Optical coherence tomography, intravascular ultrasound or angiography guidance for distal left main coronary stenting. The ROCK cohort II study.

OBJECTIVES: to test the safety and efficacy of intravascular imaging and specifically optical coherence tomography (OCT) as a diagnostic tool for left main angioplasty and analyze the mid-term outcome accordingly. BACKGROUND: Clinical data and international guidelines recommend the use of intravascular imaging ultrasound (IVUS) to guide left main (LM) angioplasty. Despite early experience using OCT in this setting is encouraging, the evidence supporting its use is still limited. METHODS: ROCK II is a multicenter, investigator-driven, retrospective European study to compare the performance of IVUS and OCT versus angiography in patients undergoing distal-LM stenting. The primary study endpoint was target-lesion failure (TLF) including cardiac death, target-vessel myocardial infarction and target-lesion revascularization. We designed this study hypothesizing the superiority of intravascular imaging over angiographic guidance alone, and the non-inferiority of OCT versus IVUS. RESULTS: A total of 730 patients, 377 with intravascular-imaging guidance (162 OCT, 215 IVUS) and 353 with angiographic guidance, were analyzed. The one-year rate of TLF was 21.2% with angiography and 12.7% with intravascular-imaging (p = 0.039), with no difference between OCT and IVUS (p = 0.26). Intravascular-imaging was predictor of freedom from TLF (HR 0.46; 95% CI 0.23-0.93: p = 0.03). Propensity-score matching identified three groups of 100 patients each with no significant differences in baseline characteristics. The one-year rate of TLF was 16% in the angiographic, 7% in the OCT and 6% in the IVUS group, respectively (p = 0.03 for IVUS or OCT vs. angiography). No between-group significant differences in the rate of individual components of TLF were found. CONCLUSIONS: Intravascular imaging was superior to angiography for distal LM stenting, with no difference between OCT and IVUS.

Real-world reasons and outcomes for 1-month versus longer dual antiplatelet therapy strategies with a polymer-free BIOLIMUS A9-coated stent.

BACKGROUND: A large trial established the favorable profile of a new polymer-free biolimus A9-eluting stent (PF-BES) with a 1-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients. This is the first study comparing outcomes for a 1-month versus longer DAPT strategies following PF-BES-percutaneous coronary intervention (PCI). METHODS: All patients undergoing PF-BES-PCI (January 2016 to July 2018) were included in the multicenter CHANCE registry. Patients were stratified according to DAPT strategy at discharge (planned 1-month vs. planned >1-month). Primary outcomes were the 390-day estimates of a patient-oriented and of a device-oriented composite endpoints (POCE: death, myocardial infarction [MI] or target vessel revascularization; DOCE: cardiac death, target vessel-MI or ischemia-driven target lesion revascularization). Landmark analyses from 1-month post-PCI were carried. RESULTS: Following PF-BES-PCI, 328(40.3%) and 485(59.6%) patients were discharged with 1-month and longer DAPT (12 months [6-12]), respectively. Patients with a previous or index MI were less likely to be discharged on 1-month DAPT. Patients prescribed with 1-month DAPT were more likely to be at HBR than those with longer DAPT (90.2% vs. 69.9%, p = .001). No between-groups differences in the primary outcomes (planned 1-month vs. planned >1-month DAPT: POCE 11.9% vs. 13.2%, p = .747; DOCE: 4.8% vs. 8.1%, p = .500) were observed, also after adjusting for confoundings (POCE: adjusted-hazard ratio [adj-HR] 1.26, 95%CI 0.74-2.13; DOCE: adj-HR 1.00, 95%CI 0.49-1.99). Landmark analyses showed similar results. CONCLUSIONS: In a large all-comers registry of PF-BES PCI, no interaction of planned DAPT strategy (1-month vs. >1-month) with outcomes was found. This observation warrants investigation in adequately powered randomized studies (ClinicalTrials.gov NCT03622203).

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.

Clinical and angiographic outcome of a single center, real world population treated with a dedicated technique of implantation for bioresorbable vascular scaffolds. The FAtebenefratelli Bioresorbable Vascular Scaffold (FABS) registry.

OBJECTIVES: With this prospective study we aim at investigating the long-term outcome of a consecutive cohort of patients successfully treated with bioresorbable scaffold (BVS) implantation. BACKGROUND: It is not clearly understood if there is a relation between the technique of BVS implantation and the outcome. METHODS: Between December 2012 and December 2014, all consecutive patients treated with BVS were included in this registry and received an angiographic follow-up. After a run-in phase, all BVS were implanted using a specific technique consisting of aggressive predilation, correct scaffold sizing, visually determined, and high-pressure post-dilation with a noncompliance balloon. Primary endpoint was late lumen loss (LLL) at 1-year angiographic follow-up and ischemia-driven target-lesion revascularization (ID-TLR) at 2-year clinical follow-up. Secondary endpoints were the occurrence of binary restenosis, major adverse cardiac events (MACE), and every single component of MACE (cardiac death, myocardial infarction, TLR) at 2 years. RESULTS: A total of 144 lesions in 122 patients treated consecutively with BVS, were enrolled. Diabetics were 29.5% and acute coronary syndrome at presentation occurred in 29.5% of patients. At the angiographic follow-up LLL was 0.38 ± 0.9. At 2-year clinical follow-up, ID-TLR occurred in eight patients (5.6%). We observed two cases of scaffold thrombosis (1.38%, one early and one very late). At multivariate statistical analysis, STEMI presentation remained a significant predictor for TLR. CONCLUSIONS: In a complex, all-comers real world population, BVS implantation with a specific, and standardized technique showed to be feasible, with acceptable mid-term angiographic and long-term clinical outcome.

Interplay between mitral regurgitation and transcatheter aortic valve replacement with the CoreValve Revalving System: a multicenter registry.

BACKGROUND: Little is known of the prognostic significance of mitral regurgitation (MR) on transcatheter aortic valve replacement (TAVR), the impact of TAVR on MR severity, and the variables associated with possible post-TAVR improvement in MR. We evaluated these issues in a multicenter registry of patients undergoing CoreValve Revalving System-TAVR. METHODS AND RESULTS: Among 1007 consecutive patients, 670 (66.5%), 243 (24.1%), and 94 (9.3%) presented with no/mild, moderate, and severe MR, respectively. At 1 month after TAVR, patients with severe or moderate MR showed comparable mortality rates (odds ratio, 1.1; 95% confidence interval [95% CI], 0.7-1.55; P=0.2), but both were significantly higher compared with patients with mild/no MR (odds ratio, 2.2; 95% CI, 1.78-3.28; P<0.001; and odds ratio, 1.9; 95% CI, 1.1-3.3; P=0.02, respectively). One-year mortality was also similar between patients with severe and those with moderate MR (hazard ratio, 1.4; 95% CI, 0.94-2.4; P=0.06) and still significantly higher compared with patients with mild/no MR (hazard ratio, 1.7; 95% CI, 1.2-3.41; P<0.001; and hazard ratio, 1.4; 95% CI, 1.2-2.2; P=0.03, respectively). Severe pulmonary hypertension, atrial fibrillation, and MR more than mild, but not an improvement of ≥1 grade in MR severity, were independent predictors of mortality at 1 year. At 1 year, an improved MR was observed in 47% and 35% of patients with severe and moderate MR, respectively. The rate of low implantation was consistent across groups with improved, unchanged, or worsened MR. A functional type of MR and the absence of severe pulmonary hypertension and atrial fibrillation independently predicted the improvement in MR severity. CONCLUSIONS: Baseline MR greater than mild is associated with higher mortality after CoreValve Revalving System-TAVR. A significant improvement in MR was more likely in patients with functional MR and without severe pulmonary hypertension or atrial fibrillation. The improvement in MR did not independently predict mortality.

Sirolimus-coated balloon in acute and chronic coronary syndromes: subanalysis of the EASTBOURNE registry.

INTRODUCTION AND OBJECTIVES: The PEACE study (Performance of a sirolimus-eluting balloon strategy in acute and chronic coronary syndromes) investigated for the first time whether a sirolimus-coated balloon (SCB) (Magic Touch, Concept Medical, India) is associated with different outcomes depending on whether it is used in acute coronary syndromes (ACS) or chronic coronary syndromes (CCS). METHODS: This was a post-hoc analysis from the all-comers EASTBOURNE Registry (NCT03085823). Out of 2083 patients enrolled, an SCB was used to treat 968 (46.5%) ACS and 1115 (53.5%) CCS patients. The primary endpoint was target lesion revascularization at 12 months, while secondary endpoints were angiographic success and major adverse cardiovascular events. RESULTS: Baseline demographics, mean reference vessel diameter and mean lesion length were comparable between ACS and CCS. Predilatation was more commonly performed in ACS (P=.007). SCB was inflated at a standard pressure in both groups with a slight trend toward longer inflation time in ACS. Angiographic success was high in both groups (ACS 97.4% vs CCS 97.7%, P=.820) with limited bailout stenting. Similarly, at 12 months the cumulative incidence of target lesion revascularization (ACS 6.6% vs CCS 5.2%, P=.258) was comparable between ACS and CCS. Conversely, a higher rate of major adverse cardiovascular events in acute presenters was mainly driven by myocardial infarction recurrencies (ACS 10.4% vs CCS 8.3%, P=.009). In-stent restenosis showed a higher proportion of target lesion revascularization and major adverse cardiovascular events than de novo lesions, independently of the type of presentation at the index procedure. CONCLUSIONS: This SCB shows good performance in terms of acute and 1-year outcomes independently of the clinical presentation.

Sirolimus-Coated Balloon in an All-Comer Population of Coronary Artery Disease Patients: The EASTBOURNE Prospective Registry.

BACKGROUND: Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications. OBJECTIVES: This study sought to understand the role of a novel SCB for the treatment of coronary artery disease. METHODS: EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee. RESULTS: A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881). CONCLUSIONS: EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823).

Usefulness of Coronary Sinus Reducer Implantation for the Treatment of Chronic Refractory Angina Pectoris.

The coronary sinus (CS) Reducer is a novel device designed for the management of patients with severe angina symptoms refractory to optimal medical therapy and not amenable to further revascularization. Aim of this study was to investigate the efficacy and the safety of the CS Reducer device in a real-world, multicenter, and country-level cohort of patients presenting with refractory angina pectoris. The study included patients affected by refractory angina pectoris who underwent CS Reducer implantation in 16 centers. Clinical follow-up was carried as per each center's protocol. One hundred eighty-seven patients were included. Technical and procedural success were achieved in 98% and 95%, respectively. Minor peri-procedural complications were recorded in 8 patients. During a median follow-up of 18.4 months, 135 (82.8%) patients demonstrated at least 1 CCS class reduction after Reducer implantation, and 80 (49%) patients at least 2 CCS class reduction. Mean CCS class improved from 3.05 ± 0.53 at baseline to 1.63 ± 0.98 at follow-up (p < 0.001). Treatment benefit was also reflected in a significant improvement in quality of life scores and in a reduction of the mean number of anti-ischemic drugs prescribed for patient. In conclusion, in this multicenter, country-level study, the implantation of CS Reducer in patients with refractory angina pectoris resulted to be safe and effective in reducing of angina pectoris and improving quality of life.

Angiographic performance of a novel sirolimus-coated balloon in native coronary lesions: the FAtebenefratelli SIrolimus COated NATIVES prospective registry.

AIMS: To evaluate the angiographic performance of a novel sirolimus-coated balloon (SCB) in de novo coronary lesions. METHODS: Out of an all-comer prospective registry of patients treated with the SCB at our center from April 2016 to September 2017, we selected those treated for a de novo stenosis on a native vessel, with a scheduled angiographic control at at least 4 months after the index procedure. We performed a centralized, blinded core-lab adjudicated quantitative coronary angiography analysis. Primary endpoint was late lumen loss. Secondary endpoints were binary restenosis and target-lesion revascularization. RESULTS: A total of 27 patients with native coronary arteries treated with SCB and with angiographic follow-up entered the study; seven patients were excluded because a stent was implanted at the lesion site during the index procedure. The degree of calcification (assessed with coronary angiography) was high in six patients (30%) and the average lesion length was 20.52 ±â€Š6.88 mm. The reference vessel diameter was 2.32 ±â€Š0.44 mm and the percentage diameter stenosis was 67 ±â€Š12. Procedural success was obtained in all patients. After a median of 6.6 ±â€Š2.5 months, late lumen loss was 0.09 ±â€Š0.34 mm and the percentage diameter stenosis was 31 ±â€Š18. We observed two cases (10%) of binary restenosis which underwent subsequent target-lesion revascularization: in one a drug-eluting stent was implanted, whereas the other patient was treated with paclitaxel-coated balloon. No myocardial infarction or death was observed during follow-up. CONCLUSION: The use of a novel SCB in native coronary arteries was associated with good angiographic outcome at 6-month follow-up.

Treatment of coronary artery disease with a new-generation drug-coated balloon: final results of the Italian Elutax SV rEgistry-DCB-RISE.

AIMS: Drug-coated balloons (DCBs) are a recognized alternative to stents for the treatment of in-stent restenosis (ISR), and there is some initial clinical evidence about their efficacy for the treatment of small coronary vessels. Newer-generation DCBs were developed to overcome the reduced deliverability of the previous generation, also warranting a more effective drug delivery to vessel wall. However, the vast majority of new-generation DCBs still lack of reliability due to paucity of clinical data. METHODS: Between 2012 and 2015, all patients treated with Elutax SV DCB (Aachen Resonance, Germany) at nine Italian centers were enrolled in this retrospective registry. Primary outcome was the occurrence of target-lesion revascularization (TLR) at the longest available follow-up. Secondary endpoints were procedural success and occurrence of device-oriented adverse cardiovascular events including cardiac death, target-vessel myocardial infarction, stroke, and TLR. A minimum 6-month clinical follow-up was required. RESULTS: We enrolled 544 consecutive patients treated at 583 sites. Fifty-three per cent of the patients had ISR, and the rest native vessel coronary artery disease. Procedural success occurred in 97.5%. At the longest available clinical follow-up (average 13.3 ±â€Š7.4 months), 5.9% of the patients suffered a TLR and 7.1% a device-oriented adverse cardiovascular event. We did not register cases of target-vessel abrupt occlusion. At multivariate analysis, severe calcification at the lesion site was the first determinant for the occurrence of TLR. CONCLUSION: This registry on the performance of a new-generation DCB shows an adequate profile of safety and efficacy at mid-term clinical follow-up.

Clinical performance of a dedicated self-apposing stent for the treatment of left main stem disease. Results of the left Main AngioplasTy wIth a Self-apposing StEnt - the MATISSE study.

BACKGROUND: In the recent years percutaneous treatment of the left main stem (LM) has gained a precise role as a result of consistent scientific evidence vs. coronary artery bypass. A self-apposing stent offers an improved adaptation to the vessel wall, especially in case of tapered vessels; aim of this study was to investigate the role of a novel self-apposing, sirolimus-eluting stent (Stentys, France) for the treatment of LM coronary artery disease. METHODS AND RESULTS: MATISSE is a retrospective, multicenter registry, which enrolled 151 patients treated with the device at 17 international centers. Primary study endpoint was the occurrence of major adverse cardiovascular events (MACE), a composite endpoint of cardiac death, target lesion revascularization (TLR) and target-vessel myocardial infarction, at 9months clinical follow-up. Secondary endpoints included procedural success, the single determinants of MACE and stent thrombosis. Lesions were located in distal LM bifurcation in 84% of the patients. Procedural success was achieved in 150 patients. The average follow-up length was 348±52days. MACE occurred in 14 (9.3%) patients with 2 (1.3%) cardiac deaths. TLR occurred in 8 patients (5.3%). There were 2 cases of definite stent thrombosis, 1 acute and 1 very late. CONCLUSIONS: A self-apposing stent, when used for LM PCI in a real world, high risk population, showed good immediate procedural results with low rates of adverse events at mid-term follow-up.

Immediate and short-term performance of a novel sirolimus-coated balloon during complex percutaneous coronary interventions. The FAtebenefratelli SIrolimus COated-balloon (FASICO) registry.

BACKGROUND AND PURPOSES: Drug-coated balloons (DCB) currently represent an alternative to drug-eluting stents (DES) for the treatment of in-stent restenosis and they are also variably used for small coronary vessel and bifurcation lesion management. All DCB variably elute paclitaxel as an anti-proliferative drug. The first sirolimus coated balloon (SCB) received the CE mark in 2016, but its clinical performance has not been shown yet. METHODS AND RESULTS: FASICO in an all-comer registry of the first consecutive patients with at least one lesion treated with SCB between March and July 2016 at the first European centre that used this device. All patients were prospectively enrolled in a dedicated database. Primary endpoint was procedural success; co-primary endpoint was the rate of major adverse cardiac events at short-term follow-up. The 32 patients (34 lesions) enrolled had at least 6-month clinical follow up available. Forty-five percent had diabetes and indication to PCI was ISR in 47% of the cases. Lesions were always pre-dilated and device deployment was successful in all the cases. Procedural success was achieved in 100% of patients. We observed 3 cases of TLR at follow-up. CONCLUSIONS: SCB shows high immediate technical performance and adequate short-term efficacy and safety. The ongoing EASTBOURNE registry will shed light on mid-and long-term performance of this device in an adequately powered population.

Final shape of biovascular scaffolds and clinical outcome. Results from a multicenter all-comers study with intravascular imaging.

AIMS: Radial strength of bioresorbable vascular scaffolds (BVS) implanted in coronary arteries is still under debate. Moreover, their final shape patterns, when implanted in an all-comer, unselected population, have not yet been completely correlated with clinical outcome and should be better investigated. METHODS AND RESULTS: A multicenter collaborative analysis was performed on all consecutive patients with native coronary artery disease undergoing PCI with intravascular imaging-guided BVS implantation. The BVS was arbitrarily categorized as having a final "oval shape" through intravascular imaging, if maximal lumen diameter was longer than 150% of minimal lumen diameter at the target lesion. Primary study-endpoint was device-oriented major adverse events (DOCE) at mid-term follow-up. Sixty-seven consecutive patients were evaluated at 6 European centers. Mean patient age was 58±11years, and 12 patients (18%) had diabetes. Mean percent diameter stenosis was 79±12.5%. Average lesion length was 24.4±13.8mm and 66% of lesions were AHA/ACC type B2/C. Postdilation rate was 91% and all BVS resulted well apposed to the vessel wall. Procedural success was achieved in all patients and 10 (14.9%) had an "oval shape" at intravascular imaging. This occurrence was not associated with an increase in periprocedural myocardial infarction (p=0.37) or DOCE during hospitalization (p=0.65). Seven-month DOCE occurred in 3 patients (5.6%) of the oval shape group, they were target-vessel revascularization and did not differ significantly between patients with vs. without final "oval shape" (p=0.34). We did not register episodes of scaffold thromboses. CONCLUSIONS: In an all-comer population with complex coronary lesions treated with BVS, a final oval shape after postdilation was not rare and not associated with immediate and medium term adverse events.

Thirty-Day Outcomes After Unrestricted Implantation of Bioresorbable Vascular Scaffold (from the Prospective RAI Registry).

The Absorb biovascular scaffold (BVS) is a bioresorbable, everolimus-eluting scaffold whose data on real-world patients with complex lesions are limited. Short-term follow-up from recent studies point to a higher rate of 30-day thrombosis than observed with drug-eluting stents. We aimed to understand the short-term safety and efficacy of BVS. Registro Absorb Italiano (RAI, ClinicalTrials.gov:NCT02298413) is an Italian, prospective, multicenter registry not funded, whose aim is to investigate BVS performance through a 5-year follow-up of all consecutive patients who have undergone successful implantation of ≥1 BVS in different clinical/lesion subsets. Co-primary end points were target lesion revascularization and definite/probable thrombosis. Secondary end point was the occurrence of device-oriented cardiac events. The registry involved 23 centers, with patient enrollment from October 2012 to December 2015. We here report the 30-day outcomes of the whole population of the registry. We enrolled 1,505 consecutive patients, of which 82% were men and 22.4% diabetic. At presentation, 59.6% of the patients had an acute coronary syndrome, including 21% ST-elevation myocardial infarction. All lesions were pre-dilated and in 96.8% of the cases BVS was post-dilated. At 30 days, the co-primary study end point target lesion revascularization occurred in 0.6% of patients and definite/probable BVS thrombosis in 0.8%. There were 2 cases of cardiac and overall death (0.13%). Device-oriented cardiac events occurred in 1% of the patients. In conclusion, our data of consecutive patients suggest that current use of BVS in a wide spectrum of coronary narrowings and clinical settings is associated with good outcome at 30 days.

Rapamycin, but not FK-506, increases endothelial tissue factor expression: implications for drug-eluting stent design.

BACKGROUND: Drugs released from stents affect the biology of vascular cells. We examined the effect of rapamycin and FK-506 on tissue factor (TF) expression in human aortic endothelial cells (HAECs) and vascular smooth muscle cells (HAVSMCs). METHODS AND RESULTS: Rapamycin enhanced thrombin- and tumor necrosis factor (TNF)-alpha-induced endothelial TF expression in a concentration-dependent manner. The maximal increase was 2.5-fold more pronounced than that by thrombin or TNF-alpha alone and was paralleled by a 1.4-fold higher TF surface activity compared with thrombin alone. Rapamycin by itself increased basal TF levels by 40%. In HAVSMCs, rapamycin did not affect thrombin- or TNF-alpha-induced TF expression. In contrast to rapamycin, FK-506 did not enhance thrombin- or TNF-alpha-induced endothelial TF expression. Thrombin induced a transient dephosphorylation of the mammalian target of rapamycin downstream target p70S6 kinase. Rapamycin completely abrogated p70S6 kinase phosphorylation, but FK-506 did not. FK-506 antagonized the effect of rapamycin on thrombin-induced TF expression. Rapamycin did not alter the pattern of p38, extracellular signal-regulated kinase, or c-Jun NH2-terminal kinase phosphorylation. Real-time polymerase chain reaction analysis revealed that rapamycin had no influence on thrombin-induced TF mRNA levels for up to 2 hours but led to an additional increase after 3 and 5 hours. CONCLUSIONS: Rapamycin, but not FK-506, enhances TF expression in HAECs but not in HAVSMCs. This effect requires binding to FK binding protein-12, is mediated through inhibition of the mammalian target of rapamycin, and partly occurs at the posttranscriptional level. These findings may be clinically relevant for patients receiving drug-eluting stents, particularly when antithrombotic drugs are withdrawn or ineffective, and may open novel perspectives for the design of such stents.

Usefulness of brain natriuretic peptide levels to discriminate patients with stable angina pectoris without and with electrocardiographic myocardial ischemia and patients with healed myocardial infarction.

Brain natriuretic peptide (BNP) levels were measured in 100 patients with coronary heart disease (CHD) who underwent myocardial stress thallium-201 single-photon emission computed tomography (30 with stable angina without basal electrocardiographic ischemia and no perfusion defects, 31 with angina with electrocardiographic ischemia and reversible perfusion defects, and 39 with myocardial infarction and irreversible defects) and in 42 controls. BNP levels progressively increased in patients with CHD and were significantly greater in patients with ischemia (p <0.01) and infarction (p <0.001) compared with controls and subjects with angina. BNP concentration was correlated positively (r = 0.923, p <0.001) with perfusion defect extent and inversely (r = -0.690, p <0.001) with the left ventricle ejection fraction (not different in the subjects examined).

Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women.

Statins are able to reduce cardiovascular morbility and mortality mainly through their hypocholesterolemic effect. Beyond the inhibition of cholesterol synthesis, the identification of "ancillary" mechanisms has motivated studies evaluating the relationship between the use of statins and the modification of bone mineral density (BMD). To date, clinical trials have provided discordant results. The aim of our study was to evaluate whether simvastatin treatment (40 mg/d) could modify BMD in hypercholesterolemic women (n = 40) after a 2-year treatment as compared with a control group treated only with diet (n = 20) and matched by gender, age, body mass index (BMI), lipids, menopausal age, and BMD and the number of osteopenic, osteoporotic, and normal women (on the basis of T-score value). Exclusion criteria were secondary hyperlipemias and osteoporosis and current or previous therapy with statins, bisphosphonates, and estrogens. The BMD was measured at the lumbar spine and hip by dual energy x-ray absorpiometry (DEXA). In the group treated by simvastatin, BMD, both on the spine and femoral hip, showed a significant increase after 8 and 24 months, respectively (0.878 +/- 0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840 +/- 0.101 v 0.854 +/- 0.101; and 0.863 +/- 0.10, P <.001); there was a percentage increase of 1.7% after 8 months and 3.3% after 24 months at the spine; at the femoral hip, BMD increased 1.6% after 8 months and 2.7% after 24 months. The group treated only with hypolipidic diet demonstrated after 8 and 24 months a slight decrease in BMD both on the spine and femoral hip (respectively, 0.884 +/- 0.175 v 0.872 +/- 0.174 and 0.861 +/- 0.164; 0.860 +/- 0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05). In conclusion, as partly suggested by retrospective or observational data, this longitudinal study indicates that simvastatin treatment exerts a beneficial effect on BMD.

Drug eluting stents versus bare metal stents in the treatment of saphenous vein graft disease: a systematic review and meta-analysis.

AIMS: Treatment of saphenous vein graft (SVG) disease is still a matter of debate given the uncertainty of the available conflicting data. Our aim was to assess, by means of a meta-analytic approach, the risk/benefit profile of drug eluting stents (DES) versus bare metal stents (BMS) in the treatment of SVG disease. METHODS AND RESULTS: A search of relevant studies in several databases was performed. The endpoints of interest such as: major adverse events (MAE) (the combination of overall death and non-fatal myocardial infarction [AMI]), target vessel revascularisation (TVR), and target lesion revascularisation (TLR) have been calculated in-hospital and at the longest follow-up. Single endpoints and the rate of stent thrombosis (ST) were also assessed. Three randomised controlled trials and 15 registry studies were appraised, totalling 3,294 patients. During hospitalisation, there was no difference in the risk of MAE, overall death, AMI and TVR. No data were available to calculate the TLR rate. At a mean follow-up of 19.8 months, no significant differences were found in the risk of MAE and AMI. BMS were associated with a trend towards a higher risk of overall death (OR 1.32 [1,00-1.74], p=0.05, number needed to treat [NNT]=55). DES showed superiority in terms of TVR (OR 1.86 [1.33-2.61], p=0.0003, NNT=16), and TLR (OR 1.77 [1.27-2.48], p<0.0001, NNT=25). According to pre-specified subgroup analyses, these effects seem less evident at the long-term follow-up. DES were not associated with an increased risk of ST. CONCLUSIONS: Use of DES in SVG substantially reduces both TVR and TLR. These data also demonstrate that using DES in SVG is safe and contradict previous reports of potential risks.