Association between carotid and coronary atherosclerotic plaque morphology: a virtual histology intravascular ultrasound study.

Background and Aim: Atherosclerosis is considered to be a systemic disease; however, evidence exists on the heterogeneous nature of atherosclerotic disease. To date, continuous research seeks to determine the morphological differences between carotid and coronary artery disease. This study aimed to evaluate the relationship of morphological characteristics assessed by virtual histology intravascular ultrasound (VH-IVUS) between carotid and coronary plaque composition among patients with and without a history of cerebrovascular events. Methods: This study was a single-center prospective study (n = 100; age 69.6 ± 8.4). All patients were scheduled for carotid or coronary artery stenting and underwent VH-IVUS examination of the carotid and coronary arteries before intervention. Results: There was a modest, but statistically significant correlation between the carotid and coronary necrotic core ([NC] r = 0.46, P < 0.01), fibrofatty ([FF] r = 0.38, P < 0.01), dense calcium (r = 0.56, P < 0.01), and fibrous (r = 0.42, P < 0.01) plaque composition. The high amount of NC was detected in both arteries of the carotid artery stenting (CAS) group with higher proportion in the coronary artery (20.2% ± 9.4 % vs. 22.7% ± 6.8%, P = 0.02). More fibrolipid content was observed in carotid plaque compared to coronary (19.6% ± 9.9% vs. 12.2% ± 8.1%, P < 0.01). Patients with a history of cerebrovascular events had a numerically greater proportion of necrotic tissue in the carotid artery compared to asymptomatic and symptomatic CAS group patients (23.5% ± 10.7% vs. 18.9% ± 8.2% and 18.7% ± 9.5%, P = 0.11). Conclusion: The percentage of all analyzed plaque components was moderately correlated between coronary and carotid artery plaques. Nevertheless, the proportion of NC plaque tissue was greater in the coronary arteries, while the carotid arteries showed more %FF atherosclerotic lesions. CAS group patients with a history of cerebrovascular events had a tendency of greater proportion of necrotic tissue in analyzed carotid plaques compared to others in the CAS group. Relevance for Patients: In this study, we found that patients with a history of cerebrovascular event had a tendency of increased NC content in culprit lesion of carotid artery. Complementary use of non-invasive and invasive imaging modalities allows to detect high-risk atherosclerotic plaques and adjust treatment strategy.

Four-Year Outcomes of Left Main Percutaneous Coronary Intervention with a Bioresorbable Scaffold in the Circumflex Ostium.

Objectives: The study aimed to investigate the long-term outcomes of a double stent scaffold strategy in patients with left main (LM) bifurcation lesions involving the ostium of the left circumflex artery (LCX), utilizing a drug-eluting stent (DES) in the LM extending into the left anterior descending artery (LAD) and a bioresorbable vascular scaffold (BVS) in the LCX ostium. Background: The high occurrence of in-stent restenosis of the LCX ostium is the major limitation of percutaneous coronary intervention (PCI) for LM lesions with a two-stent strategy. Methods: This was a single-center, prospective, single-arm study of 46 consecutively enrolled patients with a stable coronary artery disease and significant unprotected LM distal bifurcation disease. Patients underwent imaging-guided PCI using DES in the LM-LAD and BVS in the LCX using a T-stent or mini-crush technique. The primary outcome at four years was the composite of death, myocardial infarction, stroke, and target lesion revascularization (TLR). Results: At four years, the primary outcome was identified in 9 patients (19.6%). All events were TLRs except one myocardial infarction due to BVS thrombosis. Seven of the eight TLRs were a result of side branch BVS restenosis. Univariate predictors of the 4-year outcome were higher LDL cholesterol and BVS size ≤2.5 mm. On multivariate analysis, LCX lesion preparation with a cutting balloon and post-procedure use of intravascular ultrasound for optimization were found to be independent protective factors of MACE. Conclusions: In selected patients with LM distal bifurcation disease, an imaging-guided double stent scaffold strategy with DES in the LM and BVS in the LCX ostium was technically successful in all patients and was reasonably safe and effective for four years.

What Is Hidden Behind Yellow Pixels: from Pathology to Intravascular Imaging of Atherosclerotic Plaque.

PURPOSE OF REVIEW: Intravascular imaging systems can identify lipid-rich and vulnerable plaques and help in treatment guidance. The comparability of different intracoronary imaging methods remains unclear. In this paper, we review atherosclerotic plaque pathology, plaque-stabilising effects of different lipid-lowering therapies and usage of intravascular imaging modalities. We present the results of our study in which we evaluated the correlation of the intravascular ultrasound iMAP system (iMAP-IVUS) and near-infrared spectroscopy (NIRS) in the diagnosis of vulnerable coronary plaques. RECENT FINDINGS: Lipids have an essential contribution to plaque evolution and vulnerability. Increase in plaque vulnerability alone even without increase in plaque burden defines progression of atherosclerosis. Lipidic tissue has a significant diagnostic value in patient risk stratification and can serve as a treatment target. Different vulnerable plaque parameters can be visualised with iMAP-IVUS and NIRS. Intravascular imaging systems can differ with regard to their sensitivity, specificity and limitations. Lipid-lowering therapy is crucial in plaque stabilisation.

Sex Differences in Outcomes After Percutaneous Coronary Intervention or Coronary Artery Bypass Graft for Left Main Disease: From the DELTA Registries.

Background Controversy exists over whether sex has significant interaction with revascularization strategy for unprotected left main coronary artery disease. Higher mortality has been reported among women treated with percutaneous coronary intervention compared with coronary artery bypass grafting. Methods and Results The DELTA (Drug-Eluting Stents for Left Main Coronary Artery Disease) and DELTA-2 registries are international, multicentric registries evaluating the outcomes of subjects undergoing coronary revascularization for unprotected left main coronary artery disease. The primary outcome was a composite of death, myocardial infarction, or cerebrovascular accidents. The population consisted of 6253 patients, including 1689 (27%) women. Women were older and more likely to have diabetes and chronic kidney disease than men (P<0.05). At a median follow-up of 29 months (interquartile range 12-49), a significant interaction between sex and revascularization strategy was observed for the primary end point (pint=0.012) and all-cause death (pint=0.037). Among women, compared with percutaneous coronary intervention, coronary artery bypass grafting was associated with lower risk of the primary end point (event rate 9.5% versus 15.3%; adjusted hazard ratio [AHR], 0.53; 95% CI, 0.35-0.79, P<0.001) and all-cause death (event rate 5.6% versus 11.7% AHR, 0.50; 95% CI, 0.30-0.82) and no significant differences were observed in men. Conclusions In women undergoing coronary revascularization for unprotected left main coronary artery disease, coronary artery bypass grafting was associated with lower risk of death, myocardial infarction, or cerebrovascular accidents whereas no significant differences between coronary artery bypass grafting and percutaneous coronary intervention were observed in men. Further dedicated studies are needed to determine the optimal revascularization strategy in women with unprotected left main coronary artery disease.

Plasma circulating microRNAs in patients with stable coronary artery disease - Impact of different cardiovascular risk profiles and glomerular filtration rates.

BACKGROUND AND AIM: Plasma circulating microRNA (miRNA)-126, -145, and -155 are associated with vascular remodeling, atherosclerotic lesion formation, and plaque vulnerability. In this study, we evaluated the levels of plasma circulating miRNAs in patients with stable coronary artery disease (CAD), different cardiovascular risk profiles, and different glomerular filtration rates (GFR). METHODS AND RESULTS: Forty patients with stable CAD admitted for elective percutaneous coronary intervention (PCI) were enrolled in a prospective study. Before PCI, fasting blood samples were obtained to evaluate clinical parameters and miRNA-126 and miRNA-155 expression. The GFR was calculated by the MDRD and CKD-EPI formulas, and the severity of CAD was calculated according to the SYNTAX score. All these parameters were correlated with miRNAs. The association between miRNA levels and clinical characteristics was evaluated. The expression of miRNA-126 positively correlated with a higher SYNTAX score (r = 0.337; p=0.034); however, no significant correlations between miR-126, GFR, and clinical characteristics were observed. Higher plasma levels of miRNA-155 correlated with increased levels of triglycerides (r = 0.317; P = 0.049), C-peptide (r = 0.452; P = 0.011), and the HOMA index (r = 0.447; P = 0.012) and a higher body mass index (BMI) (r = 0.385; P = 0.015). GFR and miRNA-155 (MDRD - Rho=0.353; P = 0.027. CKD-EPI - Rho=0.357; P = 0.026) were found to have a moderate correlation, although miRNA-155 had no correlation with the SYNTAX score. CONCLUSION: Plasma circulating miRNA-126 levels were increased in patients with severe atherosclerosis as determined by the SYNTAX score. Elevated miRNA-155 expression was observed in patients with Stage 1 GFR but was lower in patients with Stages 2 and 3 GFR. Plasma circulating miRNA-155 had positive correlations with higher levels of BMI, HOMA index, C-peptide, and triglycerides. RELEVANCE FOR PATIENTS: Although further investigations are needed to confirm the role of miRNA-155 and miRNA-126, they may serve as potential biomarkers detecting severity of CAD, lowering of kidney function and metabolic syndrome.

Circulating plasma microRNA-126, microRNA-145, and microRNA-155 and their association with atherosclerotic plaque characteristics.

AIMS: Circulating microRNAs (miRNAs) have been identified as biomarkers for several diseases. Dysregulation of miRNA-126, microRNA-145, and microRNA-155 has been shown to be associated with atherosclerotic lesion formation. The aim of this study was to evaluate the association between atherosclerosis-related miRNAs and unfavorable atherosclerotic plaque characteristics. METHODS AND RESULTS: Forty patients with stable coronary artery disease admitted for elective percutaneous coronary intervention (PCI) were enrolled in a prospective study. After PCI, intravascular ultrasound (IVUS), and iMAP-IVUS analysis were performed to assess the proportion of fibrotic, necrotic, lipidic, and calcific tissue within atherosclerotic plaques. Total RNA was isolated from plasma to evaluate the expression of circulating miRNA-126, miRNA-145, and miRNA-155. Plasma lipid and glucose metabolism-related variables were measured to determine any association with plaque characteristics or miRNA expression. Expression of miRNA-126 was negatively correlated with plaque fibrotic tissue (r=-0.28; P=0.044), while positively correlated with plaque necrotic tissue (r=0.31; P=0.029) and necrolipidic tissue (r=0.31; P=0.031). MiRNA-145 was positively correlated with plaque lipidic (r=0.32; P=0.023) and necrolipidic tissue (r=0.31; P=0.029). Patient age was associated with plaque fibrotic tissue (r=-0.41; P=0.005), necrotic tissue (r=0.33; P=0.022), and lipid content (r=0.33; P=0.022). High-density lipoprotein cholesterol was positively correlated with plaque necrotic (r=0.28; P=0.042) and calcific (r=0.28; P=0.044) tissue volume. Calcific tissue volume was positively correlated with C-peptide (r=0.34; P=0.033). After multivariate logistic regression analysis, both miRNA-126 and miRNA-145 expressions were associated with increased necrolipidic tissue content (ß=0.34; P=0.050; and ß=0.35; P=0.037, respectively). CONCLUSIONS: Expressions of miRNA-126 and miRNA-145 were associated with increased plaque necrolipidic tissue content. RELEVANCE FOR PATIENTS: Although further research is needed to support the study data, miRNA-126 and miRNA-145 may serve as potential plaque vulnerability biomarkers in the future.

New-generation drug-eluting stents for left main coronary artery disease according to the EXCEL trial enrollment criteria: Insights from the all-comers, international, multicenter DELTA-2 registry.

BACKGROUND: Percutaneous coronary intervention (PCI) has been established as an alternative treatment option to coronary artery by-pass graft (CABG) surgery in patients with left main coronary artery disease (LMCAD). Whether the findings of randomized controlled trials are applicable to a real-world patient population is unclear. METHODS: We compared the outcomes of PCI with new-generation DES in the all-comer, international, multicenter DELTA-2 registry retrospectively evaluating mid-term clinical outcomes with the historical CABG cohort enrolled in the DELTA-1 registry according to the EXCEL key inclusion or exclusion criteria. The primary endpoint was the composite of death, myocardial infarction, or stroke at the median time of follow-up time of 501 days. The consistency of the effect of DELTA-2 PCI versus DELTA-1 CABG according to the EXCEL enrollment criteria was tested using propensity score-adjusted Cox regression models. RESULTS: Out of 3986 patients enrolled in the DELTA-2 PCI registry, 2418 were EXCEL candidates and 1568 were not EXCEL candidates. The occurrence of the primary endpoint was higher among non-EXCEL candidates compared with EXCEL candidates (15.4% vs. 6.9%; hazard ratio 2.52; 95% confidence interval 2.00-3.16; p < 0.001). Among 901 patients enrolled in the historical DELTA-1 CABG cohort, 471 were EXCEL candidates and 430 were not EXCEL candidates. When comparing the DELTA-2 PCI with the DELTA-1 CABG cohort, the occurrence of the primary endpoint was lower in the PCI group compared with the historical CABG cohort among EXCEL candidates (6.9% vs. 10.7%; adjusted hazard ratio: 0.65; 95% confidence interval: 0.45-0.92), while no significant difference was observed among non-EXCEL candidates (15.4% vs. 12.5%; adjusted hazard ratio: 0.94; 95% confidence interval: 0.67-1.33) with evidence of statistical interaction (adjusted interaction p-value = 0.002). CONCLUSIONS: In a real-world population, PCI can be selected more favorably as an alternative to CABG in patients fulfilling the enrollment criteria of the EXCEL trial.

Treatment of Knee Osteoarthritis with Bone Marrow-Derived Mononuclear Cell Injection: 12-Month Follow-up.

OBJECTIVES: To evaluate the main symptoms of knee osteoarthritis (OA) and tissue structure changes after a single dose bone marrow-derived mononuclear cell (BM MNC) intra articular injection. Case series study. Patients with knee OA Kellgren Lawrence (K-L) grade II and III received 1 injection of BM MNC. The clinical results were analyzed with the Knee injury and Osteoarthritis Outcome Score (KOOS) and Knee Society Score (KSS) before, 3, 6, and 12 months after injection. Radiological evaluation was performed with a calibrated x-ray and the magnetic resonance (MR) imaging before and 6 to 7 months postinjection. RESULTS: A total of 34 knees were treated with BM MNC injections. Mean (±SD) age of patient group was 53.96 ± 14.15 years; there were 16 males, 16 females, KL grade II, 16; KL grade III, 18. The average injected count of BM MNCs was 45.56 ± 34.94 × 106 cells. At the endpoint of 12 months 65% of patients still had minimal perceptible clinical improvement of the KOOS total score. The mean improvement of KOOS total score was +15.3 and of the KSS knee score was +21.45 and the function subscale +27.08 ( P < 0.05) points. The Whole Organ Magnetic Resonance Imaging Score (WORMS) improved from 44.31 to 42.93 points ( P < 0.05). No adverse effects after the BM-MNC injection were observed. CONCLUSIONS: The single dose BM MNC partially reduces clinical signs of the knee osteoarthritis stage II/III and in some cases, decreases degenerative changes in the joint building tissue over 12-month period.

Two-year clinical outcomes after implantation of an everolimus-eluting bioresorbable scaffold (Absorb) in stable angina and acute coronary syndrome patients. Single-centre real-life registry data.

AIM: The aim of this long-term registry data was to evaluate 2-year clinical and angiographic outcomes after implantation of everolimus-eluting bioresorbable scaffolds (Absorb) from the Latvian Centre of Cardiology Real-life Registry. MATERIAL AND METHODS: Between November 2012 and December 2014 in the Centre of Cardiology Real-life Bioresorbable Vascular Scaffold Registry, 187 patients with stable angina or acute coronary syndrome and available 2-year follow-up were selected. All patients had percutaneous coronary intervention (PCI) following bioresorbable scaffold (Absorb) implantation. At 2 years, clinical parameters were analysed in stable angina and acute coronary syndrome subgroups: all-cause death, cardiac death, non-cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), scaffold thrombosis (ST), cerebral infarction, in-scaffold restenosis and bleeding. RESULTS: The clinical follow-up rate at 2 years was 96.2%. In-hospital death occurred in 2 (1.1%) patients, and 1 (0.5%) patient had in-hospital MI. At 2 years, the rate of all-cause death was 3.9% (n = 7), MI 1.6% (n = 3), TLR 3.9% (n = 7), and TVR 8.4% (n = 15). Between hospital discharge and 2-year follow-up scaffold thrombosis occurred in 2 (1.1%) patients. In-hospital scaffold thrombosis occurred in 1 (0.5%) patient due to clopidogrel resistance, and 1 additional case of scaffold thrombosis occurred at 5 days after implantation (0.5%). CONCLUSIONS: Bioresorbable scaffolds showed acceptable efficacy (target lesion revascularization) and safety (cardiac death, myocardial infarction, and scaffold thrombosis) results at mid-term follow-up in stable angina and acute coronary syndrome patients.

The DELTA 2 Registry: A Multicenter Registry Evaluating Percutaneous Coronary Intervention With New-Generation Drug-Eluting Stents in Patients With Obstructive Left Main Coronary Artery Disease.

OBJECTIVES: The aim of this study was to evaluate clinical outcomes of unprotected left main coronary artery percutaneous coronary intervention (PCI) with new-generation drug-eluting stents in a "real world" population. BACKGROUND: PCI of the unprotected left main coronary artery is currently recommended as an alternative to coronary artery bypass grafting (CABG) in selected patients. METHODS: All consecutive patients with unprotected left main coronary artery stenosis treated by PCI with second-generation drug-eluting stents were analyzed in this international, all-comers, multicenter registry. The results were compared with those from the historical DELTA 1 (Drug Eluting Stent for Left Main Coronary Artery) CABG cohort using propensity score stratification. The primary endpoint was the composite of death, myocardial infarction (MI), or stroke at the median time of follow-up. RESULTS: A total of 3,986 patients were included. The mean age was 69.6 ± 10.9 years, diabetes was present in 30.8%, and 21% of the patients presented with acute MI. The distal left main coronary artery was involved in 84.6% of the lesions. At a median of 501 days (≈17 months) of follow-up, the occurrence of the primary endpoint of death, MI, or cerebrovascular accident was lower in the PCI DELTA 2 group compared with the historical DELTA 1 CABG cohort (10.3% vs. 11.6%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.55 to 0.98; p = 0.03). Of note, an advantage of PCI was observed with respect to cerebrovascular accident (0.8% vs. 2.0%; adjusted hazard ratio: 0.37; 95% confidence interval: 0.16 to 0.86; p = 0.02), while an advantage of CABG was observed with respect to target vessel revascularization (14.2% vs. 2.9%; adjusted hazard ratio: 3.32; 95% confidence interval: 2.12 to 5.18; p < 0.0001). CONCLUSIONS: After a median follow-up period of 17 months, PCI with new-generation drug-eluting stents was associated with an overall low rate of the composite endpoint of death, MI, or cerebrovascular accident.

The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections.

OBJECTIVE: The aim of this study was to compare treatment methods of the knee joint degenerative osteoarthritis, using autologous bone marrow-derived mononuclear cells and hyaluronic acid injections and observe prevalence of adverse effects in both groups. MATERIALS AND METHODS: A prospective randomized controlled clinical trial was carried out. The analysis of pain and changes in osteoarthritis symptoms after a single intra-articular bone marrow-derived mononuclear cell injection into the knee joint in the Kellgren-Lawrence stage II-III osteoarthritis during the 12-month period were performed. The results were compared with the control group treated routinely by hyaluronic acid injections therapy. A therapy group of patients (n=28) received single bone marrow-derived mononuclear cell intra-articular injections. A control group of patients (n=28) was treated with a total of three sodium hyaluronate intra-articular injections each one performed a week apart. The clinical results were obtained using the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before and 3, 6, and 12 months after injection. RESULTS: A statistically significant improvement was observed in the mononuclear cell group over the starting point in all scores. At the endpoint at month 12, the KOOS score improved significantly (P<0.05) on the pain subscale (+25.44), activity and daily living subscale (+21.36), quality of life subscale (+28.83), and total KOOS (+18.25). The KSS score also demonstrated a significant improvement on the symptoms subscale (+25.42) and the function subscale (+38.32) (P<0.001). The KOOS symptoms and sports subscales improved without statistical significance. The difference between the control group treated with hyaluronic acid versus the bone marrow-derived mononuclear cells group at time points 6 and 12 months demonstrated a statistically significant (P<0.05) superiority in the KOOS pain subscale over the hyaluronic acid group. In both groups serious adverse effects were not observed. CONCLUSIONS: The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed.