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

描述(申请人提供)：临床上严重心力衰竭的患者构成了美国最大和增长最快的心血管疾病患者亚群。在发病率、死亡率和医疗费用方面的负担是惊人的。在重症新发心力衰竭患者的临床管理中，由于无法立即区分对药物治疗有反应的患者和不会对其有反应的患者，导致在不需要的患者中不适当地应用高风险心力衰竭手术，同时拒绝向那些最受益的患者进行手术。基于MRI的多参数应变分析通过比较三名患者，生成了患者特有的、归一化的、高度准确的左心室微区域收缩功能描述 从15,300个网格点的特定原始应变参数值(每个患者总共45,900个数据库比较)到各自的正常平均正/负标准差(来自我们实验室的正常人类应变数据库；n&gt；70)。这种多个不同患者特定应变参数值的“标准化”允许它们组合成新的和强大的多参数应变指数，事实证明，这些指数比任何单独的应变指标都更强大。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，我们发现收缩损伤的左室局部分布具有明显的异质性。扩张型心肌病患者收缩损伤的这种意想不到的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(基底间隔和间隔中部)，并作为新发心力衰竭患者不可逆转收缩损伤的先兆。我们假设，通过基于MRI的多参数应变分析对这些前哨LV区域进行监测，可以根据新发心力衰竭患者对药物治疗的早期反应和随后发生的心力衰竭不良事件进行风险分层。1)尚未安装心脏复律/除颤器或双室起搏器、2)射血分数<30%、3)患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接受基于MRI的多参数应变分析，得出72个LV微区的平均Z分数。在心力衰竭药物治疗稳定后(ACC/AHA临床指南)，它们将在3个月后重新研究。我们将统计分析基线上的基底间隔的能力。 间隔中部前哨区域平均多参数应变Z分数预测药物治疗后的收缩恢复和心力衰竭不良事件的发生。我们将在统计上优化哨点监测区域的微观区域构成，并将我们的结果与当前标准的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后早期恢复的微局部左室收缩功能的指标将更准确地指导心力衰竭高风险外科治疗的应用。 公共卫生相关性：在危重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人和那些不会导致不适当应用高危心力衰竭的人。 对不需要手术的患者进行手术，同时拒绝对那些从中受益最大的人进行手术。我们发现，在新发心力衰竭患者中，“前哨”左心室区域可作为不可逆收缩损伤的先兆。我们推测，通过先进的基于应变的收缩功能指标(基于MRI的多参数应变分析)对这些区域的监测将更好地指导高危心脏的应用 通过对新发心力衰竭患者进行风险分层的失败外科治疗 关于药物治疗的反应和随后发生的心力衰竭不良事件。

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. PUBLIC HEALTH RELEVANCE: 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 simultaneously denying surgery to those who have the most to benefit from it. We have identified "sentinel" left ventricular regions that serve as harbingers of irreversible contractile injury in new-onset heart failure patients. We hypothesize that the surveillance of these regions by advanced strain-based metrics of contractile function (MRI-based multi- parametric strain analysis) will better direct the application of high-risk heart failure surgical therapy by allowing the risk stratification of new onset heart failure patients in regard to response to medical therapy and the subsequent occurrence of heart failure adverse events.