Pulmonary Vascular Diseases and Interventions



Pulmonary Vascular Diseases and Interventions


Eileen M. Harder, MD

Wassim H. Fares, MD, MSc






Key Points



  • Depending on patient comorbidities and the severity of the insult, PEs may cause a wide variety of symptoms, ranging from none to dyspnea to sudden death.


  • PEs can be classified by mortality risk: high (massive), intermediate (submassive), and low (nonsubmassive). These groups are defined clinically by certain prognostic factors.


  • PE treatment depends on the risk group.


  • PH has many different etiologies, and the World Health Organization (WHO) separates this disease into five different classes.


  • The best screening test for any suspected PH is transthoracic echocardiography (TTE).


  • WHO group 1 PH is pulmonary arterial hypertension (PAH). It can be idiopathic, heritable, drug or toxin related, or associated with certain conditions including congenital heart disease or portal hypertension.


  • If TTE suggests PAH, definitive diagnosis is made by right heart catheterization (RHC).


  • PAH treatment depends on the cause of PH and disease severity. It often involves advanced medical therapy; certain forms of PAH may require surgery.


  • WHO group 4 PH is caused by chronic pulmonary emboli (CTEPH).




CLINICAL PEARLS



  • High-risk PEs are defined by hemodynamic instability (sustained hypotension or shock).


  • Intermediate PEs are hemodynamically stable but have evidence of RV dysfunction and/or myocardial injury. All of these features are absent in low-risk PEs.


  • In hemodynamically unstable patients, PE can be diagnosed by TTE. Stable patients should undergo CT pulmonary angiogram (CTPA).


  • Patients with high-risk PEs should receive urgent treatment with systemic thrombolysis, surgical embolectomy, or catheter-based methods, as appropriate.


  • Intermediate and low-risk PEs should receive anticoagulation.


  • PAH on RHC is defined as a mean PAP ≥25 mm Hg with pulmonary artery wedge pressure (PAWP) ≤15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units.


  • Treatment of PAH may entail calcium channel blockers (for the small number of vasoreactive patients) or advanced therapy.


  • Uncorrected atrial septal defects (ASDs) may also cause PAH. Patients with ASD-PAH should undergo early closure, provided that they do not have Eisenmenger syndrome.



  • Portopulmonary hypertension is a form of PAH associated with portal hypertension. Liver transplant is indicated in patients with mPAP <35 mm Hg and PVR <5 Wood units.


  • CTEPH should be considered in acute PE patients whose dyspnea and other symptoms do not resolve after 3-6 months.


  • In suspected CTEPH, a positive TTE is followed by a ventilation/perfusion scan. RHC and/or pulmonary angiography are required to confirm the diagnosis.


  • The only definitive treatment for CTEPH is pulmonary endarterectomy (PEA). Balloon pulmonary angioplasty or advanced therapy may be considered in non-PEA candidates.


I. Pulmonary Vascular Disease

Pulmonary vascular disease (PVD) refers to any disease that affects the pulmonary vessels. The two most common conditions are pulmonary emboli and pulmonary hypertension, and this chapter will focus on these diseases and their management.


II. Acute Pulmonary Emboli



  • A. Epidemiology An acute pulmonary embolus (PE) occurs when a pulmonary artery (PA) or one of its branches becomes obstructed, most commonly by thrombus. The incidence of PEs is unknown, and this may be due partly to underdiagnosis—silent PEs may occur in up to 30%-50% of deep venous thrombosis (DVT) cases, and they are often only noted incidentally on autopsy.1,2,3 Recent estimates suggest that there are approximately 600,000 PEs in the United States per year, and it may contribute to death in up to one-third of these patients.4,5,6,7


  • B. Risk Factors There are many inherited and acquired PE risk factors. Inherited factors include hypercoagulable states, such as factor V Leiden or prothrombin mutations, protein C or S deficiencies, and antithrombin deficiency. Important acquired risk factors include older age, major or orthopedic surgery, leg or hip fractures, cancer, immobility, spinal cord injury, prior PE/DVT, obesity, pregnancy, oral contraceptive or hormone replacement therapy, and antiphospholipid antibody syndrome, among others.2,8 For patients with DVTs, PE risk is particularly high with proximal thigh clots.


  • C. Pathophysiology PEs and DVTs are types of venous thromboembolism, in which clot formation is based on Virchow triad of venous stasis, hypercoagulability, and endothelial injury. In normal lungs, perfusion matches ventilation—hypoxic vasoconstriction occurs in poorly ventilated areas, and well-oxygenated regions remain perfused. PEs create a ventilation-perfusion mismatch. In the most severe cases, perfusion is completely absent and systemic shunting of deoxygenated blood occurs.5,9 This results in hypoxemia, which is further worsened by cytokines that promote inflammation and vasocontriction.9 Compensatory hyperventilation occurs and as a result, respiratory alkalosis with low PCO2 is usually present.9 Hypercapnia should increase suspicion for a massive embolism.9


    PEs also cause circulatory dysfunction. Generally, hemodynamic abnormalities occur only when ≥30%-50% of the pulmonary arterial system is occluded, although even a small clot can cause dysfunction in patients with heart and lung disease.8,10,11 Obstructed vessels and the accompanying vasoconstriction of normal vasculature cause a sudden rise in pulmonary vascular resistance (PVR) and acute pulmonary hypertension (PH). The increased afterload dilates the right ventricle (RV), decreases myocardial contractility, and diminishes coronary vessel perfusion.12 A normal, nonweakened RV can generate a systolic pressure up to 40 mm Hg, but above this in the acute setting, RV failure occurs.11 Right-sided stroke volume (SV) and cardiac output (CO) are reduced. As the RV further stretches, the septum moves into the left ventricle (LV). The end result is decreased left-sided filling, preload, and CO.13

    The body triggers a complex compensatory cascade including sympathetic activation to increase PA flow and preserve systemic circulation.8 Depending on the severity of the insult, a PE can manifest as a wide spectrum of findings ranging from no hemodynamic abnormalities to RV failure, hypotension, and shock. In the most severe cases, compensation is inadequate and sudden death occurs, often by pulseless electrical activity or asystole.8,11


  • D. Classification Although PEs can be classified in multiple different ways, the most clinically relevant system stratifies disease severity based on mortality risk—high, intermediate, or low.2,11 These terms correspond to massive, submassive, and nonsubmassive PEs, respectively.

    High-risk (massive) disease is defined by the presence of sustained hypotension or shock in the setting of an acute PE that is not due to another cause. Some guidelines also suggest pulseless or persistent bradycardia (<40 beats per minute) as alternative inclusionary criteria.14 Hypotension is generally defined as a systolic blood pressure <90 mm Hg, a systolic drop ≥40 mm Hg for >15 minutes or the requirement for vasopressor support.2,11,14,15 Evidence of tissue hypoperfusion, such as a lactic acidosis, suggests a progression to shock.

    Low (nonsubmassive) and intermediate (submassive) risk PEs are hemodynamically stable. These classes are separated by RV dysfunction and/or myocardial injury—one or two of these features are present in intermediate disease, but both are lacking in low-risk PEs. RV dysfunction is defined by the presence of RV dilation, elevated NT-proBNP or BNP, or ECG changes (represented by new right bundle branch block; anteroseptal ST elevation or depression; or anteroseptal T-wave inversion).14 Myocardial injury is reflected as elevated troponin I or T.14


  • E. Presentation PE can manifest with a wide variety of symptoms—ranging from none to sudden death—depending on disease severity and patient comorbidities. Symptoms are usually nonspecific, including dyspnea, pleuritic chest pain, cough, and/or lower extremity swelling.16 Physical examination may reveal tachypnea, tachycardia, decreased breath sounds, decreased arterial oxygen saturation, and/or hypotension.16


  • F. Diagnosis Risk category dictates workup and treatment. Patients with suspected high-risk (massive) PEs should be immediately stabilized, including with vasopressors if necessary. Early diagnosis is crucial, as time to treatment affects the risk of mortality. If patients become stable enough for transport to radiology, immediate CT pulmonary
    angiogram (CTPA) should be done. Bedside echocardiography should be performed, particularly if patients are unable to undergo CTPA. Findings of severe RV dilation, decreased systolic function, septal bowing, RV wall hypokinesis or McConnell sign (RV mid-free wall akinesia with normal apical motion), visualized right-heart thrombi, and/or inspiratory lack of inferior vena cava (IVC) collapse suggest high-risk PE.17 When stable, patients should undergo confirmatory CTPA.

    Hemodynamically stable patients with suspected low- or intermediate-risk PE should undergo further workup. D-dimer may be high, although this occurs in many other conditions including infection, pregnancy, and cancer. Arterial blood gas may reveal hypoxemia, alveolar-arterial gradient, or respiratory alkalosis. Other findings may be elevated leukocytosis, BNP, or troponin. ECG usually shows sinus tachycardia and nonspecific ST- and T-wave changes; less common findings include new arrhythmia, right bundle branch block, RV strain, right axis deviation, or inferior Q-waves, among others. Chest X-ray rarely shows Hampton hump or Westermark sign.

    After assessment, the pretest probability of PE should be evaluated in hemodynamically stable patients. This can be done by either clinical suspicion or predictive calculators, such as the modified Wells or Geneva scores.11,18,19 If PE is likely, CTPA is the initial step in diagnostic workup. If it reveals clots, treatment should begin; if it is negative, other diagnoses should be considered. If scoring suggests that PE is unlikely, D-dimer testing may be done, followed by CTPA if the level is high. In patients with a contrast allergy, renal failure, or pregnancy, the initial imaging test should be ventilation/perfusion (V/Q) scan. Echocardiography may be useful in some hemodynamically stable patients to evaluate for RV strain, but it is not required.


  • G. Treatment Treatment depends on PE risk. Hemodynamically unstable patients with high-risk (massive) disease are at increased risk for early death. Supportive measures should be initiated while a treatment decision is made; these include vasopressors and oxygen as necessary.11 Definitive reperfusion treatment can be performed with systemic thrombolysis, catheter-directed interventions, or surgical embolectomy.



    • 1. High-Risk (massive) PE



      • Thrombolysis

        Thrombolysis rapidly breaks down clots to improve perfusion and off-load the RV. In high-risk PE, it is associated with decreased mortality and improved hemodynamics compared with anticoagulation alone.20,21 The most commonly used thrombolytics are recombinant tissue-type plasminogen activation (tPA, alteplase), streptokinase, and urokinase.14 Of these, tPA is usually chosen for its short infusion time (the general standard dose is 100 mg tPA over 2 h).14 If anticoagulation was started, it may be temporarily stopped during thrombolytic infusion.

        The major side effect of thrombolysis is increased bleeding risk, and so it should not be used in many patients. Absolute contraindications include active bleed; known intracranial malignancy or vascular lesion; any prior intracranial hemorrhage; suspected aortic dissection; and recent (ie, within the past 3 mo) ischemic stroke, brain or spine surgery, or significant closed-head and/or facial
        trauma.14 Relative contraindications vary between guidelines but generally include history of and/or current severe poorly controlled hypertension, prolonged CPR (>10 min) or major surgery in the previous 3 weeks, ischemic stroke >3 months ago, internal bleeding within the past 2-4 weeks, active peptic ulcer, dementia, noncompressible vascular puncture, pregnancy, current anticoagulant use, age >75 years, infective endocarditis, advanced liver disease, or diabetic retinopathy.11,14 Based on these contraindications, approximately 50%-60% of patients do not receive systemic thrombolysis.22


      • Catheter-Directed Management



        • Catheter-Directed Embolectomy

          Catheter-based PE treatment may consist of mechanical, thrombolytic, or combined interventions to off-load the RV and improve perfusion.23 For patients with absolute contraindications to thrombolysis, a mechanical procedure, such as thrombus fragmentation, rheolytic thrombectomy, suction thrombectomy, or rotational thrombectomy, may be used.11 These methods are generally recommended only for clots in the main or lobar PAs.14 Evidence for some of them is limited, and there are little data comparing their effectiveness and outcomes. A 2007 systematic review demonstrated approximately equal success rates for the first three techniques (fragmentation 82%, rheolytic 75%, and suction [aspiration] 81%); however, technology has significantly improved since this time.24 Given the required technical skill, these interventions should be performed only at expert centers.



          • Thrombus Fragmentation

            Thrombus fragmentation mechanically breaks the thrombus into smaller fragments. This immediately reduces main PAP by displacing these small fragments to the distal branches.23 In this procedure, a sheath is placed and a rotatable pigtail catheter is introduced over a guidewire. The catheter is manually rotated to break up the thrombus. It may also be performed with balloon angioplasty catheters or other devices.14 Given that it is inexpensive, this is the most common technique; it can also be combined with other mechanical methods to improve outcomes.25


          • Rheolytic Thrombectomy

            Rheolytic thrombectomy employs the Bernoulli principle through the use of high-pressure saline jets.26 In this technique, a sheath is placed, a guidewire is introduced, and the device is inserted over it. Saline jets are used to create a low-pressure zone around the catheter, which macerates the thrombus and pulls the fragments back for removal via a suction port. Local thrombolytics can also be injected and removed via this system. Of note, at least one of the rheolytic thrombectomy systems has been associated with intraprocedure bradycardia that may necessitate short treatment times, temporary breaks, or transvenous pacing.26 Other side effects may include hemoptysis, hemoglobinuria, and renal insufficiency.



          • Suction Embolectomy

            Suction embolectomy uses suction to remove thrombus and can be done alone or in combination with other techniques. In this procedure, a specific aspiration sheath with a special hemostatic valve is advanced into the thrombus.23 A syringe is used to apply suction while the catheter is moved gently over a short distance in the pulmonary artery. Clot is cleared when blood enters the syringe, and this procedure may require multiple advancements of the suction catheter over the guidewire. Alternatively, suction embolectomy can be performed with newer devices that incorporate aspiration and filtration with dual-venous access. This extracorporeal circulation bypass system aspirates blood, clears it of clot, and then reintroduces it.26


          • Rotational Thrombectomy

            Rotational thrombectomy uses rotating coils to treat PEs. A high-speed rotating metallic coil in a catheter lumen creates a negative pressure that disrupts the thrombus, macerates it, and then aspirates it. A small study has suggested this method is effective in clearing thrombus and improving PAP.27


        • Catheter-Directed Thrombolysis

          Catheter-directed thrombolysis (CDT) denotes the local infusion of thrombolytics, either alone or with mechanical interventions.23 In this procedure, a simple catheter with multiple side holes is placed into the pulmonary artery and the drug is passively infused. The thrombolytic dose used in CDT is only a small amount of that used for systemic treatment, and so bleeding risk is decreased.26

          The combination of local thrombolysis with mechanical interventions is referred to as pharmacomechanical thrombolysis (PMT). Studies suggest that the best outcomes come from PMT—one analysis demonstrated a 95% success rate when fragmentation, suction, or rheolytic therapy was used with local thrombolysis, compared with 81% when a mechanical intervention was used without CDT.14,24 Ultrasound has also been successfully combined with CDT. In this method, a specific device is used that consists of a catheter with multiple side holes and a central ultrasonic core wire. The catheter is placed into the thrombus and then the ultrasonic core is inserted and locked into place. The high-frequency waves disrupt the thrombus and promote better thrombolytic penetration.


      • Surgical Embolectomy

        Surgical embolectomy is recommended in centrally located, high-risk (massive) PE with thrombolytic contraindications or failure.28 It also is useful in patients with right atrial (RA) and RV clots or a large patent foramen ovale.28 Mortality was historically around 30%; however, it has decreased to as low as 4%-6% in more recent years.11,14


        PE embolectomy is a variation of the modified Tredenlenburg operation.28,29 Median sternotomy is made and normothermic cardiopulmonary bypass (CPB) is established. Intravenous (IV) unfractionated heparin is the preferred anticoagulation for better control and easier reversal. Arteriotomy is made into the main PA between the pulmonic valve and PA bifurcation.28 This allows for saddle and left PE access; clot is extracted by forceps whole if possible or with suction if necessary.30 If clot is in the right PA, an incision can be made in this vessel between the aorta and superior vena cava.28 Incisions can be extended distally as necessary. Certain centers use lung massage for clot extraction and others do not because of an increased risk of pulmonary damage. All main PA branches should be inspected by direct visualization or flexible surgical angioscopy. The RA and RV should also be explored and cleared; any patent foramen ovale should be closed. Of note, an inferior vena cava filter may be inserted preoperatively or within the first 24 hours postoperatively to prevent reembolization.29


    • 2. Intermediate-Risk (submassive) and Low-Risk (nonsubmassive) Pulmonary Embolus Hemodynamically stable patients should receive supportive care as needed during diagnostic workup. Patients with intermediate-risk (submassive) PE should start anticoagulation with IV unfractionated heparin or subcutaneous low-molecular-weight (LMW) heparin. When fully anticoagulated, they can be transitioned to an oral agent, namely either a direct factor Xa inhibitor, direct thrombin inhibitor, or warfarin.11,31 For the majority of patients with their first provoked PE, anticoagulation should be continued for 3 months.14 Those with unprovoked clots may benefit from a longer treatment course, depending on their risk factors.11,14 Patients with cancer or pregnancy are considered to be a special population; LMW heparin is preferred over an oral agent.11

      Thrombolysis is generally not recommended in hemodynamically stable patients with intermediate-risk (submassive) PE.31 Thrombolysis improves hemodynamics in this population (compared with anticoagulation alone), but major bleeding is more frequent, and it is generally considered that the risks outweigh the benefits.11,31 Patients with intermediate-risk disease—particularly those with significant RV dysfunction on echocardiography or borderline blood pressure—should be monitored carefully for decompensation, in the event that thrombolysis becomes necessary.14

      Thrombolysis should not be used in low-risk (nonsubmassive) disease. Hospitalization may not be required in this population, but anticoagulation should be initiated.


III. Pulmonary Hypertension

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Feb 27, 2020 | Posted by in CARDIOLOGY | Comments Off on Pulmonary Vascular Diseases and Interventions

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