Ventricular remodeling and heart failure after myocardial infarction: a community

描述(由申请人提供)：在过去的20年里，心肌梗死(MI)的流行病学发生了重大变化。其急性治疗的进展改善了短期存活率，但心力衰竭(HF)在MI后仍然频繁发生，并导致额外的死亡率。因此，以恢复血管通畅为目的的急性心肌梗死治疗不足以预防心力衰竭，强调了了解导致心梗发展的当代机制的重要性。从最初的心肌损伤到心功能不全和心衰的转变称为左心室重构，其特征是进行性的心室增大、收缩和舒张期功能的改变以及二尖瓣返流(MR)的发生。重塑是一种动态实体，定义为随着时间的变化，在有害变化无法逆转的阶段被诊断出来。因此，必须对其进行预测和预防。对心肌梗死后心脏重构的认识尚不完整，这阻碍了其预防。首先，重塑的确切发生率仍有待定义，因为数据主要与临床试验有关，具有不确定的临床相关性。其次，心肌梗死后心室重构的机制仍有待确定，目的是确定新的预测因素，以确定预防和治疗的靶点。第三，大多数关于重建的成像数据并不能反映最新的方法或当代的队列。因此，解决心梗后重构的频率和机制是确定预防心力衰竭的策略所必需的，并需要依赖于通过严格的成像技术结合新的生物标志物的测量来评估的临床相关人群。我们的三个具体目标将有助于阐明，在一个预期的社区队列中，心室重构的频率和机制，以及这些机制在心肌梗塞后心力衰竭发生中的作用。目的1将在社区人群中测量急性心肌梗死事件后左室重构的频率和模式。重塑将通过二维和三维超声心动图和斑点跟踪进行评估，并被定义为收缩或舒张期功能的变化，Aim 2先生将评估重塑的决定因素，包括临床特征和新的生物标记物。目标3将测试目标2中确定的重塑预测因子对心肌梗死后心衰的预测价值。在目标1和目标2中，我们将招募420名患者来获得序列二维 以及三维超声心动图研究。目标3将把这些发现推广到整个以人群为基础的心肌梗死发病队列。我们建议的应用程序包括几个关键的创新方面。我们正在进行的冠状动脉疾病监测将提供一个强大的招募平台和强大的背景，以优化我们数据的临床相关性。严格的成像方法将为重建过程提供独特的见解。我们将结合影像和生物标记物数据来确定可以在MI指数处测量的重构的预测因素，从而能够预测当代MI人群中的心衰风险。

DESCRIPTION (provided by applicant): Over the past 2 decades, major changes in the epidemiology of myocardial infarction (MI) have occurred. Progress in its acute treatment improved short term survival, but heart failure (HF) remains frequent after MI and leads to excess mortality. Hence, the acute treatment of MI aimed at restoring vessel patency is not sufficient to prevent HF, underscoring the importance of understanding the contemporary mechanisms leading to its development. The transition from the initial myocardial injury to ventricular dysfunction and HF is termed left ventricular remodeling and is characterized by progressive ventricular enlargement, alteration of systolic and diastolic function and occurrence of mitral regurgitation (MR). Remodeling is a dynamic entity, defined as a change over time, diagnosed at a stage where deleterious changes cannot be reversed. Hence, it must be predicted and prevented. Knowledge on cardiac remodeling after MI is incomplete, which hinders its prevention. Firstly, the exact incidence of remodeling remains to be defined as data pertain mostly to clinical trials, of uncertain clinical relevance. Secondly, the mechanisms of ventricular remodeling after MI remain to be defined with the goal of identifying novel predictors that could define targets for prevention and treatment. Thirdly, most imaging data on remodeling do not reflect state of the art methods or contemporary cohorts. Thus, addressing the frequency and mechanisms of remodeling after MI is needed to define strategies to prevent HF and requires relying on clinically relevant populations evaluated by rigorous imaging techniques integrated with measurements of novel biomarkers. Our 3 specific aims will help elucidate, within a prospective community cohort, the frequency and mechanisms of ventricular remodeling and the responsibilities of these mechanisms in the genesis of post MI HF. Aim 1 will measure the frequency and patterns of left ventricular remodeling after incident MI in a community-based population. Remodeling will be evaluated by two- and three-dimensional echocardiography and speckle tracking and defined as changes in systolic or diastolic function and MR. Aim 2 will assess the determinants of remodeling, including clinical characteristics and novel biomarkers. Aim 3 will test the value of the predictors of remodeling identified in Aim 2 to predict HF after MI. In Aims 1 and 2, we will recruit 420 patients to obtain serial two-dimensional and three-dimensional echocardiographic studies. Aim 3 will extend these findings to the entire population-based MI incidence cohort. Our proposed application comprises several key innovative aspects. Our ongoing surveillance of coronary disease will provide a strong recruitment platform and a robust backdrop to optimize the clinical relevance of our data. Rigorous imaging approaches will provide unique insights into the remodeling process. We will integrate imaging and biomarker data to identify predictors of remodeling that can be measured at index MI to enable risk prediction of HF in contemporary MI populations.