Differenzialdiagnostik der pulmonalen Hypertonie am Beispiel der Kollagenose assoziierten PAH im Kontext chronischer Lungen- und Linksherzerkrankungen

Zusammenfassung

Die pulmonale Hypertonie (PH) ist eine regelmäßige Komplikation von Kollagenosen und wird zudem im Zusammenhang mit Lungen- und Linksherzerkrankungen diagnostiziert.

Die korrekte Differenzierung und Klassifikation der PH ist essenziell, um Therapien möglichst zielgerichtet einsetzen zu können und ein Vorenthalten von wichtigen Therapien ebenso zu vermeiden wie eine Übertherapie.

Bei den Kollagenosen umfasst die Differenzialdiagnostik und Klassifikation die Differenzierung innerhalb der assoziierten pulmonalarteriellen Hypertonie (APAH) Gruppe 1, aber auch, Klassifikationsgruppen übergreifend, die Gruppe 2 (mit führender linkskardialer Beteiligung), Gruppe 3 (mit führender parenchymatöser Lungenerkrankung), Gruppe 4 (chronisch thromboembolische PH) und letztlich die Gruppe 5 (z. B. bei terminaler Niereninsuffizienz und Dialysepflicht).

Ähnliches trifft auch auf die zunehmend älteren Patienten zu, die mit einer PAH diagnostiziert werden und Komorbiditäten aufweisen, die entweder selbst eine PH hervorrufen können oder als Komorbiditäten einer echten PAH auftreten.

Die abnehmende Trennschärfe zwischen den einzelnen PH-Gruppen erschwert die korrekte Klassifikation und stellt eine große klinische Herausforderung dar.

Auf dem Boden unterschiedlicher klinischer Szenarien wird im vorliegenden Artikel die Differenzialdiagnostik der PH sowohl bei Kollagenosen als auch bei chronischen Linksherz- und Lungenerkrankungen aufgearbeitet und objektive Kriterien vorgestellt, die diese Differenzierung erleichtern.

Abstract

Pulmonary hypertension (PH) can be diagnosed in the context of connective tissue diseases (CTD) as well as in elderly patients with multiple comorbidities. A correct clinical differential diagnosis and classification is essential before adequate therapeutic decisions can be made. Differential diagnosis of PH in CTD comprises associated pulmonary arterial hypertension (APAH), group 2 or 3 PH (PH arising from left heart or chronic lung disease), chronic thromboembolic PH (PH) and group 5 (e. g. in the context of terminal renal insufficiency). This is also true of elderly patients in whom the decision has to be made if the increasing number of coincident diseases lead to PH or have to be interpreted as comorbidities. In this manuscript, the differential diagnosis of PH is elucidated, focusing on CTD, in the context of left heart disease and chronic lung disease. Furthermore, criteria are presented facilitating an objective approach in this context.

Publikationsverlauf

Eingereicht: 17. Juni 2020

Angenommen: 21. Juni 2021

Artikel online veröffentlicht:
12. Februar 2021

• 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 Nathan SD, Barbera JA, Gaine SP. et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J 2019;
• 3 Vachiery JL, Tedford RJ, Rosenkranz S. et al. Pulmonary hypertension due to left heart disease. Eur Respir J 2019;
• 4 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
• 5 Simonneau G, Montani D, Celermajer DS. et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019;
• 6 Humbert M, Sitbon O, Chaouat A. et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 2006; 173: 1023-1030
• 7 Benza RL, Miller DP, Gomberg-Maitland M. et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 2010; 122: 164-172
• 8 Hoeper MM, Kramer T, Pan Z. et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J 2017;
• 9 Benza RL, Gomberg-Maitland M, Elliott CG. et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest 2019; 156: 323-337
• 10 Chung L, Liu J, Parsons L. et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest 2010; 138: 1383-1394
• 11 Yang X, Mardekian J, Sanders KN. et al. Prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature. Clin Rheumatol 2013; 32: 1519-1531
• 12 Moinzadeh P, Riemekasten G, Siegert E. et al. Vasoactive Therapy in Systemic Sclerosis: Real-life Therapeutic Practice in More Than 3000 Patients. J Rheumatol 2016; 43: 66-74
• 13 Lefevre G, Dauchet L, Hachulla E. et al. Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis. Arthritis Rheum 2013; 65: 2412-2423
• 14 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
• 15 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
• 16 Weatherald J, Montani D, Jevnikar M. et al. Screening for pulmonary arterial hypertension in systemic sclerosis. Eur Respir Rev 2019;
• 17 Kovacs G, Dumitrescu D, Barner A. et al. Definition, clinical classification and initial diagnosis of pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol 2018; 272S: 11-19
• 18 Dumitrescu D, Nagel C, Kovacs G. et al. Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis. Heart 2017; 103: 774-782
• 19 Kovacs G, Berghold A, Scheidl S. et al. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 2009; 34: 888-894
• 20 Rosenkranz S, Diller GP, Dumitrescu D. et al. Hemodynamic Definition of Pulmonary Hypertension: Commentary on the Proposed Change by the 6th World Symposium on Pulmonary Hypertension. Dtsch Med Wochenschr 2019; 144: 1367-1372
• 21 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
• 22 Coghlan JG, Wolf M, Distler O. et al. Incidence of pulmonary hypertension and determining factors in patients with systemic sclerosis. Eur Respir J 2018;
• 23 Hoffmann-Vold AM, Fretheim H, Midtvedt O. et al. Frequencies of borderline pulmonary hypertension before and after the DETECT algorithm: results from a prospective systemic sclerosis cohort. Rheumatology (Oxford) 2018; 57: 480-487
• 24 Kovacs G, Maier R, Aberer E. et al. Pulmonary arterial hypertension therapy may be safe and effective in patients with systemic sclerosis and borderline pulmonary artery pressure. Arthritis Rheum 2012; 64: 1257-1262
• 25 Dorfmuller P, Humbert M, Perros F. et al. Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol 2007; 38: 893-902
• 26 De Santis M, Crotti C, Selmi C. Liver abnormalities in connective tissue diseases. Best Pract Res Clin Gastroenterol 2013; 27: 543-551
• 27 Riviere E, Vergniol J, Reffet A. et al. Gastric variceal bleeding uncovering a rare association of CREST syndrome, primary biliary cirrhosis, nodular regenerative hyperplasia and pulmonary hypertension. Eur J Gastroenterol Hepatol 2010; 22: 1145-1148
• 28 Graf L, Dobrota R, Jordan S. et al. Nodular Regenerative Hyperplasia of the Liver: A Rare Vascular Complication in Systemic Sclerosis. J Rheumatol 2018; 45: 103-106
• 29 Fox BD, Shimony A, Langleben D. et al. High prevalence of occult left heart disease in scleroderma-pulmonary hypertension. Eur Respir J 2013; 42: 1083-1091
• 30 Thakkar V, Lau EM. Connective tissue disease-related pulmonary arterial hypertension. Best Pract Res Clin Rheumatol 2016; 30: 22-38
• 31 Allanore Y, Meune C, Vonk MC. et al. Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis. Ann Rheum Dis 2010; 69: 218-221
• 32 Meune C, Vignaux O, Kahan A. et al. Heart involvement in systemic sclerosis: evolving concept and diagnostic methodologies. Arch Cardiovasc Dis 2010; 103: 46-52
• 33 Nihtyanova SI, Sari A, Harvey JC. et al. Using Autoantibodies and Cutaneous Subset to Develop Outcome-Based Disease Classification in Systemic Sclerosis. Arthritis Rheumatol 2020; 72: 465-476
• 34 Hoeper MM, McLaughlin VV, Dalaan AM. et al. Treatment of pulmonary hypertension. Lancet Respir Med 2016; 4: 323-336
• 35 Guazzi M, Vicenzi M, Arena R. et al. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation 2011; 124: 164-174
• 36 Bonderman D, Ghio S, Felix SB. et al. Left Ventricular Systolic Dysfunction Associated With Pulmonary Hypertension Riociguat Trial Study G. Riociguat for patients with pulmonary hypertension caused by systolic left ventricular dysfunction: a phase IIb double-blind, randomized, placebo-controlled, dose-ranging hemodynamic study. Circulation 2013; 128: 502-511
• 37 Hoendermis ES, Liu LC, Hummel YM. et al. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J 2015; 36: 2565-2573
• 38 Bermejo J, Yotti R, Garcia-Orta R. et al. Sildenafil for Improving Outcomes after VCi. Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial. Eur Heart J 2018; 39: 1255-1264
• 39 Vachiery JL, Delcroix M, Al-Hiti H. et al. Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J 2018;
• 40 Badesch DB, Raskob GE, Elliott CG. et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest 2010; 137: 376-387
• 41 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
• 42 Rosenkranz S, Gibbs JS, Wachter R. et al. Left ventricular heart failure and pulmonary hypertension. Eur Heart J 2016; 37: 942-954
• 43 Halpern SD, Taichman DB. Misclassification of pulmonary hypertension due to reliance on pulmonary capillary wedge pressure rather than left ventricular end-diastolic pressure. Chest 2009; 136: 37-43
• 44 Kovacs G, Herve P, Barbera JA. et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J 2017;
• 45 Houston BA, Tedford RJ. What We Talk About When We Talk About the Wedge Pressure. Circ Heart Fail 2017;
• 46 Nagy AI, Venkateshvaran A, Merkely B. et al. Determinants and prognostic implications of the negative diastolic pulmonary pressure gradient in patients with pulmonary hypertension due to left heart disease. Eur J Heart Fail 2017; 19: 88-97
• 47 Reddy YNV, El-Sabbagh A, Nishimura RA. Comparing Pulmonary Arterial Wedge Pressure and Left Ventricular End Diastolic Pressure for Assessment of Left-Sided Filling Pressures. JAMA Cardiol 2018; 3: 453-454
• 48 Opitz CF, Hoeper MM, Gibbs JS. et al. Pre-Capillary, Combined, and Post-Capillary Pulmonary Hypertension: A Pathophysiological Continuum. J Am Coll Cardiol 2016; 68: 368-378
• 49 McLaughlin VV, Vachiery JL, Oudiz RJ. et al. Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: Results from the AMBITION trial. J Heart Lung Transplant 2019; 38: 1286-1295
• 50 Fujimoto N, Borlaug BA, Lewis GD. et al. Hemodynamic responses to rapid saline loading: the impact of age, sex, and heart failure. Circulation 2013; 127: 55-62
• 51 Lewis GD, Bossone E, Naeije R. et al. Pulmonary vascular hemodynamic response to exercise in cardiopulmonary diseases. Circulation 2013; 128: 1470-1479
• 52 Andersen MJ, Olson TP, Melenovsky V. et al. Differential hemodynamic effects of exercise and volume expansion in people with and without heart failure. Circ Heart Fail 2015; 8: 41-48
• 53 Maor E, Grossman Y, Balmor RG. et al. Exercise haemodynamics may unmask the diagnosis of diastolic dysfunction among patients with pulmonary hypertension. Eur J Heart Fail 2015; 17: 151-158
• 54 Fayyaz AU, Edwards WD, Maleszewski JJ. et al. Global Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Heart Failure and Preserved or Reduced Ejection Fraction. Circulation 2018; 137: 1796-1810
• 55 Galie N, Channick RN, Frantz RP. et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J 2019;
• 56 Leuchte HH, Neurohr C, Baumgartner R. et al. Brain natriuretic peptide and exercise capacity in lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med 2004; 170: 360-365
• 57 Chaouat A, Bugnet AS, Kadaoui N. et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 172: 189-194
• 58 Hayes Jr D, Higgins RS, Kirkby S. et al. Impact of pulmonary hypertension on survival in patients with cystic fibrosis undergoing lung transplantation: an analysis of the UNOS registry. J Cyst Fibros 2014; 13: 416-423
• 59 Hayes Jr D, Black SM, Tobias JD. et al. Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation. Ann Thorac Surg 2016; 101: 246-252
• 60 Hayes Jr D, Black SM, Tobias JD. et al. Prevalence of Pulmonary Hypertension and its Influence on Survival in Patients With Advanced Chronic Obstructive Pulmonary Disease Prior to Lung Transplantation. COPD 2016; 13: 50-56
• 61 Thabut G, Dauriat G, Stern JB. et al. Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation. Chest 2005; 127: 1531-1536
• 62 Weitzenblum E, Chaouat A. Severe pulmonary hypertension in COPD: is it a distinct disease?. Chest 2005; 127: 1480-1482
• 63 Kessler R, Faller M, Fourgaut G. et al. Predictive factors of hospitalization for acute exacerbation in a series of 64 patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 159: 158-164
• 64 Hamada K, Nagai S, Tanaka S. et al. Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis. Chest 2007; 131: 650-656
• 65 Poms AD, Turner M, Farber HW. et al. Comorbid conditions and outcomes in patients with pulmonary arterial hypertension: a REVEAL registry analysis. Chest 2013; 144: 169-176
• 66 Peacock AJ, Ling Y, Johnson MK. et al. Idiopathic pulmonary arterial hypertension and co-existing lung disease: is this a new phenotype?. Pulm Circ 2020; 10: 2045894020914851
• 67 Hayes Jr D, Tobias JD, Mansour HM. et al. Pulmonary hypertension in cystic fibrosis with advanced lung disease. Am J Respir Crit Care Med 2014; 190: 898-905
• 68 Leuchte HH, Baumgartner RA, Nounou ME. et al. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med 2006; 173: 744-750
• 69 Olschewski H, Behr J, Bremer H. et al. Pulmonary hypertension due to lung diseases: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol 2018; 272S: 63-68
• 70 Distler O, Gahlemann M, Maher TM. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. Reply. N Engl J Med 2019; 381: 1596-1597
• 71 Raghu G, Nathan SD, Behr J. et al. Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction. Eur Respir J 2015; 46: 1370-1377
• 72 Cottin V. Clinical case: Combined pulmonary fibrosis and emphysema with pulmonary hypertension -- clinical management. BMC Res Notes 2013; 6 (Suppl. 01) S2
• 73 Pulido T, Rubin LJ, Simonneau G. et al. Macitentan and pulmonary arterial hypertension. N Engl J Med 2014; 370: 82-83
• 74 Ghofrani HA, Galie N, Grimminger F. et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 2013; 369: 330-340
• 75 Moll M, Christmann RB, Zhang Y. et al. Patients with systemic sclerosis-associated pulmonary arterial hypertension express a genomic signature distinct from patients with interstitial lung disease. J Scleroderma Relat Disord 2018; 3: 242-248
• 76 Aithala R, Alex AG, Danda D. Pulmonary hypertension in connective tissue diseases: an update. Int J Rheum Dis 2017; 20: 5-24
• 77 C SHKRS-N. 12-Monats-Prävalenz der bekannten chronisch obstruktiven Lungenerkrankung (COPD) in Deutschland. J Health Monitoring 2017; 46-54
• 78 Kovacs G, Agusti A, Barbera JA. et al. Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype?. Am J Respir Crit Care Med 2018; 198: 1000-1011
• 79 Eddahibi S, Chaouat A, Morrell N. et al. Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease. Circulation 2003; 108: 1839-1844
• 80 Rutten FH, Cramer MJ, Grobbee DE. et al. Unrecognized heart failure in elderly patients with stable chronic obstructive pulmonary disease. Eur Heart J 2005; 26: 1887-1894
• 81 Funk GC, Lang I, Schenk P. et al. Left ventricular diastolic dysfunction in patients with COPD in the presence and absence of elevated pulmonary arterial pressure. Chest 2008; 133: 1354-1359
• 82 Miller J, Edwards LD, Agusti A. et al. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respir Med 2013; 107: 1376-1384
• 83 Andrea R, Lopez-Giraldo A, Falces C. et al. Lung function abnormalities are highly frequent in patients with heart failure and preserved ejection fraction. Heart Lung Circ 2014; 23: 273-279
• 84 Rennard SI, Locantore N, Delafont B. et al. Evaluation of CLtIPSE. Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis. Ann Am Thorac Soc 2015; 12: 303-312
• 85 Hilde JM, Skjorten I, Hansteen V. et al. Haemodynamic responses to exercise in patients with COPD. Eur Respir J 2013; 41: 1031-1041
• 86 Portillo K, Torralba Y, Blanco I. et al. Pulmonary hemodynamic profile in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2015; 10: 1313-1320
• 87 Cuttica MJ, Kalhan R, Shlobin OA. et al. Categorization and impact of pulmonary hypertension in patients with advanced COPD. Respir Med 2010; 104: 1877-1882
• 88 Andersen KH, Iversen M, Kjaergaard J. et al. Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease. J Heart Lung Transplant 2012; 31: 373-380
• 89 Hurdman J, Condliffe R, Elliot CA. et al. Pulmonary hypertension in COPD: results from the ASPIRE registry. Eur Respir J 2013; 41: 1292-1301
• 90 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
• 91 Washko GR, Nardelli P, Ash SY. et al. Arterial Vascular Pruning, Right Ventricular Size, and Clinical Outcomes in Chronic Obstructive Pulmonary Disease. A Longitudinal Observational Study. Am J Respir Crit Care Med 2019; 200: 454-461
• 92 Marchetti T, Ribi C, Perneger T. et al. Prevalence, persistence and clinical correlations of classic and novel antiphospholipid antibodies in systemic lupus erythematosus. Rheumatology (Oxford) 2018; 57: 1350-1357
• 93 Perez-Penate GM, Rua-Figueroa I, Julia-Serda G. et al. Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: Prevalence and Predictors. J Rheumatol 2016; 43: 323-329