Klinische Klassifikation der pulmonalen Hypertonie und initiale Diagnostik: Empfehlungen der Kölner Konsensus Konferenz 2016

Zusammenfassung

Die 2015 veröffentlichten Europäischen Leitlinien zur Diagnostik und Therapie der pulmonalen Hypertonie (PH) sind nunmehr auch in Deutschland gültig. Die Leitlinien befassen sich eingehend mit der Klassifikation und Diagnostik der PH, und bieten darüber hinaus neue Empfehlungen zur Risikostratifizierung und Verlaufskontrollen bei Patienten mit diagnostizierter PAH. Für die praktische Umsetzung der Europäischen Leitlinien in Deutschland sind jedoch zahlreiche für Deutschland spezifische Gesichtspunkte und bereits wieder neue Daten bedeutsam, die eine ausführliche Kommentierung der Leitlinien und in einigen Punkten eine Aktualisierung notwendig machen. Im Juni 2016 fand in Köln eine Konsensus-Konferenz statt, die von den Arbeitsgruppen PH der Deutschen Gesellschaften für Kardiologie (DGK), Pneumologie (DGP) und Pädiatrische Kardiologie (DGPK) organisiert wurde. Die Konferenz befasste sich mit der Umsetzung der Europäischen Leitlinien im deutschsprachigen Raum. Dazu wurden verschiedene Arbeitsgruppen eingesetzt, von denen sich eine gezielt der Klassifikation und initialen Diagnostik der PH widmete. Die Ergebnisse und Beschlüsse dieser Arbeitsgruppe werden in dem vorliegenden Manuskript detailliert beschrieben.

Abstract

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the clinical classification and diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. 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. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.

Schlüsselwörter

pulmonale Hypertonie - Diagnostik - Klassifikation - Definition

Keywords

pulmonary hypertension - diagnosis - classification - definition

^* geteilte Erstautorenschaft

• 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 Respir J 2015; 46: 903-975
• 2 Hoeper MM, Bogaard HJ, Condliffe R et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol 2013; 62: D42-50
• 3 Kovacs G, Avian A, Tscherner M et al. Characterization of patients with borderline pulmonary arterial pressure. Chest 2014; 146: 1486-1493
• 4 Heresi GA, Minai OA, Tonelli AR et al. Clinical characterization and survival of patients with borderline elevation in pulmonary artery pressure. Pulm Circ 2013; 3: 916-925
• 5 Maron BA, Hess E, Maddox TM et al. Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the VA-CART Program. Circulation 2016; 133: 1240-1248
• 6 Valerio CJ, Schreiber BE, Handler CE et al. Borderline mean pulmonary artery pressure in patients with systemic sclerosis: transpulmonary gradient predicts risk of developing pulmonary hypertension. Arthritis Rheum 2013; 65: 1074-1084
• 7 Lau EM, Godinas L, Sitbon O et al. Resting pulmonary artery pressure of 21–24 mmHg predicts abnormal exercise haemodynamics. Eur Respir J 2016; 47: 1436-1444
• 8 Herve P, Lau EM, Sitbon O et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J 2015; 46: 728-737
• 9 Naeije R, Vanderpool R, Dhakal BP et al. Exercise-induced pulmonary hypertension: physiological basis and methodological concerns. Am J Respir Crit Care Med 2013; 187: 576-583
• 10 Condliffe R, Kiely DG, Peacock AJ et al. Connective tissue disease-associated pulmonary arterial hypertension in the modern treatment era. Am J Respir Crit Care Med 2009; 179: 151-157
• 11 Codullo V, Caporali R, Cuomo G et al. Stress Doppler echocardiography in systemic sclerosis: evidence for a role in the prediction of pulmonary hypertension. Arthritis Rheum 2013; 65: 2403-2411
• 12 Kusunose K, Yamada H, Hotchi J et al. Prediction of Future Overt Pulmonary Hypertension by 6-Min Walk Stress Echocardiography in Patients With Connective Tissue Disease. J Am Coll Cardiol 2015; 66: 376-384
• 13 Kessler R, Faller M, Weitzenblum E et al. „Natural history“ of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease. Am J Respir Crit Care Med 2001; 164: 219-224
• 14 Grunig E, Weissmann S, Ehlken N et al. Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia. Circulation 2009; 119: 1747-1457
• 15 Hoeper MM, Huscher D, Ghofrani HA et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol 2013; 168: 871-880
• 16 Badesch DB, Raskob GE, Elliott CG et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010; 137: 376-387
• 17 Seeger W, Adir Y, Barbera JA et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol 2013; 62: D109-116
• 18 Giordano N, Montella A, Corallo C et al. Pulmonary hypertension: a correct diagnosis for a suitable therapy in scleroderma patients. Clin Exp Rheumatol 2015; 33: S182-189
• 19 Avouac J, Airo P, Meune C et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. J Rheumatol 2010; 37: 2290-2298
• 20 Coghlan JG, Denton CP, Grunig E et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis 2014; 73: 1340-1349
• 21 Visovatti SH, Distler O, Coghlan J et al. Borderline pulmonary arterial pressure in systemic sclerosis patients: a post-hoc analysis of the DETECT study. Arthritis Res Ther 2014; 16: 493
• 22 Fischer A, Swigris JJ, Bolster MB et al. Pulmonary hypertension and interstitial lung disease within PHAROS: impact of extent of fibrosis and pulmonary physiology on cardiac haemodynamic parameters. Clin Exp Rheumatol 2014; 32: S109-214
• 23 Rich S, Dantzker DR, Ayres SM et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med 1987; 107: 216-223
• 24 Held M, Grun 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
• 25 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
• 26 Humbert M, Yaici A, de Groote P et al. Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival. Arthritis Rheum 2011; 63: 3522-3530
• 27 Dumitrescu D, Gerhardt F, Viethen T, Schmidt M, Mayer E, Rosenkranz S. Case report: Subjective loss of performance after pulmonary embolism in an athlete- beyond normal values. BMC Pulm Med 2016; 16: 21
• 28 Al-Naamani K, Hijal T, Nguyen V et al. Predictive values of the electrocardiogram in diagnosing pulmonary hypertension. Int J Cardiol 2008; 127: 214-218
• 29 Kovacs G, Avian A, Foris L et al. Role Of Simple Non-Invasive Tools To Assess Pulmonary Hypertension. Am J Respir Crit Care Med 2014; 189: A4750
• 30 Held M, Linke M, Jany B. Echocardiography and right heart catheterization in pulmonal hypertension. Dtsch Med Wochenschr 2014; 139: 1511-1517
• 31 Fisher MR, Criner GJ, Fishman AP et al. Estimating pulmonary artery pressures by echocardiography in patients with emphysema. Eur Respir J 2007; 30: 914-921
• 32 D‘Andrea A, Naeije R, Grunig E et al. Echocardiography of the pulmonary circulation and right ventricular function: exploring the physiologic spectrum in 1, 480 normal subjects. Chest 2014; 145: 1071-1078
• 33 Grunig E, Henn P, D‘Andrea A et al. Reference values for and determinants of right atrial area in healthy adults by 2-dimensional echocardiography. Circ Cardiovasc Imaging 2013; 6: 117-124
• 34 Lang RM, Badano LP, Mor-Avi V et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2015; 16: 233-270
• 35 Greiner S, Jud A, Aurich M et al. Reliability of noninvasive assessment of systolic pulmonary artery pressure by Doppler echocardiography compared to right heart catheterization: analysis in a large patient population. J Am Heart Assoc 2014; 3: e001103
• 36 Fisher MR, Forfia PR, Chamera E et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med 2009; 179: 615-621
• 37 Kittipovanonth M, Bellavia D, Chandrasekaran K et al. Doppler myocardial imaging for early detection of right ventricular dysfunction in patients with pulmonary hypertension. J Am Soc Echocardiogr 2008; 21: 1035-1041
• 38 Sachdev A, Villarraga HR, Frantz RP et al. Right ventricular strain for prediction of survival in patients with pulmonary arterial hypertension. Chest 2011; 139: 1299-1309
• 39 Haeck ML, Scherptong RW, Marsan NA et al. Prognostic value of right ventricular longitudinal peak systolic strain in patients with pulmonary hypertension. Circ Cardiovasc Imaging 2012; 5: 628-636
• 40 Olsson KM, Sommer L, Fuge J et al. Capillary pCO2 helps distinguishing idiopathic pulmonary arterial hypertension from pulmonary hypertension due to heart failure with preserved ejection fraction. Respir Res 2015; 16: 34
• 41 Hoeper MM, Pletz MW, Golpon H et al. Prognostic value of blood gas analyses in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2007; 29: 944-950
• 42 Held M, Walthelm J, Baron S et al. Functional impact of pulmonary hypertension due to hypoventilation and changes under noninvasive ventilation. Eur Respir J 2014; 43: 156-165
• 43 Jilwan FN, Escourrou P, Garcia G et al. High occurrence of hypoxemic sleep respiratory disorders in precapillary pulmonary hypertension and mechanisms. Chest 2013; 143: 47-55
• 44 Meyer FJ, Lossnitzer D, Kristen AV et al. Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension. Eur Respir J 2005; 25: 125-130
• 45 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
• 46 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
• 47 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
• 48 Montani D, Lau EM, Dorfmuller P et al. Pulmonary veno-occlusive disease. Eur Respir J 2016;
• 49 Truong QA, Massaro JM, Rogers IS et al. Reference values for normal pulmonary artery dimensions by noncontrast cardiac computed tomography: the Framingham Heart Study. Circ Cardiovasc Imaging 2012; 5: 147-154
• 50 Dornia C, Lange TJ, Behrens G et al. Multidetector computed tomography for detection and characterization of pulmonary hypertension in consideration of WHO classification. J Comput Assist Tomogr 2012; 36: 175-180
• 51 Iyer AS, Wells JM, Vishin S et al. CT scan-measured pulmonary artery to aorta ratio and echocardiography for detecting pulmonary hypertension in severe COPD. Chest 2014; 145: 824-832
• 52 Ng CS, Wells AU, Padley SP. A CT sign of chronic pulmonary arterial hypertension: the ratio of main pulmonary artery to aortic diameter. J Thorac Imaging 1999; 14: 270-278
• 53 Pienn M, Kovacs G, Tscherner M et al. Non-invasive determination of pulmonary hypertension with dynamic contrast-enhanced computed tomography: a pilot study. Eur Radiol 2014; 24: 668-676
• 54 Pienn M, Kovacs G, Tscherner M et al. Determination of cardiac output with dynamic contrast-enhanced computed tomography. Int J Cardiovasc Imaging 2013; 29: 1871-1878
• 55 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
• 56 Wirth G, Bruggemann K, Bostel T et al. Chronic Thromboembolic Pulmonary Hypertension (CTEPH) – Potential Role of Multidetector-Row CT (MD-CT) and MR Imaging in the Diagnosis and Differential Diagnosis of the Disease. Rofo 2014; 186: 751-761
• 57 Kreitner KF, Wirth GM, Krummenauer F et al. Noninvasive assessment of pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension by high temporal resolution phase-contrast MRI: correlation with simultaneous invasive pressure recordings. Circ Cardiovasc Imaging 2013; 6: 722-729
• 58 Swift AJ, Rajaram S, Hurdman J et al. Noninvasive estimation of PA pressure, flow, and resistance with CMR imaging: derivation and prospective validation study from the ASPIRE registry. JACC Cardiovasc Imaging 2013; 6: 1036-1047
• 59 Reiter G, Reiter U, Kovacs G et al. Blood Flow Vortices along the Main Pulmonary Artery Measured with MR Imaging for Diagnosis of Pulmonary Hypertension. Radiology 2015; 275: 71-79
• 60 Foris V, Kovacs G, Tscherner M et al. Biomarkers in pulmonary hypertension: what do we know?. Chest 2013; 144: 274-283
• 61 Tiede SL, Gall H, Dorr O et al. New potential diagnostic biomarkers for pulmonary hypertension. Eur Respir J 2015; 46: 1390-1396
• 62 Calvier L, Legchenko E, Grimm L et al. Galectin-3 and aldosterone as potential tandem biomarkers in pulmonary arterial hypertension. Heart 2016; 102: 390-396
• 63 Hoeper MM, Lee SH, Voswinckel R et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J Am Coll Cardiol 2006; 48: 2546-2552
• 64 Kovacs G, Avian A, Olschewski A et al. Zero reference level for right heart catheterisation. Eur Respir J 2013; 42: 1586-1594
• 65 Kovacs G, Avian A, Pienn M et al. Reading pulmonary vascular pressure tracings. How to handle the problems of zero leveling and respiratory swings. Am J Respir Crit Care Med 2014; 190: 252-257
• 66 Jing ZC, Jiang X, Han ZY et al. Iloprost for pulmonary vasodilator testing in idiopathic pulmonary arterial hypertension. Eur Respir J 2009; 33: 1354-1360
• 67 Opitz CF, Rubin LJ. Acute vasodilator testing in idiopathic pulmonary arterial hypertension: must we take NO for the answer?. Eur Respir J 2009; 33: 1247-1249
• 68 Leuchte HH, Baezner C, Baumgartner RA et al. Residual pulmonary vasodilative reserve predicts outcome in idiopathic pulmonary hypertension. Heart 2015; 101: 972-976
• 69 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
• 70 Beghetti M, Berger RM, Schulze-Neick I et al. Diagnostic evaluation of paediatric pulmonary hypertension in current clinical practice. Eur Respir J 2013; 42: 689-700
• 71 Held M, Grun M, Holl R et al. Cardiopulmonary exercise testing to detect chronic thromboembolic pulmonary hypertension in patients with normal echocardiography. Respiration 2014; 87: 379-387
• 72 Wensel R, Opitz CF, Anker SD et al. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation 2002; 106: 319-324
• 73 Wensel R, Francis DP, Meyer FJ et al. Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension. Int J Cardiol 2013; 167: 1193-1198
• 74 Yasunobu Y, Oudiz RJ, Sun XG et al. End-tidal PCO2 abnormality and exercise limitation in patients with primary pulmonary hypertension. Chest 2005; 127: 1637-1646
• 75 Dumitrescu D, Oudiz RJ, Karpouzas G et al. Developing pulmonary vasculopathy in systemic sclerosis, detected with non-invasive cardiopulmonary exercise testing. PLoS One 2010; 5: e14293
• 76 Boerrigter BG, Bogaard HJ, Trip P et al. Ventilatory and cardiocirculatory exercise profiles in COPD: the role of pulmonary hypertension. Chest 2012; 142: 1166-1174
• 77 Scheidl SJ, Englisch C, Kovacs G et al. Diagnosis of CTEPH versus IPAH using capillary to end-tidal carbon dioxide gradients. Eur Respir J 2012; 39: 119-124
• 78 Nagel C, Henn P, Ehlken N et al. Stress Doppler echocardiography for early detection of systemic sclerosis-associated pulmonary arterial hypertension. Arthritis Res Ther 2015; 17: 165-015–0673–7
• 79 Grunig E, Janssen B, Mereles D et al. Abnormal pulmonary artery pressure response in asymptomatic carriers of primary pulmonary hypertension gene. Circulation 2000; 102: 1145-1150
• 80 Grunig E, Tiede H, Enyimayew EO et al. Assessment and prognostic relevance of right ventricular contractile reserve in patients with severe pulmonary hypertension. Circulation 2013; 128: 2005-2015
• 81 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
• 82 Eyries M, Montani D, Girerd B et al. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension. Nat Genet 2014; 46: 65-69
• 83 Machado RD, Southgate L, Eichstaedt CA et al. Pulmonary Arterial Hypertension: A Current Perspective on Established and Emerging Molecular Genetic Defects. Hum Mutat 2015; 36: 1113-1127
• 84 Xi Q, Liu Z, Zhao Z et al. High Frequency of Pulmonary Hypertension-Causing Gene Mutation in Chinese Patients with Chronic Thromboembolic Pulmonary Hypertension. PLoS One 2016; 11: e0147396
• 85 Viales RR, Eichstaedt CA, Ehlken N et al. Mutation in BMPR2 Promoter: A ‚Second Hit‘ for Manifestation of Pulmonary Arterial Hypertension?. PLoS One 2015; 10: e0133042
• 86 Wang G, Knight L, Ji R et al. Early onset severe pulmonary arterial hypertension with ‚two-hit‘ digenic mutations in both BMPR2 and KCNA5 genes. Int J Cardiol 2014; 177: e167-179
• 87 Soubrier F, Chung WK, Machado R et al. Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol 2013; 62: D13-21
• 88 Larkin EK, Newman JH, Austin ED et al. Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med 2012; 186: 892-896
• 89 Hinderhofer K, Fischer C, Pfarr N et al. Identification of a new intronic BMPR2-mutation and early diagnosis of heritable pulmonary arterial hypertension in a large family with mean clinical follow-up of 12 years. PLoS One 2014; 9: e91374
• 90 Opitz CF, Hoeper MM, Gibbs JS et al. Pre-Capillary, Combined, and Post-Capillary Pulmonary Hypertension: A Pathophysiological Continuum. J Am Coll Cardiol 2016; 26 (68) 368-378