Publications

Aims: The aim of this study was to evaluate the impact of a novel antiplatelet regimen in patients with increasing total stent length (TSL).Methods and results: This is a post hoc analysis of the GLOBAL LEADERS trial, a prospective, multicentre, open-label, randomised trial, investigating the impact of the experimental strategy (one-month dual antiplatelet therapy [DAPT] followed by 23month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) in patients with a Biolimus A9-eluting stent (BES).The primary endpoint was the composite of all-cause death and new Q-wave myocardial infarction (MI), and the secondary endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at two years.To investigate the association between total stent length and outcomes, groups were compared in quartiles according to TSL; the fourth quartile group was at significantly higher ischaemic risk at two years.In that stratum (TSL 46 mm), the experimental strategy significantly reduced the risk of the primary endpoint (hazard ratio [HR] 0.67, 95% confidence interval [CI]: 0.49-0.90;pinteraction=0.043),while demonstrating a similar risk of BARC type 3 or 5 bleeding (HR 0.99, 95% CI: 0.66-1.49;pinteraction=0.975).Conclusions: Ticagrelor monotherapy could potentially balance ischaemic and bleeding risks, thereby achieving a net clinical benefit in patients with a TSL 46 mm with a BES.

No abstract is provided for this article.

No abstract is provided for this article.

Inflammation is a hallmark of COPD and contributes to its pathogenesis. Inflammatory cells, such as alveolar macrophages, release inflammatory mediators including TNFα. We investigated basal and bacteria stimulated TNFα release by monocyte-derived macrophages (MDMs) at stable and exacerbation states. MDMs were cultured from 26 COPD patients at paired stable and exacerbation states. The MDMs were incubated for 4 h at 37 o C with 100μl of RPMI (controls), inert beads (4.5x10 9 microspheres/ml), or heat-killed Haemophilus influenzae (HI) or Streptococcus pneumoniae (SP) (both at 5x10 8 cfu/ml). Subsequent TNFα release was measured by ELISA. There was no difference in basal TNFα release from MDMs at stable and exacerbation states (p=0.247). There was a significant difference in TNFα release between the inert beads, HI and SP (p 0.05). In response to SP, TNFα release significantly increased at exacerbation compared to stable state (p=0.007, Figure 1A), but not in response to HI (p=0.513, Figure 1B). HI is more pro-inflammatory than SP at both stable and exacerbation COPD states. However, a significant increase in TNFα release from stable to exacerbation state is only seen in response to SP. Further work is needed to investigate this response and the relationship with phagocytosis.

No abstract is provided for this article.

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy.

Introducción y objetivos Se ha demostrado que el armazón vascular bioabsorbible Absorb produce una disminución del área total de las placas en el segmento tratado. Sin embargo, no se sabe si el tamaño de la placa se modifica tan solo en los segmentos tratados con armazones o si la modificación se extiende también a otros segmentos coronarios. Métodos El Absorb Cohort A es un estudio prospectivo de un solo grupo, en el que se evalúan variables de valoración de seguridad y de resultados en exploraciones de imagen en 30 pacientes tratados mediante intervención coronaria percutánea con el armazón vascular bioabsorbible Absorb de primera generación. Se utilizaron exploraciones de tomografía computarizada multicorte no invasivas de 18 pacientes a los 18 meses y a los 5 años de seguimiento. El presente estudio es una comparación intraindividual de segmentos de características comparables (normalizados respecto a la longitud del segmento) de la región tratada con armazones frente a segmentos no tratados, en la que se evaluó el volumen de la luz vascular, el volumen del vaso, el volumen de las placas, la carga de placa y el cambio porcentual en el volumen de ateroma de las placas. Resultados Se pudo analizar los 18 segmentos tratados con armazones. De los segmentos a los que no se aplicó la intervención, 1 de un total de 72 presentó un artefacto de movimiento y fue excluido. La comparación de exploraciones secuenciales puso de manifiesto que los segmentos tratados con armazones no presentaban un cambio significativo de la carga media de placas, el volumen total de ateroma, el volumen total de la luz o el volumen del vaso entre los 18 meses y los 5 años. En cambio, los segmentos no tratados mostraban un aumento significativo de la carga de placa (2,7 ± 6,5%; p < 0,01) y los volúmenes de placas normalizados (8,0 ± 22,8mm3; p < 0,01). Esto dio lugar a una diferencia significativa en la carga de placa entre los segmentos tratados con armazones y los no tratados (p = 0,03). Conclusiones En esta pequeña serie, el armazón vascular bioabsorbible Absorb mostró potencial de aportar un beneficio adicional al del tratamiento farmacológico en cuanto a la reducción local de la progresión en el porcentaje de carga de placa. Se deberá confirmar estos resultados en estudios más amplios. Introduction and objectives The Absorb bioresorbable vascular scaffold has been shown to decrease total plaque areas in the treated segment. However, it is unknown whether plaque size is modified in scaffolded segments only or whether the modification extends to other coronary segments. Methods Absorb Cohort A is a single-arm, prospective study, with safety and imaging endpoints, in which 30 patients underwent percutaneous coronary intervention with the first generation Absorb bioresorbable vascular scaffold. Noninvasive multislice computed tomography imaging was performed in 18 patients at 18 months and 5 years of follow-up. The present study was an intrapatient comparison of matched segments (normalized by the segment length) of the scaffolded region with nonintervened segments for lumen volume, vessel volume, plaque volume, plaque burden, and percent change in plaque atheroma volume. Results All 18 scaffolded segments could be analyzed. In the nonintervened segments, 1 of 72 segments had a motion artifact and was excluded. Serial comparison showed that the scaffolded segments showed no significant change in the mean plaque burden, total atheroma volume, total lumen volume, or vessel volume between 18 months and 5 years. Conversely, the untreated segments showed a significant increase in plaque burden (2.7 ± 6.5%; P < .01) and normalized plaque volumes (8.0 ± 22.8mm3; P < .01). This resulted in a significant difference in plaque burden between scaffolded and nonintervened segments (P = .03). Conclusions In this small series, the Absorb bioresorbable vascular scaffold showed the potential to provide an additional benefit to pharmacological therapy in locally reducing progression of percent plaque burden. These findings need to be confirmed in larger studies. Full English text available from: www.revespcardiol.org/en

Rupture of vulnerable plaques is the main cause of acute coronary syndrome and myocardial infarction. Identification of vulnerable plaques is therefore essential to enable the development of treatment modalities to stabilize such plaques. Several diagnostic methods are currently tested to detect vulnerable plaques. Angiography has a low discriminatory power to identify the vulnerable plaque, but does provide information about the entire coronary tree and serves as guide for invasive imaging techniques and therapy. Angioscopy offers a direct visualization of the plaque surface and intra-luminal structures like thrombi and tears. However, angioscopy is difficult to perform, invasive and only the proximal part of the vessels can be investigated. IVUS (intravascular ultrasound) provides some insight into the composition of plaques. The detection of vulnerable plaques is mainly based on series of case reports with a lack of prospectivity and follow-up. Palpography, an IVUS derived technique, reveals information, which is not recognizable in IVUS. It can differentiate between deformable and non-deformable tissue, which enables the technique to detect vulnerable plaques with a positive predictive value. The clinical value of palpography is currently under investigation. Thermography assesses the temperature heterogeneity as an indicator of the metabolic state of the plaque. A coincidence of temperature rise and localization of vulnerable plaque was suggested. OCT (optical coherence tomography) can provide images with ultrahigh resolution utilizing the back-reflection of near-infrared light from optical interfaces in tissue. Drawbacks are the low penetration depth into tissue and the absorbance of light by blood. Raman spectroscopy can provide quantification about the molecular composition of the plaque. Long acquisition time, the low penetration depth and light absorbance by blood limit the performance of the technique. Another light emitting technique is NIR (near infrared spectroscopy), which identifies lipid loaded plaques and is tested currently in clinical trials. Non-invasive MRI (magnetic resonance imaging) and multislice spiral computed tomography (MSCT), with their excellent ability to identify lipid-rich tissue, have been utilized to characterize potentially vulnerable plaques foremost in non-moving structures like the carotid arteries. Due to the resolution of the techniques small plaque structure cannot be assessed. The role of non-invasive imaging in vulnerable plaque detection is currently under investigation. Several invasive and non-invasive techniques are currently under development to assess the vulnerable plaque. Most of the techniques show exiting features, but none have proven their value in an extensive in vivo validation and all have a lack of prospective data.

Little information is available on the specific role of alveolar macro- phages (AMs) in modulating local cellular reactions to inhaled allergens in atopic asthma. We investigated the influence of alveolar macrophages obtained by bronchoalve- olar lavage (BAL) on the proliferative responses of lavage and peripheral lympho- cytes from 12 patients with atopic asthma, 6 nonasthmatic symptomatic atopic subjects, and 6 nonatopic normal volunteers, in the context of in vitro exposure to relevant and nonrelevant allergens. Fresh nonadherent bronchoalveolar lavage cells from atopic asthmatic patients, depleted of alveolar macrophages, proliferated spontaneously more than nonad- herent bronchoalveolar lavage cells from normal subjects. Addition of autologous asthmatic alveolar macrophages reduced this endogenous activation. Asthmatic and normal alveolar macrophages also inhibited phytohaemagglutinin-stimulated proliferation of both autologous and allogeneic nonadherent peripheral blood mono- nuclear cells (PBMC). In contrast, autologous asthmatic alveolar macrophages induced strong proliferation of peripheral blood mononuclear cells when stimula- ted with allergen to which the patient was skin test and radio allergosorbent test (RAST) reactive; however, no response was seen with allergens to which the patient was insensitive. No such allergen-specific proliferation was seen with alveolar macrophages from nonasthmatic atopic subjects. These data support the presence of functionally-active alveolar macrophages within the airways of atopic asthmatic patients, that under normal stable condi- tions suppress the induction of peripheral blood mononuclear cell responses, and which only on contact with specific allergen appear to switch to inducer alveolar macrophages, with consequent peripheral blood mononuclear cell hyperactiva- tion.

The role of shear stress in atherosclerosis has been well documented. However, its role in restenosis was underexposed. In this paper a novel in vivo measuring technique and several of its applications related to restenosis will be described. The technique consists of a combination of 3D reconstruction of blood vessels and computational fluid dynamics (CFD). The 3D imaging techniques use either of 3D intravascular ultrasound (IVUS) as a stand-alone technique or a fusion of biplane angiography and IVUS (ANGUS). CFD is applied in order to relate local shear stress distribution to the morphology of the vessel wall. In the applications of these techniques it will be demonstrated that shear stress plays a role in the prediction of neointimal formation in in-stent restenosis and in vascular remodeling after balloon angioplasty. Attempts to locally increase shear stress by a newly developed flow divider indicate that shear stress reduce in-stent neointimal formation by 50%.

Although transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk.We evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement.A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, -5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic-valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group.TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910 .).