Aims: Smaller low-density lipoprotein (LDL) particle size has been suggested to result in the development of endothelial dysfunction, atherosclerosis, and in-stent restenosis (ISR); however, little ...is known regarding the impact of the LDL particle size on the neointima formation leading to ISR after everolimus-eluting stent (EES) implantation. Methods: In this study, we have included 100 patients to examine the relationship between an LDL-C/apolipoprotein B (Apo B) ≤ 1.2, reportedly representing the LDL particle size, and the neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during the follow-up coronary angiography (CAG) period (8.8±2.5 months) after EES implantation. We divided them into two groups: LDL-C/Apo B ≤ 1.2 group (low LDL-C/Apo B group, n=53) and LDL-C/Apo B >1.2 group (high LDL-C/Apo B group, n=47). Results: The low LDL-C/Apo B group had a significantly larger neointimal volume (12.8±5.3 vs. 10.3±4.9 mm3, p=0.021) and lower incidence of a neointimal homogeneous pattern (71 vs. 89 %), higher incidence of a neointimal heterogeneous pattern (25 vs. 9 %) (p=0.006) and higher prevalence of macrophage accumulation (9 vs. 2 %) (p=0.030) as assessed via OCT, and, as per the CAS findings, a higher prevalence of yellow grade ≥ 2 (grade 2; adjusted residual: 2.94, grade 3; adjusted residual: 2.00, p=0.017) than the high LDL-C/Apo B group. Conclusions: A low LDL-C/Apo B ratio was found to be strongly associated with neointimal proliferation and neointimal instability evidenced chronically by OCT and CAS. An LDL-C/Apo B ≤ 1.2 will be of aid in terms of identifying high-risk patients after EES implantation.
Aims: Though the number of patients with peripheral arterial disease (PAD) and critical limb ischemia (CLI) is increasing, few histopathological studies of PAD, particularly that involving ...below-the-knee arteries, has been reported. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) specimens obtained from patients who underwent lower extremity amputation due to CLIMethods: Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 histological sections. This protocol was approved by the Ethics Review Board of Nihon University Itabashi Hospital (RK-190910-01) and Kyorin University Hospital (R02-179).Results: The calcified area distribution was significantly larger in PTAs than in ATAs on soft X-ray radiographic images (ATAs, 48.3% ±19.2 versus PTAs, 61.6% ±23.9; p<0.001). Eccentric plaque with necrotic core and macrophage infiltration were more prominent in ATAs than in PTAs (eccentric plaque: ATAs, 63.7% versus PTAs, 49.1%; p<0.0001, macrophage: ATAs, 0.29% 0.095 - 1.1% versus PTAs, 0.12% 0.029 - 0.36%; p<0.001), histopathologically. Thromboembolic lesions were more frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%; p<0.05). Moreover, post-balloon injury pathology differed between ATAs and PTAs.Conclusions: Histological features differed strikingly between ATAs and PTAs obtained from CLI patients. Clarifying the pathological features of CLI would contribute to establishing therapeutic strategies for PAD, particularly disease involving below-the knee-arteries.
Aim: Coronary plaque rupture is the main cause of acute coronary syndrome (ACS), but the role of blood flow features around plaque rupture for ACS is still unknown. The present study aimed to assess ...the relationship between the geometric configuration of ruptured plaque and ACS occurrence using computational fluid dynamics (CFD) by moving particle method in patients with coronary artery disease. Methods: In this study, 45 patients with coronary artery disease who underwent three-dimensional intravascular ultrasound (IVUS) and had a coronary ruptured plaque (24 plaques with provoked ACS, 21 without) were included. To compare the difference in blood flow profile around ruptured plaque between the patients with and without ACS, the IVUS images were analyzed via the novel CFD analysis. Results: There were no significant differences in localized flow profile around ruptured plaque between the two groups when the initial particle velocity was 10.0 cm/s corresponded to a higher coronary flow velocity at ventricular diastole. However, when it was 1.0 cm/s corresponded to lower coronary flow velocity at ventricular systole, particles with lower velocity (0 ≤ V ≤ 5 cm/s) were more prevalent around ACS-PR ( p=0.035), whereas particles with higher velocity (10 ≤ V ≤ 20 cm/s) were more often detected in silent plaque ruptures (p=0.018). Conclusions: Three-dimensional IVUS revealed that coronary plaque rupture was a complex one with a wide variety of its stereoscopic configuration, leading to various patterns of the local coronary flow profile. A novel CFD analysis suggested that the local flow was more stagnant around ACS-provoked ruptures than in silent ones.
Aim: According to recent clinical trials, a combination of direct oral anticoagulants with antiplatelet drugs is often recommended for atrial fibrillation patients who receive drug-eluting stents ...(DESs). Although the optimal combination comprises direct factor Xa inhibitors and a P2Y12 receptor antagonist (or aspirin), their influence on vascular responses to DESs remains unclear. Methods: Pigs were given either aspirin and clopidogrel (dual antiplatelet therapy DAPT group), aspirin and rivaroxaban (AR group), or clopidogrel and rivaroxaban (CR group), followed by everolimus-eluting stent (Promus Element) implantation into the coronary artery. Stented coronary arteries were evaluated via intravascular optical coherence tomography (OCT) and histological analysis at 1 and 3 months. Results: OCT revealed lower neointimal thickness in the DAPT group and comparable thickness among all groups at 1 and 3 months, respectively. Histological analyses revealed comparable neointimal area among all groups and the smallest neointimal area in the CR group at 1 and 3 months, respectively. In the DAPT and AR groups, the neointima continued to grow from 1 to 3 months. A shortened time course for neointima growth was observed in the CR group, with rapid growth within a month (maintained for 3 months). A higher incidence of in-stent thrombi was observed in the AR group at 1 month; no thrombi were found in either group at 3 months. More smooth muscle cells with contractile features were found in the CR group at both 1 and 3 months. Conclusions: Our results proved the noninferiority of the combination of rivaroxaban with an antiplatelet drug, particularly the dual therapy using rivaroxaban and clopidogrel, compared to DAPT after DES implantation.
Low wall shear stress (WSS) is associated with plaque formation. However, the relationship between WSS and coronary plaque vulnerability remains unclear. Therefore, this study aimed to clarify the in ...vivo relationship between luminal WSS derived from three-dimensional (3D) computed tomography (CT) and plaque vulnerability within the coronary artery. Forty-three consecutive patients with ischemic heart disease and coronary stenotic lesions were enrolled and underwent coronary angiography and color-coded intravascular ultrasonography (iMap™) followed by multi-slice coronary CT angiography. CT-derived high-risk plaque was defined by specific CT characteristics, including low CT intensity (< 30 HU) and positive remodeling. The Student’s
t
test, Mann–Whitney
U
test,
χ
2
test, repeated measures analysis of variance, and logistic and multiple regression were used for statistical analyses. CT-derived high-risk plaque (
n
= 15) had higher values of maximum and average shear stress than CT-derived stable plaque (474 ± 453 vs. 158 ± 138 Pa,
p
= 0.018; 4.2 ± 3.1 vs. 1.6 ± 1.2 Pa,
p
= 0.007, respectively). Compared with patients with CT-derived stable plaque, those with CT-derived high-risk plaque had a higher prevalence of necrotic and lipidic characteristics (44 ± 13 vs. 31 ± 11%,
p
= 0.001) based on iMap™. Multivariate logistic regression analysis showed that the average WSS and necrotic plus lipidic content were independent determinants of CT-derived high-risk plaque (average WSS: odds ratio 2.996,
p
= 0.014; necrotic plus lipidic content: odds ratio 1.306,
p
= 0.036). Our findings suggested that CT-derived high-risk plaque may coexist with high shear stress on the plaque surface.
Aims: Wall shear stress (WSS) has been considered a major determinant of aortic atherosclerosis. Recently, non-obstructive general angioscopy (NOGA) was developed to visualize various atherosclerotic ...pathologies, including in vivo ruptured plaque (RP) in the aorta. However, the relationship between aortic RP and WSS distribution within the aortic wall is unclear. This study aimed to investigate the relationship between aortic NOGA-derived RP and the stereographic distribution of WSS by computational fluid dynamics (CFD) modeling using three-dimensional computed tomography (3D-CT) angiography. Methods: We investigated 45 consecutive patients who underwent 3D-CT before coronary angiography and NOGA during coronary angiography. WSS in the aortic arch was measured by CFD analysis based on the finite element method using uniform inlet and outlet flow conditions. Aortic RP was detected by NOGA. Results: Patients with a distinct RP showed a significantly higher maximum WSS value in the aortic arch than those without aortic RP (56.2±30.6 Pa vs 36.2±19.8 Pa, p=0.017), no significant difference was noted in the mean WSS between those with and without aortic RP. In a multivariate logistic regression analysis, the presence of a maximum WSS value more than a specific value was a significant predictor of aortic RP (odds ratio 7.21, 95% confidence interval 1.78-37.1,p=0.005). Conclusions: Aortic RP detected by NOGA was strongly associated with a higher maximum WSS in the aortic arch derived by CFD using 3D-CT. The maximum WSS value may have an important role in the underlying mechanism of not only aortic atherosclerosis, but also aortic RP.
Pathological changes after third-generation drug-eluting stent implantation remain unclear. We compared the tissue responses of coronary arteries after the implantation of third-generation abluminal ...biodegradable-polymer everolimus-eluting stent (3rd EES) and second-generation durable-polymer EES (2nd EES) using autopsy specimens and an atherosclerotic porcine model. We compared the histology of stented coronary arteries obtained by autopsy performed 1-10 months after 3rd EES (n (number of cases) = 4, stent-implanted period of 3-7 months) and 2nd EES (n (number of cases) = 9, stent-implanted period of 1-10 months) implantations. The ratio of covered stent struts was higher with 3rd EESs than with 2nd EESs (3rd; 0.824 ± 0.032 vs. 2nd; 0.736 ± 0.022, p = 0.035). Low-density lipoprotein receptor knockout minipigs were stented with 3rd or 2nd EES in the coronary arteries and the stented regions were investigated. The fibrin deposition around the 2nd EES was more prominent. Additionally, higher density of smooth muscle cells was confirmed after the 3rd EES implantation. Pathological examination after the 3rd EES demonstrated a combination of less fibrin deposition and more rapid acquisition of well-developed neointima as compared to the 2nd EES at autopsy and the atherosclerotic porcine model.
There are a few Japanese data regarding the incidence and outcomes of acute myocardial infarction (AMI) after the coronavirus disease 2019 (COVID-19) outbreak. We retrospectively reviewed the data of ...AMI patients admitted to the Nihon University Itabashi Hospital after a COVID-19 outbreak in 2020 (COVID-19 period) and the same period from 2017 to 2019 (control period). The patients’ characteristics, time course of admission, diagnosis, and treatment of AMI, and 30-day mortality were compared between the two period-groups for both ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI), respectively. The AMI inpatients decreased by 5.7% after the COVID-19 outbreak. There were no differences among most patient backgrounds between the two-period groups. For NSTEMI, the time from the symptom onset to admission was significantly longer, and that from the AMI diagnosis to the catheter examination tended to be longer during the COVID-19 period than the control period, but not for STEMI. The 30-day mortality was significantly higher during the COVID-19 period for NSTEMI (23.1% vs. 1.9%,
P
= 0.004), but not for STEMI (9.4% vs. 8.3%,
P
= 0.77). In conclusion, hospitalizations for AMI decreased after the COVID-19 outbreak. Acute cardiac care for STEMI and the associated outcome did not change, but NSTEMI outcome worsened after the COVID-19 outbreak, which may have been associated with delayed medical treatment due to the indirect impact of the COVID-19 pandemic.
In this retrospective observational study, we have examined the incidence, characteristics, and treatment of serious myocardial infarction (MI) -associated mechanical complications (MCs) occurring in ...Japanese patients in this era of percutaneous coronary intervention (PCI), focusing on frailty, nutrition, and clinical implication of surgery. Included were 883 patients who, having suffered an MI, had been admitted to Nihon University Hospital between January 2013 and April 2020. Fifteen (1.70%) of these patients had suffered a potentially catastrophic MC-ventricular free wall rupture (VFWR, n = 8), ventricular septal rupture (VSR, n = 6), or papillary muscle rupture (PMR, n = 1). Factors associated with the MCs were age, poor nutritional status, a high Killip class, delayed diagnosis of MI, a high lactate concentration, a low thrombolysis in myocardial infarction flow grade, and single-vessel disease. Thirty-day mortality among MC patients was 60% (9/15): 87.5% associated with VFWR, 33.3% associated with VSR and 0% associated with PMR. On adjusted multivariate analysis, occurrence of an MC was independently associated with 30-day mortality. Despite a high surgical risk (EuroSCORE II: 11.8 ± 4.7) with less frailty, 30-day mortality was lower among patients whose MC was treated surgically than among those whose MC was treated conservatively (40.0% versus 100.0%, respectively; P = 0.044).Our data suggest that surgical intervention can save patients with a life-threatening MI-associated MC and should be considered, if they are not particularly frail.
The clinical efficacy of the Impella for high-risk percutaneous coronary intervention (PCI) and cardiogenic shock remains under debate. We thus sought to investigate the protective effects on the ...heart with the Impella's early use pre-PCI using cardiac magnetic resonance imaging (CMRI).
We retrospectively evaluated the difference in the subacute phase CMR imaging results (19 ± 9 days after admission) between patients undergoing an Impella (n = 7) or not (non-Impella group: n = 18 12 intra-aortic balloon pumps (1 plus veno-arterial extracorporeal membrane oxygenation) and 6 no mechanical circulation systems) in broad anterior ST-elevation myocardial infarction (STEMI) cases. A mechanical circulation system was implanted pre-PCI.
No differences were found in the door-to-balloon time, peak creatine kinase, and hospital admission days between the Impella and non-Impella groups; however, the CMRI-derived left ventricular ejection fraction was significantly greater (45 ± 13% vs. 34 ± 7.6%, P = 0.034) and end-diastolic and systolic volumes smaller in the Impella group (149 ± 29 vs. 187 ± 41 mL, P = 0.006: 80 ± 29 vs. 121 ± 40 mL, P = 0.012). Although the global longitudinal peak strain did not differ, the global radial (GRS) and circumferential peak strain (GCS) were significantly higher in the IMPELLA than non-IMPELLA group. Greater systolic and diastolic strain rates (SRs) in the Impella than non-Impella group were observed in non-infarcted rather than infarcted areas.
Early implantation of an Impella before PCIs for STEMIs sub-acutely prevented cardiac dysfunction through preserving the GRS, GCS, and systolic and diastolic SRs in the remote myocardium. This study provided mechanistic insight into understanding the usefulness of the Impella to prevent future heart failure.