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Gas-chromatography hyphenated with low-resolution mass spectrometry is a very flexible tool for the cost-effective identification and quantification of volatile compounds in complex matrices. In some analytical fields, criteria for the agreement between retention time and mass spectra of the analyte in calibrators and samples are defined based on the general understanding of the performance of these parameters. However, since this harmonisation is not based on experimental performance observed for specific GC-MS conditions and analyte it leads to false identifications. This research proposes a novel and robust tool for defining statistically sound criteria for the identification of compounds by GC-MS and LC-MS using experimental data. The Monte Carlo Method (MCM) simulation of the correlated abundance of characteristic ions of analyte mass spectrum allows simulating the abundance ratio difference of the analyte in a calibrator and sample used for statistically sound identifications. The Cholesky decomposition of the covariance matrix of ion abundances for MCM simulations allows the reliable use of many ion abundance ratios in identifications. The developed methodology was implemented in a user-friendly Excel spreadsheet and applied to the identification of tear gas agents in tear gas sprays. Criteria defined by SANTE for identifying pesticide residues in foodstuffs were compared with the developed tool. The cross-validation of computational and SANTE tools allowed concluding that the statistical control of retention time and mass spectra performs according to the defined confidence level. On the other hand, the SANTE criteria can produce up to 92 % false identifications for being too strict considering signal dispersion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Exercise is an important physiological activity with several health benefits. In the setting of ischemic heart disease (IHD), the view toward exercise has greatly evolved throughout the years, concurrently to several major advances in the management of this complex entity. Currently, exercise training has broad applications across the IHD continuum as a powerful tool in its overall management, being a core component of comprehensive cardiac rehabilitation programs. Beyond this, exercise has also been incorporated as an integral part of contemporary methodologies aiming to provide diagnostic and prognostic data, such as cardiopulmonary exercise stress testing or stress echocardiography. In this article, we provide a pragmatic overview concerning the role of exercise in IHD, with a focus on its incorporation in cardiac rehabilitation frameworks, while also discussing some of the challenges and unmet needs concerning these interventions., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society.)

Objectives: To develop and share a deep learning method that can accurately identify optimal inversion time (TI) from multi-vendor, multi-institutional and multi-field strength inversion scout (TI scout) sequences for late gadolinium enhancement cardiac MRI., Materials and Methods: Retrospective multicentre study conducted on 1136 1.5-T and 3-T cardiac MRI examinations from four centres and three scanner vendors. Deep learning models, comprising a convolutional neural network (CNN) that provides input to a long short-term memory (LSTM) network, were trained on TI scout pixel data from centres 1 to 3 to identify optimal TI, using ground truth annotations by two readers. Accuracy within 50 ms, mean absolute error (MAE), Lin's concordance coefficient (LCCC) and reduced major axis regression (RMAR) were used to select the best model from validation results, and applied to holdout test data. Robustness of the best-performing model was also tested on imaging data from centre 4., Results: The best model (SE-ResNet18-LSTM) produced accuracy of 96.1%, MAE 22.9 ms and LCCC 0.47 compared to ground truth on the holdout test set and accuracy of 97.3%, MAE 15.2 ms and LCCC 0.64 when tested on unseen external (centre 4) data. Differences in vendor performance were observed, with greatest accuracy for the most commonly represented vendor in the training data., Conclusion: A deep learning model was developed that can identify optimal inversion time from TI scout images on multi-vendor data with high accuracy, including on previously unseen external data. We make this model available to the scientific community for further assessment or development., Clinical Relevance Statement: A robust automated inversion time selection tool for late gadolinium-enhanced imaging allows for reproducible and efficient cross-vendor inversion time selection., Key Points: • A model comprising convolutional and recurrent neural networks was developed to extract optimal TI from TI scout images. • Model accuracy within 50 ms of ground truth on multi-vendor holdout and external data of 96.1% and 97.3% respectively was achieved. • This model could improve workflow efficiency and standardise optimal TI selection for consistent LGE imaging., (© 2024. The Author(s).)

Objectives: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone., Methods: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis., Results: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities., Conclusion: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone., Clinical Relevance Statement: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic., Key Points: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders., (© 2023. The Author(s).)

The cardiovascular response to exercise has long been a focus of interest. Over a century ago, the first descriptions of electrocardiographic changes occurring during exercise highlighted the possible relevance of this dynamic assessment. In this background, the inception of the Bruce protocol circa 60 years ago allowed for a major leap in this field by providing a standardized framework with which to address this issue, by means of an integrated and structured methodology. Since then, exercise stress testing with electrocardiographic monitoring (ExECG) has become one of the most widely appraised tests in cardiovascular medicine. Notably, past few decades have been profoundly marked by substantial advances in the approach to cardiovascular disease, challenging prior notions concerning both its physiopathology and overall management. Among these, the ever-evolving presentations of cardiovascular disease coupled with the development and implementation of several novel diagnostic modalities (both invasive and noninvasive) has led to a shifting paradigm in the application of ExECG. This technique, however, has continuously shown to be of added value across various momentums of the cardiovascular continuum, as depicted in several contemporary guidelines. This review provides a pragmatical reflexion on the development of ExECG, presenting a comprehensive overview concerning the current role of this modality, its challenges, and its future perspectives., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society.)

Mitral annular disjunction (MAD) is an easily identifiable entity on transthoracic echocardiography, but is still poorly recognized or ignored. It is often associated with mitral valve prolapse and is itself a risk marker for ventricular arrhythmias and sudden cardiac death, but the management and risk stratification of these patients is not systematized. Two clinical cases of MAD associated with mitral valve prolapse and ventricular arrhythmias are presented. The first case is of a patient with a history of surgical intervention on the mitral valve due to Barlow's disease. He presented to the emergency department with sustained monomorphic ventricular tachycardia requiring emergent electrical cardioversion. MAD with transmural fibrosis at the level of the inferolateral wall was documented. The second report is of a young woman with palpitations and frequent premature ventricular contractions on Holter with documentation of valvular prolapse and MAD, and focuses on the risk stratification approach. The present article offers a review of the literature regarding the arrhythmic risk of MAD and mitral valve prolapse, as well as a review of risk stratification in these patients., (Copyright © 2023. Publicado por Elsevier España, S.L.U.)

The telehealth sector of health care delivery experienced significant growth at the start of the pandemic as web-based care quickly became essential for the ongoing safety of patients and health care providers, such as clinicians and other health care professionals. After vaccines were introduced, however, telehealth companies lost value as the need for web-based care appeared to lessen. Presently, both existing telehealth companies and new entrants to the space are seeking ways to innovate, gain investor and customer buy-in, and overcome competitors. New companies are hoping to be seen not as pandemic-era substitutes, but instead as reinforcements to in-person care, valuable in their own right thanks to the convenience and technological advancements they bring. This struggle to reframe the value proposition, or perceived benefit, of telehealth is reflected in fluctuating stock prices and dropping valuations. This viewpoint summarizes the market volatility seen in the telehealth sector since the start of the COVID-19 pandemic and suggests potential opportunities for growth in the space. This is accomplished through a qualitative secondary research approach, leveraging contemporary sources, financial references such as Yahoo! Finance, and peer-reviewed literature to support predictions for the future market. We found that, in 2020, the size of the US telehealth market rose to US $17.9 billion and is estimated to reach US $140.7 billion by 2030. Additionally, digital health venture funding nearly doubled in 2020 over the prior 2 years with total funding rising to US $14.1 billion. However, these factors produced an oversaturated market in which the volume of supply was higher than demand, resulting in a sharp drop in valuations for some as vaccination rates climbed in 2021. In the face of this rebalancing, or return to normal following excessively high or unsustainable valuations, we suggest a possible path forward for telehealth companies in the postpandemic era. Suppliers' current role in the telehealth space-whether health care industry incumbents, that is, traditional health care delivery systems and companies, or "telehealth-first" challengers-are especially relevant to the specific growth strategies they should pursue. Furthermore, consideration of the areas of medicine and characteristics that best lend themselves to web-based care may lead to a greater chance for long-term success in a postpandemic health care delivery system. In the future, we believe investors should expect a bullish market, that is, one characterized by growing share prices. Success is likely to occur in part through changing the actual models of care, as opposed to moving traditional care to a web-based format. The oversaturated market will likely condense into select established telehealth giants who were able to adapt to the changing landscape. While investors may be reasonably hesitant regarding individual telehealth companies, the industry can expect slowed but continued growth., (©Nicholas Bettencourt, Conor John Wilson, Philippa Jaye Johnson, Fabian D'Souza. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.07.2023.)

Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH ( n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients.

We report the case of a 17-year-old athlete who resorted to the emergency department for palpitations and dizziness while exercising. He mentioned two exercise-associated episodes of syncope in the last six months. He was tachycardic and hypotensive. The electrocardiogram showed regular wide complex tachycardia, left bundle branch block morphology with superior axis restored to sinus rhythm after electrical cardioversion. In sinus rhythm, it showed T-wave inversion in V1-V5. Transthoracic echocardiography revealed mild dilation and dysfunction of the right ventricle (RV) with global hypocontractility. Cardiac magnetic resonance (CMR) revealed a RV end diastolic volume indexed to body surface area of 180 ml/m 2 , global hypokinesia and RV dyssynchrony, subepicardial late enhancement in the distal septum and in the middle segment of the inferoseptal wall. The patient underwent a genetic study which showed a mutation in the gene that encodes the desmocolin-2 protein (DSC-2), which is involved in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC). According to the modified Task Force Criteria for this diagnosis, the patient presented four major criteria for ARVC. Thus, a subcutaneous cardioverter was implanted, and the patient was followed up at the cardiology department. Arrhythmogenic right ventricular cardiomyopathy diagnosis is based on structural, functional, electrophysiological and genetic criteria reflecting underlying histological changes. This case depicts the essential characteristics for disease recognition., (Copyright © 2022 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Amyloidosis is a systemic disease, characterized by deposition of amyloid fibrils in various organs, including the heart. For the diagnosis of cardiac amyloidosis (CA) it is required a high level of clinical suspicion and in the presence of clinical, laboratorial, and electrocardiographic red flags, a comprehensive multimodality imaging evaluation is warranted, including echocardiography, magnetic resonance, scintigraphy, and computed tomography, that will confirm diagnosis and define the CA subtype, which is of the utmost importance to plan a treatment strategy. We will review the use of multimodality imaging in the evaluation of CA, including the latest applications, and a practical flow-chart will sum-up this evidence., (© 2022 Wiley Periodicals LLC.)

Objectives: To develop an image-based automatic deep learning method to classify cardiac MR images by sequence type and imaging plane for improved clinical post-processing efficiency., Methods: Multivendor cardiac MRI studies were retrospectively collected from 4 centres and 3 vendors. A two-head convolutional neural network ('CardiSort') was trained to classify 35 sequences by imaging sequence (n = 17) and plane (n = 10). Single vendor training (SVT) on single-centre images (n = 234 patients) and multivendor training (MVT) with multicentre images (n = 434 patients, 3 centres) were performed. Model accuracy and F1 scores on a hold-out test set were calculated, with ground truth labels by an expert radiologist. External validation of MVT (MVT external ) was performed on data from 3 previously unseen magnet systems from 2 vendors (n = 80 patients)., Results: Model sequence/plane/overall accuracy and F1-scores were 85.2%/93.2%/81.8% and 0.82 for SVT and 96.1%/97.9%/94.3% and 0.94 MVT on the hold-out test set. MVT external yielded sequence/plane/combined accuracy and F1-scores of 92.7%/93.0%/86.6% and 0.86. There was high accuracy for common sequences and conventional cardiac planes. Poor accuracy was observed for underrepresented classes and sequences where there was greater variability in acquisition parameters across centres, such as perfusion imaging., Conclusions: A deep learning network was developed on multivendor data to classify MRI studies into component sequences and planes, with external validation. With refinement, it has potential to improve workflow by enabling automated sequence selection, an important first step in completely automated post-processing pipelines., Key Points: • Deep learning can be applied for consistent and efficient classification of cardiac MR image types. • A multicentre, multivendor study using a deep learning algorithm (CardiSort) showed high classification accuracy on a hold-out test set with good generalisation to images from previously unseen magnet systems. • CardiSort has potential to improve clinical workflows, as a vital first step in developing fully automated post-processing pipelines., (© 2022. The Author(s).)

Aims: Epicardial adipose tissue (EAT) volume and attenuation on computed tomography (CT) have been associated with atrial fibrillation. Beyond these conventional CT measures, radiomics allows extraction of high-dimensional data and deep quantitative adipose tissue phenotyping, which may capture its underlying biology. We aimed to explore the EAT proteomic and CT-radiomic signatures associated with impaired left atrial (LA) remodelling and post-operative atrial fibrillation (POAF)., Methods and Results: We prospectively included 132 patients with severe aortic stenosis with no prior atrial fibrillation referred for aortic valve replacement. Pre-operative non-contrast CT images were obtained for extraction of EAT volume and other radiomic features describing EAT texture. The LA function was assessed by 2D-speckle-tracking echocardiography peak atrial longitudinal strain and peak atrial contraction strain. The EAT biopsies were performed during surgery for proteomic analysis by sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS). The POAF incidence was monitored from surgery until discharge. Impaired LA function and incident POAF were associated with EAT up-regulation of inflammatory and thrombotic proteins, and down-regulation of cardioprotective proteins with anti-inflammatory and anti-lipotoxic properties. The EAT volume was independently associated with LA enlargement, impaired function, and POAF risk. On CT images, EAT texture of patients with POAF was heterogeneous and exhibited higher maximum grey-level values than sinus rhythm patients, which correlated with up-regulation of inflammatory and down-regulation of lipid droplet-formation EAT proteins. The CT radiomics of EAT provided an area under the curve of 0.80 (95% confidence interval: 0.68-0.92) for discrimination between patients with POAF and sinus rhythm., Conclusion: Pre-operative CT-radiomic profile of EAT detected adverse EAT proteomics and identified patients at risk of developing POAF., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD)., Purpose: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD., Methods: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard., Results: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000)., Conclusions: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD., Key Points: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease., (© 2022. The Author(s).)

Despite constant medical evolution, the reimbursement policy of Portuguese National Health Service (NHS) for the study and risk stratification of coronary heart disease has remained unchanged for several decades. Lack of adjustment to contemporary clinical practice has long been evident. However, the recent publication of the European Guidelines for diagnosis and treatment of chronic coronary syndromes further highlighted this gap and the urgent need for a change. Prompted by these Guidelines, the Working Group on Nuclear Cardiology, Cardiac Magnetic Resonance and Cardiac CT, the Working Group on Echocardiography and the Working Group on Stress Pathophysiology and Cardiac Rehabilitation of the Portuguese Society of Cardiology, began a process of joint reflection on the current limitations and how these recommendations could be applied in Portugal. To this end, the authors suggest that the new imaging methods (stress echocardiogram, cardiac computed tomography and cardiac magnetic resonance), should be added to exercise treadmill stress test and myocardial perfusion scintigraphy in the available exam portfolio within the Portuguese NHS. This change would allow full adoption of European guidelines and a better use of tests, according to clinical context, availability and local specificities. The adoption of clinical guidance standards, based on these assumptions, would translate into a qualitative improvement in the management of these patients and would promote an effective use of the available resources, with potential health and financial gains., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

The use of the unified pH concept, [Formula: see text] , applicable to aqueous and non-aqueous solutions, which allows interpreting and comparison of the acidity of different types of solutions, requires reliable and objective determination. The [Formula: see text] can be determined by a single differential potentiometry measurement referenced to an aqueous reference buffer or by a ladder of differential potentiometric measurements that allows minimisation of inconsistencies of various determinations. This work describes and assesses bottom-up evaluations of the uncertainty of these measurements, where uncertainty components are combined by the Monte Carlo Method (MCM) or Taylor Series Approximation (TSM). The MCM allows a detailed simulation of the measurements, including an iterative process involving in minimising ladder deviations. On the other hand, the TSM requires the approximate determination of minimisation uncertainty. The uncertainty evaluation was successfully applied to measuring aqueous buffers with pH of 2.00, 4.00, 7.00, and 10.00, with a standard uncertainty of 0.01. The reference and estimated values from both approaches are metrologically compatible for a 95% confidence level even when a negligible contribution of liquid junction potential uncertainty is assumed. The MCM estimated pH values with an expanded uncertainty, for the 95% confidence level, between 0.26 and 0.51, depending on the pH value and ladder inconsistencies. The minimisation uncertainty is negligible or responsible for up to 87% of the measurement uncertainty. The TSM quantified measurement uncertainties on average only 0.05 units larger than the MCM estimated ones. Additional experimental tests should be performed to test these uncertainty models for analysis performed in other laboratories and on non-aqueous solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Metabolic syndrome (MetS) affects one out of 3 adults in the western world and is associated with preclinical diastolic dysfunction that impairs functional capacity and quality of life (QoL). This randomized trial was designed to evaluate if the addition of metformin to the standard treatment of non-diabetic patients with MetS improves diastolic dysfunction., Methods: Prospective, randomized, open-label, blinded-endpoint trial. Fifty-four non-diabetic adults with MetS and diastolic dysfunction were randomized to lifestyle counseling or lifestyle counseling plus metformin (target dose 1000 mg bid). The primary endpoint was the change in mean e' velocity (assessed at baseline, 6, 12 and 24 months). Secondary endpoints were improvements in insulin resistance, functional capacity and QoL. Linear mixed effects modeling was used for longitudinal data analysis using modified intention-to-treat (mITT) and per-protocol (PP) approaches., Results: Forty-nine patients were included in the mITT analysis (mean age = 51.8 ± 6.4; 55% males). Metformin treatment was associated with a significant decrease in HOMA-IR. There was a significantly different mean change in e' velocity during the study period between trial arms, both in the mITT (at 24 months, change of +0.67 ± 1.90 cm/s in metformin arm vs. -0.33 ± 1.50 cm/s in control arm) and PP populations (+0.80 ± 1.99 cm/s in metformin arm vs. -0.37 ± 1.52 cm/s in control arm), using a random intercept linear mixed model. There were no significant differences in peak oxygen uptake and SF-36 scores between trial arms., Conclusions: Treatment with metformin of non-diabetic MetS patients with diastolic dysfunction, on top of lifestyle counseling, is associated with improved diastolic function.

Introduction and Objectives: In severe aortic stenosis (AS), the impact of aortic valve replacement (AVR) on left ventricular (LV) systolic function assessed by strain and measured by echocardiography or cardiac magnetic resonance (CMR) has been controversial. We aimed to investigate LV systolic myocardial function changes six months after AVR using global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain derived from CMR imaging., Methods: We included 39 severe AS patients (69.3±7.8 years; 61.5% male) with preserved LV ejection fraction (LVEF) who were recruited as part of the EPICHEART study and underwent successful AVR (aortic valvular area: 0.8 cm 2 (IQR: 0.2) pre- to 1.8 cm 2 (IQR:0.5) post-AVR). Structural and functional parameters were assessed at baseline and six months after AVR, including LV GRS, GCS and GLS analysis by CMR, using cine short-axial and two-, three-, and four-chamber long-axial view. Comparison between baseline and postoperative LV remodeling was performed using Student t-test and Wilcoxon test., Results: At six-month follow-up, LV mass, end-diastolic and end-systolic volumes, stroke volume, cardiac output, lateral E/e', tricuspid annular plane systolic excursion, right ventricular (RV) S wave velocity, GLS [-15.6% (IQR: 4.39) to -13.7% (IQR: 4.62)] and GCS [-17.8±3.58% to -16.1±2.94%] reduced significantly, while LVEF and GRS remained unchanged and lateral e' velocity increased., Conclusions: Despite favorable reverse LV structural and diastolic functional remodeling six months following AVR, GLS and GCS assessed by CMR reduced compared to baseline, LVEF remained unchanged. The clinical utility and timing of assessment of postoperative strain changes as a marker of systolic function progression needs further research., (Copyright © 2021 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Accumulation of epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD) and increased risk of coronary events in asymptomatic subjects and low-risk patients, suggesting that EAT promotes atherosclerosis in its early stage. Recent studies have shown that the presence of CAD affects the properties of adjacent EAT, leading to dynamic changes in the molecular players involved in the interplay between EAT and the coronary arteries over the history of the disease. The role of EAT in late-stage CAD has not been investigated., Objectives: In a comparative analysis with mediastinal and subcutaneous adipose tissue, we aim to investigate whether the volume of EAT assessed by computed tomography and its proteome assessed by SWATH-MS mass spectrometry are associated with late stages of CAD in an elderly cohort of severe aortic stenosis patients., Methods: The EPICHEART study (NCT03280433) is a prospective study enrolling patients with severe degenerative aortic stenosis referred for elective aortic valve replacement, whose protocol includes preoperative clinical, nutritional, echocardiographic, cardiac computed tomography and invasive coronary angiographic assessments. During cardiac surgery, samples of EAT and mediastinal and subcutaneous thoracic adipose tissue are collected for proteomics analysis by SWATH-MS. In addition, pericardial fluid and peripheral and coronary sinus blood samples are collected to identify circulating and local adipose tissue-derived biomarkers of CAD., Conclusion: We designed a translational study to explore the association of EAT quantity and quality with advanced CAD. We expect to identify new biochemical factors and biomarkers in the crosstalk between EAT and the coronary arteries that are involved in the pathogenesis of late coronary atherosclerosis, especially coronary calcification, which might be translated into new therapeutic targets and imaging tools by biomedical engineering., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

The differential diagnosis of true aneurysms and pseudoaneurysms is challenging, and multimodality cardiac imaging is often necessary. We report a case in which the limitations of these techniques are exposed, showing that post-operative evaluation of tissue layers remains the gold standard in establishing this diagnosis. ( Level of Difficulty: Beginner. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose. The authors confirm that written consent for submission and publication of this case report including images and associated text has been obtained from the patient in line with COPE guidance., (© 2021 The Authors.)

Septic cardiomyopathy is an increasingly relevant topic in clinical management of septic shock. However, pathophysiological mechanisms and long-term consequences of sepsis-induced myocardial injury are still poorly understood. Herein, new clinical and histological evidence is provided suggesting an association of myocardial edema formation with tissue injury and subsequent remodeling in septic shock patients. This preliminary data supports myocardial edema as a potentially relevant and largely unexplored mechanism of human septic cardiomyopathy.

The decision on the fitness of a measurement for its intended use and the interpretation of an analytical result requires the assessment of the measurement uncertainty. Frequently, the determination of analytes in complex matrices involves demanding sample preparations in which analyte losses are observed. These losses should be considered when reporting the results, which can be corrected for low recovery by taking the mean recovery observed in the analysis of reference items (e.g. spiked samples) or, alternatively, by subjecting calibrators to the same pre-treatment performed on the samples. In these cases, neat (NC) or adjusted (AC) calibrators are used, respectively. The way analyte losses are handled impacts on the measurement uncertainty. The top-down evaluation of the measurement uncertainty involves combining precision, trueness and additional uncertainty components. The trueness component is quantified by pooling various analyte recovery determinations. This work assesses and compares the uncertainty of polycyclic aromatic hydrocarbons (PAHs) measurements in water based on HPLC-FD calibrations with NC or AC. The trueness component is estimated by pooling mean recoveries observed from the analysis of different spiked samples to which mean recovery uncertainty and degrees of freedom are used to estimate a weighted mean recovery and respective uncertainty. The performance of measurements based on NC and AC are associated with equivalent uncertainty except when large analyte losses are observed, namely in the determination of Naphtalene. In this case, the processing of AC reduces the expanded relative uncertainty from 9.9% to 3.5%. The evaluated expanded uncertainty ranged from 3.5% to 12% of the measured value., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background & Aims: The role of epicardial adipose tissue (EAT) in the pathophysiology of late stage-coronary artery disease (CAD) has not been investigated. We explored the association of EAT volume and its proteome with advanced coronary atherosclerosis., Methods: The EPICHEART Study prospectively enrolled 574 severe aortic stenosis patients referred to cardiac surgery. Before surgery, EAT volume was quantified by computed tomography (CT). During surgery, epicardial, mediastinal (MAT) and subcutaneous (SAT) adipose tissue samples were collected to explore fat phenotype by analyzing the proteomic profile using SWATH-mass spectrometry; pericardial fluid and peripheral venous blood were also collected. CAD presence was defined as coronary artery stenosis ≥50% in invasive angiography and by CT-derived Agatston coronary calcium score (CCS)., Results: EAT volume adjusted for body fat was associated with higher CCS, but not with the presence of coronary stenosis. In comparison with mediastinal and subcutaneous fat depots, EAT exhibited a pro-calcifying proteomic profile in patients with CAD characterized by upregulation of annexin-A2 and downregulation of fetuin-A; annexin-A2 protein levels in EAT samples were also positively correlated with CCS. We confirmed that the annexin-A2 gene was overexpressed in EAT samples of CAD patients and positively correlated with CCS. Fetuin-A gene was not detected in EAT samples, but systemic fetuin-A was higher in CAD than in non-CAD patients, suggesting that fetuin-A was locally downregulated., Conclusions: In an elderly cohort of stable patients, CCS was associated with EAT volume and annexin-A2/fetuin-A signaling, suggesting that EAT might orchestrate pro-calcifying conditions in the late phases of CAD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The indirect identification of doping in sports can be performed by assessing athletes' hematological perturbations from the analysis of blood collected on different occasions. Because prosecution for doping based on this information requires expensive and time-consuming interpretation of blood analysis results by various expert hematologists, mathematical data screening is performed to decide which cases should be forwarded to hematologists. The current Bayesian and univariate screening of data does not process the multivariate trends of blood parameters or take the time interval between samplings into account. This work presents a computational tool that overcomes these limitations by calculating a single score, the hematological perturbation index (HP Ix ), for which a threshold is defined above which hematologists should be asked to assess the athlete's biological passport. The doping detection from this index, normalized for days difference between samplings based on 3, 4 or 5 consecutive samplings, is associated with true positive result rates (TP) not below 98% and false positive result rates (FP) less than 0.9%. Therefore, this tool can be useful as an early warning system of hematological perturbations to decide which athletes should be more closely monitored and which biological passports should be forwarded to hematologists for medical interpretation of data., Competing Interests: Authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: In patients with stable angina, two strategies are often used to guide revascularization: one involves myocardial-perfusion cardiovascular magnetic resonance imaging (MRI), and the other involves invasive angiography and measurement of fractional flow reserve (FFR). Whether a cardiovascular MRI-based strategy is noninferior to an FFR-based strategy with respect to major adverse cardiac events has not been established., Methods: We performed an unblinded, multicenter, clinical-effectiveness trial by randomly assigning 918 patients with typical angina and either two or more cardiovascular risk factors or a positive exercise treadmill test to a cardiovascular MRI-based strategy or an FFR-based strategy. Revascularization was recommended for patients in the cardiovascular-MRI group with ischemia in at least 6% of the myocardium or in the FFR group with an FFR of 0.8 or less. The composite primary outcome was death, nonfatal myocardial infarction, or target-vessel revascularization within 1 year. The noninferiority margin was a risk difference of 6 percentage points., Results: A total of 184 of 454 patients (40.5%) in the cardiovascular-MRI group and 213 of 464 patients (45.9%) in the FFR group met criteria to recommend revascularization (P = 0.11). Fewer patients in the cardiovascular-MRI group than in the FFR group underwent index revascularization (162 [35.7%] vs. 209 [45.0%], P = 0.005). The primary outcome occurred in 15 of 421 patients (3.6%) in the cardiovascular-MRI group and 16 of 430 patients (3.7%) in the FFR group (risk difference, -0.2 percentage points; 95% confidence interval, -2.7 to 2.4), findings that met the noninferiority threshold. The percentage of patients free from angina at 12 months did not differ significantly between the two groups (49.2% in the cardiovascular-MRI group and 43.8% in the FFR group, P = 0.21)., Conclusions: Among patients with stable angina and risk factors for coronary artery disease, myocardial-perfusion cardiovascular MRI was associated with a lower incidence of coronary revascularization than FFR and was noninferior to FFR with respect to major adverse cardiac events. (Funded by the Guy's and St. Thomas' Biomedical Research Centre of the National Institute for Health Research and others; MR-INFORM ClinicalTrials.gov number, NCT01236807.)., (Copyright © 2019 Massachusetts Medical Society.)

Purpose: Coronary artery geometry can have a significant impact in the hemodynamic behavior of coronary blood flow, influencing atherosclerotic plaque formation. The present work focuses on, through a statistical study, the connection between several geometric parameters of the right coronary artery-ostium cross-sectional area, angles between the common trunk and the side-branches, tortuosity, curvature and cross-sectional area in each side-branch-and their influence on hemodynamic descriptors. Parameters such as low wall shear stress and local disturbed flow, which are associated with atherosclerosis formation, were analysed., Methods: Computed tomography images of ten healthy individuals were selected to reconstruct in vivo three-dimensional models of right coronary arteries. Blood flow was simulated through a compliant model with realistic boundary conditions. Calculated hemodynamic descriptors values were correlated with the geometric parameters using the Pearson correlation coefficient (r) and the p value., Results: The strongest correlations were found in the middle and distal segments of the right coronary artery. A decrease in the ostium area promotes a decrease in the WSS magnitude from the proximal to the distal segment (r = 0.82). Very strong correlations (r > 0.90) were achieved between geometric parameters (cross-sectional area, angle, tortuosity) of the right-ventricular branch and the wall shear stress magnitude in the middle and distal segments., Conclusions: Low values of tortuosity, smaller cross-sectional area and higher angle of the right-ventricular branch leads to a hemodynamic behavior more propitious to atherosclerosis formation, within the study cases. The right-ventricular branch seems to have the highest influence in the hemodynamic behavior of the right coronary artery.

The hemodynamics conditioned by coronary geometry may play an important role in the creation of a pro-atherogenic environment in specific locations of the coronary tree. The aim of this study is to identify how several geometric parameters of the left coronary artery - cross-section areas, proximal left anterior descending artery length, angles between the branches and the septum, curvature and tortuosity - can be related with hemodynamic descriptors, using a computational fluid-structure interaction method. It is widely accepted that the hemodynamic indicators play an important role in identifying possible pro-atherogenic locations. A statistical study, using Pearson correlation coefficient and P value, was performed for a population study of 8 normal human left coronary arteries presenting right-dominant circulation. Within the study cases, arteries with high caliber (r = 0.88), high angles LMS-LAD (r = 0.49), LAD-LCx (r = 0.57) and LAD-Septum (r = 0.52), and high tortuosity LMS-LCx (r = 0.63) were correlated with a hemodynamic behavior propitious to plaque formation in the left anterior descending artery. In contrast, high proximal left anterior descending artery length (r = -0.41), high angle LMS-LCx (r = -0.59), high tortuosity LMS-LAD (r = -0.56) and LAD-LCx (r = -0.55) and high curvature of LMS (r = -0.60) and LCx (r = -0.56) can lead to non-favorable hemodynamic conditions for atheroma formation. Graphical abstract.

Many studies have explored the hypothesis that epicardial adipose tissue (EAT) accumulation adversely affects cardiac remodeling. We assessed, through a systematic review and meta-analysis, whether EAT is linked to left atrial (LA) and left ventricular (LV) structure and function, irrespective of global or abdominal visceral adiposity. We searched MEDLINE, Scopus, and Web of Science for studies evaluating the association of EAT volume quantified by computed tomography with cardiac morphology and function. We used DerSimonian and Laird random-effects models to summarize the adjusted-effect of 10 ml variation of EAT on LA size, LV mass, LV diastolic and systolic functions parameters, and presence of diastolic dysfunction. We quantified heterogeneity using I 2 statistic. We included 19 studies. Quantitative analysis by cardiac parameters, including LA dimension (n = 2,719), LV mass (n = 2,519), diastolic function (n = 3,741), and systolic function (n = 2,037) showed that EAT was associated with LA dilation (pooled B-coefficient: 0.12 mm; 95% confidence interval [CI] 0.08 to 0.17; I 2 : 97%), LV hypertrophy (pooled B-coefficient: 1.21 g; 95% CI 0.63 to 1.79; I 2 : 77%), diastolic dysfunction (odds ratio: 1.35; 95% CI 1.16 to 1.57; I 2 : 0%), higher E/E' ratio (pooled B-coefficient: 0.28 cm/s; 95% CI 0.08 to 0.49; I 2 : 67%), lower E' velocity (pooled B-coefficient: -0.16 cm/s; 95% CI -0.22 to -0.09; I 2 : 43%), and E/A ratio (pooled B-coefficient: -0.01; 95% CI -0.02 to -0.001; I 2 : 70%), independently of body mass index. There was no association between EAT and LV systolic function. In conclusion, EAT volume measured by computed tomography was independently associated with LA dilation, LV hypertrophy, and diastolic dysfunction., (Copyright © 2018. Published by Elsevier Inc.)

Many measurements in chemistry are affected by matrix effects responsible for larger deviation between results from the analysis of various matrices than observed from the replicate analysis of the same matrix. The identification of cases where matrix effects are relevant is useful to know if measurement robustness to matrix effects can significantly reduce the measurement uncertainty, e.g. by performing time-consuming standard addition calibrations or additional matrix clean-up. This work presents a methodology to estimate the percentage contribution of matrix effects to the measurement uncertainty by comparing the intermediate precision estimated from the analysis of a sample with the dispersion of analyte recovery observed form the analyses of samples with different matrices. The measurement model was divide in two intervals of the studied quantity: Interval I between the limit of detection and two times the limit of quantification, where the absolute measurement uncertainty is constant, and Interval II above or equal to two times the limit of quantification where the relative measurement uncertainty is constant. The division of measurements scope in these intervals allowed the comparison of information collected at different values of the studied quantity. The developed methodology was successfully applied to the analysis of total Cr, Cu, Li, Mn and Zn using a procedure developed by OSPAR and acid extractable Ni and Pb according to the EPA3051A standard in marine sediments. Matrix effects are responsible for 7.7 to 79% of the global uncertainty. For Interval II, the relative expanded uncertainty ranged from 12% to 25% and is fit for the environmental monitoring of sediments according to the way the performance of laboratories is assessed in QUASIMEME proficiency tests. The developed measurement uncertainty models produced results compatible with reference values of one Certified Reference Material and 65 proficient test samples independent of the ones used to estimate the measurement uncertainty. The used data and performed calculations are presented in a user-friendly MS-Excel spreadsheet, available as Electronic Supplementary Material, that can be used for other determinations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Clinical evaluation of stress perfusion cardiovascular magnetic resonance (CMR) is currently based on visual assessment and has shown high diagnostic accuracy in previous clinical trials, when performed by expert readers or core laboratories. However, these results may not be generalizable to clinical practice, particularly when less experienced readers are concerned. Other factors, such as the level of training, the extent of ischemia, and image quality could affect the diagnostic accuracy. Moreover, the role of rest images has not been clarified. The aim of this study was to assess the diagnostic accuracy of visual assessment for operators with different levels of training and the additional value of rest perfusion imaging, and to compare visual assessment and automated quantitative analysis in the assessment of coronary artery disease (CAD)., Methods: We evaluated 53 patients with known or suspected CAD referred for stress-perfusion CMR. Nine operators (equally divided in 3 levels of competency) blindly reviewed each case twice with a 2-week interval, in a randomised order, with and without rest images. Semi-automated Fermi deconvolution was used for quantitative analysis and estimation of myocardial perfusion reserve as the ratio of stress to rest perfusion estimates., Results: Level-3 operators correctly identified significant CAD in 83.6% of the cases. This percentage dropped to 65.7% for Level-2 operators and to 55.7% for Level-1 operators (p < 0.001). Quantitative analysis correctly identified CAD in 86.3% of the cases and was non-inferior to expert readers (p = 0.56). When rest images were available, a significantly higher level of confidence was reported (p = 0.022), but no significant differences in diagnostic accuracy were measured (p = 0.34)., Conclusions: Our study demonstrates that the level of training is the main determinant of the diagnostic accuracy in the identification of CAD. Level-3 operators performed at levels comparable with the results from clinical trials. Rest images did not significantly improve diagnostic accuracy, but contributed to higher confidence in the results. Automated quantitative analysis performed similarly to level-3 operators. This is of increasing relevance as recent technical advances in image reconstruction and analysis techniques are likely to permit the clinical translation of robust and fully automated quantitative analysis into routine clinical practice.

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Objectives: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset., Methods: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT)., Results: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models., Conclusions: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations., Key Points: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.