Pulmonale Hypertonie bei Linksherzerkrankungen

Zusammenfassung

Die 2009 veröffentlichen Europäischen Leitlinien zur Diagnostik und Therapie der pulmonalen Hypertonie (PH) sind nunmehr auch in Deutschland gültig. Während sich die Leitlinien eingehend mit der pulmonal arteriellen Hypertonie (PAH) befassen, wird die häufig vorkommende PH infolge von Linksherzerkrankungen nur relativ kurz behandelt. Aktuell lässt sich in zunehmendem Maße ein unkritischer Einsatz gezielter PAH-Medikamente bei Patienten mit PH infolge von Linksherzerkrankungen beobachten, obwohl keine entsprechenden Wirksamkeitsdaten vorliegen. Diese Entwicklung gibt Anlass zur Sorge. Andererseits ist die PH bei Patienten mit Linksherzinsuffizienz ein häufiges Problem welches für die Morbidität und Prognose der Patienten bedeutsam ist, so dass sich bei ausgewählten Patienten die Frage nach einer gezielten Behandlung der PH stellt. Diesbezüglich sind für die praktische Umsetzung der Europäischen Leitlinien in Deutschland zahlreiche spezifische Gesichtspunkte und bereits wieder neue Daten bedeutsam, die eine ausführliche Kommentierung der Leitlinien und in einigen Punkten eine Aktualisierung notwendig machen. Im Juni 2010 fand in Köln eine Konsensuskonferenz 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 in Deutschland. Dazu wurden verschiedene Arbeitsgruppen eingesetzt, von denen sich eine gezielt der PH bei Linksherzerkrankungen widmete. Die Ergebnisse und Empfehlungen dieser Arbeitsgruppe werden in dem vorliegenden Manuskript detailliert beschrieben.

Abstract

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, so that it may be speculated whether selected patients may benefit from targeted PH therapy. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several 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 2010, 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 PH due to left heart disease. This commentary summarizes the results and recommendations of this working group.

Schlüsselwörter

pulmonale Hypertonie - PH - pulmonal arterielle Hypertonie - PAH - Linksherzerkrankung - Herzinsuffizienz

Keywords

pulmonary hypertension - PH - pulmonary arterial hypertension - PAH - left heart disease - heart failure

Literatur

• 1 Abramson S V, Burke J F, Kelly Jr J J. et al . Pulmonary hypertension predicts mortality and morbidity in patients with dilated cardiomyopathy.  Ann Intern Med. 1992;  116 888-895
• 2 Alaeddini J, Uber P A, Park M H, Scott R L, Ventura H O, Mehra M R. Efficacy and safety of sildenafil in the evaluation of pulmonary hypertension in severe heart failure.  Am J Cardiol. 2004;  94 1475-1477
• 3 Anand I, McMurray J, Cohn J N. et al, EARTH investigators . Long-term effects of darusentan on left ventricular remodeling and clinical outcomes in the Endothelin A Receptor Antagonist Trial in Heart Failure (EARTH): randomized, double-blind, placebo-controlled trial.  Lancet. 2004;  364 437-354
• 4 Aurigemma G P, Gaasch W H. Clinical practice. Diastolic heart failure.  N Engl J Med. 2004;  351 1097-1105
• 5 Badesch B D, Champion H C, Gomez-Sanchez M A, Hoeper M, Loyd J, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz R, Torbicki A. Diagnosis and assessment of pulmonary arterial hypertension.  J Am Coll Cardiol. 2009;  54 S55-S56
• 6 Barst R J, Rubin L J, Long W A. et al . A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension The Primary Pulmonary Hypertension Study Group.  N Engl J Med. 1996;  334 296-302
• 7 Behling A, Rohde L E, Colombo F C, Goldraich L A, Stein R, Clausell N. Effects of 5Ž-phosphodiesterase four-week long inhibition with sildenafil in patients with chronic heart failure: a double-blind, placebo-controlled clinical trial.  J Cardiac Fail. 2008;  14 189-197
• 8 Califf R M, Adams K F, McKenna W J, Gheorghiade M, Uretsky B F, McNulty S E, Darius H, Schulman K, Zannad F, Handberg-Thurmond E, Harrell Jr F E, Wheeler W, Soler-Soler J, Swedberg K. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST).  Am Heart J. 1997;  134 44-54
• 9 Cappola T P, Felker G M, Kao W H, Hare J M, Baughman K L, Kasper E K. Pulmonary hypertension and risk of death in cardiomyopathy: patients with myocarditis are at higher risk.  Circulation. 2002;  105 1663-1668
• 10 Chang P P, Longenecker J C, Wang N Y, Baughman K L, Conte J V, Hare J M, Kasper E K. Mild vs severe pulmonary hypertension before heart transplantation: different effects on posttransplantation pulmonary hypertension and mortality.  J Heart Lung Transplant. 2005;  24 998-1007
• 11 Costanzo M R, Augustine S, Bourge R, Bristow M, O’Connell J B, Driscoll D, Rose E. Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association.  Circulation. 1995;  92 3593-3612
• 12 Costard-Jackle A, Fowler M B. Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group.  J Am Coll Cardiol. 1992;  19 48-54
• 13 Davidson C J, Fishman R F, Bonow R O. Cardiac catheterization. In: Libby P, Bonow RO, Mann DL (Eds.) Braunwald’s Heart Disease. 8th ed. 2007: 177-203
• 14 De Groote P, Millaire A, Foucher-Hossein C, Nugue O, Marchandise X, Ducloux G, Lablanche J M. Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure.  J Am Coll Cardiol. 1998;  32 948-954
• 15 Delgado J F. The right heart and pulmonary circulation (III): The pulmonary circulation in heart failure.  Rev Esp Cardiol. 2010;  63 334-345
• 16 Delgado J F, Conde E, Sanchez V, Lopez-Rios F, Gomez-Sanchez M A, Escribano P, Sotelo T, Gomez de la Camara A, Cortina J, de la Calzada C S. Pulmonary vascular remodeling in pulmonary hypertension due to chronic heart failure.  Eur J Heart Fail. 2005;  7 1011-1016
• 17 Dickstein K, Cohen-Solal A, Filippatos G, McMurray J JV, Ponikowski P, Poole-Wilson P A, Stromberg A, van Veldhuisen D J, Atar D, Hoes A W, Keren A, Mebazaa A, Nieminen M, Priori S G, Swedberg K, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen S D, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano J L. ESC Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of European Society of Cardiology . ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).  Eur Heart J. 2008;  29 2388-2442
• 18 Faggiano P, Antonini-Canterin F, Ribichini F. et al . Pulmonary artery hypertension in adult patients with symptomatic valvular aortic stenosis.  Am J Cardiol. 2000;  85 204-208
• 19 Fisher M R, Forfia P R, 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
• 20 Galiè N, Hoeper M M, Humbert M. et al . Guidelines for the diagnosis and treatment of pulmonary hypertension: The 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 the International Society of Heart and Lung Transplantation (ISHLT).  Eur Heart J. 2009;  30 2493-2537
• 21 Galie N, Hoeper M M, Humbert M. et al . Guidelines for the diagnosis and treatment of pulmonary hypertension. The 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 the International Society of Heart and Lung Transplantation (ISHLT).  Eur Respir J. 2009;  34 1219-1263
• 22 Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, Arbustini E, Recusani F, Tavazzi L. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure.  J Am Coll Cardiol. 2001;  37 183-188
• 23 Gnaegi A, Feihl F, Perret C. Intensive care physicians’ insufficient knowledge of right-heart catheterization at the bedside: time to act?.  Crit Care Med. 1997;  25 213-220
• 24 Grigioni F, Potena L, Galie N, Fallani F, Bigliardi M, Coccolo F, Magnani G, Manes A, Barbieri A, Fucili A, Magelli C, Branzi A. Prognostic implications of serial assessments of pulmonary hypertension in severe chronic heart failure.  J Heart Lung Transplant. 2006;  25 1241-1246
• 25 Guazzi M, Guazzi M D. Endothelium-mediated modulation of ergoreflex and improvement in exercise ventilation by acute sildenafil in heart failure patients.  Clin Pharmacol Ther. 2008;  83 336-341
• 26 Guazzi M, Samaja M, Arena R, Vicenzi M, Guazzi M D. Long-term use of sildenafil in the therapeutic management of heart failure.  J Am Coll Cardiol. 2007;  50 2136-2144
• 27 Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi M D. The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure.  J Am Coll Cardiol. 2004;  44 2339-2348
• 28 Halpern S D, Taichman D B. Misclassification of pulmonary hypertension due to reliance on pulmonary capillary wedge pressure rather than left ventricular end-diastolic pressure.  Chest. 2009;  136 37-43
• 29 Haraldsson A, Kieler-Jensen N, Ricksten S. The additive pulmonary vasodilator effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension.  Anesth Analg. 2001;  93 1439-1445
• 30 Hoeper M, Barbera J A, Channick R, Hassoun P M, Lang I, Manes A, Martinez F, Naeije R, Olschewski H, Pepke-Zaba J, Redfield M, Robbins I, Souza R, Torbicki A, McGoon M. Diagnosis, assessment, and treatment of non-PAH pulmonary hypertension.  J Am Coll Cardiol. 2009;  54 S85-S96
• 31 Hoeper M M, Ghofrani H A, Gorenflo M, Grünig E, Schranz D, Rosenkranz S. Diagnostik und Therapie der pulmonalen Hypertonie: Europäische Leitlinien 2009.  Pneumologie. 2010;  64 401-414
• 32 Jacka M J, Cohen M M, To T, Devitt J H, Byrick R. Pulmonary artery occlusion pressure estimation: how confident are anesthesiologists?.  Crit Care Med. 2002;  30 1197-1203
• 33 Kalra P R, Moon J C, Coats A J. Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study spell the end for non-selective endothelin antagonism in heart failure?.  Int J Cardiol. 2002;  85 195-197
• 34 Kjaergaard J, Akkan D, Iversen K K, Kjoller E, Kober L, Torp-Pedersen C, Hassager C. Prognostic importance of pulmonary hypertension in patients with heart failure.  Am J Cardiol. 2007;  99 1146-1150
• 35 Kovac G, Berghold A, Scheidl  S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects. A systematic review.  Eur Respir J. 2009;  34 888-894
• 36 Kuznetsova T, Herbots L, López B, Jin Y, Richart T, Thijs L, González A, Herregods M C, Fagard R H, Díez J, Staessen J A. Prevalence of left ventricular diastolic dysfunction in the general population.  Circ Heart Fail. 2009;  2 105-112
• 37 Lam C S, Roger V L, Rodeheffer R J, Borlaug B A, Enders F T, Redfield M M. Pulmonary hypertension in heart failure with preserved ejection fraction.  J Am Coll Cardiol. 2009;  53 1119-1126
• 38 Leuchte H H, Baumgartner R A, Nounou M E. et al . Brain natriuretic peptide is a prognostic parameter in chronic lung disease.  Am J Respir Crit Care Med. 2006;  173 744-750
• 39 Lewis G D, Lachmann J, Camuso J, Lepore J J, Shin J, Martinovic M E, Systrom D M, Bloch K D, Semigran M J. Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure.  Circulation. 2007;  115 59-66
• 40 Lewis G D, Shah R, Shahzad K, Camuso J M, Pappagianopoulos P P, Hung J, Tawakol A, Gerszten R E, Systrom D M, Bloch K D, Semigran M J. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension.  Circulation. 2007;  116 1555-1562
• 41 Luscher T F, Enseleit F, Pacher R, Mitrovic V, Schulze M R, Willenbrock R. et al . Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure (ET(A) Receptor Blockade Trial (HEAT).  Circulation. 2002;  106 2666-2672
• 42 Mc Laughlin V V, Archer S L, Badesch D B. et al . ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association.  J Am Coll Cardiol. 2009;  53 1573-1619
• 43 Mehra M R, Kobashigawa J, Starling R, Russell S, Uber P A, Parameshwar J. et al . Listing criteria for heart transplantation: International society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates – 2006.  J Heart Lung Transplant. 2006;  25 1024-1042
• 44 Moraes D L, Colucci W S, Givertz M M. Secondary pulmonary hypertension in chronic heart failure: the role of the endothelium in pathophysiology and management.  Circulation. 2000;  102 1718-1723
• 45 Morris A H, Chapman R H, Gardner R M. Frequency of technical problems encountered in the measurement of pulmonary artery wedge pressure.  Crit Care Med. 1984;  12 164-170
• 46 Nagendran J, Archer S L, Soliman D. et al . Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility.  Circulation. 2007;  116 238-248
• 47 Oudiz R J. Pulmonary hypertension associated with left-sided heart disease.  Clin Chest Med. 2007;  28 233-241
• 48 Packer M, Carver J R, Rodeheffer R J. et al . Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group.  N Engl J Med. 1991;  325 1468-1475
• 49 Packer M, McMurray J, Massie B M, Caspi A, Charlon V, Cohen-Solal A, Kiowski W, Kostuk W, Krum H, Levine B, Rizzon P, Soler J, Swedberg K, Anderson S, Demets D L. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study.  J Card Fail. 2005;  11 12-20
• 50 Paulus W J, Tschope C, Sanderson J E, Rusconi C, Flachskampf F A, Rademakers F E, Marino P, Smiseth O A, De Keulenaer G, Leite-Moreira A F, Borbely A, Edes I, Handoko M L, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser A G, Brutsaert D L. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology.  Eur Heart J. 2007;  28 2539-2550
• 51 Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX). 2010. Available at: www.clinicaltrials.gov
• 52 Rich S, McLaughlin V V. Endothelin receptor blockers in cardiovascular disease.  Circulation. 2003;  108 2184-2190
• 53 Roques F, Nashef S A, Michel P, Gauducheau E, de Vincentiis C, Baudet E, Cortina J, David M, Faichney A, Gabrielle F, Gams E, Harjula A, Jones M T, Pintor P P, Salamon R, Thulin L. Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients.  Eur J Cardiothorac Surg. 1999;  15 816-822
• 54 Rudski L G, Lai W W, Afilalo J, Hua L, Handschumacher M D, Chandrasekaran K, Solomon S D, Louie E K, Schiller N B. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography.  Am Soc Echocardiogr. 2010;  23 685-713
• 55 Sablotzki A, Czeslick E, Schubert S. et al . Iloprost improves hemodynamics in patients with severe chronic cardiac failure and secondary pulmonary hypertension.  Can J Anaesth. 2002;  49 1076-1080
• 56 Semigran M J, Cockrill B A, Kacmarek R. et al . Hemodynamic effects of inhaled nitric oxide in heart failure.  J Am Coll Cardiol. 1994;  24 982-988
• 57 Simonneau G, Robbins I M, Beghetti M, Channick R N, Delcroix M, Denton C P, Elliott C G, Gaine S P, Gladwin M T, Jing Z -C, Krowka M J, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension.  J Am Coll Cardiol. 2009;  54 S43-S54
• 58 Torre-Amione G, Young J B, Colucci W S, Lewis B S, Pratt C, Cotter G. et al . Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure.  J Am Coll Cardiol. 2003;  42 140-147
• 59 Tribouilloy C, Rusinaru D, Mahjoub H, Soulière V, Lévy F, Peltier M, Slama M, Massy Z. Prognosis of heart failure with preserved efection fraction: a 5 year prospective population-based study.  Eur Heart J. 2008;  29 339-347
• 60 Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A. Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology . ESC Committee for Practice Guidelines. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology.  Eur Heart J. 2007;  28 230-268
• 61 Zanchetti A, Cuspidi C, Comarella L, Rosei E A, Ambrosioni E, Chiariello M, Leonetti G, Mancia G, Pessina A C, Salvetti A, Trimarco B, Volpe M, Grassivaro N, Vargiu G. Left ventricular diastolic dysfunction in elderly hypertensives: Results of the APROS-diadys study.  J Hypertens. 2007;  25 2158-2167