Skewed Cytokine Responses Rather Than the Magnitude of the Cytokine Storm May Drive Cardiac Dysfunction in Multisystem Inflammatory Syndrome in Children.
Skewed Cytokine Responses Rather Than the Magnitude of the Cytokine Storm May Drive Cardiac Dysfunction in Multisystem Inflammatory Syndrome in Children.
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DOI：
10.1161/jaha.121.021428
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发表时间：
2021-08-17
影响因子：
5.4
通讯作者：
Banerjee A
中科院分区：
文献类型：
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作者：
Chang JC;Matsubara D;Morgan RW;Diorio C;Nadaraj S;Teachey DT;Bassiri H;Behrens EM;Banerjee A
心功能不全是儿童多系统炎性综合征（MIS-C）的一个突出特征，但病因尚不清楚。我们确定了功能障碍是全局性的还是局部性的，以及它是否与细胞因子环境、微血管病或休克的严重程度相关。我们分析了心肌变形的超声心动图参数，并比较了43例年龄≤18岁的MIS-C患者和40例对照组的整体和节段性左心室应变。主要结局包括左心室整体纵向应变、右心室游离壁应变和左心房应变。我们评估了10种促炎细胞因子、微血管病变特征（可溶性C5 b 9）和血管活性正性肌力需求之间的关系。与对照组相比，MIS-C病例的收缩和舒张功能的所有参数均显著受损。65%的MIS-C患者左心室功能异常（|整体纵向应变|<17%），尽管细胞因子的升高是适度的。所有左室节段均受累，无心尖或基底优势提示急性应激性心肌病。更差的整体纵向应变与白细胞介素-6（ρ −0.43）和白细胞介素-8（ρ −0.43）与总高细胞因子血症的比率较高相关，但与白细胞介素-6或白细胞介素-8或总高细胞因子血症的绝对水平无关。同样，右心室游离壁应变差与白细胞介素-8相对表达较高相关（ρ −0.59）。功能与微血管病或血管活性正性肌力需求之间无显著相关性。MIS-C患者的心肌功能总体下降，不能用急性应激性心肌病解释。心功能不全可能是由免疫应答对白细胞介素-6和白细胞介素-8通路的相对偏斜驱动的，而不是炎症过度的程度，从而改善了MIS-C中心肌受累的当前范例。
Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS‐C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine milieu, microangiopathy, or severity of shock. We analyzed echocardiographic parameters of myocardial deformation and compared global and segmental left ventricular strain between 43 cases with MIS‐C ≤18 years old and 40 controls. Primary outcomes included left ventricular global longitudinal strain, right ventricular free wall strain), and left atrial strain. We evaluated relationships between strain and profiles of 10 proinflammatory cytokines, microangiopathic features (soluble C5b9), and vasoactive‐inotropic requirements. Compared with controls, cases with MIS‐C had significant impairments in all parameters of systolic and diastolic function. 65% of cases with MIS‐C had abnormal left ventricular function (|global longitudinal strain|<17%), although elevations of cytokines were modest. All left ventricular segments were involved, without apical or basal dominance to suggest acute stress cardiomyopathy. Worse global longitudinal strain correlated with higher ratios of interleukin‐6 (ρ −0.43) and interleukin‐8 (ρ −0.43) to total hypercytokinemia, but not absolute levels of interleukin‐6 or interleukin‐8, or total hypercytokinemia. Similarly, worse right ventricular free wall strain correlated with higher relative interleukin‐8 expression (ρ −0.59). There were no significant associations between function and microangiopathy or vasoactive‐inotropic requirements. Myocardial function is globally decreased in MIS‐C and not explained by acute stress cardiomyopathy. Cardiac dysfunction may be driven by the relative skew of the immune response toward interleukin‐6 and interleukin‐8 pathways, more so than degree of hyperinflammation, refining the current paradigm of myocardial involvement in MIS‐C.