Article Review Adam Brown, DO, PGY-1 November 14, 2016 Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism Article Review Adam Brown, DO, PGY-1 November 14, 2016

Published October 2016 in American Journal of Emergency Medicine Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism James Daley, MD, MPH a,⁎, John Grotberg, BS b, Joseph Pare, MD a, Amanda Medoro, MD a, Rachel Liu, MD a, Michael Kennedy Hall, MD, MHS c, Andrew Taylor, MD a, Christopher L. Moore, MD a a DepartmentofEmergencyMedicine,YaleNewHavenHospital,NewHaven,CT b YaleSchoolofMedicine,NewHaven,CT c DivisionofEmergencyMedicine,UniversityofWashingtonSchoolofMedicine,Seattle,WA Published October 2016 in American Journal of Emergency Medicine

BACKGROUND Pulmonary Embolism is a time sensitive diagnosis in the ED, with potential for significant mortality and morbidity if not identified. Incidence of PE is estimated at ~69/100,000 in the US* CTA is the criterion standard for diagnosing PE. CTA is costly and confers the risks of radiation and contrast, therefore it is not ideal especially in patients who are pregnant, have renal impairment, or contrast allergies to name a few. Ultrasound has the benefits of being low cost, rapid, with no radiation, nor contrast needed. Daniel R Ouellette, MD, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  Pulmonary Embolism Overview, Medscape

BACKGROUND Right ventricular dysfunction (RVD) is often present with PE and has been shown to be associated with, “increased in-hospital mortality, longer lengths of stay, and the development of pulmonary hypertension.” (2) Emergency Physician FOCUS exams look for dynamic visual evidence of RVD; RV dilation; ‘D’ sign-RV dilation with associated interventricular septum flattening so that the appearance of the left ventricle in parasternal short likens to a ‘D’ shape rather than the ‘O’ or donut shape we usually see; McConnell’s sign, where the mid wall of the RV loses motion, but the apex continues to move as normal, best seen in Apical 4; Tricuspid Regurgitation; IVC dilation with inspiratory collapse. (3) (2) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018 (3) Patel AN, Nickels LC, Flach FE, De Portu G, Ganti L. The Use of Bedside Ultrasound in the Evaluation of Patients Presenting with Signs and Symptoms of Pulmonary Embolism. Case Reports in Emergency Medicine. 2013;2013:312632. doi:10.1155/2013/312632.

BACKGROUND TAPSE or Tricuspid annular plane systolic excursion measures movement of the tricuspid valve annulus throughout its contraction. (4) TAPSE use as a proxy for RVD had been previously studied in cardiologists, and was shown to be predictive of increased mortality, the need for ICU, and thrombolysis, and had less user-dependent variability. (5) TAPSE use by Emergency Physicians using point of care ultrasound had not been previously studied. (4,5) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

Goals: To identify the diagnostic characteristics of (TAPSE), “and…optimize the measurement cutoff…for pulmonary embolism (PE),” while assessing the inter-operator “reliability and the quantitative visual estimation of TAPSE.” (6) (6) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

Setting April, 2015 to April, 2016 Urban ED with over 100,000 visits Sonologists: 3 US fellowship trained EPs, 4 EM ultrasound fellows, 1 EM resident, and one medical student.

Participants: Inclusion Criteria Exclusion Criteria Age: 18 years or older presenting to ED w/ clinical suspicion of PE and receiving a CTA. Exclusion Criteria Prisoners, Wards of the State, and non-English speaking patients.

METHODS and MEASUREMENTS A FOCUS exam was done bedside (if possible), before patient was brought for CTA, otherwise investigators were blinded from CTA results when assessing the FOCUS exam. RVD was identified as characteristic signs on FOCUS exam (talked about earlier), and/or measurement of TAPSE as less than 1.7 cm. To test inter-operator reliability 2 investigators measured TAPSE independently identical patients blinded to CTA and the other physician’s findings.

(7) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018 Tricuspid annular plane systolic excursion was obtained in the apical 4-chamber view by placing the m-mode cursor along the lateral tricuspid valve annulus and measuring the change in height of the resultant tracing from trough to peak

Primary Outcome Secondary Outcomes Determine diagnostic characteristics sensitivity, specificity, likelihood ratios, of TAPSE for PE Identify a cutoff for TAPSE for diagnosis of PE by utilizing a ROC curve. Secondary Outcomes Inter-operator reliability of TAPSE Assessment of EPs ability to visually estimate TAPSE, Initially they wanted to look test characteristics of other RVD criteria, but decided during the study that they would do a “post hoc analysis of the sensitivity of FOCUS and TAPSE in patient with tachycardia or hypotension.” (8) (8) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

ANALYSIS Sample size of 150 subjects were, based on a estimated 20% of enrolled subjects would be diagnosed as having PE. 30 patients were ultrasounded by two separate physicians to test for interrater reliability of TAPSE, and an intraclass correlation coefficient (ICC) was, “assessed using a 2-way absolute agreement model.” (9) EPs visually estimated TAPSE in 68 patients as normal or abnormal. (9) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

ANALYSIS Diagnostic test characteristics, ROC curve, “and calculation of the area under the curve, ICC, and the κ statistic.” (10) 3 subjects excluded due to inadequate echocardiographic windows. (10) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

RESULTS When threshold for TAPSE was 1.7cm the sensitivity/specificity for PE was 56% (95%CI, 38-74), 79% (95%CI, 78-86) respectively. When threshold for TAPSE was 2.0cm the sensitivity/specificity for PE was 72% (95%CI, 63-86), 66% (95%CI, 57-75) respectively. Analysis of the receiver operator curve yielded a threshold for TAPSE of 2.0 cm as optimal for diagnosis of PE, correlating to an area under the curve of 0.73 Test Characteristics for other RVD measurements ranged from 13%-43% and are shown in the table on the next slide.

RESULTS Interrater reliability showed an ICC of, “0.87 (95% CI, 0.79-0.93) with a sum of squares of 0.02 between raters on analysis of variance.“ (11) In the 68 patients where EPs visually estimated the TAPSE as normal/abnormal, 13 were estimated to have an abnormal TAPSE. 16 of the 68 patients were diagnosed with a PE (11) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

RESULTS (12) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

DISCUSSION This is the first study where TAPSE was studied as a diagnostic rather than prognostic marker, which led to raising the threshold from 1.7 cm (which had been previously used), to 2.0 cm (as determined by the ROC), as it proved to be more sensitive. Overall though, the sensitivity/specificity of TAPSE in the diagnosis of PE was not great, though it was superior to other measurements of RVD in the FOCUS exam, and when used in a patient with tachycardia or hypotension. During the study there were 17 patients with hypotension and or tachycardia and a PE, all had at least 1 sign of RVD on FOCUS, and 16/17 had abnormal TAPSE. In that scenario the sensitivity of TAPSE for PE was calculated as “94% (95% CI, 71-99) and the combined sensitivity of FOCUS for PE was 100% (95% CI, 80-100).” (13) This was a retrospective analysis and would need further validation with a prospective study. If the sensitivity of TAPSE plus FOCUS in the unstable patient population (hypotensive/tachycardic) held up to further studies, it would be extremely useful, as it is often that patient population (hemodynamically unstable) where we are often unable to send out of the Edfor definitive imaging. (13) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

DISCUSSION An Abnormal TAPSE is not specific especially among patients with COPD, CHF, and Pulmonary HTN. This is the first study that showed that EPs are able to measure TAPSE with significant reproducibility, and that TAPSE is more reproducible than, other signifiers of RVD. EPs were consistent in their ability to visually estimate TAPSE. Therefore it seems it would follow that an EP experienced with TAPSE would only need to calculate it in M-Mode in borderline cases.

LIMITATIONS Single-center study (academic center), from a selected sample of patients (those already being sent for CTAs for suspected PE). Investigators were trained in TAPSE and FOCUS exams, so might not be fully representative of EP with less US experience. Retrospective analysis of patients with tachycardia and hypotension. Possible Selection Bias. Generalizable? Of Note the one medical student in the study was able after limited training had a ICC for his measurements of 0.97 when compared to the other providers in the study. Could lay foundation for prospective study to replicate and validate results further.

CONCLUSION Ultrasound trained Emergency physicians are able to measure TAPSE with “precision comparable to that reported in cardiology literature.” (14) EPs are able to reliably visually estimate whether TAPSE is normal/abnormal based on cutoff of 1.7cm. For diagnosis of PE the optimal cutoff was found to be 2.0 cm. TAPSE is more sensitive, but less specific than other comparable RVD measures. The combination of TAPSE and FOCUS in patients with tachycardia and hypotension is highly sensitive. (14) Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018

REFERENCES Daley J, et al, Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism, Am J Emerg Med (2016), http://dx.doi.org/10.1016/j.ajem.2016.10.018 Patel AN, Nickels LC, Flach FE, De Portu G, Ganti L. The Use of Bedside Ultrasound in the Evaluation of Patients Presenting with Signs and Symptoms of Pulmonary Embolism. Case Reports in Emergency Medicine. 2013;2013:312632. doi:10.1155/2013/312632. 3. Daniel R Ouellette, MD, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  Pulmonary Embolism Overview, Medscape