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Evaluation and Management of the Patient with Pulmonary Arterial Hypertension

Lewis J. Rubin, MD; and David B. Badesch, MD
[+] Article, Author, and Disclosure Information

From the University of California, San Diego, Medical Center, La Jolla, California; and University of Colorado Health Sciences Center, Denver, Colorado.

Acknowledgments: The authors thank their colleagues who participated in the 3rd World Symposium on Pulmonary Artery Hypertension and who served on the ACCP Evidence-Based Guidelines panel, from whose work they have drawn in the preparation of this manuscript.

Potential Financial Conflicts of Interest: Consultancies: L.J. Rubin (Actelion, Pfizer Inc., Schering, CoTherix, United Therapeutics, Myogen), D.B. Badesch (GlaxoWellcome/GlaxoSmithKline, Actelion, Berlex, Astra Merck, AstraZeneca, Myogen, Intermune, Forest Laboratories, Encysive, Exhale Therapeutics/CoTherix, Pfizer, Scios, MondoBiotech, PR Pharmaceuticals); Honoraria: L.J. Rubin (Actelion, Myogen), D.B. Badesch (Glaxo Wellcome/GlaxoSmithKline, Actelion, Pfizer Inc., Encysive, United Therapeutics); Stock ownership or options (other than mutual funds): D.B. Badesch (Johnson & Johnson); Expert testimony: L.J. Rubin (Appetite suppressant litigation), D.B. Badesch (Appetite suppressant litigation); Grants received: L.J. Rubin (Actelion, Pfizer Inc., CoTherix, Myogen, National Institutes of Health), D.B. Badesch (Glaxo Wellcome/GlaxoSmithKline, United Therapeutics, Boehringer Ingelheim, Actelion, ICOS Corp./Texas Biotechnologies, Encysive, Pfizer Inc., Myogen, CoTherix, Lilly/ICOS, American Lung Association, American Heart Association, National Institutes of Health, Scleroderma Foundation).

Requests for Single Reprints: Lewis J. Rubin, MD, University of California, San Diego, Medical Center, 9300 Campus Point Drive, M/C 7381, La Jolla, CA 92037-7381.

Current Author Addresses: Dr. Rubin: University of California, San Diego, Medical Center, 9300 Campus Point Drive, La Jolla, CA 92037-7381.

Dr. Badesch: University of Colorado Health Sciences Center, Box C-272, 4200 East Ninth Avenue, Denver, CO 80262.

Ann Intern Med. 2005;143(4):282-292. doi:10.7326/0003-4819-143-4-200508160-00009
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Increased pressure in the pulmonary circulation, or pulmonary hypertension, is a common disorder that may complicate various cardiopulmonary conditions, including severe obstructive airways disease and left ventricular dysfunction. An increase in pulmonary arterial pressure that is not due to coexistent cardiopulmonary disease, known as pulmonary arterial hypertension, may occur in the absence of a demonstrable cause (idiopathic or familial); as a complication of systemic conditions, such as connective tissue disease, HIV infection, or chronic liver disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or cocaine. The development of disease-specific therapies for pulmonary arterial hypertension over the past decade underscores the importance of diagnosing pulmonary hypertension early in the course of the condition and implementing a treatment strategy that is based on the condition's cause and severity. In this review, the authors present approaches to the diagnosis and management of pulmonary arterial hypertension, using a hypothetical case to highlight the key management points.


Grahic Jump Location
Guideline for approaching the differential diagnosis of pulmonary hypertension (PH).

CHD = congenital heart disease; CO = cardiac output; CT = contrast-enhanced computed tomography of the chest; CTD = connective tissue disease; ECG = electrocardiogram; Echo = Doppler transthoracic echocardiogram; IPAH = idiopathic pulmonary arterial hypertension; LA = left atrial; LV = left ventricular; MRI = magnetic resonance imaging; PA = pulmonary arterial; PAH = pulmonary arterial hypertension; PCWP = pulmonary capillary wedge pressure; PE = pulmonary embolism; PFTs = pulmonary function tests; PVR = pulmonary vascular resistance; RA = right atrial; RAE = right atrial enlargement; RV = right ventricular; RVE = right ventricular enlargement; RVSP = right ventricular systolic pressure; SLE = systemic lupus erythematosus; SvO = mixed venous oxygen saturation; TRV = tricuspid regurgitant velocity; VQ = ventilation–perfusion. (Adapted with permission from reference .)

Grahic Jump Location




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Thyrotoxicosis as a risk factor for pulmonary hypertension
Posted on August 30, 2005
Ronald C Ma
Prince of Wales Hospital, Chinese University of Hong Kong
Conflict of Interest: None Declared

Dear sir,

We read with interest the recent review by Rubin et al on the evaluation and management of patients with pulmonary arterial hypertension. Whilst the authors have pointed out the importance of assessing for underlying autoimmune ¡Vcollagen vascular disease, the need to assess for thyroid dysfunction and autoimmune thyroid disease was not addressed. Previous studies have suggested a link between primary pulmonary hypertension and autoimmune thyroid disease (1). More recently, it has become apparent that thyrotoxicosis is itself an important risk factor for pulmonary hypertension (2, 3). This may partly be due to the haemodynamic effects of hyperthyroidism, as biochemical improvement in thyroid function following treatment has been associated with improvement in pulmonary hypertension on Doppler echocardiography (2, 4). However, there is also evidence suggesting that thyroid autoantibodies present in autoimmune thyroid disease may have a direct role in the pathogenesis of the pulmonary hypertension by contributing to pulmonary vascular endothelial injury. This is supported by a report of pulmonary hypertension associated with neonatal thyrotoxicosis due to transplacental passage of thyroid-stimulating immunoglobulins, and complete reversal of pulmonary hypertension following treatment of the thyrotoxicosis (5). All patients with pulmonary arterial hypertension should be evaluated for thyroid dysfunction as this may be a readily treatable and reversible cause of pulmonary arterial hypertension.

1. Chu JW, Kao PN, Faul JL, Doyle RL. High prevalence of autoimmune thyroid disease in pulmonary arterial hypertension. Chest. 2002;122(5):1668-73.

2. Nakchbandi IA, Wirth JA, Inzucchi SE. Pulmonary hypertension caused by Graves' thyrotoxicosis: normal pulmonary hemodynamics restored by (131)I treatment. Chest. 1999;116(5):1483-5.

3. Marvisi M, Brianti M, Marani G, Del Borello R, Bortesi ML, Guariglia A. Hyperthyroidism and pulmonary hypertension. Respir Med. 2002;96(4):215-20.

4. Merce J, Ferras S, Oltra C, et al. Cardiovascular abnormalities in hyperthyroidism: a prospective Doppler echocardiographic study. Am J Med. 2005;118(2):126-31.

5. O'Donovan D, McMahon C, Costigan C, Oslizlok P, Duff D. Reversible pulmonary hypertension in neonatal Graves disease. Ir Med J. 1997;90(4):147-8.

Thyroid Disease and Pulmonary Artery Hypertension
Posted on October 17, 2005
Lewis J Rubin
University of California, San Diego
Conflict of Interest: None Declared

Dear Sir:

We agree with Ma and Chow that there is some justification for screening patients with pulmonary arterial hypertension (PAH) for thyroid dysfunction. We were among the first to make the observation that thyroid abnormalities might occur with increased frequency in patients with PAH (1). In that report, we speculated that there might be a common underlying autoimmune disorder. The concept that antithyroid antibodies could play a role in the pathogenesis of PAH is indeed quite intriguing, and there have been a number of subsequent reports of both hypo- and hyper-thyroidism occurring in patients with pulmonary hypertension (2-5), although a causal relationship has not been proven.

Irrespective of whether thyroid disease and PAH share a common pathogenic mechanism, their frequent coexistence is important to recognize: thyroid disease produces cardiovascular stresses that are poorly tolerated in the setting of PAH and should therefore be treated aggressively. However, beta adrenergic-receptor blockers, which are commonly used as adjunct therapy in hyperthyroidism, may precipitate worsening of right ventricular dysfunction and should be avoided or used very cautiously.

Lewis J. Rubin, MD La Jolla, CA

David B. Badesch, MD Denver, CO

1 Badesch DB, Wynne KM, Bonvallet S, et al. Hypothyroidism and primary pulmonary hypertension: an autoimmune pathogenetic link? Ann Intern Med 1993; 119:44-46 2 Arroliga AC, Dweik RA, Rafanan AL. Primary pulmonary hypertension and thyroid disease. Chest 2000; 118:1224-1225 3 Curnock AL, Dweik RA, Higgins BH, et al. High prevalence of hypothyroidism in patients with primary pulmonary hypertension. Am J Med Sci 1999; 318:289-292 4 Ferris A, Jacobs T, Widlitz A, et al. Pulmonary arterial hypertension and thyroid disease. Chest 2001; 119:1980-1981 5 Kashyap AS, Kashyap S. Thyroid disease and primary pulmonary hypertension. JAMA 2001; 285:2853-2854

Conflict of Interest:

None declared

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