Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Kyoto, Japan.
Department of Nephrology and Dialysis, Kyoritsu Hospital, Kawanishi, Japan.
Cochrane Database Syst Rev. 2022 May 9;5(5):CD012809. doi: 10.1002/14651858.CD012809.pub2.
BACKGROUND: Pulmonary hypertension (PH) is an important cause of morbidity and mortality, which leads to a substantial loss of exercise capacity. PH ultimately leads to right ventricular overload and subsequent heart failure and early death. Although early detection and treatment of PH are recommended, due to the limited responsiveness to therapy at late disease stages, many patients are diagnosed at a later stage of the disease because symptoms and signs of PH are nonspecific at earlier stages. While direct pressure measurement with right-heart catheterisation is the clinical reference standard for PH, it is not routinely used due to its invasiveness and complications. Trans-thoracic Doppler echocardiography is less invasive, less expensive, and widely available compared to right-heart catheterisation; it is therefore recommended that echocardiography be used as an initial diagnosis method in guidelines. However, several studies have questioned the accuracy of noninvasively measured pulmonary artery pressure. There is substantial uncertainty about the diagnostic accuracy of echocardiography for the diagnosis of PH. OBJECTIVES: To determine the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH. SEARCH METHODS: We searched MEDLINE, Embase, Web of Science Core Collection, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform from database inception to August 2021, reference lists of articles, and contacted study authors. We applied no restrictions on language or type of publication. SELECTION CRITERIA: We included studies that evaluated the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH, where right-heart catheterisation was the reference standard. We excluded diagnostic case-control studies (two-gate design), studies where right-heart catheterisation was not the reference standard, and those in which the reference standard threshold differed from 25 mmHg. We also excluded studies that did not provide sufficient diagnostic test accuracy data (true-positive [TP], false-positive [FP], true-negative [TN], and false-negative [FN] values, based on the reference standard). We included studies that provided data from which we could extract TP, FP, TN, and FN values, based on the reference standard. Two authors independently screened and assessed the eligibility based on the titles and abstracts of records identified by the search. After the title and abstract screening, the full-text reports of all potentially eligible studies were obtained, and two authors independently assessed the eligibility of the full-text reports. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data from each of the included studies. We contacted the authors of the included studies to obtain missing data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non-linear mixed model. We explored sources of heterogeneity regarding types of PH, methods to estimate the right atrial pressure, and threshold of index test to diagnose PH. All analyses were performed using the Review Manager 5, SAS and STATA statistical software. MAIN RESULTS: We included 17 studies (comprising 3656 adult patients) assessing the diagnostic accuracy of Doppler trans-thoracic echocardiography for the diagnosis of PH. The included studies were heterogeneous in terms of patient distribution of age, sex, WHO classification, setting, country, positivity threshold, and year of publication. The prevalence of PH reported in the included studies varied widely (from 6% to 88%). The threshold of index test for PH diagnosis varied widely (from 30 mmHg to 47 mmHg) and was not always prespecified. No study was assigned low risk of bias or low concern in each QUADAS-2 domain assessed. Poor reporting, especially in the index test and reference standard domains, hampered conclusive judgement about the risk of bias. There was little consistency in the thresholds used in the included studies; therefore, common thresholds contained very sparse data, which prevented us from calculating summary points of accuracy estimates. With a fixed specificity of 86% (the median specificity), the estimated sensitivity derived from the median value of specificity using HSROC model was 87% (95% confidence interval [CI]: 78% to 96%). Using a prevalence of PH of 68%, which was the median among the included studies conducted mainly in tertiary hospitals, diagnosing a cohort of 1000 adult patients under suspicion of PH would result in 88 patients being undiagnosed with PH (false negatives) and 275 patients would avoid unnecessary referral for a right-heart catheterisation (true negatives). In addition, 592 of 1000 patients would receive an appropriate and timely referral for a right-heart catheterisation (true positives), while 45 patients would be wrongly considered to have PH (false positives). Conversely, when we assumed low prevalence of PH (10%), as in the case of preoperative examinations for liver transplantation, the number of false negatives and false positives would be 13 and 126, respectively. AUTHORS' CONCLUSIONS: Our evidence assessment of echocardiography for the diagnosis of PH in adult patients revealed several limitations. We were unable to determine the average sensitivity and specificity at any particular index test threshold and to explain the observed variability in results. The high heterogeneity of the collected data and the poor methodological quality would constrain the implementation of this result into clinical practice. Further studies relative to the accuracy of Doppler trans-thoracic echocardiography for the diagnosis of PH in adults, that apply a rigorous methodology for conducting diagnostic test accuracy studies, are needed.
背景:肺动脉高压(PH)是发病率和死亡率的重要原因,导致运动能力显著下降。PH 最终导致右心室过载,随后发生心力衰竭和早期死亡。尽管建议早期发现和治疗 PH,但由于在疾病晚期对治疗的反应有限,许多患者在疾病的晚期才被诊断出来,因为 PH 的症状和体征在早期阶段并不特异。虽然右心导管检查是 PH 的临床参考标准,但由于其具有侵入性和并发症,因此并未常规使用。经胸多普勒超声心动图的侵入性较小、费用较低且广泛可用,与右心导管检查相比;因此,指南建议将超声心动图作为初始诊断方法。然而,几项研究对非侵入性测量肺动脉压的准确性提出了质疑。对于 PH 的诊断,超声心动图的诊断准确性存在很大的不确定性。
目的:评估经胸多普勒超声心动图检测 PH 的诊断准确性。
检索方法:我们检索了 MEDLINE、Embase、Web of Science 核心合集、ClinicalTrials.gov、世界卫生组织国际临床试验注册平台,从数据库建立到 2021 年 8 月,还检索了文章的参考文献,并联系了研究作者。我们对语言或出版物类型没有任何限制。
选择标准:我们纳入了评估经胸多普勒超声心动图检测 PH 的诊断准确性的研究,其中右心导管检查为参考标准。我们排除了诊断病例对照研究(双门设计)、右心导管检查不是参考标准的研究,以及参考标准阈值不同于 25mmHg 的研究。我们还排除了未提供足够诊断测试准确性数据(根据参考标准的真阳性[TP]、假阳性[FP]、真阴性[TN]和假阴性[FN]值)的研究。我们纳入了提供了基于参考标准的 TP、FP、TN 和 FN 值的研究。两名作者独立筛选和评估了基于记录标题和摘要的纳入标准。在标题和摘要筛选后,获得了所有潜在合格研究的全文报告,并由两名作者独立评估了全文报告的合格性。
数据收集和分析:两名综述作者独立评估了纳入研究的偏倚风险,并从每项纳入研究中提取数据。我们联系了纳入研究的作者以获取缺失的数据。我们使用 QUADAS-2 工具评估了研究的方法学质量。我们通过拟合分层汇总 ROC(HSROC)非线性混合模型来估计汇总接收者操作特征(SROC)曲线。我们探讨了不同类型的 PH、估计右心房压力的方法以及用于诊断 PH 的指数测试阈值对结果的异质性来源。所有分析均使用 Review Manager 5、SAS 和 STATA 统计软件进行。
主要结果:我们纳入了 17 项研究(共纳入 3656 名成年患者),评估了多普勒经胸超声心动图对 PH 的诊断准确性。纳入的研究在年龄、性别、WHO 分类、设置、国家、阳性阈值和发表年份方面存在异质性。纳入研究中 PH 的患病率差异很大(6%至 88%)。用于诊断 PH 的指数测试的阈值差异很大(30mmHg 至 47mmHg),且并不总是预先指定。在评估的每个 QUADAS-2 领域中,没有研究被评为低偏倚风险或低关注。索引测试和参考标准领域的报告较差,尤其是在索引测试和参考标准领域,这阻碍了对偏倚风险的明确判断。纳入研究中使用的阈值一致性较差;因此,常见阈值包含非常稀疏的数据,这使得我们无法计算汇总准确性估计值。在特异性固定为 86%(中位数特异性)的情况下,使用 HSROC 模型从特异性的中位数中得出的估计敏感性为 87%(95%置信区间[CI]:78%至 96%)。在主要在三级医院进行的纳入研究中,以 PH 可疑的 1000 名成年患者为研究对象,PH 的患病率为 68%,中位数为 68%,这意味着将有 88 名患者被漏诊为 PH(假阴性),275 名患者将避免不必要的右心导管检查(真阴性)。此外,在 1000 名患者中,592 名将接受适当和及时的右心导管检查(真阳性),而 45 名将被错误地认为患有 PH(假阳性)。相反,当我们假设 PH 的患病率较低(10%),如肝移植术前检查时,假阴性和假阳性的数量将分别为 13 和 126。
作者结论:我们对超声心动图在成年患者 PH 诊断中的证据评估显示出了一些局限性。我们无法确定任何特定指数测试阈值的平均敏感性和特异性,也无法解释结果中的可变性。纳入数据的高度异质性和较差的方法学质量将限制这一结果在临床实践中的实施。需要进一步开展有关多普勒经胸超声心动图在成人 PH 诊断中的准确性的研究,这些研究应用严格的诊断测试准确性研究方法。
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