Unanticipated Pseudocoarctation Highlights the Importance of Visualizing Aortic Arch Anatomy Before Transfemoral Transcatheter Aortic Valve Implantation

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Comparison of VerifyNow-P2Y12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy?

<p>Abstract</p> <p>Background</p> <p>Dual anti-platelet therapy with aspirin and a thienopyridine (DAT) is used to prevent stent thrombosis after percutaneous coronary intervention (PCI). Low response to clopidogrel therapy (LR) occurs, but laboratory tests have a controversial role in the identification of this condition.</p> <p>Methods</p> <p>We studied LR in patients with stable angina undergoing elective PCI, all on DAT for at least 7 days, by comparing: 1) Flow cytometry (FC) to measure platelet membrane expression of P-selectin (CD62P) and PAC-1 binding following double stimulation with ADP and collagen type I either in the presence of prostaglandin (PG) E₁; 2) VerifyNow-P2Y₁₂test, in which results are reported as absolute P2Y₁₂-Reaction-Units (PRU) or % of inhibition (% inhibition).</p> <p>Results</p> <p>Thirty controls and 52 patients were analyzed. The median percentage of platelets exhibiting CD62P expression and PAC-1 binding by FC evaluation after stimulation in the presence of PG E₁was 25.4% (IQR: 21.4–33.1%) and 3.5% (1.7–9.4%), respectively. Only 6 patients receiving DAT (11.5%) had both values above the 1^stquartile of controls, and were defined as LR. Evaluation of the same patients with the VerifyNow-P2Y₁₂test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84–0.98, p < 0.0001) for % inhibition and 0.85 (0.72–0.93, p < 0.005) for PRU. Cut-off values of ≤ 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC.</p> <p>Conclusion</p> <p>In conclusion our findings show that a cut-off value of ≤ 15% inhibition or > 213 PRU in the VerifyNow-P2Y₁₂test may provide the best accuracy for the identification of patients with LR.</p

Impact of structural features of very thin stents implanted in unprotected left main or coronary bifurcations on clinical outcomes

Objectives: To evaluate the independent clinical impact of stent structural features in a large cohort of patients undergoing unprotected left main (ULM) or coronary bifurcation percutaneous coronary intervention (PCI) with a range of very thin strut stents. Background: Clinical impact of structural features of contemporary stents remains to be defined. Methods: All consecutive patients enrolled in the veRy thin stents for patients with left mAIn or bifurcatioN in real life (RAIN) registry were included. The following stent structural features were studied: antiproliferative drugs (everolimus vs. sirolimus vs. zotarolimus), strut material (platinum-chromium vs. cobalt-chromium), polymer (bioresorbable vs. durable), number of crowns (<8 vs. ≥8) and number of connectors (<3 vs. ≥3). For small diameter stents (≤2.5 mm), struct thickness (74 vs. 80/81 μm) was also tested. Target lesion failure (TLF), a composite of target lesion revascularization and stent thrombosis, was the primary endpoint. Multivariate analysis was performed with Cox regression models. Results: Out of 2,707 patients, 110 (4.1%) experienced a TLF event after 16 months (12–18). After adjustment for confounders, an increased number of connectors (adjusted hazard ratio [adj-HR] 0.62, 95% confidence interval (CI) 0.39–0.99, p =.04) reduced risk of TLF, driven by stents with ≥2.5 mm diameter (HR 0.54, 95% CI 0.32–0.93, p =.02). This independent relationship was lost for stents with diameter <2.5 mm, where only strut thickness appeared to impact. Conversely, no independent relationship of polymer type, number of crowns, and the specific limus-family eluted drug with outcomes was observed. Conclusions: Among a range of contemporary very thin stent models, an increased number of connectors improved device-related outcomes in this investigated high-risk procedural setting

Daily risk of adverse outcomes in patients undergoing complex lesions revascularization: a subgroup analysis from the RAIN-CARDIOGROUP VII study (veRy thin stents for patients with left mAIn or bifurcatioN in real life)

Introduction: Percutaneous coronary intervention (PCI) for complex lesions, including unprotected left main (ULM) and bifurcations, is gaining a relevant role in treating coronary artery disease with good outcomes, also thanks to new generation stents. The daily risk of adverse cardiovascular events and their temporal distribution after these procedures is not known.Methods: All consecutive patients presenting with a critical lesion of ULM or bifurcation treated with very thin struts stents, enrolled in the RAIN-Cardiogroup VII study, were analyzed. The daily risk of major acute cardiovascular events (MACE), target lesion revascularization (TLR) and stent thrombosis (ST) and their temporal distribution in the first year of follow-up was the primary endpoint. Differences among subgroups (ULM, patient presentation, kind of stent polymer) were the secondary endpoint.Results: 2745 patients were included, mean age 68 ± 11 years, 33.3% diabetics, 54.5% had an acute coronary syndrome (ACS); 88.5% of treated lesions were bifurcations, 27.2% ULM. Average daily risk was 0.022% for MACE, 0.005% for TLR and 0.004% for ST, in the first year. Bimodal distribution of adverse events, especially TLR, with an early peak in the first 50 days and a late one after 150 days, was observed. Patients with ULM presented a significantly higher daily risk of events, and ACS patients presented higher MACE risk. No difference emerged according to the type of stent polymer.Conclusions: The daily risk of adverse events in the first year after complex PCI in our study is acceptably low. PCI on ULM carries a higher risk of complications

Incidence of adverse events at 3 months versus at 12 months after dual antiplatelet therapy cessation in patients treated with thin stents with unprotected left main or coronary bifurcations

Incidence and predictors of adverse events after dual antiplatelet therapy (DAPT) cessation in patients treated with thin stents (<100 microns) in unprotected left main (ULM) or coronary bifurcation remain undefined. All consecutive patients presenting with a critical lesion of an ULM or involving a main coronary bifurcation who were treated with very thin strut stents were included. MACE (a composite end point of cardiovascular death, myocardial infarction [MI], target lesion revascularization [TLR], and stent thrombosis [ST]) was the primary endpoint, whereas target vessel revascularization (TVR) was the secondary endpoint, with particular attention to type and occurrence of ST and occurrence of ST, CV death, and MI during DAPT or after DAPT discontinuation. All analyses were performed according to length of DAPT dividing the patients in 3 groups: Short DAPT (3-months), intermediate DAPT (3 to 12 months), and long DAPT (12-months). A total of 117 patients were discharged with an indication for DAPT ≤3 months (median 1: 1 to 2.5), 200 for DAPT between 3 and 12 months (median 8: 7 to 10), and 1,958 with 12 months DAPT. After 12.8 months (8 to 20), MACE was significantly higher in the 3-month group compared with 3 to 12 and 12-month groups (9.4% vs 4.0% vs 7.2%, p ≤0.001), mainly driven by MI (4.4% vs 1.5% vs 3%, p ≤0.001) and overall ST (4.3% vs 1.5% vs 1.8%, p ≤0.001). Independent predictors of MACE were low GFR and a 2 stent strategy. Independent predictors of ST were DAPT duration <3 months and the use of a 2-stent strategy. In conclusion, even stents with very thin strut when implanted in real-life ULM or coronary bifurcation patients discharged with short DAPT have a relevant risk of ST, which remains high although not significant after DAPT cessation

An Intense and Short-Lasting Burst of Neutrophil Activation Differentiates Early Acute Myocardial Infarction from Systemic Inflammatory Syndromes

BACKGROUND: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases. METHODS AND FINDINGS: The myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. CONCLUSIONS: ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin interactions. This paroxysmal activation could contribute to occlusive thrombosis