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Beth Israel Deaconess Medical Center Echocardiography in Pulmonary Embolism Gregory Piazza, M.D. Beth Israel Deaconess Medical Center January 26, 2005.

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Presentation on theme: "Beth Israel Deaconess Medical Center Echocardiography in Pulmonary Embolism Gregory Piazza, M.D. Beth Israel Deaconess Medical Center January 26, 2005."— Presentation transcript:

1 Beth Israel Deaconess Medical Center Echocardiography in Pulmonary Embolism Gregory Piazza, M.D. Beth Israel Deaconess Medical Center January 26, 2005

2 Beth Israel Deaconess Medical Center Objectives To present a brief overview of the epidemiology, pathophysiology, diagnosis, and management of acute pulmonary embolism (PE).To present a brief overview of the epidemiology, pathophysiology, diagnosis, and management of acute pulmonary embolism (PE). To review the role of echocardiography in the diagnosis of PE.To review the role of echocardiography in the diagnosis of PE. To highlight the role of echocardiography in risk stratification of patients with PE.To highlight the role of echocardiography in risk stratification of patients with PE.

3 Beth Israel Deaconess Medical Center Epidemiology The incidence of PE in the U.S. is approximately 1 per 1000 per year.The incidence of PE in the U.S. is approximately 1 per 1000 per year. Only 1 out of every 3 cases of venous thromboembolism (VTE), including DVT and PE, is diagnosed.Only 1 out of every 3 cases of venous thromboembolism (VTE), including DVT and PE, is diagnosed. With approximately 450,000 cases detected per year, a staggering 900,000 VTE cases may go undiagnosed annually.With approximately 450,000 cases detected per year, a staggering 900,000 VTE cases may go undiagnosed annually. Lancet 1999;353: Lancet 2004;363:

4 Beth Israel Deaconess Medical Center Epidemiology In the Olmsted County registry, 30-day mortality after PE or DVT has been reported as high as 28%.In the Olmsted County registry, 30-day mortality after PE or DVT has been reported as high as 28%. The International Cooperative Pulmonary Embolism Registry (ICOPER) estimates a 3-month mortality of 17.4%.The International Cooperative Pulmonary Embolism Registry (ICOPER) estimates a 3-month mortality of 17.4%. These data suggest PE is possibly as deadly as acute myocardial infarction.These data suggest PE is possibly as deadly as acute myocardial infarction. Arch Intern Med 1999;159: Circulation 2003;108:

5 Beth Israel Deaconess Medical Center Pathophysiology The most common sources of PE are the deep veins of the lower extremities and pelvis.The most common sources of PE are the deep veins of the lower extremities and pelvis. Thrombi dislodge from these veins and embolize to the pulmonary arterial tree where they trigger pathophysiologic changes in hemodynamics and gas exchange.Thrombi dislodge from these veins and embolize to the pulmonary arterial tree where they trigger pathophysiologic changes in hemodynamics and gas exchange. The size of the embolus, underlying cardiopulmonary status, and neurohumoral adaptations determine the hemodynamic response to PE.The size of the embolus, underlying cardiopulmonary status, and neurohumoral adaptations determine the hemodynamic response to PE. Circulation 2003;108:

6 Beth Israel Deaconess Medical Center Pathophysiology pulmonary_embolism_main.html

7 Beth Israel Deaconess Medical Center Pathophysiology Physical obstruction, release of vasoconstrictors, and hypoxia lead to increased pulmonary vascular resistance (PVR) and right ventricular (RV) afterload.Physical obstruction, release of vasoconstrictors, and hypoxia lead to increased pulmonary vascular resistance (PVR) and right ventricular (RV) afterload. RV pressure overload leads to chamber dilatation and hypokinesis, tricuspid regurgitation, and eventual RV failure.RV pressure overload leads to chamber dilatation and hypokinesis, tricuspid regurgitation, and eventual RV failure. RV pressure overload also causes interventricular septal flattening during systole and deviation towards the left ventricle (LV) during diastole leading to impaired LV filling.RV pressure overload also causes interventricular septal flattening during systole and deviation towards the left ventricle (LV) during diastole leading to impaired LV filling. As RV pressure overload worsens, RV wall stress and ischemia develop secondary to increased myocardial oxygen demand and decreased supply.As RV pressure overload worsens, RV wall stress and ischemia develop secondary to increased myocardial oxygen demand and decreased supply. Am Heart J 1995;130:

8 Beth Israel Deaconess Medical Center Pathophysiology ↑ PA pressure ↑ RV afterload ↑ RV wall tension ↑ RV O 2 demand RV dilatation and dysfunction RV ischemia +/- infarction ↓ RV O 2 supply ↓ coronary perfusion Hypotension ↓ RV cardiac output Septal shift toward the LV ↓ LV preload ↓ LV cardiac output Pulmonary embolism Am Heart J 1995;130:

9 Beth Israel Deaconess Medical Center Spectrum of Disease A variety of clinical syndromes may be seen:A variety of clinical syndromes may be seen: 1.Normotensive with normal RV function 2.Normotensive with RV dysfunction (submassive PE) 3.Cardiogenic shock (massive PE) 4.Cardiac arrest (massive PE)

10 Beth Israel Deaconess Medical Center Diagnosis: History and Physical History: Dyspnea (most frequent symptom)Dyspnea (most frequent symptom) Pleuritic chest painPleuritic chest pain CoughCough HemoptysisHemoptysis SyncopeSyncopePhysical: Tachypnea (most frequent sign)Tachypnea (most frequent sign) Anxious appearanceAnxious appearance TachycardiaTachycardia FeverFever Elevated JVD (most specific sign)Elevated JVD (most specific sign) Loud P2Loud P2 Tricuspid regurgitationTricuspid regurgitation Paradoxical bradycardiaParadoxical bradycardia

11 Beth Israel Deaconess Medical Center The Diagnostic Armamentarium Arterial blood gasesArterial blood gases ElectrocardiographyElectrocardiography Chest X-rayChest X-ray Plasma D-dimerPlasma D-dimer Lower extremity ultrasoundLower extremity ultrasound Echocardiography (TTE and TEE)Echocardiography (TTE and TEE) Ventilation-perfusion lung scanningVentilation-perfusion lung scanning Spiral chest CTSpiral chest CT Magnetic resonance (MR) angiographyMagnetic resonance (MR) angiography Contrast pulmonary angiographyContrast pulmonary angiography

12 Beth Israel Deaconess Medical Center Diagnosis: An Integrated Approach History and Physical Eval. clinical likelihood Electrocardiogram Chest radiograph Patient already in hospital Patient in ED D-dimer HighNormal Chest CT V/Q if dye allergy or renal insufficiency NormalPositiveEquivocalNormal Ultrasonography PositiveNegative No PETreat for PEConsider PA-gram No PE Lancet 2004;363:

13 Beth Israel Deaconess Medical Center Diagnosis: Transthoracic Echocardiography Transthoracic echocardiography (TTE) is insensitive in the diagnosis of acute PE.Transthoracic echocardiography (TTE) is insensitive in the diagnosis of acute PE. In a prospective study, TTE failed to diagnose 50% of patients with angiographically proven PE.In a prospective study, TTE failed to diagnose 50% of patients with angiographically proven PE. However, in the appropriate clinical setting, findings of right ventricular pressure overload may help suggest acute PE as a diagnosis.However, in the appropriate clinical setting, findings of right ventricular pressure overload may help suggest acute PE as a diagnosis. Lancet 2004;363: Am J Med 2001;110:

14 Beth Israel Deaconess Medical Center Diagnosis: Transthoracic Echocardiography Am J Respir Crit Care Med 2002;166: Apical 4- chamber Parasternal short-axis Parasternal long-axis

15 Beth Israel Deaconess Medical Center Echocardiographic Findings In Acute PE RV dilatation and hypokinesisRV dilatation and hypokinesis Interventricular septal flattening and paradoxical motionInterventricular septal flattening and paradoxical motion Alteration of transmitral gradients with A wave > or = E waveAlteration of transmitral gradients with A wave > or = E wave Tricuspid regurgitation (TR)Tricuspid regurgitation (TR) Pulmonary artery (PA) hypertension as estimated by the modified Bernoulli equationPulmonary artery (PA) hypertension as estimated by the modified Bernoulli equation RA dilatationRA dilatation Loss of respiratory-phasic IVC collapse with inspirationLoss of respiratory-phasic IVC collapse with inspiration Patent foramen ovalePatent foramen ovale RA, RV, or pulmonary artery thrombusRA, RV, or pulmonary artery thrombus Ann Intern Med 2002;136:

16 Beth Israel Deaconess Medical Center RV Dilatation In the apical 4 chamber view, a ratio RVEDA (area) to LVEDA > 0.6 correlates with moderate RV dilatation.In the apical 4 chamber view, a ratio RVEDA (area) to LVEDA > 0.6 correlates with moderate RV dilatation. A ratio > or = 1.0 correlates with major RV dilatation.A ratio > or = 1.0 correlates with major RV dilatation. Am J Respir Crit Care Med 2002;166:

17 Beth Israel Deaconess Medical Center RV Hypokinesis RV hypokinesis is frequently diagnosed in a qualitative fashion.RV hypokinesis is frequently diagnosed in a qualitative fashion. Quantitative methods, such as RV fractional area contraction, have not proven more accurate.Quantitative methods, such as RV fractional area contraction, have not proven more accurate. McConnell et al. noted a specific qualitative finding in patients with RV dysfunction and acute PE compared to patients with other causes of RV failure.McConnell et al. noted a specific qualitative finding in patients with RV dysfunction and acute PE compared to patients with other causes of RV failure. The McConnell sign is noted when RV free-wall hypokinesis in observed in the setting of relatively normal RV apical contraction.The McConnell sign is noted when RV free-wall hypokinesis in observed in the setting of relatively normal RV apical contraction. Am J Respir Crit Care Med 2002;166: Ann Intern Med 2002;136: Am J Cardiol 1996;78:

18 Beth Israel Deaconess Medical Center RV Hypokinesis Am J Cardiol 1996;78: The RV free-wall endocardium was traced in the apical 4-chamber view from base to apex at end- systole and end-diastole.The RV free-wall endocardium was traced in the apical 4-chamber view from base to apex at end- systole and end-diastole. Tracings from patients with RV dysfunction from acute PE were compared to those with RV dysfunction from pulmonary arterial hypertension.Tracings from patients with RV dysfunction from acute PE were compared to those with RV dysfunction from pulmonary arterial hypertension. For PE, the McConnell sign had a sensitivity of 77%, specificity of 94%, PPV of 71%, and NPV of 96%.For PE, the McConnell sign had a sensitivity of 77%, specificity of 94%, PPV of 71%, and NPV of 96%.

19 Beth Israel Deaconess Medical Center RV Hypokinesis Courtesy of A. Rosen

20 Beth Israel Deaconess Medical Center Interventricular septal flattening and paradoxical motion Right ventricular pressure overload leads to deviation of the interventricular septum towards the LV in diastole.Right ventricular pressure overload leads to deviation of the interventricular septum towards the LV in diastole. Interventricular septal flattening is seen during systole creating a so- called D-shaped LV.Interventricular septal flattening is seen during systole creating a so- called D-shaped LV. Diastole Systole Am J Respir Crit Care Med 2002;166: Ann Intern Med 2002;136: J Am Coll Cardiol 1987;10:

21 Beth Israel Deaconess Medical Center Interventricular septal flattening and paradoxical motion Am J Respir Crit Care Med 2002;166: Normal (diastole)Acute PE (diastole)

22 Beth Israel Deaconess Medical Center Alteration of Transmitral Gradients In the setting of pericardial constraint, interventricular septal motion towards the LV during diastole leads to impaired LV filling.In the setting of pericardial constraint, interventricular septal motion towards the LV during diastole leads to impaired LV filling. Diastolic impairment leads to an A wave that is > or = to the E wave, signifying increased dependence on atrial contraction for LV filling.Diastolic impairment leads to an A wave that is > or = to the E wave, signifying increased dependence on atrial contraction for LV filling. Normal PE Am J Respir Crit Care Med 2002;166:

23 Beth Israel Deaconess Medical Center Alteration of Transmitral Gradients Courtesy of A. Rosen

24 Beth Israel Deaconess Medical Center Tricuspid Regurgitation RV pressure overload frequently results in tricuspid regurgitation detected on color flow and Doppler.RV pressure overload frequently results in tricuspid regurgitation detected on color flow and Doppler. RV RALA Ann Intern Med 2002;136: Cove/2045/echo55.htm

25 Beth Israel Deaconess Medical Center Pulmonary Hypertension PA systolic pressure is estimated by using the modified Bernoulli equation:PA systolic pressure is estimated by using the modified Bernoulli equation: P = 4V 2 where P = peak pressure gradient V = peak velocity of the TR jet V = peak velocity of the TR jet Estimated RA pressure is added to the gradient to approximate PA systolic pressure.Estimated RA pressure is added to the gradient to approximate PA systolic pressure. Am J Respir Crit Care Med 2002;166: Ann Intern Med 2002;136: Courtesy of A. Rosen

26 Beth Israel Deaconess Medical Center Thrombus In The Right Main PA Ann Intern Med 2002;136:

27 Beth Israel Deaconess Medical Center Diagnosis: Transesophageal Echocardiography Transesophageal echocardiography (TEE) can diagnose PE by direct visualization of the proximal pulmonary arteries.Transesophageal echocardiography (TEE) can diagnose PE by direct visualization of the proximal pulmonary arteries. Because the left main bronchus obstructs the view of the middle portion of the left pulmonary artery, PE is more difficult to detect in the left PA.Because the left main bronchus obstructs the view of the middle portion of the left pulmonary artery, PE is more difficult to detect in the left PA. TEE may play a unique role in the diagnosis of PE in patients with unexplained cardiac arrest (especially pulseless electrical activity).TEE may play a unique role in the diagnosis of PE in patients with unexplained cardiac arrest (especially pulseless electrical activity). Ann Intern Med 2002;136:

28 Beth Israel Deaconess Medical Center Diagnosis: Transesophageal Echocardiography Long-axis transesophageal Short-axis transgastric Oblique transgastric Am J Respir Crit Care Med 2002;166:

29 Beth Israel Deaconess Medical Center Diagnosis: Transesophageal Echocardiography Ann Intern Med 2002;136:

30 Beth Israel Deaconess Medical Center Case Study A 67 year old male with history of CAD, HTN, and prostate cancer presents with acute onset dyspnea and dull chest pressure.A 67 year old male with history of CAD, HTN, and prostate cancer presents with acute onset dyspnea and dull chest pressure. On exam, he is tachycardic, tachypneic, hypoxic, but normotensive. He has elevated neck veins and new lower extremity edema.On exam, he is tachycardic, tachypneic, hypoxic, but normotensive. He has elevated neck veins and new lower extremity edema. His EKG reveals sinus tachycardia.His EKG reveals sinus tachycardia. His chest X-ray is read as “no pneumonia, no CHF.”His chest X-ray is read as “no pneumonia, no CHF.” Because of high clinical suspicion for PE, he undergoes chest CT.Because of high clinical suspicion for PE, he undergoes chest CT.

31 Beth Israel Deaconess Medical Center Case Study

32 Beth Israel Deaconess Medical Center Case Study The patient is started on a weight-based protocol of intravenous unfractionated heparin and admitted to a telemetry floor.The patient is started on a weight-based protocol of intravenous unfractionated heparin and admitted to a telemetry floor. That evening, the patient’s roommate calls the nurses station to report that the patient has “slumped over in his chair.”That evening, the patient’s roommate calls the nurses station to report that the patient has “slumped over in his chair.” The patient is found unresponsive and a code is called.The patient is found unresponsive and a code is called. The patient is found to be in pulseless electrical activity (PEA) and expires after resuscitative efforts are unsuccessful.The patient is found to be in pulseless electrical activity (PEA) and expires after resuscitative efforts are unsuccessful.

33 Beth Israel Deaconess Medical Center Risk Stratification Risk Stratification Tools: History and physicalHistory and physical Clinical prognostic scoresClinical prognostic scores Cardiac biomarkers including cardiac troponin and brain-type natriuretic peptide (BNP)Cardiac biomarkers including cardiac troponin and brain-type natriuretic peptide (BNP) Chest CTChest CT EchocardiographyEchocardiography

34 Beth Israel Deaconess Medical Center History and Physical ICOPER reported several independent clinical predictors of increased mortality at 3 months.ICOPER reported several independent clinical predictors of increased mortality at 3 months. Lancet 1999;353:1386-9

35 Beth Israel Deaconess Medical Center Cardiac Biomarkers Cardiac troponins and BNP have been extensively studied in the evaluation of patients with acute PE.Cardiac troponins and BNP have been extensively studied in the evaluation of patients with acute PE. Cardiac troponins and BNP accurately identify low- risk PE patients with negative predictive values for in- hospital death ranging from 97 to 100%.Cardiac troponins and BNP accurately identify low- risk PE patients with negative predictive values for in- hospital death ranging from 97 to 100%. Patients presenting with acute PE and elevated cardiac biomarkers should undergo transthoracic echocardiography to assess RV function.Patients presenting with acute PE and elevated cardiac biomarkers should undergo transthoracic echocardiography to assess RV function. In patients with acute PE and normal levels of cardiac biomarkers, echocardiography is not routinely required as RV function will most often be normal.In patients with acute PE and normal levels of cardiac biomarkers, echocardiography is not routinely required as RV function will most often be normal. Circulation 2003;108:

36 Beth Israel Deaconess Medical Center Cardiac Biomarkers ReferencenBiomarkerAssayCut-off levelTest +,%NPV,%PPV,% Konstantinides et al cTnICentaur (Bayer)0.07 ng/ml Konstantinides et al cTnTElecsys (Roche)0.04 ng/ml Giannitsis et al 20 56cTnTTropT (Roche)0.10 ng/ml Janata et al cTnTElecsys (Roche)0.09 ng/ml Pruszczyk et al 23 64cTnTElecsys (Roche)0.01 ng/ml ten Wolde et al BNPShionoria (CIS Bio)21.7 pmol/L Kucher et al 26 73Pro-BNPElecsys (Roche)500 pg/ml Kucher et al 25 73BNPTriage (Biosite)50 pg/ml Pruszczyk et al 22 79Pro-BNPElecsys (Roche) pg/ml * * Age and gender adjusted cut-off levels according to manufacturer. Abbreviations: n, number; NPV, negative predictive value; PPV, positive predictive value; cTnI, cardiac troponin I; cTnT, cardiac troponin T; BNP, brain-type natriuretic peptide; pro-BNP, pro-brain-type natriuretic peptide Accuracy of cardiac biomarkers for the prediction of in-hospital death in acute pulmonary embolism. Circulation 2003;108:

37 Beth Israel Deaconess Medical Center Cardiac Biomarkers ↑ RV pressure ↑ PVR RV micro- infarction ↑ RV shear stress Myofibril degradation ↑ Natriuretic peptide mRNA ↑ Troponins↑ BNP Circulation 2003;108:

38 Beth Israel Deaconess Medical Center Chest CT Scan Although chest CT is used primarily for the diagnosis of PE, RV dilatation may also be observed.Although chest CT is used primarily for the diagnosis of PE, RV dilatation may also be observed. In a study of 431 patients with acute PE diagnosed by chest CT, multiplanar reformats of axial CT data into CT 4-chamber views were performed.In a study of 431 patients with acute PE diagnosed by chest CT, multiplanar reformats of axial CT data into CT 4-chamber views were performed. Right and left ventricular dimensions (RV D and LV D ) were measured. RV enlargement was defined as RV D /LV D > 0.9.Right and left ventricular dimensions (RV D and LV D ) were measured. RV enlargement was defined as RV D /LV D > 0.9. RV enlargement predicted 30-day death (hazard ratio, 5.17, p = 0.005) after adjusting for pneumonia, cancer, chronic lung disease, and age.RV enlargement predicted 30-day death (hazard ratio, 5.17, p = 0.005) after adjusting for pneumonia, cancer, chronic lung disease, and age. Circulation 2004;110:

39 Beth Israel Deaconess Medical Center Chest CT Scan Circulation 2004;109:

40 Beth Israel Deaconess Medical Center Echocardiography RV dysfunction on echocardiography has been reliably established as a predictor of adverse outcomes in PE.RV dysfunction on echocardiography has been reliably established as a predictor of adverse outcomes in PE. The most commonly accepted quantitative standards are:The most commonly accepted quantitative standards are: 1. RV to LV end-diastolic diameter ratio > 1 in the apical 4-chamber view 2. RV end-diastolic diameter > 30 mm 3. Paradoxical interventricular septal systolic motion Ann Intern Med 2002;136:

41 Beth Israel Deaconess Medical Center Echocardiography At the Karolinska Institute in Sweden, 126 consecutive patients with PE were examined with TTE on the day of diagnosis.At the Karolinska Institute in Sweden, 126 consecutive patients with PE were examined with TTE on the day of diagnosis. After multivariate analysis, RV dysfunction emerged as the most powerful predictor of in- hospital death.After multivariate analysis, RV dysfunction emerged as the most powerful predictor of in- hospital death. A 6-fold increase in relative risk was noted in the patients with RV dysfunction compared to those with normal RV function.A 6-fold increase in relative risk was noted in the patients with RV dysfunction compared to those with normal RV function. Am Heart J 1997;134:

42 Beth Israel Deaconess Medical Center Echocardiography In a cohort of 209 consecutive patients with PE, 31% presented with a combination of normal blood pressure and echocardiographic evidence of RV dysfunction.In a cohort of 209 consecutive patients with PE, 31% presented with a combination of normal blood pressure and echocardiographic evidence of RV dysfunction. Of these patients, 10% developed cardiogenic shock within 25 hours and 5% died in hospital.Of these patients, 10% developed cardiogenic shock within 25 hours and 5% died in hospital. None of the patients with normal RV function died from PE.None of the patients with normal RV function died from PE. Circulation 2000;101:

43 Beth Israel Deaconess Medical Center Echocardiography In ICOPER, 90-day mortality rate was increased in patients with RV dysfunction.In ICOPER, 90-day mortality rate was increased in patients with RV dysfunction. After multiple regression analysis, RV dysfunction was found to be an independent predictor of death at 90 days.After multiple regression analysis, RV dysfunction was found to be an independent predictor of death at 90 days. Lancet 1999;353:

44 Beth Israel Deaconess Medical Center Risk Stratification Algorithm No shockShock BNP ↓ Troponin ↓ BNP ↑ Troponin ↑ RV dysfunctionNo RV dysfunction Anticoagulation aloneConsider thrombolysis or embolectomy Echocardiography Circulation 2003;108:

45 Beth Israel Deaconess Medical Center Management Primary therapy: ThrombolysisThrombolysis Open surgical embolectomyOpen surgical embolectomy Catheter-assisted embolectomyCatheter-assisted embolectomy Secondary therapy: IV unfractionated heparinIV unfractionated heparin Low-molecular weight heparin (LMWH)Low-molecular weight heparin (LMWH) FondaparinuxFondaparinux WarfarinWarfarin IVC filterIVC filter

46 Beth Israel Deaconess Medical Center Management In patients with massive PE, primary therapy with thrombolytics is considered a lifesaving intervention.In patients with massive PE, primary therapy with thrombolytics is considered a lifesaving intervention. Surgical or catheter-assisted embolectomy may be considered for massive PE if thrombolysis is contraindicated.Surgical or catheter-assisted embolectomy may be considered for massive PE if thrombolysis is contraindicated. For submassive PE, thrombolysis remains controversial as no mortality benefit has been shown in this patient population.For submassive PE, thrombolysis remains controversial as no mortality benefit has been shown in this patient population. However, MAPPET-3 demonstrated a reduction in need for escalation of therapy in patients receiving up-front t-PA (alteplase) for submassive PE.However, MAPPET-3 demonstrated a reduction in need for escalation of therapy in patients receiving up-front t-PA (alteplase) for submassive PE. Normotensive patients with normal RV function are considered low-risk and receive standard anticoagulation.Normotensive patients with normal RV function are considered low-risk and receive standard anticoagulation. J Thromb Thrombolysis 1995;2: N Engl J Med 2002;347:

47 Beth Israel Deaconess Medical Center Thrombolysis in PE: Pre-Lytics *Following echo loops are courtesy of A. Kothavale

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52 Thrombolysis in PE: Post-Lytics

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57 Conclusions Pulmonary embolism is a common and potentially life-threatening disorder.Pulmonary embolism is a common and potentially life-threatening disorder. Echocardiography is insensitive in the diagnosis of acute PE.Echocardiography is insensitive in the diagnosis of acute PE. In conjunction with cardiac biomarkers, echocardiography plays a important role in risk stratification of patient with PE.In conjunction with cardiac biomarkers, echocardiography plays a important role in risk stratification of patient with PE.

58 Beth Israel Deaconess Medical Center The End…


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