Pulmonary embolism - diagnosis and treatment Radka Adlová

Definition Penetration of material into branches of the pulmonary artery a situation mostly when venous emboli becomes dislodged from their site of origin and they embolize to the pulmonary arterial circulation

Epidemiology - Third most common acute cardiovascular disease after coronary ischemia and stroke - 90% of pulmonary emboli originate in the deep venous system of the lower extremities - Other locations include: uterine and prostatic veins upper extremities renal veins right side of the heart

Introduction PE is the most common preventable cause of death in hospitalized patients Pts. are Male>Female, old > young 80% of pulmonary emboli occur without prior warning signs or symptoms 75% of deaths due to pulmonary emboli occur within 30 minutes of embolization Death due to massive PE is often immediate Diagnosis can be difficult Early treatment is highly effective

Risk factors inherited acquired Virchow’s Triad: - Rudolf Virchow postulated more than a century ago that a triad of factors predisposed to venous thrombosis: Local trauma of the vessel wall Hypercoagulability Stasis of blood flow inherited acquired

Risk factors Previous or current DVT Venous Stasis - Immobilization - Stroke/paralysis,… Surgery requiring > 30 minutes within last 3 months Age > 70 Obesity Malignancy, autoimmune diseases Air travel Coagulopathy - Factor V Leiden mutation , Protein C deficiency , Protein S deficiency , Antithrombin deficiency ,Prothrombin gene mutation A20210 , Anticardiolipin antibodies , Lupus anticoagulant In Women - pregnancy, smoking

Clinical presentation Most common symptoms: dyspnoea tachypnoea chest pain (RV ischemia) pleuritic pain (pleural irritation) syncope (indicates severely reduced hemodynamic reserve)

Clinical presentation

How do we make a diagnosis? History Physical examination ECG Serum studies - D - dimer, troponins, natriuretic peptide, arterial blood gases (Hypoxemie, hypocapnia, respiratory alkalosis) Chest X-Ray Echocardiography V/Q scan - Ventilation-Perfusion Scans CT angiography Pulmonary Angiography MRI angiography

Chest X-Ray Usually abnormal, only a small portion of patients with PE have a normal Chest X-Ray Not a sensitive or specific test for the diagnosis of PE Findings: Cardiac enlargement (27%) Normal (24%) Pleural effusion (23%) Elevated hemidiaphragm (20%) Pulmonary artery enlargement (19%) Atelectasis (18%) Parenchymal pulmonary infiltrates (17%)

Radiographic Signs - Westermark Sign disappearance of vascularity (oligemia) on the affected side

Radiographic Signs - Hamptons Hump pleuraly based opacification

Atelectasis collapse of segment of a lung lobe

Prominent PA

ECG most commonly sinus tachycardia, with possible nonspecific ST/T wave changes RV strain patterns suggest severe PE: Inverted T waves V1-V4 QR in V1 Incomplete RBBB S1Q3T3 - only 10% of patients Other ECG abnormalities including atrial arrhythmias, right bundle branch block, inferior Q-waves, and precordial T-wave inversion and ST-segment changes

S1Q3T3 and T wave changes

D-dimer Fibrin degradation product ELISA tests are highly sensitive (>95%) Non specific (~40%): cancer, sepsis, inflammation increase D-dimer levels Negative result excludes PE safely For D-dimer <500ng/mL - negative predictive value (NPV) 91-99% For D-dimer >500ng/mL, sens = 93%, spec = 25%, and positive predictive value (PPV) = 30%

D-dimer False Positive: False Negative: Pregnancy Trauma Postoperative Recovery Inflammation Cancer Rheumatoid Factor Older Age False Negative: Heparin

Echocardiography Useful for rapid triage of pts, sensitive indicator of massive or unstable PE should be done on any patient with suspected massive or unstable PE also useful for selecting patients for thrombolysis or other aggressive therapy may be used for chronic monitoring durint treatment to exclude other diagnosis (dif. Dg.)

Echocardiography Findings: Right ventricle - dilated hypokinetic Abnormal septal motion - distortion of the interventricular septum in diastole Thrombus - right-heart, main pulmonary arteries Tricuspid regurgitation associated with increase in systolic pressure in pulmonary artery

Echocardiography Dilated RV and RA, distortion of the interventricular septum

Echocardiography Dilated RV

Echocardiography Tricuspid regurgitation Increase in systolic pressure in pulmonary artery

Echocardiography - clot in RA and RV

Ventilation - Perfusion Scans Historically, the principal imaging test for the diagnosis of PE A perfusion defect indicates absent or decreased blood flow Ventilation scan obtained with radiolabeled gases A high probability scan is defined as two or more segmental perfusion defects in presence of normal ventilation scan

Ventilation - Perfusion Scans Useful if normal (negative predictive value of 97%) Also useful if high probability (positive predictive value of 85 to 90%) Unfortunately, only diagnostic in 30 to 50% of patients (normal V/Q scan and high probability V/Q scans are helpful in ruling out, but intermediate category required additional testing)

High Probability V/Q Scan

CT Angiography Direct visualization of emboli Advantage: both parenchymal and mediastinal structures can be evaluated - an ability to detect alternative pulmonary abnormalities that may explain the patient's symptoms and signs Studies have shown sensitivity to 95% with an experienced observer Disadvantage: radiation dose

CT Angiography

CT - infarction

CT - pre and postlytic therapy thrombus in the pulmonary artery branch

CT

RV/LV

Pulmonary Angiography This had been the “gold standard” for diagnosis but it is highly invasive Positive result is a filling defect in a pulmonary artery branch - can detect emboli as small as 1-2 mm A negative pulmonary angiogram excludes clinically relevant PE - the risk of embolization in patients with a negative angiogram is extremely low  The pulmonary catheter may also be used therapeutically

Pulmonary Angiography

Magnetic Resonance Angiography Estimated sensitivity ~80% (~100% for larger emboli), specificity 95% Dynamic gadolinium enhancement is used, allowing high quality images Advantages: no radiation non-invasive without iodinated contrast media Disadvantages: low availability high time demand often not suitable for evaluation examination artifacts

Magnetic Resonance Angiography Emboli in segmental an subsegmental arteries

Magnetic Resonance Angiography vs. CT angiography

Diagnostic Algorithm

Case report A 63-year-old woman with stage IV lymphoma has acute shortness of breath History - she is also taking hormone replacement therapy On the day of admission - she develops a sudden shortenss of breath and pleuritic chest pain Physical examination - her pulse is 115 bpm, respiratory rate = 36/min, O2 sat = 88% , her lungs are clear, and her extremities are normal A chest x-ray shows mild right-sided atelectasis, An ABG shows hypoxemie, hypocapnia, respiratory alkalosis What is this patient’s pretest probability for having a pulmonary embolism? What diagnostic method would you use to confirm this?

Treatment Pain Relief Oxygen Dobutamine - pts with right heart failure and cardiogenic shock Anticoagulant therapy : - unfractioned heparin - LMWH - Thrombolysis Embolectomy

Therapy RISK STRATIFICATION Question: For the hemodynamically stable patient, how can we differentiate between patients who are going to do well with anticoagulation alone versus those with worse prognosis who might benefit from more aggressive therapy? RISK STRATIFICATION

Risk stratification Poor Prognostic Signs: Hypotension (SBP <90 mm Hg ) Syncope Shock Troponin levels - correlate with in-hospital mortality and clinical course in PE (Significantly increased mortality in patients with troponin level >0.1 ng/ml) Brain natriuretic peptide (elevated levels related to worse outcomes) RV dilation ( RV/LV short axis >1.5)

Treatment - unstable patient Thrombolysis rtPA (recombinant tissue plasminogen activator - alteplase) 100 mg over 2 h or 0.6 mg/kg over 15 min (maximum dose 50 mg) 1. Hemodynamically compromised by PE 2. Pulmonary hypertension or right ventricular dysfunction detected by echocardiography, pulmonary arterial catheterization Embolectomy Reserved for pts at high risk for death and those at risk for recurrent PE despite adequate anticoagulation, contraindication for thrombolytics

Trombolytic therapy Indications : Absolute Contraindications: Hemodynamic instability RV dysfunction (by echocardiogram) - RV dilatation, abnormal septal motion Anatomically large PE - multiple segments on V/Q Scan or angiogram Extensive DVT - controversial use (probably decreases post-thrombotic syndrome) Absolute Contraindications: Active or recent internal bleeding History of hemorrhagic stroke Intracranial neoplasm Recent cranial surgery or head trauma

Catheter Embolectomy & Fragmentation An alternative in high-risk PE patients when thrombolysis is absolutely contraindicated or has failed

Treatment Surgical Embolectomy Surgical embolectomy (thrombectomy) only in very selective cases Perioperative morality is 25-50% Massive pulmonary embolism where thrombolysis contraindicated Chronic thromboembolic pulmonary hypertension

Therapy Intermediate Risk PE - Hemodynamic stability yet with evidence of RV dysfunction/injury: Controversial No clinical trial or meta-analysis has been large enough to demonstrate a mortality benefit of thrombolysis compared to anticoagulation alone. The decision to use thrombolytic therapy in the intermediate risk PE group should be made on a case-by-case basis after carefully thinking the strength of the indication, the potential benefits, the contraindications, and potential adverse effects.

Therapy Non-High Risk PE: Anticoagulation should be initiated without delay in patients with high or intermediate clinical probability of PE while diagnostic workup is still ongoing Use of LMWH is the recommended for of initial treatment for most patients with non-high-risk PE In patients at high risk of bleeding and in those with severe renal dysfunction, unfractionated heparin with an aPTT target range of 1.5 - 2.5 times normal is a recommended form of initial treatment

Therapy Non-High Risk PE: Initial treatment with unfractionated heparin, or LMWH should be continued for at least 5 days and may be replaced by vitamin K antagonists only after achieving target INR levels for at least 2 consecutive days Duration of Anticoagulation Dependent upon the clinical situation Cancer, and Obesity most likely will need indefinite treatment For other pts with isolated calf vein thrombosis (3 months), proximal leg DVT (6 months) and PE (1 year)

Prevention Heparin        LMW heparin appears to be more effective for prophylaxis than standard heparin Variety of low dose heparins and heparinoids have been used Enoxaparin or Dalteparin (sc qd) Low dose (INR ~1.5X control) warfarin may also be effective        Compression stockings should be used in ALL patients unless contraindicated

Prevention IVC Filters implantation: - usually "Bird's Nest Filter" is placed in IVC - May provide lifelong protection against PE Use: pts. with absolute contraindications to anticoagulation and a high risk of VTE recurrence pts. for patients with recurrent PE on anti-coagulation in pregnant women with extensive thrombosis

Prevention Optimal duration of retrievable filters is unclear IVC Filters: Optimal duration of retrievable filters is unclear Generally an accepted therapy and safe to implant

Conclusion The clinical presentation of acute pulmonary embolism is variable and nonspecific PE is often a misdiagnosed clinical disorder The major diagnostic tests employed in the evaluation of a patient with suspected PE include D-dimer testing, CTPA, V/Q scanning, venous ultrasonography and clinical assessment Rapid identification and appropriate treatment may often prevent unnecessary morbidity and mortality

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