Ferrari Margaret R, Schäfer Michal, Hunter Kendall S, Di Maria Michael V
SafeBeat Rx Inc, Carson CA, United States.
Division of Cardiothoracic Surgery, University of Utah Health, Salt Lake City, Utah, 84132, United States.
medRxiv. 2024 Jul 12:2024.07.11.24310309. doi: 10.1101/2024.07.11.24310309.
Single ventricle heart disease is a severe and life-threatening illness, and improvements in clinical outcomes of those with Fontan circulation have not yet yielded acceptable survival over the past two decades. Patients are at risk of developing a diverse variety of Fontan-associated comorbidities that ultimately requires heart transplant. Our observational cohort study goal was to determine if principal component analysis (PCA) applied to data collected from a substantial Fontan cohort can predict functional decline (N=140). Heterogeneous data broadly consisting of measures of cardiac and vascular function, exercise (VO), lymphatic biomarkers, and blood biomarkers were collected over 11 years at a single site; in that time, 16 events occurred that are considered here in a composite outcome measure. After standardization and PCA, principal components (PCs) representing >5% of total variance were thematically labeled based on their constituents and tested for association with the composite outcome. Our main findings suggest that the 6 PC (PC6), representing 7.1% percent of the total variance in the set, is greatly influenced by blood serum biomarkers and superior vena cava flow, is a superior measure of proportional hazard compared to EF, and displayed the greatest accuracy for classifying Fontan patients as determined by AUC. In bivariate hazard analysis, we found that models combining systolic function (EF or PC5) and lymphatic dysfunction (PC6) were most predictive, with the former having the greatest AIC, and the latter having the highest c-statistic. Our findings support our hypothesis that a multifactorial model must be considered to improve prognosis in the Fontan population.
单心室心脏病是一种严重的、危及生命的疾病，在过去二十年中，Fontan循环患者临床结局的改善尚未带来可接受的生存率。患者有发生多种Fontan相关合并症的风险，最终需要进行心脏移植。我们的观察性队列研究目标是确定应用于从大量Fontan队列收集的数据的主成分分析（PCA）是否可以预测功能衰退（N = 140）。在单一研究地点，历时11年收集了广泛的异质性数据，这些数据主要包括心脏和血管功能、运动（VO）、淋巴生物标志物和血液生物标志物的测量值；在此期间，发生了16起事件，在综合结局指标中予以考虑。经过标准化和主成分分析后，根据其组成成分对代表总方差>5%的主成分（PC）进行主题标记，并测试其与综合结局的关联。我们的主要研究结果表明，代表该组总方差7.1%的第6主成分（PC6）受血清生物标志物和上腔静脉血流的影响很大，与射血分数相比，是比例风险的更好衡量指标，并且根据曲线下面积（AUC）确定，在对Fontan患者进行分类时显示出最高的准确性。在双变量风险分析中，我们发现结合收缩功能（射血分数或PC5）和淋巴功能障碍（PC6）的模型预测性最强，前者具有最大的赤池信息准则（AIC），后者具有最高的一致性指数（c统计量）。我们的研究结果支持我们的假设，即必须考虑采用多因素模型来改善Fontan人群的预后。
