History

Important medical history to be mindful of in patients suspected of having pulmonary hypertension secondary to a group 3 condition include the following:

Chronic obstructive pulmonary disease (COPD)
Obstructive or restrictive lung disease
Interstitial lung disease (ILD)
Obesity
Daytime sleepiness
Snoring
Tonsillary hypertrophy
Macroglossia
Retrognathia/micrognathia
Upper airway mass lesions
Chest wall deformity
Neuromuscular disease
Kyphoscoliosis
Long-term exposure to high altitude
Opiate use (associated with central sleep apnea)
Brainstem lesion

Symptoms that may be present in patients with pulmonary hypertension due to a group 3 condition include the following:

Dyspnea upon exertion
Fatigue
Lethargy
Syncope
Cough
Hoarseness

Physical Examination

The intensity of the pulmonic component of the second heart sound (P₂) may be increased, and the P₂ may demonstrate fixed or paradoxic splitting. A systolic ejection murmur may be heard over the left sternal border. The murmur may be augmented by inspiration. A right ventricular heave may be palpated.

A prominent A wave may be observed in the jugular venous pulse. A right-sided fourth heart sound (S₄) with a left parasternal heave may be auscultated.

Right ventricular failure leads to systemic venous hypertension and cor pulmonale. The signs of right ventricular failure include a high-pitched systolic murmur of tricuspid regurgitation, hepatomegaly, a pulsatile liver, ascites, and peripheral edema. In this scenario, a right ventricular third heart (S₃) sound is also heard.

Signs of underlying cardiac, pulmonary, hepatic, or collagen-vascular disease are often present.

Patients with group 3 pulmonary hypertension often develop cor pulmonale, which further worsens hypoxemia and perpetuates pulmonary hypertension.

Differential Diagnoses

Galiè N, McLaughlin VV, Rubin LJ, Simonneau G. An overview of the 6th World Symposium on Pulmonary Hypertension. Eur Respir J. 2019 Jan. 53 (1):[QxMD MEDLINE Link].
Dunham-Snary KJ, Wu D, Sykes EA, Thakrar A, Parlow LR, Mewburn JD, et al. Hypoxic Pulmonary Vasoconstriction: From Molecular Mechanisms to Medicine. Chest. 2017 Jan. 151 (1):181-192. [QxMD MEDLINE Link].
Hong Z, Kutty S, Toth PT, Marsboom G, Hammel JM, Chamberlain C, et al. Role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in oxygen sensing and constriction of the ductus arteriosus. Circ Res. 2013 Mar 1. 112 (5):802-15. [QxMD MEDLINE Link].
Weir EK, López-Barneo J, Buckler KJ, Archer SL. Acute oxygen-sensing mechanisms. N Engl J Med. 2005 Nov 10. 353 (19):2042-55. [QxMD MEDLINE Link].
McMurtry IF, Davidson AB, Reeves JT, Grover RF. Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. Circ Res. 1976 Feb. 38 (2):99-104. [QxMD MEDLINE Link].
Post JM, Hume JR, Archer SL, Weir EK. Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol. 1992 Apr. 262 (4 Pt 1):C882-90. [QxMD MEDLINE Link].
Archer SL, Weir EK, Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation. 2010 May 11. 121 (18):2045-66. [QxMD MEDLINE Link].
Ang SO, Chen H, Hirota K, Gordeuk VR, Jelinek J, Guan Y, et al. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat Genet. 2002 Dec. 32 (4):614-21. [QxMD MEDLINE Link].
Hickey MM, Richardson T, Wang T, Mosqueira M, Arguiri E, Yu H, et al. The von Hippel-Lindau Chuvash mutation promotes pulmonary hypertension and fibrosis in mice. J Clin Invest. 2010 Mar. 120 (3):827-39. [QxMD MEDLINE Link].
Smith TG, Brooks JT, Balanos GM, Lappin TR, Layton DM, Leedham DL, et al. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology. PLoS Med. 2006 Jul. 3 (7):e290. [QxMD MEDLINE Link].
Glover RH, Newsou L. Further Studies on Brisket Disease. J Agricult Res. 1918. 15(0):409.
Groves BM, Droma T, Sutton JR, McCullough RG, McCullough RE, Zhuang J, et al. Minimal hypoxic pulmonary hypertension in normal Tibetans at 3,658 m. J Appl Physiol (1985). 1993 Jan. 74 (1):312-8. [QxMD MEDLINE Link].
Moore LG. Comparative human ventilatory adaptation to high altitude. Respir Physiol. 2000 Jul. 121 (2-3):257-76. [QxMD MEDLINE Link].
Peñaloza D, Sime F, Banchero N, Gamboa R, Cruz J, Marticorena E. Pulmonary hypertension in healthy men born and living at high altitudes. Am J Cardiol. 1963. 11(2):150-57.
Tsangaris I, Tsaknis G, Anthi A, Orfanos SE. Pulmonary hypertension in parenchymal lung disease. Pulm Med. 2012. 2012:684781. [QxMD MEDLINE Link].
Naeije R, Barberà JA. Pulmonary hypertension associated with COPD. Crit Care. 2001 Dec. 5 (6):286-9. [QxMD MEDLINE Link].
Wilkinson M, Langhorne CA, Heath D, Barer GR, Howard P. A pathophysiological study of 10 cases of hypoxic cor pulmonale. Q J Med. 1988 Jan. 66 (249):65-85. [QxMD MEDLINE Link].
Peinado VI, Barberá JA, Abate P, Ramírez J, Roca J, Santos S, et al. Inflammatory reaction in pulmonary muscular arteries of patients with mild chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 May. 159 (5 Pt 1):1605-11. [QxMD MEDLINE Link].
Jarman ER, Khambata VS, Yun Ye L, Cheung K, Thomas M, Duggan N, et al. A translational preclinical model of interstitial pulmonary fibrosis and pulmonary hypertension: mechanistic pathways driving disease pathophysiology. Physiol Rep. 2014 Sep 1. 2 (9):1605-11. [QxMD MEDLINE Link].
Adegunsoye A, Ramachandran S. Etiopathogenetic mechanisms of pulmonary hypertension in sleep-related breathing disorders. Pulm Med. 2012. 2012:273591. [QxMD MEDLINE Link].
Elwing J, Panos RJ. Pulmonary hypertension associated with COPD. Int J Chron Obstruct Pulmon Dis. 2008. 3 (1):55-70. [QxMD MEDLINE Link].
Nathan SD, Shlobin OA, Ahmad S, Koch J, Barnett SD, Ad N, et al. Serial development of pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Respiration. 2008. 76 (3):288-94. [QxMD MEDLINE Link].
Kessler R, Chaouat A, Weitzenblum E, Oswald M, Ehrhart M, Apprill M, et al. Pulmonary hypertension in the obstructive sleep apnoea syndrome: prevalence, causes and therapeutic consequences. Eur Respir J. 1996 Apr. 9 (4):787-94. [QxMD MEDLINE Link].
Roux F, D'Ambrosio C, Mohsenin V. Sleep-related breathing disorders and cardiovascular disease. Am J Med. 2000 Apr 1. 108 (5):396-402. [QxMD MEDLINE Link].
Houtchens J, Martin D, Klinger JR. Diagnosis and management of pulmonary arterial hypertension. Pulm Med. 2011. 2011:845864. [QxMD MEDLINE Link].
Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004 Mar 4. 350 (10):1005-12. [QxMD MEDLINE Link].
Leuchte HH, Baumgartner RA, Nounou ME, Vogeser M, Neurohr C, Trautnitz M, et al. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med. 2006 Apr 1. 173 (7):744-50. [QxMD MEDLINE Link].
Fang A, Studer S, Kawut SM, Ahya VN, Lee J, Wille K, et al. Elevated pulmonary artery pressure is a risk factor for primary graft dysfunction following lung transplantation for idiopathic pulmonary fibrosis. Chest. 2011 Apr. 139 (4):782-787. [QxMD MEDLINE Link].
Oswald-Mammosser M, Weitzenblum E, Quoix E, Moser G, Chaouat A, Charpentier C, et al. Prognostic factors in COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure. Chest. 1995 May. 107 (5):1193-8. [QxMD MEDLINE Link].
Sajkov D, Wang T, Saunders NA, Bune AJ, Mcevoy RD. Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2002 Jan 15. 165 (2):152-8. [QxMD MEDLINE Link].
Hurdman J, Condliffe R, Elliot CA, Swift A, Rajaram S, Davies C, et al. Pulmonary hypertension in COPD: results from the ASPIRE registry. Eur Respir J. 2013 Jun. 41 (6):1292-301. [QxMD MEDLINE Link].
Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J. 2008 Nov. 32 (5):1371-85. [QxMD MEDLINE Link].
Saadjian AY, Philip-Joet FF, Vestri R, Arnaud AG. Long-term treatment of chronic obstructive lung disease by Nifedipine: an 18-month haemodynamic study. Eur Respir J. 1988 Aug. 1 (8):716-20. [QxMD MEDLINE Link].
Stolz D, Rasch H, Linka A, Di Valentino M, Meyer A, Brutsche M, et al. A randomised, controlled trial of bosentan in severe COPD. Eur Respir J. 2008 Sep. 32 (3):619-28. [QxMD MEDLINE Link].
D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991 Sep 1. 115 (5):343-9. [QxMD MEDLINE Link].

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Author

Varun Halani, MD Fellow in Pulmonary Disease and Critical Care Medicine, St Louis University Hospital, St Louis University School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Edward Charbek, MD, FCCP Assistant Professor of Internal Medicine, Associate Director of Pulmonary and Critical Care Fellowship Program, Division of Pulmonary, Critical Care and Sleep Medicine, St Louis University School of Medicine; Medical Director, Kindred Hospital-St Louis

Edward Charbek, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.