Two Silver Standards in the Imaging of Pulmonary Embolism – Reply

We thank the authors of the letter ”Two Silver Standards in the Imaging of Pulmonary Embolism” for their valuable comments related to our meta-analysis [1].

Meta-analyses can of course be seen with criticism, but they remain an important tool for entire medicine and represent one of the milestones for evidence based medicine. According to MeSH (Medical Subject Headings), meta-analysis is a quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions [2]. To date, most meta-analyses in medicine have been conducted to deal with treatment effects following a therapeutic intervention. But radiologic research is usually concerned with the accuracy of a diagnostic test rather than the effect of its implementation on patients’ clinical outcome. This is why performance characteristics are a crucial information in interpreting the results of imaging. Like the articles on which they are based, the quality of systematic reviews is also variable and the scientific method of meta-analysis has its supporters and detractors among scientific community [3]. To improve quality of a meta-analysis standards as the QUOROM statement have been established [4]. The article cited [1] was based on the QUOROM statement. Thus, reviewing and interpreting results of radiological meta-analyses requires more than only reading abstracts. As mentioned in the letter, factors like time, equipment availability, and technical details are important criteria when trying to transfer scientific results to clinical routine.

In daily practice pulmonary embolism (PE) remains an emergency scenario that needs a rapid work-up. Over the last years there was a steady increase in the number of CT scanners in whole Europe [5]. Both, a steady increase in the number of CT examinations and an increasing collective radiation dose administered could be demonstrated over the last years, raising concern in the radiologic community. The paper cited was part of the EURATOM FP 6 project: Safety and Efficacy in Computed Tomography (SECT) [6].

Mortality because of untreated PE is considered to be approximately 25 %, and is lowered to 8 % by anticoagulant treatment. Three months of anticoagulant treatment combined with an initial heparin course followed by cumarins carries a 0.1 – 0.4 % risk of mortality and a 0.6 – 1.2 % risk of major hemorrhage [7]. The probability of permanent and disabling sequelae from a major bleeding, especially an hemorrhagic stroke, is approximately 8 % [7].

There is still uncertainty regarding the clinical significance of depicting subsegmental clots and therefore the necessity to treat patients with isolated subsegmental PE and so the clinical impact remains unclear [8]. Patients with isolated subsegmental defects appear to have a more benign clinical presentation than patients with segmental or more proximal PE, including lack of associated DVT, less frequent dyspnea, and low clinical probability of PE [9]. Some authors consider that one of the functions of the pulmonary circulation is to prevent small emboli from entering the systemic circulation and believe that such distal emboli may occur even in healthy subjects [10] [11]. On the other hand, small peripheral PE may prove clinically relevant in the case of diminished cardio-respiratory reserve but no data are yet available on the long-term consequences of such events, especially on the occurrence of chronic pulmonary hypertension.

Advances over the last decade in CT scanner technology accompanied by the introduction of multidetector CT have replaced pulmonary angiography as the reference standard for the diagnosis of pulmonary embolism [12]. CTA has become the method of choice for imaging the pulmonary vessels when PE is suspected in routine clinical practice. Because CT images contain additional diagnostic information in the majority of patients who are suspected of having acute PE it may lead to alternative diagnosis. The increased use of CT has improved patient care by minimizing diagnostic delays that may be incurred when alternative imaging tests are used. The recent possibility of performing electrocardiographically gated examinations of the entire thorax and further decrease of acquisition time using newest generation CT has further reinforced the role of CTA in this clinical setting, adding coronary artery disease to the list of alternative diagnoses detectable and enabling the use of CTA to provide prognostic information from the same data set as that used to help diagnose acute PE.

Concerning special settings, when the use of contrast enhanced CT was contraindicated due to allergy, renal failure, metformin use or pregnancy, numerous papers focus on measures of precaution to prevent and minimize adverse events [13] [14] [15] [16]. Though, if other imaging procedures are informative one should, in principle, avoid radiation exposure and CT in pregnancy.

TUS in combination with laboratory tests definitely is an alternative to CT, particularly when the latter or V/Q scanning is not available or in cases of CT contraindication. Given the ubiquitous availability of TUS it can also be recommended in the out-patient setting and the emergency room in the context of ”killing three birds with one stone”, since the source, transmission, and arrival of thromboembolic disease can be detected with a single ultrasound system.

In conclusion, TUS for detection of pulmonary embolism obviously is a possible diagnostic approach, based on the data of the meta-analysis. Though especially in an emergency setting, CT allows depicting much more possible differential diagnosis and contains much more additional diagnostic information in the patient presenting with acute chest pain and suspected pulmonary embolism. In dedicated clinical settings TUS is a diagnostic alternative, but always extremely depending on the examiners’ sonographic skills, and always only applicable in the context of a wider diagnostic approach, including clinical assessment, d-dimers etc.

In routinely used diagnostic algorithms for suspected PE, CT represents the golden standard to date in radiologic diagnostic algorithms.

In direct response to the letter we take the liberty to refine one of the two proposed silver standards by promoting CTA as the golden standard in suspected pulmonary embolism while TUS may remain as proposed: silver. There is wide consensus in international guidelines and published literature. In this context TUS remains a rather exotic imaging possibility but of true diagnostic value as could be shown be our meta-analysis. The diagnostic benefits that are achieved by CTA in the routine patient in a routine hospital in the setting of acute chest pain/ suspected pulmonary embolism are far beyond the possibilities of TUS.

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