Background
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH) and right heart failure. CTEPH is associated with considerable morbidity and mortalities. Even if more recent papers suggest that the prevalence of CTEPH is up to 3.8% in survivors of acute pulmonary embolism, most experts believe that the true incidence of CTEPH after acute pulmonary embolism is 0.5–2%. CTEPH can be found in patients without any previous clinical episode of acute pulmonary embolism or deep venous thrombosis. No specific genetic mutations have been found in CTEPH.
Case presentation
42 year-old female is being treated due to the thromboembolic pulmonary hypertension in Hospital of Lithuanian University of Health Sciences. She was placed on the urgent waiting list for heart-lung transplant in 2010. The patient was was completely healthy (two healthy children, former smoker) untill May 2002 when dyspnea on exertion, fatique, dizziness, syncope episodes and leg swelling appeared. Before the symptoms started (during the pregnancy in 2002) the patient developed left calf thrombophlebitis. Family physician was giving treatment with sc LMMH but the dose was not adequate. No previous symptoms or history of VTE (including family). No confirmed risk factors for inherited thrombophilias. Three years later she was admitted to the hospital due to the severe dyspnea. Physical examination revealed normal breath and heart sounds. Respiratory alkalosis with slight hypoxemia and hypocapnia were presented in arterial blood gas test: pH – 7.47, PaO2 – 83 mmHg, PaCO2- 30 mmHg. No signs of DVT during echoscopy. Chest CT scan revealed multiple emboli were found in the segmental pulmonary arteries of right superior, middle and both left lung lobes. Echocardiography showed mobile thrombus in right ventricle 2.7×1.7 cm bound to papillary muscles, increased tricuspid regurgitation velocity – 3.8 m/s and normal ejection fraction (EF – 50%). The patient underwent successful thrombectomy and tricuspid valve plastic repair in 30 Dec 2005 with subsequent treatment with ivheparin and warfarin. Two weeks after echocardiography showed no masses in right ventricle, tricuspid regurgitation velocity 3.3 m/s, two small nodules-thrombi (12×10 and 12×9 mm) on anterior and posterior tricuspid valves. Thrombolysis with alteplase was performed, subsequent treatment with IV heparin and warfarin was given. The patient was discharged from the hospital in good condition one month later. The patient was hospitalised due to the progressive dyspnea on exertion and left leg swelling in 23 03 2009. There was no adequate anticoagulation during all these years. Physical examination revealed normal breath and heart sounds, left leg edema, normal saturation. She was on FC III. Slightly elevated creatinin – 100 mkmol/L and NT-pro-BNP- 4800 pg/ml were presented. Chest CT showed small emboli in the lower right lobe segmental artery, enlarged right ventricle and pulmonary artery. Deep leg vein echoscopy revealed old organised thrombi in the left femoral and popliteal vein. Right heart catheterization revealed increased PA pressure 89/21 mmHg and increased PVR – 928 dynes*sec*cm-5, possitivevasoreactivity test with adenosine. Warfarin 4.5 mg daily (INR 2,5), torasemide 5 mg twice per week and diltiazem was started (60 mg TID, trying to achieve the dose of 360 mg BID). Three months after dyspnea increased, FC became IV, she was unable to perform 6 min test. Echocardiography showed increased tricuspid regurgitation velocity 4.1 m/s, dilated right ventricle. decreased EF – 45%. Treatment with bosentan was started 62.5 mg BID, after one month dose increased to 125mg BID. Despite of treatment condition remained severe – FC III-IV. Bosentan was continued. In April 2010 the patient was placed on the waiting list for heart and lung transplantation. Since May 2010 the patient is being treated with long-term oxygen therapy due to the chronic respiratory failure. Since Jan 2011 treatment with sildenafil 20 mg TID, was added. Patient’s condition significantly improved: dyspnea decreased, 6 min walk test 20->118->245 m. FC-III, as well as hypoxemia., but remains increased tricuspid regurgitation velocity 4.7 m/s, dilation o right heart chambers and decreased EF-40%.
Current guidelines
Symptoms – dyspnea on exertion, fatique, dizziness, syncope episodes and leg swelling, physical examination – swollen left calf, later – desaturation. Disease history: left calf thrombophlebitis, no adequate teratment; later pulmonary embolism – no adequate treatment.CT pulmonary angiograpgy (Enlarged pulmonary arteries, multiple emboli were found in the segmental pulmonary arteries bilateraly.). Perform RHC (right heart catheterization) – PA pressure 55 mmHg (89/21mmHg), after adenosine – mean PAP 40 mmHg. Treatment: – life long oral anticuagulants (INR 2-3), if chronic respiratory failure – oxygen at least 15h/day. Surgical pulmonary endarterectomy is the recommended treatment for patients with CTEPH. PAH-specific drug therapy may be indicated in selected CTEPH patients such as patients not
candidates for surgery or patients with residual PH after pulmonary endarterectomy. For the present time, no medical therapy has been approved in Europe or the USA for CTEPH. Bilateral lung transplantation is an option for advanced cases that are not suited for PEA. Start with calcium channel blockers if vasoreactivity test possitive (daily doses of these drugs that have shown efficacy in IPAH are relatively high, ex. 240–720 mg for diltiazem). If this treatment not well tolerated or condition deteriorating – specific PH treatment (Prostanoids, ERAs, and phosphodiesterase type-5 inhibitors may exert haemodynamic and clinical benefits in patients with CTEPH )
References
1. Guidelines for diagnosis and treatment of pulmonary hypertension. European heart journal 2009; 30: 2493-2537
2. Humbert M., Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology, EurRespir Rev 2010; 19: 115, 59–63
3. Lung I.M., Managing chronic thromboembolic pulmonary hypertension: pharmacological treatment options, EurRespir Rev 2009; 18: 111, 24–28
4. Becattini C, Agnelli G, Pesavento R, et al. Incidence of chronic thromboembolic pulmonary hypertension after a first episode of pulmonary embolism. Chest2006; 130: 172–175.
5. Skoro-Sajer N, Hack N, Sadushi R, et al. Abstract 2305: Pulmonary vascular reactivity and prognosis in patients with chronic thromboembolic pulmonary hypertension.
Circulation2007; 116: II503–II504
6. Mellemkjaer S, Ilkjaer LB, Klaaborg KE, et al. Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Ten yearsexperience in Denmark. Scand
Cardiovasc J 2006; 40: 49–53
Expert’s comments:(Written authorization required from each expert)
1. Grzegorz Kopeć MD, PhD
Identification of patients with chronic thromboembolic pulmonary hypertension who are unlikely to benefit hemodynamically form thromboendartherectomy is a particular chalange. This results from the fact that the increased pulmonary vascular resistance arises not only from the surgically accessible thromboembolic obstructions but also from small vessel arteriopathy. Importantly, long term survival after pulmonary thrombendartherectomy depends on the lowering of pulmonary artery pressure and pulmonary vascular resistance after pulmonary endartherectomy. In patients in whom high pulmonary vascular resistance and pulmonary artery pressure persist after the operation the perioperative and long term prognosis is poor. These patients however can currently be offered a treatment with pulmonary arterial hypertension specific drugs such as phosphodiesterase 5 inhibitors, endothelin receptor antagonists, prostacyclin analogues. Clinical studies showed that NO test can predict a long term response to calcium channel blockers only in patients with idiopathic pulmonary arterial hypertension. Therefore calcium channel blockers are not recommended in chronic thromboembolic pulmonary hypertension.
Authors:
Skaidrius MiliauskasMD, PhD1, Deimante Hoppenot MD, PhD1
Experts:
Grzegorz Kopeć MD, PhD2
1Department of Pulmonology and Immunology Hospital of Lithuanian University of Health Sciences Kaunas Clinics
2Department of Cardiac and Vascular Diseases, Jagiellonian University College of Medicine, John Paul II Hospital, Krakow, Poland
