What was studied in this review?
Pulmonary hypertension is high blood pressure in the blood vessels that supply blood from the right half of the heart to the lungs. It is a serious condition that can damage the right side of the heart. The walls in the blood vessels become thick and stiff which makes it harder for the blood to flow. This can lead to heart failure. Symptoms can include shortness of breath, tiredness, chest pain, a racing heartbeat or swelling in the lower limbs and abdomen.
The symptoms can be similar to other heart and lung diseases, so diagnosis can take time. Early diagnosis is beneficial because treatment can start early. Starting treatment early is better because people respond better to treatment in the early stages of the disease. Not being diagnosed early can have severe consequences such as disability in daily life or death.
The most accurate way to diagnose pulmonary hypertension is using a pressure measurement called right-heart catheterisation. However, this is invasive and can cause complications. Another technique, called Doppler echocardiography is noninvasive, cheaper and more widely available in hospitals. Therefore, many guidelines recommend the use of echocardiography as an initial diagnosis method. We wanted to do this review because several studies have questioned the accuracy of echocardiography. We wanted to find out how good echocardiography is compared to right-heart catheterisation for the diagnosis of pulmonary hypertension.
What was the aim of this review?
To evaluate evidence on the ability of echocardiography to identify pulmonary hypertension in adults compared to right-heart catheterisation.
What were the main results of the review?
We found 17 studies involving 3656 people who had suspected pulmonary hypertension.
There was a lot of variation in the studies. We found the characteristics of participants varied in terms of age, sex, cause of pulmonary hypertension, setting and country. The cut-off values for the echocardiography readings chosen to diagnose pulmonary hypertension also varied. We used the available data to estimate how well the echocardiography performed compared to right-heart catheterisation. In tertiary care hospitals, where most of the included studies were conducted, it is assumed that 680 of 1000 patients have pulmonary hypertension. We found that 592 people of 1000 would be correctly diagnosed with pulmonary hypertension using echocardiography. But 45 of 1000 patients would be wrongly considered as having pulmonary hypertension (false positive), while 88 of 1000 patients might be incorrectly considered as not having pulmonary hypertension (false negative) and 275 of 1000 patients would avoid unnecessary referral for a right-heart catheterisation. In a scenario where the preoperative examination for liver transplantation is conducted, 100 of 1000 are assumed to have pulmonary hypertension. We found the number of false negatives and false positives would be 13 and 126, respectively.
How reliable were the results of the studies?
We judged the included studies to have important limitations in their validity, which means that they were at high risk of providing distorted results. Therefore, we cannot be certain if the number of false negatives is correct (i.e. it could be even higher).
Who do the results of this review apply to?
These results apply to adults who are suspected of having pulmonary hypertension. However, the diagnostic accuracy of echocardiography varied considerably among studies and it is yet unclear what causes this diversity of test accuracy. Of note, the results are from studies conducted in relatively high prevalence settings. Therefore, care should be taken when applying this result to individual situations.
How up-to-date was the review?
This review is current to August 2021.
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.
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.
To determine the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH.
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.
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.
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.
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.