REGIONAL VENTRICULAR STRAIN METRICS TO PREDICT NEW-ONSET HEART FAILURE COURSE

描述（由申请人提供）：具有临床意义的心力衰竭患者是美国心血管疾病患者中最大且增长最快的亚组。发病率、死亡率和医疗保健费用方面的负担令人震惊。在重症新发心力衰竭患者的临床管理中，无法立即区分那些对药物治疗有反应的患者和那些不会对药物治疗有反应的患者，导致对不需要的患者不适当地应用高危心力衰竭手术，同时也拒绝对那些最能从中受益的患者进行手术。基于MRI的多参数应变分析生成患者特异性，通过比较三名患者的微区域左心室（LV）收缩功能， 来自15，300个网格点中的每一个的特定原始应变参数值（每个患者总共45，900个数据库比较）与相应的正常平均值+/-标准偏差（来自我们实验室的正常人应变数据库; n>70）。多个不同的患者特异性应变参数值的这种“归一化”允许它们组合成新颖且强大的多参数应变指数，其已被证明比任何单独的应变度量更强大。 通过对新发心力衰竭（扩张型心肌病）患者应用基于MRI的多参数应变分析，我们发现收缩性损伤的LV区域分布具有显著的异质性。扩张型心肌病患者收缩性损伤的这种意外异质性以一致的模式发生，这使我们能够识别对早期损伤更敏感的“前哨”LV区域（基底隔和中隔），并作为新发心力衰竭患者不可逆收缩性损伤的先兆。我们假设，通过基于MRI的多参数应变分析监测这些前哨LV区域，可以根据对药物治疗的早期反应和随后发生的心力衰竭不良事件对新发心力衰竭患者进行风险分层。1）尚未具有心律转复器/除颤器或双心室起搏器，2）具有射血分数<30%，和3）具有特发性扩张型心肌病（无冠状动脉或瓣膜疾病）的新发心力衰竭患者将经历基于MRI的多参数应变分析以产生72个LV微区域的平均Z分数。在心力衰竭药物治疗（ACC/AHA临床指南）稳定后，将在3个月后重新研究。我们将对基线基底间隔的能力进行统计学表征， 和中间隔哨兵区域平均多参数应变Z分数来预测药物治疗的收缩恢复和心力衰竭不良事件的发生。我们将在统计学上优化前哨监测区域的微区域构成，并将我们的结果与当前标准超声心动图射血分数的预测能力进行比较。预测心力衰竭药物治疗早期恢复的微区域LV收缩功能的度量将更准确地指导心力衰竭高风险手术治疗的应用。

DESCRIPTION (provided by applicant): Patients with clinically significant heart failure comprise the largest and most rapidly growing subset of patients with cardiovascular disease in the U.S. The burden in regard to morbidity, mortality, and health care expense is staggering. In the clinical management of critically ill new-onset heart failure patients, the inability to immediately differentiate those who will respond to medical therapy from those who will not results in the inappropriate application of high-risk heart failure surgery in patients who do not need it, while also denying surgery to those who have the most to benefit from it. MRI-based multi-parametric strain analysis generates a patient-specific, "normalized," and highly accurate description of micro-regional left ventricular (LV) contractile function by comparing three patient specific raw strain parameter values from each of 15,300 grid points (a total of 45,900 database comparisons per patient) to the respective normal average +/- standard deviation (from our laboratory's normal human strain database; n>70). This "normalization" of multiple different patient- specific strain parameter values allows their combination into novel and powerful multi-parametric strain indices that have proven more powerful than any individual strain metric. By applying MRI-based multi-parametric strain analysis in new-onset heart failure (dilated cardiomyopathy) patients, we have discovered marked heterogeneity in the LV regional distribution of contractile injury. This unexpected heterogeneity of contractile injury in dilated cardiomyopathy patients occurs in a consistent pattern that has allowed us to identify "sentinel" LV regions (basilar-septal and mid-septal) that are more sensitive to early injury and that serve as harbingers of irreversible contractile injury in new-onset heart failure patients. We hypothesize that the surveillance of these sentinel LV regions by MRI-based multi-parametric strain analysis allows the risk stratification of new onset heart failure patients in regard to eary response to medical therapy and the subsequent occurrence of heart failure adverse events. New-onset heart failure patients who 1) do not yet have a cardioverter/defibrillator or biventricular pacemaker, 2) have an ejection fraction <30%, and 3) have idiopathic dilated cardiomyopathy (no coronary artery or valvular disease) will undergo MRI-based multi- parametric strain analysis to produce average Z-scores for 72 LV micro-regions. After stabilization on heart failure medical therapy (ACC/AHA Clinical Guidelines), they will be restudied 3 months later. We will statistically characterize the ability of baseline basilar-septal and mid-septal sentinel regional average multi- parametric strain Z-scores to predict both contractile recovery on medical therapy and the occurrence of heart failure adverse events. We will statistically optimize the micro-regional makeup of our sentinel surveillance region and compare our results to the predictive capabilities of the current standard, echocardiographic ejection fraction. A metric of micro-regional LV contractile function that predicts early recovery on heart failure medical therapy would more accurately direct the application of high-risk surgical therapy for heart failure.