Is the Adenosine Test Obsolete in the Clinical Assessment of Syncope of Unknown Origin?

Syncope is a common clinical condition affecting 50% of the general population; however, its exact pathophysiology and underlying mechanisms remain elusive. The adenosine test (ADT) has been proposed as a complementary diagnostic test in the work-up of syncope of unknown origin aiming to further elucidate the underlying pathogenetic mechanism of spontaneous syncope. Although ADT has not been endorsed by the recent European Society of Cardiology guidelines on syncope management, the use of a quick, safe and non-invasive test which can contribute to an accurate diagnosis and rationalised therapy, may deserve further consideration. This review summarises the evidence on the role of ADT in the investigation and management of syncope of unknown origin and highlights future perspectives in this area. The authors also analyse the current challenges and research targets on adenosine plasma levels and its receptors due to the involvement of the adenosine pathway in the ADT response

Adult Congenital Heart Disease Investigated with Cardiac Catheterization Over A 20-Year Period

BACKGROUND: Recent advances in diagnosis and treatment have increased the life expectancy of patients with congenital heart disease. METHODS: To investigate the prevalence of adult congenital heart disease (ACHD) in a large registry of patients over a 20-year period, we retrospectively assessed data of 14,012 males and 4,461 females who underwent clinically indicated cardiac catheterization from 1984 to 2003. RESULTS: ACHD was recorded in 234 subjects aged from 18 to 66 years, [95 males (40.7%) and 139 females (59.3%)]. Females were more likely to present with ACHD than males (p<0.001). Atrial septal defect was the most common defect (43.3%) followed by partial anomalous pulmonary venous return (12.0%), pulmonary valve stenosis (11.3%) ventricular septal defect (8.0%), coarctation of aorta (5.5%) patent ductus arteriosus (4.0%) and Fallot's tetralogy (3.3%). Atrial septal defect was more common in females (p<0.01), while pulmonary valve stenosis was more frequent in males (p<0.05). No difference across sexes was found in the other forms of ACHD. Females with ACHD were significantly older than males at the time of catheterization (median age 41 years, interquartile range 26 to 53 years vs. median age 35 years, interquartile range 22 to 48 years, p<0.05). CONCLUSIONS: In adulthood ACHD is found more commonly in females and is diagnosed later in life than in males. Atrial septal defect is the most prevalent form of ACHD and occurs most commonly in females

The impact of hydraulic retention time on the performance of two configurations of anaerobic pond for municipal sewage treatment

Anaerobic ponds have the potential to contribute to low carbon wastewater treatment, however are currently restricted by long hydraulic residence time (HRT) which leads to large land requirements. A two-stage anaerobic pond (SAP) design was trialled against a single-stage control (CAP) over four HRTs down to 0.5 days, to determine the lowest HRT at which the ponds could operate effectively. No statistical differences were observed in particulate removal between the ponds over all four HRTs, suggesting solids loading is not a critical factor in AP design. Significantly higher biogas production rates were observed in the SAP than the CAP at 1.5 d and 1.0 d HRT, and microbial community profiling suggests the two-stage design may be facilitating spatial separation of the anaerobic digestion process along reactor length. Hydrogenotrophic methanogensis dominated over aceticlastic, with acetate oxidisation a likely degradation pathway. Experimental tracer studies were compared to CFD simulations, with the SAP showing greater hydraulic efficiency, and differences more pronounced at shorter HRTs. Greater flow recirculation between baffles was observed in CFD velocity profiles, demonstrating baffles can dissipate preferential flow patterns and increase effective pond volume, especially at high flow rates. The study demonstrates the potential of APs to be operated at shorter HRTs in psychrophilic conditions, presenting an opportunity for use as pre-treatments (in place of septic tanks) and primary treatment for full wastewater flows. Two-stage designs should be investigated to separate the stages of the anaerobic digestion process by creating preferential conditions along the pond length

Clinical validation of an algorithm for rapid and accurate automated segmentation of intracoronary optical coherence tomography images

Objectives: The analysis of intracoronary optical coherence tomography (OCT) images is based on manual identification of the lumen contours and relevant structures. However, manual image segmentation is a cumbersome and time-consuming process, subject to significant intra- and inter-observer variability. This study aims to present and validate a fully-automated method for segmentation of intracoronary OCT images. Methods: We studied 20 coronary arteries (mean length = 39.7 ± 10.0 mm) from 20 patients who underwent a clinically-indicated cardiac catheterization. The OCT images (n = 1812) were segmented manually, as well as with a fully-automated approach. A semi-automated variation of the fully-automated algorithm was also applied. Using certain lumen size and lumen shape characteristics, the fully- and semi-automated segmentation algorithms were validated over manual segmentation, which was considered as the gold standard. Results: Linear regression and Bland–Altman analysis demonstrated that both the fully-automated and semiautomated segmentation had a very high agreement with the manual segmentation, with the semi-automated approach being slightly more accurate than the fully-automated method. The fully-automated and semiautomated OCT segmentation reduced the analysis time by more than 97% and 86%, respectively, compared to manual segmentation. Conclusions: In the current work we validated a fully-automated OCT segmentation algorithm, as well as a semiautomated variation of it in an extensive “real-life” dataset of OCT images. The study showed that our algorithm can perform rapid and reliable segmentation of OCT images

Thin-Capped Atheromata With Reduced Collagen Content in Pigs Develop in Coronary Arterial Regions Exposed to Persistently Low Endothelial Shear Stress

Objective—The mechanisms promoting the focal formation of rupture-prone coronary plaques in vivo remain incompletely understood. This study tested the hypothesis that coronary regions exposed to low endothelial shear stress (ESS) favor subsequent development of collagen-poor, thin-capped plaques. Approach and Results—Coronary angiography and 3-vessel intravascular ultrasound were serially performed at 5 consecutive time points in vivo in 5 diabetic, hypercholesterolemic pigs. ESS was calculated along the course of each artery with computational fluid dynamics at all 5 time points. At follow-up, 184 arterial segments with previously identified in vivo ESS underwent histopathologic analysis. Compared with other plaque types, eccentric thin-capped atheromata developed more in segments that experienced lower ESS during their evolution. Compared with lesions with higher preceding ESS, segments persistently exposed to low ESS (<1.2 Pa) exhibited reduced intimal smooth muscle cell content; marked intimal smooth muscle cell phenotypic modulation; attenuated procollagen-I gene expression; increased gene and protein expression of the interstitial collagenases matrix-metalloproteinase-1, -8, -13, and -14; increased collagenolytic activity; reduced collagen content; and marked thinning of the fibrous cap. Conclusions—Eccentric thin-capped atheromata, lesions particularly prone to rupture, form more frequently in coronary regions exposed to low ESS throughout their evolution. By promoting an imbalance of attenuated synthesis and augmented collagen breakdown, low ESS favors the focal evolution of early lesions toward plaques with reduced collagen content and thin fibrous caps—2 critical determinants of coronary plaque vulnerability.Novartis (Firm)Boston Scientific CorporationBehrakis Foundation (Research Fellowship)Hellenic Heart FoundationHellenic Atherosclerosis SocietyNational Institutes of Health (U.S.) (Grant RO1 GM49039

Arterial Remodeling and Endothelial Shear Stress Exhibit Significant Longitudinal Heterogeneity Along the Length of Coronary Plaques

Atherosclerosis is determined by both systemic risk factors and local vascular mechanisms. The arterial remodeling in response to plaque development plays a key role in atherosclerosis. Compensatory expansive remodeling is an adaptive mechanism that maintains lumen patency as a plaque develops. In contrast, excessive expansive remodeling, signifying an enlargement in vascular and lumen volume as a result of local plaque buildup, is a consistent attribute of high-risk plaques. Local hemodynamic factors, in particular low endothelial shear stress (ESS), is an intensely proinflammatory and proatherogenic stimulus and largely accounts for the spatially diverse distribution of atherosclerotic plaques. However, plaque, remodeling and ESS have hitherto been investigated only in the cross-sectional arterial axis and their distribution in the longitudinal axis of individual plaques has not been characterized

Accurate and reproducible reconstruction of coronary arteries and endothelial shear stress calculation using 3D OCT: Comparative study to 3D IVUS and 3D QCA

Background: Geometrically-correct 3D OCT is a new imaging modality with the potential to investigate the association of local hemodynamic microenvironment with OCT-derived high-risk features. We aimed to describe the methodology of 3D OCT and investigate the accuracy, inter- and intra-observer agreement of 3D OCT in reconstructing coronary arteries and calculating ESS, using 3D IVUS and 3D QCA as references. Methods-Results: 35 coronary artery segments derived from 30 patients were reconstructed in 3D space using 3D OCT. 3D OCT was validated against 3D IVUS and 3D QCA. The agreement in artery reconstruction among 3D OCT, 3D IVUS and 3D QCA was assessed in 3-mm-long subsegments using lumen morphometry and ESS parameters. The inter- and intra-observer agreement of 3D OCT, 3D IVUS and 3D QCA were assessed in a representative sample of 61 subsegments (n ¼ 5 arteries). The data processing times for each reconstruction methodology were also calculated. There was a very high agreement between 3D OCT vs. 3D IVUS and 3D OCT vs. 3D QCA in terms of total reconstructed artery length and volume, as well as in terms of segmental morphometric and ESS metrics with mean differences close to zero and narrow limits of agreement (BlandeAltman analysis). 3D OCT exhibited excellent inter- and intra-observer agreement. The analysis time with 3D OCT was significantly lower compared to 3D IVUS. Conclusions: Geometrically-correct 3D OCT is a feasible, accurate and reproducible 3D reconstruction technique that can perform reliable ESS calculations in coronary arteries

Effects of Low Endothelial Shear Stress After Stent Implantation on Subsequent Neointimal Hyperplasia and Clinical Outcomes in Humans

Background: In‐stent hyperplasia (ISH) may develop in regions of low endothelial shear stress (ESS), but the relationship between the magnitude of low ESS, the extent of ISH, and subsequent clinical events has not been investigated. Methods and Results: We assessed the association of poststent ESS with neointimal ISH and clinical outcomes in patients treated with percutaneous coronary interventions (PCI). Three‐dimensional coronary reconstruction was performed in 374 post‐PCI patients at baseline and 6 to 10 months follow‐up as part of the PREDICTION Study. Each vessel was divided into 1.5‐mm‐long segments, and we calculated the local ESS within each stented segment at baseline. At follow‐up, we assessed ISH and the occurrence of a clinically indicated repeat PCI for in‐stent restenosis. In 246 total stents (54 overlapping), 100 (40.7%) were bare‐metal stents (BMS), 104 (42.3%) sirolimus‐eluting stents, and 42 (17.1%) paclitaxel‐eluting stents. In BMS, low ESS post‐PCI at baseline was independently associated with ISH (β=1.47 mm2 per 1‐Pa decrease; 95% CI, 0.38–2.56; P<0.01). ISH was minimal in drug‐eluting stents. During follow‐up, repeat PCI in BMS was performed in 21 stents (8.5%). There was no significant association between post‐PCI ESS and in‐stent restenosis requiring PCI. Conclusions: Low ESS after BMS implantation is associated with subsequent ISH. ISH is strongly inhibited by drug‐eluting stents. Post‐PCI ESS is not associated with in‐stent restenosis requiring repeat PCI. ESS is an important determinant of ISH in BMS, but ISH of large magnitude to require PCI for in‐stent restenosis is likely attributed to factors other than ESS within the stent