Evaluating the natural evolution of myocardial stiffness in aging, sex differences, and through menopause transition in women, using a free-breathing magnetic resonance elastography approach

使用自由呼吸磁共振弹性成像方法评估衰老、性别差异以及女性更年期过渡过程中心肌僵硬度的自然演变

• 批准号: 10583713
• 负责人: Arvin Forghanian-Arani
• 金额: $ 55.38万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10583713
• 关键词: 3-Dimensional; Acceleration; Adoption; Affect; Age; Aging; Biological; Biological Markers; Biomechanics; Blood Tests; Breathing; Cardiac; Cardiac Volume; Cardiovascular Diseases; Cause of Death; Clinical; Data; Development; Diagnostic; Diastole; Disease; Dyspnea; EFRAC; Echocardiography; Enrollment; Evolution; Failure; Follicle Stimulating Hormone; Functional disorder; Future; Goals; Heart; Heart failure; Hormonal Change; Image; Intervention; Left; Left Ventricular Ejection Fraction; Longitudinal Studies; Magnetic Resonance Elastography; Measurement; Measures; Mechanics; Menopausal Status; Menopause; Methods; Modeling; Monitor; Motion; Myocardial; Myocardial tissue; Participant; Patients; Perimenopause; Phase; Pilot Projects; Postmenopause; Premenopause; Prevalence; Prevention; Prognosis; Radial; Resolution; Risk; Risk Factors; Sampling; Sex Bias; Sex Differences; Shortness of Breath; Slice; Symptoms; System; Systole; Techniques; Technology; Testing; Therapeutic Trials; Time; Validation; Ventricular; Woman; age effect; cardiac magnetic resonance imaging; cardiovascular disorder risk; clinical biomarkers; clinical examination; clinical imaging; critical period; disorder prevention; follow-up; hospitalization rates; imaging biomarker; improved; in vivo; men; patient population; preservation; pressure; prevent; preventive intervention; quantitative imaging; reconstruction; reproductive; respiratory; response; routine imaging; sex; tool; trend; volunteer

PROJECT SUMMARY/ABSTRACT While cardiovascular disease (CVD) is the leading cause of death in men and women, substantial sex differences exist in disease prevalence and prognosis. A key impact of menopause is risk of future CVD. Post-menopausal women are twice as likely to have heart failure with preserved ejection fraction (HFpEF) and heart failure hospitalization rates disproportionately increase in women as they age. We hypothesize that a key contributor to this trend are hormonal changes during menopausal transition which accelerate myocardial stiffening. The impact of menopausal transition on myocardial stiffness is unknown. If understood, new disease prevention and therapy monitory strategies with significant potential for long-term benefits could be investigated. Elevated myocardial stiffness, a precursor of several CVDs, can go undetected prior to heart failure symptoms from diastolic dysfunction because left ventricular (LV) ejection fraction is preserved, and absolute LV chamber stiffness is not routinely measured. Current quantitative stiffness measurements require ex vivo mechanical testing or invasive pressure-volume measurements, hampering their adoption as practical clinical biomarkers. This proposal’s objective are to 1) establish a baseline for normal stiffness values during natural aging through menopausal transition and 2) identify sex as a biological variable. To accomplish these goals, we will develop a free breathing 3D non-invasive cardiac magnetic resonance elastography (cMRE) technique to measure myocardial stiffness. The technological advances in this study will make myocardial stiffness imaging in heart failure patients with dyspnea more reliably, regional, and enable quantitative cross-sectional and longitudinal monitoring of myocardial stiffness. Our preliminary data shows that LV myocardial stiffness increases significantly in healthy women, but not men, after the age of 50, which corresponds to the average age of menopausal transition. If cMRE can be used to detect elevated myocardial stiffening during menopausal transition and prior to the development of diastolic disfunction, the monitoring of current and new preventive interventions prior to heart failure symptoms will be made possible. To accomplish these objectives, we will: • Develop a 3D, free-breathing cMRE application. • Retrospectively bin cMRE data for multiple 3D MRE volumes that vary during the cardiac cycle. • Validate cMRE in static and pulsatile realistic cardiac phantoms. • Identify a clinical and technically feasible acquisition durations in a normal volunteer pilot study. • Evaluate the influence of natural aging, sex, and menopausal transition on myocardial stiffness. The natural evolution of myocardial stiffness in natural aging, in relation to sex-biases, and throughout menopausal transition will be evaluated using a newly developed and implemented free breathing non-invasive quantitative cMRE approach, which may have significant implications for the prevention of heart failure.

项目摘要/摘要 虽然心血管疾病（CVD）是男性和女性死亡的主要原因，但性别差异很大。 存在于疾病的流行和预后中。更年期的一个关键影响是未来CVD的风险。绝经后 女性射血分数正常的心力衰竭（HFpEF）和心力衰竭的可能性是男性的两倍。 随着年龄的增长，妇女的住院率不成比例地增加。我们假设，一个关键因素， 这种趋势是绝经过渡期的激素变化，加速了心肌硬化。的影响 绝经过渡期对心肌硬度的影响尚不清楚。如果了解，新的疾病预防和 可以研究具有显著的长期益处潜力的治疗监测策略。 心肌僵硬度升高是几种心血管疾病的前兆，在出现心力衰竭症状之前， 舒张功能障碍，因为左心室（LV）射血分数保持不变，并且绝对LV腔室僵硬 不是常规测量的。目前的定量刚度测量需要体外机械测试或 侵入性压力-容积测量，阻碍了它们作为实际临床生物标志物的采用。 本提案的目标是：1）通过以下方式建立自然老化期间正常刚度值的基线： 绝经过渡期和2）确定性别作为一个生物变量。为了实现这些目标，我们将开发一个免费的 呼吸3D无创心脏磁共振弹性成像（cMRE）技术测量心肌 刚度这项研究的技术进步将使心力衰竭患者的心肌硬度成像 呼吸困难更可靠，区域性，并能够定量横截面和纵向监测， 心肌僵硬我们的初步数据显示，健康人左室心肌硬度显著增加， 女性，而不是男性，在50岁之后，这相当于绝经过渡的平均年龄。如果cMRE 可用于检测绝经过渡期和发展前心肌硬化的升高， 舒张功能障碍，监测当前和新的预防性干预措施之前，心力衰竭症状将 使之成为可能。为了实现这些目标，我们将： ·开发3D自由呼吸cMRE应用程序。 ·针对在心动周期期间变化的多个3D MRE体积的逆向图仓cMRE数据。 ·在静态和脉动真实心脏模型中的MRE。 ·在正常志愿者试点研究中确定临床和技术上可行的采集持续时间。 ·评估自然衰老、性别和绝经过渡对心肌硬度的影响。 自然衰老中心肌硬度的自然演变与性别偏差及整个绝经期 将使用新开发和实施的自由呼吸非侵入性定量 cMRE方法，这可能对预防心力衰竭有重要意义。