CMR Myocardial Tissue Based Prediction of Ischemic MR Revascularization Response

 描述（由申请人提供）：二尖瓣返流（MR）存在于五分之一接受血运重建的冠状动脉疾病（CAD）患者中，导致发病率和死亡率显著增加。在我们小组和其他人的先前研究中，CAD患者的MR与二尖瓣下心肌缺血和梗死密切相关。血运重建可以逆转缺血，而梗死不能。然而，在临床实践中，对血运重建的MR反应知之甚少。在近一半的患者中，仅通过手术或经皮冠状动脉血运重建术即可改善二尖瓣返流-其余患者二尖瓣返流持续存在或停止。不确定哪些二尖瓣返流患者会对单独的血运重建产生反应，限制了优化治疗的能力。心脏磁共振（CMR）成像是识别缺血和梗死以及功能和几何形状的有力工具。已知CMR组织表征可预测血运重建诱导的LV功能和重塑改善，但以前从未作为MR的计划工具进行过测试。我们的中心假设是，在通过CMR治疗之前，可以预测对血运重建的MR反应，MR改善取决于支持二尖瓣的存活（存活）心肌中缺血的存在和程度。此外，我们假设CAD患者的非缺血性纤维化与血运重建后的持续性MR相关，可归因于不良的整体心肌重塑，从而减弱二尖瓣对血运重建的反应能力。为了验证这些假设，我们将研究至少156例仅接受冠状动脉血运重建的晚期（≥中度）二尖瓣返流的CAD患者。将在血运重建前后进行负荷灌注CMR，以评估基线心肌组织特性和血运重建诱导的缺血变化。超声心动图（术前、术后3个月和术后6个月）将作为二尖瓣返流的参考，以便应用与既往NIH研究和广泛临床实践一致的经过充分验证的标准。目标1将比较MR改善和未改善患者之间缺血和梗死的存在和程度。目标2将比较各组之间的非缺血性纤维化，包括局灶性中壁纤维化和整体细胞外体积。目标3将使用主要CMR数据和有限元建模开发MR对血运重建反应的预测模型。我们在CMR、超声心动图、二尖瓣生理学和计算建模方面的记录使我们能够独特地解决这些问题。从本研究中获得的新信息将有助于开发预测模型，以区分仅通过血运重建改善MR的患者与MR持续存在的患者（从而避免辅助干预治疗MR并可能避免其长期临床后果）。结果将提供有关MR生理学的关键基础见解，从而为未来研究的设计提供信息，这些研究的重点是优化既定和新兴的治疗策略，以治疗仅对血运重建无反应的患者的MR。

 DESCRIPTION (provided by applicant): Mitral regurgitation (MR) is present in one in five coronary artery disease (CAD) patients undergoing revascularization, conferring markedly increased morbidity and mortality. In prior research by our group and others, MR in patients with CAD has been strongly linked to ischemia and infarction in myocardium underlying the mitral valve. Ischemia can be reversed with revascularization, whereas infarction cannot. However, in clinical practice, MR response to revascularization is poorly understood. In nearly half of patients, MR improves with surgical or percutaneous coronary revascularization alone - in the remainder MR persists or worsens. Uncer- tainty as to which patients with MR will respond to revascularization alone limits the ability to optimize therapy. Cardiac magnetic resonance (CMR) imaging is a powerful tool to identity ischemia and infarction, as well as function and geometry. CMR tissue characterization is known to predict revascularization-induced improvement in LV function and remodeling, but has never before been tested as a planning tool for MR. Our central hypothesis is that MR response to revascularization can be predicted prior to therapy via CMR, with MR improvement dependent on presence and magnitude of ischemia in viable (alive) myocardium supporting the mitral valve. Additionally, we hypothesize that non-ischemic fibrosis in patients with CAD is associated with persistent MR after revascularization, attributable to adverse global myocardial remodeling that blunts the ability of the mitral valve to respond to revascularization. To test these hypotheses, we will study at least 156 CAD patients with advanced (≥moderate) MR undergoing coronary revascularization alone. Stress perfusion CMR will be performed pre and post-revascularization to assess baseline myocardial tissue properties and revascularization induced change in ischemia. Echocardiography (pre, 3, and 6 months post) will be the reference for MR, so as to apply a well-validated standard concordant with prior NIH studies and widespread clinical practice. Aim 1 will compare presence and magnitude of ischemia and infarction between patients with and without improved MR. Aim 2 will compare non-ischemic fibrosis between groups, including focal mid-wall fibrosis and global extracellular volume. Aim 3 will develop predictive models for MR response to revascularization, using both primary CMR data and finite element modeling. Our track record in CMR, echocardiography, mitral valve physiology, and computational modeling makes us uniquely poised to address these issues. The novel information to be gained from this research will enable development of predictive models to differentiate a priori those patients in whom MR will improve with revascularization alone from those in whom MR will persist (thereby warranting ancillary interventions to treat MR and potentially avoid its long term clinical consequences). Results will provide key foundational insights concerning MR physiology, and thus will inform the design of future research focused on optimization of established and emerging therapeutic strategies to treat MR in patients unresponsive to revascularization alone.