Article, Cardiology

Emergency physician performed tricuspid annular plane systolic excursion in the evaluation of suspected pulmonary embolism

a b s t r a c t

Objectives: The primary objectives were to describe the diagnostic characteristics tricuspid annular plane systolic excursion (TAPSE) for pulmonary embolism (PE) and to optimize the measurement cutoff of TAPSE for the diag- nosis of PE. Secondary objectives included assessment of interrater reliability and the quantitative visual estima- tion of TAPSE. Methods: This is a prospective observational cohort study involving a convenience sample of patients at an urban academic emergency department. Patients underwent focused right heart echocardiogram (FOCUS) before com- puted tomographic angiography (CTA) for suspected PE. Results: A total of 150 patients were enrolled, 32 of whom (21.3%) were diagnosed as having a PE. A receiver op- erating characteristic curve analysis yielded 2.0 cm as the optimal cutoff for TAPSE in the diagnosis of PE, with a sensitivity of 72% (95% confidence interval [CI], 53-86), a specificity of 66% (95% CI, 57-75), and an area under the curve of 0.73 (95% CI, 0.65-0.83). In patients with tachycardia or hypotension, post hoc analysis demonstrated that FOCUS is 100% (95% CI, 80-100) sensitive for PE, whereas TAPSE is 94% (95% CI, 71-99) sensitive for PE. The intraclass correlation coefficient was 0.87 (95% CI, 0.79-0.93). Emergency physicians with training in echo- cardiography accurately visually estimated TAPSE, with a ? statistic of 0.94 (95% CI, 0.87-0.98).

Conclusions: Emergency physicians with training in echocardiography can reliably measure TAPSE and are able

to accurately visually estimate TAPSE as either normal or abnormal. When using an abnormal cutoff of less than

2.0 cm, TAPSE has moderate diagnostic value in patients with suspected PE. On post hoc analysis, TAPSE and FOCUS appear to be highly sensitive for PE in patients with tachycardia or hypotension.

(C) 2016

Introduction

Background

The evaluation of a patient with chest pain or dyspnea in the emer- gency department (ED) often prompts the emergency physician to consider the diagnosis of pulmonary embolism (PE). right ventricular dysfunction occurs in 30% to 70% of patients with PE, and the ab- sence of RVD in patients with Hemodynamic compromise makes PE an unlikely etiology [1]. In the setting of known PE, findings of RVD have been shown to be associated with increased in-hospital mortality, lon- ger lengths of stay, and the development of pulmonary hypertension [2-4]. Emergency physician-performed focused transthoracic cardiac ultrasound (FOCUS) has been shown to be effective in detecting RVD [2,3,5-7]. However, commonly used FOCUS findings of RVD such as

* Corresponding author. Department of Emergency Medicine, 464 Congress Avenue, Suite 260, Yale New Haven Hospital, New Haven, CT 06510.

E-mail address: [email protected] (J. Daley).

right ventricular enlargement can be challenging to assess, with variable reproducibility among operators [8,9].

Tricuspid annular plane systolic excursion (TAPSE) assesses for RVD by using M-mode to measure the dynamic movement of the Tricuspid valve annulus over the course of a contraction [10]. Tricuspid annular plane systolic excursion performed by cardiologists has been shown to be a reliable measure of RVD that correlates well with more complex global measures, such as cardiac magnetic resonance imaging and right heart angiography [11-18]. First described in the cardiology litera- ture in the 1980s [10], TAPSE has been used in the evaluation of right ventricular function in a variety of conditions such as pulmonary hyper- tension, congestive heart failure, PE, acute respiratory distress syn- drome, and cardiac surgery [2,8,12-14,19-29].

Importance

In the setting of known PE, TAPSE is of significant prognostic utility relative to other measures of RVD, as abnormal values are independent- ly predictive of increased mortality, increased intensive care unit (ICU)

http://dx.doi.org/10.1016/j.ajem.2016.10.018

0735-6757/(C) 2016

Image of Fig. 1

Fig. 1. test performance characteristics of TAPSE for PE by operator based on a cutoff of 1.7 cm, where values below this were considered a positive test and values equal to or above this were considered a negative test. Diagnostic test results were compared with CTA as the criterion standard. FN, false negative; TP, true positive; FP, false positive; TN, true negative; A, attending; F, fellow; R, resident; S, student.

length of stay, and thrombolysis [2,3,8,29-31]. Tricuspid annular plane systolic excursion has previously been shown to be the least user- dependent measure of RVD [8]; however, this has not been studied among EPs. The use of TAPSE in the diagnosis of PE has not been studied.

Goals

The primary objectives of this study were to describe the diagnostic characteristics of TAPSE for PE and to optimize the measurement cutoff of TAPSE for the diagnosis of PE, by developing a receiver operating characteristic (ROC) curve. Secondary objectives were 3-fold: first, to assess the interrater reliability when measuring TAPSE among EPs at the bedside; second, to determine the ability to visually estimate TAPSE qualitatively as normal or abnormal before its measurement; and third, to describe the diagnostic characteristics of other measures of right heart strain assessed on FOCUS for PE.

Methods

Study design and setting

This was a prospective, observational convenience sample of FOCUS in ED patients undergoing evaluation for suspected PE from April 2015 to April 2016. This study was approved by the institutional review board and conducted in accordance with the STARD guidelines for reporting diagnostic accuracy studies [32]. Patients were recruited from an Urban academic medical center with more than 100 000 annual ED visits.

Selection of participants

Patients were enrolled when a study investigator was available, often working clinically in the ED. Subjects were eligible if they were adults (18 years or older) undergoing computed tomographic angiogra- phy (CTA) for evaluation of possible PE in the ED. Prisoners, wards of the state, and non-English-speaking patients were excluded.

Study personnel were notified about potential subjects by text page alert when a CTA was ordered in the ED. Subjects were then screened for enrollment eligibility in person by Research staff, and if deemed eligible, written consent was obtained. Three patients were unable to provide consent at the time of enrollment due to the severity of their illness and were approached for consent later in their hospital stay, as permit- ted by the institutional review board.

Methods and measurements

Investigators performed and interpreted FOCUS at the bedside dur- ing the patient’s ED stay, if possible before the patient underwent CTA. If performed after CTA, echocardiographers were blinded to CTA results. Data were recorded at the bedside using a mobile device that automat- ically updated a secure database located on the Yale internal network. Investigators included 3 point-of-care ultrasound fellowship trained EPs (CLM, RL, RAT), 4 emergency medicine ultrasound fellows (MKH, AM, JP, and JS), 1 emergency medicine resident (JD), and one medical student (JG) (Fig. 1). Investigators (except for JG) underwent emergen- cy ultrasound training during residency and have significant experience in emergency ultrasound. Before enrolling patients for this study, inves- tigators underwent a standardized 1-hour didactic training session and at least 20 practiced TAPSE measurements before enrolling patients. The medical student, JG, did not have prior experience in point-of-care ultra- sound. He underwent a 2-week period of training in point-of-care ultra- sound by the co-investigators, performing greater than 50 practice FOCUS examinations before enrolling patients. Investigators were blinded to CTA findings as well as co-investigator echocardiographic results.

FOCUS is a structured right heart echocardiogram that included the measurement of TAPSE and evaluation for other signs of RVD, defined as follows: right ventricular enlargement (appearance of the right ven- tricle being equal to or greater in size than the left ventricle), septal flat- tening, tricuspid regurgitation (any regurgitant jet seen on Color Doppler in the Apical 4-chamber window), or McConnell’s sign. Pres- ence of RVD included any of these characteristics, or a TAPSE measure- ment less than 1.7 cm. 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 (Fig. 2) [10]. Prior lit- erature has established a testing threshold for TAPSE when diagnosing RVD to be 1.7 cm, meaning that any values equal to or greater than this are considered normal and any values less than 1.7 cm are abnormal [33]. This predefined cutoff value was used for study purposes, although investigators also sought to determine the optimal cutoff for the diagno- sis of PE based on the collected data. The criterion standard for diagnos- ing PE was the presence of a filling defect on CTA consistent with PE as reported by radiology. All patients who were enrolled underwent CTA in the ED.

In a subset of patients, 2 investigators measured TAPSE indepen-

dently on the same patient to determine interrater reliability. They were blinded to each other’s results. These patients were selected based on convenience; if 2 study investigators were present at the

Image of Fig. 2

Fig. 2. Measuring TAPSE. TAPSE is measured in the apical 4-chamber view, with the M-mode cursor placed over. The lateral tricuspid valve annulus. This creates a wave form, which can then be measured from trough to peak.

time of enrollment, then each measured TAPSE. Selection was not relat- ed to Image quality, the clinical condition of the patient, or any other criteria. In another subset of patients, qualitative TAPSE was visually es- timated as normal or abnormal before measurement and compared with quantitative values.

Key outcome measurements

The primary outcomes of this study were to describe the Diagnostic test characteristics (sensitivity, specificity, and likelihood ratios) of TAPSE for PE and to optimize the measurement cutoff of TAPSE for the diagnosis of PE by developing an ROC curve. The secondary outcomes were 3-fold: interrater reliability of TAPSE, assessed by using the intraclass correlation coefficient ; EPs ability to visually estimate TAPSE, assessed using the ? statistic; and the diagnostic test characteris- tics of other measures of RVD for PE.

By approximately half way through the study period, it became anectodally apparent to the investigators that FOCUS and TAPSE seemed to be highly sensitive for PE in patients with tachycardia or hypotension. At that time, it was decided that upon study completion, investigators would undertake a post hoc analysis of the sensitivity of FOCUS and TAPSE in patients with tachycardia or hypotension (heart rate N100 beats/min or systolic blood pressure b90 mm Hg).

Data analysis

JMP Pro 12 (SAS Institute Inc, Cary, NC, 1989-2016) was used to cal- culate key outcome measures, including diagnostic test characteristics,

the development of an ROC curve, and calculation of the area under the curve, ICC, and the ? statistic. Intraclass correlation coefficient was assessed using a 2-way absolute agreement model. The 95% confidence intervals (CIs) for diagnostic measures of components of FOCUS were compared with each other. Differences were considered statistically sig- nificant at the ? level of .05 if the 95% CIs between 2 components did not overlap. Three patients, all without PE, were excluded from analysis be- cause of inability to obtain the necessary echocardiographic windows and measurements at the bedside.

To determine sample size, we chose to conduct a Power calculation to minimize the 95% CI for the sensitivity of TAPSE in the diagnosis of PE. For the width of the 95% CI to be 40% or less, it was necessary to en- roll 30 subjects with confirmed PE. We estimated that 20% of enrolled subjects would be diagnosed as having PE, yielding a necessary sample size of 150 subjects.

Results

Characteristics of study subjects

There were 150 subjects enrolled during the study period (Fig. 3), of whom 32 (21.3%) were diagnosed as having PE (Table 1). Three patients were enrolled without initial consent, as they were obtunded at the time of enrollment. Two of these patients later provided written con- sent. The third patient declined to consent and was subsequently removed from the study database. There were 10 patients who underwent CTA; 7 were not enrolled because they did not speak English, whereas 3 were not enrolled because of inability to attain

Table 2

Patients underoing CTA (161)

Eligible for enrollment (154)

Not eligible for enrollment (7)

Enrolled, unable Enrolled, Unable to

to consent (3) consented (148) obtain adequate

images (3)

Unable to consent, un-enrolled (1)

Consented at later date (2)

Frequency and proportion of ED diagnoses

Diagnosis n (% of total population)

All PE 32 (21.3)

Massive PEa 2 (1.4)

Congestive heart failure 10 (6.6)

Pneumonia 22 (14.6)

COPD/ILD/Pulm HTN 7 (4.7)

Chest pain NOS 48 (32.0)

Otherb 29 (19.4)

Abbreviations: COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease; NOS, not otherwise specified; Pulm HTN, pulmonary hypertension.

a PE with systolic blood pressure less than 90 mm Hg for at least 15 minutes.

b All other diagnoses including pericardial effusion, pleural effusion, progression of cancer, syncope, arrhythmias, and progression of amyotrophic lateral sclerosis.

Fig. 3. Patient enrollment flow diagram (n).

necessary echocardiographic windows and measurements at the bed- side (Fig. 3). Patients diagnosed as having PE were more likely to be ad- mitted to the ICU, had longer length of stays, and had higher heart rates (Table 2). The most common alternative diagnosis was nonspecific chest pain, whereas pneumonia was the most frequent specific alterna- tive diagnosis (Table 2).

Main results

Using a threshold of 1.7 cm, TAPSE was 56% (95% CI, 38-74) sensitive and 79% (95% CI, 78-86) specific for PE. A threshold of 2.0 cm yielded a sensitivity of 72% (95% CI, 53-86) and specificity of 66% (95% CI, 57-75). Sensitivities for other measures of RVD ranged from 13% to 43% (Table 3). receiver operating characteristic curve analysis determined

2.0 cm to be the optimal test threshold for TAPSE with an area under the curve of 0.73 (95% CI, 0.65-0.83; Fig. 4). Test performance character- istics of TAPSE did not vary significantly by operator (Fig. 1).

Measurements of TAPSE by 2 different EPs in 30 subjects yielded 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. In 68 patients, EPs visually estimated TAPSE as normal or abnormal before its measurement (using TAPSE of 1.7 cm or greater as normal), with a ? statistic of 0.94 (95% CI, 0.84- 0.99). Sixteen of those 68 subjects were diagnosed as having PE, 13 of 68 were estimated to have an abnormal TAPSE, and measured TAPSEs ranged from 1.0 to 3.8 cm.

Table 1

Demographic and clinical characteristics of enrolled subjects by disease status

Discussion

Diagnostic test characteristics of TAPSE for PE

To date, there have not been any studies that evaluate the use of TAPSE in the diagnosis of PE, although there has been much research de- lineating its prognostic utility in this setting [2,3,8,29-31]. Because the historically used normal TAPSE cutoff of 1.7 cm was not developed for the diagnosis of PE, we performed an ROC curve analysis to determine the optimal test threshold for TAPSE. Our data suggest that a cutoff of

2.0 cm may be more appropriate for the diagnosis of PE in the ED, as using a higher cutoff value improves sensitivity of TAPSE for PE.

Tricuspid annular plane systolic excursion appears to be more accu- rate in the diagnosis of PE than other measures of RVD; however, not all differences were statistically significant (Table 3). The sensitivities of TAPSE and other measures of RVD for PE were moderate at best, limiting the diagnostic utility of FOCUS in all patients presenting with concern for PE. Despite this, we suspect that FOCUS and TAPSE will be of clinical utility in certain patient populations, specifically those presenting with signs of hemodynamic instability.

Increased sensitivity of FOCUS in the potentially unstable patient

Prior studies have shown that hemodynamically unstable patients with PE have higher rates of RVD [1]. If the etiology of a patient’s abnor- mal vital signs is a PE, it seems likely that at least some degree of RVD may be evident on FOCUS. Approximately half way through patient en- rollment, the investigators’ anecdotal experience suggested that FOCUS may be of increased diagnostic utility in patients with tachycardia or hy- potension, which prompted a post hoc analysis of this patient subgroup. There were 17 subjects with tachycardia and/or hypotension who were diagnosed as having PE, all of whom showed at least one sign of RVD on FOCUS, and 16 of 17 had an abnormal TAPSE. In this patient population,

Table 3

All subjects (n = 150)

PE+ (n = 32) PE- (n = 118)

Diagnostic test characteristics of TAPSE and other measures of right heart strain for pulmo- nary embolus

Age (y), mean +- SD (range)

Female, n (%)

59 +- 17 (19-89)

90 (60)

58 +- 14 (32-84)

15 (47)

63 +- 18 (19-89)

75 (64)

Sensitivity, % (95% CI)

Specificity, % (95% CI)

+Likelihood ratio (95%CI)

-Likelihood ratio (95% CI)

Disposition

TAPSE 1.7 cm

56 (38-74)

79 (71-86)

2.6 (1.8-4.2)

0.56 (0.37-0.83)

Discharged, n (%)

39 (26)

1 (3)

38 (32)

TAPSE 2.0 cm

72 (53-86)

66 (57-75)

2.1 (1.5-2.9)

0.43 (0.24-0.75)

Admit to floor, n (%)

79 (53)

20 (63)

59 (50)

RVEa

37 (21-56)

85 (78-91)

2.6 (1.4-4.8)

0.73 (0.55-0.97)

Admit to SDU/ICU, n (%)

32 (21)

11 (34)

21 (18)

Septal

31 (16-50)

94 (88-97)

5.3 (2.1-12.7)

0.35 (0.58-0.93)

LOS, mean +- SD

3.8 +- 4.8

6.3 +- 5.3

3.2 +- 4.5

flatteningb

ICU/SDU LOS (d),

1.0 +- 2.6

1.7 +- 3.3

0.7 +- 2.3

TRc

43 (25-62)

80 (71-87)

2.2 (1.3-3.7)

0.71 (0.51-0.98)

mean +- SD

McConnell’s signd

13 (4-29)

97 (92-99)

4.8 (1.2-21.0)

0.90 (0.79-1.03)

Vital signs a Right ventricular enlargement, appearance of right ventricle as being equal to or larger

Abbreviations: BP, blood pressure; LOS, length of stay; SDU, step down unit.

Heart rate (beats/min)

mean +- SD

91 +-20

96 +- 20

89 +- 19

Systolic BP (mm Hg), mean (SD)

127 +-19

129 +- 22

126 +- 19

than the left ventricle.

b Abnormal flattening of the interventricular septum during systole.

c Tricuspid regurgitation, any regurgitant jet visualized on color Doppler.

d McConnell’s sign–visualization of hypokinesis of the right ventricle with apical sparing.

1

0.9

0.8

Sensitivity (True positive rate)

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

1-Specificity (False Postive Rate)

Fig. 4. An ROC curve depicting true-positive and false-positive rates of TAPSE for the diagnosis of PE. Area under the curve, 0.73. Diamond marks optimal testing threshold of

2.0 cm, yielding a sensitivity of 72% (99% CI 53%-86%) and specificity of 66% (99% CI 57%-75%), as compared with CTA as the diagnostic criterion standard.

the sensitivity of TAPSE for PE was 94% (95% CI, 71-99) and the com- bined sensitivity of FOCUS for PE was 100% (95% CI, 80-100).

A higher sensitivity of TAPSE and FOCUS in patients with tachycardia or hypotension could help significantly reduce the index of suspicion for PE in this population. This could be of utility in patients who are too he- modynamically unstable to leave the ED for Definitive imaging, for EPs practicing in a resource-limited setting where CTA is unavailable, or pa- tients who have a contraindication to CTA such as contrast allergy, acute kidney injury, or pregnancy. Although these results are thought provok- ing, they require further prospective study before any conclusions may be drawn. Future research will center on testing the sensitivity of FOCUS, including TAPSE, in patients with tachycardia or hypotension who are suspected of having a PE.

Although TAPSE is of moderate sensitivity for PE, an abnormal TAPSE is not specific for PE. Patients with pulmonary hypertension, chronic ob- structive pulmonary disease, and congestive heart failure had higher false-positive rates, which reduced the specificity of TAPSE for PE. This reflects the ability of TAPSE to detect smaller changes in right ventricu- lar function caused by these Disease states, as compared with other measures of RVD, which were more often normal in these patients [13].

Reproducibility of TAPSE

This study demonstrates that TAPSE, performed by EPs who have ad- vanced training in Emergency bedside ultrasound, is a reliable bedside test and may be used in both the prognosis and diagnosis of PE. Prior re- search has shown TAPSE to be a highly reproducible measurement when performed by cardiologists and experienced sonographers, with ICCs ranging from 0.86 to 0.93 [8,10,13,30]. To date, there have been 2 studies of TAPSE in the emergency medicine literature, neither of which examined the reproducibility of TAPSE in the hands of the EP [3,31]. This study is the first to demonstrate that EPs who have advanced training in emergency bedside ultrasound are capable of measuring TAPSE with a high degree of reproducibility. Prior research has shown that other diagnostic measures, such as right ventricular enlargement, can be variable [8,9]. Reproducibility is an essential characteristic of any diagnostic test. Our results suggest that EPs are capable of measur- ing TAPSE with reproducibility that is superior to other measures of RVD as previously reported in the literature [8,9].

We have also shown that EPs are able to visually estimate TAPSE with a high degree of accuracy. This implies that once a practitioner has gained some experience measuring TAPSE, it is reasonable to visual- ly estimate TAPSE and only measure it using M-mode in cases of uncertainty.

Limitations

This study was limited by derivation of subjects from a convenience sample of patients, which may introduce selection bias. Investigators had significant experience in Bedside echocardiography. They received dedicated training in measuring TAPSE with precision and results may not be generalizable to EP populations with more variable ultrasound experience. However, a medical student without any prior experience in point-of-care ultrasound was able to learn the technique. The ICC for the student’s measurements when compared with others was 0.97, indicating excellent agreement between the student and the more ex- perienced operators. This ICC is higher than that between only the most experienced operators (0.85), although not statistically different, suggesting that TAPSE can be readily adopted by EPs with limited expe- rience. In addition, one fellow (F3, Fig. 1) was noted to have a higher proportion of false-positive TAPSE measurements when compared with other investigators. This may be related to measuring technique, although it is likely to be related to random statistical variation, as dif- ferences were not statistically significant between operators. Further limitations include the post hoc nature of the analysis of patients with Abnormal vital signs. Although these findings provide for exciting future directions, because the analysis was not part of the initial research plan, firm conclusions may not be drawn until these results are prospectively replicated.

Conclusions

Emergency physicians with advanced training in emergency ultra- sound are capable of measuring TAPSE with precision comparable to that reported in the cardiology literature. Emergency physicians are able to accurately visually estimate TAPSE as either normal or abnormal, based on an a priori cutoff of 1.7 cm. As a more reliable measure of RVD, TAPSE may also help EPs to determine the severity and prognosis of a patient diagnosed as having a PE.

The optimal cutoff for diagnosis of PE using TAPSE was determined to be 2.0 cm. The diagnostic test characteristics of TAPSE for PE are com- parable to other measures of RVD, although TAPSE appears to be some- what more sensitive and less specific. The incorporation of TAPSE into the evaluation of the right heart may increase the accuracy and reliabil- ity of beside echocardiography for the detection of PE, although our data suggest that FOCUS is of limited utility in all patients presenting with concern for PE. However, FOCUS and TAPSE appear to be highly sensitive for PE in patients with tachycardia or hypotension. Future di- rections will include a follow-up study to prospectively test the sensitiv- ity of FOCUS and TAPSE for PE in this potentially critically ill patient population.

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