Pulmonary Arterial Hypertension: Evaluation of the Newly Diagnosed Patient

ABSTRACT

With a quickly growing range of therapeutic options precise prognostic stratification became particularly important for clinical decision making in patients with pulmonary arterial hypertension (PAH). Assessment of disease-specific functional class remains the simplest method and is a fairly reliable way of assessing severity of PAH, and current guidelines recommend a therapeutic algorithm based on functional class evaluation. Six-minute walk is the most widely used test assessing exercise tolerance both in clinical practice and in clinical trials testing new therapies in PAH. Right heart catheterization with a vasoreactivity test is mandatory to identify a subgroup that has good long-term prognosis when treated with calcium channel blockers alone. Echocardiographic variables of documented prognostic value in PAH are not those directly correlated with pulmonary arterial pressure (PAP). Instead, the presence of pericardial effusion, enlarged right atrium, and elevated Doppler index of right ventricular performance have been the most consistently reported signs of poor prognosis. Low or decreasing brain natriuretic peptide (BNP) suggests a good outcome whereas troponin T leak persisting despite therapy is a poor prognostic sign. Biomarkers seem particularly useful for noninvasive follow-up of patients with PAH, and due to simplicity and low costs may successfully compete with echocardiography.

KEYWORDS

Pulmonary arterial hypertension - prognosis - six-minute walk test - echocardiography - biomarkers - vasoreactivity testing

REFERENCES

• 1 McLaughlin V V, Presberg K W, Doyle R L et al.. Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.  Chest. 2004;  126 78S-92S
• 2 Frank H, Mlczoch J, Huber K, Schuster E, Gurtner H P, Kneussl M. The effect of anticoagulant therapy in primary and anorectic drug-induced pulmonary hypertension.  Chest. 1997;  112 714-721
• 3 Hoeper M M, Oudiz R J, Peacock A et al.. End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives.  J Am Coll Cardiol. 2004;  43 48S-55S
• 4 Badesch D B, Abman S H, Ahearn G S et al.. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.  Chest. 2004;  126 35S-62S
• 5 Galie N, Torbicki A, Barst R et al.. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology.  Eur Heart J. 2004;  25 2243-2278
• 6 D'Alonzo G E, Barst R J, Ayres S M et al.. Survival in patients with primary pulmonary hypertension: results from a national prospective registry.  Ann Intern Med. 1991;  115 343-349
• 7 Sitbon O, Humbert M, Nunes H et al.. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival.  J Am Coll Cardiol. 2002;  40 780-788
• 8 McLaughlin V V, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy.  Circulation. 2002;  106 1477-1482
• 9 Raymond R J, Hinderliter A L, Willis P W et al.. Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension.  J Am Coll Cardiol. 2002;  39 1214-1219
• 10 Miyamoto S, Nagaya N, Satoh T et al.. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension: comparison with cardiopulmonary exercise testing.  Am J Respir Crit Care Med. 2000;  161 487-492
• 11 Torbicki A, Kurzyna M, Kuca P et al.. Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension.  Circulation. 2003;  108 844-848
• 12 Frost A E, Langleben D, Oudiz R et al.. The 6-min walk test (6MW) as an efficacy endpoint in pulmonary arterial hypertension clinical trials: demonstration of a ceiling effect.  Vascul Pharmacol. 2005;  43 36-39
• 13 Paciocco G, Martinez F J, Bossone E, Pielsticker E, Gillespie B, Rubenfire M. Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension.  Eur Respir J. 2001;  17 647-652
• 14 Wensel R, Opitz C F, Anker S D et al.. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing.  Circulation. 2002;  106 319-324
• 15 Sandoval J, Bauerle O, Palomar A et al.. Survival in primary pulmonary hypertension: validation of a prognostic equation.  Circulation. 1994;  89 1733-1744
• 16 Sitbon O, Humbert M, Jagot J L et al.. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension.  Eur Respir J. 1998;  12 265-270
• 17 Rich S, Kaufmann E, Levy P S. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension.  N Engl J Med. 1992;  327 76-81
• 18 Barst R J, McGoon M, Torbicki A et al.. Diagnosis and differential assessment of pulmonary arterial hypertension.  J Am Coll Cardiol. 2004;  43 40S-47S
• 19 Hinderliter A L, Willis P W, Long W et al.. Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension.  Am J Cardiol. 1999;  84 481-484, A10
• 20 Eysmann S B, Palevsky H I, Reichek N, Hackney K, Douglas P S. Two-dimensional and Doppler-echocardiographic and cardiac catheterization correlates of survival in primary pulmonary hypertension.  Circulation. 1989;  80 353-360
• 21 Tei C, Dujardin K S, Hodge D O et al.. Doppler echocardiographic index for assessment of global right ventricular function.  J Am Soc Echocardiogr. 1996;  9 838-847
• 22 Yeo T C, Dujardin K S, Tei C, Mahoney D W, McGoon M D, Seward J B. Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension.  Am J Cardiol. 1998;  81 1157-1161
• 23 Senbaklavaci O, Kaneko Y, Bartunek A et al.. Rupture and dissection in pulmonary artery aneurysms: incidence, cause, and treatment: review and case report.  J Thorac Cardiovasc Surg. 2001;  121 1006-1008
• 24 Galie N, Hinderliter A L, Torbicki A 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 1380-1386
• 25 Voelkel M A, Wynne K M, Badesch D B, Groves B M, Voelkel N F. Hyperuricemia in severe pulmonary hypertension.  Chest. 2000;  117 19-24
• 26 Nagaya N, Nishikimi T, Uematsu M et al.. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension.  Circulation. 2000;  102 865-870