Section of Gastroenterology, Department of Medicine, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway.
BMC Cancer. 2010 Jan 6;10:6. doi: 10.1186/1471-2407-10-6.
Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease.
Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation.
Mean strain was -21% +/- 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% +/- 3). Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR). Thirty-six patients had normal or mildly reduced RV function (strain < or = -20%, mean -25% +/- 3). There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p < 0.001). Patients with reduced RV function had higher plasma CCN2 levels than those with normal or mildly reduced RV function (p < 0.001). Plasma CCN2 > or = 77 microg/L was an independent predictor of reduced RV function (odds ratio 15.36 [95% CI 4.15;56.86]) and had 88% sensitivity and 69% specificity for its detection (p < 0.001). Plasma CCN2 was elevated in patients with mild or greater TR/PR compared to those with no or minimal TR/PR (p = 0.008), with the highest levels seen in moderate to severe TR/PR (p = 0.03).
Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.
类癌性心脏病是神经内分泌肿瘤的已知并发症，其特征为右心纤维性病变。类癌性心脏病传统上是根据瓣膜受累程度来定义的。由于壁层受累，右心室（RV）功能障碍也可能是一种表现。结缔组织生长因子（CCN2）在许多纤维性疾病中升高。其在类癌性心脏病中的作用尚不清楚。我们试图研究血浆 CCN2 与类癌性心脏病中瓣膜和壁层受累之间的关系。
对 69 例神经内分泌肿瘤患者进行超声心动图检查。使用心肌收缩应变的组织多普勒分析评估 RV 功能。使用酶联免疫吸附试验分析血浆 CCN2。适当情况下使用 Mann-Whitney U、Kruskal-Wallis、卡方和 Fisher 确切检验进行组间比较。使用线性回归评估相关性。
平均应变值为-21% +/- 5。33 例患者 RV 功能降低（应变>-20%，平均-16% +/- 3）。其中 8 例三尖瓣和/或肺动脉瓣反流（TR/PR）无或轻度。36 例患者 RV 功能正常或轻度降低（应变≤-20%，平均-25% +/- 3）。RV 功能与血浆 CCN2 水平呈显著负相关（r = 0.47，p < 0.001）。RV 功能降低的患者血浆 CCN2 水平高于 RV 功能正常或轻度降低的患者（p < 0.001）。血浆 CCN2 >或= 77μg/L 是 RV 功能降低的独立预测因子（优势比 15.36[95%置信区间 4.15;56.86]），其检测的敏感性为 88%，特异性为 69%（p < 0.001）。与无或轻度 TR/PR 相比，轻度或更严重 TR/PR 的患者血浆 CCN2 水平升高（p = 0.008），中度至重度 TR/PR 的患者血浆 CCN2 水平最高（p = 0.03）。
神经内分泌肿瘤患者中，血浆 CCN2 水平升高与 RV 功能障碍和瓣膜反流相关。CCN2 可能在神经内分泌肿瘤相关的心脏纤维化中发挥作用，并可能作为其早期阶段的标志物。
