Pulmonary thromboendarterectomy is a curative resolution for chronic thromboembolic pulmonary hypertension associated with antiphospholipid syndrome: a retrospective cohort study

Abstract

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening condition with poor prognosis in patients with antiphospholipid syndrome (APS). Pulmonary thromboendarterectomy (PTE) is the optimal surgical option for CTEPH.

Objectives

This retrospective cohort study aimed to evaluate the efficacy and risk of PTE in patients with APS-associated CTEPH.

Methods

Consecutive patients with APS-associated CTEPH diagnosed between January 2012 and September 2017 at Peking Union Medical College Hospital were retrospectively evaluated. Demographics, clinical manifestations, antiphospholipid antibody (aPL) profiles, and pulmonary arterial hypertension–targeted medications were collected. Deterioration of cardiac function and death were chosen as the endpoints, in order to assess the effect of PTE on short-term and long-term prognoses (evaluated by the change of cardiac function after treatment and cardiac deterioration or death in the follow-up, respectively).

Results

A total of 20 patients with APS-associated CTEPH were enrolled, and eight patients underwent PTE. Chi-square test (p = 0.01) and Kaplan–Meier curves (log rank test, p = 0.04) showed that there were statistically significant differences in both short-term and long-term prognoses between patients with and without PTE.

Conclusion

These results provide strong evidence that PTE is a curative resolution in patients with APS-associated CTEPH. Following a full specialized and multidisciplinary risk-benefit evaluation to limit the risk of thrombosis or bleeding and to manage possible thrombocytopenia, PTE is at least a temporal curative resolution for CTEPH complicated with APS.

Keywords

Antiphospholipid syndrome chronic thromboembolic pulmonary hypertension pulmonary thromboendarterectomy

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References

Miyakis

Lockshin

Atsumi

et al.

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306.

Cervera

Serrano

Pons-Estel

et al.

Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2015; 74: 1011–1018.

Zhao

Sun

Zhang

et al.

The clinical manifestations and thrombotic risk factors in primary antiphospholipid syndrome. Chin J Intern Med 2016; 55: 386–391.

Galiè

Humbert

Vachiery

et al.

2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015; 46: 903–975.

Matthews

Hemnes

. Current concepts in the pathogenesis of chronic thromboembolic pulmonary hypertension. Pulm Circ 2016; 6: 145–154.

Robbins

Pugh

Hemnes

. Update on chronic thromboembolic pulmonary hypertension. Trends Cardiovasc Med 2017; 27: 29–37.

Madani

Auger

Pretorius

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.

Mayer

Jenkins

Lindner

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: 702–710.

Galli

Finazzi

Barbui

. Thrombocytopenia in the antiphospholipid syndrome. Br J Haematol 1996; 93: 1–5.

10.

Espinosa

Santos

Cervera

et al.

Adrenal involvement in the antiphospholipid syndrome: clinical and immunologic characteristics of 86 patients. Medicine (Baltimore) 2003; 82: 106–118.

11.

Mayer

Cerovec

Rados

et al.

Antiphospholipid syndrome and central nervous system. Clin Neurol Neurosurg 2010; 112: 602–608.

12.

Camous

Decrombecque

Louvain-Quintard

et al.

Outcomes of patients with antiphospholipid syndrome after pulmonary endarterectomy. Eur J Cardiothorac Surg 2014; 46: 116–120.

13.

Cucurull

Ordi Ros

Murtra

et al.

Pulmonary thromboendarterectomy in a patient with primary antiphospholipid syndrome. Med Clin (Barc) 1996; 106: 498–500.

14.

Sandoval

Amigo

Barragan

et al.

Primary antiphospholipid syndrome presenting as chronic thromboembolic pulmonary hypertension. Treatment with thromboendarterectomy. J Rheumatol 1996; 23: 772–775.

15.

Kamezaki

Tasaki

Yamanaka

et al.

Successful thromboendarterectomy for severe chronic thromboembolic pulmonary hypertension caused by primary antiphospholipid syndrome. J UOEH 2004; 26: 287–294.

16.

Kuzenko

Sciascia

Silvestro

et al.

Resolutive pulmonary endarterectomy in a non-compliant patient with systemic lupus erythematosus and antiphospholipid syndrome. Rheumatol Int 2013; 33: 1889–1893.

17.

Gopalan

Blanchard

Auger

. Diagnostic evaluation of chronic thromboembolic pulmonary hypertension. Ann Am Thorac Soc 2016; 13(Suppl 3): S222–239.

18.

Tan

Cohen

Fries

et al.

The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–1277.

19.

D'Armini

Morsolini

Mattiucci

et al.

Pulmonary endarterectomy for distal chronic thromboembolic pulmonary hypertension. J Thorac Cardiovasc Surg 2014; 148: 1005–1011.

20.

Luo

Huang

Lin

et al.

Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension—a single-center experience in Taiwan. J Formos Med Assoc 2015; 114: 1197–1203.

21.

Stojanovich

Kontic

Djokovic

et al.

Pulmonary events in antiphospholipid syndrome: influence of antiphospholipid antibody type and levels. Scand J Rheumatol 2012; 41: 223–226.

22.

Becattini

Manina

Busti

et al.

Bosentan for chronic thromboembolic pulmonary hypertension: findings from a systematic review and meta-analysis. Thromb Res 2010; 126: e51–56.

23.

Ghofrani

Schermuly

Rose

et al.

Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 2003; 167: 1139–1141.

24.

Reichenberger

Voswinckel

Enke

et al.

Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur Respir J 2007; 30: 922–927.

25.

Suntharalingam

Treacy

Doughty

et al.

Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension. Chest 2008; 134: 229–236.

26.

Condliffe

Kiely

Gibbs

et al.

Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension. Eur Respir J 2009; 33: 332–338.

27.

Cuadrado

Mujic

Muñoz

et al.

Thrombocytopenia in the antiphospholipid syndrome. Ann Rheum Dis 1997; 56: 194–196.

28.

Krause

Blank

Fraser

et al.

The association of thrombocytopenia with systemic manifestations in the antiphospholipid syndrome. Immunobiology 2005; 210: 749–754.

29.

Cervera

Piette

Font

et al.

Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46: 1019–1027.

30.

Sipek-Dolnicar

Hojnik

Rozman

et al.

Small vessel thrombosis without major thrombotic events in systemic lupus erythematosus patients with antiphospholipid syndrome. Wien Klin Wochenschr 2000; 112: 707–710.

31.

Nageswara Rao

Elwood

Kaur

et al.

A retrospective review of pediatric antiphospholipid syndrome and thrombosis outcomes. Blood Coagul Fibrinolysis 2017; 28: 205–210.

32.

Cervera

. Antiphospholipid syndrome. Thromb Res 2017; 151(Suppl 1): S43–S47.

33.

Larici

Franchi

Occhipinti

et al.

Diagnosis and management of hemoptysis. Diagn Interv Radiol 2014; 20: 299–309.

34.

Fernandes

Poch

Auger

. Treatment of chronic thromboembolic pulmonary hypertension: the role of medical therapy and balloon pulmonary angioplasty. Methodist Debakey Cardiovasc J 2016; 12: 205–212.

35.

Andersen

Korsholm

Mellemkjær

et al.

Switching from sildenafil to riociguat for the treatment of PAH and inoperable CTEPH: real-life experiences. Respir Med Case Rep 2017; 22: 39–43.

36.

Chen

Zhai

Huang

et al.

Bosentan therapy for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a systemic review and meta-analysis. Clin Respir J 2018, pp. 1–10.

37.

Pengo

Denas

. Diagnostics and treatment of thrombotic antiphospholipid syndrome (APS): A personal perspective. Thromb Res 2018; 169: 35–40.

38.

Sciascia S, Radin M, Cecchi I, et al. Long-term effect of B-cells depletion alone as rescue therapy for severe thrombocytopenia in primary antiphospholipid syndrome. Semin Arthritis Rheum. Epub ahead of print 11 April 2018. doi: 10.1016/j.semarthrit.2018.04.001..

39.

Rymarz

Niemczyk

. The complex treatment including rituximab in the management of catastrophic antiphospholid syndrome with renal involvement. BMC Nephrol 2018; 19: 132.

40.

Bala

Celinska-Lowenhoff

Szot

et al.

Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome. Cochrane Database Syst Rev 2017; 10: CD012169.

41.

Jackson

Oromendia

Unlu

et al.

Recurrent thrombosis in patients with antiphospholipid antibodies and arterial thrombosis on antithrombotic therapy. Blood Adv 2017; 1: 2320–2324.

42.

Schreiber

Sciascia

de Groot

et al.

Antiphospholipid syndrome. Nat Rev Dis Primers 2018; 4: 17103.

43.

Watanabe

Oku

Amengual

et al.

Effects of statins on thrombosis development in patients with systemic lupus erythematosus and antiphospholipid antibodies. Lupus 2018; 27: 225234.

44.

Piazza

Goldhaber

. Chronic thromboembolic pulmonary hypertension. N Engl J Med 2011; 364: 351–360.

45.

Delcroix

Kerr

Fedullo

. Chronic thromboembolic pulmonary hypertension. Epidemiology and risk factors. Ann Am Thorac Soc 2016; 13(Suppl 3): S201–206.

46.

Zuily

Wahl

. Pulmonary hypertension in antiphospholipid syndrome. Curr Rheumatol Rep 2015; 17: 478–487.

47.

LeVarge

Channick

. Chronic thromboembolic pulmonary hypertension: evolution in management. Curr Opin Pulm Med 2014; 20: 400–408.

48.

Wolf

Boyer-Neumann

Parent

et al.

Thrombotic risk factors in pulmonary hypertension. Eur Respir J 2000; 15: 395–399.