Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease characterized by recurrent, unresolved pulmonary artery emboli and/or progressive pulmonary artery thrombosis and scar formation, as well as pulmonary artery obstruction due to pulmonary artery remodeling.CTEPH is a severe, progressive and fatal disease.
The pathogenesis of CTEPH is not well understood. Death is significantly higher in untreated CTEPH disease, with a median 2-3 year survival rate as low as 10-20%. Pulmonary artery thromboendarterectomy may lead to a cure for patients with CTEPH. Targeted treatment of inoperable patients with pulmonary arterial hypertension (PAH) has shown improvements in exercise tolerance, hemodynamics, and NYHA cardiac function class, but numerous prospective studies are needed to confirm its effectiveness and safety. In this article, we present the epidemiology, imaging, diagnosis and treatment of CTEPH.
1. Epidemiology
Due to the insidiousness and complexity of the onset and clinical manifestations of PTE, as well as the imperfection of the previous examination techniques, this disease was once regarded as “rare” by the medical profession in China, but this view has been completely changed in recent years. The prevalence of CTEPH in the United States is 63 per million (<65 years old) and 1007 per million (>65 years old), and there are studies in China that show no significant differences in the incidence of CTEPH between men and women.
The risk factors for PTE are surgery and trauma as the main cause, followed by malignancy, and connective tissue as the third major risk factor, and age is also an independent risk factor, and the incidence increases with age. In addition to this, genetically related genetic susceptibility and a tendency for the onset of the disease to cluster in families. Even with the active application of more complete technical tools, a significant proportion of cases are still clinically difficult to identify risk factors.
Other risk factors for CTEPH have been found to include recurrent or unprovoked pulmonary embolism, massive pulmonary embolism, pulmonary embolism in middle-aged and young adults, chronic inflammatory diseases, cancer, thyroid replacement therapy, positive anticardiolipin antibodies, positive lupus anticoagulant, elevated factor VIII, splenectomy, and genetic factors.
2.Clinical manifestations
Patients with a clear history of PE may experience an asymptomatic period of several months to years after the first PE and then gradually develop pulmonary hypertension. However, 63% of patients do not have a history of acute pulmonary embolism and have an insidious onset, and once detected, they have pulmonary hypertension, which is easily missed and misdiagnosed. In the late stage of the disease, there may be manifestations of right heart failure, such as hepatomegaly, ascites and swelling of lower limbs, etc. In severe cases, there is limitation of activity, exertional vertigo or syncope, which seriously affect the health of patients.
3.Diagnosis and differential diagnosis
CTEPH is usually asymptomatic in its early stages, which can easily lead to missed diagnosis. A high degree of suspicion must be maintained for patients with exertional dyspnea with no obvious etiology or history of venous thromboembolism. CTEPH should be suspected in any patient presenting with unexplained pulmonary hypertension and should be highly suspected when the patient has a history of VTE. The ECG shows right ventricular hypertrophy and hypertonicity. An echocardiogram provides the initial objective evidence of PH.
Chest X-rays may be normal or show hilar enlargement and peripheral vascular thinning. A V/Q lung scan is recommended as a primary screen to rule out CTEPH, with completely normal perfusion ruling out CTEPH and abnormal V/Q perfusion requiring further workup. Cardiac pulmonary artery nuclear imaging (MRA) may suggest right heart enlargement and pulmonary vascular thickening and stenosis, etc. CT pulmonary angiography (CTPA) is the most important tool for the diagnosis of CTEPH, with diagnostic images including pouch, mesh or banding with or without post-stenotic enlargement of the pulmonary arteries, intimal disturbances, sudden narrowing or complete obstruction. Invasive tests such as right heart catheterization and traditional gold standard pulmonary angiography are often used not only to confirm the diagnosis of CTEPH, but also as an important tool to determine the treatment strategy for CTEPH.
The differential diagnosis of CTEPH is mainly to distinguish primary pulmonary hypertension from other causes of secondary PAH, such as connective tissue disease, pulmonary vasculitis, and aortitis. It should also be distinguished from other cardiopulmonary diseases that cause dyspnea, such as coronary heart disease, rheumatic heart disease, congenital heart disease, bronchial asthma, chronic obstructive pulmonary disease, etc.
4.Treatment
The treatment of CTEPH is still controversial, and the treatment plan for CTEPH patients depends on the evaluation of a multidisciplinary team, including respiratory, cardiac, cardiothoracic, extracorporeal circulation and radiologists. Surgical treatment is currently the only way to achieve a cure.
4.1 Surgical treatment
PEA significantly improves the prognosis of patients with CTEPH, with an average operative mortality rate of 10.9%, including an in-hospital mortality rate of <5% in experienced surgical centers, and PEA is more effective than lung transplantation or long-term drug therapy, with immediate improvement and stabilization of right ventricular hemodynamics for more than 2 years after surgery. Imaging is the basis for the decision to operate on a patient, but currently surgery is guided primarily by surgical experience. pea offers the opportunity for a cure.
The American College of Chest Physicians recommends the following indications for PEA surgery.
1, NYHA functional class III or IV;
2, Preoperative PVR > 300 dyn/s/cm-5; 3, mPAP > 40 mmHg;
4, Imaging results show that the thrombus is located in the surgically accessible pulmonary artery trunk, lobar artery, segmental artery or subsegmental artery;
5, no serious concomitant disease;
6. Predicted postoperative reduction in pulmonary artery resistance may exceed 50%;
7, no secondary arterial disease;
8, Experienced surgical center;
9, patient consent.
Contraindications are.
1, distal pulmonary artery thromboembolism;
2. severe underlying lung disease (e.g., severe obstructive pulmonary disease or severe left ventricular dysfunction) and risk factors (e.g., microvascular disease).
Lung transplantation can improve the quality of life and survival of patients who are not candidates for surgery or who have recurrent pulmonary hypertension and WHO cardiac class III or IV after PEA, despite receiving optimal drug therapy. Lifelong immunosuppressive therapy is required after lung transplantation. Types of surgery include unilateral lung transplantation, bilateral lung transplantation, and heart-lung transplantation.
4.2 Drug therapy
Anticoagulation therapy Most patients with CTEPH require anticoagulation therapy, such as warfarin, which is based on the principle of preventing re-embolism or extension of in situ thrombosis, and in patients with unprovoked and primary PAH, anticoagulation reduces the risk of recurrent venous thrombosis.
Pulmonary vasodilators may improve survival in inoperable patients. In the presence of symptoms of right heart failure, diuretics or vasoactive substances such as calcium channel antagonists, adrenergic receptor blockers, and adenosine are used to relieve PAH.
New drug therapy endothelin receptor antagonists such as sitaxsentan inhibit pulmonary hypertension by selectively inhibiting endothelin receptor A. Bosentan and anritsuentan, phosphodiesterase inhibitor tadalafil can enhance the antihypertensive effect of nitrates, and soluble guanylate cyclase stimulator riociguat is effective in improving pulmonary hemodynamics, right heart hypertrophy, and can remodel pulmonary hypertension of the pulmonary vascular structure. Among them, bosentan can effectively improve the hemodynamics and exercise capacity of CTEPH patients.