Publications

In the drug-eluting stent (DES) era, patients with acute coronary syndrome (ACS) had a higher risk of early stent thrombosis compared with stable patients. The present study aimed to evaluate whether the same is true for the bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA, USA).We assessed the relationship between the incidence of definite/probable scaffold thrombosis (ScT) (overall ScT and early ScT) and ACS percentage with the latest publications, including the most recent large randomised controlled trials. Out of a total study population of 13,708 devices in 45 trials, overall ScT was observed in 185 devices (1.35%) at a weighted mean follow-up period of 9.4 months, while early ScT was reported in 125 devices (0.97%) out of 12,896 devices in 44 trials. Meta-regression analysis demonstrated no significant correlation between overall/early ScT and the percentage of patients with ACS (overall ScT: R2=0.030, p=0.255; early ScT: R2=0.067, p=0.090).ACS appeared to have little impact on the incidence of ScT after the implantation of BVS. Further clinical study is warranted to investigate the predictors of ScT using multivariate analysis with sufficient statistical power.

Nitric oxide (NO) production and carbon monoxide (CO) production are increased in inflammatory lung diseases. Although there are some pieces of evidence for hormonal modulation by estrogen, little is known about exhaled NO and CO during the ovarian cycle. In 23 subjects, we measured exhaled NO and CO by an online analyzer. Significantly higher levels of exhaled NO were found at the midcycle compared with those in the premenstrual period or during menstruation. Higher levels of CO were after ovulation and reached a peak in the premenstrual phase. The lowest levels of CO were observed in the first days of the estrogen phase. In males, there was no significant variation in exhaled NO and CO. Exhaled NO and CO levels vary during the ovarian cycle in women, and this fact should be taken into account during serial measurements of these markers in the female population.

Aims: The role of oral immunosuppressive therapy (OIT) after percutaneous coronary intervention (PCI) and stenting still remains to be defined. We sought to evaluate the efficacy and safety of oral administration of sirolimus or prednisone to prevent in-stent restenosis. Methods: We undertook a meta-analysis of trials in which PCI-patients were randomly assigned to OIT or control therapy. The primary endpoint was the composite of death/myocardial infarction (MI) or target lesion revascularization (TLR). Secondary endpoints were the composite of death/MI, the individual components of the primary endpoint and in-stent late lumen loss (LLL) at angiographic surveillance. Results: We obtained individual data of seven trials enrolling 1,246 patients (OIT, n= 608 versus control therapy, n= 638) with 1,456 coronary lesions. Median follow-up was 360 days [interquartile range 360-1440]. OIT as compared to control therapy significantly reduced the risk of the composite primary endpoint (hazard ratio [95% CI]= 0.62 [0.39-0.96], P= 0.03), without significant difference in terms of death/MI (0.84 [0.46-1.52], P= 0.57), death (1.12 [0.61-2.06], P= 0.71) and MI (0.67 [0.33-1.38], P= 0.28). OIT as compared to control therapy significantly reduced the risk of TLR (0.55 [0.34-0.89], P= 0.01) as well as the degree of in-stent LLL (0.62±0.65 mm versus 0.94±0.70 mm; mean difference 0.32 mm [0.22-0.42], P<0.001). The proportion of patients complaining side effects associated with OIT was 13.4% and 1.1% permanently discontinued the therapy. Conclusions: The use of oral immunosuppressive therapy as compared to control therapy reduces the composite of death/myocardial infarction or target lesion revascularization after stenting without safety issues. The advantage of oral immunosuppressive therapy is predominantly related to the lower risk of restenosis after revascularization.

Los stents liberadores de fármacos de primera generación han reducido considerablemente las reestenosis en el stent y han ampliado las aplicaciones de las intervenciones coronarias percutáneas en el tratamiento de la enfermedad coronaria. El polímero es parte integrante de los stents liberadores de fármacos, ya que controla la liberación de un fármaco antiproliferativo. La principal preocupación respecto a los stents liberadores de fármacos de primera generación con polímeros permanentes —la trombosis del stent— se ha debido a la hipersensibilidad local, la cicatrización tardía del vaso y la disfunción endotelial. Esto ha llevado al desarrollo de stents liberadores de fármacos de nueva generación con polímeros biodegradables o incluso sin polímero. En ensayos clínicos recientes se ha observado la seguridad y la eficacia de los stents liberadores de fármacos con polímero biodegradable, que han mostrado una reducción demostrada de la trombosis de stent muy tardía, comparados con los de primera generación. Sin embargo, el concepto de utilizar prótesis metálicas permanentes tiene importantes inconvenientes, como la presencia de un cuerpo extraño en el interior de la arteria coronaria nativa, que causa inflamación vascular y neoaterosclerosis e impide también el restablecimiento de la función vasomotora del segmento tratado con el stent. Para superar esas limitaciones, se han introducido las estructuras de base bioabsorbible, que proporcionan un armazón temporal y luego al desaparecer liberan el vaso tratado de la jaula que le imponían. En este artículo de puesta al día se presenta el estado actual de estas nuevas tecnologías y se resaltan sus perspectivas futuras en cardiología intervencionista. First generation drug-eluting stents have considerably reduced in-stent restenosis and broadened the applications of percutaneous coronary interventions for the treatment of coronary artery disease. The polymer is an integral part of drug-eluting stents in that, it controls the release of an antiproliferative drug. The main safety concern of first generation drug-eluting stents with permanent polymers—stent thrombosis—has been caused by local hypersensitivity, delayed vessel healing, and endothelial dysfunction. This has prompted the development of newer generation drug-eluting stents with biodegradable polymers or even polymer-free drug-eluting stents. Recent clinical trials have shown the safety and efficacy of drug-eluting stents with biodegradable polymer, with proven reductions in very late stent thrombosis as compared to first generation drug-eluting stents. However, the concept of using a permanent metallic prosthesis implies major drawbacks, such as the presence of a foreign material within the native coronary artery that causes vascular inflammation and neoatherosclerosis, and also impedes the restoration of the vasomotor function of the stented segment. Bioresorbable scaffolds have been introduced to overcome these limitations, since they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage. This update article presents the current status of these new technologies and highlights their future perspectives in interventional cardiology. Full English text available from: www.revespcardiol.org

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

The effects of tumor necrosis factor (TNF) on hypoxic pulmonary vasoconstriction (HPV) and endothelium-dependent relaxation were examined in a blood-perfused rat lung preparation. Lungs from TNF-treated rats (0.26 mg/kg iv 12 h before experimentation) had a significantly greater HPV and a reduced vasorelaxant response to the endothelium-dependent vasodilator acetylcholine (ACh) but a similar vasorelaxant response to the endothelium-independent vasodilator nitroprusside compared with lungs from control rats (pretreated with 0.1 ml saline iv). Pentoxifylline (20 mg/kg iv and ip 20 min before administration of TNF) had no detectable effect on either HPV or ACh-induced relaxation but completely negated the augmentation on HPV and the inhibiting action on ACh-induced relaxation caused by TNF. The TNF effect on ACh relaxation was unaffected by pretreatment with L-arginine. These results indicate that TNF induces endothelial dysfunction and enhances HPV, effects that are inhibited by pentoxifylline.

Objectives This study investigated coronary artery remodeling patterns associated with clinical outcomes. Background In the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm2, a plaque burden ≥70%, and a IVUS–virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling. Methods Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI <0.88, intermediate remodeling as an RI of 0.88 to 1.00, and positive remodeling as an RI >1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort). Results Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions. Conclusions The present study showed the novel concept that positive and negative lesion site remodeling was associated with unanticipated NCL MACE in the PROSPECT study. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT]; NCT00180466)