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

项目摘要/摘要 虽然心血管疾病(CVD)是男性和女性的主要死亡原因，但显著的性别差异 存在于疾病的患病率和预后中。更年期的一个关键影响是未来患心血管疾病的风险。绝经后 女性发生心力衰竭并保留射血分数(HFpEF)和心力衰竭的可能性是女性的两倍 女性的住院率随着年龄的增长而不成比例地增加。我们假设一个关键的贡献者 这种趋势是绝经过渡期间荷尔蒙的变化，加速了心肌僵硬。其影响 绝经过渡期对心肌僵硬的影响尚不清楚。如果了解，新的疾病预防和 可以研究具有显著长期益处潜力的治疗监测策略。 心肌僵硬升高是几种心血管疾病的先兆，在出现心力衰竭症状之前可能无法检测到 舒张期功能障碍，因为左心室射血分数被保留，且左室室壁绝对僵硬 不是常规测量的。目前的定量硬度测量需要体外机械测试或 侵入性压力-体积测量，阻碍了它们作为实用的临床生物标记物的采用。 该提案的目标是：1)建立自然老化过程中正常刚度值的基线 更年期转变和2)将性别确定为生物变量。为了实现这些目标，我们将开发一种免费的 呼吸三维无创性心脏磁共振弹性成像技术测量心肌 僵硬。这项研究的技术进步将使心力衰竭患者的心肌僵硬成像 使用呼吸困难更可靠，区域性，并支持定量横断面和纵向监测 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，但不是男性，在50岁之后，这对应于更年期过渡的平均年龄。如果CMRE 可用于在绝经过渡期间和发展之前检测心肌僵硬升高 在出现心力衰竭症状之前，监测现有的和新的预防性干预措施将有助于舒张期功能不全 使之成为可能。为达致这些目标，我们会： ·开发一款3D、自由呼吸的CMRE应用程序。 ·回顾在心脏周期中变化的多个3D MRE体积的Bin CMRE数据。 ·在静态和搏动的真实心脏模型中验证CMRE。 ·在一项正常的志愿者试点研究中，确定临床和技术上可行的获取持续时间。 ·评估自然衰老、性别和绝经过渡对心肌僵硬的影响。 自然衰老中心肌硬度的自然演变，与性别偏见有关，以及整个更年期 将使用新开发和实施的自由呼吸非侵入性定量测量来评估过渡 CMRE方法，这可能对预防心力衰竭有重要意义。

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.