Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Soluble Guanylate Cyclase Stimulators
Class Summary
These agents facilitate the pathways that play a role in vasodilation.
Riociguat (Adempas)
Riociguat stimulates vasodilation by increasing generation of cyclic guanosine monophosphate (cGMP) as it stimulates the soluble guanylate cyclase-cGMP pathway.
Endothelin Receptor Antagonists
Class Summary
Endothelin-receptor antagonists competitively bind to the endothelin-1 receptors EtA and EtB, causing reductions in pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP).
Bosentan (Tracleer)
Bosentan inhibits vessel constriction and elevation of blood pressure by competitively binding to EtA and EtB receptors in endothelium and vascular smooth muscle. This leads to a significant increase in cardiac index associated with significant reductions in PAP, PVR, and mean RAP.
Macitentan (Opsumit)
Macitentan blocks the binding of endothelin-1 to endothelin receptor subtypes ETa and ETb on smooth muscle and vascular endothelium. The stimulation of these receptors is associated with fibrosis, inflammation, hypertrophy, and vasoconstriction.
Ambrisentan (Letairis)
Ambrisentan improves exercise ability and slows the progression of clinical symptoms. It inhibits vessel constriction and elevation of blood pressure by competitively binding to EtA and EtB receptors in endothelium and vascular smooth muscle. This leads to a significant increase in cardiac index associated with significant reductions in PAP, PVR, and mean RAP.
Phosphodiesterase-5 Enzyme Inhibitors
Class Summary
The antiproliferative effects of the phosphodiesterase type 5 (PDE5) pathway, which regulates cGMP hydrolysis, may be significant in the long-term treatment of pulmonary arterial hypertension (PAH) with PDE5 inhibitors.
Sildenafil (Revatio)
Sildenafil promotes selective smooth-muscle relaxation in lung vasculature, possibly by inhibiting PDE5. This results in a subsequent reduction of blood pressure in pulmonary arteries and an increase in cardiac output.
Tadalafil (Adcirca)
Tadalafil is a PDE5 inhibitor indicated for improving exercise capacity in patients with WHO class 1 PAH. It increases cGMP, the final mediator in the nitric oxide pathway.
PAH, Prostacyclin Analogs
Class Summary
Prostacyclin is a strong vasodilator of all vascular beds and a potent endogenous inhibitor of platelet aggregation. Platelet effects result from activation of intracellular adenylate cyclase and from increased cyclic adenosine monophosphate (cAMP) concentrations within platelets. Prostacyclin may decrease thrombogenesis and platelet clumping in the lungs by inhibiting platelet aggregation.
Iloprost (Ventavis)
Iloprost is a synthetic analogue of prostacyclin that dilates systemic and pulmonary arterial vascular beds. It is indicated in patients with New York Heart Association class III or IV symptoms to improve exercise tolerance and symptoms and to delay deterioration.
Diuretics, Loop
Class Summary
Judicious use of diuretics helps reduce systemic congestion and edema. Conversely, excessive hypovolemia may interfere with tissue oxygenation by lowering cardiac output.
Furosemide (Lasix)
Furosemide increases excretion of water by interfering with the chloride-binding cotransport system, thereby, in turn, inhibiting sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule. The dosage must be individualized to the patient. Depending on the response, administer furosemide in increments of 20-40 mg, no sooner than 6-8 hours after the previous dose, until the desired diuresis occurs. When treating infants, titrate with increments of 1 mg/kg until a satisfactory effect is achieved.
Bumetanide (Bumex, Burinex)
Bumetanide increases excretion of water by interfering with the chloride-binding cotransport system; this, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle. Bumetanide does not appear to act in the distal renal tubule.
Anticoagulants, Hematologic
Class Summary
Long-term anticoagulation with warfarin should be considered in selected patients with secondary PAH. These include patients with chronic pulmonary embolism (PE), pulmonary veno-occlusive disease, and atrial fibrillation induced by left- or right-side heart failure who are at high risk for developing venous thromboembolism (eg, those with cor pulmonale or immobility secondary to severe dyspnea).
Warfarin (Coumadin, Jantoven)
Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors. It is used for prophylaxis and treatment of deep venous thrombosis, PE, and thromboembolic disorders.
Tailor the dose to maintain an international normalized ratio (INR) in the range of 2-3. Recurrence of deep venous thrombosis and PE increases dramatically when the INR drops below 2 and decreases when it is kept between 2 and 3. Serious bleeding risk (including hemorrhagic stroke) is approximately constant when the INR is between 2.5 and 4.5 but rises dramatically when it exceeds 5.
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Ventilation perfusion scan showing bilateral large wedge-shaped mismatched perfusion defects and areas of gray indicating decreased perfusion. Right-sided heart catheterization for this patient showed combined precapillary and postcapillary pulmonary hypertension and the following: right atrial pressure 10 mm Hg, right ventricular pressure 82/8 mm Hg, pulmonary artery wedge pressure 22 mm Hg, and pulmonary artery pressure 83/27 mm Hg with a mean of 49 mm Hg. He was referred to an expert center for pulmonary endarterectomy evaluation, where he underwent pulmonary angiography. Findings from the right side showed an occluded upper lobe anterior segment, a proximal web in the upper lobe, and disease in all lower segments. Findings from the left side showed an occluded superior segment of the lower lobe with disease in basal segments, proximal web in lingula, and intact upper lobe vessels. He underwent pulmonary endarterectomy with intraoperative University of California San Diego classification of thrombus as right 1 and left 2. Postoperatively, he has had dramatic improvement in his symptoms and is off all pulmonary arterial hypertension therapy.
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Extensive pulmonary emboli are seen in both lungs, with a dominant, eccentric thrombus related to the left main pulmonary artery. More distal emboli were noted in the subsegmental pulmonary arteries (not shown). This is a 42-year-old woman with a history of multiple pulmonary emboli and protein S deficiency who initially presented with severe dyspnea (New York Heart Association functional class IV) and was initiated on multiple pulmonary arterial hypertension medications, including intravenous prostacyclin. She underwent pulmonary endarterectomy, and the images of the clots that were removed intraoperatively are shown in another image.
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The heart is enlarged, with right atrial and ventricular enlargement in addition to reflux of contrast into the intrahepatic inferior vena cava. The main pulmonary artery itself measures approximately 3 cm. There was mosaic attenuation of both lungs, most pronounced related to the right-middle and upper lobes (not shown).
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Mosaic pattern seen on expiratory images of a chest CT scan in a patient with chronic thromboembolic pulmonary hypertension. The same patient’s ventilation/perfusion scan is also shown. The areas of hypovascularity in blood vessels with clots cause areas of relative hypoperfusion, which appear darker than normal lung and give rise to the differential opacities seen on this image.
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Intraoperative clot during pulmonary endarterectomy. This is a 42-year-old woman with a history of multiple pulmonary emboli and protein S deficiency who initially presented with severe dyspnea (New York Heart Association functional class IV) and was initiated on multiple pulmonary arterial hypertension medications, including intravenous prostacyclin. Preoperative right-sided heart catheterization showed right atrial pressure of 16 mm Hg, pulmonary artery pressure of 124/29 mm Hg with a mean of 67 mm Hg, cardiac output of 4.53, and pulmonary vascular resistance of 12 Wood units. Immediate postoperative right-sided heart catheterization showed right atrial pressure of 9 mm Hg, pulmonary artery pressure of 40/15 mm Hg with a mean of 25 mm Hg, cardiac output of 5.15, and pulmonary vascular resistance of 2.9 Wood units. She came off all her pulmonary arterial hypertension therapy immediately postoperatively and continues to do well.
