Cardiac MR Characterization of Arrhythmogenic Scar in Patients with Myocardial Infarction

 描述（由申请人提供）：在美国，与瘢痕相关的室性心动过速和室颤（VT/VF）相关的心源性猝死（SCD）是主要死亡原因之一。几项随机、多中心试验已经证明植入式心律转复除颤器（ICD）的生存益处，但社会支出为20 - 40亿美元。不幸的是，大多数（=90%）接受ICD进行一级预防的患者并未从ICD中获益，但仍面临相关成本和发病率。因此，识别最能从ICD植入中获益的患者的成像生物标志物将具有重大的临床和经济影响。本提案的总体目标是在VT猪模型以及既往心肌梗死（MI）患者中确定室性心律失常底物的心脏MR（CMR）生物标志物，从而确定可以区分ICD植入对SCD一级预防最有益的患者的CMR生物标志物。CMR允许使用晚期钆增强（LGE）和使用心肌T1标测的间质弥漫性纤维化来表征心肌梗死。LGE的不均匀瘢痕区域，即致密瘢痕周围或内部具有中等LGE信号水平的区域，已被认为是致瘤性瘢痕的CMR生物标志物。然而，这种异质区域的可重复测量是具有挑战性的。我们在VT猪模型中的初步数据以及最近在接受侵入性左心室（LV）电压标测的VT患者中的数据表明，从高分辨率3D LGE中识别的传导通道是致瘤性瘢痕的替代物，从而表明3D LGE可用于识别致瘤性瘢痕。此外，我们最近对间质弥漫性纤维化成像的能力可能从根本上改变我们评估未来SCD风险的能力。我们最近开发了一种多切片心肌T1标测序列，可对整个心室的T1标测进行准确、可重复和精确的量化。成功完成该提案将通过表征我们在猪模型和患者中测量的CMR（解剖学）与侵入性电描记图（电气）之间的关系，提高我们对VT基质的理解;此外，它将提供额外的基于成像的风险因素，以改善当前的风险分层方案，以确定从一级预防ICD中获益最多的患者。

 DESCRIPTION (provided by applicant): Sudden cardiac death (SCD) associated with scar-related ventricular tachycardia and fibrillation (VT/VF) is one of the main causes of death in the United States. Several randomized, multi-center trials have demonstrated a survival benefit with implantable cardioverter-defibrillator (ICDs), but with a societal expenditure of $2-4 billion. Unfortunately, a majority (=90%) of patients receiving an ICD for primary prevention do not benefit from the ICD, yet are exposed to the associated costs and morbidity. Therefore, imaging biomarkers that identify patients who will most benefit from ICD implantation will have substantial clinical and economic impact. The overall objective of this proposal is to identify cardiac MR (CMR) biomarkers of the substrate of ventricular arrhythmia in a swine model of VT as well as in patients with prior myocardial infarction (MI) and thereby identify the CMR biomarkers that can discriminate the patients who will most benefit from an ICD implantation for primary prevention of SCD. CMR allows for the characterization of myocardial infarcts using late gadolinium enhancement (LGE) and interstitial diffuse fibrosis using myocardial T1 mapping. Heterogeneous scar area of LGE, i.e. areas with intermediate LGE signal level surrounding or within dense scar, have been suggested to be the CMR biomarker for the arrhythmogenic scar. However, reproducible measurement of this heterogeneous area is challenging. Our preliminary data in swine model of VT as well as recent data in VT patients undergoing invasive left ventricular (LV) voltage mapping suggest that the conducting channels identified from high-resolution 3D LGE are surrogates of arrhythmogenic scar, thereby suggesting that 3D LGE could be used to identify arrhythmogenic scar. Furthermore, our recent ability in imaging the interstitial diffuse fibrosis could fundamentally change our ability in assessing future SCD risk. We recently developed a multi-slice myocardial T1 mapping sequence that allows accurate, reproducible and precise quantification of T1 mapping over the entire ventricle. Successful completion of this proposal will improve our understanding of VT substrate by characterizing the relationship between what we measure in CMR (anatomical) vs. invasive electrograms (electrical) in both swine model and patient; Furthermore it will provide additional imaging-based risk factors to improve current risk stratification scheme to identify patients who most benefit from the primary prevention ICD.