Chronic Pulmonary Thromboembolism
Among all patients with pulmonary emboli, between 0.8 to 3.8% will develop chronic thromboembolic pulmonary hypertension (CTEPH) after 2 years. This disease is defined as a mean pulmonary artery pressure (PA) above 25 mm Hg at 6 months after a patient has a pulmonary embolism. Among patients with a clinically recognized pulmonary embolism, only about 1% will develop CTEPH. This presents a dilemma, as most of the patients diagnosed with chronic thromboembolism never had preceding acute symptoms from a pulmonary embolus. Therefore, the true incidence of this disease is not fully understood.
About 500,000 patients survive symptomatic pulmonary embolus annually. With anticoagulation, the vast majority of these patients will lyse the clot over the following few weeks. Yet a small percentage of these patients will have persistence of the clot. For this small cohort of patients, the clot becomes adherent to the vessel wall. This tissue is progressively converted into connective tissue, and bands and webs begin to form as the pulmonary arteries recanalize. Acute clots, which are mostly red cells and platelets in a fibrin mesh, turn into yellow, chronic adherent clots made of collagen, elastin, inflammatory cells, and even occasionally calcifications.
The eventual development of pulmonary hypertension in these patients is complex and involves multiple mechanisms. (Figure 1) Distally in affected arteries, small vessels develop hypertrophy and intimal proliferation, microvascular thrombosis, and plexiform lesions. Other arteries develop complete obstruction. As time progresses, PA pressure rises and flow decreases as a result of macrovascular obstruction, small vessel arteriopathy, and vasoconstriction of the pulmonary arteries. This results in a rise in right ventricular pressures eventually leading to right heart failure.
It is not clear why certain patients develop CTEPH. The inability to lyse these pulmonary emboli suggests that perhaps a hypercoagulable disorder puts these patients at risk. Lupus anticoagulant can be detected in about 10% of patients with chronic thromboembolic disease. Studies have suggested that patients with CTEPH may have elevated levels of factor VIII, fibrin that resists lysis, and lower plasma thrombomodulin levels. Despite these correlations, the vast majority of these cases occur spontaneously, and no defined hypercoaguable state can be identified. The natural history of CTEPH portends a steady decline for most patients. One study found a survival of 30% just 5 years after diagnosis.
Patients with CTEPH usually present with exercise intolerance, fatigue, and dyspnea. Other symptoms include syncope, hemoptysis, chest pain, light-headedness, or peripheral edema. The presentation can also include vague symptoms such as early satiety or epigastric or right upper quadrant fullness. Signs include a large A-wave jugular pulse, which may transition to a large V wave as right ventricular failure ensues. There may be a palpable right ventricular heave near the lower left sternal border. A previously closed (or unrecognized) patent foramen ovale may reopen, and patients with Eisenmenger syndrome may appear cyanotic be hypoxic. On auscultation, patients might have a narrowly split S2 sound along with an accentuated P2 heart sound. A PA ejection click can be present. If the right heart is failing, a right atrial gallop can be found. In these patients, a high pitched murmur over the tricuspid valve can often be heard in addition to a pulmonic regurgitation murmer.
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