Transthoracic echocardiography (TTE) in acute pulmonary embolism

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Transthoracic echocardiography (TTE) in acute pulmonary embolism. Stanislaw P. A. Stawicki, MD 1,4 , Thomas J. Papadimos, MD MPH 2,4, David P. Bahner, ...
OPUS 12 Scientist 2011 Vol. 5, No. 2

S. P. A. Stawicki et al

Submitted 06/2011 – Accepted 08/2011 – Published 11/2011

Evidence tables: Transthoracic echocardiography (TTE) in acute pulmonary embolism Stanislaw P. A. Stawicki, MD 1,4 , Thomas J. Papadimos, MD MPH 2,4, David P. Bahner, MD RDMS 3,4 1

Department of Surgery, Division of Critical Care, Trauma, and Burn, The Ohio State University College of Medicine, Columbus, OH, USA

2

Department of Anesthesiology, The Ohio State University College of Medicine, Columbus, OH, USA

3

Department of Emergency Medicine, The Ohio State University College of Medicine, Columbus, OH, USA

4

OPUS 12 Foundation Global

ABSTRACT As the number of medical journals and related publications is increasing on global scale, identification of truly impactful contributions becomes more difficult. The goal of the current series of publications is to highlight the most significant recent publications in a specific topic area. This issue features the most impactful articles on the clinical application of the Transthoracic echocardiography (TTE) in the diagnosis of pulmonary embolism (PE) in the intensive care unit (ICU).

Cite as: Stawicki SPA, Papadimos TJ, Bahner DP. Evidence tables: Transthoracic echocardiography (TTE) in acute pulmonary embolism. OPUS 12 Scientist 2011;5(2):13-16. Correspondence to: Stanislaw P. A. Stawicki, MD, Department of Surgery, Division of Critical Care, Trauma, and Burn, The Ohio State University College of Medicine, Columbus, OH 43210 USA. Email: [email protected]. Keywords: Evidence table, Internet search, High-impact publications.

BACKGROUND, DEFINITIONS, AND METRICS [Background] Controversies persist regarding the most optimal and practical approaches to diagnosis and management of pulmonary embolism (PE) in the critically ill population. Although high-definition helical computed tomography (CT) and angiography are clearly superior to most other imaging modalities in the diagnosis of PE, not all patients with PE are stable enough to be transported to the CT or angiography suite. [Context] Transthoracic echocardiography (TTE) has been previously described as a potentially useful adjunct in both diagnosis and follow-up of acute PE in the unstable, critically ill patient. [Metrics] For the period between Jul 2006 – Jun 2011, relevant manuscripts with highest Google™ Scholar “times cited” count were selected. Excluded were case reports, reviews, and articles only indirectly related to the current topic.

ARTICLE SUMMARIES Author (Year)

Article Focus

Study Methods and Patient Characteristics

An investigation of the value of echocardiography combined with cardiac troponin-I for risk stratification among patients with acute PE

Prospective, multi-center study of 90 patients with confirmed acute PE

Main Outcomes / Notable Results

[Ref No] {Citations} Zhu et al (2007) [1] {19}

The diagnosis of acute right ventricular dysfunction (RVD) on TTE was made based on at least 2 of the following: (a) right ventricle dilatation {without hypertrophy}; (b) loss of inspiratory IVC collapse; (c) right ventricular hypokinesis; and (d) tricuspid regurgitant jet velocity >2.8 m/sec Study patients were divided into two groups: (a) 50 patients with RVD and (b) 40 patients without RVD

Nearly 56% of patients (50/90) had RVD Nearly 29% had elevated cardiac troponin I, which decreased to about 4% on the fourth day of treatment Multiple logistic regression demonstrated that RVD, right and left ventricular diameter ratio (RVED/LVED), and cardiac troponin I independently predicted adverse 14-day outcomes. In addition, the incidence of adverse clinical events in patients with elevated cardiac troponin I and RVD was significantly greater (41%) than in patients with positive RVD or elevated cardiac troponin I alone (8% and 0%, respectively) Subsequent receiver operating characteristics (ROC) curves demonstrated that the cut-off values for cardiac troponin I and RVED/LVED ratio were 0.11 ng/mL and 0.65, respectively

Zhu et al (2008)

Investigation of the role of right ventricular dysfunction (RVD) as a prognostic factor in pulmonary embolism (PE)

[2] {17}

Prospective randomized trial of 520 patients with acute PE between June 2002 and November 2004 Criteria used for diagnosing RVD included at least 2 of the following: (a) right ventricular dilatation; (b) loss of inspiratory collapse of the inferior vena cava (IVC); (c) right ventricular hypokinesis; and (d) tricuspid regurgitant jet velocity >2.8 meters/second

The 14-day mortality in normotensive patients with RVD was significantly higher (2.0% versus 0.4%) than for normotensive patients without RVD Right ventricular dysfunction increased the odds of adverse 14-day outcomes over 5-fold. Multiple regression demonstrated that RVD, right/left ventricular end-diastolic diameter ratio, and systolic pulmonary artery pressures were independently associated with adverse 14-day outcomes Hemodynamic instability, 14-day clinical outcome, and systolic pulmonary artery pressure were among independent predictors of clinical outcomes at 3 months

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OPUS 12 Scientist 2011 Vol. 5, No. 2

S. P. A. Stawicki et al

Submitted 06/2011 – Accepted 08/2011 – Published 11/2011

Author (Year)

Article Focus

Study Methods and Patient Characteristics

Main Outcomes / Notable Results

To better define the incremental diagnostic information from quantitative measures of right ventricular (RV) size, pressure, and function in risk assessment of patients with PE

Transthoracic echocardiography studies were obtained prospectively in 300 patients who underwent ventilation-perfusion (V/Q) scanning for suspected PE

Two predictive models were constructed. In the first model, right ventricular (RV) outflow acceleration time of 0.78, RV outflow tract fractional shortening 4.1 mmol/L were added to the analysis, with subsequent increase in AUC to 0.88. The final list of independent predictors of PE in this model included ECG signs of RV strain, PA acceleration time >89 ms, and D-dimer >4.1 mmol/L

{17}

The negative and positive predictive values in the presence of 2 out of 3 factors in the final (second) model were 88% and 70%, respectively Of note, the commonly utilized Wells pretest risk score was found not to be independently associated with PE in either of the predictive models studied

Chung et al (2006)

To better define the correlation of echocardiographic abnormalities with the degree of thromboembolic burden in elderly patients with acute PE

Retrospective study of transthoracic echocardiograms of 63 elderly patients with acute PE Mean patient age was 71±16 years

[4] {15}

Lodato et al (2008) [5]

To determine the relative predictive accuracy of suggested quantitative sonographic indices among patients undergoing computed tomography (CT) scanning for suspected PE

{10}

The authors determined that right ventricular hypokinesis (visual grade 0-3), right ventricular end-systolic area, and right ventricular ejection area were all associated with greater degrees of pulmonary artery obstruction

Predictive value of transthoracic echocardiographic findings was assessed for their ability to identify >30% pulmonary artery obstruction as determined by quantitative ventilation/perfusion pulmonary scintigraphy

In addition, the ratio of right-to-left ventricular end-diastolic area and the radio of right-to-left atrial end-systolic area were both strongly associated with the degree of pulmonary artery obstruction

Retrospective review of 67 patients who underwent CT imaging for suspected PE and had a TTE within 48 hours of the CT study

Pulmonary embolism was demonstrated on CT in 41 of 67 (61%) cases. In the PE group, mean patient age was 54 years, with 73% male predominance. Among clinical findings associated with PE, tachycardia and new-onset atrial fibrillation were noted to be common

The authors focused on sonographic findings that were deemed to be “highly suggestive” of PE: (a) measured RV/LV area ratio; (b) RV/LV end diastolic dimension ratio; (c) the “McConnell sign”; (d) the “Dsign” or interventricular septal shift; (e) pulmonary artery diameter; (f) tricuspid regurgitation velocity; (g) the “60/60 sign” or TR velocity 0.7 and/or the “McConnell sign” are highly suggestive of acute PE and should prompt further diagnostic evaluation

Kjaergaard et al (2009)

To investigate prognostic implications of routine echocardiography in patients with suspected pulmonary embolism

[6] {8}

Transthoracic echocardiography (including tissue Doppler imaging) was performed prospectively in 283 consecutive patients with suspected non-massive PE All patients underwent ventilation/perfusion (V/Q) scanning Investigation of prognostic TTE factors included right ventricular (RV) size, function, and pressure. In addition, patients with PE received follow-up TTE at 1 year to assess long-term changes in TTE parameters

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Mortality was similar for patients with and without PE (10% vs 12%). Of interest, patients with “indeterminate” V/Q scans were noted to have poorer overall prognosis [Editor’s comment: this was likely due to greater incidence of pre-existing pulmonary diseases in that group]. Among patients with confirmed PE, the PA acceleration time was predictive of event-free survival (all-cause mortality and heart failure hospitalization) when adjusted for LV ejection fraction, age, and gender Left ventricular (LV) ejection fraction and shortening of PA acceleration time (i.e., measure of RV afterload) both correlated with patient survival, regardless of the presence of PE

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OPUS 12 Scientist 2011 Vol. 5, No. 2

S. P. A. Stawicki et al

Submitted 06/2011 – Accepted 08/2011 – Published 11/2011

Author (Year)

Article Focus

Study Methods and Patient Characteristics

Single-institution review of clinical experience with TTE in the setting of pulmonary embolism

Retrospective study of 31 critically ill surgical patients who underwent TTE within 72 hours of diagnosis of pulmonary embolism

Main Outcomes / Notable Results

[Ref] {Citations} Stawicki et al (2008)

All patients had helical CT or V/Q scan-supported diagnosis of pulmonary embolism prior to inclusion

[7] {6}

Mean patient age was 66 years, with mean APACHE II score of 18 Twenty-two had high and 9 had moderate clinical suspicion for PE. Diagnosis of PE was supported by helical CT (25/31) or V/Q scanning (6/31). In addition, 12/31 patients were found to have deep venous thrombosis on extremity Duplex ultrasonography The most common TTE findings, in descending order, included tricuspid regurgitation (28/31), pulmonary hypertension (24/31), right ventricular dilatation (23/31), right heart strain (19/31) and underfilled, hyperdynamic left ventricle (17/31) Seventeen patients underwent pre-PE “baseline” echocardiography. All patients in that group had worsening in at least one TTE finding when post-PE studies were compared to “baseline” studies In addition, echocardiographic improvement was seen on post-PE TTE studies at 24 and 48 hours when compared to “index” TTE studies performed following the diagnosis of PE

Zhu et al (2008) [8]

To determine changes in right ventricular functional characteristics on TTE occurring after different therapeutic strategies among patient with acute PE

{6}

Prospective, randomized, two-year study of 520 patients with acute PE across 41 hospitals in China

Most patients were male (62.1%) with mean age of 57 years for the study group

Based on clinical acuity, patients were classified into two PE groups: (a) “major PE” {52 patients with hemodynamic instability and 198 normotensive patients with RV dysfunction} and (b) “minor PE” {270 normotensive patients without RV dysfunction}

At each measurement point, indices of RV function on TTE in the “major PE” group were significantly improved compared to same indices in the “minor PE” group

Patients in the “major PE” group were further subdivided into the following therapeutic groups: (a) urokinase 12 hrs; (b) urokinase 2 hrs; (c) recombinant tissue-type plasminogen activator (rtPA) 50 mg; and (d) rtPA 100 mg Patients in the “minor PE” group were also sub-divided according to the anticoagulant administered: (a) heparin group; (b) nadroparin group

Ouldzein et al

To determine the value of TTE in the diagnosis of PE

(2009)

The systolic pulmonary artery pressure (SPAP) was noted to be significantly improved after anticoagulant administration in the “minor PE” patient group. Of interest, there were no differences among the different thrombolytic sub-groups of “major PE” group. Likewise, no differences were noted among the different anticoagulation sub-groups of the “minor PE” group The presence of RVD was significantly lower (34% vs 100%) at 24 hours post-thrombolytic therapy in “major PE” patients. Of note, even at the 3 month follow-up, both TRPG and SPAP were significantly higher in the “major PE” group when compared to the “minor PE” group

TTE exams were performed before the therapy, and at 24 hours, 14 days, and 3 months following therapy

In summary, TTE demonstrated similar effect of various thrombolytic agents among patients with “major PE”. Likewise, the type of heparin administered did not seem to influence TTE findings among patients with “minor PE”. The authors advocate the use of TTE as a monitoring tool during thrombolytic therapy for PE. They further postulate that persistent pulmonary hypertension on TTE may facilitate early identification of patients likely to develop chronic thromboembolic pulmonary hypertension [Editor’s comment: based on these findings, TTE may be useful in monitoring and management of both acute PE and the chronic sequelae of PE]

Retrospective study of 43 patients who underwent TTE and evidence of PE by ventilation-perfusion (V/Q) scanning and pulmonary artery helical CT as the diagnostic gold standard

The authors found that the overall sensitivity and specificity of TTE for acute PE were 74% and 25%, respectively

[9]

The most commonly seen echocardiographic signs in acute PE included right heart dilatation and increases in right-sided cardiac chamber pressures

{2} Overall, the authors advocate the use of TTE as a good screening test in the setting of suspected PE

Table legend. Article rank [square brackets] is determined by the {number of citations}; AUC = Area under curve; CT = Computed tomography; ECG = Electrocardiography; EDD = End-diastolic dimension; IVC = Inferior vena cava; LV = Left ventricle; LVED = Left ventricular end-diastolic; PA = Pulmonary artery; PE = Pulmonary embolism; ROC = Receiver operating characteristics; RV = Right ventricle; RVED = Right ventricular end-diastolic; RVD = Right ventricular dysfunction; SPAP = Systolic pulmonary arterial pressure; TR = Tricuspid regurgitation; TTE = Transthoracic echocardiography; V/Q scan = Ventilation-perfusion scan.

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OPUS 12 Scientist 2011 Vol. 5, No. 2

S. P. A. Stawicki et al

Submitted 06/2011 – Accepted 08/2011 – Published 11/2011

REFERENCES [1] Zhu L, Yang Y-H, Wu Y-F, Zhai Z-G, Wang C. Value of transthoracic echocardiography combined with cardiac troponin I in risk stratification in acute pulmonary thromboembolism. Chin Med J 2007;120(1):17-21. [2] Zhu L, Yang Y, Wu Y, Zhai Z, Wang C. Value of right ventricular dysfunction for prognosis in pulmonary embolism. International Journal of Cardiology 2008;127:40-45. [3] Kjaergaard J, Schaadt BK, Lund JO, Hassager C. Quantitative measures of right ventricular dysfunction by echocardiography in the diagnosis of acute nonmassive pulmonary embolism. J Am Soc Echocardiogr 2006;19:1264-1271. [4] Chung T, Emmett L, Khoury V, Lau GT, Elsik M, Foo F, Allman KC, Kritharides L. Atrial and ventricular echocardiographic correlates of the extent of pulmonary embolism in the elderly. J Am Soc Echocardiogr 2006;19:347353.

[6] Kjaergaard J, Schaadt BK, Lund JO, Hassager C. Prognostic importance of quantitative echocardiographic evaluation in patients suspected of first nonmassive pulmonary embolism. European Journal of Echocardiography 2009;10:89-95. [7] Stawicki SP, Seamon MJ, Kim PK, Meredith DM, Chovanes J, Schwab CW, Gracias VH. Transthoracic echocardiography for pulmonary embolism in the ICU: finding the “right” findings. J Am Coll Surg 2008;206:42-47. [8] Zhu L, Wang C, Yang Y, Wu Y, Zhai Z, Dai H, Pang B, Tong Z. Value of transthoracic echocardiography in therapy regimens evaluation in pulmonary embolism. J Thromb Thrombolysis 2008;26:251-256. [9] Ouldzein H, Rahal N, Cherradi R, Zouaoui W, Mechmeche R, Haouala H. Role of transthoracic echocardiography in the diagnosis of acute pulmonary embolism. Mali Med 2009;24:14-18.

[5] Lodato JA, Ward RP, Lang RM. Echocardiographic predictors of pulmonary embolism in patients referred for helical CT. Echocardiography 2008;6:584590.

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