Supplementary Material for: Cardiopulmonary Exercise Testing to Detect Chronic Thromboembolic Pulmonary Hypertension in Patients with Normal Echocardiography

<b><i>Background:</i></b> Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious complication of pulmonary embolism (PE). Taking into account the reported incidence of CTEPH after acute PE, the number of patients with undiagnosed CTEPH may be high. <b><i>Objectives:</i></b> We aimed to determine if cardiopulmonary exercise testing (CPET) could serve as complementary tool in the diagnosis of CTEPH and can detect CTEPH in patients with normal echocardiography. <b><i>Methods:</i></b> At diagnosis, we analyzed the data of CPET parameters in 42 patients with proven CTEPH and 51 controls, and evaluated the performance of two scores. <b><i>Results:</i></b> VE/VCO₂ slope, EQO₂, EQCO₂, P(A-a)O₂, end-tidal partial pressure of CO₂ at anaerobic threshold (PETCO₂) and capillary to end-tidal carbon dioxide gradient [P(c-ET)CO₂] were significantly different between patients with CTEPH and controls (p &lt; 0.001). P(c-ET)CO₂ was the single parameter with the highest sensitivity (85.7%) and specificity (88.2%). A score combining VE/VCO₂ slope, P(A-a)O₂, P(c-ET)CO₂, PETCO₂ [4-parameter-CPET (4-P-CPET) score] reached a sensitivity of 83.3% and a specificity of 92.2% after cross-validation. In 42 patients with CTEPH, echocardiography identified PH in 29 patients (69%), but it was normal in 13 patients (31%). All patients with normal or unmeasurable right ventricular systolic pressure had a pathological CPET. Twelve of the 13 patients (92%) were detected by both CPET scores. <b><i>Conclusion:</i></b> CPET is a useful noninvasive diagnostic tool for the detection of CTEPH in patients with suspected PH but normal echocardiography. The 4-P-CPET score provides a high sensitivity with the highest specificity.

<b><i>背景：</i></b> 慢性血栓栓塞性肺动脉高压（Chronic thromboembolic pulmonary hypertension, CTEPH）是肺栓塞（pulmonary embolism, PE）的严重并发症。鉴于已有报道的急性肺栓塞后CTEPH发生率，未被确诊的CTEPH患者群体规模可能较高。<b><i>研究目的：</i></b> 本研究旨在明确心肺运动试验（cardiopulmonary exercise testing, CPET）能否作为CTEPH诊断的补充工具，并可在超声心动图结果正常的患者中检出CTEPH。<b><i>研究方法：</i></b> 于确诊节点，我们分析了42例经证实的CTEPH患者与51例对照者的CPET参数数据，并评估了两种评分模型的诊断效能。<b><i>研究结果：</i></b> CTEPH患者与对照者的通气当量CO₂斜率（VE/VCO₂ slope）、氧摄取效率（EQO₂）、CO₂排出效率（EQCO₂）、肺泡动脉氧分压差（P(A-a)O₂）、无氧阈潮气末CO₂分压（PETCO₂）以及毛细血管-潮气末CO₂梯度[P(c-ET)CO₂]均存在显著统计学差异（p < 0.001）。其中毛细血管-潮气末CO₂梯度[P(c-ET)CO₂]是单一参数中灵敏度最高（85.7%）、特异度最高（88.2%）的指标。结合通气当量CO₂斜率、肺泡动脉氧分压差、毛细血管-潮气末CO₂梯度及潮气末CO₂分压的评分模型[四参数心肺运动试验评分（4-parameter-CPET score, 4-P-CPET score）]经交叉验证后，灵敏度达83.3%，特异度达92.2%。在42例CTEPH患者中，超声心动图检出肺动脉高压（pulmonary hypertension, PH）29例（69%），但13例患者（31%）的超声心动图结果正常。所有右心室收缩压（right ventricular systolic pressure）正常或无法测得的患者，其CPET结果均存在异常。13例超声心动图正常的患者中，有12例（92%）被两种CPET评分模型检出。<b><i>研究结论：</i></b> CPET是一项实用的无创诊断工具，可用于疑似肺动脉高压但超声心动图结果正常的患者的CTEPH筛查。四参数CPET评分模型兼具较高的灵敏度与最优的特异度。