Pulmonary Disease and Right Ventricular Function

  • Emma Weiss
  • Elisabeta Bădilă


Respiratory diseases have become major players in mortality and morbidity charts and their influence on cardiac function has brought them in research focus, especially when investigating their role on the pathobiology of the less well understood right ventricle. By insulting pulmonary vasculature it leads to micro and macrovessel injury which results in pulmonary hypertension, increased right ventricle afterload along with its consequences—right ventricle hypertrophy and dilation. From the initial physical stimuli of hypoxia, translated by the vessel wall cells into a biological response of vasoconstriction and remodeling, pulmonary hypertension develops in a process modulated by the endothelium and many other epigenetic factors. Pulmonary hypertension is rarely severe when associated purely with chronic lung disease but carries a poor prognosis nevertheless, especially when associating right ventricle dysfunction. The primary diagnostic tools remain the echocardiography parameters generally used in all forms of the disorder and invasive procedures are infrequently necessary for evaluation. Unfortunately, this class of pulmonary hypertension shares much of the prognosis and complications with other groups of the, disorder, but less of the therapeutic arsenal which has become more recently available in the latter.


Chronic lung disease Hypoxia-induced pulmonary vasoconstriction Right ventricle dysfunction in respiratory disease 


  1. 1.
    WHO. The top 10 causes of death. 2017.
  2. 2.
    Voelkel NF, Gomez-Arroyo J, Abbate A, Bogaard HJ. Mechanisms of right heart failure-A work in progress and a plea for failure prevention. Pulm Circ. 2013;3(1):137–43.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Voelkel NF, Mizuno S, Bogaard HJ. The role of hypoxia in pulmonary vascular diseases: a perspective. AJP. 2013;304(7):L457–65.Google Scholar
  4. 4.
    Rigolin VH, Robiolio PA, Wilson JS, Kevin Harrison J, Bashore TM. The forgotten chamber: the importance of the right ventricle. Physiology. 1995;28:18–28.Google Scholar
  5. 5.
    Baker BJ, Wilen MM, Boyd CM, Dinh H, Franciosa JA. Relation of right ventricular ejection fraction to exercise capacity in chronic left ventricular failure. Am J Cardiol. 1984;54(6):596–9.CrossRefPubMedGoogle Scholar
  6. 6.
    de Groote P, et al. Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure. J Am Coll Cardiol. 1998;32(4):948–54.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Polak JF, Holman BL, Wynne J, Colucci WS. Right ventricular ejection fraction: an indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease. J Am Coll Cardiol. 1983;2(2):217–24.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol. 1995;25(5):1143–53.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Melenovsky V, Hwang S-J, Lin G, Redfield MM, Borlaug BA. Right heart dysfunction in heart failure with preserved ejection fraction. Eur Heart J. 2014;35(48):3452–62.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Simonneau G, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41.CrossRefPubMedGoogle Scholar
  11. 11.
    Ho SY. Anatomy, echocardiography, and normal right ventricular dimensions. Heart. 2006;92(suppl_1):i2–13.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Dell’Italia LJ. Anatomy and physiology of the right ventricle. Cardiol Clin. 2012;30(2):167–87.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Voelkel NF, Dietmar S. The right ventricle in health and disease. New York: Springer; 2014.Google Scholar
  14. 14.
    Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right ventricular function in cardiovascular disease, part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation. 2008;117(11):1436–48.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    West JB. Role of the fragility of the pulmonary blood-gas barrier in the evolution of the pulmonary circulation. AJP. 2013;304(3):R171–6.Google Scholar
  16. 16.
    Berlin DA, Bakker J. Understanding venous return. Intensive Care Med. 2014;40(10):1564–6.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kass DA. Alterations in ventricular function in systolic heart failure - beat-to-beat regulation of systolic function. In: Mann DL, Felker GM, editors. Heart failure: a companion to Braunwald’s heart disease. Philadelphia: Elsevier; 2016.Google Scholar
  18. 18.
    Harjola V-P, et al. Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the working group on pulmonary circulation and right ventricular function of the European Society of Cardiology. Eur J Heart Fail. 2016;18(3):226–41.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wagner PD. Operation everest II. High Alt Med Biol. 2010;11(2):111–9.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Demiryurek AT, Wadsworth RM, Kane KA, Peacock AJ. The role of endothelium in hypoxic constriction of human pulmonary artery rings. Am Rev Respir Dis. 1993;147(2):283–90.CrossRefPubMedGoogle Scholar
  21. 21.
    Ohe M, Ogata M, Katayose D, Takishima T. Hypoxic contraction of pre-stretched human pulmonary artery. Respir Physiol. 1992;87(1):105–14.CrossRefPubMedGoogle Scholar
  22. 22.
    Berg JT, Breen EC, Fu Z, Mathieu-Costello O, West JB. Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma. Am J Respir Crit Care Med. 1998;158(6):1920–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Sylvester JT, Shimoda LA, Aaronson PI, Ward JPT. Hypoxic pulmonary vasoconstriction. Physiol Rev. 2012;92(1):367–520.CrossRefPubMedGoogle Scholar
  24. 24.
    Weissmann N, Grimminger F, Walmrath D, Seeger W. Hypoxic vasoconstriction in buffer-perfused rabbit lungs. Respir Physiol. 1995;100(2):159–69.CrossRefPubMedGoogle Scholar
  25. 25.
    Peake MD, Harabin AL, Brennan NJ, Sylvester JT. Steady-state vascular responses to graded hypoxia in isolated lungs of five species. J Appl Physiol Respir Environ Exerc Physiol. 1981;51(5):1214–9.PubMedGoogle Scholar
  26. 26.
    Lumb AB, Slinger P. Hypoxic pulmonary vasoconstriction physiology and anesthetic implications. Anesthesiology. 2015;122(4):932–46.CrossRefPubMedGoogle Scholar
  27. 27.
    Kay JM. Comparative morphologic features of the pulmonary vasculature in mammals 1, 2. Am Rev Respir Dis. 1983;128(2P2):S53–7.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Hong Z, et al. Role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in oxygen sensing and constriction of the ductus arteriosus. Circ Res. 2013;112(5):802–15.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Longo DL, Archer SL. Mitochondrial dynamics — mitochondrial fission and fusion in human diseases. N Engl J Med. 2013;369(23):2236–51.CrossRefGoogle Scholar
  30. 30.
    Palmer BF, Clegg DJ. Oxygen sensing and metabolic homeostasis. Mol Cell Endocrinol. 2014;397(1–2):51–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Waypa GB, et al. Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes. Circ Res. 2002;91(8):719–26.CrossRefPubMedGoogle Scholar
  32. 32.
    Waypa GB, Chandel NS, Schumacker PT. Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res. 2001;88(12):1259–66.CrossRefPubMedGoogle Scholar
  33. 33.
    Weir EK, Archer SL. Counterpoint: hypoxic pulmonary vasoconstriction is not mediated by increased production of reactive oxygen species. J Appl Physiol. 2006;101(3):995 LP–998.CrossRefGoogle Scholar
  34. 34.
    Weir EK, López-Barneo J, Buckler KJ, Archer SL. Acute oxygen-sensing mechanisms. N Engl J Med. 2005;353:2042–55.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Moudgil R, Michelakis ED, Archer SL, Archer SL. Hypoxic pulmonary vasoconstriction. J Appl Physiol. 2005;123:390–403.CrossRefGoogle Scholar
  36. 36.
    Talbot NP, Balanos GM, Dorrington KL, Robbins PA. Two temporal components within the human pulmonary vascular response to ~2 H of isocapnic hypoxia. J Appl Physiol. 2005;98(3):1125–39.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Smith TG, et al. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol. 2008;586(24):5999–6005.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wang J, Juhaszova M, Rubin LJ, Yuan XJ. Hypoxia inhibits gene expression of voltage-gated K+ channel alpha subunits in pulmonary artery smooth muscle cells. J Clin Investig. 1997;100(9):2347–53.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Charolidi N, Carroll VA. Hypoxia and pulmonary hypertension. In: Zheng J, editor. Hypoxia and human diseases. Rijeka: InTech; 2017.Google Scholar
  40. 40.
    Swenson E. Hypoxic pulmonary vasoconstriction and chronic lung disease. Adv Pulm Hypertens. 2013;12(3):135–44.Google Scholar
  41. 41.
    Weidemann A, Johnson RS. Biology of HIF-1alpha. Cell Death Differ. 2008;15(4):621–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Engebretsen BJ, et al. Acute hypobaric hypoxia (5486 M) induces greater pulmonary HIF-1 activation in hilltop compared to Madison rats. High Alt Med Biol. 2007;8(4):312–21.CrossRefPubMedGoogle Scholar
  43. 43.
    Beall CM, et al. Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders. Proc Natl Acad Sci U S A. 2010;107(25):11459–64.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Lorenzo FR, et al. A genetic mechanism for tibetan high-altitude adaptation. Nat Genet. 2014;46(9):951–6.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sarangi S, et al. The homozygous VHL(D126N) missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension. Pediatr Blood Cancer. 2014;61(11):2104–6.CrossRefPubMedGoogle Scholar
  46. 46.
    Tao H, et al. Expression and significance of hypoxia-inducible factor-1alpha in patients with chronic obstructive pulmonary disease and smokers with normal lung function. Chin J Cell Mol Immunol. 2014;30(8):852–5.Google Scholar
  47. 47.
    Daijo H, et al. Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner. Sci Rep. 2016;6:34424.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004;109(2):159–65.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Quy S, Duong. Physiopathology of pulmonary hypertension: from bio-molecular mechanism to target treatment. J Vasc Med Surg. 2016;4(6):294.Google Scholar
  50. 50.
    Aird WC. Endothelial cell heterogeneity. Crit Care Med. 2003;31(Supplement):S221–30.CrossRefPubMedGoogle Scholar
  51. 51.
    Tonelli AR, Haserodt S, Aytekin M, Dweik RA. Nitric oxide deficiency in pulmonary hypertension: pathobiology and implications for therapy. Pulm. Circ. 2013;3(1):20–30.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Aaronson PI, Robertson TP, Ward JPT. Endothelium-derived mediators and hypoxic pulmonary vasoconstriction. Respir Physiol Neurobiol. 2002;132(1):107–20.CrossRefPubMedGoogle Scholar
  53. 53.
    Yang Q, et al. NO and EDHF pathways in pulmonary arteries and veins are impaired in COPD patients. Vasc Pharmacol. 2012;57(2–4):113–8.CrossRefGoogle Scholar
  54. 54.
    Tuder RM, Zaiman AL. Perspective prostacyclin analogs as the brakes for pulmonary artery smooth muscle cell proliferation is it sufficient to treat severe pulmonary hypertension. Am J Respir Cell Mol Biol. 2002;26:171–4.CrossRefPubMedGoogle Scholar
  55. 55.
    Tuder RM, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med. 1999;159(6):1925–32.CrossRefPubMedGoogle Scholar
  56. 56.
    Christman BW, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992;327(2):70–5.CrossRefPubMedGoogle Scholar
  57. 57.
    Katugampola SD, Davenport AP. Thromboxane receptor density is increased in human cardiovascular disease with evidence for inhibition at therapeutic concentrations by the AT(1) receptor antagonist losartan. Br J Pharmacol. 2001;134(7):1385–92.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Langleben D, et al. Effects of the thromboxane synthetase inhibitor and receptor antagonist terbogrel in patients with primary pulmonary hypertension. Am Heart J. 2002;143(5):E4.CrossRefPubMedGoogle Scholar
  59. 59.
    Frasch HF, Marshall C, Marshall BE. Endothelin-1 is elevated in monocrotaline pulmonary hypertension. Am J Phys. 1999;276(2 Pt 1):L304–10.Google Scholar
  60. 60.
    Giaid A, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993;328(24):1732–9.CrossRefPubMedGoogle Scholar
  61. 61.
    Li H, et al. Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia. J Appl Physiol. 1994;77(3):1451 LP–459.CrossRefGoogle Scholar
  62. 62.
    MacLean MR, Herve P, Eddahibi S, Adnot S. 5-Hydroxytryptamine and the pulmonary circulation: receptors, transporters and relevance to pulmonary arterial hypertension. Br J Pharmacol. 2000;131(2):161–8.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Le C, Timothy D, Markham NE, Tuder RM, Voelkel NF, Abman SH. Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure. Am J Physiol. 2002;283(3):L555–62.Google Scholar
  64. 64.
    Partovian C, et al. Adenovirus-mediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats. Am J Respir Cell Mol Biol. 2000;23(6):762–71.CrossRefPubMedGoogle Scholar
  65. 65.
    Ketabchi F, et al. Effects of hypercapnia with and without acidosis on hypoxic pulmonary vasoconstriction. Am J Physiol. 2009;297(5):L977–83.Google Scholar
  66. 66.
    Dunham-Snary KJ, et al. Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine. Chest. 2017;151(1):181–92.CrossRefPubMedGoogle Scholar
  67. 67.
    Vogelmeier CF, et al. Global strategy for the diagnosis, management and prevention of chronic obstructive lung disease 2017 report. Respirology. 2017;22(3):575–601.CrossRefPubMedGoogle Scholar
  68. 68.
    Peinado VI, et al. Endothelial dysfunction in pulmonary arteries of patients with mild COPD. Am J Phys. 1998;274(6):908–13.Google Scholar
  69. 69.
    Green CE, Turner AM. The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD). Respir Res. 2017;18:20.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Tuder RM, Voelkel NF. Angiogenesis and pulmonary hypertension: a unique process in a unique disease. Antioxid Redox Signal. 2002;4(5):833–43.CrossRefPubMedGoogle Scholar
  71. 71.
    Muller WA. Transendothelial migration: unifying principles from the endothelial perspective. Immunol Rev. 2016;273(1):61–75.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Liao JK. Linking endothelial dysfunction with endothelial cell activation. J Clin Invest. 2013;123(2):540–1.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Oelsner EC, et al. Adhesion molecules, endothelin-1 and lung function in seven population-based cohorts. Biomarkers. 2013;18(3):196–203.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Aaron CP, et al. Intercellular adhesion molecule 1 and progression of percent emphysema: the MESA lung study. Respir Med. 2015;109(2):255–64.CrossRefPubMedGoogle Scholar
  75. 75.
    Riise GC, Larsson S, Lofdahl CG, Andersson BA. Circulating cell adhesion molecules in bronchial lavage and serum in COPD patients with chronic bronchitis. Eur Respir J. 1994;7(9):1673–7.CrossRefPubMedGoogle Scholar
  76. 76.
    Janson C, et al. Circulating adhesion molecules in allergic and non-allergic asthma. Respir Med. 2005;99(1):45–51.CrossRefPubMedGoogle Scholar
  77. 77.
    Mukhopadhyay S, Malik P, Arora SK, Mukherjee TK. Intercellular adhesion molecule-1 as a drug target in asthma and rhinitis. Respirology. 2014;19(4):508–13.CrossRefPubMedGoogle Scholar
  78. 78.
    Hirata N, et al. Allergen exposure induces the expression of endothelial adhesion molecules in passively sensitized human bronchus: time course and the role of cytokines. Am J Respir Cell Mol Biol. 1998;18(1):12–20.CrossRefPubMedGoogle Scholar
  79. 79.
    Malli F, et al. Endothelial progenitor cells in the pathogenesis of idiopathic pulmonary fibrosis: an evolving concept. PLoS ONE. 2013;8(1):e53658.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Lu D, Li N, Yao X, Zhou L. Potential inflammatory markers in obstructive sleep apnea-hypopnea syndrome. Bosn J Basic Med Sci. 2017;17(1):47–53.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Portillo K, Morera J. Combined pulmonary fibrosis and emphysema syndrome: a new phenotype within the spectrum of smoking-related interstitial lung disease. Pulm Med. 2012;2012:867870.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Stenmark KR, Fagan KA, Frid MG. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res. 2006;99(7):675–91.CrossRefPubMedGoogle Scholar
  83. 83.
    Santos S, et al. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD. Eur Respir J. 2002;19(4):632–8.CrossRefPubMedGoogle Scholar
  84. 84.
    Carlsen J, et al. Pulmonary arterial lesions in explanted lungs after transplantation correlate with severity of pulmonary hypertension in chronic obstructive pulmonary disease. J Heart Lung Transplant. 2013;32(3):347–54.CrossRefPubMedGoogle Scholar
  85. 85.
    Chen H, Strappe P, Chen S, Wang L-X. Endothelial progenitor cells and pulmonary arterial hypertension. Heart Lung Circ. 2014;23(7):595–601.CrossRefPubMedGoogle Scholar
  86. 86.
    Granton J, et al. Endothelial NO-synthase gene-enhanced progenitor cell therapy for pulmonary arterial hypertension: The PHACeT trial. Circ Res. 2015;117(7):645–54.CrossRefPubMedGoogle Scholar
  87. 87.
    Marsboom G, et al. Sustained endothelial progenitor cell dysfunction after chronic hypoxia-induced pulmonary hypertension. Stem Cells. 2008;26(4):1017–26.CrossRefPubMedGoogle Scholar
  88. 88.
    Hopkins N, McLoughlin P. The structural basis of pulmonary hypertension in chronic lung disease: remodelling, rarefaction or angiogenesis? J Anat. 2002;201(4):335–48.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation? Hypertension. 2006;48(6):1012–7.CrossRefPubMedGoogle Scholar
  90. 90.
    Howell K, Preston RJ, McLoughlin P. Chronic hypoxia causes angiogenesis in addition to remodelling in the adult rat pulmonary circulation. J Physiol. 2003;547(Pt 1):133–45.CrossRefPubMedGoogle Scholar
  91. 91.
    Pascaud M-A, et al. Lung overexpression of angiostatin aggravates pulmonary hypertension in chronically hypoxic mice. Am J Respir Cell Mol Biol. 2003;29(4):449–57.CrossRefPubMedGoogle Scholar
  92. 92.
    Sajkov D, McEvoy RD. Obstructive sleep apnea and pulmonary hypertension. Prog Cardiovasc Dis. 2009;51(5):363–70.CrossRefPubMedGoogle Scholar
  93. 93.
    Kholdani C, Fares WH, Mohsenin V. Pulmonary hypertension in obstructive sleep apnea: is it clinically significant? A critical analysis of the association and pathophysiology. Pulmonary Circulation. 2015;5(2):220–7.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Shlobin OA, Nathan SD. Pulmonary hypertension secondary to interstitial lung disease. Expert Rev Respir Med. 2011;5(2):179–89.CrossRefPubMedGoogle Scholar
  95. 95.
    Fagan KA, Badesch DB. Pulmonary hypertension associated with connective tissue disease. Prog Cardiovasc Dis. 2002;45(3):225–34.CrossRefPubMedGoogle Scholar
  96. 96.
    Authors/Task Force Members, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(36):2768–801.CrossRefGoogle Scholar
  97. 97.
    Wiggins J, Strickland B, Turner-Warwick M. Combined cryptogenic fibrosing alveolitis andemphysema: the value of high resolution computed tomography in assessment. Respir Med. 2017;84(5):365–9.CrossRefGoogle Scholar
  98. 98.
    Cottin V, Nunes H, Brillet P. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J. 2005;26(4):586–93.CrossRefPubMedGoogle Scholar
  99. 99.
    Budev MM, Arroliga AC, Wiedemann HP, Matthay RA. Cor pulmonale: an overview. Semin Respir Crit Care Med. 2003;24(3):233–43.CrossRefPubMedGoogle Scholar
  100. 100.
    World Health Organization. Chronic cor pulmonale: a report of the expert committee. Circulation. 1963;27:594–8.CrossRefGoogle Scholar
  101. 101.
    Weitzenblum E, Chaouat A, Canuet M, Kessler R. Pulmonary hypertension in chronic obstructive pulmonary disease and interstitial lung diseases. Crit Care. 2009;1(212):458–70.Google Scholar
  102. 102.
    Kolb TM, Hassoun PM. Right ventricular dysfunction in chronic lung disease. Cardiol Clin. 2012;30(2):243–56.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Hilde JM, et al. Right ventricular dysfunction and remodeling in chronic obstructive pulmonary disease without pulmonary hypertension. J Am Coll Cardiol. 2013;62(12):1103–11.CrossRefPubMedGoogle Scholar
  104. 104.
    Watz H, et al. Decreasing cardiac chamber sizes and associated heart dysfunction in COPD: role of hyperinflation. Chest. 2010;138(1):32–8.CrossRefPubMedGoogle Scholar
  105. 105.
    Zangiabadi A, De Pasquale CG, Sajkov D. Pulmonary hypertension and right heart dysfunction in chronic lung disease. Biomed Res Int. 2014;2014:739674.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Bogaard HJ, Abe K, Noordegmaf AV, Voelkel NF. The Right ventricle under pressure. Chest. 2009;135(3):794–804.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Harston RK, Kuppuswamy D. Integrins are the necessary links to hypertrophic growth in cardiomyocytes. J Signal Transduction. 2011;2011:1–8.CrossRefGoogle Scholar
  108. 108.
    Voelkel NF, et al. Right ventricular function and failure: report of a national heart, lung, and blood institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006;114(17):1883–91.CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Samson N, Paulin R. Epigenetics, inflammation and metabolism in right heart failure associated with pulmonary hypertension. Pulm Circ. 2017;7(3):572–87.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Scharf SM, et al. Hemodynamic characterization of patients with severe emphysema. Am J Respir Crit Care Med. 2002;166(3):314–22.CrossRefPubMedGoogle Scholar
  111. 111.
    Chaouat A, et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;172(2):189–94.CrossRefPubMedGoogle Scholar
  112. 112.
    Pugh ME, et al. Causes of pulmonary hypertension in the elderly. Chest. 2014;146(1):159–66.CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Klings ES. Pulmonary hypertension due to lung disease and/or hypoxemia (Group 3 pulmonary hypertension): epidemiology, pathogenesis, and diagnostic evaluation in adults. UpToDate. 2017.
  114. 114.
    Arcasoy SM, et al. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. Am J Respir Crit Care Med. 2003;167(5):735–40.CrossRefPubMedGoogle Scholar
  115. 115.
    Javaheri S, Javaheri S, Javaheri A. Sleep apnea, heart failure, and pulmonary hypertension. Curr Heart Fail Rep. 2013;10(4):315–20.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Bradley TD, et al. Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome. Am Rev Respir Dis. 1985;131(0003–0805):835–9.PubMedPubMedCentralGoogle Scholar
  117. 117.
    Tzilas V, Bouros D. Combined pulmonary fibrosis and emphysema, a clinical review. COPD Res Pract. 2016;2(1):2.CrossRefGoogle Scholar
  118. 118.
    Sugino K, Ishida F, Kikuchi N. Comparison of clinical characteristics and prognostic factors of combined pulmonary fibrosis and emphysema versus idiopathic pulmonary fibrosis alone. Respirology. 2014;19:239–45.CrossRefPubMedGoogle Scholar
  119. 119.
    Galiè N, Humbert M, Vachiery JL. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endor. Eur Respir J. 2015;46:903–75.CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Seeger W, et al. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol. 2013;62(25 Suppl):D109–16.CrossRefPubMedGoogle Scholar
  121. 121.
    Høiseth AD, Omland T, Hagve T-A, Brekke PH, Søyseth V. NT-proBNP independently predicts long term mortality after acute exacerbation of COPD – a prospective cohort study. Respir Res. 2012;13(1):97.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Adrish M, Nannaka VB, Cano EJ, Bajantri B, Diaz-Fuentes G. Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction. Int J Chron Obstruct Pulmon Dis. 2017;12:1183–9.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Ouanes-Besbes L, Hamouda Z, Ouanes I, Dachraoui F, Abroug F. NT-proBNP accurately reflects the impact of severe COPD exacerbation on the right ventricle (RV). Eur Respir J. 2014;42(Suppl 57):P2434.Google Scholar
  124. 124.
    Leuchte HH, et al. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med. 2006;173(7):744–50.CrossRefPubMedGoogle Scholar
  125. 125.
    Dupont MVM, Drǎgean CA, Coche EE. Right ventricle function assessment by MDCT. Am J Roentgenol. 2011;196(1):77–86.CrossRefGoogle Scholar
  126. 126.
    Gao Y, et al. Evaluation of right ventricular function by 64-row ct in patients with chronic obstructive pulmonary disease and cor pulmonale. Eur J Radiol. 2012;81(2):345–53.CrossRefPubMedGoogle Scholar
  127. 127.
    Hur J, Kim TH, Kim SJ, Ryu YH, Kim HJ. Assessment of the right ventricular function and mass using cardiac multi-detector computed tomography in patients with chronic obstructive pulmonary disease. Korean J Radiol. 2007;8(1):15–21.CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Vitarelli A. Assessment of right ventricular function by strain rate imaging in chronic obstructive pulmonary disease. Eur Respir J. 2006;27(2):268–75.CrossRefPubMedGoogle Scholar
  129. 129.
    Turhan S, et al. Value of tissue doppler myocardial velocities of tricuspid lateral annulus for the diagnosis of right heart failure in patients with COPD. Echocardiography. 2007;24(2):126–33.CrossRefPubMedGoogle Scholar
  130. 130.
    Ozben B, et al. Acute exacerbation impairs right ventricular function in COPD patients. Hell J Cardiol. 2015;56(4):324–31.Google Scholar
  131. 131.
    Burgess MI, et al. Comparison of echocardiographic markers of right ventricular function in determining prognosis in chronic pulmonary disease. J Am Soc Echocardiogr. 2002;15(6):633–9.CrossRefPubMedGoogle Scholar
  132. 132.
    Kato S, et al. Prognostic value of cardiovascular magnetic resonance derived right ventricular function in patients with interstitial lung disease. J Cardiovasc Magn Reson. 2015;17(1):10.CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Vonbank K, et al. Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD. Thorax. 2003;58(4):289–93.CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134. Inhaled nitric oxide to prevent and treat bronchopulmonary dysplasia (NO-BPD) NCT01503801. 2017.
  135. 135.
    Warren NJ. Bellerophon to Present Positive Clinical Data on INOpulse® at the American Thoracic Society 113th International Conference. 2017."ID=2268250.
  136. 136. Study in subjects with PAH and PH secondary to IPF using inhaled GeNOsyl. (PHiano) NCT01503801. 2017.
  137. 137.
    Stolz D, et al. A randomised, controlled trial of Bosentan in severe COPD. Eur Respir J. 2008;32(3):619–28.CrossRefPubMedGoogle Scholar
  138. 138.
    Badesch DB, et al. ARIES-3: ambrisentan therapy in a diverse population of patients with pulmonary hypertension. Cardiovasc Ther. 2012;30(2):93–9.CrossRefPubMedGoogle Scholar
  139. 139.
    Valerio G, Bracciale P, D’Agostino AG. Effect of Bosentan upon pulmonary hypertension in chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2009;3(1):15–21.CrossRefPubMedGoogle Scholar
  140. 140.
    Duarte JD, Hanson RL, Machado RF. Pharmacologic treatments for pulmonary hypertension: exploring pharmacogenomics. Futur Cardiol. 2013;9(3):335–49.CrossRefGoogle Scholar
  141. 141.
    Taichman DB, et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report. Chest. 2014;146(2):449–75.CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Medarov BI, Judson MA. The role of calcium channel blockers for the treatment of pulmonary arterial hypertension: how much do we actually know and how could they be positioned today? Respir Med. 2017;109(5):557–64.CrossRefGoogle Scholar
  143. 143.
    Nice Guidelines. Chronic obstructive pulmonary disease in over 16s: diagnosis and management; 2010. pp. 1–31.Google Scholar
  144. 144.
    Criner GJ, et al. Effect of lung volume reduction surgery on resting pulmonary hemodynamics in severe emphysema. Am J Respir Crit Care Med. 2007;176(3):253–60.CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Wise R, Connett J, Weinmann G, Scanlon P, Skeans M. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med. 2000;343(26):1902–9.CrossRefPubMedGoogle Scholar
  146. 146.
    Mapel DW, Dedrick D, Davis K. Trends and cardiovascular co-morbidities of COPD patients in the veterans administration medical system, 1991-1999. COPD. 2005;2(1):35–41.CrossRefPubMedGoogle Scholar
  147. 147.
    Global Initiative for Chronic Obstructive Lung Disease. Global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease (Updated 2014). i-84. 2014.Google Scholar
  148. 148.
    Aleva FE, et al. Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: a systematic review and meta-analysis. Chest. 2017;151(3):544–54.CrossRefPubMedGoogle Scholar
  149. 149.
    Rowan SC, Keane MP, Gaine S, McLoughlin P. Hypoxic pulmonary hypertension in chronic lung diseases: novel vasoconstrictor pathways. Lancet Respir Med. 2016;4(3):225–36.CrossRefPubMedGoogle Scholar
  150. 150.
    Hurdman J, et al. Pulmonary hypertension in COPD: results from the ASPIRE registry. Eur Respir J. 2013;41(6):1292 LP–1301.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Emma Weiss
    • 1
  • Elisabeta Bădilă
    • 1
  1. 1.Internal Medicine, Emergency Clinical Hospital BucharestUniversity of Medicine and Pharmacy Carol Davila BucharestBucharestRomania

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