Monocyte Chemoattractant Protein-1 Is an Independent Predictor of Coronary Artery Ectasia in Patients with Acute Coronary Syndrome.

Our purpose was to assess a possible association of inflammatory, lipid and mineral metabolism biomarkers with coronary artery ectasia (CAE) and to determine a possible association of this with acute atherotrombotic events (AAT). We studied 270 patients who underwent coronary angiography during an acute coronary syndrome 6 months before. Plasma levels of several biomarkers were assessed, and patients were followed during a median of 5.35 (3.88-6.65) years. Two interventional cardiologists reviewed the coronary angiograms, diagnosing CAE according to previously published criteria in 23 patients (8.5%). Multivariate binary logistic regression analysis was used to search for independent predictors of CAE. Multivariate analysis revealed that, aside from gender and a diagnosis of dyslipidemia, only monocyte chemoattractant protein-1 (MCP-1) (OR = 2.25, 95%CI = (1.35-3.76) for each increase of 100 pg/mL, p = 0.001) was independent predictor of CAE, whereas mineral metabolism markers or proprotein convertase subtilisin/kexin type 9 were not. Moreover, CAE was a strong predictor of AAT during follow-up after adjustment for other clinically relevant variables (HR = 2.67, 95%CI = (1.22-5.82), p = 0.013). This is the first report showing that MCP-1 is an independent predictor of CAE, suggesting that CAE and coronary artery disease may share pathogenic mechanisms. Furthermore, CAE was associated with an increased incidence of AAT.

Optical coherence tomography: Translation from 3D-printed vascular models of the anterior cerebral circulation to the first human images of implanted surface modified flow diverters.

BACKGROUND: The new generation of flow diverters includes a surface modification with a synthetic biocompatible polymer, which makes the device more biocompatible and less thrombogenic. Optical coherence tomography (OCT) can be used to visualize perforators, stent wall apposition, and intra-stent thrombus. Unfortunately real world application of this technology has been limited because of the limited navigability of these devices in the intracranial vessels. In this report, we share our experience of using 3D-printed neurovascular anatomy models to simulate and test the navigability of a commercially available OCT system and to show the application of this device in a patient treated with the new generation of surface modified flow diverters. MATERIAL AND METHODS: Navigability of OCT catheters was tested in vitro using four different 3D-printed silicone replicas of the intracranial anterior circulation, after the implantation of surface modified devices. Intermediate catheters were used in different tortuous anatomies and positions. After this assessment, we describe the OCT image analysis of a Pipeline Shield for treating an unruptured posterior communicating artery (PCOM) aneurysm. RESULTS: Use of intermediate catheters in the 3D-printed replicas was associated with better navigation of the OCT catheters in favorable anatomies but did not help as much in unfavorable anatomies. OCT image analysis of a PCOM aneurysm treated with Pipeline Embolization Device Shield demonstrated areas of unsatisfactory apposition with no thrombus formation. CONCLUSIONS: OCT improves the understanding of the flow diversion technology. The development of less thrombogenic devices, like the Pipeline Flex with Shield Technology, reinforces the need for intraluminal imaging for neurovascular application.

Baseline Risk Stratification of Patients Older Than 75 Years With Infarction and Cardiogenic Shock Undergoing Primary Angioplasty.

BACKGROUND AND OBJECTIVES: Patients older than 75 years with ST-segment elevation myocardial infarction undergoing primary angioplasty in cardiogenic shock have high mortality. Identification of preprocedural predictors of short- and long-term mortality could be useful to guide decision-making and further interventions. METHODS: We analyzed a nationwide registry of primary angioplasty in the elderly (ESTROFA MI+75) comprising 3576 patients. The characteristics and outcomes of the subgroup of patients in cardiogenic shock were analyzed to identify associated factors and prognostic predictors in order to derive a baseline risk prediction score for 1-year mortality. The score was validated in an independent cohort. RESULTS: A total of 332 patients were included. Baseline independent predictors of mortality were anterior myocardial infarction (HR 2.8, 95%CI, 1.4-6.0 P=.005), ejection fraction<40% (HR 2.3, 95%CI, 1.14-4.50 P=.018), and time from symptom onset to angioplasty >6hours (HR 3.2, 95%CI, 1.6-7.5; P=.001). A score was designed that included these predictive factors (score "6-ANT-40"). Survival at 1 year was 54.5% for patients with score 0, 32.3% for score 1, 27.4% for score 2 and 17% for score 3 (P=.004, c-statistic 0.70). The score was validated in an independent cohort of 124 patients, showing 1-year survival rates of 64.5%, 40.0%, 28.9%, and 22.2%, respectively (P=.008, c-statistic 0.68). CONCLUSIONS: A preprocedural score based on 3 simple clinical variables (anterior location, ejection fraction<40%, and delay time >6 hours) may be used to estimate survival after primary angioplasty in elderly patients with cardiogenic shock and to guide preinterventional decision-making.

Multivessel disease in patients over 75years old with ST elevated myocardial infarction. Current management strategies and related clinical outcomes in the ESTROFA MI+75 nation-wide registry.

BACKGROUND: In elderly patients with ST elevated myocardial infarction (STEMI) and multivessel disease (MVD the outcomes related with different revascularization strategies are not well known. METHODS: Subgroup-analysis of a nation-wide registry of primary angioplasty in the elderly (ESTROFA MI+75) with 3576 patients over 75years old from 31 centers. Patients with MVD were analyzed to describe treatment approaches and 2years outcomes. RESULTS: Of 1830 (51%) with MVD, 847 (46%) underwent multivessel revascularization either in acute (51%), staged (44%) or both procedures (5%). Patients with previous myocardial infarction and those receiving drug-eluting stents or IIb-IIIa inhibitors were more prone to be revascularized, whereas older patients, females and those with Killip III-IV, renal failure and higher ejection fraction were less likely. Survival free of cardiac death and infarction at 2years was better for those undergoing multivessel PCI (85.8% vs. 80.4%, p<0.0008), regardless of Killip class. Multivessel PCI was protective of cardiac death and infarction (HR 0.60, 95% CI 0.40-0.89; p=0.011). Complete revascularization made no difference in outcomes among those patients undergoing multivessel PCI. The best prognosis corresponded to those undergoing multivessel PCI in staged procedures (p<0.001). A propensity score matching analysis (514 patients in each group) yielded similar results. CONCLUSIONS: In elderly patients with STEMI and MVD, multivessel PCI was related with better outcomes especially after staged procedures. Among those undergoing multivessel PCI, anatomically defined completeness of revascularization had not prognostic influence. SUMMARY: We sought to investigate the revascularization strategies applied and their prognostic implications in patients aged over 75years with ST elevated myocardial infarction showing multivessel disease. Of 1830 patients, 847 (46%) underwent multivessel PCI either in acute (51%), staged (44%) or both procedures (5%). Multivessel PCI was independent predictor of cardiac death and infarction with the best prognosis corresponding to those undergoing staged procedures.

Primary Angioplasty in Patients Older Than 75 Years. Profile of Patients and Procedures, Outcomes, and Predictors of Prognosis in the ESTROFA IM+75 Registry.

INTRODUCTION AND OBJECTIVES: The proportion of elderly patients undergoing primary angioplasty is growing. The present study describes the clinical profile, procedural characteristics, outcomes, and predictors of outcome. METHODS: A 31-center registry of consecutive patients older than 75 years treated with primary angioplasty. Clinical and procedural data were collected, and the patients underwent clinical follow-up. RESULTS: The study included 3576 patients (39.3% women, 48.5% with renal failure, 11.5% in Killip III or IV, and 29.8% with>6hours of chest pain). Multivessel disease was present in 55.4% and nonculprit lesions were additionally treated in 24.8%. Radial access was used in 56.4%, bivalirudin in 11.8%, thromboaspiration in 55.9%, and drug-eluting stents in 26.6%. The 1-month and 2-year incidences of cardiovascular death were 10.1% and 14.7%, respectively. The 2-year rates of definite or probable thrombosis, repeat revascularization, and BARC bleeding>2 were 3.1%, 2.3%, and 4.2%, respectively. Predictive factors were diabetes mellitus, renal failure, atrial fibrillation, delay to reperfusion>6hours, ejection fraction<45%, Killip class III-IV, radial access, bivalirudin, drug-eluting stents, final TIMI flow of III, and incomplete revascularization at discharge. CONCLUSIONS: Notable registry findings include frequently delayed presentation and a high prevalence of adverse factors such as renal failure and multivessel disease. Positive procedure-related predictors include shorter delay, use of radial access, bivalirudin, drug-eluting stents, and complete revascularization before discharge.

The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting FFR (MEMENTO-FFR) Study.

AIMS: Adenosine administration is needed for the achievement of maximal hyperaemia fractional flow reserve (FFR) assessment. The objective was to test the accuracy of Pd/Pa ratio registered during submaximal hyperaemia induced by non-ionic contrast medium (contrast FFR [cFFR]) in predicting FFR and comparing it to the performance of resting Pd/Pa in a collaborative registry of 926 patients enrolled in 10 hospitals from four European countries (Italy, Spain, France and Portugal). METHODS AND RESULTS: Resting Pd/Pa, cFFR and FFR were measured in 1,026 coronary stenoses functionally evaluated using commercially available pressure wires. cFFR was obtained after intracoronary injection of contrast medium, while FFR was measured after administration of adenosine. Resting Pd/Pa and cFFR were significantly higher than FFR (0.93±0.05 vs. 0.87±0.08 vs. 0.84±0.08, p<0.001). A strong correlation and a close agreement at Bland-Altman analysis between cFFR and FFR were observed (r=0.90, p<0.001 and 95% CI of disagreement: from -0.042 to 0.11). ROC curve analysis showed an excellent accuracy (89%) of the cFFR cut-off of ≤0.85 in predicting an FFR value ≤0.80 (AUC 0.95 [95% CI: 0.94-0.96]), significantly better than that observed using resting Pd/Pa (AUC: 0.90, 95% CI: 0.88-0.91; p<0.001). A cFFR/FFR hybrid approach showed a significantly lower number of lesions requiring adenosine than a resting Pd/Pa/FFR hybrid approach (22% vs. 44%, p<0.0001). CONCLUSIONS: cFFR is accurate in predicting the functional significance of coronary stenosis. This could allow limiting the use of adenosine to obtain FFR to a minority of stenoses with considerable savings of time and costs.

Plasma Levels of Monocyte Chemoattractant Protein-1, n-Terminal Fragment of Brain Natriuretic Peptide and Calcidiol Are Independently Associated with the Complexity of Coronary Artery Disease.

BACKGROUND AND OBJECTIVES: We investigated the relationship of the Syntax Score (SS) and coronary artery calcification (CAC), with plasma levels of biomarkers related to cardiovascular damage and mineral metabolism, as there is sparse information in this field. METHODS: We studied 270 patients with coronary disease that had an acute coronary syndrome (ACS) six months before. Calcidiol, fibroblast growth factor-23, parathormone, phosphate and monocyte chemoattractant protein-1 [MCP-1], high-sensitivity C-reactive protein, galectin-3, and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, among other biomarkers, were determined. CAC was assessed by coronary angiogram as low-grade (0-1) and high-grade (2-3) calcification, measured with a semiquantitative scale ranging from 0 (none) to 3 (severe). For the SS study patients were divided in SS<14 and SS≥14. Multivariate linear and logistic regression analyses were performed. RESULTS: MCP-1 predicted independently the SS (RC = 1.73 [95%CI = 0.08-3.39]; p = 0.040), along with NT-proBNP (RC = 0.17 [95%CI = 0.05-0.28]; p = 0.004), male sex (RC = 4.15 [95%CI = 1.47-6.83]; p = 0.003), age (RC = 0.13 [95%CI = 0.02-0.24]; p = 0.020), hypertension (RC = 3.64, [95%CI = 0.77-6.50]; p = 0.013), hyperlipidemia (RC = 2.78, [95%CI = 0.28-5.29]; p = 0.030), and statins (RC = 6.12 [95%CI = 1.28-10.96]; p = 0.013). Low calcidiol predicted high-grade calcification independently (OR = 0.57 [95% CI = 0.36-0.90]; p = 0.013) along with ST-elevation myocardial infarction (OR = 0.38 [95%CI = 0.19-0.78]; p = 0.006), diabetes (OR = 2.35 [95%CI = 1.11-4.98]; p = 0.028) and age (OR = 1.37 [95%CI = 1.18-1.59]; p<0.001). During follow-up (1.79 [0.94-2.86] years), 27 patients developed ACS, stroke, or transient ischemic attack. A combined score using SS and CAC predicted independently the development of the outcome. CONCLUSIONS: MCP-1 and NT-proBNP are independent predictors of SS, while low calcidiol plasma levels are associated with CAC. More studies are needed to confirm these data.

Secondary forms of Takotsubo cardiomyopathy: A whole different prognosis.

BACKGROUND: Takotsubo syndrome (TKS) usually mimics an acute coronary syndrome. However, several clinical forms have been reported. Our aim was to assess if different stressful triggers had prognostic influence on TKS, and to establish a working classification. METHODS: We performed an analysis including patients with TKS between 2003-2013 from our prospective local database and the RETAKO National Registry, fulfilling Mayo criteria. Patients were divided in two groups regarding their potential triggers: (a) none/psychic stress as 'primary forms' and (b) physical factors (asthma, surgery, trauma, etc.) as 'secondary forms'. RESULTS: Finally, 328 patients were included, 90.2% women, with a mean age of 69.7 years. Patients were divided into primary TKS (n=265) and 63 secondary TKS groups. Age, gender, previous functional class and cardiovascular risk profile displayed no differences between groups before admission. However, primary-TKS patients suffered a main complaint of chest pain (89.4% vs 50.7%, p<0.0001) with frequent vegetative symptoms. Regarding treatment before admission, there were no differences either. During admission, differences were related to more intensive antithrombotic and anxiolytic drug use in the primary TKS group. Inotropic and mechanical ventilation use was higher in the secondary cohort. After discharge, a more frequent prescription of beta-blockers and statins in primary-TKS patients was seen. Secondary forms displayed more in-hospital stay and evolutive complications: death (hazard ratio (HR): 3.41; 95% confidence interval (CI): 1.14-10.16, p=0.02), combined event variable (MACE) (HR: 1.61; 95% CI: 1.01-2.6, p=0.04) and recurrences (HR: 1.85; 95% CI: 1.06-3.22, p=0.02). CONCLUSION: Secondary TKS could present or mark worse short and long-term prognoses in terms of mortality, recurrences and readmissions. We propose a simple working nomenclature for TKS.

Comparison of the safety between first- and second-generation drug eluting stents: meta-analysis from 19 randomized trials and 16,924 patients.

BACKGROUND/OBJECTIVE: Despite the effectiveness of first generation drug eluting stent, DES-1 (Taxus and Cypher) in avoiding restenosis and the need for new revascularizations, a slightly increase in stent thrombosis, ST have been published. Second generation drug eluting stent, DES-2 has been developed to optimize the results of percutaneous coronary intervention in terms of efficacy and safety, for avoiding early and late ST. Our objective was to compare the risk of ST between DES-1 and DES-2. METHODS: We performed a meta-analysis of 19 randomized trials. Overall 16,924 patients; 7294 were allocated to DES-1 and 9630 were allocated to DES-2. The primary endpoint was to compare the risk of overall ST during the first year. Other clinical outcomes of interest were to compare the incidence of early (<1 month) and late ST (>1 month-<1 year). RESULTS: The incidence of overall ST was not increased in patients receiving DES-1 (1.13% DES-1 vs 0.75% DES-2, OR 0.79, 95% CI:0.45-1.40, p 0.43). There were no significant differences in the incidence of; early ST (0.85% DES-1 vs 0.53% DES-2, OR 0.68, 95% CI:0.31-1.51, p 0.35) and late ST (0.40% DES-1 vs 0.25% DES-2, OR 0.69, 95% CI:0.39-1.24, p 0.22). CONCLUSIONS: During the first year after stent implantation, we didn't found differences in ST between DES-1 and DES-2. Most of ST was produced under appropriate anti-platelet therapy so it is possible that many other factors such as; clopidogrel resistance, procedural complications or stent malapposition were implicated. Safety after longer follow-up (>1 year) remains unclear.

Primary percutaneous coronary intervention for ST-segment elevation acute myocardial infarction in nonagenarian patients: results from a Spanish multicentre registry.

AIMS: Data on primary percutaneous coronary intervention for ST-segment elevation in nonagenarian patients are very limited. Our aim was to evaluate the results of primary percutaneous coronary intervention in patients ≥ 90 years old with ST-segment elevation acute myocardial infarction. METHODS AND RESULTS: We conducted a multicentre registry focused on nonagenarians treated with percutaneous coronary interventions, gathering data from five tertiary centres in Spain. We included 38 patients with ST-segment elevation acute myocardial infarction who presented within 12 hours after symptoms onset and who were treated with primary percutaneous intervention. Mean age was 91.5 (90-98). Angiographic success was achieved in 90%, and TIMI 3 flow in 76% of cases. In-hospital mortality was 34.2%, concentrated in patients with major bleeding (100% vs. 31.4%), final TIMI flow grade <3 (71.4% vs. 22.7%), and Killip class > I at admission (53.3% vs. 21.7%). CONCLUSIONS: Primary percutaneous coronary intervention in nonagenarians with ST-segment elevation acute myocardial infarction is associated with high rate of successful recanalisation of the infarct-related artery. Mortality is concentrated in patients with severe bleeding during hospitalisation, heart failure at admission, and final TIMI flow <3.

Treatment of coronary atherosclerosis aneurysm with a combination of stent-graft and in-stent drug-eluting stent.

Coronary atherosclerotic aneurysms (CAA) are a very uncommon finding in patients presenting with coronary artery disease. In order to prevent spontaneous vessel rupture in patients presenting with large CAA, these patients are frequently treated with the implantation of a stent-graft. However, these devices have a high rate of restenosis, which limits the clinical success of this strategy at mid-term. We present a patient with a native CAA who was treated with the implantation of a stent-graft with in-stent ad- hoc implantation of a paclitaxel-eluting stent. Coronary angiography and intravascular ultrasound demonstrated absence of restenosis and persistence of the exclusion of the aneurysm at 1-year follow-up.

Subacute drug-eluting stent thrombosis caused by stent underexpansion: evaluation by optical coherence tomography.

We present the case report of a patient presenting with ST segment elevation myocardial infarction due to a subacute drug-eluting stent trombosis within the proximal segment of the left circumflex artery (LCX). Six days before a total chronic occlusion was treated at the mid segment of the LCX by overlapping two drug-eluting stents. Optical coherence tomography (OCT) was helpful to demonstrate stent underexpansion of the overlaping segment as the main mechanism of early stent thrombosis. This case is illustrative about the potential role of OCT to identify the mechanisms of ST and thus guiding the PCI procedure. Moreover, our case shows the capability of the Imagewire to cross a severe stenosis due to stent underexpansion that could not be crossed by the IVUS catheter.

Periprocedural (30-day) risk of myocardial infarction after drug-eluting coronary stent implantation: a meta-analysis comparing cobalt-chromium and stainless steel drug-eluting coronary stents.

AIMS: Because of the reduction in the rate events related with in-stent restenosis, most events after drug-eluting stent implantation occur shortly after coronary stenting. Cobalt-chromium alloys allow to reduce strut thickness and improve flexibility and deliverability of coronary stent platforms, and thus could be associated with lower short-term events after stenting. The aim of this study was to test the hypothesis that drug-eluting coronary stents with a cobalt-chromium platform reduce the incidence of periprocedural (30-day) myocardial infarction in comparison with stainless steel drug-eluting coronary stents. METHODS AND RESULTS: A meta-analysis from nine randomised trials comparing cobalt-chromium and stainless steel drug-eluting coronary stents that overall included 11,313 patients was performed. The incidence of myocardial infarction, stent thrombosis, and cardiac death at 30 days was compared between both types of stents. At 30 days, the incidence of acute myocardial infarction was significantly lower in patients allocated to cobalt-chromium drug-eluting stents (2.3% vs. 3.9%, respectively; p=0.006; odds ratio 0.72, 95% confidence interval 0.58-0.91), due to a significant reduction in the rate of non-Q-wave myocardial infarction (odds ratio 0.67, 95% confidence interval 0.51-0.88). The incidence of stent thrombosis was similar between both groups of patients, (0.5% vs. 0.5%, p=0.76; odds ratio 1.09, 95% confidence interval 0.63-1.89). CONCLUSIONS: Drug-eluting coronary stents that use cobalt-chromium stent platforms have a better safety profile at 30 days in comparison with stainless steel drug-eluting stents, due to a significant reduction in the rate of myocardial infarction.

Determining clinical benefits of drug-eluting coronary stents according to the population risk profile: a meta-regression from 31 randomized trials.

BACKGROUND: The use of drug-eluting stents (DES) in unfavourable patients has been associated with higher rates of clinical complications and stent thrombosis, and because of that concerns about the use of DES in high-risk settings have been raised. OBJECTIVE: This study sought to demonstrate that the clinical benefit of DES increases as the risk profile of the patients increases. METHODS: A meta-regression analysis from 31 randomized trials that compared DES and bare-metal stents, including overall 12,035 patients, was performed. The relationship between the clinical benefit of using DES (number of patients to treat [NNT] to prevent one episode of target lesion revascularization [TLR]), and the risk profile of the population (rate of TLR in patients allocated to bare-metal stents) in each trial was evaluated. RESULTS: The clinical benefit of DES increased as the risk profile of each study population increased: NNT for TLR=31.1-1.2 (TLR for bare-metal stents); p<0.001. The use of DES was safe regardless of the risk profile of each study population, since the effect of DES in mortality, myocardial infarction, and stent thrombosis, was not adversely affected by the risk profile of each study population (95% confidence interval for ß value 0.09 to 0.11, -0.12 to 0.19, and -0.03 to-0.15 for mortality, myocardial infarction, and stent thrombosis, respectively). CONCLUSIONS: The clinical benefit of DES increases as the risk profile of the patients increases, without affecting safety.

Intravascular ultrasound and histology findings in very late bare-metal stent thrombosis.

Very late thrombosis in an implanted bare-metal stent is a very uncommon event outside the context of brachytherapy and few data about its pathophysiology are available. We performed an intravascular ultrasound study during primary angioplasty in five patients with very late bare-metal stent thrombosis and carried out a histological analysis of the material removed by manual thrombectomy. The mean time from the index procedure was 7 ± 4 years. Intravascular ultrasound findings were: calcified atherosclerosis with in-stent plaque rupture, complex plaque in the distal segment of the stent, in-stent neointimal proliferation associated with underexpansion, and severe in-stent proliferation. Histological findings were consistent with the intravascular ultrasound images: recent thrombus with areas of old thrombosis in all cases and remnant atheromatous plaque and endothelium. Consequently, in-stent or distal stent atherosclerosis progression and progressive neointimal proliferation were the likely pathophysiological mechanisms.