Skip to main content
Log in

Chronic Thromboembolic Pulmonary Hypertension: the End Result of Pulmonary Embolism

  • Peripheral Vascular Disease (MR Jaff, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when a pulmonary embolism fails to undergo complete thrombolysis leading to vascular occlusion and pulmonary hypertension. Despite the fact that CTEPH is a potential consequence of pulmonary embolism, diagnosis requires a high degree of vigilance as many patients will not have a history of thromboembolic disease. The ventilation perfusion scan is used to evaluate for the possibility of CTEPH although right heart catheterization and pulmonary artery angiogram are needed to confirm the diagnosis. Pulmonary thromboendarterectomy is the first-line treatment for patients who are surgical candidates. Recently, riociguat has been approved for patients with nonsurgical disease or residual pulmonary hypertension despite surgical intervention. This review describes the pathophysiology, risk factors, diagnosis, and management of CTEPH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Condliffe R, Kiely DG, Gibbs JS, et al. Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension. Eur Respir J. 2009;33:332–8.

    Article  CAS  PubMed  Google Scholar 

  2. Pepke-Zaba J, Delcroix M, Lang I, et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation. 2011;124:1973–81.

    Article  PubMed  Google Scholar 

  3. 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;41:462–8.

    Article  PubMed  Google Scholar 

  4. Piazza G, Goldhaber SZ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2011;364:351–60.

    Article  CAS  PubMed  Google Scholar 

  5. Moser KM, Braunwald NS. Successful surgical intervention in severe chronic thromboembolic pulmonary hypertension. Chest. 1973;64:29–35.

    Article  CAS  PubMed  Google Scholar 

  6. Ribeiro A, Lindmarker P, Johnsson H, Juhlin-Dannfelt A, Jorfeldt L. Pulmonary embolism: one-year follow-up with echocardiography doppler and five-year survival analysis. Circulation. 1999;99:1325–30.

    Article  CAS  PubMed  Google Scholar 

  7. Nijkeuter M, Hovens MMC, Davidson BL, Huisman MV. Resolution of thromboemboli in patients with acute pulmonary embolism. Chest. 2006;129:192–7.

    Article  PubMed  Google Scholar 

  8. Pengo V, Lensing AW, Prins MH, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004;350:2257–64.

    Article  CAS  PubMed  Google Scholar 

  9. Becattini C, Agnelli G, Pesavento R, et al. Incidence of chronic thromboembolic pulmonary hypertension after a first episode of pulmonary embolism. Chest. 2006;130:172–5.

    Article  PubMed  Google Scholar 

  10. Guerin L, Couturaud F, Parent F, et al. Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Thromb Haemost. 2014;112:598–605.

    Article  CAS  PubMed  Google Scholar 

  11. Dentali F, Donadini M, Gianni M, et al. Incidence of chronic pulmonary hypertension in patients with previous pulmonary embolism. Throm Res. 2009;124:256–8.

    Article  CAS  Google Scholar 

  12. Wolf M, Boyer-Neumann C, Parent F, et al. Thrombotic risk factors in pulmonary hypertension. Eur Respir J. 2000;15:395–9.

    Article  CAS  PubMed  Google Scholar 

  13. 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;99:392–6.

    Article  CAS  PubMed  Google Scholar 

  14. Bonderman D, Turecek PL, Jakowitsch J, et al. High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension. Thromb Haemost. 2003;90:372–6.

    CAS  PubMed  Google Scholar 

  15. Morris TA, Marsh JJ, Chiles PG, Auger WR, Fedullo PF, Woods VL. Fibrin derived from patients with chronic thromboembolic pulmonary hypertension is resistant to lysis. Am J Respir Crit Care Med. 2006;173:1270–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Morris TA, Marsh JJ, Chiles PG, et al. High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension. Blood. 2009;114:1929–36.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Suntharalingam J, Goldsmith K, van Marion V, et al. Fibrinogen Aalpha Thr312Ala polymorphism is associated with chronic thromboembolic pulmonary hypertension. Eur Respir J. 2008;31:736–41.

    Article  CAS  PubMed  Google Scholar 

  18. Bonderman D, Wilkens H, Wakounig S, et al. Risk factors for chronic thromboembolic pulmonary hypertension. Eur Respir J. 2009;33:325–31.

    Article  CAS  PubMed  Google Scholar 

  19. Bonderman D, Jakowitsch J, Adlbrecht C, et al. Medical conditions increasing the risk of chronic thromboembolic pulmonary hypertension. Thromb Haemost. 2005;93:512–6.

    CAS  PubMed  Google Scholar 

  20. Kominami S, Tanabe N, Ota M, et al. HLA-DPB1 and NFKBIL1 may confer the susceptibility to chronic thromboembolic pulmonary hypertension in the absence of deep vein thrombosis. J Hum Genet. 2009;54:108–14.

    Article  CAS  PubMed  Google Scholar 

  21. Moser KM, Auger WR, Fedullo PF. Chronic major-vessel thromboembolic pulmonary hypertension. Circulation. 1990;81:1735–43.

    Article  CAS  PubMed  Google Scholar 

  22. ZuWallack RL, Liss JP, Lahiri B. Acquired continuous murmur associated with acute pulmonary thromboembolism. Chest. 1976;70:557–9.

    Article  CAS  PubMed  Google Scholar 

  23. Galiè N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009;34:1219–63.

    Article  PubMed  Google Scholar 

  24. McIntyre KM, Sasahara AA. The hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. Am J Cardiol. 1971;28:288–94.

    Article  CAS  PubMed  Google Scholar 

  25. 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: Off Publ Soc Nucl Med. 2007;48:680–4.

    Article  Google Scholar 

  26. Reichelt A, Hoeper MM, Galanski M, Keberle M. Chronic thromboembolic pulmonary hypertension: evaluation with 64-detector row CT versus digital substraction angiography. Eur J Radiol. 2009;71:49–54.

    Article  PubMed  Google Scholar 

  27. Sugiura T, Tanabe N, Matsuura Y, et al. Role of 320-slice CT imaging in the diagnostic workup of patients with chronic thromboembolic pulmonary hypertension. Chest. 2013;143:1070–7.

    Article  PubMed  Google Scholar 

  28. King MA, Ysrael M, Bergin CJ. Chronic thromboembolic pulmonary hypertension: CT findings. AJR Am J Roentgenol. 1998;170:955–60.

    Article  CAS  PubMed  Google Scholar 

  29. Kim NH, Delcroix M, Jenkins DP, et al. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol. 2013;62:D92–9. This review highlights expert guidelines on the management of pulmonary hypertension.

    Article  PubMed  Google Scholar 

  30. 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;182:67–72.

    Article  PubMed  Google Scholar 

  31. Auger WR, Fedullo PF, Moser KM, Buchbinder M, Peterson KL. Chronic major-vessel thromboembolic pulmonary artery obstruction: appearance at angiography. Radiology. 1992;182:393–8.

    Article  CAS  PubMed  Google Scholar 

  32. Coskun U, Sinan UY, Calpar I, et al. Pulmonary artery sarcoma masquerading as chronic pulmonary thromboembolism. Texas Heart Inst J Texas Heart Inst St Luke’s Episcopal Hosp Texas Children’s Hosp. 2014;41:518–22.

    Google Scholar 

  33. Kerr KM, Auger WR, Fedullo PF, Channick RH, Yi ES, Moser KM. Large vessel pulmonary arteritis mimicking chronic thromboembolic disease. Am J Respir Crit Care Med. 1995;152:367–73.

    Article  CAS  PubMed  Google Scholar 

  34. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e419S–94.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Mayer E, Jenkins D, Lindner J, et al. Surgical management and outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. J Thorac Cardiovasc Surg. 2011;141:702–10.

    Article  PubMed  Google Scholar 

  36. Condliffe R, Kiely DG, Gibbs JS, et al. Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med. 2008;177:1122–7.

    Article  PubMed  Google Scholar 

  37. Jamieson SW, Kapelanski DP, Sakakibara N, et al. Pulmonary endarterectomy: experience and lessons learned in 1,500 cases. Ann Thorac Surg. 2003;76:1457–62. discussion 62-4.

    Article  PubMed  Google Scholar 

  38. Jamieson SW, Kapelanski DP. Pulmonary endarterectomy. Curr Probl Surg. 2000;37:165–252.

    Article  CAS  PubMed  Google Scholar 

  39. Thistlethwaite PA, Auger WR, Madani MM, Pradhan S, Kapelanski DP, Jamieson SW. Pulmonary thromboendarterectomy combined with other cardiac operations: indications, surgical approach, and outcome. Ann Thorac Surg. 2001;72:13–7. discussion 7-9.

    Article  CAS  PubMed  Google Scholar 

  40. Jamieson SW, Nomura K. Indications for and the results of pulmonary thromboendarterectomy for thromboembolic pulmonary hypertension. Semin Vasc Surg. 2000;13:236–44.

    CAS  PubMed  Google Scholar 

  41. Moser KM, Metersky ML, Auger WR, Fedullo PF. Resolution of vascular steal after pulmonary thromboendarterectomy. Chest. 1993;104:1441–4.

    Article  CAS  PubMed  Google Scholar 

  42. Levinson RM, Shure D, Moser KM. Reperfusion pulmonary edema after pulmonary artery thromboendarterectomy. Am Rev Respir Dis. 1986;134:1241–5.

    CAS  PubMed  Google Scholar 

  43. Madani MM, Auger WR, Pretorius V, et al. Pulmonary endarterectomy: recent changes in a single institution’s experience of more than 2,700 patients. Ann Thorac Surg. 2012;94:97–103. This is the largest case series published of the use of pulmonary endarterectomy for the treatment of CTEPH.

    Article  PubMed  Google Scholar 

  44. Ghofrani HA, D’Armini AM, Grimminger F, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013;369:319–29. This study describes the efficacy of riociguat in the treatment of chronic thromboembolic pulmonary hypertension.

    Article  CAS  PubMed  Google Scholar 

  45. Jaïs X, D’Armini AM, Jansa P, et al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol. 2008;52:2127–34.

    Article  PubMed  Google Scholar 

  46. Hoeper MM, Kramm T, Wilkens H, et al. Bosentan therapy for inoperable chronic thromboembolic pulmonary hypertension. Chest. 2005;128:2363–7.

    Article  CAS  PubMed  Google Scholar 

  47. Seyfarth HJ, Hammerschmidt S, Pankau H, Winkler J, Wirtz H. Long-term bosentan in chronic thromboembolic pulmonary hypertension. Respiration. 2007;74:287–92.

    Article  CAS  PubMed  Google Scholar 

  48. Hughes RJ, Jais X, Bonderman D, et al. The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study. Eur Respir J. 2006;28:138–43.

    Article  CAS  PubMed  Google Scholar 

  49. Reichenberger F, Voswinckel R, Enke B, et al. Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur Respir J. 2007;30:922–7.

    Article  CAS  PubMed  Google Scholar 

  50. Skoro-Sajer N, Bonderman D, Wiesbauer F, et al. Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension. J Thromb Haemost. 2007;5:483–9.

    Article  CAS  PubMed  Google Scholar 

  51. Bresser P, Fedullo PF, Auger WR, et al. Continuous intravenous epoprostenol for chronic thromboembolic pulmonary hypertension. Eur Respir J. 2004;23:595–600.

    Article  CAS  PubMed  Google Scholar 

  52. Feinstein JA, Goldhaber SZ, Lock JE, Ferndandes SM, Landzberg MJ. Balloon pulmonary angioplasty for treatment of chronic thromboembolic pulmonary hypertension. Circulation. 2001;103:10–3.

    Article  CAS  PubMed  Google Scholar 

  53. Mizoguchi H, Ogawa A, Munemasa M, Mikouchi H, Ito H, Matsubara H. Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv. 2012;5:748–55.

    Article  PubMed  Google Scholar 

  54. D’Armini AM, Cattadori B, Monterosso C, Emmi V, Piovella F, Vigano M. Surgical therapy for chronic thromboembolic pulmonary hypertension: criteria for choosing lung transplant vs trhomboendarterectomy. J Heart Lung Transplant. 2001;20:218.

    Article  PubMed  Google Scholar 

  55. Corsico AG, D’Armini AM, Cerveri I, et al. Long-term outcome after pulmonary endarterectomy. Am J Respir Crit Care Med. 2008;178:419–24.

    Article  PubMed  Google Scholar 

  56. Reesink HJ, Marcus JT, Tulevski II, et al. Reverse right ventricular remodeling after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: utility of magnetic resonance imaging to demonstrate restoration of the right ventricle. J Thorac Cardiovasc Surg. 2007;133:58–64.

    Article  PubMed  Google Scholar 

  57. Iino M, Dymarkowski S, Chaothawee L, Delcroix M, Bogaert J. Time course of reversed cardiac remodeling after pulmonary endarterectomy in patients with chronic pulmonary thromboembolism. Eur Radiol. 2008;18:792–9.

    Article  PubMed  Google Scholar 

  58. Casaclang-Verzosa G, McCully RB, Oh JK, Miller FA, McGregor CG. Effects of pulmonary thromboendarterectomy on right-sided echocardiographic parameters in patients with chronic thromboembolic pulmonary hypertension. Mayo Clin Proc. 2006;81:777–82.

    Article  PubMed  Google Scholar 

  59. Matsuda H, Ogino H, Minatoya K, et al. Long-term recovery of exercise ability after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Ann Thorac Surg. 2006;82:1338–43.

    Article  PubMed  Google Scholar 

  60. Bonderman D, Skoro-Sajer N, Jakowitsch J, et al. Predictors of outcome in chronic thromboembolic pulmonary hypertension. Circulation. 2007;115:2153–8.

    Article  PubMed  Google Scholar 

  61. Mo M, Kapelanski DP, Mitruka SN, et al. Reoperative pulmonary thromboendarterectomy. Ann Thorac Surg. 1999;68:1770–6. discussion 6-7.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Alison S. Witkin declares that she has no conflict of interest. Richard N. Channick has been a consultant and received research grants from Bayer Pharmaceuticals, Actelion Pharmaceuticals, and United Therapeutics Corporation.

Human and Animal Rights and Informed Consent

This article does reference studies with human subjects performed by Richard N. Channick. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alison S. Witkin.

Additional information

This article is part of the Topical Collection on Peripheral Vascular Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Witkin, A.S., Channick, R.N. Chronic Thromboembolic Pulmonary Hypertension: the End Result of Pulmonary Embolism. Curr Cardiol Rep 17, 63 (2015). https://doi.org/10.1007/s11886-015-0621-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-015-0621-9

Keywords

Navigation