Publications

Coronary CT angiography (CCTA) demonstrated high diagnostic accuracy for detecting coronary artery disease (CAD) and a key role in the management of patients with low-to-intermediate pretest likelihood of CAD. However, the clinical information provided by this noninvasive method is still regarded insufficient in patients with diffuse and complex CAD and for planning percutaneous coronary intervention (PCI) and surgical revascularization procedures. On the other hand, technology advancements have recently shown to improve CCTA diagnostic accuracy in patients with diffuse and calcific stenoses. Moreover, stress CT myocardial perfusion imaging (CT-MPI) and fractional flow reserve derived from CCTA (CT-FFR) have been introduced in clinical practice as new tools for evaluating the functional relevance of coronary stenoses, with the possibility to overcome the main CCTA drawback, i.e. anatomical assessment only. The potential value of CCTA to plan and guide interventional procedures lies in the wide range of information it can provide: a) detailed evaluation of plaque extension, volume and composition; b) prediction of procedural success of CTO PCI using scores derived from CCTA; c) identification of coronary lesions requiring additional techniques (e.g., atherectomy and lithotripsy) to improve stent implantation success by assessing calcium score and calcific plaque distribution; d) assessment of CCTA-derived Syntax Score and Syntax Score II, which allows to select the mode of revascularization (PCI or CABG) in patients with complex and multivessel CAD. The aim of this Consensus Document is to review and discuss the available data supporting the role of CCTA, CT-FFR and stress CT-MPI in the preprocedural and possibly intraprocedural planning and guidance of myocardial revascularization interventions.

Background Procedural technique may affect clinical outcomes after bioresorbable vascular scaffold (BVS) implantation. Prior studies suggesting such a relationship have not adjusted for baseline patient and lesion characteristics that may have influenced operator choice of technique and outcomes. Objectives This study sought to determine whether target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) and scaffold thrombosis (ScT) rates within 3 years of BVS implantation are affected by operator technique (vessel size selection and pre- and post-dilation parameters). Methods TLF and ScT rates were determined in 2,973 patients with 3,149 BVS-treated coronary artery lesions from 5 prospective studies (ABSORB II, ABSORB China, ABSORB Japan, ABSORB III, and ABSORB Extend). Outcomes through 3 years (and between 0 to 1 and 1 to 3 years) were assessed according to pre-specified definitions of optimal technique (pre-dilation, vessel sizing, and post-dilation). Multivariable analysis was used to adjust for differences in up to 18 patient and lesion characteristics. Results Optimal pre-dilation (balloon to core laboratory-derived reference vessel diameter ratio ≥1:1), vessel size selection (reference vessel diameter ≥2.25 mm and ≤3.75 mm), and post-dilation (with a noncompliant balloon at ≥18 atm and larger than the nominal scaffold diameter, but not by >0.5 mm larger) in all BVS-treated lesions were performed in 59.2%, 81.6%, and 12.4% of patients, respectively. BVS implantation in properly sized vessels was an independent predictor of freedom from TLF through 1 year (hazard ratio [HR]: 0.67; p = 0.01) and through 3 years (HR: 0.72; p = 0.01), and of freedom from ScT through 1 year (HR: 0.36; p = 0.004). Aggressive pre-dilation was an independent predictor of freedom from ScT between 1 and 3 years (HR: 0.44; p = 0.03), and optimal post-dilation was an independent predictor of freedom from TLF between 1 and 3 years (HR: 0.55; p = 0.05). Conclusions In the present large-scale analysis from the major ABSORB studies, after multivariable adjustment for baseline patient and lesion characteristics, vessel sizing and operator technique were strongly associated with BVS-related outcomes during 3-year follow-up. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281; ABSORB III Randomized Controlled Trial [RCT] [ABSORB-III]; NCT01751906; A Clinical Evaluation of Absorb Bioresorbable Vascular Scaffold [Absorb BVS] System in Chinese Population—ABSORB CHINA Randomized Controlled Trial [RCT] [ABSORB CHINA]; NCT01923740; ABSORB EXTEND Clinical Investigation [ABSORB EXTEND]; NCT01023789; AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284)

Endogenous vasodilators such as endothelially derived relaxant factor have been shown to modulate hypoxic pulmonary vasoconstriction. Sensory peptides such as substance P (SP) and calcitonin gene related peptide (CGRP) are also potent pulmonary vasodilators in both animals and humans. Their possible role in the modulation of the normal hypoxic pressor response has been examined in an isolated, ventilated, and blood perfused rat lung preparation.Animals (n = 7) were pretreated with 50 mg/kg capsaicin administered subcutaneously to deplete nerve endings of sensory neuropeptides. A control group (n = 7) received a subcutaneous dose of capsaicin vehicle. One week later the rats were killed and the rise in pulmonary artery pressure was measured during four successive periods of hypoxic ventilation (FIO2 0.03), and after four injections of angiotensin II (1.0 microgram).A 60% depletion of SP levels was measured in the sciatic nerves of animals treated with capsaicin. The hypoxic pressor response was not significantly altered in capsaicin treated animals compared with controls, except during the fourth hypoxic episode when it was augmented. The angiotensin II pressor response was the same in both groups during each of the injections.The sensory neuropeptide SP (and possibly CGRP) does not have a major role in modulating the pulmonary vascular response to hypoxia.

In the design of clinical trials we strive to extract the maximum amount of information from a minimum number of patients and vet retain statistical validity. Matching has become acknowledged as a useful and valid surrogate for the randomized trial. By using data from matched trials along with power calculations we can accurately predict the number of patients required to achieve statistical significance in a related randomized trial. (J Interven Cardiol 1994; 7:581–585)

BackgroundSmall airways dysfunction and inflammation contribute significantly to the clinical impact of asthma, yet conventional methods of assessing airways function in the clinic cannot reliably evaluate its presence. However, most recently, promising methods of assessment are being utilised.MethodsWe conducted a systematic literature review, using PubMed, with the aim of determining the prevalence of small airways disease in adult patients with asthma. We ascertained how small airways disease prevalence compared between different studies when measured using distinct techniques of small airways assessment.ResultsFifteen publications were identified determining the prevalence of small airways disease in asthma. Methods of assessments included impulse oscillometry, spirometry, body plethysmography, multiple-breath nitrogen washout, and high-resolution computed tomography. These studies used differing inclusion characteristics and recruited patients with a broad range of asthma severity, yet collectively they reported an overall prevalence of small airways disease of 50–60%. Small airways disease was present across all asthma severities, with evidence of distal airway disease even in the absence of proximal airway obstruction.ConclusionsSmall airways disease is highly prevalent in asthma, even in patients with milder disease. Given the clinical impact of small airways disease, its presence should not be underestimated or overlooked as part of the daily management of patients with asthma.

<h3>Background:</h3> Anecdotal evidence suggests that transcatheter aortic valve implantation (TAVI) is being used beyond pre-market label indications. <h3>Methods:</h3> To assess the frequency and outcomes associated with "off-label" use of TAVI, we conducted a retrospective study, examining adherence to patient selection criteria in 63 patients undergoing implantation with the 18F CoreValve ReValving System (CRS). Label status (on-label vs off-label) was determined by following (1) inclusion/exclusion criteria indicated in the 18F CRS safety and efficacy trial and (2) a patient selection matrix indicating anatomical boundaries to guide patient selection. Off-label use was defined as the presence of at least one exclusion criterion or "non-acceptable" criteria based on the patient selection matrix. <h3>Results:</h3> Off-label implantation was identified in 42 patients (67%)—40% had one, 19% had two and 8% had three or more off-label criteria. Baseline demographics were similar between the groups except for a higher logistic EuroSCORE in the on-label group (19.8 (11.2) vs 14.5 (7.3), p = 0.029). There was no significant difference in the procedural success rates between the on-label and off-label groups (91% vs 95%, respectively, p = 0.47). The frequency of angiographic moderate-severe aortic regurgitation, post-implant dilatation or implantation of a second valve was also similar between the groups. At 30 days, the cumulative death rate was 10%; there were four deaths in the "on-label" and three deaths in the "off-label" group. <h3>Conclusion:</h3> In this study we found that "off-label" implantation of the CRS was common. Further studies are needed to evaluate the consequences of "label status" for patients undergoing TAVI.

Aims Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation.

No abstract is provided for this article.

DiSodium Cromoglycate (DSCG) has been used as an effective asthma therapy for over 50 years with a good clinical safety history but with poor pharmacokinetics. An analogue of DSCG with a more preferable profile could aid the development of novel asthma drugs, however, the mechanism of action is currently unknown. Previous pre-clinical data has linked the late asthmatic response (LAR) with activation of the Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel on airway sensory nerves¹ and DSCG has been shown to inhibit this response in clinical studies². Thus we hypothesised that the effectiveness of DSCG is via the modulation of sensory nerves. In a rat allergic model of asthma, DSCG inhibited the LAR. Using rat, guinea pig and human isolated vagal nerves and rat airway vagal ganglia cells it was shown that DSCG modulates TRPA1-driven nerve activation and calcium influx. DSCG is an agonist at the orphan G protein coupled receptor 35 (GPR35). TRPA1 and GPR35 are expressed in vagal ganglia cells therefore it was hypothesised that GPR35 is involved in the mechanism by which DSCG inhibits TRPA1 mediated sensory nerve activity. Utilising a range of GPR35 agonists and channel blockers we identified that this effect of DSCG was dependent on GPR35 via signalling through Gi and N-type calcium channels. Finally, using <i>in vivo</i> models we show that DSCG inhibition of airway nerve firing and LAR was attenuated by the GPR35 antagonist, ML 145. DSCG attenuates the TRPA1-mediated nerve-driven asthma symptoms via a direct action on sensory nerves through GPR35. Thus, GPR35 could be a novel, safe and effective target for the development of future asthma therapy. Raemdonck et al (2012) Thorax 67: 19 Howell &amp; Altounyan (1967) Lancet 2: 539.

The aim of this paper was to determine the incidence of bioresorbable vascular scaffold thrombosis.A systematic review of the published literature between October 2012 and August 2016 was performed using PubMed, Medline and Embase databases. Articles published in the English language that reported the rate of bioresorbable scaffold thrombosis according to Academic Research Consortium criteria were included. Titles and abstracts were screened independently by two authors and further evaluated and assessed for study details, population characteristics and scaffold thrombosis rates. Scaffold thrombosis rates were pooled with meta-analysis using a random effect model. Meta-regression was performed to explore the predictors of device thrombosis. Randomized clinical trials (RCT), observational registries and case series of patients with obstructive coronary artery disease treated with the ABSORB bioresorbable scaffolds (BVS) that reported the rate of definite or probable scaffold thrombosis and the time of the event after implantation (i.e., acute, sub-acute, late and very late) were selected.Overall, 16,830 patients treated with ABSORB BVS in 59 studies were included. A total of 256 definite or probable scaffold thrombosis (ScT) were identified and included in the present analysis. The overall rate of definite or probable ScT was 1.8% (CI 95% 1.5% to 2.0%) the median follow-up was 12.0 months (interquartile range 7.5 to 15). The rate of very late definite or probable ScT was 1.0% (95% CI 0.6% to 1.5%; 10 studies, 2331 patients). A higher rate of definite and probable scaffold thrombosis was found in studies with patients presenting with acute myocardial infarction (3.6% vs. 1.8%, Q=13.9, df=1, P=0.010). In the meta-regression analysis, the residual per cent diameter stenosis was the only factor associated with ST after scaffold implantation (coefficient 0.091, 95% CI -0.0009 to 0.183, P=0.052).Using the largest available dataset of patients treated in randomized trials and observational registries, the present meta-analysis shows that the overall rate of definite or probable ScT is 1.8%, with a rate of very late ST of 1.0%. Residual stenosis after scaffold implantation was associated with the occurrence of scaffold thrombosis.

Background The shear stress distribution assessment can provide useful insights for the hemodynamic performance of the implanted stent/scaffold. Our aim was to investigate the effect of a novel bioresorbable scaffold, Mirage on local hemodynamics in animal models. Method The main epicardial coronary arteries of 7 healthy mini‐pigs were implanted with 11 Mirage Microfiber sirolimus‐eluting Bioresorbable Scaffolds (MMSES). Optical coherence tomography (OCT) was performed post scaffold implantation and the obtained images were fused with angiographic data to reconstruct the coronary artery anatomy. Blood flow simulation was performed and Endothelial Shear Stress(ESS) distribution was estimated for each of the 11 scaffolds. ESS data were extracted in each circumferential 5‐degree subunit of each cross‐section in the scaffolded segment. The generalized linear mixed‐effect analysis was implemented for the comparison of ESS in two scaffold groups; 150‐µm strut thickness MMSES and 125‐µm strut thickness MMSES. Results ESS was significantly higher in MMSES (150 µm) [0.85(0.49–1.40) Pa], compared to MMSES (125 µm) [0.68(0.35–1.18) Pa]. Both MMSES (150 µm) and MMSES (125 µm) revealed low recirculation zone percentages per luminal surface area [3.17% ± 1.97% in MMSES (150 µm), 2.71% ± 1.32% in MMSES (125 µm)]. Conclusion Thinner strut Mirage scaffolds induced lower shear stress due to the small size vessels treated as compared to the thick strut version of the Mirage which was implanted in relatively bigger size vessels. Vessel size should be taken into account in planning BRS implantation. Small vessels may not get benefit from BRS implantation even with a streamlined strut profile. This pilot study warrants comparative assessment with commercially available bioresorbable scaffolds.

Drug eluting stents (DESs) made with biodegradable polymer have been developed in an attempt to improve clinical outcomes. However, the impact of biodegradable polymers on clinical events and stent thrombosis (ST) remains controversial.We searched Medline, the Cochrane Library and other internet sources, without language or date restrictions for articles comparing clinical outcomes between biodegradable polymer DES and durable polymer DES. Safety endpoints were ST (definite, definite/probable), mortality, and myocardial infarction (MI). Efficacy endpoints were major adverse cardiac event (MACE) and target lesion revascularization (TLR).We identified 15 randomized controlled trials (n = 17 068) with a weighted mean follow-up of 20.6 months. There was no statistical difference in the incidence of definite/probable ST between durable polymer- and biodegradable polymer- DES; relative risk (RR) 0.83; 95% confidence interval (CI) 0.62-1.11; P = 0.22. Biodegradable polymer DES had similar rates of definite ST (RR 0.94, 95% CI 0.66-1.33, P = 0.72), mortality (RR 0.94, 95% CI 0.82-1.09, P = 0.43), MI (RR 1.08, 95% CI 0.92-1.26. P = 0.35), MACE (RR 0.99, 95% CI 0.91-1.09, P = 0.85), and TLR (RR, 0.94, 95% CI 0.83-1.06, P = 0.30) compared with durable polymer DES. Based on the stratified analysis of the included trials, the treatment effect on definite ST was different at different follow-up times: ≤ 1 year favoring durable polymer DES and >1 year favoring biodegradable polymer DES.Biodegradable polymer DES has similar safety and efficacy for treating patients with coronary artery disease compared with durable polymer DES. Further data with longer term follow-up are warranted to confirm the potential benefits of biodegradable polymer DES.

Objectives We report on the procedural and six-month results of the first percutaneous and stand-alone study on myocardial repair with autologous skeletal myoblasts. Background Preclinical studies have shown that skeletal myoblast transplantation to injured myocardium can partially restore left ventricular (LV) function. Methods In a pilot safety and feasibility study of five patients with symptomatic heart failure (HF) after an anterior wall infarction, autologous skeletal myoblasts were obtained from the quadriceps muscle and cultured in vitro for cell expansion. After a culturing process, 296 ± 199 million cells were harvested (positive desmin staining 55 ± 30%). With a NOGA-guided catheter system (Biosense-Webster, Waterloo, Belgium), 196 ± 105 million cells were transendocardially injected into the infarcted area. Electrocardiographic and LV function assessment was done by Holter monitoring, LV angiography, nuclear radiography, dobutamine stress echocardiography, and magnetic resonance imaging (MRI). Results All cell transplantation procedures were uneventful, and no serious adverse events occurred during follow-up. One patient received an implantable cardioverter-defibrillator after transplantation because of asymptomatic runs of nonsustained ventricular tachycardia. Compared with baseline, the LV ejection fraction increased from 36 ± 11% to 41 ± 9% (3 months, p = 0.009) and 45 ± 8% (6 months, p = 0.23). Regional wall analysis by MRI showed significantly increased wall thickening at the target areas and less wall thickening in remote areas (wall thickening at target areas vs. 3 months follow-up: 0.9 ± 2.3 mm vs. 1.8 ± 2.4 mm, p = 0.008). Conclusions This pilot study is the first to demonstrate the potential and feasibility of percutaneous skeletal myoblast delivery as a stand-alone procedure for myocardial repair in patients with post-infarction HF. More data are needed to confirm its safety.