Assessing the role of Computed Tomography Pulmonary Angiogram in diagnosing right heart strain related to acute pulmonary embolism

1. INTRODUCTION

Right ventricular failure (RVF) is a well-documented and serious complication of acute pulmonary embolism (PE). RVF-due to acute pressure overload is the leading cause of death in PE [1]. PE is also the third most common cause of cardiovascular death in the USA [2]. The absence of haemodynamic instability does not exclude the presence of right heart strain (RHS).

In this study, we have defined RHS in terms of echocardiographic findings- an example of some listed later in this introduction- to see if computed tomography pulmonary angiogram (CTPA) correlates with these findings. CTPA has taken over from ventilation-perfusion scanning and invasive pulmonary angiography as the gold standard for the radiological diagnosis of PE [3]. CTPA allows radiologists to accurately assess pulmonary vasculature to the subsegmental level [4]. A recent North American study reported a PE diagnosis rate on CTPA as low as 5%, reflecting a changing culture toward increased use and availability of CTPA. This altered approach to PE diagnosis reflects a significant change from nearly 50% positivity on testing for PE in the 1980s [5]. The provision and increased utilisation of these tests need to balance the benefits of diagnosing PE (or finding an alternative explanation for the patients’ symptoms) on CTPA with the risks of radiation exposure and the use of intravenous contrast.

Using transthoracic echocardiography (TTE) as the standard-bearer in diagnosing RHS, we aimed to assess how accurate CTPA and serum biomarkers are at predicting echocardiographic evidence of RHS. Signs of right heart strain on TTE include increased right: left ventricular ratio, abnormal septal motion, McConnell’s sign, tricuspid regurgitation, elevated pulmonary artery systolic pressure, decreased tricuspid annular plane systolic excursion (TAPSE), decreased S', pulmonary artery mid-systolic notching, 60/60 sign, and speckle tracking demonstrating decreased right ventricular free wall strain [6, 7].

Serum biomarkers of cardiac dysfunction and injury are often routinely checked in patients with confirmed or suspected PE awaiting confirmation. Troponin I is a protein subunit that inhibits muscle contraction in the absence of calcium. Primarily used as a marker to aid diagnosis of myocardial infarction, it is also useful in acute PE -when raised in this setting, it is believed to be an indicator of cardiac muscle damage and potentially signal RHS. Troponin is a recognised marker of short-term mortality in PE [8]. N-terminal prohormone brain natriuretic peptide (NT-pro-BNP) is a biomarker primarily measured in patients with suspected heart failure. It is released in greater quantities when cardiac muscle is stretched (most commonly in the setting of volume overload). Hence, it may be a possible marker of right heart strain in PE. Meta-analysis shows that echocardiographic RHS and elevated natriuretic peptides are useful short-term mortality markers, whereas the role of RHS on CTPA as a prognostic marker remains unclear [9]. Another meta-analysis suggests that an increased CTPA RV/LV ratio >1 is associated with a 2.5-fold increase in all-cause mortality and a 5-fold increase in PE-related mortality [10]. Other CTPA markers of right heart strain include septal deviation and inferior vena cava [11].

Our centre is a tertiary, university teaching hospital. As TTE isn’t readily available in all hospitals out of hours, we aimed to ascertain whether CTPA, troponin and NT-pro-BNP would provide a reliable and time-sensitive indication as to whether or not there may be co-existent cardiac injury as part of a patient's presentation with PE, as this in turn would have potential implications for prognosis and clinical management.

2. STUDY DESIGN AND METHODS

3. RESULTS

4. DISCUSSION

Acute pulmonary embolism with right heart strain is a life-threatening condition. Assessment of cardiac function is routinely performed as part of risk stratification following an acute PE. In this study, we aimed to ascertain the most reliable way to assess for RHS in the setting of acute PE. Many centres don’t have access to immediate out-of-hours echocardiography, so objective means of assessing severity of PE independent of TTE would potentially be of practical clinical utility. We have demonstrated that in our centre, CTPAs have a reasonable but not excellent sensitivity and specificity for diagnosing RHS. NT-pro-BNP has an excellent sensitivity but poor specificity. Using a troponin cut-off of three times the upper limit of normal maintains a reasonable sensitivity with a very good specificity for RHS in CTPA-diagnosed PE, provided an appropriate work-up has excluded acute coronary syndrome and other causes for an elevated troponin.

Prior research tells us that CT is highly sensitive, but not as specific as TTE for diagnosing RHS, hence why we use TTE as an accessible comparator in our work [14]. Other modalities such as cardiac MRI and right heart catheterization are more accurate but are not readily accessible in most centres and would be expensive, invasive, and burdensome on patients to perform in every PE case. International PE guidelines mentioned later in this discussion tell us that TTE is recommended for diagnosing RHS [3].

In a review comparing internationally recognised PE guidelines, the use of validated prognostic scores such as PESI was endorsed by the European Respiratory Society (ERS) and the European Society of Cardiology (ESC), as well as other organisations such as the American Society of Haematology (ASH). ESC/ERS and CHEST also recommend assessing right ventricular size and function to identify low-risk patients. The American Heart Association (AHA) and ASH recommend diagnosing patients as intermediate risk when RHS is detected, while ESC and ERS further divide this group into intermediate-low and intermediate-high risk categories based on combined imaging and biomarker abnormalities [15].

One of the major advantages of performing CTPA is that even when the CTPA shows that no PE is present, the detailed images of the lungs and related structures may afford an alternative explanation for dyspnoea, chest pain, or other symptoms that initially prompted the need for the scan. 2.3% of patients in our study had a likely new malignancy found, and 2.1% had acute rib, vertebral or sternal fractures. The counterargument that is often made is that the introduction of CTPA has led to overdiagnosis of PE, with rising incidence, minimal change in mortality, and lower-case fatality [16]. The proposed explanation is that more clinically insignificant emboli are being picked up through excessive CTPA use. However, it is noteworthy that available evidence has suggested that the risk of PE recurrence is similar in those with subsegmental PE and those with central PE [17].

One study reported that 45% of patients with acute PE will have RHS. In our study, it was approximately 24% on CTPA, rising to 35.9% on TTE [2]. Diagnosing the severity of PE is important in the initial clinical management and estimating outcomes in patients with acute PE. Patients diagnosed with any severity of PE will usually receive a minimum of three months of anticoagulation. The American College of Chest Physicians’ guidelines for venous thromboembolism give a weak, low-certainty recommendation that observation could be chosen over anticoagulation in patients with subsegmental PE, who are low risk for recurrence and have no evidence of proximal lower limb deep vein thrombosis. Patients with evidence of hypotension (i.e., massive PE) who are not at a high bleeding risk should have systemically administered thrombolytic therapy [18]. The necessary major distinctions in initial therapy between different patient risk groups is why risk stratification is so important in acute PE.

Troponin is an established marker used in assessing PE. It has significance for predicting PE (50.8% versus 11.6% in those with PE compared with those without PE in one study, p<0.001); however, there was no statistical significance between TTE findings in those with PE with or without elevated troponin [19]. In prior studies, PE patients with elevated NT-pro-BNP or troponin were more likely to have adverse TTE findings than those without elevated biomarkers- as high as a twelve-fold increase in those with elevated NT-pro-BNP. The authors of that study suggest the possibility of not performing TTE in patients with normal biomarkers[20figr]. Our NT-pro-BNP findings mirror this finding, with 92.9% sensitivity observed; however, troponin was only 75% sensitive, and both performed poorly in terms of specificity and positive predictive value.

The 2019 ESC guidelines on management of acute PE recognise that right ventricular dysfunction may be present and affect early outcomes in patients with low clinical risk scores [3]. This adds additional importance to performing a thorough cardiac work-up in all patients with PE, regardless of clot burden on CTPA or severity of clinical presentation. This is highlighted in our study, whereby 17.9% of patients with no evidence of RHS on CTPA who went on to have a TTE had echocardiographic evidence of RHS. Our data reflects the recommendations of the above-mentioned 2019 guidelines, which also give a grade IIa recommendation to assess the right ventricle with echocardiography or biomarkers in all patients, regardless of PESI score.

Our study reports a mortality rate of 18.8% at 6 months in those diagnosed with PE, but interestingly there was still a 17.5% mortality rate at 6 months in those with no PE, with no statistical difference between the two groups (p = 0.78). This may reflect better understanding and advances in PE management, as well as the fact that significant proportions of patients referred for CTPA have malignancy, chronic respiratory disease, or other significant underlying conditions.

A limitation of our study is that it is retrospective and single centre, and not all patients in the cohort were cared for or received dedicated input from the respiratory service. Also, this study is subject to some selection bias given that more unwell patients were more likely to get a TTE as an inpatient.

INTERPRETATION/CONCLUSION

Our study demonstrates that while CTPA and biomarkers are useful and readily available indicators for cardiac involvement in PE, they lack the reliability and reassurance of quality provided by echocardiography. Our data suggest that patients who are diagnosed with an acute PE should be considered for TTE. Larger, multicentre, and prospective data are needed to truly assess the legitimacy of these diagnostic tools.

REFERENCES