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      Echocardiographic Strain Analysis for the Early Detection of Left Ventricular Systolic/Diastolic Dysfunction and Dyssynchrony in a Mouse Model of Physiological Aging

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          Abstract

          Heart disease is the leading cause of hospitalization and death worldwide, severely affecting health care costs. Aging is a significant risk factor for heart disease, and the senescent heart is characterized by structural and functional changes including diastolic and systolic dysfunction as well as left ventricular (LV) dyssynchrony. Speckle tracking–based strain echocardiography (STE) has been shown as a noninvasive, reproducible, and highly sensitive methodology to evaluate LV function in both animal models and humans. Herein, we describe the efficiency of this technique as a comprehensive and sensitive method for the detection of age-related cardiac dysfunction in mice. Compared with conventional echocardiographic measurements, radial and longitudinal strain, and reverse longitudinal strain were able to detect subtle changes in systolic and diastolic cardiac function in mice at an earlier time point during aging. Additionally, the data show a gradual and consistent decrease with age in regional contractility throughout the entire LV, in both radial and longitudinal axes. Furthermore, we observed that LV segmental dyssynchrony in longitudinal axis reliably differentiated between aged and young mice. Therefore, we propose the use of echocardiographic strain as a highly sensitive and accurate technology enabling and evaluating the effect of new treatments to fight age-induced cardiac disease.

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          Aging-associated cardiovascular changes and their relationship to heart failure.

          Aging represents a convergence of declining cardioprotective systems and increasing disease processes that is fertile ground for the development of heart failure. Fifty percent of all heart failure diagnoses and 90% of all heart failure deaths occur in individuals older than 70. This article discusses the microscopic and macroscopic changes in cardiovascular structure, function, protective systems, and disease associated with aging. In addition to outlining important clinical considerations and conditions in older persons, the link between normal aging and the elevated risk for development of stage B heart failure is explained and potential therapeutic pathways are highlighted. Published by Elsevier Inc.
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            Assessment of Left Ventricular Function by Echocardiography

            Left ventricular (LV) ejection fraction (LVEF) is a simple measure of global systolic function that pervades the risk evaluation and management of many cardiovascular diseases. However, this parameter is limited not only by technical challenges, but also by pathophysiological entities where the ratio of stroke volume to LV cavity size is preserved. The assessment of global longitudinal strain (GLS) from speckle-tracking analysis of 2-dimensional echocardiography has become a clinically feasible alternative to LVEF for the measurement of myocardial function. Evidence gathered over the last decade has shown GLS to be more sensitive to left ventricular dysfunction (LVD) than LVEF and to provide additional prognostic information. The technology is validated, reproducible within an acceptable range, and widely available. GLS has been proposed as the test of choice in guidelines for monitoring of asymptomatic cardiotoxicity related to chemotherapy. It also has the potential to improve risk stratification, redefine criteria for disease classification, and determine treatment in asymptomatic LVD resulting from a variety of etiologies. GLS provides utility across the spectrum of heart failure (and LVEF) as well as in the evaluation of valvular heart disease. There is a strong case for incorporation of GLS into clinical decision making. This review appraises the evidence addressing the utility of GLS as a complementary metric to LVEF for incorporation into mainstream clinical practice.
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              Cardiac aging: from molecular mechanisms to significance in human health and disease.

              Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several "anti-aging" strategies that treat CVDs and improve healthy cardiac aging.
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                Author and article information

                Journal
                J Gerontol A Biol Sci Med Sci
                J. Gerontol. A Biol. Sci. Med. Sci
                gerona
                The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
                Oxford University Press (US )
                1079-5006
                1758-535X
                March 2019
                18 June 2018
                18 June 2018
                : 74
                : 4
                : 455-461
                Affiliations
                [1 ]Center for Translational Medicine and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania
                [2 ]Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania
                [3 ]Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
                [4 ]Department of Clinical Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania
                Author notes

                Drs. de Lucia and Wallner equally contributed to this article.

                Address correspondence to: Walter J. Koch, PhD, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, 3500 N. Broad Street, 940-MERB, Philadelphia, PA-19140, E-mail: walter.koch@ 123456temple.edu
                Author information
                http://orcid.org/0000-0002-4346-111X
                Article
                gly139
                10.1093/gerona/gly139
                6417453
                29917053
                87723d52-602d-455c-acfb-9cb6622400d0
                © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 07 March 2018
                Page count
                Pages: 7
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: NIH P01 HL091799
                Award ID: NIH R37 HL061690
                Award ID: NIH P01 HL075443
                Award ID: NIH P01 HL091799
                Funded by: American Heart Association 10.13039/100000968
                Award ID: 17POST33660942
                Categories
                The Journal of Gerontology: Biological Sciences
                Articles

                Geriatric medicine
                cardiovascular,animal model,mice,senescence,speckle-tracking echocardiography
                Geriatric medicine
                cardiovascular, animal model, mice, senescence, speckle-tracking echocardiography

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