279 LAYERED PLAQUES: NOT ALL ARE HEALED Ciardetti, Niccolò; Mattesini, Alessio; Di Muro, Francesca Maria ...
European heart journal supplements,
12/2022, Volume:
24, Issue:
Supplement_K
Journal Article
Peer reviewed
Open access
Abstract
Layered plaques are the effect of a previous plaque event. They are associated with coronary spasm and found in more than 50% of patients with stable angina and a quarter of those with an ...acute coronary syndrome. Nevertheless, it is not clear whether their presence is indicative of a healing process or rather is predictive of an increased risk of future events. A 71-year-old male, heavy smoker and hypertensive, presented with episodes of angina at rest that resolved spontaneously in less than 5 minutes, with evidence of ST-segment elevation (STE) in the lower leads during one of these episodes. Coronary angiography showed an intermediate stenosis at the end of the mid segment of the dominant right coronary artery (RCA) (Figure A). Optical coherence tomography (OCT) revealed a layered plaque, consisting of high backscattering layers alternated with low reflection layers (Figures A1-3). Given the minimum luminal area of 3.65 mm2 and the absence of other criteria for plaque instability (erosion, thin-cap, etc.), we treated the patient conservatively with medical therapy alone, consisting of a single antiplatelet agent and a high-dose statin with ezetimibe. A non-dihydropyridine calcium antagonist and a long-acting nitrate were started given the suspicion of coronary spasm. Four months later the patient returned to the emergency department for persistent oppressive chest pain unresponsive to sublingual nitrates with evidence of STE in the lower leads. Emergency coronary angiography showed an acute occlusion of RCA with TIMI 0 flow in correspondence to the layered plaque highlighted 4 months earlier on OCT (Figure B). Antegrade flow was restored with manual thrombus aspiration (Figure C) and OCT showed lesion progression with many new layers, together with a cavity suggestive of plaque rupture (Figures C1-3). A 3.5×38 mm everolimus eluting stent was deployed – based on OCT sizing – and post-dilated with a 4.0×8 mm non-compliant balloon, obtaining an excellent angiographic result with TIMI 3 flow (Figure D). Low-reflecting layers within layered plaques are generally considered to be lipid deposits, but they could also represent intraplaque haemorrhages, generated by coronary spasm. The haematoma can be reorganised within the plaque to create a new layer, leading to lesion progression without necessarily requiring a loss of endothelial integrity. The progressive increase of the haematoma may lead to plaque rupture when the pressure exceeds the resistance of superficial layers. This case reveals a new possible mechanism of plaque progression in patients with coronary spasm and explains how layered plaques can be ambivalently considered to be either stable or vulnerable. Their treatment should be meticulously tailored not only based on classical criteria of plaque instability but also according to the underlying trigger mechanism.
Abstract
Transcatheter aortic valve implantation (TAVI) has emerged as an alternative treatment for symptomatic severe aortic stenosis in patients deemed to be at high operative risk for the surgery. ...Despite its high success, TAVI is associated with rare life-threatening complications. The frequency of aortic annular rupture (AAR) has been reduced by advances in pre-procedural screening and patient selection but, when occurs, often requires emergency surgery with a very high mortality. We described an unusual case managed conservatively.
A 86-year-old female patient with NYHA Class III and STS score for mortality of 4.8% underwent TAVI via a transfemoral approach. At preprocedural MDCT the aortic annular area was 293 mm2 with severe calcification of the valve leaflets extending in the outflow tract and in the sinotubular junction with effacement of the coronary sinuses (Fig. 1A-B). Following deployment of a 23-mm self-expanding valve (Medtronic Evolut Pro+) without predilatation, moderate-to-severe residual aortic regurgitation (AR) was observed (Vid. 1). After balloon post-dilatation using a 20×40mm noncompliant (NC) OSYPKA - VACS III balloon, mild-to-moderate AR still persisted (Fig. 1C, Vid. 2). Accordingly, we decided to perform a second post-dilatation using a 22×40mm NC balloon which reduced AR to mild but caused a contained AAR was observed (Fig. D&E, Vid. 3). The patient remained hemodynamically stable with no chest pain and had no pericardial effusion on echo. The risk of a Bentall operation in such a frail elderly patient was judged prohibitive and a conservative strategy was recommended. Postprocedural MDCT confirmed the presence of a pseudoaneurysm with the maximum dimensions of 24×15 mm (Fig. 1F). Patient was followed-up for 23 days first in hospital keeping a low blood pressure with iv nitrates and then in a rehabilitation centre. An MDCT control on day 10 showed no growth of the pseudoaneurysm with a reduction of the brisk filling initially observed. She was discharged without additional problems, and scheduled for a three month control MDCT.
Established risk factors for AAR include valve and balloon oversizing, bicuspid valve, small annulus, shallow Valsalva sinuses, and massive annular or sub/supra-annular calcification. When these recognized risk factors are present, a conservative strategy for valve postdilatation is strongly recommended. Early recognition and prompt surgical management of AAR are essential but occasionally also a conserative strategy can prove successful.
Network infrastructure must support emerging applications, fulfill 5G requirements, and respond to the sudden increase of societal need for remote communications. Remarkably, crowdsourced live video ...streaming (CLVS) challenges operators’ infrastructure with tides of users attending major sport or public events that demand high bandwidth and low latency jointly with computing capabilities at the networks’ edge. The Metro-Haul project entered the scene proposing a cost-effective, agile, and disaggregated infrastructure for the metro segment encompassing optical and packet resources jointly with computing capabilities. Recently, a major Metro-Haul outcome took the form of a field trial of network function virtualization (NFV) orchestration over the multi-layer packet and disaggregated optical network testbed that demonstrated a CLVS use case. We showcased the average service creation time below 5 min, which met the key performance indicator as defined by the 5G infrastructure public private partnership. In this paper, we expand our field trial demonstration with a detailed view of the Metro-Haul testbed for the CLVS use case, the employed components, and their performance. The throughput of the service is increased from approximately 9.6 Gbps up to 35 Gbps per virtual local area network with high-performance VNFs based on single-root input/output virtualization technology.
To compare US Food and Drug Administration (FDA) and European Medicines Agency (EMA) labeling for evidence based on patient-reported outcomes (PROs) of new oncology treatments approved by both ...agencies.
Oncology drugs and indications approved between 2012 and 2016 by both the FDA and the EMA were identified. PRO-related language and analysis reported in US product labels and drug approval packages and EMA summaries of product characteristics were compared for each indication.
In total, 49 oncology drugs were approved for a total of 64 indications. Of the 64 indications, 45 (70.3%) included PRO data in either regulatory submission. No FDA PRO labeling was identified. PRO language was included in the summary of product characteristics for 21 (46.7%) of 45 indications. European Organisation for Research and Treatment of Cancer and Functional Assessment of Cancer Therapy measures were used frequently in submissions. FDA’s comments suggest that aspects of study design (eg, open labels) or the validity of PRO measures was the primary reason for the lack of labeling based on PRO endpoints. Both agencies identified missing PRO data as problematic for interpretation.
During this time period, the FDA and the EMA used different evidentiary standards to assess PRO data from oncology studies, with the EMA more likely to accept data from open-label studies and broad concepts such as health-related quality of life. An understanding of the key differences between the agencies may guide sponsor PRO strategy when pursuing labeling. Patient-focused proximal concepts are more likely than distal concepts to receive positive reviews.
•In recent years, the Food and Drug Administration (FDA) has granted patient-reported outcome (PRO) labeling to very few oncology drugs.•The FDA and the European Medicines Agency (EMA) use different evidentiary standards to assess PRO data from oncology studies. PRO labeling by the EMA was frequently based on open-label studies, on broad concepts such as health-related quality of life, and on PRO measures that may be outdated and unsuitable for contemporary oncology clinical trials.•There are key differences in evidentiary standards between the FDA and the EMA. An understanding of these differences may be useful to guide PRO measurement strategies as study sponsors pursue PRO labeling. Sponsors pursuing labeling from both agencies should include in clinical trials PRO measures that assess patient-focused proximal concepts of core disease symptoms, treatment-related symptoms, and impacts on physical functioning. The addition of health-related quality-of-life assessments may also be useful for EMA reviews.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Identify disease categories in which single-item global impression (GI) scales were included in product labeling of new drugs approved by the US Food and Drug Administration (FDA) in January ...2009-December 2019 and review the characteristics of GIs included in product labeling of new FDA-approved drugs (January 2017-December 2019).
FDA Clinical Outcome Assessment (COA) Compendium was reviewed for drug labels that included GIs for drugs approved in 2009-2016. The indication, year of approval, ICD-10 code, and GI respondent were noted. A manual review of labels of FDA-approved drugs (2017-2019) was undertaken to identify GIs included in the labels. Corresponding drug approval packages were reviewed to identify details of any regulatory reviewer comments related to GIs. GI characteristics were noted from the drug label or the review documents, including the respondent, type of measure (static or dynamic), item wording, concept assessed, and response options.
Product labeling containing GIs was most common in diseases related to the skin, nervous system, behavioral disorders, and the musculoskeletal system. GIs were included in 30/77 (39.0%) drug labels in the four disease categories.
In the past 10 years, GIs have been included as endpoint measures in confirmatory clinical trials and have generated evidence of treatment benefit in diseases related to the skin, nervous system, behavioral disorders, and the musculoskeletal system. GIs frequently provide important insights into the patient experience. Before GIs are included in clinical trials to assess treatment benefit, it is important to ensure that they are valid, reliable, and responsive.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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