the primary endpoint of the target lesion ...failure at 12 months, the scaffold/stent thrombosis (ST) rates with the BVS at 24 months were higher than those with the EES (Absorb BVS 3.1% vs. EES 1.5%), the ST rate of 3.1% with Absorb BVS is not an acceptable level in Japan. A cause-of-ST analysis revealed that cases in which diagnostic imaging and ensuing post-dilatation had been performed appropriately had lower ST rates than those without such management (within 1 year: 1.37% vs. 7.69%, from 1 to 2 years: 0.00% vs. 8.33%). Therefore, a further evaluation was needed to confirm that the ST rate with the Absorb BVS would be reduced by a proper implementation procedure. Regulatory approval was given conditionally to initiate rigorous post-marketing data collection in order to ensure the proper use of this device in limited facilities. The One-year Use-Result Survey in Japan for the Absorb BVS revealed no instances of ST. This approach to reducing the premarket regulatory burden of clinical trials and enhancing the post-marketing commitments of medical device regulation is useful for expediting patient access to innovative medical devices.
In 2018, the CorPath GRX system (Corindus) was approved for use in Japan, marking the introduction of the first robotic-assisted system for percutaneous coronary intervention (PCI) in the country. ...The present report describes the first experience of robotic-assisted PCI for four coronary lesions in two cases in a single center. All procedures succeeded without any complications, although one procedure was converted to manual PCI by the operator's decision. Post-marketing surveillance to assess the impact of this novel system on both Japanese patients and physicians is currently ongoing in Japan.
The detection and analysis of rare blood biomarkers is necessary for early diagnosis of cancer and to facilitate the development of tailored therapies. However, current methods for the isolation of ...circulating tumour cells (CTCs) or nucleic acids present in a standard clinical sample of only 5-10 ml of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. Here, we report the development of a flexible magnetic wire that can retrieve rare biomarkers from the subject's blood in vivo at a much higher yield. The wire is inserted and removed through a standard intravenous catheter and captures biomarkers that have been previously labelled with injected magnetic particles. In a proof-of-concept experiment in a live porcine model, we demonstrate the in vivo labelling and single-pass capture of viable model CTCs in less than 10 s. The wire achieves capture efficiencies that correspond to enrichments of 10-80 times the amount of CTCs in a 5-ml blood draw, and 500-5,000 times the enrichments achieved using the commercially available Gilupi CellCollector.
•MitraClip provides significant clinical improvements in DMR and FMR patients.•Informative data indicated TMVR using MitraClip did not increase mortality rate.•The medical need of MitraClip is very ...high.•MitraClip was approved in Japan for DMR and FMR with preserved cardiac function.
The indication for MitraClip (Abbott Vascular, Santa Clara, CA, USA) in the USA is degenerative mitral regurgitation (DMR), but the Japanese indication includes both DMR and functional mitral regurgitation (FMR), in patients without severe left ventricular dysfunction. One of the reasons for this difference is that the Japanese Circulation Society submitted a formal request to the Japanese government for early approval of MitraClip for both DMR and FMR on the basis of unmet medical need for MR patients resistant to medical therapy, but at prohibitive risk for mitral valve surgery.
Here, we describe the regulatory approval review process of MitraClip in Japan. Clinical data from outside Japan indicated that MitraClip provides significant improvements from baseline in New York Heart Association Class and hospitalizations for heart failure due to the reduction of MR grade without adversely affecting long-term prognosis in FMR patients as well as DMR patients. Also, a Japanese domestic trial showed a favorable acute procedural success rate without serious adverse events with MitraClip in both DMR and FMR patients. Further, it is considered in Japan that improvement of MR mechanically is clinically important in both DMR and FMR, in patients without severe left ventricular dysfunction. On the basis of these considerations, the MitraClip was approved in Japan for indications of both DMR and FMR with preserved cardiac function in patients at prohibitive risk for mitral valve surgery.
Cardiac regeneration strategies using stem cells have shown variable and inconsistent results with respect to patient cardiac function and clinical outcomes. There has been increasing consensus that ...improving the efficiency of delivery may improve results. The Helix transendocardial delivery system (BioCardia Inc.) has been developed to enable percutaneous transendocardial biotherapeutic delivery. Therefore, we evaluated cell retention using this unique system compared with direct transepicardial injection and intracoronary infusion in an animal model.Twelve healthy swine were used in this study. 18Fluorodeoxyglucose (FDG)-labeled bone marrow mononuclear cells were delivered via percutaneous transendocardial route using the Helix system (TE group, n = 5), via direct transepicardial injection using a straight 27-gauge needle in an open chest procedure (TP group, n = 4), or via percutaneous intracoronary (IC) infusion (IC group, n = 3). One hour after cell delivery, the distribution of injected cells within the myocardium was assessed by PET-CT. Regions of interest were defined and their signals were compared in each group. Retention rates were calculated as a percentage of the comparing signal.The distribution of injected cells in the myocardium was higher in the TE group (17.9%) than in the TP group (6.0%, versus TE, P < 0.001) and the IC group (1.0%, versus TE, P < 0.001). Consistent with previous reports, there were signal distributions in the lungs, liver, and kidneys in qualitative whole body PET assessment.TE cell delivery using a helical infusion catheter is more efficient in cell retention than either TP delivery or IC delivery using PET-CT analysis.
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