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.

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.

Randomised comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch: the Nordic-Baltic Bifurcation Study IV.

Background: It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation. Methods: The study was a randomised, superiority trial. Enrolment required a SB≥2.75 mm, ≥50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates. Results: A total of 450 patients were assigned to simple stenting (n=221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p=0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p=0.10) after simple versus complex treatment. Conclusion: In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years. Trial registration number: NCT01496638.

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 SABRE Trial (Sirolimus Angioplasty Balloon for Coronary In-Stent Restenosis): Angiographic Results and 1-Year Clinical Outcomes.

OBJECTIVES: The aim of this first-in-human study was to assess the safety and effectiveness of the Virtue sirolimus-eluting balloon in a cohort of patients with in-stent restenosis (ISR). BACKGROUND: Angioplasty balloons coated with the cytotoxic drug paclitaxel have been widely used for ISR treatment. The Virtue angioplasty balloon (Caliber Therapeutics, New Hope, Pennsylvania) delivers sirolimus in a nanoencapsulated liquid formulation. This clinical trial is the first to examine a sirolimus-eluting balloon for ISR. METHODS: In this prospective, single-arm feasibility study at 9 European centers, 50 ISR patients were treated with the Virtue balloon. Angiographic measurements at 6 months are reported, along with 12-month clinical follow-up. RESULTS: Procedural success in the intention-to-treat population was 100%. The primary safety endpoint was target lesion failure (TLF) (cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization) assessed at 30 days (0%, n = 50). The primary performance endpoint was in-segment late lumen loss (LLL) at 6 months (0.31 ± 0.52 mm; n = 47). Secondary 6-month endpoints include binary restenosis (19.1%), diameter stenosis (30.3 ± 19.9%), and major adverse cardiac events (MACE) (10.2%, n = 49). In the 36-patient per-protocol population (excluding major protocol violations and previously stented ISR), LLL was 0.12 ± 0.33 mm at 6 months. Clinical outcomes at 1 year for the intention-to-treat group were 12.2% TLF and 14.3% MACE and for the per-protocol population were 2.8% TLF and 2.8% MACE. CONCLUSIONS: This first-in-human study showed excellent procedural success for the Virtue sirolimus-eluting angioplasty balloon, 6-month LLL rates in line with current stent-free ISR treatment options, and clinical outcomes that warrant further evaluation in dedicated randomized studies.

Clinical outcome after crush versus culotte stenting of coronary artery bifurcation lesions: the Nordic Stent Technique Study 36-month follow-up results.

OBJECTIVES: The aim of the study was to compare long-term follow-up results of crush versus culotte stent techniques in coronary bifurcation lesions. BACKGROUND: The randomized Nordic Stent Technique Study showed similar 6-month clinical and 8-month angiographic results with the crush and culotte stent techniques of de novo coronary artery bifurcation lesions using sirolimus-eluting stents. Here, we report the 36-month efficacy and safety of the Nordic Stent Technique Study. METHODS: A total of 424 patients with a bifurcation lesion were randomized to stenting of both main vessel and side branch with the crush or the culotte technique and followed for 36 months. Major adverse cardiac events-the composite of cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization-were the primary endpoint. RESULTS: Follow-up was complete for all patients. At 36 months, the rates of the primary endpoint were 20.6% versus 16.7% (p = 0.32), index lesion restenosis 11.5% versus 6.5% (p = 0.09), and definite stent thrombosis 1.4% versus 4.7% (p = 0.09) in the crush and the culotte groups, respectively. CONCLUSIONS: At 36-month follow-up, the clinical outcomes were similar for patients with coronary bifurcation lesions treated with the culotte or the crush stent technique. (Nordic Bifurcation Study. How to Use Drug Eluting Stents [DES] in Bifurcation Lesions? NCT00376571).

Side branch fractional flow reserve measurements after main vessel stenting: a Nordic-Baltic Bifurcation Study III substudy.

AIMS: The substudy was performed to evaluate the acute and eight-month follow-up effect of final kissing balloon dilatation (FKBD) on fractional flow reserve (FFR) in the side branch (SB) after main vessel (MV) stenting. METHODS AND RESULTS: We included 75 patients in the Nordic-Baltic Bifurcation Study III FFR substudy: 42 in the FKBD group and 33 in the no-FKBD group. Complete angiographic and FFR eight-month follow-up was obtained in 25 (60%) patients in the FKBD group and 21 (63%) patients in the no-FKBD group. In the FKBD group the post-PCI mean SB FFR was significantly higher compared to the no-FKBD group (0.92 vs. 0.85, respectively; p=0.011). No significant difference in FFR value between treatments was detected at eight-month follow-up (0.91 vs. 0.87; p=0.19). There were no significant changes in mean SB FFR during the follow-up period (0.92 vs. 0.91; p=0.80) in the FKBD group and (0.87 vs. 0.87; p=0.91) in the no-FKBD group. CONCLUSIONS: FKBD in simple stenting of bifurcation lesions improved acute functional outcome in SB compared to leaving the SB jailed. No significant difference was detected at follow-up. In both groups there was no significant functional late loss during follow-up. Thus, both strategies were equally effective in ensuring that side branch jailing would not cause ischaemia in the long term.

Are paclitaxel-eluting stents better in unprotected left main coronary artery disease? Three-year clinical and intravascular imaging results from a randomized study.

BACKGROUND AND OBJECTIVE: Recent publications have demonstrated superior outcomes in unprotected left main patients after paclitaxel-eluting stent (PES) implantation. Long-term data in these patients are limited. The aim of this study was to evaluate if intravascular ultrasound (IVUS)-guided PES implantation is superior to bare metal stent (BMS) implantation in unprotected left main disease after lesion pretreatment with cutting balloon during long-term follow-up. MATERIAL AND METHODS: Unprotected left main patients were randomized to BMS (n=50) or PES implantation (n=53). All interventions were IVUS-guided and cutting balloon pretreatment before stenting was performed in all patients. All patients were scheduled for 6-month and 3-year follow-up. Subgroups of patients who underwend IVUS and OCT imaging at 3-year follow-up were analyzed. The primary endpoint was the major adverse cardiac events (MACEs) defined as death, Q-wave myocardial infarction, or target lesion revascularization. RESULTS: Baseline characteristics were similar in both the groups with a mean SYNTAX score of 31.4±14.5 in BMS and 32.6±11.7 in PES patients (P=0.718). At 3 years, MACEs occurred in 18 patients (36.0%) in the BMS and 7 patients (13.2%) in the PES group (P=0.011). By IVUS, percent neointimal volume obstruction at 3 years was reduced from 18.1%±8.7% with BMSs to 10.0%±5.4% with PESs (P<0.001). The total number of uncovered stent struts per OCT image and IVUS image was 0.4±0.8 and 1.2±1.5, respectively (P<0.001). CONCLUSIONS: The current study demonstrated that IVUS-guided PES implantation was superior to BMS implantation after cutting balloon pretreatment in unprotected left main disease at 3 years. If compared with IVUS, OCT was more precise in the assessment of stent endothelization.

Randomized comparison of coronary bifurcation stenting with the crush versus the culotte technique using sirolimus eluting stents: the Nordic stent technique study.

BACKGROUND: In a number of coronary bifurcation lesions, both the main vessel and the side branch need stent coverage. Using sirolimus eluting stents, we compared 2 dedicated bifurcation stent techniques, the crush and the culotte techniques in a randomized trial with separate clinical and angiographic end-points. METHODS AND RESULTS: A total of 424 patients with a bifurcation lesion were randomized to crush (n=209) and culotte (n=215) stenting. The primary end point was major adverse cardiac events; cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis after 6 months. At 6 months there were no significant differences in major adverse cardiac event rates between the groups; crush 4.3%, culotte 3.7% (P=0.87). Procedure and fluoroscopy times and contrast volumes were similar in the 2 groups. The rates of procedure-related increase in biomarkers of myocardial injury were 15.5% in crush versus 8.8% in culotte group (P=0.08). A total of 324 patients had a quantitative coronary assessment at the index procedure and after 8 months. The angiographic end-points of in-segment and in-stent restenosis of main vessel and/or side branch after 8 months were found in 12.1% versus 6.6% (P=0.10) and in 10.5% versus 4.5% (P=0.046) in the crush and culotte groups, respectively. CONCLUSIONS: Both the crush and the culotte bifurcation stenting techniques were associated with similar and excellent clinical and angiographic results. Angiographically, there was a trend toward less in-segment restenosis and significantly reduced in-stent restenosis following culotte stenting.