Publications by authors named "Sho Torii"

87 Publications

Pathology of severe coronary artery calcification treated with orbital atherectomy followed by balloon modification.

Eur Heart J Case Rep 2021 Jul 1;5(7):ytab231. Epub 2021 Jul 1.

Department of Cardiology, Kindai University School of Medicine, 3-4-1 Kowakae, Higashiosaka city, Osaka 577-8502, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjcr/ytab231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453419PMC
July 2021

Multiple Cardiovascular Diseases or Risk Factors Increase the Severity of Coronavirus Disease 2019.

Circ J 2021 Sep 22. Epub 2021 Sep 22.

Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Faculty of Medicine.

Background: This study aimed to determine whether disease severity varied according to whether coronavirus disease 2019 (COVID-19) patients had multiple or single cardiovascular diseases and risk factors (CVDRFs).Methods and Results:COVID-19 patients with single (n=281) or multiple (n=412) CVDRFs were included retrospectively. Multivariable logistic regression showed no significant difference in the risk of in-hospital death between groups, but patients with multiple CVDRFs had a significantly higher risk of acute respiratory distress syndrome (odds ratio: 1.75, 95% confidence interval: 1.09-2.81).

Conclusions: COVID-19 patients with multiple CVDRFs have a higher risk of complications than those with a single CDVRF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-21-0684DOI Listing
September 2021

External validation of the 4C Mortality Score for patients with COVID-19 and pre-existing cardiovascular diseases/risk factors.

BMJ Open 2021 09 8;11(9):e052708. Epub 2021 Sep 8.

Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Japan

Objectives: Predictive algorithms to inform risk management decisions are needed for patients with COVID-19, although the traditional risk scores have not been adequately assessed in Asian patients. We aimed to evaluate the performance of a COVID-19-specific prediction model, the 4C (Coronavirus Clinical Characterisation Consortium) Mortality Score, along with other conventional critical care risk models in Japanese nationwide registry data.

Design: Retrospective cohort study.

Setting And Participants: Hospitalised patients with COVID-19 and cardiovascular disease or coronary risk factors from January to May 2020 in 49 hospitals in Japan.

Main Outcome Measures: Two different types of outcomes, in-hospital mortality and a composite outcome, defined as the need for invasive mechanical ventilation and mortality.

Results: The risk scores for 693 patients were tested by predicting in-hospital mortality for all patients and composite endpoint among those not intubated at baseline (n=659). The number of events was 108 (15.6%) for mortality and 178 (27.0%) for composite endpoints. After missing values were multiply imputed, the performance of the 4C Mortality Score was assessed and compared with three prediction models that have shown good discriminatory ability (RISE UP score, A-DROP score and the Rapid Emergency Medicine Score (REMS)). The area under the receiver operating characteristic curve (AUC) for the 4C Mortality Score was 0.84 (95% CI 0.80 to 0.88) for in-hospital mortality and 0.78 (95% CI 0.74 to 0.81) for the composite endpoint. It showed greater discriminatory ability compared with other scores, except for the RISE UP score, for predicting in-hospital mortality (AUC: 0.82, 95% CI 0.78 to 0.86). Similarly, the 4C Mortality Score showed a positive net reclassification improvement index over the A-DROP and REMS for mortality and over all three scores for the composite endpoint. The 4C Mortality Score model showed good calibration, regardless of outcome.

Conclusions: The 4C Mortality Score performed well in an independent external COVID-19 cohort and may enable appropriate disposition of patients and allocation of medical resources. UMIN000040598.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-052708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438580PMC
September 2021

Inflammatory and Hypercoagulable Biomarkers and Clinical Outcomes in COVID-19 Patients.

J Clin Med 2021 Jul 13;10(14). Epub 2021 Jul 13.

Department of Cardiovascular Medicine, Department of Internal Medicine, Toho University Faculty of Medicine, Tokyo 143-8540, Japan.

Systemic inflammation and hypercoagulopathy are known pathophysiological processes of coronavirus disease 2019 (COVID-19), particularly in patients with known cardiovascular disease or its risk factors (CVD). However, whether a cumulative assessment of these biomarkers at admission could contribute to the prediction of in-hospital outcomes remains unknown. The CLAVIS-COVID registry was a Japanese nationwide retrospective multicenter observational study, supported by the Japanese Circulation Society. Consecutive hospitalized patients with pre-existing CVD and COVID-19 were enrolled. Patients were stratified by the tertiles of CRP and D-dimer values at the time of admission. Multivariable Cox proportional hazard models were constructed. In 461 patients (65.5% male; median age, 70.0), the median baseline CRP and D-dimer was 58.3 (interquartile range, 18.2-116.0) mg/L and 1.5 (interquartile range, 0.8-3.0) mg/L, respectively. Overall, the in-hospital mortality rate was 16.5%, and the rates steadily increased in concordance with both CRP (5.0%, 15.0%, and 28.2%, respectively < 0.001) and D-dimer values (6.8%, 19.6%, and 22.5%, respectively = 0.001). Patients with the lowest tertiles of both biomarkers (CRP, 29.0 mg/L; D-dimer, 1.00 mg/L) were at extremely low risk of in-hospital mortality (0% until day 50, and 1.4% overall). Conversely, the elevation of both CRP and D-dimer levels was a significant predictor of in-hospital mortality (Hazard ratio, 2.97; 95% confidence interval, 1.57-5.60). A similar trend was observed when the biomarker threshold was set at a clinically relevant threshold. In conclusion, the combination of these abnormalities may provide a framework for rapid risk estimation for in-hospital COVID-19 patients with CVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10143086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304719PMC
July 2021

Intensive Care Unit Admission for Moderate-to-Severe COVID-19 Patients With Known Cardiovascular Diseases or Their Risk Factors - Insights From a Nationwide Japanese Cohort Study.

Circ Rep 2021 Jul 25;3(7):375-380. Epub 2021 Jun 25.

Department of Cardiovascular Medicine, Saga University Saga Japan.

The COVID-19 pandemic has challenged healthcare systems, at times overwhelming intensive care units (ICUs). We aimed to describe the length and rate of ICU admission, and explore the clinical variables influencing ICU use, for COVID-19 patients with known cardiovascular diseases or their risk factors (CVDRF). A post hoc analysis was performed of 693 Japanese COVID-19 patients with CVDRF enrolled in the nationwide CLAVIS-COVID registration system between January and May 2020 (mean [±SD] age 68.3±14.9 years; 35% female); 199 patients (28.7%) required ICU management. The mean (±SD) ICU length of stay (LOS) was 19.3±18.5 days, and the rate of in-hospital death and hospital LOS were significantly higher (P<0.001) and longer (P<0.001), respectively, in the ICU than non-ICU group. Logistic regression analysis revealed that clinical variables reflecting impaired general condition (e.g., high C-reactive protein, low Glasgow Coma Scale score, SpO, albumin level), male sex, and previous use of β-blockers) were associated with ICU admission (all P<0.001). Notably, age was inversely associated with ICU admission, and this was particularly prominent among elderly patients (OR 0.97, 95% confidence interval 0.95-0.99; P=0.0018). One-third of COVID patients with CVDRF required ICU care during the first phase of the pandemic in Japan. Other than anticipated clinical variables, such as hypoxia and altered mental status, age was inversely associated with the use of the ICU, warranting further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circrep.CR-21-0066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258186PMC
July 2021

Genetic Variants Associated With Unexplained Sudden Cardiac Death in Adult White and African American Individuals.

JAMA Cardiol 2021 Sep;6(9):1013-1022

CVPath Institute, Gaithersburg, Maryland.

Importance: Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined.

Objective: To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes.

Design, Setting, And Participants: This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021.

Main Outcomes And Measures: The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD.

Results: The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants.

Conclusions And Relevance: In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2021.1573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173469PMC
September 2021

Reduction of door-to-balloon time in patients with ST-elevation myocardial infarction by single-catheter primary percutaneous coronary intervention method.

Catheter Cardiovasc Interv 2021 May 31. Epub 2021 May 31.

Cardiology, Tokai University Hospital, Isehara, Kanagawa, Japan.

Objectives: The objectives of this study is to confirm reduction of door-to-balloon (D2B) time with single-catheter percutaneous coronary intervention (SC-PCI) method.

Background: Reduction of total ischemic time is important in the emergency treatment of ST-elevation myocardial infarction (STEMI). There have been no established methods in primary percutaneous coronary intervention (PCI) to shorten ischemic time via radial access. Ikari left curve was reported as a universal guiding catheter for left and right coronary arteries. Several procedure steps can be skipped by SC-PCI method as the advantage of a universal catheter.

Methods: This study is a retrospective analysis of a total of 1,275 consecutive STEMI cases treated with primary PCI in 14 hospitals. Patients were divided into two groups, SC-PCI method (n = 298) and conventional PCI method (n = 977). Primary endpoints were door-to-balloon (D2B) time and radiation exposure dose.

Results: The mean age was 68 ± 13 years old. Radial access was used in 85% of participants. PCI success was achieved in 99.5% of participants and the SC-PCI method was successfully performed in 92.6%. The D2B time was shorter (68 ± 46 vs. 74 ± 50 min, respectively; p = .02), and the radiation exposure dose was lower (1,664 ± 970 vs. 2008 ± 1,605 mGy, respectively; p < .0001) in the SC-PCI group than in the conventional group.

Conclusion: Primary PCI with SC-PCI method for patients with STEMI demonstrated shorter D2B time and lower radiation exposure dose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.29797DOI Listing
May 2021

Late neointimal volume reduction is observed following biodegradable polymer-based drug eluting stent in porcine model.

Int J Cardiol Heart Vasc 2021 Jun 11;34:100792. Epub 2021 May 11.

Department of Cardiology, Tokai University, School of Medicine, Kanagawa, Japan.

Background: The BP-SES has an abluminally applied biodegradable polymer that is fully resorbed after 3-4 months but may have longer-lasting effects. The aim of this study was to determine the long-term vascular response to the novel Ultimaster™ sirolimus-eluting stent (BP-SES).

Methods: BP-SESs, everolimus-eluting stents (DP-EESs), and bare metal stents were implanted in 22 coronary arteries of 15 mini-swine. All animals underwent optical frequent domain imaging (OFDI) to assess neointimal volume and quality at either 1 (n = 7) or 3 (n = 8) months and at 9 (n = 15) months and were euthanized at 9 months. Stents were subsequently histologically investigated to analyze the vascular response and maturity of neointimal tissue according to cell density.

Results: OFDI revealed greater regression in neointimal volume from 3 to 9 months with BP-SESs than with DP-EESs (-0.6 ± 0.5 mm vs. 0.00 ± 0.4 mm,  = 0.07). Although there was no significant difference between BP-SESs and DP-EESs in the inflammation score (BMS, BP-SES, and DP-EES: 0.1 ± 0.1, 0.3 ± 0.4, and 0.4 ± 0.4, respectively;  < 0.0001) in histological analysis, BP-SESs showed slightly greater maturity than DP-EESs (1.8 ± 0.3, 1.7 ± 0.3, and 1.6 ± 0.3,  = 0.09).

Conclusions: While both BP-SESs and DP-EESs showed minimal inflammatory responses at 9 months, BP-SESs showed a trend for greater neointimal maturity and regression, which may be related to earlier completion of the vascular response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcha.2021.100792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134975PMC
June 2021

Clinical and Biomarker Profiles and Prognosis of Elderly Patients With Coronavirus Disease 2019 (COVID-19) With Cardiovascular Diseases and/or Risk Factors.

Circ J 2021 05 29;85(6):921-928. Epub 2021 Apr 29.

Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine.

Background: This study investigated the effects of age on the outcomes of coronavirus disease 2019 (COVID-19) and on cardiac biomarker profiles, especially in patients with cardiovascular diseases and/or risk factors (CVDRF).Methods and Results:A nationwide multicenter retrospective study included 1,518 patients with COVID-19. Of these patients, 693 with underlying CVDRF were analyzed; patients were divided into age groups (<55, 55-64, 65-79, and ≥80 years) and in-hospital mortality and age-specific clinical and cardiac biomarker profiles on admission evaluated. Overall, the mean age of patients was 68 years, 449 (64.8%) were male, and 693 (45.7%) had underlying CVDRF. Elderly (≥80 years) patients had a significantly higher risk of in-hospital mortality regardless of concomitant CVDRF than younger patients (P<0.001). Typical characteristics related to COVID-19, including symptoms and abnormal findings on baseline chest X-ray and computed tomography scans, were significantly less prevalent in the elderly group than in the younger groups. However, a significantly (P<0.001) higher proportion of elderly patients were positive for cardiac troponin (cTn), and B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP) levels on admission were significantly higher among elderly than younger patients (P<0.001 and P=0.001, respectively).

Conclusions: Elderly patients with COVID-19 had a higher risk of mortality during the hospital course, regardless of their history of CVDRF, were more likely to be cTn positive, and had significantly higher BNP/NT-proBNP levels than younger patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-21-0160DOI Listing
May 2021

Association Between Statin Use Prior to Admission and Lower Coronavirus Disease 2019 (COVID-19) Severity in Patients With Cardiovascular Disease or Risk Factors.

Circ J 2021 05 29;85(6):939-943. Epub 2021 Apr 29.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine.

Background: Cardiovascular diseases and/or risk factors (CVDRF) have been reported as risk factors for severe coronavirus disease 2019 (COVID-19).Methods and Results:In total, we selected 693 patients with CVDRF from the CLAVIS-COVID database of 1,518 cases in Japan. The mean age was 68 years (35% females). Statin use was reported by 31% patients at admission. Statin users exhibited lower incidence of extracorporeal membrane oxygenation (ECMO) insertion (1.4% vs. 4.6%, odds ratio [OR]: 0.295, P=0.037) and septic shock (1.4% vs. 6.5%, OR: 0.205, P=0.004) despite having more comorbidities such as diabetes mellitus.

Conclusions: This study suggests the potential benefits of statins use against COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-21-0087DOI Listing
May 2021

Intravascular Imaging and Histological Correlates of Medial and Intimal Calcification in Peripheral Artery Disease.

EuroIntervention 2021 Apr 26. Epub 2021 Apr 26.

CVPath Institute, Gaithersburg, MD, USA.

Background: In peripheral artery disease, two different types of calcifications are frequently observed, i.e., medial and intimal calcification.

Aims: The aim of this study is to determine the ability of intra-vessel ultrasound imaging (IVUS) and optical frequency domain imaging (OFDI) to detect medial and intimal calcification in human peripheral arteries.

Methods: We performed ex vivo intravascular imaging of cadaveric human peripheral arteries with calcifications. IVUS and OFDI images were co-registered with histology. A total 12 legs from 9 patients were examined, and 438 cross-sectional images were co-registered with histology.

Results: OFDI could detected 183 of 231 intimal calcification by histology, whereas IVUS could detect 194 [OFDI; sensitivity, 79%, specificity, 86%, area under the curve (AUC), 0.83; IVUS; sensitivity, 84%, specificity, 85%, AUC, 0.85]. Of 245 medial calcifications by histology, 160 and 164 were detected by OFDI and IVUS, respectively (OFDI; sensitivity, 65%, specificity, 85%, AUC, 0.75; IVUS; sensitivity, 67%, specificity, 80%, AUC, 0.74). Medial calcification with overlying intimal calcification (overlapped calcification) and unclear border between intima and media were the main reasons for misdiagnosis. Without those 89 overlapped calcifications, sensitivity in both OFDI and IVUS was improved (OFDI; sensitivity, 81%, specificity, 85%, AUC, 0.83; IVUS; sensitivity, 88%, specificity, 80%, AUC, 0.84).

Conclusions: There are limitation in detecting medial calcification in overlapped intimal calcification and with unclear border between intima and media by both IVUS and OFDI. It is important to distinguish medial calcification from intimal calcification before proceeding with endovascular therapy since different approaches should be required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4244/EIJ-D-20-01336DOI Listing
April 2021

Eruptive Calcified Nodules as a Potential Mechanism of Acute Coronary Thrombosis and Sudden Death.

J Am Coll Cardiol 2021 Apr;77(13):1599-1611

CVPath Institute, Gaithersburg, Maryland, USA. Electronic address:

Background: Calcified nodule (CN) has a unique plaque morphology, in which an area of nodular calcification causes disruption of the fibrous cap with overlying luminal thrombus. CN is reported to be the least frequent cause of acute coronary thrombosis, and the pathogenesis of CN has not been well studied.

Objectives: The purpose of this study is to provide a comprehensive morphologic assessment of the CN in addition to providing an evolutionary perspective as to how CN causes acute coronary thrombosis in patients with acute coronary syndromes.

Methods: A total of 26 consecutive CN lesions from 25 subjects from our autopsy registry were evaluated. Detailed morphometric analysis was performed to understand the plaque characteristics of CN and nodular calcification.

Results: The mean age was 70 years, with a high prevalence of diabetes and chronic kidney disease. CNs were equally distributed between men and women, with 61.5% of CNs found in the right coronary artery (n = 16), mainly within its mid-portion (56%). All CNs demonstrated surface nonocclusive luminal thrombus, consisting of multiple nodular fragments of calcification, protruding and disrupting the overlying fibrous cap, with evidence of endothelial cell loss. The degree of circumferential sheet calcification was significantly less in the culprit section (89° [interquartile range: 54° to 177°]) than in the adjacent proximal (206° [interquartile range: 157° to 269°], p = 0.0034) and distal (240° [interquartile range: 178° to 333°], p = 0.0004) sections. Polarized picrosirius red staining showed the presence of necrotic core calcium at culprit sites of CNs, whereas collagen calcium was more prevalent at the proximal and distal regions of CNs.

Conclusions: Our study suggests that fibrous cap disruption in CN with overlying thrombosis is initiated through the fragmentation of necrotic core calcifications, which is flanked-proximally and distally-by hard, collagen-rich calcification in coronary arteries, which are susceptible to mechanical stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2021.02.016DOI Listing
April 2021

Vascular Response of a Polymer-Free Paclitaxel-Coated Stent (Zilver PTX) versus a Polymer-Coated Paclitaxel-Eluting Stent (Eluvia) in Healthy Swine Femoropopliteal Arteries.

J Vasc Interv Radiol 2021 06 4;32(6):792-801.e5. Epub 2021 Mar 4.

CVPath Institute, Gaithersburg, Maryland; Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland. Electronic address:

Purpose: To compare the long-term vascular healing responses of healthy swine iliofemoral arteries treated with a polymer-free paclitaxel-eluting stent (Z-PES, Zilver PTX) or a fluoropolymer-based paclitaxel-eluting stent (FP-PES, Eluvia).

Materials And Methods: Bilateral iliofemoral arteries in 20 swine were treated with a Z-PES (n = 16) or a FP-PES (n = 24) and were examined histologically at 1, 3, 6, and 12 months.

Results: Morphometric analysis revealed larger external and internal elastic lamina, stent expansion, and lumen area in the FP-PES than in the Z-PES at all timepoints. Luminal narrowing was similar in the 2 groups at 1 month; however, greater stenosis was observed in the Z-PES group at 3 months, with significant regression thereafter, resulting in equivalent stenosis at 6 and 12 months. Greater drug effect and less complete vessel healing were found in the FP-PES group at all timepoints, including greater numbers of malapposed struts with excessive fibrin deposition at 1 and 3 months, than in the Z-PES group. Three of 12 FP-PESs from the 6- and 12-month cohorts also showed circumferential medial disruption with peri-strut inflammation, whereas no abnormal findings were observed in contralateral Z-PESs.

Conclusions: Prolonged paclitaxel release with the presence of a permanent polymer may contribute to the differential vascular responses seen for the Z-PES and FP-PES groups, including medial layer disruption and aneurysmal vessel degeneration that was sometimes observed in the FP-PES group. These distinct features should be confirmed by pathology and in vivo imaging of human superficial femoral arteries to determine their clinical significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvir.2021.02.014DOI Listing
June 2021

Co-Registration of Peripheral Atherosclerotic Plaques Assessed by Conventional CT Angiography, MicroCT and Histology in Patients with Chronic Limb Threatening Ischaemia.

Eur J Vasc Endovasc Surg 2021 Jan 10;61(1):146-154. Epub 2020 Nov 10.

CVPath Institute, Gaithersburg, MD, USA. Electronic address:

Objective: To co-register conventional computed tomography angiography (CTA), with ex vivo micro-computed tomography (microCT) and histology of popliteal atherosclerotic plaques. Improving the non-invasive imaging capabilities may be valuable to advance patient care with peripheral arterial obstructive disease towards lesion and individual based treatment.

Methods: In this prospective observational study, 12 popliteal arteries from 11 symptomatic patients who had undergone transfemoral amputations for chronic limb threatening ischaemia and who had pre-operative CTA, were analysed ex vivo by microCT and histology. A total of 353 histological cross sections were co-registered with microCT and CTA, and classified as: lipid rich (LP, n = 26), fibrous (FP, n = 80), or calcific (CP, n = 247) plaques. CTA and microCT plaque density was calculated in 791 regions of interest as Hounsfield units (HU).

Results: CTA and microCT could identify plaque components that were confirmed by histology such as fibrous tissue (FP), lipid pool/core (LP), and calcification (CP). MicroCT densities were 77.8 HU for FP (IQR 52.8, 129.5 HU), -28.4 HU for LP (IQR -87.1, 13.2 HU), and 3826.0 HU for CP (IQR 2989.0, 4501.0 HU). CTA densities of the three components of the plaque were: 78.0 HU for FP (IQR 59.5, 119.8 HU), 32.5 HU for LP (IQR 15.0, 42 HU), and 641.5 HU for CP (IQR 425.8, 1135 HU). The differences were statistically significant between the HU densitometric characteristics among the three groups (p < .0001) for both imaging modalities. Overall, microCT performed better diagnostically than conventional CTA for the three types of plaques: areas under the receiving operator characteristics curve were greater for microCT than CTA for FP (0.97 vs. 0.90), for LP (0.88 vs. 0.67), and for CP (0.97 vs. 0.90).

Conclusion: CTA and microCT can be used to identify histological atherosclerotic plaque components, with better diagnostic performance for microCT. This study demonstrates the feasibility of using microCT to assess plaque morphology lesions in a manner that approaches histology thus becoming a useful tool for ex vivo assessment of atherosclerosis and towards lesion based treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejvs.2020.08.037DOI Listing
January 2021

Formation of Calcified Nodule as a Cause of Early In-Stent Restenosis in Patients Undergoing Dialysis.

J Am Heart Assoc 2020 10 23;9(19):e016595. Epub 2020 Sep 23.

Department of Cardiology Kindai University Osaka Japan.

Background Dialysis is an independent risk factor for in-stent restenosis (ISR) after stent implantation in coronary arteries. However, the characteristics of ISR in patients undergoing dialysis remain unclear, as there are no histological studies evaluating the causes of this condition. The aim of the present study was to investigate the causes of ISR between patients who are undergoing dialysis and those who are not by evaluating tissues obtained from ISR lesions using directional coronary atherectomy. Methods and Results A total of 29 ISR lesions from 29 patients included in a multicenter directional coronary atherectomy registry of 128 patients were selected for analysis and divided into a dialysis group (n=8) and a nondialysis group (n=21). Histopathological evaluation demonstrated that an in-stent calcified nodule was a major histological characteristic of ISR lesions in the dialysis group and the prevalence of an in-stent calcified nodule was significantly higher in the dialysis group compared with the nondialysis group (75% versus 5%, respectively; <0.01). On the other hand, the prevalence of an in-stent lipid-rich plaque was significantly lower in the dialysis group compared with the nondialysis group (0% versus 43%, respectively; =0.03). In all cases with an in-stent calcified nodule, the underlying calcification before stent implantation was moderate to severe. When tissue characteristics were stratified according to duration post-stent implantation, an in-stent calcified nodule in the dialysis group was mainly observed within 1 year after stent implantation. Conclusions In-stent calcified nodules are a common cause of ISR in patients undergoing dialysis and are observed within 1 year after stent implantation, suggesting different causes of ISR between patients undergoing dialysis and those who are not.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.016595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792410PMC
October 2020

Comparison of Endothelial Barrier Functional Recovery After Implantation of a Novel Biodegradable-Polymer Sirolimus-Eluting Stent in Comparison to Durable- and Biodegradable-Polymer Everolimus-Eluting Stents.

Cardiovasc Revasc Med 2021 03 13;24:1-10. Epub 2020 Aug 13.

CVPath institute, Gaithersburg, MD, United States of America; University of Maryland, School of Medicine, Baltimore, MD, United States of America. Electronic address:

Aims: The advantage of biodegradable-polymer drug-eluting stents (BP-DES) versus durable-polymer (DP) DES remains uncertain. We compared neointimal formation and endothelial barrier function of new BP sirolimus-eluting stents (BP-SES, BuMA Supreme®) to other contemporary BP-DES, DP-DES, and bare metal stents (BMS).

Methods And Results: Light microscopic assessment in swine coronary arteries showed comparable neointimal formation between BP-SES and DP everolimus-eluting stent (DP-EES). The performance of BP-SES was compared with DP-EES (Xience Xpedition®), BP-EES (Synergy®), and BMS (Multi-Link Vision®) at 45- and 90-days in rabbit ilio-femoral arteries using Evans blue dye (EBD) followed by immunostaining for endothelial barrier proteins (p120/vascular endothelial-cadherin [VE-cad]) to evaluate endothelial barrier function and scanning electron microscopy (SEM) to determine strut tissue coverage. BMS followed by BP-SES and BP-EES exhibited smaller EBD positive areas versus that of DP-EES at 45- and 90-days. p120/VE-cad immunostaining and SEM-determined strut coverage was greater at 45- and 90-days for BMS followed by all DESs. Regardless of stent type, the lack of p120/VE-cad co-localization showed greater leukocyte and platelet aggregation.

Conclusion: Three types of DES showed different endothelial healing pattern regardless their equivalent suppression of neointimal formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carrev.2020.08.012DOI Listing
March 2021

Advances in mammalian target of rapamycin kinase inhibitors: application to devices used in the treatment of coronary artery disease.

Future Med Chem 2020 06 20;12(12):1181-1195. Epub 2020 May 20.

Cardiovascular Department, CVPath Institute, Gaithersburg, MD 20878, USA.

Mammalian target of rapamycin (mTOR) inhibitors have been applied to vascular coronary devices to avoid neointimal growth and have become the predominant pharmacological agents used to prevent restenosis. mTOR inhibitors can affect not only proliferating vascular smooth muscle cells but also endothelial cells and therefore can result in delayed healing of the vessel including endothelialization. Emerging evidence suggests accelerated atherosclerosis due to the downstream negative effects on endothelial barrier functional recovery. The development of neoatherosclerosis within the neointima of drug-eluting stents can result in late thrombotic events. This type of problematic healing response may open the way for specific mTOR kinase inhibitors, such as ATP-competitive mTOR inhibitors. These inhibitors demonstrate a better healing profile than traditional limus-based drug-eluting stent and their clinical efficacy remains unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4155/fmc-2019-0304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333590PMC
June 2020

Healthy Strut Coverage After Coronary Stent Implantation: An Ex Vivo Human Autopsy Study.

Circ Cardiovasc Interv 2020 05 27;13(5):e008869. Epub 2020 Apr 27.

CVPath Institute, Gaithersburg, MD (H.J., F.O., Y.S., R.R.B., A.S., S.T., K.Y., A.C., M.M., R.K., F.D.K., R.V., A.V.F.).

Background: Struts have been considered as covered when tissue overlying the struts is >0 μm by optical coherence tomography (OCT). However, there is no confirmatory study to validate this definition by histology which is the gold standard. The aim of the present study was to assess the appropriate cutoff value of neointimal thickness of stent strut coverage by OCT with histology confirmation.

Methods: We performed ex vivo OCT imaging of human coronary arteries with stents at autopsy. A total of 46 stents in 39 vessels from 25 patients were examined in this study, and a total of 165 cross-sectional images were co-registered with histology to determine the optimal cutoff value for strut coverage by OCT which was defined as luminal endothelial cells with 2 abluminal layers of smooth muscles cells and matrix. Considering the resolution of OCT is 10 to 20 μm, the cutoff values were assessed at ≥20, ≥40, and ≥60 μm.

Results: A total of 2235 struts were reviewed by histology, 1216 were considered as well-matched struts which were analyzed in this study. By histology, 160 struts were identified as uncovered, while 1056 struts were covered. The OCT assessment without consideration of neointimal thickness yielded a poor specificity of 37.5% and sensitivity 100%. Of 3 cutoff values, the cutoff value of ≥40 μm yielded the best sensitivity (99.3%), specificity (91.0%), positive predictive value (98.6%), and negative predictive value (95.6%) as compared with ≥20 and ≥60 μm.

Conclusions: Neointimal thickness ≥40 μm by OCT yielded the most accurate cutoff value to identify stent strut coverage validated by histology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008869DOI Listing
May 2020

Detection of cholesterol crystals by optical coherence tomography.

EuroIntervention 2020 Aug;16(5):395-403

CVPath Institute, Gaithersburg, MD, USA.

Aims: The aim of this study was to determine the ability of optical frequency domain imaging (OFDI)/optical coherence tomography (OCT) imaging systems to visualise the presence of cholesterol crystals (CCR) in human atherosclerotic coronary arteries.

Methods And Results: We performed ex vivo imaging of human coronary arteries by OFDI/OCT. A total of 559 cross-sectional images from 45 autopsy cases were co-registered with histology; 117 histologic sections showed presence of necrotic core with cholesterol clefts (CC). We modified a previously used OFDI/OCT definition for identification of CCRs which we now define as a linear and discrete high-intensity signal (bright area) within the plaque with sharp borders between it and adjacent low-/intermediate-intensity tissue. Additionally, the high-intensity signal is not a spot but a well-defined area distinguishing it from macrophages which lack sharp borders. OFDI/OCT imaging identified the presence of CCR in 30 of the 117 histologic sections. The sensitivity and specificity of OFDI/OCT for detection of CCR was 25.6% and 100.0%, respectively. By multivariate analysis, significant predictors to visualise CCR by OCT/OFDI were 1) an overlying fibrous plaque, and 2) the presence of stacked CC, defined as CC arranged one on top of another with >3 layers of CC. The prevalence of complicated plaques (i.e., plaque haemorrhage and late necrotic core) was significantly higher in detectable CCR by OFDI/OCT as compared to undetectable CCR.

Conclusions: The presence of stacked CCs is required to detect CCR by OFDI/OCT. Detection of CCR by OCT/OFDI may help us to identify the late stages of atherosclerotic coronary plaque progression and improve risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4244/EIJ-D-20-00202DOI Listing
August 2020

No Epicardial Fat, No Plaque Rupture.

Circ J 2020 04 11;84(5):702-703. Epub 2020 Apr 11.

Department of Cardiology, Kindai University Faculty of Medicine.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-20-0249DOI Listing
April 2020

Comparison of acute thrombogenicity and albumin adsorption in three different durable polymer coronary drug-eluting stents.

EuroIntervention 2021 Jun;17(3):248-256

CVPath Institute, Gaithersburg, MD, USA.

Background: The relative thrombogenicity and albumin adsorption and retention of different durable polymers used in coronary stents has not been tested.

Aims: This study sought to compare the thromboresistance and albumin binding capacity of different durable polymer drug-eluting stents (DES) using dedicated preclinical and in vitro models.

Methods: In an ex vivo swine arteriovenous shunt model, a fluoropolymer everolimus-eluting stent (FP-EES) (n=14) was compared with two durable polymer DES, the BioLinx polymer-coated zotarolimus-eluting stent (BL-ZES) (n=9) and a CarboSil elastomer polymer-coated ridaforolimus-eluting stent (EP-RES) (n=6), and bare metal stents (BMS) (n=10). Stents underwent immunostaining using a cocktail of antiplatelet antibodies and a marker for inflammation and were then evaluated by confocal microscopy (CM). Albumin retention was assessed using a flow loop model with labelled human serum albumin (FP-EES [n=8], BL-ZES [n=4], EP-RES [n=4], and BMS [n=7]), and scanned by CM.

Results: The area of platelet adherence (normalised to total stent surface area) was lower in the order FP-EES (9.8%), BL-ZES (32.7%), EP-RES (87.6%) and BMS (202.0%), and inflammatory cell density was least for FP-EES
Conclusions: These results suggest that thromboresistance and albumin retention vary by polymer type and that these differences might result in different suitability for short-term dual antiplatelet therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4244/EIJ-D-19-00938DOI Listing
June 2021

Pathology and Multimodality Imaging of Acute and Chronic Femoral Stenting in Humans.

JACC Cardiovasc Interv 2020 02;13(4):418-427

CVPath Institute, Gaithersburg, Maryland. Electronic address:

Objectives: The objective of this study was to comprehensively evaluate the pathology of acute and chronic femoral stenting in symptomatic atherosclerotic patients and to understand the causes of stent failure (SF) using multimodality imaging including micro-computed tomography.

Background: Although the pathology of coronary stenting has been well studied, the pathology of lower extremity femoral stenting remains poorly understood.

Methods: Twelve stented femoral lesions removed at surgery (n = 10) and at autopsy (n = 2) were obtained from 10 patients (median age 74 years; interquartile range [IQR]: 66 to 82 years) with histories of peripheral artery disease (critical limb ischemia in 7) (7 men and 3 women). All specimens underwent radiography, micro-computed tomography, and histological assessment.

Results: The median duration of implantation was 150 days (IQR: 30 to 365 days), the median stent diameter was 5.90 mm (IQR: 5.44 to 7.16 mm), and the median stent length was 39.5 mm (IQR: 27 to 107.5 mm). Of the 12 stented lesions, 2 had drug-eluting stents, and 10 had bare-metal stents. SF was observed in 8 of 12 lesions. The major cause of SF was acute thrombosis (6 of 8), but causes varied (delayed healing, stent underexpansion, false lumen stenting, and fracture), and 2 had restenosis. Stent fractures were observed in 3 cases by micro-computed tomography. Both drug-eluting stents, implanted for >1 year, showed delayed healing with circumferential peristrut fibrin deposition and SF.

Conclusions: This histological study is the first to examine the pathological cause of SF. Stent thrombosis was the major cause of SF. Delayed healing was a common feature of bare-metal stents implanted for <90 days, while all drug-eluting stents, despite implantation duration >1 year, showed delayed healing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcin.2019.10.060DOI Listing
February 2020

Vascular responses to coronary calcification following implantation of newer-generation drug-eluting stents in humans: impact on healing.

Eur Heart J 2020 02;41(6):786-796

Department of Cardiovascular Pathology, CVPath Institute, 19 Firstfield Road, Gaithersburg, MD 20878, USA.

Aims: Vascular calcification is routinely encountered in percutaneous coronary intervention (PCI) and severe coronary calcification is a known predictor of in-stent restenosis and stent thrombosis. However, the histopathologic mechanisms behind such events have not been systematically described.

Methods And Results: From our registry of 1211 stents, a total of 134 newer-generation drug-eluting stents (DES) (Xience, Resolute-Integrity, PROMUS-Element, and Synergy) with duration of implant ≥30 days were histologically analysed. The extent of calcification of the stented lesions was evaluated radiographically and divided into severe (SC, n = 46) and non-severely calcified lesions (NC, n = 88). The percent-uncovered struts per section {SC vs. NC; median 2.4 [interquartile range (IQR) 0.0-19.0] % vs. 0.0 (IQR 0.0-4.6) %, P = 0.02} and the presence of severe medial tears (MTs) (59% vs. 44%, respectively, P = 0.03) were greater in SC than NC. In addition, SC had a higher prevalence of ≥3 consecutive struts lying directly in contact with surface calcified area (3SC) (52% vs. 8%, respectively, P < 0.0001). Multivariate analysis demonstrated that sections with duration of implantation ≤6 months [odds ratio (OR): 7.7, P < 0.0001], 3SC (OR: 6.5, P < 0.0001), strut malapposition (OR: 5.0, P < 0.0001), and lack of MTs (OR: 2.5, P = 0.0005) were independent predictors of uncovered struts. Prevalence of neoatherosclerosis was significantly lower in SC than that of NC (24% vs. 44%, P = 0.02).

Conclusion: Severe calcification, especially surface calcified area is an independent predictor of uncovered struts and delayed healing after newer-generation DES implantation. These data expand of knowledge of the vascular responses of stenting of calcified arteries and suggests further understand of how best to deal with calcification in patients undergoing PCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehz850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828465PMC
February 2020

Imaging Human Platelet Adhesion and Albumin Retention to Coronary Stents in Real Time.

Cardiovasc Revasc Med 2020 02 12;21(2):245-248. Epub 2019 Sep 12.

CVPath Institute, Gaithersburg, MD, United States of America. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carrev.2019.09.006DOI Listing
February 2020

Diversity of macrophage phenotypes and responses in atherosclerosis.

Cell Mol Life Sci 2020 May 12;77(10):1919-1932. Epub 2019 Nov 12.

CVPath Institute, 19 Firstfield Road, Gaithersburg, MD, 20878, USA.

The presence of macrophages within the plaque is a defining hallmark of atherosclerosis. Macrophages are exposed to various microenvironments such as oxidized lipids and cytokines which effect their phenotypic differentiation and activation. Classically, macrophages have been divided into two groups: M1 and M2 macrophages induced by T-helper 1 and T-helper 2 cytokines, respectively. However, for a decade, greater phenotypic heterogeneity and plasticity of these cells have since been reported in various models. In addition to M1 and M2 macrophage phenotypes, the concept of additional macrophage phenotypes such as M (Hb), Mox, and M4 has emerged. Understanding the mechanisms and functions of distinct phenotype of macrophages can lead to determination of their potential role in atherosclerotic plaque pathogenesis. However, there are still many unresolved controversies regarding their phenotype and function with respect to atherosclerosis. Here, we summarize and focus on the differential subtypes of macrophages in atherosclerotic plaques and their differing functional roles based upon microenvironments such as lipid, intraplaque hemorrhage, and plaque regression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-019-03371-3DOI Listing
May 2020

Drug-eluting coronary stents: insights from preclinical and pathology studies.

Nat Rev Cardiol 2020 01 25;17(1):37-51. Epub 2019 Jul 25.

CVPath Institute, Gaithersburg, MD, USA.

Implantation of drug-eluting stents (DES) is the dominant treatment strategy for patients with symptomatic coronary artery disease. However, the first-generation DES had substantial drawbacks, including delayed healing, local hypersensitivity reactions and neoatherosclerosis, which all led to a steady increase in major adverse cardiovascular events over time. Subsequently, newer-generation DES were introduced with thinner struts, different scaffold designs (to improve deliverability while maintaining radial strength), different durable and biodegradable polymers - and in some cases no polymer (to improve vascular biocompatibility) - and new antiproliferative drug types and doses. Currently, >30 different DES are commercially available in Europe, with fewer available in the USA but with many new entrants coming onto the US market in the next few years. Never before have cardiologists been faced with so many choices of stent, each with its own unique design. In this Review, we detail preclinical and pathology studies for each stent design, examining thromboresistance, speed of neointimal coverage and completeness of healing, including endothelialization. We conclude by discussing how these design characteristics might affect the potential for shortening the minimum duration of dual antiplatelet therapy needed after coronary intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41569-019-0234-xDOI Listing
January 2020

IN.PACT™ Admiral™ drug-coated balloons in peripheral artery disease: current perspectives.

Med Devices (Auckl) 2019 12;12:53-64. Epub 2019 Feb 12.

Cardiovascular Pathology, CVPath Institute, Inc., Gaithersburg, MD, USA,

Endovascular therapy has evolved as a main treatment option especially in patients with short (<25 cm) femoropopliteal lesion. The latest guideline recommends the use of drug-eluting devices (both drug-coated balloons [DCBs] and drug-eluting stents) in short femoro-popliteal lesions as class IIb recommendation. DCB usage is also recommended for in-stent restenosis lesions (class IIb). DCBs are a more attractive treatment option because the lack of metal prosthesis allows for more flexibility in future treatment options including the option of treating nonstenting zones, previously DCB-treated zones with DCBs again. The IN.PACT™ Admiral™ DCB has shown promising clinical performance in several randomized control trials and global registries, and is currently the market DCB leader for the treatment of femoropopliteal lesions with more than 200,000 patients treated thus far. Currently, more than 10 DCBs have received Conformité Européene mark for the treatment of femoropopliteal atherosclerotic disease. Three of these (including IN.PACT Admiral DCBs) have also received Food and Drug Administration approval in the USA. However, some Conformité Européene-marked DCBs have failed to show consistent results in their clinical studies suggesting all DCBs are not created equal. Each DCB is unique (ie, drug type, drug dose, crystallinity, and excipient) with different clinical outcomes. In the current review, we will focus on the preclinical and clinical results of not only IN.PACT Admiral DCB, but also the other currently available DCBs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/MDER.S165620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385763PMC
February 2019

Comparisons of early vascular reactions in biodegradable and durable polymer-based drug-eluting stents in the porcine coronary artery.

PLoS One 2019 10;14(1):e0209841. Epub 2019 Jan 10.

Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan.

Current drug-eluting stents have abluminal polymer coating; however, thrombus formation in these compared with that in uniformly coated stents remains controversial. We evaluated thrombus formation and early endothelialization after using abluminal biodegradable polymer-coated sirolimus- (BP-SES), and everolimus-eluting stents (BP-EES) versus a durable polymer-coated everolimus-eluting stent (DP-EES) in an in vivo setting. BP-SES, BP-EES, and DP-EES (n = 6 each) were implanted in coronary arteries of 12 mini-pigs that were then sacrificed after 7 and 10 days. Stents were stained with hematoxylin and eosin, and a combined Verhoeff and Masson trichrome stain. Areas of fibrin deposition were digitally detected and measured with off-line morphometric software. Stents were investigated for re-endothelialization by transmission electron microscopy. At 7 days, histological analysis revealed the lowest area of fibrin deposition in BP-SES (BP-SES vs. BP-EES vs. DP-EES; 0.10 ± 0.06 mm2 vs. 0.15 ± 0.07 mm2 vs. 0.19 ± 0.06 mm2, p = 0.0004). At 10 days, the area of fibrin deposition was significantly greater in DP-EES (0.13 ± 0.04 mm2 vs. 0.14 ± 0.05 mm2 vs. 0.19 ± 0.08 mm2, p = 0.007). Endothelial cells in BP-SES demonstrated a significantly greater number of tight junctions than those in DP-EES according to by transmission electron microscopy for both days (p<0.05). Various parameters, including an inflammatory reaction and neointimal formation, were comparable among the groups at 7 and 10 days. An abluminal biodegradable polymer-coated SES showed the least fibrin deposition and greatest endothelial cell recovery at an early stage following implantation in the coronary arteries of mini-pigs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209841PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328177PMC
September 2019
-->