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      The Role of Cardiovascular Magnetic Resonance Imaging in the Assessment of Myocardial Fibrosis in Young and Veteran Athletes: Insights From a Meta-Analysis

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          Abstract

          Background: Cardiac magnetic resonance (CMR) combined with late gadolinium enhancement (LGE) has revealed a non-negligible increased incidence of myocardial fibrosis (MF) in athletes compared to healthy sedentary controls.

          Objective: The aim of this systematic research and meta-analysis is to investigate and present our perspective regarding CMR indices in athletes compared to sedentary controls, including T1 values, myocardial extracellular volume (ECV) and positive LGE indicative of non-specific fibrosis, also to discuss the differences between young and veteran athletes.

          Methods: The protocol included searching, up to October 2021, of MEDLINE, EMBASE, SPORTDiscus, Web of Science and Cochrane databases for original studies assessing fibrosis via CMR in athletes. A mean age of 40 years differentiated studies' athletic populations to veteran and young.

          Results: The research yielded 14 studies including in total 1,312 individuals. There was a statistically significant difference in LGE fibrosis between the 118/759 athletes and 16/553 controls ( Z = 5.2, P < 0.001, I 2 = 0%, P I = 0.45). Notably, LGE fibrosis differed significantly between 546 (14.6%) veteran and 140 (25.7%) young athletes ( P = 0.002). At 1.5T, T1 values differed between 117 athletes and 48 controls ( P < 0.0001). A statistically significant difference was also shown at 3T (110 athletes vs. 41 controls, P = 0.0004), as well as when pooling both 1.5T and 3T populations ( P < 0.00001). Mean ECV showed no statistically significant difference between these groups.

          Conclusions: Based on currently available data, we reported that overall LGE based non-specific fibrosis and T1 values differ between athletes and sedentary controls, in contrast to ECV values. Age of athletes seems to have impact on the incidence of MF. Future prospective studies should focus on the investigation of the underlying pathophysiological mechanisms.

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          Most cited references33

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          Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement

          Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)–a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.
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            Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle–Ottawa Scale and the RTI item bank

            Background The study objective was to compare the Newcastle–Ottawa Scale (NOS) and the RTI item bank (RTI-IB) and estimate interrater agreement using the RTI-IB within a systematic review on the cardiovascular safety of glucose-lowering drugs. Methods We tailored both tools and added four questions to the RTI-IB. Two reviewers assessed the quality of the 44 included studies with both tools, (independently for the RTI-IB) and agreed on which responses conveyed low, unclear, or high risk of bias. For each question in the RTI-IB (n=31), the observed interrater agreement was calculated as the percentage of studies given the same bias assessment by both reviewers; chance-adjusted interrater agreement was estimated with the first-order agreement coefficient (AC1) statistic. Results The NOS required less tailoring and was easier to use than the RTI-IB, but the RTI-IB produced a more thorough assessment. The RTI-IB includes most of the domains measured in the NOS. Median observed interrater agreement for the RTI-IB was 75% (25th percentile [p25] =61%; p75 =89%); median AC1 statistic was 0.64 (p25 =0.51; p75 =0.86). Conclusion The RTI-IB facilitates a more complete quality assessment than the NOS but is more burdensome. The observed agreement and AC1 statistic in this study were higher than those reported by the RTI-IB’s developers.
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              Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile

              Background: Studies in middle-age and older (masters) athletes with atherosclerotic risk factors for coronary artery disease report higher coronary artery calcium (CAC) scores compared with sedentary individuals. Few studies have assessed the prevalence of coronary artery disease in masters athletes with a low atherosclerotic risk profile. Methods: We assessed 152 masters athletes 54.4±8.5 years of age (70% male) and 92 controls of similar age, sex, and low Framingham 10-year coronary artery disease risk scores with an echocardiogram, exercise stress test, computerized tomographic coronary angiogram, and cardiovascular magnetic resonance imaging with late gadolinium enhancement and a 24-hour Holter. Athletes had participated in endurance exercise for an average of 31±12.6 years. The majority (77%) were runners, with a median of 13 marathon runs per athlete. Results: Most athletes (60%) and controls (63%) had a normal CAC score. Male athletes had a higher prevalence of atherosclerotic plaques of any luminal irregularity (44.3% versus 22.2%; P =0.009) compared with sedentary males, and only male athletes showed a CAC ≥300 Agatston units (11.3%) and a luminal stenosis ≥50% (7.5%). Male athletes demonstrated predominantly calcific plaques (72.7%), whereas sedentary males showed predominantly mixed morphology plaques (61.5%). The number of years of training was the only independent variable associated with increased risk of CAC >70th percentile for age or luminal stenosis ≥50% in male athletes (odds ratio, 1.08; 95% confidence interval, 1.01–1.15; P =0.016); 15 (14%) male athletes but none of the controls revealed late gadolinium enhancement on cardiovascular magnetic resonance imaging. Of these athletes, 7 had a pattern consistent with previous myocardial infarction, including 3(42%) with a luminal stenosis ≥50% in the corresponding artery. Conclusions: Most lifelong masters endurance athletes with a low atherosclerotic risk profile have normal CAC scores. Male athletes are more likely to have a CAC score >300 Agatston units or coronary plaques compared with sedentary males with a similar risk profile. The significance of these observations is uncertain, but the predominantly calcific morphology of the plaques in athletes indicates potentially different pathophysiological mechanisms for plaque formation in athletic versus sedentary men. Coronary plaques are more abundant in athletes, whereas their stable nature could mitigate the risk of plaque rupture and acute myocardial infarction.
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                Author and article information

                Contributors
                Journal
                Front Cardiovasc Med
                Front Cardiovasc Med
                Front. Cardiovasc. Med.
                Frontiers in Cardiovascular Medicine
                Frontiers Media S.A.
                2297-055X
                21 December 2021
                2021
                : 8
                : 784474
                Affiliations
                [1] 1Royal Brompton Hospital, Imaging Centre, Cardiac Magnetic Resonance Unit , London, United Kingdom
                [2] 2Third Department of Cardiology, Aristotle University of Thessaloniki , Thessaloniki, Greece
                [3] 3Unit of Inherited Cardiac Conditions, First Cardiology Department, University of Athens , Athens, Greece
                Author notes

                Edited by: Thomas A. Treibel, University College London, United Kingdom

                Reviewed by: Stephen C. Kolwicz Jr., Ursinus College, United States; Mariana Vasconcelos, São João University Hospital Center, Portugal

                *Correspondence: Emmanuel Androulakis e.androulakis@ 123456rbht.nhs.uk

                This article was submitted to Cardiovascular Imaging, a section of the journal Frontiers in Cardiovascular Medicine

                †These authors have contributed equally to this work

                Article
                10.3389/fcvm.2021.784474
                8724053
                34993239
                e12c3967-eb17-40fa-8605-00311b75efbd
                Copyright © 2021 Androulakis, Mouselimis, Tsarouchas, Antonopoulos, Bakogiannis, Papagkikas and Vlachopoulos.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 September 2021
                : 30 November 2021
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 33, Pages: 9, Words: 5424
                Categories
                Cardiovascular Medicine
                Perspective

                athletes,myocardial fibrosis,lge,cmr,meta-analysis,mapping
                athletes, myocardial fibrosis, lge, cmr, meta-analysis, mapping

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