Age- and Gender-Related Changes in Ventricular Performance in Wild-Type FVB/N Mice as Evaluated by Conventional and Vector Velocity Echocardiography Imaging: A Retrospective Study

Koch, Sheryl E.; Haworth, Kevin J.; Robbins, Nathan; Smith, Margaret A.; Lather, Navneet; Anjak, Ahmad; Jiang, Min; Varma, Priyanka; Jones, W. Keith; Rubinstein, Jack

doi:10.1016/j.ultrasmedbio.2013.04.002

Cited by 22 publications

(18 citation statements)

References 65 publications

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“…[1][2][3] Recent experimental and clinical studies indicate that there are significant sex-and age-specific differences in baseline left ventricular ejection fraction (LVEF). [4][5][6] Indeed, LV function is significantly higher in women than in men, and these differences further augment with age. [4][5][6] The latter is consistent with the observation that the risk of cardiovascular events starts at higher LVEF indices in women than in men.…”

Section: Introductionmentioning

confidence: 99%

Increased long-term mortality in women with high left ventricular ejection fraction: data from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) long-term registry

Gebhard

Marędziak

Messerli

et al. 2020

European Heart Journal - Cardiovascular Imaging

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Aims There are significant sex-specific differences in left ventricular ejection fraction (LVEF), with a higher LVEF being observed in women. We sought to assess the clinical relevance of an increased LVEF in women and men. Methods and results A total of 4632 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry (44.8% women; mean age 58.7 ± 13.2 years in men and 59.5 ± 13.3 years in women, P = 0.05), in whom LVEF was measured by cardiac computed tomography, were categorized according to LVEF (low <55%, normal 55–65%, and high >65%). The prevalence of high LVEF was similar in both sexes (33.5% in women and 32.5% in men, P = 0.46). After 6 years of follow-up, no difference in mortality was observed in patients with high LVEF in the overall cohort (P = 0.41). When data were stratified by sex, women with high LVEF died more often from any cause as compared to women with normal LVEF (8.6% vs. 7.1%, log rank P = 0.032), while an opposite trend was observed in men (5.8% vs. 6.8% in normal LVEF, log rank P = 0.89). Accordingly, a first order interaction term of male sex and high LVEF was significant (hazard ratios 0.63, 95% confidence intervals 0.41–0.98, P = 0.043) in a Cox regression model of all-cause mortality adjusted for age, cardiovascular risk factors, and severity of coronary artery disease (CAD). Conclusion Increased LVEF is highly prevalent in patients referred for evaluation of CAD and is associated with an increased risk of death in women, but not in men. Differentiating between normal and hyperdynamic left ventricles might improve risk stratification in women with CAD. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT01443637.

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Section: Introductionmentioning

confidence: 99%

Increased long-term mortality in women with high left ventricular ejection fraction: data from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) long-term registry

Gebhard

Marędziak

Messerli

et al. 2020

European Heart Journal - Cardiovascular Imaging

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“…Aging models of cardiac dysfunction have been previously proposed. This includes the spontaneous senescence-prone (SAMP8) mice ( Reed et al, 2011 ), male FVB/N mice ( Koch et al, 2013 ), Fischer 344 rats ( Forman et al, 1997 ), and crossed between Fischer 344 and Brown Norway rats ( Hacker et al, 2006 ). These models, however, are not specific of HFPEF and present several other aging phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…SAMP8 mice, for example, did not develop heart failure despite evidence of diastolic dysfunction ( Reed et al, 2011 ). In others, the development of heart failure was sex-specific ( Forman et al, 1997 ; Koch et al, 2013 ). A common factor in aging models, however, was increased cardiac fibrosis with higher inflammatory markers ( Hacker et al, 2006 ; Reed et al, 2011 ), which is consistent with the present study.…”

Section: Discussionmentioning

confidence: 99%

“…This preranked list was used for pathway analysis using gene-set enrichment analysis (GSEA) ( Glasscock et al, 2015 ). Gene sets used included REACTOME ( Reed et al, 2011 ), Molecular Signatures Database (MSigDB) ( Koch et al, 2013 ), and Encode TFBS we have used previously ( Forman et al, 1997 ). GSEA FDR < 0.05 is considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

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Age-Related Differential Structural and Transcriptomic Responses in the Hypertensive Heart

et al. 2018

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While aging is a critical risk factor for heart failure, it remains uncertain whether the aging heart responds differentially to a hypertensive stimuli. Here we investigated phenotypic and transcriptomic differences between the young and aging heart using a mineralocorticoid-excess model of hypertension. Ten-week (“young”) and 36-week (“aging”) mice underwent a unilateral uninephrectomy with deoxycorticosterone acetate (DOCA) pellet implantation (n = 6–8/group) and were followed for 6 weeks. Cardiac structure and function, blood pressure (BP) and the cardiac transcriptome were subsequently examined. Young and aging DOCA mice had high BP, increased cardiac mass, cardiac hypertrophy, and fibrosis. Left ventricular end-diastolic pressure increased in aging DOCA-treated mice in contrast to young DOCA mice. Interstitial and perivascular fibrosis occurred in response to DOCA, but perivascular fibrosis was greater in aging mice. Transcriptomic analysis showed that young mice had features of higher oxidative stress, likely due to activation of the respiratory electron transport chain. In contrast, aging mice showed up-regulation of collagen formation in association with activation of innate immunity together with markers of inflammation including cytokine and platelet signaling. In comparison to younger mice, aging mice demonstrated different phenotypic and molecular responses to hypertensive stress. These findings have potential implications for the pathogenesis of age-related forms of cardiovascular disease, particularly heart failure.

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“…FVB/N mice represent a robust inbred strain and males display diastolic dysfunction at 12 months, with an E/A < 1 while, in females, this phenotype is not observed [ 30 ]. In contrast, Fischer 344 ageing rats showed more prominent LV hypertrophy and diastolic dysfunction in females compared to males, as assessed by increased IVRT and decreased septal E’.…”

Section: Animal Models Of Hfpefmentioning

confidence: 99%

Animal models of heart failure with preserved ejection fraction

et al. 2016

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Heart failure with preserved ejection fraction (HFpEF) constitutes a clinical syndrome in which the diagnostic criteria of heart failure are not accompanied by gross disturbances of systolic function, as assessed by ejection fraction. In turn, under most circumstances, diastolic function is impaired. Although it now represents over 50 % of all patients with heart failure, the mechanisms of HFpEF remain understood, precluding effective therapy. Understanding the pathophysiology of HFpEF has been restricted by both limited access to human myocardial biopsies and by the lack of animal models that fully mimic human pathology. Animal models are valuable research tools to clarify subcellular and molecular mechanisms under conditions where the comorbidities and other confounding factors can be precisely controlled. Although most of the heart failure animal models currently available represent heart failure with reduced ejection fraction, several HFpEF animal models have been proposed. However, few of these fulfil all the features present in human disease. In this review we will provide an overview of the currently available models to study HFpEF from rodents to large animals as well as present advantages and disadvantages of these models.

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Age- and Gender-Related Changes in Ventricular Performance in Wild-Type FVB/N Mice as Evaluated by Conventional and Vector Velocity Echocardiography Imaging: A Retrospective Study

Cited by 22 publications

References 65 publications

Increased long-term mortality in women with high left ventricular ejection fraction: data from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) long-term registry

Increased long-term mortality in women with high left ventricular ejection fraction: data from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) long-term registry

Age-Related Differential Structural and Transcriptomic Responses in the Hypertensive Heart

Animal models of heart failure with preserved ejection fraction

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