Chronisch thromboembolische pulmonale Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016

Zusammenfassung

Die 2015 veröffentlichen Europäischen Leitlinien zur Diagnostik und Therapie der Pulmonalen Hypertonie (PH) befassen sich nicht nur mit der pulmonal arteriellen Hypertonie (PAH), sondern auch mit den anderen Formen der PH. Im Juni 2016 fand in Köln eine Konsensus-Konferenz statt, die von den Deutschen Gesellschaften für Kardiologie, Pneumologie und Pädiatrische Kardiologie (DGK, DGP und DGPK) organisiert wurde, und die sich mit strittigen Themen in der praktischen Umsetzung der Europäischen Leitlinien in Deutschland auseinandersetzte. Dazu wurden verschiedene Arbeitsgruppen eingesetzt, von denen eine sich gezielt der Diagnostik und Therapie der chronisch thromboembolischen pulmonalen Hypertonie (CTEPH) bzw. der chronisch thromboembolischen Lungengefäßerkrankung (CTED) widmete. Jeder Patient mit präkapillärer PH unklarer Ursache sollte auf das Vorliegen einer CTEPH untersucht werden. Primäre Therapieoption ist die chirurgische pulmonale Endarteriektomie (PEA) in einem spezialisierten multidisziplinären Team. Bei inoperablen Patienten oder bei persistierender bzw. wiederaufgetretener CTEPH nach PEA besteht die Indikation zur medikamentösen Therapie. Zur pulmonalen Ballonangioplastie (BPA) existieren derzeit nur begrenzte Erfahrungen; auch diese Option bleibt – wie die PEA – spezialisierten Zentren mit Expertise für diese Behandlungsmethode vorbehalten. Zusätzlich wird eine kurze Übersicht zum Pulmonalarteriensarkom gegeben, da die chirurgische Therapie oft analog zur PEA erfolgt. Die Ergebnisse und Beschlüsse dieser Arbeitsgruppe werden in dem vorliegenden Beitrag detailliert beschrieben.

Abstract

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH), but also other significant subgroups of pulmonary hypertension (PH). In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). In every patient with PH of unknown cause CTEPH should be excluded. The primary treatment option is surgical pulmonary endarterectomy (PEA) in a specialized multidisciplinary CTEPH center. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. For balloon pulmonary angioplasty (BPA), there is currently only limited experience. This option – as PEA – is reserved to specialized centers with expertise for this treatment method. In addition, a brief overview is given on pulmonary artery sarcoma, since its surgical treatment is often analogous to PEA. The recommendations of this working group are summarized in the present paper.

Schlüsselwörter

chronisch thromboembolische pulmonale Hypertonie - Diagnose - Therapie - pulmonale Endarteriektomie

Keywords

chronic thromboembolic pulmonary hypertension - diagnosis - therapy - pulmonary endarterectomy

• Literatur

• 1 Galie N, Humbert M, Vachiery JL 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 Heart J 2016; 37: 67-119
• 2 Konstantinides SV, Torbicki A, Agnelli G et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35: 3033-3069 69a-69k
• 3 Klok FA, Tesche C, Rappold L et al. External validation of a simple non-invasive algorithm to rule out chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Thromb Res 2015; 135: 796-801
• 4 Taboada D, Pepke-Zaba J, Jenkins DP et al. Outcome of pulmonary endarterectomy in symptomatic chronic thromboembolic disease. The European respiratory journal 2014; 44: 1635-1645
• 5 Hoeper MM, Humbert M, Souza R et al. A global view of pulmonary hypertension. Lancet Respir Med 2016; 4: 306-322
• 6 Poli D, Grifoni E, Antonucci E et al. Incidence of recurrent venous thromboembolism and of chronic thromboembolic pulmonary hypertension in patients after a first episode of pulmonary embolism. J Thromb Thrombolysis 2010; 30: 294-299
• 7 Marti D, Gomez V, Escobar C et al. [Incidence of symptomatic and asymptomatic chronic thromboembolic pulmonary hypertension]. Arch Bronconeumol 2010; 46: 628-633
• 8 Lang IM, Madani M. Update on chronic thromboembolic pulmonary hypertension. Circulation 2014; 130: 508-518
• 9 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: 121-128
• 10 Pepke-Zaba J, Delcroix M, Lang I et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation 2011; 124: 1973-1981
• 11 Bonderman D, Turecek PL, Jakowitsch J et al. High prevalence of elevated clotting factor VIII in chronic thromboembolic pulmonary hypertension. Thromb Haemost 2003; 90: 372-376
• 12 Bonderman D, Jakowitsch J, Adlbrecht C et al. Medical conditions increasing the risk of chronic thromboembolic pulmonary hypertension. Thromb Haemost 2005; 93: 512-516
• 13 Lang IM, Simonneau G, Pepke-Zaba JW et al. Factors associated with diagnosis and operability of chronic thromboembolic pulmonary hypertension. A case-control study. Thromb Haemost 2013; 110: 83-91
• 14 Bonderman D, Wilkens H, Wakounig S et al. Risk factors for chronic thromboembolic pulmonary hypertension. The European respiratory journal 2009; 33: 325-331
• 15 Bonderman D, Jakowitsch J, Redwan B et al. Role for staphylococci in misguided thrombus resolution of chronic thromboembolic pulmonary hypertension. Arterioscler Thromb Vasc Biol 2008; 28: 678-684
• 16 Zabini D, Nagaraj C, Stacher E et al. Angiostatic factors in the pulmonary endarterectomy material from chronic thromboembolic pulmonary hypertension patients cause endothelial dysfunction. PLoS One 2012; 7: e43793
• 17 Alias S, Redwan B, Panzenbock A et al. Defective angiogenesis delays thrombus resolution: a potential pathogenetic mechanism underlying chronic thromboembolic pulmonary hypertension. Arterioscler Thromb Vasc Biol 2014; 34: 810-819
• 18 Frey MK, Alias S, Winter MP et al. Splenectomy is modifying the vascular remodeling of thrombosis. J Am Heart Assoc 2014; 3: e000772
• 19 Morris TA, Marsh JJ, Chiles PG et al. High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension. Blood 2009; 114: 1929-1936
• 20 Held M, Hesse A, Gott F et al. A symptom-related monitoring program following pulmonary embolism for the early detection of CTEPH: a prospective observational registry study. BMC Pulm Med 2014; 14: 141
• 21 Held M, Grün M, Holl R et al. [Chronic thromboembolic pulmonary hypertension: Time delay from onset of symtoms to diagnosis and clinical condition at diagnosis]. Dtsch Med Wochenschr 2014; 139: 1647-1652
• 22 Berger RM, Beghetti M, Humpl T et al. Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 2012; 379: 537-546
• 23 Tscholl D, Langer F, Wendler O et al. Pulmonary thromboendarterectomy – risk factors for early survival and hemodynamic improvement. Eur J Cardiothorac Surg 2001; 19: 771-776
• 24 Held M, Grün M, Holl R et al. Cardiopulmonary exercise testing to detect chronic thromboembolic pulmonary hypertension in patients with normal echocardiography. Respiration 2014; 87: 379-387
• 25 Held M, Kolb P, Grün M et al. Functional characterization of patients with Chronic Thromboembolic Disease. Respiration 2016; 91: 503-509
• 26 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: 680-684
• 27 Seferian A, Helal B, Jais X et al. Ventilation / perfusion lung scan in pulmonary veno-occlusive disease. Eur Respir J 2012; 40: 75-83
• 28 He J, Fang W, Lv B et al. Diagnosis of chronic thromboembolic pulmonary hypertension: comparison of ventilation / perfusion scanning and multidetector computed tomography pulmonary angiography with pulmonary angiography. Nucl Med Commun 2012; 33: 459-463
• 29 Hoeper MM, Mayer E, Simonneau G, Rubin LJ. Chronic thromboembolic pulmonary hypertension. Circulation 2006; 113: 2011-2020
• 30 Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson B. EANM guidelines for ventilation / perfusion scintigraphy : Part 2. Algorithms and clinical considerations for diagnosis of pulmonary emboli with V / P(SPECT) and MDCT. Eur J Nucl Med Mol Imaging 2009; 36: 1528-1538
• 31 Bajc M, Neilly JB, Miniati M et al. EANM guidelines for ventilation / perfusion scintigraphy : Part 1. Pulmonary imaging with ventilation / perfusion single photon emission tomography. Eur J Nucl Med Mol Imaging 2009; 36: 1356-1370
• 32 Soler X, Kerr KM, Marsh JJ et al. Pilot study comparing SPECT perfusion scintigraphy with CT pulmonary angiography in chronic thromboembolic pulmonary hypertension. Respirology 2012; 17: 180-184
• 33 McLaughlin VV, Langer A, Tan M et al. Contemporary trends in the diagnosis and management of pulmonary arterial hypertension: an initiative to close the care gap. Chest 2013; 143: 324-332
• 34 Sherrick AD, Swensen SJ, Hartman TE. Mosaic pattern of lung attenuation on CT scans: frequency among patients with pulmonary artery hypertension of different causes. AJR Am J Roentgenol 1997; 169: 79-82
• 35 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: 1070-1077
• 36 Ley S, Ley-Zaporozhan J, Pitton MB et al. Diagnostic performance of state-of-the-art imaging techniques for morphological assessment of vascular abnormalities in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Eur Radiol 2012; 22: 607-616
• 37 Heinrich M, Uder M, Tscholl D et al. CT scan findings in chronic thromboembolic pulmonary hypertension: predictors of hemodynamic improvement after pulmonary thromboendarterectomy. Chest 2005; 127: 1606-1613
• 38 Grgic A, Miodek F, Schäfers HJ et al. Assessment of operability by means of CTPA and perfusion SPECT in patients with chronic thromboembolic pulmonary hypertension. Acta Radiol 2016; 57: 33-40
• 39 Dournes G, Verdier D, Montaudon M et al. Dual-energy CT perfusion and angiography in chronic thromboembolic pulmonary hypertension: diagnostic accuracy and concordance with radionuclide scintigraphy. Eur Radiol 2014; 24: 42-51
• 40 Sugiyama M, Fukuda T, Sanda Y et al. Organized thrombus in pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension; imaging with cone beam computed tomography. Jpn J Radiol 2014; 32: 375-382
• 41 Hinrichs JB, Marquardt S, von Falck C et al. Comparison of C-arm Computed Tomography and Digital Subtraction Angiography in Patients with Chronic Thromboembolic Pulmonary Hypertension. Cardiovasc Intervent Radiol 2016; 39: 53-63
• 42 Shure D, Gregoratos G, Moser KM. Fiberoptic angioscopy: role in the diagnosis of chronic pulmonary arterial obstruction. Ann Intern Med 1985; 103: 844-850
• 43 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: 677-678
• 44 Tanabe N, Sugiura T, Jujo T et al. Subpleural perfusion as a predictor for a poor surgical outcome in chronic thromboembolic pulmonary hypertension. Chest 2012; 141: 929-934
• 45 Skoro-Sajer N, Marta G, Gerges C et al. Surgical specimens, haemodynamics and long-term outcomes after pulmonary endarterectomy. Thorax 2014; 69: 116-122
• 46 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
• 47 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: 702-710
• 48 Vuylsteke A, Sharples L, Charman G et al. Circulatory arrest versus cerebral perfusion during pulmonary endarterectomy surgery (PEACOG): a randomised controlled trial. Lancet 2011; 378: 1379-1387
• 49 Cannon JE, Su L, Kiely DG et al. Dynamic Risk Stratification of Patient Long-Term Outcome After Pulmonary Endarterectomy: Results From the United Kingdom National Cohort. Circulation 2016; 133: 1761-1771
• 50 Berman M, Tsui S, Vuylsteke A et al. Successful extracorporeal membrane oxygenation support after pulmonary thromboendarterectomy. Ann Thorac Surg 2008; 86: 1261-1267
• 51 Mydin M, Berman M, Klein A et al. Extracorporeal membrane oxygenation as a bridge to pulmonary endarterectomy. Ann Thorac Surg 2011; 92: e101-103
• 52 Thistlethwaite PA, Madani MM, Kemp AD et al. Venovenous extracorporeal life support after pulmonary endarterectomy: indications, techniques, and outcomes. Ann Thorac Surg 2006; 82: 2139-2145
• 53 Kim NH, Delcroix M, Jenkins DP et al. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol 2013; 62: D92-99
• 54 Wilkens H, Lang I, Blankenburg T et al. [Chronic thromboembolic pulmonary hypertension – a position paper]. Dtsch Med Wochenschr 2014; 139: 2204-2206
• 55 Gruenig E, Lichtblau M, Ehlken N et al. Safety and efficacy of exercise training in various forms of pulmonary hypertension. Eur Respir J 2012; 40: 84-92
• 56 Reesink HJ, Surie S, Kloek JJ et al. Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. J Thorac Cardiovasc Surg 2010; 139: 85-91
• 57 Jensen KW, Kerr KM, Fedullo PF et al. Pulmonary hypertensive medical therapy in chronic thromboembolic pulmonary hypertension before pulmonary thromboendarterectomy. Circulation 2009; 120: 1248-1254
• 58 Simonneau G, D’Armini AM, Ghofrani HA et al. Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial. Lancet Respir Med 2016; 4: 372-380
• 59 Jais 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: 2127-2134
• 60 Feinstein JA, Goldhaber SZ, Lock JE et al. Balloon pulmonary angioplasty for treatment of chronic thromboembolic pulmonary hypertension. Circulation 2001; 103: 10-13
• 61 Kataoka M, Inami T, Hayashida K et al. Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2012; 5: 756-762
• 62 Fukui S, Ogo T, Morita Y et al. Right ventricular reverse remodelling after balloon pulmonary angioplasty. The European respiratory journal 2014; 43: 1394-1402
• 63 Mizoguchi H, Ogawa A, Munemasa M et al. Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2012; 5: 748-755
• 64 Andreassen AK, Ragnarsson A, Gude E et al. Heart 2013; 99: 1415-1420
• 65 Wong HH, Gounaris I, McCormack A et al. Presentation and management of pulmonary artery sarcoma. Clin Sarcoma Res 2015; 5: 3
• 66 Gan HL, Zhang JQ, Huang XY et al. The wall eclipsing sign on pulmonary artery computed tomography angiography is pathognomonic for pulmonary artery sarcoma. PLoS One 2013; 8: e83200
• 67 Choong CK, Lawton JS, Moon MR, Damiano Jr RJ. Failure of medical therapy for pulmonary „thromboembolic“ disease: beware the unsuspected primary sarcoma of the pulmonary artery. J Thorac Cardiovasc Surg 2004; 128: 763-765
• 68 Lee EJ, Moon SH, Choi JY et al. Usefulness of fluorodeoxyglucose positron emission tomography in malignancy of pulmonary artery mimicking pulmonary embolism. ANZ J Surg 2013; 83: 342-347
• 69 Said SM, Sundt 3 rd TM, Garces YI et al. 5-year survival after multiple repeat metastasectomy for pulmonary artery angiosarcoma. Ann Thorac Surg 2011; 91: e49-51
• 70 Deutsche Gesellschaft für Kardiologie. ESC / DGK Pocket-Leitlinien: Diagnostik und Therapie der pulmonalen Hypertonie. http://leitlinien.dgk.org/files/2010_Pocket-Leitlinien_Pulmonale_Hypertonie.pdf Zuletzt aufgerufen am 13.09.2016