Chronic thromboembolic pulmonary hypertension

Clinical symptoms and signs are often non-specific or absent in early CTEPH, with signs of right heart failure only in advanced disease. The main symptom of CTEPH is exertional breathlessness (shortness of breath during exertion, such as exercise), which is nonspecific and may often be attributed to other, more common diseases by physicians. When present, the clinical symptoms of CTEPH may resemble those of acute PE, or of idiopathic pulmonary arterial hypertension (iPAH). Leg oedema (swelling) and haemoptysis (blood in mucus) occur more often in CTEPH, while syncope (fainting) is more common in iPAH. == Pathogenesis ==

People with CTEPH lack traditional thrombosis risk factors. Current understanding is that CTEPH is a result of “inflammatory thrombosis”: When pro-thrombotic (blood-clot forming) conditions combine with chronic inflammation and infection, non-resolution of thrombus may ensue. Risk factors for CTEPH include splenectomy, inflammatory bowel disease, chronic thyroid hormone replacement, blood types other than 0, malignancy, infected ventriculo-atrial shunt, and permanent intravenous leads. == Diagnosis ==

Early diagnosis remains a challenge in CTEPH, with a median time of 14 months between symptom onset and diagnosis in expert centres. CTPA alone cannot exclude the disease, but may help identify pulmonary artery distension resulting in left main coronary artery compression, pulmonary parenchymal lesions (e.g. as complications from previous pulmonary infarctions), and bleeding from bronchial collateral arteries. == Treatment ==

Decision-making for patients with CTEPH can be complex and needs to be managed by CTEPH teams in expert centres. CTEPH teams comprise cardiologists and pulmonologists with specialist PH training, radiologists, experienced PEA surgeons with a significant caseload of CTEPH patients per year, and physicians with percutaneous interventional expertise. Currently, three recognised targeted treatment options are available, including the standard treatment of pulmonary endarterectomy (PEA). Balloon pulmonary angioplasty (BPA) and pulmonary vasodilator drug treatment may be considered for those who are not suitable for surgery. Specialist imaging using either magnetic resonance or invasive PA is necessary to determine risks and benefits of interventional treatment with PEA or BPA. Other drug trials are ongoing in patients with inoperable CTEPH, with macitentan recently proving efficacy and safety in MERIT Pulmonary endarterectomy in a patient with chronic thromboembolic pulmonary hypertension. Pulmonary endarterectomy (PEA) is the gold standard treatment for suitable CTEPH patients. Operability of patients with CTEPH is determined by multiple factors, among which the surgical accessibility of thrombi and the patient-determined risk-benefit ratio are most important. There is no haemodynamic (e.g., considering pulmonary pressure) or age threshold that should exclude patients from surgery, and concomitant cardiac procedures can be included if necessary. About 60% of patients are classified as operable across Europe and Canada. which is not complicated by cognitive dysfunction. The majority of patients experience substantial relief from symptoms and improvement in haemodynamics after PEA. In Europe, in-hospital mortality during PEA is currently 4.7% or lower in high volume single centres. The definition of post-PEA PH is still not clear, but some data suggest that 500–590 dynes·s·cm−5 may represent a pulmonary vascular resistance (PVR) threshold for poor long-term outcome. Recent data from National UK PEA cohort suggests residual PH post PEA only impacts on longer term survival when mPAP is >38 mmHg or PVR >425 dynes·s·cm−5. Bridging therapy with PAH-targeted drugs, complications, and additional procedures during PEA, and residual PH after PEA are associated with worse outcomes. Immediate postoperative PVR is a long-term predictor of prognosis. and initial reports have confirmed the safety and efficacy of the technique, based on data showing haemodynamic improvement and recovery of right ventricular function. Research is ongoing. == Prognosis ==

Historically, the prognosis for patients with untreated CTEPH was poor, with a 5-year survival of 40 mmHg at presentation. More contemporary data from the European CTEPH registry have demonstrated a 70% 3-year survival in patients with CTEPH who do not undergo the surgical procedure of pulmonary endarterectomy (PEA). Recent data from an international CTEPH registry demonstrate that mortality in CTEPH is associated with New York Heart Association (NYHA) functional class IV, increased right atrial pressure, and a history of cancer. Furthermore, comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease (COPD) are risk factors for mortality. == Epidemiology ==

CTEPH is an orphan disease with an estimated incidence of 5 cases per million, but CTEPH is likely under-diagnosed as symptoms are non-specific. Although a cumulative incidence of CTEPH between 0.1% and 9.1% within the first 2 years after a symptomatic PE has been reported, it is currently unclear whether acute symptomatic PE begets CTEPH. Routine screening for CTEPH after PE is not recommended because a significant number of CTEPH cases develops in the absence of previous acute symptomatic PE. == References ==