|Year : 2020 | Volume
| Issue : 2 | Page : 64-69
|Correlating computed tomography pulmonary angiography signs of right ventricular strain in pulmonary embolisms to clinical outcomes
Jay Karri1, Tiffany Truong1, Joseph Hasapes2, Daniel Ocazionez Trujillo2, Steven Chua2, Kaustubh Shiralkar2, Gabriel Aisenberg1
1 Department of Internal Medicine, McGovern Medical School, UTHSC, Houston, Texas, USA
2 Department of Diagnostic and Interventional Imaging, McGovern Medical School, UTHSC, Houston, Texas, USA
|Date of Submission||07-Sep-2019|
|Date of Acceptance||27-Nov-2019|
|Date of Web Publication||03-Mar-2020|
Dr. Gabriel Aisenberg
6432 Fannin St., MSB 1.122, Houston 77030, Texas
| Abstract|| |
INTRODUCTION: Right ventricular strain (RVS) in pulmonary embolism (PE) can be used to stratify risk and direct intervention. The clinical significance of computed tomography pulmonary angiogram (CTPA)-derived radiologic signs of RVS, however, remains incompletely characterized. We retrospectively analyzed a cohort of persons with acute PE to determine which, if any, findings of RVS on CTPA correlate with clinical outcomes.
METHODS: All patients with PE diagnosed on CTPA from March 2013 through February 2015 at Lyndon B. Johnson Hospital were identified. Their records were retrospectively reviewed to identify length of stay, intensive care unit (ICU) placement, hemodynamic failure, use of thrombolytics, vasopressor requirement, mechanical ventilation, and attributable mortality. Three radiologists, blinded to clinical outcomes, separately reviewed the cohort's CTPAs to identify signs of RVS – pulmonary trunk size, internal size of the right and left ventricles, paradoxical interventricular septal bowing, inferior vena cava (IVC) contrast reflux, and hepatic vein contrast reflux.
RESULTS: In our cohort of 102 persons, 12 demonstrated hemodynamic failure, 13 required ICU placement, 3 received thrombolysis, and 5 had death attributable to PE. The greatest interobserver agreement among radiologists existed for the presence of increased pulmonary trunk size (0.76 kappa by %agreement) and hepatic vein contrast reflux (0.92 kappa by %agreement). A multiple regression analysis found that when 100% radiologist agreement existed, presence of paradoxical intravenous septal bowing predicted thrombolytic usage (P = 0.02), and the presence of IVC reflux predicted attributable mortality (P = 0.03).
CONCLUSION: Only IVC contrast reflux was associated with increased mortality, and no other sign of RVS on CTPA correlated with clinical outcomes. This suggests that most signs of RVS on CTPA do not reliably predict PE severity. Therefore, RVS seen by CTPA should be used cautiously in weighing the decision to initiate thrombolytics.
Keywords: Computed tomography pulmonary angiography, pulmonary embolism, right ventricular strain
|How to cite this article:|
Karri J, Truong T, Hasapes J, Trujillo DO, Chua S, Shiralkar K, Aisenberg G. Correlating computed tomography pulmonary angiography signs of right ventricular strain in pulmonary embolisms to clinical outcomes. Ann Thorac Med 2020;15:64-9
|How to cite this URL:|
Karri J, Truong T, Hasapes J, Trujillo DO, Chua S, Shiralkar K, Aisenberg G. Correlating computed tomography pulmonary angiography signs of right ventricular strain in pulmonary embolisms to clinical outcomes. Ann Thorac Med [serial online] 2020 [cited 2021 Jan 26];15:64-9. Available from: https://www.thoracicmedicine.org/text.asp?2020/15/2/64/281866
In the United States, 500,000–600,000 patients are diagnosed each year with pulmonary embolism (PE); about 100,000 of those patients die as a result of this disease. For this reason, urgent diagnosis and treatment of PE are essential. The gold standard for diagnosis is computed tomography pulmonary angiography (CTPA). Echocardiographic or CTPA evidence of right ventricular strain (RVS) is an accepted sign of clinical severity in patients with PE., The diagnosis of RVS has been correlated with greater success using thrombolytic therapy to re-establish pulmonary artery (PA) patency and reduce mortality. Massive hemorrhage, the most serious side effect reported from thrombolysis, limits its benefit. Therefore, strict selection of candidates for this therapy is essential.
Several studies have shown that echocardiographic or CTPA findings of RVS predict mortality among normotensive patients with PE.,, However, that association has not been fully studied with multiple radiologists blinded to outcome variables such as hemodynamic failure, use of thrombolysis, use of mechanical ventilation, use of vasopressors, use of intensive care unit (ICU), and mortality attributable to PE. The purpose of this study is to fill that gap of knowledge.
| Methods|| |
The study was undertaken at Lyndon B. Johnson Hospital, a tertiary-care, county-based center in Houston, Texas, after waivered Institutional Review Board approval (HSC-MS-17-0983); patient consent requirements were obtained. We collected information from electronic medical records from March 1, 2013 to February 1, 2015. At the time, radiological signs of RVS were not customarily reported. Our intention was to avoid bias related to the existing reports of the evaluated CTPA.
From the hospital radiology database, we reviewed all CTPAs from patients 18 years of age and older and selected all studies positive for acute PE. Of these identified patients, we enrolled those who were admitted to the hospital.
Patients younger than 18 years of age and/or those with a nondiagnostic CTPA were excluded from the study. Patients transferred to other hospitals after the CTPA or those who left the hospital without adequate follow-up were also excluded from the study.
From the examined medical records, we retrieved patients' age, gender, and date of the CTPA. We also recorded length of in-hospital stay and ICU placement, if applicable, coexistence of other pulmonary abnormalities (other masses, atelectasis, presumably infectious infiltrates, pleural effusion, and presumed primary or secondary malignant disease to the lungs). We also extracted whether they suffered hemodynamic failure, required use of thrombolytic therapy, vasopressors, mechanical ventilation, or if they died as a result of the PE. Hemodynamic failure was defined as the condition when systolic blood pressure was lower than 100 mmHg for more than an hour with a concomitant heart rate >100 beats/min during that same period. We documented alternative causes of hemodynamic failure when applicable.
From the selected CTPA patient data set, three separate board-certified radiologists, blinded to each other's observations, reported the presence or absence of the following signs of RVS, as reported in the literature: increased size of the PA trunk (>3 cm), increased ratio of the internal right to left ventricle size (maximum inner wall to inner wall diameter ratio >1), paradoxical interventricular septal bowing, inferior vena cava (IVC) contrast reflux, and hepatic vein contrast reflux. Given that radiographic interpretations of CTPA imaging may be dependent on radiologist expertise and experience, we chose to utilize three radiologists in order to obviate any potential subjectivity in reporting.
MedCalc statistical software Version 18 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2018) was utilized for the statistical analysis. Interrater reliability (IRR) of the five signs of RVS was calculated using average percent agreement and Cohen kappa. We considered adequate IRR values 0.7 or above, as recommended. Categorical variables were analyzed using the Fisher exact test, and discrete variables were analyzed using the Student's t-test for unpaired samples. A multiple regression model was used to compare the association of the explored signs of RVS with the clinical outcomes. A two-sided P < 0.05 was considered indicative of statistical significance.
| Results|| |
Study cohort characteristics
One hundred and two patients fulfilled the inclusion criteria. Of them, 44 (45%) were men; the median age was 55 years (range 24–97). Clinical outcomes for our cohort are displayed in [Table 1]; hemodynamic failure was present in 12 persons (12%) and PE attributable death was present in five persons (5%). Of the patients considered hemodynamically unstable, two had concomitant presumption of sepsis from pleural empyema, and one was suspected to have a major gastrointestinal bleed and died prior to obtaining an endoscopy.
|Table 1: Clinical outcomes in our cohort of 102 persons with acute pulmonary embolism|
Click here to view
Radiological signs of PE and RVS with associated IRR for each sign are presented in [Table 2]. The presence of hepatic vein contrast reflux was the variable with the highest interrater agreement.
|Table 2: Radiological signs of pulmonary embolism and right ventricular strain with associated interrater reliability for each sign|
Click here to view
Correlating right ventricular strain on computed tomography pulmonary angiogram and clinical outcomes
Correlation of RVS indicators with clinical outcomes was assessed for every individual radiologist first. Only one of them found that the risk for ICU admission was lower in the presence of pulmonary trunk >3 cm (3% vs. 18%, P = 0.03); all other signs of RVS were not associated with significantly different risk of evaluated clinical outcomes.
[Table 3] shows that the correlation between the individual radiological indicators of RVS and the clinical outcome variables is poor. This occurred regardless of the strictness of the radiologist coincidence for the presence or absence of these signs: we accepted the variables when the three of them agreed or when two of them agreed. [Table 4] depicts a multiple regression analysis to assess the impact of all radiological findings considered together (at 100% and 67% agreement) for each one of the evaluated clinical outcomes. When considered at 100% agreement, the presence of IVC contrast reflux predicted mortality and paradoxical interventricular septal bowing (the sign of RVS that in our cohort showed the lowest IRR) predicted thrombolytic use. Three patients received thrombolytic therapy; two of them required ICU care; none died.
|Table 3: Univariate analysis correlating radiological signs of right ventricular strain with clinical outcomes|
Click here to view
|Table 4: Multiple regression correlating radiological signs of right ventricular strain to clinical outcomes|
Click here to view
| Discussion|| |
In our study, we found a poor correlation between RVS signs and negative clinical outcomes. The gold standard for the objective determination of RVS, a reliable determinant of clinical severity, is transthoracic echocardiography (TTE).,, Unfortunately, TTE is limited by availability and a slow turnaround time., On the contrary, CTPA can produce results in minutes but is limited to the analysis of static cardiac imaging.,,, Thus, the value of CTPA inappropriately and reliably determining clinically relevant RVS has been questioned. Although several studies have investigated the degree of correlation between CTPA and TTE findings suggestive of RVS, the capacity of CTPA as a standalone predictor for clinically relevant outcomes has received less attention. Thus, the clinical thrust of this study was to determine if and how CTPA signs of RVS correlate to clinical outcomes in persons with acute PE.
We present data demonstrating that most radiological signs of RVS per CTPA have limited capacity in predicting short term clinical outcomes. This lack of clinical correlation is likely secondary to both the subjectivity of appropriately identifying radiological signs of RVS and the inability of these static signs to reflect hemodynamic patterns.,, As shown in [Table 2], there existed a wide range of IRR across the RVS variables (75%–92% kappa by percent agreement). This high degree of discordance amongst three radiologists seems to suggest that these radiological signs do not possess the reliability that may have otherwise been present if these parameters were clearly delineated to clinically correlate. Nevertheless, we demonstrate in [Table 3] that even when variables are considered at a 100% agreement amongst radiologists, there is limited capacity for these parameters to predict clinical outcomes. However, we did find that the presence of paradoxical interventricular septal bowing correlated to thrombolytic use (P = 0.02) and that IVC reflux correlated to death attributable to PE (P = 0.03). Of note, however, both of these clinical outcomes – thrombolytic use and death due to PE – were rare events in our cohort and such, these findings may be underpowered. Similarly, per one radiologist's review of the CTPAs, increased pulmonary trunk size was also found to predict a lower ICU admission risk. Our cohort's being underpowered may also justify this seemingly contradictory finding. In effect, we were unable to find that CTPA findings could predict any clinically relevant measure. This novel information suggests that CTPA findings of RVS should be judiciously incorporated into patient management.
There exist several studies that have attempted to qualify the capacity of CTPA signs of RVS across numerous contexts including ability to correlate to echocardiography, appropriately risk-stratify patients, and predict clinical outcomes.,,,, Unfortunately, these studies and the ability to incorporate CTPA findings risk stratification of persons with acute PE are limited by the inherent shortfalls of static imaging and the poor reliability of RVS radiological signs.,
As mentioned earlier, the images gathered from a CTPA are fixed and stationary. Consequently, the static nature of this modality poses numerous problems when analyzing for presence several RVS parameters, notably interventricular diameter ratios and increased PA size, both of which vary and are dependent on the phase of the cardiac cycle captured on imaging.,, In essence, both these parameters may be quantified differently if the CTPA was captured during peak systole versus peak diastole versus any phase in between. Interestingly, both the interventricular diameter ratio and increased pulmonary trunk size were parameters found by others to demonstrate higher reproducibility compared to other RVS signs and have also been correlated with disease severity.,,
The reproducibility and reliability of radiological signs of RVS has come into question in prior similar studies., Similar to our own findings displayed in [Table 2], others have also demonstrated that appropriately identifying paradoxical interventricular septal bowing and contrast reflux is highly radiologist dependent., Regardless, studies have concluded that certain RVS signs on CTPA are able to predict certain clinical outcomes, including mortality.,,, Of note, despite the issue of IRR in identifying RVS being prevalent, to our knowledge, this is the only such study utilizing three blinded radiologists to survey the CTPAs in our study cohort; other studies utilized only 1 or 2 radiologists.,,, Incorporating radiological findings of RVS into patient management is further hindered by the fact that in clinical practice only one given radiologist analyses and reports on a CTPA study. Consequently, the limited utility demonstrated in our study of 100% radiologist agreement of RVS in correlating with short term clinical outcomes becomes further compromised with only one radiologist report in real-world practice. Incorporation of additional clinical data, namely TTE findings and hemodynamic parameters, are paramount in dictating patient management and deciding to initiate thrombolytic therapy.
The major limitations of this study are secondary to our cohort having a limited sample size; our analysis incorporated only 102 persons with acute PE, of which only a small minority can be characterized as clinically severe cases (12% hemodynamic failure and 5% attributable death to PE). This limited power prevents findings from this study being fully and appropriately generalizable, in particular to those persons with more severe manifestations.
| Conclusion|| |
Only IVC contrast reflux is associated with increased mortality, and no other sign of RVS on CTPA correlates with short term clinical outcomes. This suggests that most signs of RVS on CTPA do not reliably predict the increased severity of PE. Evidence of RVS as determined per CTPA should be cautiously incorporated in weighing the decision to initiate thrombolytic therapy. We conclude that the ability of RVS findings on CTPA to predict clinical outcomes is limited.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Giordano NJ, Jansson PS, Young MN, Hagan KA, Kabrhel C. Epidemiology, pathophysiology, stratification, and natural history of pulmonary embolism. Tech Vasc Interv Radiol 2017;20:135-40.
Nural MS, Elmali M, Findik S, Yapici O, Uzun O, Sunter AT, et al
. Computed tomographic pulmonary angiography in the assessment of severity of acute pulmonary embolism and right ventricular dysfunction. Acta Radiol 2009;50:629-37.
Jiménez D, Aujesky D, Yusen RD. Risk stratification of normotensive patients with acute symptomatic pulmonary embolism. Br J Haematol 2010;151:415-24.
Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, et al
. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014;35:3033-69, 3069a-3069k.
Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, et al
. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: A scientific statement from the American Heart Association. Circulation 2011;123:1788-830.
Weekes AJ, Johnson AK, Troha D, Thacker G, Chanler-Berat J, Runyon M. Prognostic value of right ventricular dysfunction markers for serious adverse events in acute normotensive pulmonary embolism. J Emerg Med 2017;52:137-50.
Ghuysen A, Ghaye B, Willems V, Lambermont B, Gerard P, Dondelinger RF, et al
. Computed tomographic pulmonary angiography and prognostic significance in patients with acute pulmonary embolism. Thorax 2005;60:956-61.
Meinel FG, Nance JW Jr., Schoepf UJ, Hoffmann VS, Thierfelder KM, Costello P, et al
. Predictive value of computed tomography in acute pulmonary embolism: Systematic review and meta-analysis. Am J Med 2015;128:747-59.
McHugh ML. Interrater reliability: The kappa statistic. Biochem Med (Zagreb) 2012;22:276-82.
Jones AE, Kline JA. Availability of technology to evaluate for pulmonary embolism in academic emergency departments in the United States. J Thromb Haemost 2003;1:2240-2.
Dudzinski DM, Hariharan P, Parry BA, Chang Y, Kabrhel C. Assessment of right ventricular strain by computed tomography versus echocardiography in acute pulmonary embolism. Acad Emerg Med 2017;24:337-43.
Araoz PA, Gotway MB, Trowbridge RL, Bailey RA, Auerbach AD, Reddy GP, et al
. Helical CT pulmonary angiography predictors of in-hospital morbidity and mortality in patients with acute pulmonary embolism. J Thorac Imaging 2003;18:207-16.
Kang DK, Ramos-Duran L, Schoepf UJ, Armstrong AM, Abro JA, Ravenel JG, et al
. Reproducibility of CT signs of right ventricular dysfunction in acute pulmonary embolism. AJR Am J Roentgenol 2010;194:1500-6.
Wake N, Kumamaru KK, George E, Bedayat A, Ghosh N, Gonzalez Quesada C, et al
. Computed tomography and echocardiography in patients with acute pulmonary embolism: Part 1: Correlation of findings of right ventricular enlargement. J Thorac Imaging 2014;29:W1-6.
Kumamaru KK, George E, Ghosh N, Quesada CG, Wake N, Gerhard-Herman M, et al
. Normal ventricular diameter ratio on CT provides adequate assessment for critical right ventricular strain among patients with acute pulmonary embolism. Int J Cardiovasc Imaging 2016;32:1153-61.
George E, Kumamaru KK, Ghosh N, Gonzalez Quesada C, Wake N, Bedayat A, et al
. Computed tomography and echocardiography in patients with acute pulmonary embolism: Part 2: prognostic value. J Thorac Imaging 2014;29:W7-12.
Ende-Verhaar YM, Kroft LJ, Mos IC, Huisman MV, Klok FA. Accuracy and reproducibility of CT right-to-left ventricular diameter measurement in patients with acute pulmonary embolism. PLoS One 2017;12:e0188862.
Quiroz R, Kucher N, Schoepf UJ, Kipfmueller F, Solomon SD, Costello P, et al
. Right ventricular enlargement on chest computed tomography: Prognostic role in acute pulmonary embolism. Circulation 2004;109:2401-4.
Collomb D, Paramelle PJ, Calaque O, Bosson JL, Vanzetto G, Barnoud D, et al
. Severity assessment of acute pulmonary embolism: Evaluation using helical CT. Eur Radiol 2003;13:1508-14.
Park JR, Chang SA, Jang SY, No HJ, Park SJ, Choi SH, et al
. Evaluation of right ventricular dysfunction and prediction of clinical outcomes in acute pulmonary embolism by chest computed tomography: Comparisons with echocardiography. Int J Cardiovasc Imaging 2012;28:979-87.
[Table 1], [Table 2], [Table 3], [Table 4]