Diagnosis and Hemodynamic Assessment of Pulmonary Arterial Hypertension

ABSTRACT

Pulmonary hypertension (PH) can occur as either a primary or a secondary process, and in general, its presence increases overall morbidity and mortality. Importantly, the majority of prior studies have been in the setting of idiopathic pulmonary arterial hypertension (IPAH); thus the following discussion focuses on IPAH. Because the majority of available diagnostic strategies lack sensitivity and specificity, the physician must maintain a high index of suspicion in considering PAH. This article provides an overview of the available diagnostic studies for PAH with a particular focus on hemodynamic assessment. Novel approaches to the often delayed diagnosis of PAH are being studied and are also discussed here.

KEYWORDS

Pulmonary hypertension - hemodynamic - echocardiogram - diagnosis - right heart catheterization

REFERENCES

• 1 Romberg E. Ueber sklerose der lungen arterie.  Dtsch Arch Klin Med. 1891;  48 197-206
• 2 Rich S, Dantzker D R, Ayres S M et al.. Primary pulmonary hypertension: a national prospective study.  Ann Intern Med. 1987;  107 216-223
• 3 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
• 4 Fishman A P. Handbook of Physiology. Bethesda, MD; American Physiological Society 1985
• 5 West J. Respiratory Physiology: The Essentials. 8th ed. Baltimore; Lippincott Williams & Wilkins 2008
• 6 McGoon M, Gutterman D, Steen V American College of Chest Physicians et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.  Chest. 2004;  126(1, Suppl) 14S-34S
• 7 McGoon M D, Krichman A, Farber H W et al.. Design of the REVEAL registry for US patients with pulmonary arterial hypertension.  Mayo Clin Proc. 2008;  83 923-931
• 8 Bossone E, Paciocco G, Iarussi D et al.. The prognostic role of the ECG in primary pulmonary hypertension.  Chest. 2002;  121 513-518
• 9 Henkens I R, Gan C T, van Wolferen S A et al.. ECG monitoring of treatment response in pulmonary arterial hypertension patients.  Chest. 2008;  134 1250-1257
• 10 Ahearn G S, Tapson V F, Rebeiz A, Greenfield Jr J C. Electrocardiography to define clinical status in primary pulmonary hypertension and pulmonary arterial hypertension secondary to collagen vascular disease.  Chest. 2002;  122 524-527
• 11 Algeo S, Morrison D, Ovitt T, Goldman S. Noninvasive detection of pulmonary hypertension.  Clin Cardiol. 1984;  7 148-156
• 12 Lupi E, Dumont C, Tejada V M, Horwitz S, Galland F. A radiologic index of pulmonary arterial hypertension.  Chest. 1975;  68 28-31
• 13 Teichmann V, Jezek V, Herles F. Relevance of width of right descending branch of pulmonary artery as a radiological sign of pulmonary hypertension.  Thorax. 1970;  25 91-96
• 14 Matthay R A, Schwarz M I, Ellis Jr J H et al.. Pulmonary artery hypertension in chronic obstructive pulmonary disease: determination by chest radiography.  Invest Radiol. 1981;  16 95-100
• 15 Chetty K G, Brown S E, Light R W. Identification of pulmonary hypertension in chronic obstructive pulmonary disease from routine chest radiographs.  Am Rev Respir Dis. 1982;  126 338-341
• 16 Schmidt H C, Kauczor H U, Schild H H et al.. Pulmonary hypertension in patients with chronic pulmonary thromboembolism: chest radiograph and CT evaluation before and after surgery.  Eur Radiol. 1996;  6 817-825
• 17 Sun X G, Hansen J E, Oudiz R J, Wasserman K. Pulmonary function in primary pulmonary hypertension.  J Am Coll Cardiol. 2003;  41 1028-1035
• 18 Meyer F J, Ewert R, Hoeper M M German PPH Study Group et al. Peripheral airway obstruction in primary pulmonary hypertension.  Thorax. 2002;  57 473-476
• 19 Meyer F J, Lossnitzer D, Kristen A V et al.. Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension.  Eur Respir J. 2005;  25 125-130
• 20 Kabitz H J, Schwoerer A, Bremer H C et al.. Impairment of respiratory muscle function in pulmonary hypertension.  Clin Sci (Lond). 2008;  114 165-171
• 21 Chang B, Schachna L, White B, Wigley F M, Wise R A. Natural history of mild-moderate pulmonary hypertension and the risk factors for severe pulmonary hypertension in scleroderma.  J Rheumatol. 2006;  33 269-274
• 22 Steen V, Medsger Jr T A. Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement.  Arthritis Rheum. 2003;  48 516-522
• 23 Launay D, Mouthon L, Hachulla E et al.. Prevalence and characteristics of moderate to severe pulmonary hypertension in systemic sclerosis with and without interstitial lung disease.  J Rheumatol. 2007;  34 1005-1011
• 24 Steen V D, Graham G, Conte C, Owens G, Medsger Jr T A. Isolated diffusing capacity reduction in systemic sclerosis.  Arthritis Rheum. 1992;  35 765-770
• 25 Hsu V M, Moreyra A E, Wilson A C et al.. Assessment of pulmonary arterial hypertension in patients with systemic sclerosis: comparison of noninvasive tests with results of right-heart catheterization.  J Rheumatol. 2008;  35 458-465
• 26 Oudiz R J. The role of exercise testing in the management of pulmonary arterial hypertension.  Semin Respir Crit Care Med. 2005;  26 379-384
• 27 Tolle J J, Waxman A B, Van Horn T L, Pappagianopoulos P P, Systrom D M. Exercise-induced pulmonary arterial hypertension.  Circulation. 2008;  118 2183-2189
• 28 Dantzker D R, D'Alonzo G E, Bower J S, Popat K, Crevey B J. Pulmonary gas exchange during exercise in patients with chronic obliterative pulmonary hypertension.  Am Rev Respir Dis. 1984;  130 412-416
• 29 Riley M S, Pórszász J, Engelen M P, Brundage B H, Wasserman K. Gas exchange responses to continuous incremental cycle ergometry exercise in primary pulmonary hypertension in humans.  Eur J Appl Physiol. 2000;  83 63-70
• 30 D'Alonzo G E, Gianotti L A, Pohil R L et al.. Comparison of progressive exercise performance of normal subjects and patients with primary pulmonary hypertension.  Chest. 1987;  92 57-62
• 31 Dantzker D R, Bower J S. Mechanisms of gas exchange abnormality in patients with chronic obliterative pulmonary vascular disease.  J Clin Invest. 1979;  64 1050-1055
• 32 Hansen J E, Ulubay G, Chow B F, Sun X G, Wasserman K. Mixed-expired and end-tidal CO₂ distinguish between ventilation and perfusion defects during exercise testing in patients with lung and heart diseases.  Chest. 2007;  132 977-983
• 33 Sun X G, Hansen J E, Oudiz R J, Wasserman K. Exercise pathophysiology in patients with primary pulmonary hypertension.  Circulation. 2001;  104 429-435
• 34 Markowitz D H, Systrom D M. Diagnosis of pulmonary vascular limit to exercise by cardiopulmonary exercise testing.  J Heart Lung Transplant. 2004;  23 88-95
• 35 Tolle J J, Waxman A B, Van Horn T L, Pappagianopoulos P P, Systrom D M. Exercise-induced pulmonary arterial hypertension.  Circulation. 2008;  118 2120-2121
• 36 Oudiz R J, Roveran G, Hansen J E, Sun X G, Wasserman K. Effect of sildenafil on ventilatory efficiency and exercise tolerance in pulmonary hypertension.  Eur J Heart Fail. 2007;  9 917-921
• 37 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
• 38 Guyatt G H, Sullivan M J, Thompson P J et al.. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure.  Can Med Assoc J. 1985;  132 919-923
• 39 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(2 Pt 1) 487-492
• 40 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
• 41 Rafanan A L, Golish J A, Dinner D S, Hague L K, Arroliga A C. Nocturnal hypoxemia is common in primary pulmonary hypertension.  Chest. 2001;  120 894-899
• 42 Minai O A, Pandya C M, Golish J A et al.. Predictors of nocturnal oxygen desaturation in pulmonary arterial hypertension.  Chest. 2007;  131 109-117
• 43 Hoeper M M, Pletz M W, Golpon H, Welte T. Prognostic value of blood gas analyses in patients with idiopathic pulmonary arterial hypertension.  Eur Respir J. 2007;  29 944-950
• 44 Njaman W, Iesaki T, Iwama Y, Takasaki Y, Daida H. Serum uric acid as a prognostic predictor in pulmonary arterial hypertension with connective tissue disease.  Int Heart J. 2007;  48 523-532
• 45 Nagaya N, Uematsu M, Satoh T et al.. Serum uric acid levels correlate with the severity and the mortality of primary pulmonary hypertension.  Am J Respir Crit Care Med. 1999;  160 487-492
• 46 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
• 47 Leuchte H H, Holzapfel M, Baumgartner R A et al.. Clinical significance of brain natriuretic peptide in primary pulmonary hypertension.  J Am Coll Cardiol. 2004;  43 764-770
• 48 Hargett C W, Tapson V F. Brain natriuretic peptide: diagnostic and therapeutic implications in pulmonary arterial hypertension.  Semin Respir Crit Care Med. 2005;  26 385-393
• 49 Gan C T, McCann G P, Marcus J T et al.. NT-proBNP reflects right ventricular structure and function in pulmonary hypertension.  Eur Respir J. 2006;  28 1190-1194
• 50 Andreassen A K, Wergeland R, Simonsen S, Geiran O, Guevara C, Ueland T. N-terminal pro-B-type natriuretic peptide as an indicator of disease severity in a heterogeneous group of patients with chronic precapillary pulmonary hypertension.  Am J Cardiol. 2006;  98 525-529
• 51 Kampolis C, Plastiras S, Vlachoyiannopoulos P, Moyssakis I, Tzelepis G. The presence of anti-centromere antibodies may predict progression of estimated pulmonary arterial systolic pressure in systemic sclerosis.  Scand J Rheumatol. 2008;  37 278-283
• 52 Shah S J, Thenappan T, Rich S, Tian L, Archer S L, Gomberg-Maitland M. Association of serum creatinine with abnormal hemodynamics and mortality in pulmonary arterial hypertension.  Circulation. 2008;  117 2475-2483
• 53 Chu J W, Kao P N, Faul J L, Doyle R L. High prevalence of autoimmune thyroid disease in pulmonary arterial hypertension.  Chest. 2002;  122 1668-1673
• 54 Falcao C A, Alves I C, Chahade W H, Duarte A L, Lucena-Silva N. Echocardiographic abnormalities and antiphospholipid antibodies in patients with systemic lupus erythematosus.  Arq Bras Cardiol. 2002;  79 285-291
• 55 Asherson R A, Higenbottam T W, Dinh Xuan A T, Khamashta M A, Hughes G R. Pulmonary hypertension in a lupus clinic: experience with twenty-four patients.  J Rheumatol. 1990;  17 1292-1298
• 56 Rich S, Kieras K, Hart K, Groves B M, Stobo J D, Brundage B H. Antinuclear antibodies in primary pulmonary hypertension.  J Am Coll Cardiol. 1986;  8 1307-1311
• 57 Isern R A, Yaneva M, Weiner E et al.. Autoantibodies in patients with primary pulmonary hypertension: association with anti-Ku.  Am J Med. 1992;  93 307-312
• 58 Lopes A A, Maeda N Y, Gonçalves R C, Bydlowski S P. Endothelial cell dysfunction correlates differentially with survival in primary and secondary pulmonary hypertension.  Am Heart J. 2000;  139 618-623
• 59 Golbin J M, Krowka M J. Portopulmonary hypertension.  Clin Chest Med. 2007;  28 203-218 , ix
• 60 Sitbon O. HIV-related pulmonary arterial hypertension: clinical presentation and management.  AIDS. 2008;  22(Suppl 3) S55-S62
• 61 Dorfmüller P, Perros F, Balabanian K, Humbert M. Inflammation in pulmonary arterial hypertension.  Eur Respir J. 2003;  22 358-363
• 62 Sanchez O, Marcos E, Perros F et al.. Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary arterial hypertension.  Am J Respir Crit Care Med. 2007;  176 1041-1047
• 63 Dorfmüller P, Zarka V, Durand-Gasselin I et al.. Chemokine RANTES in severe pulmonary arterial hypertension.  Am J Respir Crit Care Med. 2002;  165 534-539
• 64 Bakouboula B, Morel O, Faure A et al.. Procoagulant membrane microparticles correlate with the severity of pulmonary arterial hypertension.  Am J Respir Crit Care Med. 2008;  177 536-543
• 65 Miyatake K, Okamoto M, Kinoshita N et al.. Evaluation of tricuspid regurgitation by pulsed Doppler and two-dimensional echocardiography.  Circulation. 1982;  66 777-784
• 66 Simonson J S, Schiller N B. Sonospirometry: a new method for noninvasive estimation of mean right atrial pressure based on two-dimensional echographic measurements of the inferior vena cava during measured inspiration.  J Am Coll Cardiol. 1988;  11 557-564
• 67 Ommen S R, Nishimura R A, Hurrell D G, Klarich K W. Assessment of right atrial pressure with 2-dimensional and Doppler echocardiography: a simultaneous catheterization and echocardiographic study.  Mayo Clin Proc. 2000;  75 24-29
• 68 Kircher B J, Himelman R B, Schiller N B. Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava.  Am J Cardiol. 1990;  66 493-496
• 69 Bossone E, Rubenfire M, Bach D S, Ricciardi M, Armstrong W F. Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension.  J Am Coll Cardiol. 1999;  33 1662-1666
• 70 McQuillan B M, Picard M H, Leavitt M, Weyman A E. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects.  Circulation. 2001;  104 2797-2802
• 71 Yock P G, Popp R L. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation.  Circulation. 1984;  70 657-662
• 72 Kitabatake A, Inoue M, Asao M et al.. Noninvasive evaluation of pulmonary hypertension by a pulsed Doppler technique.  Circulation. 1983;  68 302-309
• 73 Dabestani A, Mahan G, Gardin J M et al.. Evaluation of pulmonary artery pressure and resistance by pulsed Doppler echocardiography.  Am J Cardiol. 1987;  59 662-668
• 74 Isobe M, Yazaki Y, Takaku F et al.. Prediction of pulmonary arterial pressure in adults by pulsed Doppler echocardiography.  Am J Cardiol. 1986;  57 316-321
• 75 Willens H J, Chirinos J A, Gomez-Marin O et al.. Noninvasive differentiation of pulmonary arterial and venous hypertension using conventional and Doppler tissue imaging echocardiography.  J Am Soc Echocardiogr. 2008;  21 715-719
• 76 Abbas A E, Fortuin F D, Schiller N B, Appleton C P, Moreno C A, Lester S J. A simple method for noninvasive estimation of pulmonary vascular resistance.  J Am Coll Cardiol. 2003;  41 1021-1027
• 77 Selimovic N, Rundqvist B, Bergh C H et al.. Assessment of pulmonary vascular resistance by Doppler echocardiography in patients with pulmonary arterial hypertension.  J Heart Lung Transplant. 2007;  26 927-934
• 78 Kim Y J, Sohn D W. Mitral annulus velocity in the estimation of left ventricular filling pressure: prospective study in 200 patients.  J Am Soc Echocardiogr. 2000;  13 980-985
• 79 Currie P J, Seward J B, Chan K L et al.. Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients.  J Am Coll Cardiol. 1985;  6 750-756
• 80 Berger M, Haimowitz A, Van Tosh A, Berdoff R L, Goldberg E. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound.  J Am Coll Cardiol. 1985;  6 359-365
• 81 Denton C P, Cailes J B, Phillips G D, Wells A U, Black C M, Bois R M. Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis.  Br J Rheumatol. 1997;  36 239-243
• 82 Shapiro S M, Oudiz R J, Cao T et al.. Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion.  J Am Coll Cardiol. 1997;  30 343-349
• 83 Kim W R, Krowka M J, Plevak D J et al.. Accuracy of Doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates.  Liver Transpl. 2000;  6 453-458
• 84 Arcasoy S M, Christie J D, Ferrari V A et al.. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease.  Am J Respir Crit Care Med. 2003;  167 735-740
• 85 Berger M, Hecht S R, Van Tosh A, Lingam U. Pulsed and continuous wave Doppler echocardiographic assessment of valvular regurgitation in normal subjects.  J Am Coll Cardiol. 1989;  13 1540-1545
• 86 Celermajer D S, Marwick T. Echocardiographic and right heart catheterization techniques in patients with pulmonary arterial hypertension.  Int J Cardiol. 2008;  125 294-303
• 87 Aessopos A, Farmakis D, Taktikou H, Loukopoulos D. Doppler-determined peak systolic tricuspid pressure gradient in persons with normal pulmonary function and tricuspid regurgitation.  J Am Soc Echocardiogr. 2000;  13 645-649
• 88 Dib J C, Abergel E, Rovani C, Raffoul H, Diebold B. The age of the patient should be taken into account when interpreting Doppler assessed pulmonary artery pressures.  J Am Soc Echocardiogr. 1997;  10 72-73
• 89 de Divitiis O, Fazio S, Petitto M, Maddalena G, Contaldo F, Mancini M. Obesity and cardiac function.  Circulation. 1981;  64 477-482
• 90 Davidson Jr W R, Fee E C. Influence of aging on pulmonary hemodynamics in a population free of coronary artery disease.  Am J Cardiol. 1990;  65 1454-1458
• 91 Ekelund L G, Holmgren A. Central hemodynamics during exercise.  Circ Res. 1967;  xx-xxi
• 92 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
• 93 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
• 94 Lanzarini L, Fontana A, Lucca E, Campana C, Klersy C. Noninvasive estimation of both systolic and diastolic pulmonary artery pressure from Doppler analysis of tricuspid regurgitant velocity spectrum in patients with chronic heart failure.  Am Heart J. 2002;  144 1087-1094
• 95 Stephen B, Dalal P, Berger M, Schweitzer P, Hecht S. Noninvasive estimation of pulmonary artery diastolic pressure in patients with tricuspid regurgitation by Doppler echocardiography.  Chest. 1999;  116 73-77
• 96 Scapellato F, Temporelli P L, Eleuteri E, Corrà U, Imparato A, Giannuzzi P. Accurate noninvasive estimation of pulmonary vascular resistance by Doppler echocardiography in patients with chronic failure heart failure.  J Am Coll Cardiol. 2001;  37 1813-1819
• 97 Ihlen H, Amlie J P, Dale J et al.. Determination of cardiac output by Doppler echocardiography.  Br Heart J. 1984;  51 54-60
• 98 Lewis J F, Kuo L C, Nelson J G, Limacher M C, Quinones M A. Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window.  Circulation. 1984;  70 425-431
• 99 Rakowski H, Appleton C, Chan K L et al.. Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography: from the Investigators of Consensus on Diastolic Dysfunction by Echocardiography.  J Am Soc Echocardiogr. 1996;  9 736-760
• 100 Schulman D S, Matthay R A. The right ventricle in pulmonary disease.  Cardiol Clin. 1992;  10 111-135
• 101 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
• 102 Ryan T, Petrovic O, Dillon J C, Feigenbaum H, Conley M J, Armstrong W F. An echocardiographic index for separation of right ventricular volume and pressure overload.  J Am Coll Cardiol. 1985;  5 918-927
• 103 Miller D, Farah M G, Liner A, Fox K, Schluchter M, Hoit B D. The relation between quantitative right ventricular ejection fraction and indices of tricuspid annular motion and myocardial performance.  J Am Soc Echocardiogr. 2004;  17 443-447
• 104 Kaul S, Tei C, Hopkins J M, Shah P M. Assessment of right ventricular function using two-dimensional echocardiography.  Am Heart J. 1984;  107 526-531
• 105 Forfia P R, Fisher M R, Mathai S C et al.. Tricuspid annular displacement predicts survival in pulmonary hypertension.  Am J Respir Crit Care Med. 2006;  174 1034-1041
• 106 Alkotob M L, Soltani P, Sheatt M A et al.. Reduced exercise capacity and stress-induced pulmonary hypertension in patients with scleroderma.  Chest. 2006;  130 176-181
• 107 Cotrim C, Simões O, Loureiro M J et al.. Stress echocardiography in the evaluation of exercise physiology in patients with severe arterial pulmonary hypertension: new methodology.  Rev Port Cardiol. 2005;  24 1451-1460
• 108 Bach D S. Stress echocardiography for evaluation of hemodynamics: valvular heart disease, prosthetic valve function, and pulmonary hypertension.  Prog Cardiovasc Dis. 1997;  39 543-554
• 109 Marwick T H. Application of stress echocardiography to the evaluation of non-coronary heart disease.  Eur J Echocardiogr. 2000;  1 171-179
• 110 Collins N, Bastian B, Quiqueree L, Jones C, Morgan R, Reeves G. Abnormal pulmonary vascular responses in patients registered with a systemic autoimmunity database: Pulmonary Hypertension Assessment and Screening Evaluation using stress echocardiography (PHASE-I).  Eur J Echocardiogr. 2006;  7 439-446
• 111 Steen V, Chou M, Shanmugam V, Mathias M, Kuru T, Morrissey R. Exercise-induced pulmonary arterial hypertension in patients with systemic sclerosis.  Chest. 2008;  134 146-151
• 112 Bossone E, Avelar E, Bach D S, Gillespie B, Rubenfire M, Armstrong W F. Diagnostic value of resting tricuspid regurgitation velocity and right ventricular ejection flow parameters for the detection of exercise induced pulmonary arterial hypertension.  Int J Card Imaging. 2000;  16 429-436
• 113 Oudiz R J, Langleben D. Cardiac catheterization in pulmonary arterial hypertension: an updated guide to proper use.  Advances in Pulmonary Hypertension. 2005;  4 15-25
• 114 Guillinta P, Peterson K L, Ben-Yehuda O. Cardiac catheterization techniques in pulmonary hypertension.  Cardiol Clin. 2004;  22 401-415 , vi
• 115 Grossman W. Cardiac Catheterization and Angiography. Philadelphia; Lea & Febiger 1980
• 116 Swan H J, Ganz W, Forrester J, Marcus H, Diamond G, Chonette D. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter.  N Engl J Med. 1970;  283 447-451
• 117 Rich S, D'Alonzo G E, Dantzker D R, Levy P S. Magnitude and implications of spontaneous hemodynamic variability in primary pulmonary hypertension.  Am J Cardiol. 1985;  55 159-163
• 118 Khalil H H. Determination of cardiac output in man by a new method based on thermodilution.  Lancet. 1963;  1 1352-1354
• 119 Yung G L, Fedullo P F, Kinninger K, Johnson W, Channick R N. Comparison of impedance cardiography to direct Fick and thermodilution cardiac output determination in pulmonary arterial hypertension.  Congest Heart Fail. 2004;  10(2, Suppl 2) 7-10
• 120 Kaluski E, Shah M, Kobrin I, Vered Z, Cotter G. Right heart catheterization: indications, technique, safety, measurements, and alternatives.  HeartDrug. 2003;  3 225-235
• 121 Fowler N O, Westcott R N, Scott R C. Normal pressure in the right heart and pulmonary artery.  Am Heart J. 1953;  46 264-267
• 122 Olschewski H. Dana Point: what is new in the diagnosis of pulmonary hypertension? [in German].  Dtsch Med Wochenschr. 2008;  133(Suppl 6) S180-S182
• 123 McGregor M, Sniderman A. On pulmonary vascular resistance: the need for more precise definition.  Am J Cardiol. 1985;  55 217-221
• 124 Naeije R, Torbicki A. More on the noninvasive diagnosis of pulmonary hypertension: Doppler echocardiography revisited.  Eur Respir J. 1995;  8 1445-1449
• 125 Chemla D, Castelain V, Hervé P, Lecarpentier Y, Brimioulle S. Haemodynamic evaluation of pulmonary hypertension.  Eur Respir J. 2002;  20 1314-1331
• 126 McLaughlin V V, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy.  Circulation. 2002;  106 1477-1482
• 127 Sitbon O, Humbert M, Jaïs X et al.. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension.  Circulation. 2005;  111 3105-3111
• 128 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
• 129 Mandel J, Mark E J, Hales C A. Pulmonary veno-occlusive disease.  Am J Respir Crit Care Med. 2000;  162 1964-1973
• 130 Ghofrani H A, Wilkins M W, Rich S. Uncertainties in the diagnosis and treatment of pulmonary arterial hypertension.  Circulation. 2008;  118 1195-1201
• 131 Komadina K H, Schenk D A, LaVeau P, Duncan C A, Chambers S L. Interobserver variability in the interpretation of pulmonary artery catheter pressure tracings.  Chest. 1991;  100 1647-1654
• 132 Braunwald E, Ross Jr J. The ventricular end-diastolic pressure: appraisal of its value in the recognition of ventricular failure in man.  Am J Med. 1963;  34 147-150
• 133 Nootens M, Wolfkiel C J, Chomka E V, Rich S. Understanding right and left ventricular systolic function and interactions at rest and with exercise in primary pulmonary hypertension.  Am J Cardiol. 1995;  75 374-377
• 134 Reeves J, Groves B M. Approach to Patient with Pulmonary Hypertension. Mount Kisco, NY; Futura 1984
• 135 Reeves J TDJ, Grover R F. Pulmonary Circulation during Exercise. New York; Marcel Dekker 1989
• 136 Groves B M, Reeves J T, Sutton J R et al.. Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen.  J Appl Physiol. 1987;  63 521-530
• 137 Wagner P D, Gale G E, Moon R E, Torre-Bueno J R, Stolp B W, Saltzman H A. Pulmonary gas exchange in humans exercising at sea level and simulated altitude.  J Appl Physiol. 1986;  61 260-270
• 138 Fowler N O. The normal pulmonary arterial pressure-flow relationships during exercise.  Am J Med. 1969;  47 1-6
• 139 Bevegard S, Holmgren A, Jonsson B. The effect of body position on the circulation at rest and during exercise, with special reference to the influence on the stroke volume.  Acta Physiol Scand. 1960;  49 279-298
• 140 Brofman B L, Charms B L, Kohn P M, Elder J, Newman R, Rizika M. Unilateral pulmonary artery occlusion in man; control studies.  J Thorac Surg. 1957;  34 206-227
• 141 Provencher S, Hervé P, Sitbon O, Humbert M, Simonneau G, Chemla D. Changes in exercise haemodynamics during treatment in pulmonary arterial hypertension.  Eur Respir J. 2008;  32 393-398
• 142 Castelain V, Chemla D, Humbert M et al.. Pulmonary artery pressure-flow relations after prostacyclin in primary pulmonary hypertension.  Am J Respir Crit Care Med. 2002;  165 338-340
• 143 Kessler R, Faller M, Weitzenblum E et al.. “Natural history” of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease.  Am J Respir Crit Care Med. 2001;  164 219-224
• 144 Sherrick A D, Swensen S J, Hartman T E. Mosaic pattern of lung attenuation on CT scans: frequency among patients with pulmonary artery hypertension of different causes.  AJR Am J Roentgenol. 1997;  169 79-82
• 145 Perloff J K, Hart E M, Greaves S M, Miner P D, Child J S. Proximal pulmonary arterial and intrapulmonary radiologic features of Eisenmenger syndrome and primary pulmonary hypertension.  Am J Cardiol. 2003;  92 182-187
• 146 Kuriyama K, Gamsu G, Stern R G, Cann C E, Herfkens R J, Brundage B H. CT-determined pulmonary artery diameters in predicting pulmonary hypertension.  Invest Radiol. 1984;  19 16-22
• 147 Haimovici J B, Trotman-Dickenson B, Halpern E F Massachusetts General Hospital Lung Transplantation Program et al. Relationship between pulmonary artery diameter at computed tomography and pulmonary artery pressures at right-sided heart catheterization.  Acad Radiol. 1997;  4 327-334
• 148 Ng C S, Wells A U, Padley S PA. A CT sign of chronic pulmonary arterial hypertension: the ratio of main pulmonary artery to aortic diameter.  J Thorac Imaging. 1999;  14 270-278
• 149 Hansell D M. Small-vessel diseases of the lung: CT-pathologic correlates.  Radiology. 2002;  225 639-653
• 150 Horton M R, Tuder R M. Primary pulmonary arterial hypertension presenting as diffuse micronodules on CT.  Crit Rev Comput Tomogr. 2004;  45 335-341
• 151 Nolan R L, McAdams H P, Sporn T A, Roggli V L, Tapson V F, Goodman P C. Pulmonary cholesterol granulomas in patients with pulmonary artery hypertension: chest radiographic and CT findings.  AJR Am J Roentgenol. 1999;  172 1317-1319
• 152 Lippert J L, White C S, Cameron E W, Sun C C, Liang X, Rubin L J. Pulmonary capillary hemangiomatosis: radiographic appearance.  J Thorac Imaging. 1998;  13 49-51
• 153 Eksinar S, Gedevanishvili A, Koroglu M et al.. Extrinsic compression of the left main coronary artery in pulmonary hypertension.  JBR-BTR. 2005;  88 190-192
• 154 Kovacs G, Reiter G, Reiter U, Rienmüller R, Peacock A, Olschewski H. The emerging role of magnetic resonance imaging in the diagnosis and management of pulmonary hypertension.  Respiration. 2008;  76 458-470
• 155 Maceira A M, Prasad S K, Khan M, Pennell D J. Reference right ventricular systolic and diastolic function normalized to age, gender and body surface area from steady-state free precession cardiovascular magnetic resonance.  Eur Heart J. 2006;  27 2879-2888
• 156 Alfakih K, Plein S, Thiele H, Jones T, Ridgway J P, Sivananthan M U. Normal human left and right ventricular dimensions for MRI as assessed by turbo gradient echo and steady-state free precession imaging sequences.  J Magn Reson Imaging. 2003;  17 323-329
• 157 Grothues F, Moon J C, Bellenger N G, Smith G S, Klein H U, Pennell D J. Interstudy reproducibility of right ventricular volumes, function, and mass with cardiovascular magnetic resonance.  Am Heart J. 2004;  147 218-223
• 158 Chatzimavroudis G P, Oshinski J N, Franch R H, Walker P G, Yoganathan A P, Pettigrew R I. Evaluation of the precision of magnetic resonance phase velocity mapping for blood flow measurements.  J Cardiovasc Magn Reson. 2001;  3 11-19
• 159 Gan C T, Lankhaar J W, Westerhof N et al.. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension.  Chest. 2007;  132 1906-1912
• 160 Chin K M, Kingman M, de Lemos J A et al.. Changes in right ventricular structure and function assessed using cardiac magnetic resonance imaging in bosentan-treated patients with pulmonary arterial hypertension.  Am J Cardiol. 2008;  101 1669-1672
• 161 Gan C T, Holverda S, Marcus J T et al.. Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients.  Chest. 2007;  132 11-17
• 162 Pietra G G, Edwards W D, Kay J M et al.. Histopathology of primary pulmonary hypertension: a qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry.  Circulation. 1989;  80 1198-1206
• 163 Nicod P, Moser K M. Primary pulmonary hypertension: the risk and benefit of lung biopsy.  Circulation. 1989;  80 1486-1488