Kostiainen Iiro, Simonen Piia, Aaltonen Katri, Lindén Riikka, Karppinen Noora, Gordin Daniel, Rapola Janne, Schalin-Jäntti Camilla, Matikainen Niina
Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions), 00280 Helsinki, Finland.
Cardiology, Heart and Lung Center, Helsinki University Hospital and University of Helsinki, 00280 Helsinki, Finland.
Cancers (Basel). 2024 Nov 21;16(23):3896. doi: 10.3390/cancers16233896.
Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of the present study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. We measured 5-HIAA and cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeated measurements, proBNP, vascular function, hepatic tumor load, and transthoracic echocardiography (TTE) at baseline and during the median 5-year follow-up. Of 65 patients with SI-NETs, 54 patients underwent a prospective follow-up. In addition, survival was evaluated during the median follow-up of 6 years. At baseline, three patients had CHD. During the median follow-up of 5 years, two patients (4%) developed CHD. Cum-5-HIAA and proBNP correlated with CHD (Westberg score, Spearman's ρ = 0.32 and 0.31, respectively). Cum-5-HIAA had a superior diagnostic capability, predicting CHD in receiver operator characteristic analysis with an AUC of 0.98 (95% CI: 0.94-1.00) and outperformed proBNP, chromogranin A (CgA), and individual serum 5-HIAA measurements (AUC = 0.75, 0.85, and 0.91, respectively). Minor changes in valve regurgitation were frequently detected but did not correlate with vascular function. Regurgitation increased or decreased in 29% of tricuspid and 30% of pulmonic valves. CHD, hepatic tumor load, serum 5-HIAA, and elevated aortic pulse wave velocity (PWV) were associated with increased mortality in SI-NET patients. Cum-5-HIAA is a promising biomarker for CHD risk and outperformed other biomarkers. CHD and hepatic tumor load are the strongest predictors of mortality. PWV is a novel predictor of survival. The incidence of CHD was low among the SI-NET patients, probably reflecting successful treatment regimens.
小肠神经内分泌肿瘤（SI-NETs）的特征为类癌综合征和类癌性心脏病（CHD）。本研究的目的是在一项前瞻性中期随访研究中确定类癌性心脏病和生存的早期风险标志物。我们在基线期和中位5年随访期间，基于重复测量结果测定了5-羟吲哚乙酸（5-HIAA）和累积5-HIAA暴露量（Cum-5-HIAA）、脑钠肽前体（proBNP）、血管功能、肝脏肿瘤负荷，并进行了经胸超声心动图（TTE）检查。在65例SI-NETs患者中，54例患者接受了前瞻性随访。此外，在中位6年随访期间评估了生存情况。基线时，有3例患者患有CHD。在中位5年随访期间，2例患者（4%）发生了CHD。Cum-5-HIAA和proBNP与CHD相关（韦斯特贝里评分，Spearman相关系数ρ分别为0.32和0.31）。Cum-5-HIAA具有更好的诊断能力，在受试者工作特征分析中预测CHD的曲线下面积（AUC）为0.98（95%可信区间：0.94-1.00），优于proBNP、嗜铬粒蛋白A（CgA）和单次血清5-HIAA测量值（AUC分别为0.75、0.85和0.91）。瓣膜反流的微小变化经常被检测到，但与血管功能无关。三尖瓣反流增加或减少的比例为29%，肺动脉瓣为30%。CHD、肝脏肿瘤负荷、血清5-HIAA和主动脉脉搏波速度（PWV）升高与SI-NETs患者死亡率增加相关。Cum-5-HIAA是一种很有前景的CHD风险生物标志物，优于其他生物标志物。CHD和肝脏肿瘤负荷是死亡率的最强预测因素。PWV是生存的一个新的预测因素。SI-NETs患者中CHD的发病率较低，这可能反映了成功的治疗方案。
