Unmet Needs in Managing Myocardial Infarction in Patients With Malignancy

Patients with cancer face a high short-term risk of arterial thromboembolism. One of the most fatal manifestations of arterial thromboembolism is myocardial infarction (MI), and patients with cancer face a 3-fold greater risk of MI than patients without cancer. The individual risk for arterial thrombotic events in patients with cancer is determined by the complex interaction of baseline cardiovascular risk factors, cancer type and stage, chemotherapeutic regimen, and other general contributing factors for thrombosis. Managing MI in patients with cancer is a clinical challenge, particularly due to cancer's unique pathophysiology, which makes it difficult to balance thrombotic and bleeding risks in this specific patient population. When patients with cancer present with MI, a limited proportion are treated with guideline-recommended therapy, such as antiplatelet therapy or invasive revascularization. Despite the limited evidence, existing reports consistently suggest similar clinical benefits of guideline-recommended therapy when administered to patients with cancer presenting with MI. In this review, we briefly summarize the available evidence, clinical challenges, and future perspectives on simultaneous management of MI and cancer, with a focus on invasive strategy

Percutaneous coronary intervention during the COVID-19 pandemic in Japan: Insights from the nationwide registration data.

[Background] Coronavirus disease 2019 (COVID-19) has negatively affected access to healthcare systems and treatment timelines. This study was designed to explore the impact of the COVID-19 pandemic on patients who underwent percutaneous coronary intervention (PCI). [Methods] From January 2019 to December 2020, 489, 001 patients from 1068 institutions were registered in the Japanese nationwide PCI (J-PCI) registry. We constructed generalized linear models to assess the difference in the daily number of patients and in-hospital outcomes between 2019 and 2020. [Findings] In total, 207 institutions (19·3%) had closed or restricted access during the first COVID-19 outbreak in May 2020; the number of closed or restricted institutions had plateaued at a median of 121 institutions (11·3%). The daily case volume of PCI significantly decreased in 2020 (by 6·7% compared with that in 2019; 95% confidence interval [CI], 6·2–7·2%; p < 0·001). Marked differences in the presentation of PCI patients were observed; more patients presented with ST-segment elevation myocardial infarction (18·3% vs. 17·5%; p < 0·001), acute heart failure (4·49% vs. 4·30%; p = 0·001), cardiogenic shock (3·79% vs. 3·45%; p < 0·001), and cardiopulmonary arrest (2·12% vs. 2·00%; p = 0·002) in 2020. The excess adjusted in-hospital mortality rate in patients treated in 2020 relative to those treated in 2019 was significant (adjusted odds ratio, 1·054; 95% CI, 1·004–1·107; p = 0·03). [Interpretation] While the number of patients who underwent PCI substantially decreased during the COVID-19 pandemic, more patients presented with high-risk characteristics and were associated with significantly higher adjusted in-hospital mortality. [Funding] The J-PCI registry is a registry led and supported by the Japanese Association of Cardiovascular Intervention and Therapeutics. The present study was supported by the Grant-in-Aid from the Ministry of Health and Labour (No. 20IA2002 and 21FA1015), the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI; No. 21K08064), and the Japan Agency for Medical Research and Development (No. 17ek0210097h000)

The Canadian WATCHMAN Registry for Percutaneous Left Atrial Appendage Closure

BACKGROUND Access to left atrial appendage closure (LAAC) in Canada is limited, due to funding restrictions. This work aimed to assess Canadian clinical practice on patient selection, postprocedural antithrombotic therapy, and safety and/or efficacy with WATCHMAN device implantation. METHODS Seven Canadian centres implanting the WATCHMAN device participated in this prospective multicentre, observational registry. All procedures were done under general anesthesia with transesophageal echocardiography guidance. Patients were prospectively followed for 2years. The long-term stroke rate was compared with the expected rate based on the CHA$_{2}$DS$_{2}$-VASc score. RESULTS A total of 272 patients who underwent LAAC with the WATCHMAN device between December 2013 and August 2019 (mean age: 75.4 years [standard deviation {SD}: 8.75]; male, 63.2%; CHA$_{2}$DS$_{2}$-VASc score: 4.35 [SD: 1.64]; HAS-BLED score: 3.55 [SD: 0.94]) were included. Most patients (90.4%) had prior history of bleeding (major, 80.5%; minor, 21.7%). The WATCHMAN device was successfully implanted in 269 patients (98.9%), with a few procedure-related complications, including 5 pericardial effusions requiring drainage (1.8%), and 1 death (0.4%; 22 days post-LAAC from respiratory failure). Post-LAAC antithrombotic therapy included dual antiplatelet therapy in 70.6%, single antiplatelet therapy in 18.4%, and oral anticoagulation in 13.6%. During the follow-up period (mean: 709.7 days [SD: 467.2]), an 81.4% reduction of the ischemic stroke rate occurred, based on the expected rate from the CHA$_{2}$DS$_{2}$-VASc score (6.0% expected vs 1.1% observed). Device-related thrombus was detected in 1.8%. CONCLUSIONS The majority of Canadian patients who underwent LAAC had oral anticoagulation contraindication due to prior bleeding, and most were safely treated with antiplatelet therapy post-LAAC, with a low device-related thrombus incidence. Long-term follow-up demonstrated that LAAC achieved a significant reduction in ischemic stroke rate

Cardiac CT angiography after percutaneous left atrial appendage closure: early versus delayed scanning after contrast administration

PURPOSECardiac computed tomography angiography (CCTA) is increasingly used for device surveillance after left atrial appendage closure (LAAC). While CT protocols with delayed scans are useful to diagnose thrombus in the LAA, an optimal protocol for post-procedural CCTA has not been established. Therefore, we assessed the role of delayed versus early scans for device surveillance.METHODSWe retrospectively reviewed patients who underwent LAAC at Vancouver General Hospital who had follow-up CCTAs using standard (early) and delayed scans. Scans were performed on Toshiba 320-detector (Aquilion ONE). Image quality was interpreted by 2 independent observers for anatomy, LAA contrast patency, and device-related thrombus (DRT) using VitreaWorkstationTM. A Likert scale of 1–5 was used (1= poor quality, 5= excellent) for assessment.RESULTSWe included 27 consecutive LAAC patients (9 Amplatzer, 18 WATCHMAN) with mean age 76.0±7.7 years, mean CHADS2 score 2.8±1.3, CHA2DS2-VASc score 4.4±1.6 and HAS-BLED score 3.4±1.0. Subjective quality assessments by both reviewers favored early scans for assessment of anatomy (reviewer 1: 4.63±0.63 [early] vs. 1.74±0.71 [delayed]; reviewer 2: 4.63±0.63 [early] vs. 1.89±0.64 [delayed]) and DRT (reviewer 1: 4.78±0.42 [early] vs. 3.11±1.16 [delayed]; reviewer 2: 4.70±0.47 [early] vs. 3.04±1.29 [delayed]). Inter-rater variability showed good correlation between reviewers (intraclass correlation 0.61–0.95). Mean LAA/LA attenuation ratios were significantly different between scans, with larger mean percent reduction of contrast opacification from LA to LAA in the early scans (57.0±36.6% reduction for early vs. 29.1±30.8% for delayed; p < 0.001)CONCLUSIONFor CT device surveillance post-LAAC early phase imaging provides superior image quality objectively and subjectively compared with delayed scanning

Variation in in-hospital mortality and its association with percutaneous coronary intervention-related bleeding complications : A report from nationwide registry in Japan.

Large-scale registries have demonstrated that in-hospital mortality after percutaneous coronary intervention (PCI) varies widely across institutions. However, whether this variation is related to major procedural complications (e.g., bleeding) is unclear. In this study, institutional variation in in-hospital mortality and its association with PCI-related bleeding complications were investigated. We analyzed 388,866 procedures at 718 hospitals performed from 2017 to 2018, using data from a nationwide PCI registry in Japan. Hospitals were stratified into quintiles according to risk-adjusted in-hospital mortality (very low, low, medium, high, and very high). Incidence of bleeding complications, defined as procedure-related bleeding events that required a blood transfusion, and in-hospital mortality in patients who developed bleeding complications were calculated for each quintile. Overall, 4,048 (1.04%) in-hospital deaths and 1,535 (0.39%) bleeding complications occurred. Among patients with bleeding complications, 270 (17.6%) died during hospitalization. In-hospital mortality ranged from 0.22% to 2.46% in very low to very high mortality hospitals. The rate of bleeding complications varied modestly from 0.27% to 0.57% (odds ratio, 1.95; 95% confidence interval, 1.58–2.39). However, mortality after bleeding complications markedly increased by quintile and was 6-fold higher in very high mortality hospitals than very low mortality hospitals (29.0% vs. 4.8%; odds ratio, 12.2; 95% confidence interval, 6.90–21.7). In conclusion, institutional variation in in-hospital mortality after PCI was associated with procedure-related bleeding complications, and this variation was largely driven by differences in mortality after bleeding complications rather than difference in their incidence. These findings underscore the importance of efforts toward reducing not only bleeding complications but also, even more importantly, subsequent mortality once they have occurred

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target