Clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension
- Peter F Fedullo, MD
Peter F Fedullo, MD
- Clinical Professor of Medicine
- University of California San Diego Medical Center
Improvement following acute pulmonary embolism is usually sufficient to restore normal pulmonary hemodynamics, gas exchange, and exercise tolerance [1-3]. However, a minority of patients develop chronic thromboembolic pulmonary hypertension (CTEPH) following an acute pulmonary embolism .
The incidence, possible etiologies, presentation, clinical features, diagnosis, and differential diagnosis of CTEPH are reviewed here. Treatment of CTEPH is discussed separately. (See "Overview of the treatment of chronic thromboembolic pulmonary hypertension" and "Chronic thromboembolic pulmonary hypertension: Surgical treatment" and "Chronic thromboembolic pulmonary hypertension: Medical treatment".)
The true incidence of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown but estimated to be between 1 and 5 percent among survivors of acute pulmonary embolism (PE) [5-8]. One retrospective series reported that among 899 patients with PE, approximately 1 percent developed CTEPH . In contrast, two prospective series reported that between 3.8 and 4.8 percent of patients developed CTEPH in a two-year period following the diagnosis of PE [6,7]. The development of CTEPH after two years is rare.
It is thought that CTEPH may represent the final manifestation of unresolved pulmonary embolism. With improved understanding of CTEPH, a population of patients has been identified with post-embolic exercise intolerance in the absence of resting pulmonary hypertension. This condition has variably been referred to as "chronic thromboembolic disease (CTED)" or "post-PE syndrome." Exercise intolerance may be due to increased dead space ventilation related to pulmonary vascular obstruction and/or limitation of maximal cardiac output with exercise [9,10]. A lower threshold to look for CTEPH in this population is appropriate.
It is unknown why some patients with acute pulmonary embolism develop chronic thromboembolic pulmonary hypertension (CTEPH) and others do not .
- Dartevelle P, Fadel E, Mussot S, et al. Chronic thromboembolic pulmonary hypertension. Eur Respir J 2004; 23:637.
- Nijkeuter M, Hovens MM, Davidson BL, Huisman MV. Resolution of thromboemboli in patients with acute pulmonary embolism: a systematic review. Chest 2006; 129:192.
- Kearon C. Natural history of venous thromboembolism. Circulation 2003; 107:I22.
- Benotti JR, Ockene IS, Alpert JS, Dalen JE. The clinical profile of unresolved pulmonary embolism. Chest 1983; 84:669.
- Klok FA, van Kralingen KW, van Dijk AP, et al. Prospective cardiopulmonary screening program to detect chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism. Haematologica 2010; 95:970.
- Guérin L, Couturaud F, Parent F, et al. Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Prevalence of CTEPH after pulmonary embolism. Thromb Haemost 2014; 112:598.
- Pengo V, Lensing AW, Prins MH, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004; 350:2257.
- Klok FA, Dzikowska-Diduch O, Kostrubiec M, et al. Derivation of a clinical prediction score for chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. J Thromb Haemost 2016; 14:121.
- Klok FA, van der Hulle T, den Exter PL, et al. The post-PE syndrome: a new concept for chronic complications of pulmonary embolism. Blood Rev 2014; 28:221.
- Taboada D, Pepke-Zaba J, Jenkins DP, et al. Outcome of pulmonary endarterectomy in symptomatic chronic thromboembolic disease. Eur Respir J 2014; 44:1635.
- Lang IM, Pesavento R, Bonderman D, Yuan JX. Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding. Eur Respir J 2013; 41:462.
- Bonderman D, Turecek PL, Jakowitsch J, et al. High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension. Thromb Haemost 2003; 90:372.
- Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343:457.
- Auger WR, Permpikul P, Moser KM. Lupus anticoagulant, heparin use, and thrombocytopenia in patients with chronic thromboembolic pulmonary hypertension: a preliminary report. Am J Med 1995; 99:392.
- Wolf M, Boyer-Neumann C, Parent F, et al. Thrombotic risk factors in pulmonary hypertension. Eur Respir J 2000; 15:395.
- Sompradeekul, S, Fedullo, PF, Le, DT. Congenital and acquired thrombophilias in patients with chronic thromboembolic pulmonary hypertension. Am J Resp Crit Care Med 1999; 159:A358.
- Morris TA, Marsh JJ, Chiles PG, et al. Fibrin derived from patients with chronic thromboembolic pulmonary hypertension is resistant to lysis. Am J Respir Crit Care Med 2006; 173:1270.
- Egermayer P, Peacock AJ. Is pulmonary embolism a common cause of chronic pulmonary hypertension? Limitations of the embolic hypothesis. Eur Respir J 2000; 15:440.
- Fedullo PF, Rubin LJ, Kerr KM, et al. The natural history of acute and chronic thromboembolic disease: the search for the missing link. Eur Respir J 2000; 15:435.
- Kim NH, Delcroix M, Jenkins DP, et al. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol 2013; 62:D92.
- Moser KM, Auger WR, Fedullo PF. Chronic major-vessel thromboembolic pulmonary hypertension. Circulation 1990; 81:1735.
- Condliffe R, Kiely DG, Gibbs JS, et al. Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension. Eur Respir J 2009; 33:332.
- Monreal M, Ruíz J, Olazabal A, et al. Deep venous thrombosis and the risk of pulmonary embolism. A systematic study. Chest 1992; 102:677.
- Pepke-Zaba J, Delcroix M, Lang I, et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation 2011; 124:1973.
- Tapson VF, Platt DM, Xia F, et al. Monitoring for Pulmonary Hypertension Following Pulmonary Embolism: The INFORM Study. Am J Med 2016; 129:978.
- Raisinghani A, Ben-Yehuda O. Echocardiography in chronic thromboembolic pulmonary hypertension. Semin Thorac Cardiovasc Surg 2006; 18:230.
- Morris TA, Auger WR, Ysrael MZ, et al. Parenchymal scarring is associated with restrictive spirometric defects in patients with chronic thromboembolic pulmonary hypertension. Chest 1996; 110:399.
- Wakamatsu K, Inoue H, Aizawa H, et al. Recurrent chest opacities in a patient with thromboembolic pulmonary hypertension. Respiration 1998; 65:492.
- Fishman AJ, Moser KM, Fedullo PF. Perfusion lung scans vs pulmonary angiography in evaluation of suspected primary pulmonary hypertension. Chest 1983; 84:679.
- Tunariu N, Gibbs SJ, Win Z, et al. Ventilation-perfusion scintigraphy is more sensitive than multidetector CTPA in detecting chronic thromboembolic pulmonary disease as a treatable cause of pulmonary hypertension. J Nucl Med 2007; 48:680.
- Ryan KL, Fedullo PF, Davis GB, et al. Perfusion scan findings understate the severity of angiographic and hemodynamic compromise in chronic thromboembolic pulmonary hypertension. Chest 1988; 93:1180.
- Nicod P, Peterson K, Levine M, et al. Pulmonary angiography in severe chronic pulmonary hypertension. Ann Intern Med 1987; 107:565.
- Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 2009; 34:888.
- Pitton MB, Düber C, Mayer E, Thelen M. Hemodynamic effects of nonionic contrast bolus injection and oxygen inhalation during pulmonary angiography in patients with chronic major-vessel thromboembolic pulmonary hypertension. Circulation 1996; 94:2485.
- Shure D, Gregoratos G, Moser KM. Fiberoptic angioscopy: role in the diagnosis of chronic pulmonary arterial obstruction. Ann Intern Med 1985; 103:844.
- Hasegawa I, Boiselle PM, Hatabu H. Bronchial artery dilatation on MDCT scans of patients with acute pulmonary embolism: comparison with chronic or recurrent pulmonary embolism. AJR Am J Roentgenol 2004; 182:67.
- King MA, Ysrael M, Bergin CJ. Chronic thromboembolic pulmonary hypertension: CT findings. AJR Am J Roentgenol 1998; 170:955.
- Bergin CJ, Sirlin CB, Hauschildt JP, et al. Chronic thromboembolism: diagnosis with helical CT and MR imaging with angiographic and surgical correlation. Radiology 1997; 204:695.
- Kreitner KF, Kunz RP, Ley S, et al. Chronic thromboembolic pulmonary hypertension - assessment by magnetic resonance imaging. Eur Radiol 2007; 17:11.
- Rajaram S, Swift AJ, Telfer A, et al. 3D contrast-enhanced lung perfusion MRI is an effective screening tool for chronic thromboembolic pulmonary hypertension: results from the ASPIRE Registry. Thorax 2013; 68:677.
- Task Force for Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC), European Respiratory Society (ERS), International Society of Heart and Lung Transplantation (ISHLT), et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2009; 34:1219.