Cell Surface Platelet Tissue Factor Expression: Regulation by P2Y12 and Link to Residual Platelet Reactivity.

BACKGROUND: ADP-induced platelet activation leads to cell surface expression of several proteins, including TF (tissue factor). The role of ADP receptors in platelet TF modulation is still unknown. We aimed to assess the (1) involvement of P2Y1 and P2Y12 receptors in ADP-induced TF exposure; (2) modulation of TFpos-platelets in anti-P2Y12-treated patients with coronary artery disease. Based on the obtained results, we revisited the intracellular localization of TF in platelets. METHODS: The effects of P2Y1 or P2Y12 antagonists on ADP-induced TF expression and activity were analyzed in vitro by flow cytometry and thrombin generation assay in blood from healthy subjects, P2Y12-/-, and patients with gray platelet syndrome. Ex vivo, P2Y12 inhibition of TF expression by clopidogrel/prasugrel/ticagrelor, assessed by VASP (vasodilator-stimulated phosphoprotein) platelet reactivity index, was investigated in coronary artery disease (n=238). Inhibition of open canalicular system externalization and electron microscopy (TEM) were used for TF localization. RESULTS: In blood from healthy subjects, stimulated in vitro by ADP, the percentage of TFpos-platelets (17.3±5.5%) was significantly reduced in a concentration-dependent manner by P2Y12 inhibition only (-81.7±9.5% with 100 nM AR-C69931MX). In coronary artery disease, inhibition of P2Y12 is paralleled by reduction of ADP-induced platelet TF expression (VASP platelet reactivity index: 17.9±11%, 20.9±11.3%, 40.3±13%; TFpos-platelets: 10.5±4.8%, 9.8±5.9%, 13.6±6.3%, in prasugrel/ticagrelor/clopidogrel-treated patients, respectively). Despite this, 15% of clopidogrel good responders had a level of TFpos-platelets similar to the poor-responder group. Indeed, a stronger P2Y12 inhibition (130-fold) is required to inhibit TF than VASP. Thus, a VASP platelet reactivity index <20% (as in prasugrel/ticagrelor-treated patients) identifies patients with TFpos-platelets <20% (92% sensitivity). Finally, colchicine impaired in vitro ADP-induced TF expression but not α-granule release, suggesting that TF is open canalicular system stored as confirmed by TEM and platelet analysis of patients with gray platelet syndrome. CONCLUSIONS: Data show that TF expression is regulated by P2Y12 and not P2Y1; P2Y12 antagonists downregulate the percentage of TFpos-platelets. In clopidogrel good-responder patients, assessment of TFpos-platelets highlights those with residual platelet reactivity. TF is stored in open canalicular system, and its membrane exposure upon activation is prevented by colchicine.

Migraine and cardiovascular disease: what cardiologists should know.

Migraine is a chronic neurovascular disease with a complex, not fully understood pathophysiology with multiple causes. People with migraine suffer from recurrent moderate to severe headache attacks varying from 4 to 72 h. The prevalence of migraine is two to three times higher in women compared with men. Importantly, it is the most disabling disease in women <50 years of age due to a high number of years lived with disability, resulting in a very high global socioeconomic burden. Robust evidence exists on the association between migraine with aura and increased incidence of cardiovascular disease (CVD), in particular ischaemic stroke. People with migraine with aura have an increased risk of atrial fibrillation, myocardial infarction, and cardiovascular death compared with those without migraine. Ongoing studies investigate the relation between migraine and angina with non-obstructive coronary arteries and migraine patients with patent foramen ovale. Medication for the treatment of migraine can be preventative medication, such as beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, antiepileptics, antidepressants, some of the long-acting calcitonin gene-related peptide receptor antagonists, or monoclonal antibodies against calcitonin gene-related peptide or its receptor, or acute medication, such as triptans and calcitonin gene-related peptide receptor antagonists. However, these medications might raise concerns when migraine patients also have CVD due to possible (coronary) side effects. Specifically, knowledge gaps remain for the contraindication to newer treatments for migraine. All cardiologists will encounter patients with CVD and migraine. This state-of-the-art review will outline the basic pathophysiology of migraine and the associations between migraine and CVD, discuss current therapies, and propose future directions for research.

Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52 816 Patients From 12 Randomized Trials.

BACKGROUND: New randomized, controlled trials have become available on oral P2Y12 inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials. METHODS: We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome. RESULTS: In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72-0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75-0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80-1.01] and HR, 0.92 [95% CI, 0.84-1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94-1.29] and 1.12 [95% CI, 0.98-1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67-0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78-1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%-50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01-1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04-1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored. CONCLUSIONS: Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019155648.

Clinical profile and prognosis in patients on oral anticoagulation before admission for COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) shows high morbidity and mortality, particularly in patients with concomitant cardiovascular diseases. Some of these patients are under oral anticoagulation (OAC) at admission, but to date, there are no data on the clinical profile, prognosis and risk factors of such patients during hospitalization for COVID-19. DESIGN: Subanalysis of the international 'real-world' HOPE COVID-19 registry. All patients with prior OAC at hospital admission for COVID-19 were suitable for the study. All-cause mortality was the primary endpoint. RESULTS: From 1002 patients included, 110 (60.9% male, median age of 81.5 [IQR 75-87] years, median Short-Form Charlson Comorbidity Index [CCI] of 1 [IQR 1-3]) were on OAC at admission, mainly for atrial fibrillation and venous thromboembolism. After propensity score matching, 67.9% of these patients died during hospitalization, which translated into a significantly higher mortality risk compared to patients without prior OAC (HR 1.53, 95% CI 1.08-2.16). After multivariate Cox regression analysis, respiratory insufficiency during hospitalization (HR 6.02, 95% CI 2.18-16.62), systemic inflammatory response syndrome (SIRS) during hospitalization (HR 2.29, 95% CI 1.34-3.91) and the Short-Form CCI (HR 1.24, 95% CI 1.03-1.49) were the main risk factors for mortality in patients on prior OAC. CONCLUSIONS: Compared to patients without prior OAC, COVID-19 patients on OAC therapy at hospital admission showed lower survival and higher mortality risk. In these patients on OAC therapy, the prevalence of several comorbidities is high. Respiratory insufficiency and SIRS during hospitalization, as well as higher comorbidity, pointed out those anticoagulated patients with increased mortality risk.

COVID-19 and the impact of arterial hypertension-An analysis of the international HOPE COVID-19 Registry (Italy-Spain-Germany).

BACKGROUND: A systematic analysis of concomitant arterial hypertension in COVID-19 patients and the impact of angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID-19 in presence and absence of arterial hypertension. MATERIALS AND METHODS: Out of 5837 COVID-19 patients, 2850 (48.8%) patients had the diagnosis arterial hypertension. 1978/2813 (70.3%) patients were already treated with ACEI or ARBs. The clinical outcome of the present subanalysis included all-cause mortality over 40 days of follow-up. RESULTS: Patients with arterial hypertension suffered significantly more from different complications including respiratory insufficiency (60.8% vs 39.5%), heart failure (9.9% vs 3.1%), acute kidney injury (25.3% vs 7.3%), pneumonia (90.6% vs 86%), sepsis (14.7% vs 7.5%), and bleeding events (3.6% vs 1.6%). The mortality rate was 29.6% in patients with concomitant arterial hypertension and 11.3% without arterial hypertension (P < .001). Invasive and non-invasive respiratory supports were significantly more required in presence of arterial hypertension as compared without it. In the multivariate cox regression analysis, while age≥65, benzodiazepine, antidepressant at admission, elevated LDH or creatinine, respiratory insufficiency and sepsis might be a positive independent predictors of mortality, antiviral drugs, interferon treatment, ACEI or ARBs at discharge or oral anticoagulation at discharge might be an independent negative predictor of the mortality. CONCLUSIONS: The mortality rate and in-hospital complications might be increased in COVID-19 patients with a concomitant history of arterial hypertension. The history of ACEI or ARBs treatments does not seem to impact the outcome of these patients.

Follow-up strategies and individual risk profile after percutaneous coronary intervention: The prospective post percutaneous coronary intervention registry.

BACKGROUND: A multidisciplinary consensus document (MCD) provided a follow-up strategy after percutaneous coronary intervention (PCI) based on individual risk profiles: A, high; B, intermediate; and C, low. AIM: To assess patterns of follow-up after PCI and to evaluate the potential reduction of cardiologic examinations with the application of the MCD. METHODS: The post-PCI registry was carried out at 31 Italian Hospitals and included consecutive patients undergoing PCI. We collected cardiologic consults (CC), noninvasive stress tests (ST), and echocardiograms (EC) actually performed at 12 months and we compared them with the expected by the MCD. RESULTS: We included 1,113 patients (58% with acute coronary syndrome) that underwent 1,567 CC, 398 ST, and 612 EC. The performed CC and ST were significantly lower compared to the expected, respectively [1.6 (95% CI, 1.5-1.7) vs. 1.9 (95% CI, 1.8-2.0), and 0.40 (95% CI, 0.4-0.5) vs. 0.61 (95% CI, 0.6-0.7), p < .001]; the performed EC were significantly higher [0.6 (95% CI, 0.6-0.7) vs. 0.3 (95% CI, 0.3-0.37), p < .001]. Patients at moderate low risk had an excess of noninvasive tests whereas patients at higher risk received less examinations than the expected. The individual risk profile was an independent predictor of increased number of cardiac examination in patients at intermediate and low risk [profile B, OR 2.56 (95%CI 1.38-4.75); profile C, OR 27.00 (95%CI 8.13-89.62), p < .001]. CONCLUSION: In real world patients undergoing PCI, the intensity of follow-up at 12 months appeared not based on individual risk profile, with a higher numbers of examinations, particularly EC, performed in low risk subjects.

Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations.

BACKGROUND: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed. METHODS: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents. RESULTS: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI. CONCLUSIONS: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

Prevalence, predictors, and outcomes of patient prosthesis mismatch in women undergoing TAVI for severe aortic stenosis: Insights from the WIN-TAVI registry.

OBJECTIVE: To evaluate the incidence, predictors and outcomes of female patients with patient-prosthesis mismatch (PPM) following transcatheter aortic valve intervention (TAVI) for severe aortic stenosis (AS). BACKGROUND: Female AS TAVI recipients have a significantly lower mortality than surgical aortic valve replacement (SAVR) recipients, which could be attributed to the potentially lower PPM rates. TAVI has been associated with lower rates of PPM compared to SAVR. PPM in females post TAVI has not been investigated to date. METHODS: The WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) registry is a multicenter registry of women undergoing TAVR for severe symptomatic AS. Two hundred and fifty patients with detailed periprocedural and follow-up echocardiographic investigations were included in the WIN-TAVI echocardiographic sub-study. PPM was defined as per European guidelines stratified by the presence of obesity. RESULTS: The incidence of PPM in our population was 32.8%. Patients with PPM had significantly higher BMI (27.4 ± 6.1 vs. 25.2 ± 5.0, p = .002), smaller sized valves implanted (percentage of TAVI ≤23 mm 61% vs. 29.2%, PPM vs. no PPM, p < .001) and were more often treated with balloon expandable valves (48.3 vs. 32.5%, p < .001) rather than self expanding ones (26.3 vs. 52.8%, <.001). BMI (OR = 1.08; 95%CI 1.02-1.14, p = .011) and valve size ≤23 mm (OR = 3.00 95%CI 1.14-7.94, p = .027) were the only independent predictors of PPM. There was no significant interaction between valve size and valve type (p = .203). No significant differences were observed in 1-year mortality or major adverse cardiovascular events. CONCLUSIONS: PPM in females undergoing TAVI occurs in one third of patients. BMI and valve size ≤23 mm are independent predictors. Larger registries are required to determine the impact of PPM on future clinical outcomes.

Incidence, predictors and clinical impact of permanent pacemaker insertion in women following transcatheter aortic valve implantation: Insights from a prospective multinational registry.

OBJECTIVES: To describe the incidence, predictors, and clinical impact of permanent pacemaker insertion (PPI) following transcatheter aortic valve replacement (TAVR) in women. BACKGROUND: Data on pacemaker insertion complicating TAVR in women are scarce. METHODS: The Women's International Transcatheter Aortic Valve implantation (WIN-TAVI) is a prospective registry evaluating the safety and efficacy of TAVR in women. We included patients without preprocedural pacemakers and divided them into two groups: (1) PPI and (2) no-PPI. We identified PPI predictors using logistic regression and studied its clinical impact on the Valve Academic Research Consortium (VARC)-2 efficacy and safety endpoints. RESULTS: Out of 1019 patients, 922 were included in the analysis. Post-TAVR PPI occurred in 132 (14.3%) patients. Clinical and procedural characteristics were similar in both groups. Pre-existing right bundle branch block (RBBB) was associated with a high risk of post-TAVR PPI (OR 3.62, 95% CI 1.85-7.06, p < 0.001), while implantation of balloon-expandable prosthesis was associated with a lower risk (OR 0.47, 95% CI 0.30-0.74, p < 0.001). Post-TAVR PPI prolonged in-hospital stay by a median of 2 days (11 [9-16] days in PPI vs. 9 [7-14] days in no-PPI, p = 0.005), yet risks of VARC-2 efficacy and safety endpoints at 1 year were similar in both groups (adj HR 0.95, 95% CI 0.60-1.52, p = 0.84 and adj HR 1.22, 95% CI 0.83-1.79, p = 0.31, respectively). CONCLUSION: Pacemaker implantation following TAVR is frequent among women and is associated with pre-existing RBBB and valve type. PPI prolongs hospital stay, albeit without any significant impact on 1-year outcomes.

Preprocedural anemia in females undergoing transcatheter aortic valve implantation: Insights from the WIN-TAVI registry.

OBJECTIVES: To assess the impact of anemia on clinical outcomes in female patients enrolled in the Women's InterNational transcatheter aortic valve implantation (WIN-TAVI) registry. BACKGROUND: Anemia is highly prevalent among females who constitute half of TAVI candidates, yet, its clinical significance remains poorly investigated. METHODS: Patients were divided into three groups according to preprocedural hemoglobin (Hb) level: (1) no anemia (Hb ≥12 g/dl), (2) mild-to-moderate anemia (10 ≤ Hb <12 g/dl), and (3) severe anemia (Hb <10 g/dl). The primary outcome was the occurrence of Valve Academic Research Consortium (VARC)-2 efficacy endpoint, a composite of mortality, stroke, myocardial infarction (MI), hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up. RESULTS: Hemoglobin level was available in 877 (86.1%) patients: 412 (47.0%) had no anemia, 363 (41.4%) had mild-to-moderate anemia, and 102 (11.6%) had severe anemia. The latter group had a higher prevalence of cardiovascular risk factors. Compared with patients without anemia, severe anemia was associated with a greater risk of VARC-2 efficacy endpoint (adj HR 1.71, 95% CI: 1.02-2.87, p = .04), all-cause death (adj HR 2.36, 95% CI: 1.31-4.26, p = .004) and a composite of death, MI or stroke (adj HR 1.88, 95% CI: 1.10-3.22, p = .02) at 1 year. Moreover, an increased risk of late mortality (adj HR 1.15, 95% CI: 1.02-1.30, p = .03) was observed with every 1 g/dl decrease in hemoglobin level. CONCLUSION: Severe anemia in females undergoing TAVI was independently associated with increased rates of VARC-2 efficacy endpoint and mortality at 1 year.

Plasma Exosome Profile in ST-Elevation Myocardial Infarction Patients with and without Out-of-Hospital Cardiac Arrest.

The identification of new biomarkers allowing an early and more accurate characterization of patients with ST-segment elevation myocardial infarction (STEMI) is still needed, and exosomes represent an attractive diagnostic tool in this context. However, the characterization of their protein cargo in relation to cardiovascular clinical manifestation is still lacking. To this end, 35 STEMI patients (17 experiencing resuscitated out-of-hospital cardiac arrest (OHCA-STEMI) and 18 uncomplicated) and 32 patients with chronic coronary syndrome (CCS) were enrolled. Plasma exosomes were characterized by the nanoparticle tracking analysis and Western blotting. Exosomes from STEMI patients displayed a higher concentration and size and a greater expression of platelet (GPIIb) and vascular endothelial (VE-cadherin) markers, but a similar amount of cardiac troponin compared to CCS. In addition, a difference in exosome expression of acute-phase proteins (ceruloplasmin, transthyretin and fibronectin) between STEMI and CCS patients was found. GPIIb and brain-associated marker PLP1 accurately discriminated between OHCA and uncomplicated STEMI. In conclusion, the exosome profile of STEMI patients has peculiar features that differentiate it from that of CCS patients, reflecting the pathophysiological mechanisms involved in STEMI. Additionally, the exosome expression of brain- and platelet-specific markers might allow the identification of patients experiencing ischemic brain injury in STEMI.

The impact of chronic kidney disease in women undergoing transcatheter aortic valve replacement: Analysis from the Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) registry.

BACKGROUND: The prevalence of both chronic kidney disease (CKD) and aortic stenosis (AS) increase with age. Although baseline CKD is frequent in patients undergoing transcatheter aortic valve replacement (TAVR), its significance among women is largely unknown. METHODS: Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) is a multinational, prospective registry of women undergoing TAVR for severe AS. We included patients with available baseline estimated glomerular filtration rate (eGFR) and completed 1-year follow-up. Patients were categorized into three groups based on their eGFR: No CKD (normal kidney function to stage 2 CKD: eGFR ≥60 ml/min/1.73 m2 ); (b) mild CKD (stage 3a CKD: eGFR = 45-59 ml/min/1.73 m2 ); and (c) moderate/severe CKD (stage ≥3b CKD: eGFR <45 ml/min/1.73 m2 ). All events were adjudicated according to the Valve Academic Research Consortium (VARC)-2 criteria. RESULT: Out of 852 women undergoing TAVR, 326 (38.3%) had no CKD, 225 (26.4%) had mild CKD, and 301 (35.3%) had moderate/severe CKD. Women with higher stage of CKD at baseline were more likely to have a history of hypertension, diabetes, atrial fibrillation, anemia, chronic lung disease, hemodialysis, prior percutaneous coronary intervention, and pacemaker implantation. After multivariate adjustment, moderate/severe CKD was associated with a greater risk of 1-year VARC-2 safety endpoints [hazard ratio (HR) 1.68, 95% confidence interval (CI): 1.10-2.60], all-cause death (HR 2.00, 95% CI: 1.03-3.90), and composite of death, myocardial infarction, stroke or life-threatening bleeding (HR 1.70, 95% CI: 1.04-2.76). There were no differences in 30-day and 1-year VARC-2 efficacy and 30-day VARC-2 safety outcomes. CONCLUSION: CKD is associated with substantial and independent risk for mortality and morbidity at 1-year follow-up in women undergoing TAVR.

Safety and efficacy of polymer-free biolimus-eluting stents versus ultrathin stents in unprotected left main or coronary bifurcation: A propensity score analysis from the RAIN and CHANCE registries.

OBJECTIVES: Evaluate safety and efficacy of polymer-free biolimus-eluting stents (PF-BESs) versus ultrathin stents in unprotected left main (ULM) or bifurcation. BACKGROUND: PF-BESs due to reduced length of dual antiplatelet therapy (DAPT) are increasingly used. However, there are limited data about safety and efficacy for ULM or bifurcation. METHODS: We selected all-patients treated for ULM or bifurcation from two multicenter real life registries (RAIN [NCT03544294] evaluating ultrathin stents, CHANCE [NCT03622203] appraising PF-BES). After propensity score with matching, the primary endpoint was major adverse cardiac events (MACE; a composite of all-cause death, myocardial infarction, target lesion revascularization [TLR], and stent thrombosis [ST]), while its components along with target vessel revascularization (TVR) secondary endpoints. RESULTS: Three thousand and three patients treated with ultrathin stents and 446 with PF-BESs, resulting respectively in 562 and 281 after propensity score with matching (33 and 22%, respectively, with ULM disease). After 12 (8-20) months, rates of MACE were similar (9 vs. 8%, p = 0.56) without difference in TLR and ST (3.0 vs. 1.7%, p = .19 and 1.8 vs. 1.1%, p = .42). These results were consistent for ULM group (3 vs. 1.7% and 1.8 vs. 1.1%, p = .49 and .76), for non-ULM group (2.1 vs. 3.4%, p = .56 and 1.2 vs. 1.7%, p = .78) and for two-stent strategy (8.7 vs. 4.5% and 4.3 vs. 3.2%, p = .75 and .91). Among patients treated with 1 month of DAPT in both groups, those with ultrathin stents experienced higher rates of MACE related to all-cause death (22 vs. 12%, p = .04) with higher although not significant rates of ST (3 vs. 0%, p = .45). CONCLUSIONS: PF-BES implanted on ULM or BiF offered freedom from TLR and ST comparable to ultrathin stents. PF-BESs patients assuming DAPT for 1 month experienced a lower despite not significant incidence of ST.

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.

Comparison of bioresorbable vs durable polymer drug-eluting stents in unprotected left main (from the RAIN-CARDIOGROUP VII Study).

BACKGROUND: There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. METHODS: In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 µm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed. RESULTS: From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12-22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES. CONCLUSION: In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03544294. Retrospectively registered June 1, 2018.

Impact of coronary artery disease and percutaneous coronary intervention in women undergoing transcatheter aortic valve replacement: From the WIN-TAVI registry.

OBJECTIVES: To evaluate the impact of coronary artery disease (CAD) with or without recent (≤ 30 days) percutaneous coronary intervention (PCI) in women undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Although women display a specific risk-profile for both PCI and TAVR, the impact of CAD and PCI in the setting of TAVR in women is unclear. METHODS: The multinational Women's International Transcatheter Aortic Valve implantation registry enrolled consecutive female patients undergoing contemporary TAVR in 19 centers between 2013 and 2015. Patients with available coronary angiography or CT scan in the pre-operative assessment of TAVR were categorized as without CAD, with CAD but no recent PCI and CAD and recent PCI (≤30 days). All events were adjudicated according to the VARC-2 criteria. RESULTS: A total of 787 patients were included in this analysis, among whom 459 (58.3%) had no CAD, 247 (31.4%) had CAD without recent PCI and 81 (10.3%) underwent recent PCI (≤ 30 days before TAVR). After multivariable adjustment, both groups of CAD patients, without and with recent PCI, presented with higher risk of death, myocardial infarction or stroke, compared with patients without CAD (adj HR 1.56, 95%CI 1.03-2.39, P = 0.038 and adj HR 1.96, 95% CI 1.1-3.5, P = .021, respectively). Patients with recent PCI had increased risk of all-cause death (adj HR 1.89, 95% CI 1.0-3.5, P = 0.04) and stroke (adj HR 3.7, 95% CI 1.0-13.5, P = 0.046) compared with patients without CAD. CONCLUSION: The presence of CAD in women undergoing TAVR, with or without recent PCI, was associated with long-term poorer outcomes.

Antiplatelet therapy and outcome in patients undergoing surgery following coronary stenting: Results of the surgery after stenting registry.

OBJECTIVES: The aim of the present study was to define the feasibility and clinical impact of complying with national consensus recommendations on perioperative management of antiplatelet therapy in patients with coronary stents undergoing cardiac and noncardiac surgery. BACKGROUND: There are limited evidence-based recommendations on the perioperative management of antiplatelet therapy in stented patients undergoing surgery. METHODS: The recommendations provided by the national consensus document were applied in a multicenter, prospective registry of consecutive patients with prior coronary stenting undergoing any type of surgery at 19 hospitals in Italy. The primary end-point was in-hospital net adverse clinical events (NACE) represented by the composite of all-cause death, myocardial infarction, probable/definite stent thrombosis and Bleeding Academic Research Consortium (BARC) grade ≥3 bleeding. Patients were followed for 30 days. RESULTS: A total of 1,082 patients were enrolled. Adherence to consensus recommendations occurred in 85% of the cases. Perioperative aspirin and dual antiplatelet therapy were maintained in 69.7 and 10.5% of the cases, respectively. In-hospital NACE rate was 12.7%, being significantly higher in patients undergoing cardiac surgery (36.3% vs. 7.3%, P < 0.01), mainly due to BARC 3 bleeding events (32.3%). At 30 days, MACE rates were similar (3.5% vs. 3.5%, P = NS) in patients undergoing cardiac and noncardiac surgery, whereas BARC ≥3 bleeding events were significantly higher with cardiac surgery (36.3% vs. 5.6%, P < 0.01). CONCLUSIONS: The results of this registry demonstrate the safety and feasibility of applying a national consensus document on the perioperative management of antiplatelet therapy in stented patients undergoing surgery. © 2016 Wiley Periodicals, Inc.

Relationship between Serum Inflammatory Biomarkers and Thrombus Characteristics in Patients with ST Segment Elevation Myocardial Infarction.

OBJECTIVES: To compare angiographic and optical coherence tomography (OCT) data pertinent to thrombi, along with the histologic characteristics of aspirated thrombi in patients presenting with ST elevation myocardial infarction (STEMI) with or without inflammation, as assessed by C-reactive protein (CRP) and myeloperoxidase (MPO). METHODS: In the OCTAVIA (Optical Coherence Tomography Assessment of Gender Diversity in Primary Angioplasty) study, 140 patients with STEMI referred for primary percutaneous intervention were enrolled. The patients underwent OCT assessment of the culprit vessel, along with blood sampling of CRP and MPO, and histologic analysis of the thrombus. RESULTS: Biomarkers were available for 129 patients, and histology and immunohistochemistry of the thrombi were available for 78 patients. Comparisons were made using the median thresholds of CRP and MPO (2.08 mg/L and 604.124 ng/mL, respectively). There was no correlation between CRP and MPO levels in the whole population (p = 0.685). Patients with high CRP levels had higher thrombus grades and more frequent TIMI flow 0/1 compared with those with low CRP levels (5 [1st quartile 3; 3rd quartile 5] vs. 3.5 mg/L [1; 5], p = 0.007, and 69.3 vs. 48.5%, p = 0.04, respectively). Patients with high MPO levels more commonly had early thrombi than had those with low MPO levels (42.5 vs. 20.0%, p = 0.04). CONCLUSIONS: CRP and MPO were not correlated in STEMI patients, possibly reflecting different pathogenic mechanisms, with CRP more related to thrombus burden and MPO to thrombus age.

Third- versus Second-Generation Stent Graft for Endovascular Aneurysm Repair: A Device-Specific Analysis.

PURPOSE: Our purpose is to analyze the outcomes of endovascular aneurysm repair (EVAR) in patients treated with Excluder endograft (W.L. Gore and Associate, Flagstaff, AZ), comparing second generation, featuring SIM-PULL delivery system (ExSP) and third generation, featuring C3 (ExC3), concerning intraprocedural data and long-term outcomes. METHODS: In our single-center, comparative study, we retrospectively analyzed all patients undergoing elective EVAR with Excluder from May 2008 to December 2015. This cohort was firstly divided according to the design of the endograft used, and then, two subgroups of complex procedures were identified according to International Standards. Preliminary end points were early- and mid-term outcomes. Primary end point was procedural data (i.e., procedural and fluoroscopy time, radiation dose (DAP), and contrast medium amount). RESULTS: The study included 64 patients (24 ExSP and 40 ExC3) with a mean follow-up of 31.6 ± 22.9 months. Patients in ExC3 group had significantly more risk factors (past or present history of smoking, P = 0.019), comorbidities (chronic heart failure and chronic kidney disease, both P = 0.032), as well as a more unfavorable anatomy (neck angulation, P = 0.035). Concerning preliminary outcome, no significant between-group difference was noted. As for intraoperative data, procedure duration was significantly shorter: 120 vs. 151 min (P = 0.002) in the overall population and 129 vs. 173 min (P = 0.004) in complex cases. A significant reduction was also found in fluoroscopy time and radiation exposure: 24,084 vs. 32,548 cGy/cm2 (P = 0.020) in the overall population and 26,770 vs. 41,104 cGy/cm2 (P = 0.003) in complex cases. No significant difference was found for contrast volume. CONCLUSIONS: The study shows that new C3 excluder enables to reduce radiation exposure and procedural time compared to the previous device. C3 excluder results are comparable to those of the previous device in spite of more comorbidities and complex anatomy of the treated patients. Further studies are needed to assess device performance on longer-term follow-up.