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Radiology > CHEST
Pulmonary Hypertension
Article Last Updated: Mar 1, 2004
AUTHOR AND EDITOR INFORMATION
Section 1 of 12  
Author: Davinder Jassal, MD, BSc, FACC, FRCPC, Clinical and Research Cardiac Echocardiography Fellow, Department of Cardiology, Massachusetts General Hospital, Harvard Medical School
Davinder Jassal is a member of the following medical societies: American College of Cardiology, American College of Physicians-American Society of Internal Medicine, American Heart Association, and Canadian Medical Association
Coauthor(s):
Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St. Boniface General Hospital;
Bruce Maycher, MD, Director of Pulmonary Radiology, St Boniface General Hospital; Associate Professor, Department of Radiology, University of Manitoba
Editors: Judith K Amorosa, MD, FACR, Clinical Professor and Program Director, Department of Radiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School; Consulting Staff, Department of Radiology, Robert Wood Johnson University Hospital; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; John D Newell, Jr, MD, FACR, FCCP, FASER, Co-Director of Thoracic Imaging, UCDHSC; Director of Lung Imaging Center, Professor of Radiology and Professor of Medicine, Department of Radiology, University of Colorado Health Sciences Center, National Jewish Medical and Research Center; Univ. Colorado Hospital; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center
Author and Editor Disclosure
Synonyms and related keywords:
pulmonary heart disease, vascular disease, hypertension, persistent fetal circulation syndrome, cardiovascular disease, primary pulmonary hypertension, PPH, secondary pulmonary arterial hypertension, SPAH
Background
Normal pulmonary circulation is a high-flow, low-resistance circuit capable of accommodating the entire right ventricular output at one fifth the pressure of the systemic circulation level. The thin-walled right ventricle functions primarily as a flow-generator pump and is particularly sensitive to increases in its afterload. Increased pulmonary artery pressure and pulmonary vascular resistance characterize pulmonary hypertension. Pulmonary hypertension may be divided into primary and secondary forms. Primary pulmonary hypertension (PPH) is a disease of unknown etiology, whereas secondary pulmonary arterial hypertension (SPAH) is due to either intrinsic parenchymal disease of the lung or disease extrinsic to the lung.
Pathophysiology
Pulmonary hypertension is conventionally categorized into primary and secondary forms. Pulmonary hypertension is present when the systolic and mean pressures in the pulmonary arteries exceed 30 and 20 mm Hg, respectively.
Causes
In PPH, the precise mechanism is unknown. Presumed mechanisms include the following:
- Endothelial dysfunction: With impaired production of both prostacyclin and nitrous oxide, endothelin is overproduced. This overproduction results in vasoconstriction and remodeling of the pulmonary vasculature.
- Voltage-gated K channel: A defect in this ion channel changes the resting membrane potential, increasing intracellular calcium and leading to pulmonary vasoconstriction.
- Thrombosis in situ: Injury to the endothelial lining of the vessel wall, abnormal fibrinolysis, and platelet abnormalities may all contribute to thrombus formation.
The etiologies of PPH include the following:
- Use of appetite suppressants such as fenfluramine and dexfenfluramine may be associated with an increased risk of PPH (odds ratio, 6.3), as shown in a recent case control study.
- PPH may also be inherited as an autosomal dominant trait.
- Cocaine or amphetamine ingestion may be another contributing factor.
In secondary hypertension, the mechanisms are often multifactorial, depending on the underlying etiology. However, 3 interactive variables exist.
- Hypoxic vasoconstriction: Chronic obstructive lung disease, sleep apnea, polio, and myasthenia gravis are some etiologies. The administration of oxygen is recommended for patients with secondary causes of SPAH due to these mechanisms.
- Decreased area of the pulmonary vascular bed: Collagen vascular disease, HIV infection, advanced liver disease, and toxins are various etiologies. Pulmonary embolism (PE) is the most common etiology and characterized by occlusion of the pulmonary arterial system. Although anticoagulation is the treatment of choice, most PEs are diagnosed at autopsy.
- Volume/pressure overload may also be a factor.
More common causes include congestive heart failure (CHF) secondary to coronary artery disease, hypertension, and valvular disease. Less commonly, atrial and ventricular septal defects are involved.
Further classification
Secondary pulmonary hypertension may be further categorized as pulmonary venous hypertension, chronic hypoxia with secondary vasoconstriction of the pulmonary vasculature, pulmonary artery obstruction, and left-to-right shunts.
Pulmonary venous hypertension is the most common form of pulmonary hypertension and usually due to left-sided heart disease. Pulmonary hypertension develops as a result of the obstruction of blood flow downstream from the pulmonary vein. Causes of pulmonary venous hypertension from distal to proximal of the pulmonary vasculature include coarctation of the aorta, aortic stenosis, aortic regurgitation, hypertrophic cardiomyopathy, constrictive pericarditis, restrictive cardiomyopathy, dilated cardiomyopathy, mitral stenosis, mitral regurgitation, and left atrial myxoma.
With chronic hypoxia with secondary vasoconstriction of the pulmonary vasculature, alveolar hypoxia induces vasoconstriction of the pulmonary vascular bed, causing high pulmonary resistance and hypertension with right ventricular failure. Causes include restrictive lung disease (obesity, pneumoconiosis, neuromuscular disorders), and obstructive lung diseases (asthma, chronic obstructive pulmonary disease [COPD], bronchiectasis).
Regarding pulmonary artery obstruction, chronic major thromboembolic vessel disease is a treatable cause of pulmonary hypertension that results in anatomical obstruction of the arteries. Thrombotic disorders include sickle cell disease and other coagulation disorder. Embolic disease includes chronic thromboemboli, connective tissue disease, lupus, and schistosomiasis.
Individuals with pulmonary hypertension due to left-to-right shunts have high blood flow to the pulmonary vessels, which leads to increased pulmonary vascular resistance over time with reversal of the shunt (Eisenmenger complex). Extracardiac shunts include patent ductus arteriosus, and intracardiac shunts include ventricular and atrial septal defects.
Frequency
United States
The incidence of PPH is approximately 2 cases per million individuals in the general population. Although most cases of PPH are sporadic, approximately 10% are familial.
The incidence of SPAH is dependent on its etiology. On the basis of the pathophysiology as described above, the most common causes include (1) Hypoxic vasoconstriction (COPD), (2) pulmonary vasculature obliteration (PE), and (3) pressure/volume overload (CHF).
COPD is the fourth leading cause of mortality in the US. Although hospital admissions have decreased for many conditions, the number of hospital discharges for COPD in the US rose from 400,000 in 1985 to 460,000 in 1993. The annual incidence of PE is 300,000 per year, with a mortality rate of 30% without treatment. Approximately 5 million patients in the US are admitted with a diagnosis of CHF, making it the leading cause of hospitalization in the population older than 65 years. According to the Framingham data, the prevalence of CHF is 8 cases per 1000 men and 6 cases per 1000 women.
International
Frequency data are difficult to confirm, as there are no international registries tracking the incidence and prevalence of pulmonary hypertension.
Mortality/Morbidity
The natural history of PPH was evaluated in the National Institutes of Health (NIH) registry in 1981-1987. Of the 194 patients included in the study, 63% were female and 37% were male. The mean age was 36 years, with no ethnic differences. The median survival after diagnosis was 2.5 years.
Functional class is a strong predictor of PPH. Patients in classes II and III have a mean survival of 3.5 years. Conversely, those in functional class IV have a mean survival of 6 months.
The most common cause of death in patients with PPH is progressive right heart failure, followed by sudden cardiac death.
The secondary causes of PPH—chronic obstructive lung disease, thromboembolic disease, and CHF— cause significant morbidity and mortality, as described below.
- COPD is estimated to affect approximately 15 million people in the US. It is the fourth leading cause of death, as described previously, and the second leading cause of disability in the US. The prevalence and mortality rates for COPD have increased 30-40% since 1982, mainly as a result of cigarette smoking. The mortality rate 10 years after diagnosis is 50%.
- The incidence of pulmonary thromboembolism is approximately 1 case per 1000 population per year, with a higher prevalence in men. In the US, more than 250,000 patients are hospitalized with PE. In the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) trial, the 3-month mortality rate was approximately 15%.
- CHF is a major public issue in the industrial world. It is the most common cardiovascular condition that is increasing in both incidence and prevalence. In the US, approximately 1 million hospital admissions and 40,000 deaths due to CHF will occur.
Race
The only database registry is that of the National Institutes of Health, and the racial data are not apparent.
Sex
In PPH, the female-to-male preponderance is 1.7:1.
Age
- Most individuals with PPH present in the third and fourth decades, with a mean patient age of 36 years.
- Exceptions do occur, and patients range from infants to the elderly.
- Most individuals with COPD, PE, and CHF present in their late 40s and early 50s.
Anatomy
The pulmonary vasculature involves a diverse system of vessels—arteries, arterioles, capillaries, venules, and veins—that are responsible for accommodating the entire cardiac output.
The pulmonary arterial system begins as the main pulmonary artery, beyond the pulmonic valve. The main pulmonary artery bifurcates into the left and right systems. The left pulmonary artery passes posteriorly above the left bronchus, whereas the right pulmonary artery passes behind the ascending aorta, anterior and inferior to the right main bronchus, toward the right hilum.
The left pulmonary artery divides into an ascending ramus supplying the upper lobe and a descending ramus supplying the lower lobe. The right pulmonary artery bifurcates into an ascending ramus supplying the upper lobe and a descending ramus supplying the middle and lower lobes.
The pulmonary venous system runs within the interlobular septa adjacent to the pulmonary arteries. The 2 superior and 2 inferior pulmonary veins empty into the left atrium. The superior pulmonary veins drain the right upper and middle lobes and the left upper lobe, whereas the inferior pulmonary veins drain the lower lobes.
Clinical Details
The interval between the onset of symptoms of PPH to diagnosis is about 2 years. The most common presenting symptoms are the following:
- Exertional dyspnea
- Fatigue and lethargy
- Angina
- Syncope
- Raynaud phenomenon
- Edema
Less common symptoms include cough, hemoptysis, and hoarseness.
Physical examination centers on detecting signs of right ventricular hypertrophy and right ventricular failure secondary to pulmonary hypertension.
On examination of the jugular venous pressure in the neck, the following may be observed:
- Prominent A wave with right ventricular hypertrophy
- Prominent V wave in acute right ventricular failure, leading to tricuspid regurgitation
- Low-volume carotid arterial pulse with a normal upstroke
On the precordial examination, the following may be observed:
- Palpable S2 from the increased intensity of the pulmonic component
- Left parasternal heaving from right ventricular hypertrophy
- Increased P2, narrowly split
- Right ventricular third heart sound
- Right ventricular fourth heart sound
- Systolic ejection murmur (a high-pitched tricuspid regurgitation murmur)
- A high-pitched early diastolic murmur of pulmonic regurgitation
Finally, on extracardiac physical examination, one may observe the following:
- Hepatosplenomegaly
- Pulsatile liver
- Ascites
- Peripheral edema
The electrocardiogram is useful for demonstrating signs of right ventricular hypertrophy and strain. These signs include the following:
- Right-axis deviation
- R/S ratio greater than 1 in lead V1
- Right atrial enlargement as indicated by an increased P-wave amplitude in lead II
- Right bundle branch block
In summary, pulmonary veno-occlusive disease is idiopathic, usually not diagnosed prior to death, occurs with pulmonary hypertension, and has no adequate treatment.
Preferred Examination
In an individual with suspected pulmonary hypertension, PPH is the diagnosis of exclusion. Hence, a designated algorithm should be used to exclude secondary causes of pulmonary hypertension. The following are proposed investigations:
- Autoantibody tests, HIV test, liver function tests
- Electrocardiography
- Chest radiography
- Pulmonary function tests
- Echocardiography
- Ventilation-perfusion (V/Q) scanning
- Computed tomographic pulmonary angiography (CTPA)
- Pulmonary angiography
- Cardiac catheterization
- Magnetic resonance imaging (MRI)
As a baseline, the first 5 tests are reasonable for substantiating the presence of increased pressures on the right side of the pulmonary vascular system. On the basis of the results, a more focused approach to establish the etiology of the pulmonary hypertension may then involve tests 6-9. Most patients with secondary pulmonary hypertension do not require right-heart catheterization before beginning a trial with vasodilators. However, select patients, such as those with collagen vascular disease, should undergo invasive investigations. Imaging studies are important in individuals with pulmonary hypertension, for the following purposes:
- Detecting pulmonary hypertension (echocardiography, cardiac catheterization)
- Differentiating the cause (echocardiography, V/Q scanning, CTPA, cardiac catheterization, pulmonary angiography, MRI)
- Determining the severity (echocardiography, cardiac catheterization)
- Evaluating the status of the right ventricle (echocardiography, cardiac catheterization, MRI)
Various imaging modalities, including chest radiography, CT, MRI, pulmonary function tests, echocardiography, and angiography, have variable success in detecting the presence and severity of pulmonary hypertension. PPH is diagnosed if no underlying etiology is found. See Image 1 for secondary causes of pulmonary hypertension.
Other Problems to be Considered
Helical CT, pulmonary embolism
Findings
Chest radiographic findings of pulmonary hypertension (see Images 2-3) include the following:
- Enlarged central pulmonary arteries that taper distally may be depicted.
- A dilated right heart due to right ventricular enlargement is seen as a decrease in the retrosternal space on the lateral image. Right atrial enlargement may be present if significant tricuspid regurgitation is present. This finding may be recognized by the widened right heart border in the frontal projection and enlargement of the right atrial appendage in the lateral projection, which is seen as increased retrosternal opacity above the expected location of the right ventricle.
- Peripheral vessel opacity-oligemic lung fields may be observed. This oligemia may be asymmetric. This is also a useful finding suggestive of chronic PE.
- An increase in the transverse diameter of the right interlobar artery is indicative of pulmonary hypertension. The upper limit of the transverse diameter of the right interlobar artery from its lateral aspect to the intermediate bronchus is 15 mm in women and 16 mm in men.
- The transverse diameter of the left interlobar artery is difficult to appreciate on the posteroanterior (PA) view. Using a lateral view, one can measure from the circular lucency of the left upper lobe bronchus to the posterior margin of the vessel; the upper limit is 18 mm.
- Evidence of right atrial dilatation and right ventricular dilatation may be noted.
- Kerley B lines may be present. These indicate the presence of pulmonary venous hypertension.
Causes of SPAH and their appearances include the following:
- Atrial septal defect is characterized by cardiomegaly, enlargement of the right atrium and ventricle, and enlargement of the central pulmonary arteries. Also present is rapid tapering, with increased vascularity in the periphery of the lung.
- Eisenmenger syndrome is characterized by peripheral oligemia, indicating the reversal of a left-to-right shunt due to increased vascular resistance. The peripheral vasculature is diminished, and the cardiac morphology is consistent with cor pulmonale.
Findings
CTPA is useful in delineating the anatomic detail of the pulmonary vasculature. Contrast-enhanced images may show intraluminal abnormalities in the arteries and veins, which are useful for confirming etiologies such as thromboembolic disease. Sometimes, if the emboli are large, they may be seen in the pulmonary arteries on a routine contrast-enhanced CT scans. CTPA, and often conventional pulmonary arteriography, is necessary for an adequate evaluation of chronic PE. The technique of CTPA includes a rapid infusion at 3-4 mL/s for a total of 80-120 mL. Careful review of the images on a workstation is the optimal method of detecting subtle emboli. Evaluation of the lung windows to detect abnormalities of perfusion (mosaic perfusion) is necessary, as occlusions of major pulmonary arterial branches may not be present in a subset of patients with chronic pulmonary thromboembolism. High-resolution CT (HRCT) of the chest has a role in the evaluation of pulmonary hypertension in patients with suspected diffuse lung disease, eg, in patients with collagen vascular disease. More than a decade ago, Kuriyama et al determined that a main pulmonary artery of 29 mm or larger, as shown on a CT scan, has a sensitivity of 69% and a specificity of 100% for predicting pulmonary hypertension. The widest portion of the main pulmonary artery within 3 cm of the bifurcation was used to determine the value. In addition, Tan et al demonstrated that individuals with intrinsic lung disease can be identified as having pulmonary hypertension if the main pulmonary artery is >29 mm. CT is a useful noninvasive procedure for confirming the presence of pulmonary hypertension (see Image 4). The upper limit of normal for the diameter of the pulmonary artery is 28.6 mm. A value greater than 28.6 mm suggests increased pressures in the pulmonary system.
Degree of Confidence
CTPA is the best method for demonstrating emboli. HRCT is useful for demonstrating lung disease, which may account for secondary pulmonary hypertension.
Findings
MRI with contrast enhancement allows one to distinguish between the pulmonary vasculature and mediastinal adenopathy.
MRI has capabilities similar to those of echocardiography in the diagnosis and treatment of patients with pulmonary hypertension. MRI is useful for measuring the mass, volume, and overall function of the right ventricle. MRI is also useful for detecting shunt lesions contributing to pulmonary hypertension. Acute and chronic pulmonary thromboembolic disease can be confirmed by using this imaging modality.
Degree of Confidence
The disadvantages with MRI include limitations in individuals with cardiac pacemakers and defibrillators, its limited availability and cost, and difficulty in assessing estimate PA pressures with MRI.
Findings
In evaluating pulmonary hypertension, echocardiography can be used to identify secondary causes, such as congenital, valvular, and myocardial disease. In addition, one may estimate pulmonary artery systolic pressure with this method. Specifically, the World Health Organization (WHO) has defined pulmonary hypertension as a systolic pressure greater than 30 mm Hg; this corresponds to a tricuspid regurgitant velocity of 3.0 m/s on echocardiography. The following findings for pulmonary hypertension are confirmed on echocardiography (see Image 5): (1) Right atrial and ventricular enlargement (If right ventricular end-diastolic pressures are greater than 20 mm hg, the risk of sudden death is relatively high.), (2) paradoxical movement of the interventricular septum, and tricuspid regurgitation. Doppler echocardiography is the most reliable noninvasive method for estimating pulmonary artery pressure. Tricuspid regurgitation is often present in pulmonary hypertension. It is detected in more than 90% of patients with severe pulmonary hypertension, with a correlation of more than 95% when the pressure is measured by means of catheterization.
Findings
Radioisotope perfusion lung scanning is performed with intravenous injection of particles of albumin labeled with technetium 99m. As these particles perfuse the lung, the lungs are imaged by using a gamma camera to obtain anterior, posterior, lateral, and oblique views. One would expect a normal distribution of these particles, which produce 2 blackened lung-shaped shadows. In PPH, the V/Q scan is usually normal. In secondary pulmonary hypertension due to chronic thromboembolic disease, emboli are responsible for blocking the branches of the pulmonary artery. The lung tissue peripheral to the block is not perfused; this block results in a defect on the scan. When findings in the perfusion scan are abnormal, a ventilation scan is obtained next by using inhalational radioactive xenon 133. A number of lung diseases, including pneumonia and COPD, can cause alterations in the ventilation component, whereas uncomplicated PE does not. Thus, a patient with a high likelihood of PE has an abnormal perfusion scan with a normal ventilation component (see Image 6).
Findings
Right heart catheterization may be required (see Image 7). Pulmonary angiography is the most accurate modality for evaluating the anatomy and pathophysiology of pulmonary hypertension. Berberich and Hirsch obtained the first pulmonary angiogram in 1923, and Robb and Steinberg later optimized the technique in 1931. This examination is the criterion standard for the diagnosis of pulmonary hypertension. Pulmonary angiography should be performed when the results of V/Q scanning cannot exclude chronic thromboembolic disease as an etiology for the elevated pulmonary pressures. The angiogram reveals large central pulmonary arteries with marked peripheral tapering. The disadvantage of pulmonary angiography is that it is an invasive procedure as one cannulates the right side of the heart and the pulmonary artery. Complications include (1) transient rhythm disturbances that respond to the removal of the catheter, (2) cardiac perforation leading to pericardial tamponade, and (3) nephrotoxicity. In patients with an elevated creatinine level (1.5 X normal), the use of high-osmolar contrast material poses a risk of nephrotoxicity. This problem is less commonly seen with the selective use of small amounts of low-osmolar nonionic contrast material. The frequency of complications with pulmonary angiography is limited to <5% of cases examined.
Unfortunately, PPH is a progressive disease that has no cure. Although spontaneous remission has been reported, this is exceptionally rare. Approximately 25-35% of individuals with PPH respond to the acute administration of vasodilators and/or anticoagulants. Vasodilation Although vasodilator therapy may decrease pulmonary vasculature resistance, few studies show long-term clinical improvement in patients with pulmonary hypertension. Vasodilators that are short acting include nitrous oxide, epoprostenol (prostacyclin), and adenosine. If the aforementioned drugs can reduce the pulmonary artery pressures, thereby increasing cardiac output, the morbidity and mortality of this disease may theoretically improve. From the perspective of evidence-based medicine, short-term therapy with calcium channel blockers has conflicting results in terms of improving pulmonary hypertension. Long-term benefits have not been demonstrated. Longer-acting medications include calcium channel blockers, such as diltiazem and dihydropuridines, which improve morbidity in 20-30% of individuals. Verapamil, with its negative inotropic effects, is not used in the treatment of PPH. Anticoagulation Patients with PPH are at an increased risk of thrombosis. Therefore, anticoagulation therapy is recommended for patients at high risk for thromboembolism; the more general use of warfarin therapy is not recommended. Studies have shown that anticoagulation with warfarin, adjusting for an international normalized ratio (INR) of 2-3, prolongs life in individuals with PPH.
Special Concerns
- Issues in pregnancy
- Physiologic changes that occur in pregnancy may activate PPH and result in considerable morbidity and mortality for both the mother and fetus.
- As the circulating blood volume increases, so does oxygen consumption, leading to an increase in right ventricular volume.
- Syncope and cardiac arrest may occur during active labor and delivery, as well.
- For the aforementioned reasons, pregnancy should be discouraged in women with PPH.
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Pulmonary hypertension. Chest radiograph in a patient with secondary pulmonary hypertension reveals enlarged pulmonary arteries. This patient was found to have an atrial septal defect. |
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Pulmonary hypertension. Spiral CT scan in a patient with pulmonary hypertension reveals enlarged pulmonary arteries and an absence of thrombosis. |
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Pulmonary hypertension. CT pulmonary angiogram in a 42-year-old man who experienced severe chest pain after a long flight. Image demonstrates clots in both the right and left main pulmonary arteries. |
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Pulmonary hypertension. Ventilation-perfusion (V/Q) scans show bilateral mismatched segmental and subsegmental defects due to chronic thromboembolic disease, which has lead to secondary pulmonary arterial hypertension. |
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Pulmonary hypertension. Selective right pulmonary arteriogram demonstrates large central pulmonary arteries and attenuation of the peripheral vessels, without any definite demonstrable thrombi. |
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Pulmonary hypertension. Selective left pulmonary arteriogram reveals large central pulmonary arteries and attenuation of the peripheral vessels, without thrombi. |
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Pulmonary hypertension. Image shows an example of the successful resolution of secondary pulmonary arterial hypertension in a patient who underwent pulmonary arterial thromboendarterectomy with the removal of thrombi. |
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- Abman SH. Neonatal pulmonary hypertension: A physiologic approach to treatment. Pediatr Pulmonol. Feb 2004;37 Suppl 26:127-8.
- Aschner JL. New therapies for pulmonary hypertension in neonates and children. Pediatr Pulmonol. Feb 2004;37 Suppl 26:132-5.
- Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med. Feb 1 1996;334(5):296-302. [Medline].
- Christman BW, McPherson CD, Newman JH, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. Jul 9 1992;327(2):70-5. [Medline].
- Frank H, Mlczoch J, Huber K, et al. The effect of anticoagulant therapy in primary and anorectic drug- induced pulmonary hypertension. Chest. Sep 1997;112(3):714-21. [Medline].
- Fraser RG, Pare JA, Pare PD. Pulmonary hypertension and edema. In: Diagnosis of Diseases of the Chest. Vol 3. 4th ed. Philadelphia: WB Saunders;. 1999.
- Gaine SP, Rubin LJ. Primary pulmonary hypertension [published erratum appears in Lancet 1999 Jan 2;353(9146):74]. Lancet. Aug 29 1998;352(9129):719-25. [Medline].
- Gonçalves RC, Buschpigell CA, Lopes AA. Circulating blood volumes in pulmonary hypertension associated with erythrocytosis--the effects of therapeutic hemodilution. Cardiol Young. Dec 2003;13(6):544-50. [Medline].
- Grossman W, Braunwald E. Pulmonary hypertension. In: Heart Disease: A Textbook of Cardiovascular Medicine. 4th ed. Philadelphia: WB Saunders;. 1997.
- Lilienfeld DE, Rubin LJ. Mortality from primary pulmonary hypertension in the United States, 1979-1996. Chest. Mar 2000;117(3):796-800. [Medline].
- Miller SW, Waltman AC. The pulmonary circulation. In: Radiology: Diagnosis, Imaging, Intervention. Philadelphia: Lippincott;. 2001.
- Morgan JM, Griffiths M, du Bois RM, Evans TW. Hypoxic pulmonary vasoconstriction in systemic sclerosis and primary pulmonary hypertension. Chest. Mar 1991;99(3):551-6. [Medline].
- Pistolesi M, Milne ENC. Radiology of cardiopulmonary hemodynamic disturbances. In: Radiology: Diagnosis, Imaging, and Intervention. Philadelphia: Lippincott;. 2001.
- Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med. Jul 9 1992;327(2):76-81. [Medline].
- Rich S, Levitsky S, Brundage BH. Pulmonary hypertension from chronic pulmonary thromboembolism. Ann Intern Med. Mar 1988;108(3):425-34. [Medline].
- Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. Aug 1987;107(2):216-23. [Medline].
- Rosenzweig EB, Kerstein D, Barst RJ. Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. Circulation. Apr 13 1999;99(14):1858-65. [Medline].
- Rubin LJ. Primary pulmonary hypertension. N Engl J Med. Jan 9 1997;336(2):111-7. [Medline].
- Rubin LJ. Primary pulmonary hypertension. Chest. Jul 1993;104(1):236-50. [Medline].
- Weiss BM, Zemp L, Seifert B, Hess OM. Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996. J Am Coll Cardiol. Jun 1998;31(7):1650-7. [Medline].
Pulmonary Hypertension excerpt Article Last Updated: Mar 1, 2004
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