scholarly journals Bone marrow-derived NGFR+ cells regulate arterial remodeling and those poor mobilizations in peripheral blood in acute coronary syndrome predicts plaque progression at the non-targeted lesion

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Takashima ◽  
S Usui ◽  
S Matsuura ◽  
C Goten ◽  
O Inoue ◽  
...  

Abstract Background In our previous 5-year cohort study, we demonstrated that low gene expression of nerve growth factor receptor (NGFR) in peripheral leucocytes in acute coronary syndrome (ACS) predicted repetitive coronary interventions at the de novo lesions. An NGFR-positive cell has been demonstrated to reside in bone marrow (BM) stromal fraction and to be increased in peripheral blood mononuclear cell (MNCs) fraction in patients with ischemic heart disease. Purpose To investigate whether the BM-NGFR+ cell is associated with arterial remodeling and the relationship between the levels of peripheral NGFR+ cells after ACS and coronary plaque progression in an experimental and prospective clinical study. Methods and results In an experimental study, 8-week-old C57B6/J wild type male mice were subjected to irradiation with 9.6 Gy and transplantation with BM (BMT) isolated from GFP-transgenic NGFR wild type (WT) or knock-out (KO) mice at day 1. Four weeks after BMT, the right carotid artery was ligated for 4 weeks. Induced neointimal area was increased (p<0.05), where cells under apoptosis were decreased (p<0.05) in NGFR-KO-BMT group compared to WT-BMT group (n=4). NGFR+ cells were not detected in wild type sham-operated artery, whereas in the ligated artery in WT-BMT group NGFR+ cells assembled in the developed neointima and exclusively presented double positive with GFP, but absent in NGFR-KO-BMT group (p<0.05, n=4). In a clinical study, thirty patients with ACS who underwent primary percutaneous coronary intervention (PCI) were enrolled. The peripheral blood sample was collected on days 0, 3 and 7, and 9 months follow-up and the number of NGFR+MNCs were measured by flowcytometric analysis. The plaque volume at non-targeted coronary lesion (non-TL:>5 mm proximal or distal to the implanted stents) were quantitatively analysed using gray-scale intravascular ultrasound (IVUS) and Q-IVUS™ software at the acute phase and 9 months follow-up. The number of NGFR+MNCs in peripheral blood was 1.5-fold increased at day 3 (0.064±0.056%) compared to day 0 (0.042±0.030%) (p<0.05). The change in normalized total plaque volume (TAVN) at non-TL at 9 months was negatively correlated with the number of NGFR+MNCs at day 0 (r=−0.51), day 3 (r=−0.51) and 9 months (r=−0.59) after ACS (p<0.05). Multiple regression analysis showed that NGFR+MNCs at day 0 (β=−0.48, p=0.01) and CRP (β=−0.53, P<0.01) are independent factors associating with TAVN change at non-TL at 9 months, regardless of LDL-cholesterol control level. ROC analysis revealed that NGFR+MNCs <0.049 at day 0 predicted the increase of TAVN with AUC 0.78; sensitivity 0.82 and specificity 0.67. Conclusions Bone marrow-derived peripheral NGFR+ cells negatively regulate arterial remodeling through appropriate apoptosis of neointimal cells and the peripheral level of NGFR+ cells in ACS predicts plaque progression at the non-targeted lesion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): KAKENHI

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Gonzalez Ferrero ◽  
B.A.A Alvarez Alvarez ◽  
C.C.A Cacho Antonio ◽  
M.P.D Perez Dominguez ◽  
P.A.M Antunez Muinos ◽  
...  

Abstract Introduction Ischaemic stroke (IS) risk after acute coronary syndrome is increasing. The aim of our study was to evaluate the stroke rate in a multicentre study and to determine the prediction ability of the PRECISE DAPT score, added to the prediction power of the GRACE score, already demonstrated. Methods This was a retrospective study, carried out in two centres with 5916 patients, with ACS discharged between 2011 and 2017 (median 66±13 years, 27.7% women). The primary endpoint was the occurrence of ischaemic stroke and its risk during follow up (median 5.5, IQR 2.6–7.0). Results A multivariable logistic regression analysis was made, where GRACE (HR 1.01, IC 95% 1.00–1.02) and PRECISE DAPT score (HR 1.03, IC 95% 1.01–1.05) were both an independent predictor of ischaemic stroke after ACS, in a model adjusted by age and AF, which was found to be the independent factor with highest risk (HR 1.67, IC 95% 1.09–2.55). Conclusions GRACE and PRECISE DAPT scores are ischaemic stroke predictors used during follow-up for patients after acute coronary syndrome. We should use both of them not only trying to predict ischaemic/haemorrhagic risk respectively but also as ischaemic stroke predictors. Figure 1. AUC Curves Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Redfern ◽  
K Hyun ◽  
D Brieger ◽  
D Chew ◽  
J French ◽  
...  

Abstract Background Cardiovascular disease is the leading cause of disease burden globally. With advancements in medical and surgical care more people are surviving initial acute coronary syndrome (ACS) and are in need of secondary prevention and cardiac rehabilitation (CR). Increasing availability of high quality individual-level data linkage provides robust estimates of outcomes long-term. Purpose To compare 3 year outcomes amongst ACS survivors who did and did not participate in Australian CR programs. Methods SNAPSHOT ACS follow-up study included 1806 patients admitted to 232 hospitals who were followed-up by data linkage (cross-jurisdictional morbidity, national death index, Pharmaceutical Benefit Schedule) at 6 and 36 months to compare those who did/not attend CR. Results In total, the cohort had a mean age of 65.8 (13.4) years, 60% were male, only 25% (461/1806) attended CR. During index admission, attendees were more likely to have had PCI (39% v 14%, p<0.001), CABG (11% v 2%, p<0.001) and a diagnosis of STEMI (21% v 5%, p<0.001) than those who did not attend. However, there was no significant difference between CR attendees/non-attendees for risk factors (LDL-cholesterol, smoking, obesity). Only 19% of eligible women attended CR compared to 30% of men (p<0.001). At 36 months, there were fewer deaths amongst CR attendees (19/461, 4.1%) than non-attendees (116/1345, 8.6%) (p=0.001). CR attendees were more likely to have repeat ACS, PCI, CABG at both 6 and 36 months (Table). At 36 months, CR attendees were more likely to have been prescribed antiplatelets (78% v 53%, p<0.001), statins (91% 73%, p<0.001), beta-blockers (11% v 13%, p=0.002) and ACEI/ARBs (72% v 61%, p<0.001) than non-attendees. Conclusions Amongst Australian ACS survivors, participation in CR was associated with less likelihood of death and increased prescription of pharmacotherapy. However, attendance at CR was associated with higher rates of repeat ACS and revascularisation. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): New South Wales Cardiovascular Research Network, National Heart Foundation


2020 ◽  
Vol 9 (5) ◽  
pp. 1578
Author(s):  
Miho Nishitani-Yokoyama ◽  
Katsumi Miyauchi ◽  
Kazunori Shimada ◽  
Takayuki Yokoyama ◽  
Shohei Ouchi ◽  
...  

Background: We investigated the combined effects of physical activity (PA) and aggressive low-density lipoprotein cholesterol (LDL-C) reduction on the changes in coronary plaque volume (PV) in patients with acute coronary syndrome (ACS) using volumetric intravascular ultrasound (IVUS) analysis. Methods: We retrospectively analyzed data from two different prospective clinical trials that involved 101 ACS patients who underwent percutaneous coronary intervention (PCI) and assessed the non-culprit sites of PCI lesions using IVUS at baseline and at the follow-up. After PCI, all the patients participated in early phase II comprehensive cardiac rehabilitation. Patients were divided into four groups based on whether the average daily step count, measured using a pedometer, was 7000 steps of more and whether the follow-up LDL-C level was <70 mg/dL. At the time of follow-up, we examined the correlation of changes in the PV with LDL-C and PA. Results: The baseline characteristics of the four study groups were comparable. At the follow-up, plaque regression in both the achievement group (PA and LDL-C reduction) was higher than that in the other three groups. In addition, plaque reduction independently correlated with increased PA and reduction in LDL-C level. Conclusions: Combined therapy of intensive PA and achievement of LDL-C target retarded coronary PV in patients with ACS.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Tomaniak ◽  
E.M.J Hartman ◽  
M.N Tovar Forero ◽  
J.J Wentzel ◽  
J Daemen

Abstract Background Serial intravascular ultrasound (IVUS) studies demonstrated patterns of either plaque progression, regression or stabilization during pharmacotherapy including statin. At present little is known on specific plaque characteristics that are associated with excessive plaque growth. Purpose To evaluate the utility of near infrared spectroscopy (NIRS) and optical coherence tomography (OCT) to identify characteristics of non-culprit plaques associated with an increase in wall thickness (WT). Methods In this prospective, single-center study, patients with acute coronary syndrome (ACS) underwent, after successful treatment of the culprit lesions, both NIRS-IVUS and OCT assessment of a non-culprit artery at baseline and 12-month follow-up. For each vessel, 1.5-mm segments were identified, matched and divided into 45° sectors. A sector was considered as NIRS positive or labeled as OCT-detected fibrous cap atheroma (FCA), lipid rich or fibrous plaque when &gt;75% of the sector area exhibited NIRS signal or specific OCT-detected feature. The relationship between change in IVUS-based WT, and the presence of NIRS positive signal or OCT-detected plaque components (FCA, lipid rich, fibrous) was evaluated using mixed ANCOVA, with NIRS status and OCT plaque components as fixed factors, and patient as random factor, adjusting for clustering effect of the data. All analyses of plaque WT change were adjusted for baseline WT. To examine the value of NIRS and OCT-detected plaque components in predicting plaque progression, a logistic mixed model was built with plaque progression defined as WT increase &gt;0.2mm over the 12-month follow-up. Results A total of 38 patients (92% male, 21% diabetic) with 9167 matched sectors were analyzed at baseline and 12 months. Mean change in WT between baseline and 12 months was 0.014mm (95% confidence interval [CI] 0.011–0.018, p&lt;0.001). Positive NIRS sectors showed more pronounced plaque progression than NIRS negative sectors (0.057mm, 95% CI 0.032–0.084 vs 0.014mm 95% CI 0.010–0.017, p=0.001) (Figure 1). FCA showed significant progression of WT over the 12-month follow-up (0.104mm, 95% CI 0.007–0.201), whereas a decrease in WT was observed in sectors with fibrous tissue (−0.031mm, 95% CI 0.048–0.014) (p=0.022). Baseline NIRS positive (OR 1.88, 95% CI 1.34–2.64) and OCT-detected lipid rich plaque (OR 1.47, 95% CI 1.20–1.81) were associated with 12-month plaque progression (&gt;0.2mm) by logistic regression. Conclusions Positive NIRS signal and OCT-detected lipid plaque components imaged at baseline in non-culprit coronary arteries of patients presenting with ACS could identify vessel wall regions prone to plaque progression over a 12-month period. Figure 1. Plaque progression and NIRS Funding Acknowledgement Type of funding source: Other. Main funding source(s): M. Tomaniak acknowledges funding received as a Laureate of the European Society of Cardiology Research and Training Programme in the form of the ESC 2018 Grant.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Szabo ◽  
A Bagonyi ◽  
Z.S Dohy ◽  
C.S Czimbalmos ◽  
A Toth ◽  
...  

Abstract Background Clinical presentation of myocarditis varies, one specific form of myocarditis appears with the clinical signs of acute coronary syndrome (ACS). Cardiac magnetic resonance (CMR) is an important method for assessing ventricular function and morphology, additionally provides accurate tissue specific and functional information of the heart. Aims Our aim was to investigate the characteristics, and prognosis of myocarditis presenting with ACS symptoms. Methods 113 patients with the clinical signs of ACS but nonobstructed coronary arteries in whom the CMR revealed acute myocarditis were included in our study. CMR was performed in acute phase and at 3–6-month follow-up. Left ventricular (LV) volumes, mass and strain parameters expressing myocardial deformity were determined. Additional images were taken to represent tissue specific information. Relationships between laboratory and CMR parameters were investigated. Parameters predicting changes in LV ejection fraction (LVEF) were analyzed by logistic regression. Results A total of 113 patients with myocarditis (98 males, 31±11 years) underwent acute and follow-up CMR. Sixty two patients reported fever or infection before the beginning of their complaints, most commonly gastroenteritis (33%) and pharyngitis (32%). The creatinine kinase MB value measured in the acute phase showed positive correlation with the extent of necrosis, and the global longitudinal- and circumferential strain. The extent of the LV necrosis showed negative correlation with LVEF and positive correlation with global circumferential strain (GCS) (p&lt;0.05). On the control CMR examination LVEF and all global strain values improved, fibrosis persisted in 82% of cases but shrank (15±11 vs 5±4 g) and LV mass decreased (p&lt;0.01) compared to the acute phase. Compared to the acute phase, 21% of the patients had lower LVEF on the follow-up CMR. Lower initial LVEF, worse acute GCS, and greater LV necrosis were independent predictors of LVEF reduction in the logistic regression model. During a median follow-up of 6-years of patients treated at our clinic (n=39) no patient suffered cardiac death, heart failure, or documented ventricular arrhythmia but 21% of them had recurrent myocarditis. Conclusion Myocarditis mimicking ACS affects predominantly young men and shows functional improvement and good prognosis on follow-up, but it may reoccur in some cases. The reduction of LV function on control CMR may be predicted by worse initial LVEF, GCS, and a larger LV scar. Strain, LGE in acute phase and follow-up Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Project no. NVKP_16-1-2016-0017 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the NVKP_16 funding scheme. This project was supported by a grant from the National Research, Development and Innovation Office (NKFIH) of Hungary (K 120277).


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Sopova ◽  
G Georgiopoulos ◽  
M Mueller-Hennessen ◽  
M Sachse ◽  
N Vlachogiannis ◽  
...  

Abstract Background Cathepsin S is an extracellular matrix degradation enzyme that plays an important role in atherosclerotic cardiovascular disease by inducing vasa vasorum development and atherosclerotic plaque rupture. Purpose To determine the prognostic and reclassification value of baseline serum cathepsin S after adjustment for the Global Registry of Acute Coronary Events (GRACE) score, which is a clinical guideline recommended risk score in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods Serum cathepsin S was measured by ELISA in 1,129 consecutive patients presenting with acute symptoms to the emergency department for whom a final adjudicated diagnosis of NSTE-ACS was made. All-cause mortality or all-cause death/non-fatal myocardial infarction (MI) after a median follow-up of 21 months were evaluated as the primary or secondary study endpoint, respectively. The Net Reclassification Index (NRI) estimated the reclassification predictive value for risk of each end-point of cathepsin S over the GRACE score. Results After a median follow-up of 21 months 101 (8.95%) deaths were reported. The combined endpoint of death or non-fatal MI occurred in 176 (15.6%) patients. Dose-response curve analysis adjusted for the effect of age, gender, diabetes mellitus, high-sensitivity-cardiac troponin T, high-sensitivity C-reactive protein, revascularization and index diagnosis revealed a non-linear association of continuous cathepsin S with all-cause death (P=0.036 for non-linearity; adjusted HR=1.60 for 80th vs. 20th percentiles, P=0.038) or with the combined endpoint (P=0.008 for non-linearity, adjusted HR=1.53 for 80th vs. 20th percentiles, P=0.011). Serum cathepsin S maintained its predictive value for all-cause death (adjusted HR=1.70 highest vs. lowest tertile, 95% CI 1.03–2.82, P=0.039) after adjusting for the GRACE Score. Similarly, cathepsin S predicted the combined endpoint of all-cause death or non-fatal MI (adjusted HR=1.67 highest vs. lowest tertile, 95% CI 1.15–2.42, P=0.007) independently of the GRACE Score. When cathepsin S was added over the GRACE Score it correctly reclassified risk for all-cause death in 20% of the population (P=0.004). Similarly, serum Cathepsin S conferred a significant reclassification value over the GRACE score for all-cause death or non-fatal MI in 15.9% of the population. Conclusions Serum cathepsin S is a predictor of mortality and improves risk stratification over the GRACE score in patients with NSTE-ACS. The clinical application of cathepsin S as a novel biomarker in NSTE-ACS should be further explored and validated. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Heart Foundation


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Chen ◽  
Y Liu ◽  
C Duan ◽  
H Fan ◽  
L Zeng ◽  
...  

Abstract Background Statins remain a standard treatment for acute coronary syndrome (ACS) patients. We aimed to determine the association between different dosages of in-hospital statins and the prognoses among patients receiving percutaneous coronary intervention (PCI). Methods NSTE-ACS patients were retrospectively enrolled from January 2010 to December 2014 from five centres in China. Patients receiving either atorvastatin or rosuvastatin during their hospitalizations were included. All the patients were categorized into high-dose statin group (40mg atorvastatin or 20mg rosuvastatin) or low-dose statin group (20mg atorvastatin or 10mg rosuvastatin). In-hospital events and long-term all-cause death was recorded. Results Of the 7,008 patients included in the study, 5,248 received low-dose intensive statin (mean age: 64.28±10.39; female: 25.2%), and 1,760 received high-dose intensive statin (mean age: 63.68±10.59; female: 23.1%). There was no significant difference in in-hospital all-cause death between the two groups (adjusted OR, 1.27; P=0.665). All-cause death was similar between the two groups during the long-term follow-up period (30-day: adjusted HR, 1.28; P=0.571; 3-year: adjusted HR, 0.83; P=0.082). However, there was a robust association between the high-dose statin and the reduction in in-hospital dialysis (adjusted OR, 0.11; P=0.030). Conclusions The in-hospital high-dose intensive statin is not associated with lower risks of in-hospital or follow-up all-cause death in NSTE-ACS patients undergoing PCI. Considering the robust beneficial effect of in-hospital dialysis, an individualized high-dose intensive statin can be rational in specified populations. Univariate and multivariate analyses Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Science and Technology Planning Project of Guangzhou City athe China Youth Research Funding


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Damien Montange ◽  
Siamak Davani ◽  
Ségolène Gambert ◽  
Marie-France Seronde ◽  
Francois Schiele ◽  
...  

Background: The presence of CD34+ and CD146+ cells in the peripheral blood in response to myocardial ischemia has been advocated as a marker of an organism’s regenerative capacity by late and early progenitor cells respectively. The aim of this study was to evaluate the relationship between circulating CD34+ and CD146+ levels and the change in infarct size, as assessed by magnetic resonance imaging (MRI) in patients (pts) with acute coronary syndrome (ACS including ST and non ST elevation myocardial infarction). Methods: Patients <75 years old, admitted with a first ACS within 12 hours of onset of symptoms were enrolled. Peripheral blood samples for cytofluorimetric analysis of CD34+ and CD146+ cells level were drawn at day 0. Initial infarct size was evaluated from peak troponin I levels determined from 5 blood samples over the first 72 hours. MRI measurements of infarct size were performed at day 5 and at 6 months follow-up. Results: In total, 34 patients aged 57±10 years were included. Mean ejection fraction was 62±11%. Log-transformed number of CD 34+ and CD146+ were significantly correlated with the relative change in infarct size between day 5 and 6 month follow-up (p=0.01, r=-0;41 and p=0.001, r=-0.52 respectively) (Figure) Conclusion: The highest CD34+ and CD146+ cell levels were associated with the greatest relative reduction in infarct size 6 months after ACS. These results support the hypothesis that these cells could be considered as a marker of regenerative capacity in patients with acute coronary syndromes.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Hyun ◽  
D Brieger ◽  
T Briffa ◽  
D Chew ◽  
M Horsfall ◽  
...  

Abstract Background Although socioeconomic status (SES) has been reported to be associated with health inequities, there are limited studies exploring the association between SES and secondary prevention of acute coronary syndrome (ACS) in countries with universal health cover. Purpose The aim is to examine whether SES has an impact on the secondary prevention of ACS in Australia. Methods Australian SNAPSHOT ACS data (2012) and its 18-month follow-up data were linked to admissions data from 6 jurisdictions covering all states and territories, national death index and Medicare Pharmaceutical Benefits Scheme data covering up to 3 years post-discharge. The five SES groups (lowest in Group 1 and highest in Group 5) were derived from the Australian Bureau of Statistics Socio-Economic Indexes for Areas (SEIFA) using the residential postcode at baseline. Outcomes were cardiac rehabilitation (CR) participation and smoking rate at 18 months post discharge as well as the use of ≥3 of the 4 indicated medications, all-cause death and cardiovascular disease (CVD) rates by 36 months of discharge. Outcomes were compared between the groups using the multilevel logistic regression with covariates of SES (5 groups), sex, GRACE risk score (4 groups), ACS diagnosis (STEMI/NSTEMI/UA) and the jurisdictions where the admissions data were linked. Results Of 1655 patients with ACS (mean age 68±13.5 yrs, 65% were male), who were discharged from hospital alive and had linked data available, 353 (21%) were in SES Group 1 (lowest SES), 369 (22%) in Group 2, 382 (23%) in Group 3, 296 (18%) in Group 4 and 255 (15%) in Group 5 (highest SES). Baseline clinical characteristics were comparable across the five SES groups. At 18-month after discharge, 1014 (61%) patients were followed-up with comparable loss to follow-up in each group. After adjustment, fewer patients in the lower SES groups (Groups 1 and 2) had participated in CR than those in the highest SES group (Group 5) (OR (95% CI): 0.60 (0.36, 0.99) and 0.56 (0.35, 0.91), respectively). Moreover, the odds of smoking was greater in Group 3 than Group 5 (2.60 (1.15, 5.89)) but no trend was found across the groups. By 36 months of discharge after adjustment, there was no difference in the odds of using ≥3 out of 4 medications between the SES groups. Despite this, patients in Groups 1 and 2 were significantly more likely to die than those in the highest SES group (1.96 (1.19, 3.21) and 1.91 (1.19, 3.07), respectively). The odds of CVD readmission did not differ across SES groups. Conclusion This study suggests that patients with low SES were less likely to participate in CR programs and more likely to die than those with high SES. Smoking rates varied between patients with intermediate and high SES but no trend was found across the groups. Despite the universal health cover available, inequity between the SES groups still exist. Future research is needed to further explore strategies to help close the evidence-practice gaps. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Australian National Heart Foundation Postdoctoral Fellowship


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