Abstract

Objectives

Serum levels of matrix metalloproteinase-12 cleaved fragment of titin (TIM), a novel circulatory biomarker specific for cardiac titin degradation, has emerged as a potential biomarker in cardiovascular diseases. In this work, we aimed to evaluate the association between TIM and maximal functional capacity assessed by the percentage of predicted peak exercise oxygen uptake (pp-peakVO2) in patients with heart failure and preserved ejection fraction (HFpEF). Design. In this post-hoc study, we included 46 stable symptomatic (New York Heart Association II-III) HFpEF patients enrolled in the TRAINING-HF study (NCT02638961). pp-peak-VO2 was calculated from baseline values. Baseline circulating levels of TIM were measured by competitive ELISA in serum from the TRAINING-HF patients. The independent association between TIM and pp-peakVO2 was evaluated by multivariate linear regression analysis. Results. The mean age of the sample was 73.8 ± 8.7 years, 56.5% were females, and 76.1% were on NYHA II. The medians of pp-peakVO2 and TIM were 60.9% (50.4–69.3), and 130.1 ng/mL (98.1–159.5), respectively. The median of NT-proBNP was 912 pg/mL (302–1826). pp-peakVO2 was significant and inversely correlated with TIM (r= −41, p = .005). In multivariate analysis, after adjusting for NYHA class, hypertension, body mass index, and glomerular filtration rate, higher TIM was significantly associated with lower pp-peak VO2 (p = .029). Conclusions. In this sample of stable and symptomatic HFpEF patients, higher serum levels of TIM identified patients with worse functional status.

中文翻译：

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基质金属蛋白酶 12 切割的肌联蛋白片段作为心力衰竭和射血分数保留患者功能能力的预测因子

摘要

目标

血清基质金属蛋白酶-12 肌联蛋白裂解片段 (TIM) 的血清水平是一种新型的心脏肌联蛋白降解特异性循环生物标志物，已成为心血管疾病的潜在生物标志物。在这项工作中，我们旨在评估 TIM 与最大功能能力之间的关联，通过预测的最大运动摄氧量百分比 (pp-peakVO2) 在心力衰竭和保留射血分数 (HFpEF) 患者中进行评估。设计。在这项事后研究中，我们纳入了 46 名参加 TRAINING-HF 研究 (NCT02638961) 的稳定症状（纽约心脏协会 II-III）HFpEF 患者。pp-peak-VO2 是根据基线值计算的。通过竞争性 ELISA 在 TRAINING-HF 患者的血清中测量 TIM 的基线循环水平。通过多元线性回归分析评估 TIM 和 pp-peakVO2 之间的独立关联。结果。样本的平均年龄为 73.8 ± 8.7 岁，56.5% 为女性，76.1% 为 NYHA II。pp-peakVO2 和 TIM 的中位数分别为 60.9% (50.4–69.3) 和 130.1 ng/mL (98.1–159.5)。NT-proBNP 的中位数为 912 pg/mL (302–1826)。pp-peakVO2 显着且与 TIM 呈负相关（r= -41，p = .005）。在多变量分析中，在调整 NYHA 分级、高血压、体重指数和肾小球滤过率后，较高的 TIM 与较低的 pp-peak VO2 显着相关 ( p  = .029)。结论。在这个稳定和有症状的 HFpEF 患者样本中，较高的 TIM 血清水平确定了功能状态较差的患者。