Diagnosis and Treatment of Pulmonary Hypertension

Login or register to view PDF.
DOI
http://dx.doi.org/10.15420/ecr.2012.8.3.213

Abstract

Pulmonary hypertension is a relatively common finding in patients with left heart disease and lung hypoxic disease. Nonetheless, some types of pulmonary hypertension, such as pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, are rare. Despite the rarity of these diseases their impact on patients' lives and healthcare system is significant because of their poor prognosis. In this review article we describe step-by-step the diagnostic algorithm for all types of pulmonary hypertension, focusing on the early detection of signs and symptoms of the disease. We are also reviewing the current vasodilatory treatments for pulmonary arterial hypertension and the therapeutic options for chronic thromboembolic pulmonary hypertension.

To view the full article in PDF or eBook formats, please click on the icons above.

References
  1. Hoeper MM, Barbera JA, Channick RN, et al., Diagnosis and treatment of non-Pulmonary Arterial Hypertension Pulmonary Hypertension, J Am Coll Cardiol, 2009;54(1):S85–96.
    Crossref | PubMed
  2. Galie N, Hoeper M, Humbert M, et al., Guidelines for the diagnosis and treatment of pulmonary hypertension, Eur Heart J, 2009;30:2493–537.
    Crossref | PubMed
  3. Meluzin J, Spinarova L, Bakala J, et al., Pulsed Doppler tissue imaging of the velocity of the tricuspid annular systolic motion; a new, rapid and non-invasive method of evaluating right ventricular systolic function, Eur Heart J, 2001;22:340–8.
    Crossref | PubMed
  4. Lopez-Candales A, Dohi K, Rajagopalan N, et al., Defining normal variables of right ventricular size and function in pulmonary hypertension: an echocardiographic study, Postgrad Med J, 2008;84:40–5.
    Crossref | PubMed
  5. Lanzarini L, Fontana A, Campana C, Klersy C, Two simple echo-Doppler measurements can accurately identify pulmonary hypertension in the large majority of patients with chronic heart failure, J Heart Lung Transplant, 2005;24:745–54.
    Crossref | PubMed
  6. Brechot N, Gambotti L, Lafitte S, Roudaut R, Usefulness of right ventricular isovulomic relaxation time in predicting systolic pulmonary artery pressure, Eur J Echocardiogr, 2008;9:547–54.
    Crossref | PubMed
  7. Vonk MC, Sander MH, van den Hoogen FH, et al., Right ventricular tei-index: a tool to increase the accuracy of non-invasive of pulmonary arterial hypertension in connective tissue diseases, Eur J Echocardiogr, 2007;8:317–21.
    Crossref | PubMed
  8. Paulus W, Tschope C, Sanderson JE, et al., 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 Association of the European Society of Cardiology, Eur Heart J, 2007;28:2539–56.
    Crossref | PubMed
  9. Lester S, Tajik AJ, Nishimura R, et al., Unlocking the mysteries of diastolic dysfunction, J Am Coll Cardiol, 2008;51:679–89.
    Crossref | PubMed
  10. Lopez-Candales A, Bazaz R, Elderman K, Gulyasy B, Altered early let ventricular diastolic wall velocities in pulmonary hypertension: a Tissue Doppler Imaging, Echocardiography, 2009;26(10):1159–65.
    Crossref | PubMed
  11. Tonelli AR, Plana JC, Heresi GA, Dweik RA, Prevalence and prognostic value of left ventricular diastolic dysfunction in idiopathic and heritable pulmonary arterial hypertension, Chest, 2011 [Epub ahead of print].
  12. Bonderman D, Wexberg P, Martischnig AM, et al., A noninvasive algorithm to exclude pre-capillary pulmonary hypertension, Eur Respir J, 2011;37:1096–103.
    Crossref | PubMed
  13. Pepke-Zaba J, Delcroix M, Lang I, et al., Chronic thromboembolic pulmonary hypertension: results from an international prospective registry, Circulation, 2011;124:1973–81.
    Crossref | PubMed
  14. Worsley DF, Alavi A, Comprehensive analysis of the results of the PIOPED study, J Nucl Med, 1995;36:2380–7.
    PubMed
  15. Montani D, Price LC, Dorfmuller P, et al., Pulmonary veno-occlusive disease, Eur Respir J, 2009;33:189–200.
    Crossref | PubMed
  16. Califf RM, Adams KF, McKenna WJ, et al., 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.
    Crossref | PubMed
  17. Kirkby NS, Hadoke PW, Bagnall AJ, Webb DJ, The endothelin system as a therapeutic target in cardiovascular disease: great expectations or bleak house?, Br J Pharmacol, 2008;153:1105–19.
    Crossref | PubMed
  18. Seed A, Love MP, McMurray JJ, Clinical experience with endothelin receptor antagonists in chronic heart failure, Heart Fail Rev, 2001;6:317–23.
    PubMed
  19. Guazzi M, Samaja M, Arena R, et al., Long-term use of sildeafil in the therapeutic management of heart failure, J Am Coll Cardiol, 2007;50:2136–44.
    Crossref | PubMed
  20. Lewis GD, Shah R, Shahzad K, et al., Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension, Circulation, 2007;116:1555–62.
    Crossref | PubMed
  21. National Heart, Lung, and Blood Institute (NHLBI), Evaluating the effectiveness of sildenafil at improving health outcomes and exercise ability in people with diastolic heart failure (The RELAX study). NCT00763867, 2008. Available at: http://clinicaltrials.gov/ct2/show/NCT00763867 (accessed 23 May 2012).
  22. Koegh AM, Mayer E, Benza RL, et al., Interventional and surgical modalities of treatment in pulmonary hypertension, J Am Coll Cardiol, 2009;54:S67–77.
    Crossref | PubMed
  23. Rubin LJ, Badesch DB, Barst RJ, et al., Bosentan therapy for pulmonary arterial hypertension, N Engl J Med, 2002;346:896–903.
    Crossref | PubMed
  24. Galie N, Beghetti M, Gatzoulis MA, et al., Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study, Circulation, 2006;114:48–54.
    Crossref | PubMed
  25. Galie N, Rubin LJ, Hoeper M, et al., Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double blind, randomized, controlled trial, Lancet, 2008;371:2093–100.
    Crossref | PubMed
  26. Galie N, Olschewski H, Oudiz RJ, et al., Ambrisentan for the treatment of pulmonary arterial hypertension: results of the Ambrisentan in Pulmonary Arterial Hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES ) study 1 and 2, Circulation, 2008;117:3010–9.
    Crossref | PubMed
  27. Galie N, Badesch D, Oudiz R, et al., Ambrisentan therapy for pulmonary arterial hypertension, J Am Coll Cardiol, 2005;46:529–35.
    Crossref | PubMed
  28. McLaughlin VV, Long-term ambrisentan therapy for pulmonary arterial hyprtension in patients who previously received placebo in ARIES-1 or ARIES-2 (abstr.), Am J Respir Crit Care Med, 2008;177:A697.
  29. Galie N, Ghofrani HA, Torbicki A, et al., Sildenafil citrate therapy for pulmonary arterial hypertension, N Engl J Med, 2005;353:2148–57.
    Crossref | PubMed
  30. Galie N, Brundage B, Ghofrani A, et al., Tadalafil therapy for pulmonary arterial hypertension, Circulation, 2009;119:2894–903.
    Crossref | PubMed
  31. Wilkins MR, Paul GA, Strange JW, et al., Sildenafil versus endothelin receptor antagonist for pulmonary hypertension (SERAPH study), Am J Respir Crit Care Med, 2005;171:1292–7.
    Crossref | PubMed
  32. Barst RJ, Rubin LJ, Long WA, 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.
    Crossref | PubMed
  33. Humbert M, Barst RJ, Robbins IM, et al., Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2, Eur Respir J, 2004;24:353–9.
    Crossref | PubMed
  34. McLaughlin VV, Oudiz R, Frost A, et al., Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension, Am J Respir Crit Care Med, 2006;174:1257–63.
    Crossref | PubMed
  35. Simonneau G, Rubin LJ, Galie N, et al., Addition of ildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension, Ann Intern Med 2008;149:521–30.
    Crossref | PubMed
  36. Cheri Hudson, Clinical Disclosure Advisor, GSK Clinical Disclosure, A study of first-line ambrisentan and tadalafil combination therapy in subjects with pulmonary arterial hypertension (PAH) (AMBITION), NCT01178073, 2010. Available at: http://clinicaltrials.gov/ct2/show/NCT01178073 (Accessed 23 May 2012).
  37. Actelion, Study of ACT-064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertension (SERAPHIN trial). NCT00660179, 2008. Available at: http://clinicaltrials.gov/ct2/show/NCT00660179 (accessed 23 May 2012).
  38. Actelion, ACT-293987 in pulmonary arterial hypertension, NCT01106014. Available at: http://clinicaltrials.gov/ct2/show/NCT01106014?term=NCT01 106014&rank=1 (accessed 23 May 2012).
  39. United Therapeutics, A 16-week, international, multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of oral UT-15C sustained release tablets in subjects with pulmonary arterial hypertension (FREEDOM-C2). NCT00887978, 2009. Available at: http://clinicaltrials.gov/ct2/show/NCT00887978 (accessed 23 May 2012).
  40. Therapeutic Area Head, Bayer Healthcare, A study to evaluate efficacy and safety of oral BAY63-2521 in patients with CTEPH (CHEST-1). NCT00855465, 2008. Available at: http://clinicaltrials.gov/ct2/show/NCT00855465 (accessed 23 May 2012).
  41. Novartis ( Novartis Pharmaceuticals ), Imatinib (QTI571) in Pulmonary Arterial Hypertension (IMPRES), NCT00902174, 2009. Available at: http://clinicaltrials.gov/ct2/show/NCT00902174 (accessed 23 May 2012).
  42. Shah SJ, Gomberg-Maitland M, Thenappan T, Rich S, Selective serotonin reuptake inhibitors and the incidence and outcome of pulmonary hypertension, Chest, 2009;136:694–700.
    Crossref | PubMed
  43. Brown LM, Chen H, Halpern S, et al., Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL registry, Chest, 2011;140:19–26.
    Crossref | PubMed