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      Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiac Imaging Parameters: A Systematic Review and Meta-analysis of Randomized Controlled Trials

      review-article
      , MBBS 1 , , MBBS 1 , , MBBS 1 , , MBBS 1 , , MBBS 1 , , MBBS 1 , , MBBS 1 , , MBBS 1 , , MBBS, MD, FRCP, FAMS, FACC, FSCAI 1 , 3 , , MBBS, MHS, MMed, MRCP, PhD 1 , 3 , , MBBChir, MA, MMed, FRCP, FAMS, FCC, FASE 1 , 3 , , MBBS, FRCR 2 , , MBChB, FRCR, MMed, FAMS, EBCR 2 , , MBBS, MRCP 3 , , MBBS, MRCP, MMed, MCI 1 , 4 , , MBBS, MRCP, MMed, ASN 1 , 4 , , MBChB, FRACP, FRCP, FESC, FACC 1 , 3 , , MBBS, MRCP, FAMS, FACC 1 , 3 , , MBBS, MRCP, FACC 1 , 3 , , MBBS, MMed, FRCP, FAMS 1 , 3 , , MBBS, MRCP, MMed, MCI, FAMS 1 , 3 ,
      Journal of Cardiovascular Imaging
      Korean Society of Echocardiography
      Echocardiography, Magnetic resonance imaging, Heart failure, Pharmacology

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          Abstract

          Recent studies have shown that sodium/glucose cotransporter 2 (SGLT2) inhibitors might exert favourable changes on cardiac parameters as observed on cardiovascular imaging. We conducted a systematic review and meta-analysis to determine the effects of SGLT2 inhibitors on cardiac imaging parameters. Four electronic databases (PubMed, Embase, Cochrane, Scopus) were searched for studies in which the effects of SGLT2 inhibitors on cardiac imaging parameters were examined. Studies in which a population was administered SGLT2 inhibitors and analysed by echocardiography and/or cardiac magnetic resonance (CMR) imaging were included. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. A total of 11 randomized controlled trials was included with a combined cohort of 910 patients. Comparing patients receiving SGLT2 inhibitors with subjects receiving placebo, the mean change in CMR-measured left ventricular mass (LVM) was −3.87 g (95% confidence interval [CI], −7.77 to 0.04), that in left ventricular end-systolic volume (LVESV) was −5.96 mL (95% CI, −10.52 to −1.41) for combined LVESV outcomes, that in left atrial volume index (LAVi) was −1.78 mL/m 2 (95% CI, −3.01 to −0.55) for combined LAVi outcomes, and that in echocardiography-measured E/e′ was −0.73 (95% CI, −1.43 to −0.03). Between-group differences were not observed in LVM and LVESV after indexation. The only between-group difference that persisted was for LAVi. Treatment with SGLT2 inhibitors resulted in reduction in LAVi and E/e′ on imaging, indicating they might have an effect on outcomes associated with LV diastolic function.

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          The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

          The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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            The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

            Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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              Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

              Summary Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury. Funding Bill & Melinda Gates Foundation.
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                Author and article information

                Journal
                J Cardiovasc Imaging
                J Cardiovasc Imaging
                JCVI
                Journal of Cardiovascular Imaging
                Korean Society of Echocardiography
                2586-7210
                2586-7296
                July 2022
                13 June 2022
                : 30
                : 3
                : 153-168
                Affiliations
                [1 ]Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
                [2 ]Department of Diagnostic Imaging, National University Hospital, Singapore.
                [3 ]Department of Cardiology, National University Heart Centre Singapore, Singapore.
                [4 ]Division of Neurology, University Medicine Cluster, National University Health System, Singapore.
                Author notes
                Address for Correspondence: Ching-Hui Sia, MBBS, MRCP, MMed, MCI, FAMS. Department of Cardiology, National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 9, Singapore 119228. ching_hui_sia@ 123456nuhs.edu.sg

                *Caitlin Fern Wee and Yao Hao Teo contributed equally to the study.

                Author information
                https://orcid.org/0000-0003-1165-1231
                https://orcid.org/0000-0003-0439-4097
                https://orcid.org/0000-0002-1150-9174
                https://orcid.org/0000-0002-6343-176X
                https://orcid.org/0000-0002-4355-9213
                https://orcid.org/0000-0002-2812-1424
                https://orcid.org/0000-0003-2529-6015
                https://orcid.org/0000-0002-9921-7685
                https://orcid.org/0000-0001-8777-2705
                https://orcid.org/0000-0003-0389-7450
                https://orcid.org/0000-0003-3515-7924
                https://orcid.org/0000-0002-6523-7303
                https://orcid.org/0000-0002-2817-9458
                https://orcid.org/0000-0003-1824-9077
                https://orcid.org/0000-0003-3515-7924
                https://orcid.org/0000-0001-7366-8966
                https://orcid.org/0000-0002-2374-1069
                https://orcid.org/0000-0001-6224-4543
                https://orcid.org/0000-0003-1134-6667
                https://orcid.org/0000-0002-2764-2869
                Article
                10.4250/jcvi.2021.0159
                9314220
                35879251
                6e4dedd3-0f9e-4cb2-993d-0d84ead3675c
                Copyright © 2022 Korean Society of Echocardiography

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 September 2021
                : 22 January 2022
                : 14 May 2022
                Funding
                Funded by: National University of Singapore Yong Loo Lin School of Medicine
                Categories
                Review Article

                echocardiography,magnetic resonance imaging,heart failure,pharmacology

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