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| Year : 2011 | Volume
: 1
| Issue : 1 | Page : 122-124 |
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Diagnostic and therapeutic algorithm for pulmonary arterial hypertension
Ankit A Desai, Roberto F Machado
Department of Medicine (Section of Pulmonary, Critical Care, Sleep and Allergy Medicine and Section of Cardiology), Institute for Personalized Respiratory Medicine, University of Illinois, Chicago, Illinois, USA
| Date of Web Publication | 16-Mar-2011 |
Correspondence Address:
Ankit A Desai
Department of Medicine, University of Illinois COMRB 3128 (MC 719), 909 South Wolcott Avenue, Chicago, Illinois 60612
USA
DOI: 10.4103/2045-8932.78096 PMID: 22034600
How to cite this article:
Desai AA, Machado RF. Diagnostic and therapeutic algorithm for pulmonary arterial hypertension. Pulm Circ 2011;1:122-4 |
 Pulmonary Arterial Hypertension Diagnostic Algorithm | |  |
Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (mPAP) ≥25 mmHg, irrespective of etiology. In contrast to PH, the definition of pulmonary arterial hypertension (PAH) requires the exclusion of elevated pulmonary venous pressure, an established cause of PH, as reflected by a normal wedge pressure or left ventricular end-diastolic pressure (LVEDP) (≤15 mmHg). If PH is suspected in a patient, suitable screening tests are conducted to confirm the presence of PH and delineate the etiology to appropriately tailor an optimal therapeutic regimen. The diagnostic algorithm [Figure 1] reflects an integration of assessment pathways that help differentiate patients with WHO groups II-IV of pulmonary hypertension from WHO group I PAH as well as the subgroups of PAH. Caution is advised to apply the algorithm to any individual patient as the evaluation process of any patient with suspected PH requires a variety of investigations intended to confirm PH and the specific PAH subtype and, once confirmed, evaluate the functional and hemodynamic impairments of those patients. Right heart catheterization is universally considered to be an indispensable part of the diagnostic assessment. | Figure 1: PAH diagnostic algorithm. (ABG - Arterial blood gas; ALK-1 - Activin-receptor-like kinase; ANA - Anti-nuclear antibodies; BMPR2 - Bone morphogenetic protein receptor 2; CHD - Congenital heart disease; CMR - Cardiac magnetic resonance; CT - Computed tomography; CTD - Connective tissue disease; ECG - Electrocardiogram; FMHx - Family medical history; HHT - Hereditary hemorrhagic telangiectasia; HRCT - High-resolution computed tomography; LFTs - Liver function tests; LH - Left heart; PAP - Pulmonary arterial pressure; LVEDP - Left ventricular end-diastolic pressure; PAH - Pulmonary arterial hypertension; IPAH - Idiopathic pulmonary arterial hypertension; PCH - Pulmonary capillary hemangiomatosis; PE - Pulmonary thromboembolic disease; PFT - Pulmonary function test; PH - Pulmonary hypertension; PVOD - Pulmonary venoocclusive disease; RHC - Right heart catheterization; TEE - Transesophageal echocardiography; TTE - Transthoracic echocardiography; US - Ultrasonography; V/Q - Ventilation/perfusion lung scan; WHO - World Health Organization)
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| PAH RX Algorithm | | |
The treatment algorithm is based on a consensus of the PH community based on the majority of randomized controlled clinical trials (RCTs) for PAH. The grading system is based on the recently published consensus for these drug trials. [1] Additionally, most trials were conducted in idiopathic or heritable PAH and PAH associated with scleroderma or anorexigen use; hence, the therapeutic effect on other PAH subpopulations may not be equal. Although there are no RCTs to substantiate the use of the following therapies, oral anticoagulation, diuretics in cases of fluid retention and supplemental oxygen in cases of hypoxemia (oxygen saturation <92%) are still considered the first line of treatment in patients with PAH. Acute vasoreactivity testing should be performed in all patients with PAH. Vasoreactivity is defined as reduction of mPAP ≥10 mmHg to reach an mPAP ≤40 mmHg with a normalized or increased cardiac output with acute pulmonary vasodilator challenge (either inhaled nitric oxide, adenosine or intravenous epoprostenol). Vasoreactive patients should be treated with high-dose calcium channel blockers with maintenance of response, defined as WHO functional class I or II with near-normal hemodynamic status, being confirmed by repeat right heart catheterization and clinical assessment after 3-6 months of treatment. Non-responders to acute vasoreactivity testing are defined both hemodynamically as well as by functional class II-IV, and should be considered candidates for other treatments as shown in [Figure 2]. The choice of the agent is dependent on a variety of factors, including route of administration, side-effect profile, patient preference and the physician's experience and clinical judgment. Continuous IV epoprostenol is the first-line therapy for IPAH and HPAH patients in WHO functional class IV because of its demonstrated survival benefit. Combination therapy should be considered for patients who fail monotherapy.[39] | Figure 2: PAH treatment algorithm. (PAH - Pulmonary arterial hypertension; FC - Functional class; ERA - Endothelin receptor antagonist; PDE-I - Phosphodiesterase type 5 inhibitor; IV - Intravenous; PO - Oral; SC - Subcutaneous; NA - Not approved; WHO - World Health Organization; PAP - Pulmonary arterial pressure; RCT - Randomized controlled trial. Strength of recommendation: A - Strong recommendation; B - Moderate recommendation; C - Weak recommendation; D - Negative recommendation; E/A - Strong recommendation on the basis of expert opinion only; E/B - Moderate recommendation on the basis of expert opinion only; E/C - Weak recommendation on the basis of expert opinion only; E/D - Negative recommendation on the basis of expert opinion only)
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| References | | |
| 1. | Barst RJ, Gibbs JS, Ghofrani HA, Hoeper MM, McLaughlin VV, Rubin LJ, et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol 2009;54:78-84. 
|
| 2. | Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992;327:76-81.
|
| 3. | Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation 1987;76:135-41.
|
| 4. | Raffy O, Azarian R, Brenot F, Parent F, Sitbon O, Petitpretz P, et al. Clinical significance of the pulmonary vasodilator response during short-term infusion of prostacyclin in primary pulmonary hypertension. Circulation 1996;93:484-8.
|
| 5. | Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children. Circulation 1999;99:1197-208.
|
| 6. | Sitbon O, Humbert M, Jaïs X, Ioos V, Hamid AM, Provencher S, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005;111:3105-11.
|
| 7. | Yung D, Widlitz AC, Rosenzweig EB, Kerstein D, Maislin G, Barst RJ. Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation 2004;110:660-5.
|
| 8. | Rich S, Seidlitz M, Dodin E, Osimani D, Judd D, Genthner D, et al. The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest 1998;114:787-92.
|
| 9. | Fuster V, Steele PM, Edwards WD, Gersh BJ, McGoon MD, Frye RL. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984;70:580-7.
|
| 10. | Frank H, Mlczoch J, Huber K, Schuster E, Gurtner HP, Kneussl M. The effect of anticoagulant therapy in primary and anorectic drug-induced pulmonary hypertension. Chest 1997;112:714-21.
|
| 11. | Johnson SR, Mehta S, Granton JT. Anticoagulation in pulmonary arterial hypertension: a qualitative systematic review. Eur Respir J 2006;28:999-1004.
|
| 12. | Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001;358:1119-23.
|
| 13. | Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002;346:896-903.
|
| 14. | Galiè N, Beghetti M, Gatzoulis MA, Granton J, Berger RM, Lauer A, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation 2006;144:48-54.
|
| 15. | Galiè N, Rubin Lj, Hoeper M, Jansa P, Al-Hiti H, Meyer G, et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 2008;371:2093-100.
|
| 16. | Galiè N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation 2009;119:2894-903.
|
| 17. | Galiè N, Hinderliter AL, Torbicki A, Fourme T, Simonneau G, Pulido T, et al. Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension. J Am Coll Cardiol 2003;41:1380-6.
|
| 18. | 18 Galiè N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, 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.
|
| 19. | Galié N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM, et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2005;46:529-35.
|
| 20. | Oudiz RJ, Galiè N, Olschewski H, Torres F, Frost A, Ghofrani HA, et al. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol 2009;54:1971-81.
|
| 21. | Galiè N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005;353:2148-57.
|
| 22. | Galiè N, Humbert M, Vachiéry JL, Vizza CD, Kneussl M, Manes A, et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2002;39:1496-502.
|
| 23. | Barst RJ, McGoon M, McLaughlin V, Tapson V, Rich S, Rubin L, et al. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2003;41:2119-25.
|
| 24. | Olschewski H, Simonneau G, Galiè N, Higenbottam T, Naeije R, Rubin LJ, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347:322-9.
|
| 25. | McLaughlin VV, Benza RL, Rubin LJ, Channick RN, Voswinckel R, Tapson VF, et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol 2010;55:915-22.
|
| 26. | Higenbottam TW, Butt AY, Dinh-Xaun AT, Takao M, Cremona G, Akamine S. Treatment of pulmonary hypertension with the continuous infusion of a prostacyclin analogue, iloprost. Heart 1998;79:175-9.
|
| 27. | Rubin LJ, Mendoza J, Hood M, McGoon M, Barst R, Williams WB, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med 1990;112:485-91.
|
| 28. | Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, et al. A comparison of continuous intravenous epoprostenol (prostacyclin)
|
| 29. | with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 1996;334:296-301.
|
| 30. | Tapson VF, Gomberg-Maitland M, McLaughlin VV, Benza RL, Widlitz AC, Krichman A, et al. Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest 2006;129:683-8.
|
| 31. | Gomberg-Maitland M, Tapson VF, Benza RL, McLaughlin VV, Krichman A, Widlitz AC, et al. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med 2005;172:1586-9.
|
| 32. | Simonneau G, Barst RJ, Galie N, Naeije R, Rich S, Bourge RC, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002;165:800-4.
|
| 33. | McLaughlin VV, Gaine SP, Barst RJ, Oudiz RJ, Bourge RC, Frost A, et al. Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension. J Cardiovasc Pharmacol 2003;41:293-9.
|
| 34. | McLaughlin VV, Benza RL, Rubin LJ, Channick RN, Voswinckel R, Tapson VF, et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol 2010;55:1915-22.
|
| 35. | Simonneau G, Rubin LJ, Galiè N, Barst RJ, Fleming TR, Frost AE, et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med 2008;149:521-30.
|
| 36. | Humbert M, Barst RJ, Robbins IM, Channick RN, Galiè N, Boonstra A, et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 2004;24:353-9.
|
| 37. | Hoeper MM, Leuchte H, Halank M, Wilkens H, Meyer FJ, Seyfarth HJ, et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J2006;28:691-4.
|
| 38. | McLaughlin VV, Oudiz RJ, Frost A, Tapson VF, Murali S, Channick RN, 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.
|
| 39. | McLaughlin VV, Benza RL, Rubin LJ, Channick RN, Voswinckel R, Tapson VF, et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol 2010;55:1915-22.
|
[Figure 1], [Figure 2]
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