INCREMENTAL PROGNOSTIC VALUE OF ARTERIAL ELASTANCE IN MILD-TO-MODERATE IDIOPATHIC PULMONARY FIBROSIS

<strong>PURPOSE: </strong>Previous reports suggested that poor pulmonary function was associated with increased arterial elastance (Ea) in patients with chronic obstructive pulmonary disease and systemic sclerosis. The mechanisms connecting pulmonary function and Ea have not yet been accurately studied in patients with idiopathic pulmonary fibrosis (IPF). The present study was designed to assess Ea in IPF patients without chronic severe pulmonary hypertension and to determine its prognostic role over a medium-term follow-up. <strong>METHODS: </strong>This retrospective study included 60 consecutive patients with mild-to-moderate IPF (73.8±6.6 yrs, 75% males) and 60 controls matched by age, sex and cardiovascular risk factors. All patients underwent physical examination, spirometry, blood tests, modified Haller index (MHI, chest transverse diameter over the distance between sternum and spine) assessment, conventional transthoracic echocardiography implemented with speckle tracking analysis of left atrial positive global strain (LA-GSA+) and finally carotid Doppler ultrasonography, at basal evaluation. The effective arterial elastance index (EaI) was calculated as the ratio of end-systolic pressure to stroke volume index. During follow-up period, we evaluated the composite endpoint of 1) pulmonary or cardiovascular hospitalizations; 2) all-cause mortality. <strong>RESULTS: </strong>At baseline, EaI was significantly higher in IPF patients than controls (4.1±1.3 vs 3.5±1.0 mmHg/ml/m², p=0.01). EaI was strongly correlated to the following variables: C-reactive protein (CRP) (r=0.86), forced vital capacity (FVC) (r=-0.91), E/e’ ratio (r=0.91), LA-GSA+ (r=-0.92), common carotid artery-cross sectional area (CCA-CSA) (r=0.89) and MHI (r=0.86), in IPF patients. Mean follow-up time was 2.4±1.3 yrs. During follow-up, 12 patients died and 17 were hospitalized due to major adverse clinical events. At univariate Cox analysis, CRP (HR 1.51, 95%CI 1.25-1.82), FVC (HR 0.88, 95%CI 0.85-0.91), LA-GSA+ (HR 0.85, 95%CI 0.77-0.94), CCA-CSA (HR 1.12, 95%CI 1.03-1.22) and EaI (HR 2.43, 95%CI 1.75-3.37) were significantly associated with outcome. At multivariate Cox analysis, only EaI (HR 1.60, 95%CI 1.03-2.50) retained statistical significance. An EaI ≥4 mmHg/ml/m²showed 100% sensitivity and 99.4% specificity for predicting outcome (AUC=0.98). <strong>CONCLUSIONS: </strong>In patients with mild-to-moderate IPF, an EaI ≥4 mmHg/ml/m²is a negative prognostic factor over a medium-term follow-up.**研究目的**：既往研究提示，慢性阻塞性肺疾病与系统性硬化症患者的肺功能低下与动脉弹性（arterial elastance, Ea）升高相关。目前针对特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）患者的肺功能与动脉弹性之间的关联机制尚未得到精准研究。本研究旨在评估无慢性重症肺动脉高压的IPF患者的有效动脉弹性指数（effective arterial elastance index, EaI），并明确其在中期随访中的预后价值。**研究方法**：本回顾性研究纳入60例轻中度IPF患者（年龄73.8±6.6岁，男性占比75%），以及60例年龄、性别与心血管危险因素匹配的对照者。所有受试者均接受基线评估，内容包括体格检查、肺量测定、血液检测、改良Haller指数（modified Haller index, MHI，即胸廓横径与胸骨-脊柱间距的比值）评估、采用斑点追踪分析左心房整体正向应变（left atrial positive global strain, LA-GSA+）的常规经胸超声心动图，最终完成颈动脉多普勒超声检查。有效动脉弹性指数以收缩末期压力与每搏输出量指数的比值计算得到。随访期间，我们评估以下复合终点事件：1）肺部或心血管疾病住院；2）全因死亡率。**研究结果**：基线时，IPF患者的EaI显著高于对照组（4.1±1.3 vs 3.5±1.0 mmHg/ml/m²，p=0.01）。在IPF患者中，EaI与以下指标显著相关：C反应蛋白（C-reactive protein, CRP，r=0.86）、用力肺活量（forced vital capacity, FVC，r=-0.91）、E/e’比值（r=0.91）、LA-GSA+（r=-0.92）、颈总动脉横截面积（common carotid artery-cross sectional area, CCA-CSA，r=0.89）以及MHI（r=0.86）。平均随访时间为2.4±1.3年。随访期间，共12例患者死亡，17例因主要不良临床事件住院。单变量Cox回归分析显示，CRP（风险比HR=1.51，95%置信区间CI:1.25-1.82）、FVC（HR=0.88，95%CI:0.85-0.91）、LA-GSA+（HR=0.85，95%CI:0.77-0.94）、CCA-CSA（HR=1.12，95%CI:1.03-1.22）与EaI（HR=2.43，95%CI:1.75-3.37）均与临床结局显著相关。多变量Cox回归分析显示，仅EaI（HR=1.60，95%CI:1.03-2.50）仍具有统计学意义。当EaI≥4 mmHg/ml/m²时，预测临床结局的灵敏度为100%，特异度为99.4%（受试者工作特征曲线下面积AUC=0.98）。**研究结论**：在轻中度IPF患者中，EaI≥4 mmHg/ml/m²是中期随访中的不良预后因素。