Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom; Institute for Cardiovascular Science, University College of London, London, United Kingdom.
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; UPMC Cardiovascular Magnetic Resonance Center, Pittsburgh, Pennsylvania; Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
JACC Cardiovasc Imaging. 2020 Jan;13(1 Pt 1):44-54. doi: 10.1016/j.jcmg.2019.03.017. Epub 2019 May 15.
Because risk stratification data represents a key domain of biomarker validation, we compared associations between outcomes and various cardiovascular magnetic resonance (CMR) metrics quantifying myocardial fibrosis (MF) in noninfarcted myocardium: extracellular volume fraction (ECV), native T1, post-contrast T1, and partition coefficient.
MF associates with vulnerability to adverse events (e.g., mortality and hospitalization for heart failure [HHF]), but investigators still debate its optimal measurement; most histological validation data show strongest ECV correlations with MF.
We enrolled 1,714 consecutive patients without amyloidosis or hypertrophic cardiomyopathy from a single CMR referral center serving an integrated healthcare network. We measured T1 (MOdified Look-Locker Inversion recovery [MOLLI]) in nonenhanced myocardium, averaged from 2 short-axis slices (basal and mid) before and 15 to 20 min after a gadolinium contrast bolus. We compared chi-square test values from CMR MF measures in univariable and multivariable Cox regression models. We assessed "dose-response" relationships in Kaplan-Meier curves using log-rank statistics for quartile strata. We also computed net reclassification improvement (NRI) and integrated discrimination improvement (IDI for Cox models with ECV vs. native T1).
Over a median of 5.6 years, 374 events occurred after CMR (162 HHF events and 279 deaths, 67 with both). ECV yielded the best separation of Kaplan-Meier curves and the highest log-rank statistics. In univariable and multivariable models, ECV associated most strongly with outcomes, demonstrating the highest chi-square test values. Native T1 or post-contrast T1 did not associate with outcomes in the multivariable model. ECV provided added prognostic value to models with native T1, for example, in multivariable models IDI = 0.0037 (95% confidence interval [CI]: 0.0009 to 0.0071), p = 0.02; NRI = 0.151 (95% CI: 0.022 to 0.292), p = 0.04.
Analogous to histological previously published validation data, ECV myocardial fibrosis measures exhibited more robust associations with outcomes than other surrogate CMR MF measures. Superior risk stratification by ECV supports claims that ECV optimally measures MF in noninfarcted myocardium.
由于风险分层数据代表了生物标志物验证的关键领域，我们比较了各种在非梗死心肌中定量心肌纤维化（MF）的心血管磁共振（CMR）指标与结局之间的关联：细胞外容积分数（ECV）、心肌固有 T1 值、对比后 T1 值和分配系数。
MF 与不良事件（如死亡率和心力衰竭住院治疗 [HHF]）的易感性相关，但研究人员仍在争论其最佳测量方法；大多数组织学验证数据显示与 MF 的相关性最强的是 ECV。
我们从一个服务于综合医疗网络的单一 CMR 转诊中心招募了 1714 例连续的无淀粉样变或肥厚型心肌病患者。我们在非增强心肌中测量了 T1（改良 Look-Locker 反转恢复[MOLLI]），来自两个短轴切片（基底和中部）的平均值，在钆对比剂团块前和 15 至 20 分钟后。我们比较了单变量和多变量 Cox 回归模型中 CMR MF 测量的卡方检验值。我们使用对数秩统计评估 Kaplan-Meier 曲线中的“剂量反应”关系，用于四分位数分层。我们还计算了净重新分类改善（NRI）和整合判别改善（IDI 用于 ECV 与固有 T1 的 Cox 模型）。
在中位时间为 5.6 年的随访中，CMR 后发生了 374 例事件（162 例 HHF 事件和 279 例死亡，67 例两者均有）。ECV 可最好地区分 Kaplan-Meier 曲线和最高的对数秩统计值。在单变量和多变量模型中，ECV 与结局的相关性最强，显示出最高的卡方检验值。固有 T1 或对比后 T1 在多变量模型中与结局无关。ECV 为包含固有 T1 的模型提供了额外的预后价值，例如，在多变量模型中 IDI=0.0037（95%置信区间[CI]：0.0009 至 0.0071），p=0.02；NRI=0.151（95%CI：0.022 至 0.292），p=0.04。
与之前发表的组织学验证数据类似，ECV 心肌纤维化测量值与结局的相关性比其他替代 CMR MF 测量值更强。ECV 更好的风险分层支持 ECV 可最佳测量非梗死心肌中 MF 的说法。
