eMedicine Specialties > Pediatrics: General Medicine > Pulmonology
Pulmonary Hypertension, Idiopathic
Updated: Jul 21, 2008
Introduction
Background
Idiopathic pulmonary artery hypertension (IPAH), previously referred to as primary pulmonary hypertension (PPH), is a relatively recently described entity with an unclear etiology. A new classification scheme has been defined, based on the World Health Organization conference on pulmonary hypertension in 2003. The classification system includes the following:
- (Group 1) Pulmonary artery hypertension
- (1.1) Idiopathic pulmonary hypertension
- (1.2) Familial
- (1.3) Pulmonary hypertension associated with the following:
- (a) Collagen vascular disease
- (b) Congenital heart disease with left-to-right shunt
- (c) Portal hypertension
- (d) Human immunodeficiency virus (HIV) infection
- (e) Drugs (Anorexigens or other toxins)
- (f) Thyroid disorders
- (g) Other entities (Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies)
- (1.4) Persistent pulmonary hypertension of the newborn
- (1.5) Pulmonary veno-occlusive disease
- (Group 2) Pulmonary hypertension with left heart disease
- (2.1) Left atrial or left ventricular disease
- (2.2) Left-sided valvular disease
- (Group 3) Pulmonary hypertension associated with respiratory disorders and/or hypoxemia
- (3.1) Chronic obstructive lung disease
- (3.2) Interstitial lung disease
- (3.3) Sleep-disordered breathing
- (3.4) Alveolar hypoventilation
- (3.5) Chronic exposure to high altitude
- (3.6) Neonatal lung disease
- (3.7) Alveolar-capillary dysplasia
- (3.8) Other
- (Group 4) Pulmonary hypertension due to chronic thrombotic/embolic disease
- (4.1) Thrombotic obstruction of proximal pulmonary arteries
- (4.2) Obstruction of distal pulmonary arteries
- Pulmonary embolism (thrombus, tumor, parasites)
- In situ thrombosis
- (Group 5) Miscellaneous (eg, sarcoid)
IPAH is a serious syndrome, with significant morbidity and mortality. It can be associated with progressive elevation of pulmonary artery pressure and can lead to right ventricular failure. By definition, the cause is unexplained and implies that associated causes of pulmonary hypertension have been ruled out. The definition, therefore, is the same as IPAH in adults: a mean pulmonary artery pressure greater than 25 mm Hg at rest with normal pulmonary capillary wedge pressure and the absence of associated causes of pulmonary hypertension. Some authors believe that including exercise hemodynamic abnormalities in the definition of IPAH is important, especially in the pediatric population; therefore, a mean pulmonary artery pressure of greater than 30 mm Hg with exercise is also considered to be an abnormal response and is consistent with the definition of IPAH.
Pathophysiology
The exact pathogenesis and pathophysiology of IPAH is unclear. The mechanism that appears to be most widely accepted is that of pulmonary vasoconstriction. Studies have suggested that individuals who are predisposed may be exposed to certain stimuli that initiate the characteristic vascular lesions. Various triggers, such as high altitude, hypoxemia, drugs, toxins, sympathetic tone, and autoimmune disorders, can cause pulmonary vasoconstriction in susceptible individuals. Other studies also invoke an imbalance of vasoactive mediators, favoring those of vasoconstriction. Factors such as thromboxane, arachidonate metabolites, and prostacyclin, as well as other endothelial factors, have been invoked. In addition, coagulation abnormalities may occur, supporting the finding of microthrombi in the pulmonary vascular bed, noted at the time of lung biopsy, autopsy, or in explanted lungs at the time of lung transplantation. Whether this is a primary or secondary finding is unknown.
Much experimental work is being conducted in the area of endothelial metabolism of vasoactive substances. Hopefully, this will lead to a better understanding of the control of the pulmonary circulation and to improved and more specific therapies for IPAH.
Frequency
United States
Frequency in children as well as adults is not known. Conceivably, more patients have the disease than previously suspected. As more knowledge of IPAH is currently available, the disease may be more easily recognized. Finally, incidence of familial IPAH has been thought to be 5-10%, with a mode of genetic appearance that appears to be autosomal dominant with incomplete penetrance.
Mortality/Morbidity
Before the age of vasodilator therapy, most children died within 1-2 years of diagnosis whereas adults had a median survival of 2-3 years. Survival has improved, although morbidity and mortality remain significant. Morbidity and mortality rates vary and depend on the age, the degree of pulmonary hypertension, and the response to vasodilator therapy. Death as a result of both acute and chronic right heart failure and its associated arrhythmias may occur. Additionally, patients can be affected by the complications associated with low output. Finally, the morbidity associated with chronic vasodilator therapy and frequent intravenous line infections in patients on long-term continuous intravenous prostacyclin as well as long-term anticoagulation are well known.
Sex
The male-to-female ratio in adults is reported to be 1:1.7. In children, the ratio varies, with some studies showing an equal distribution between females and males in younger children, whereas other studies have shown a female preponderance of 1.5:1.
Clinical
History
Infants and children usually present with symptoms of low cardiac output. The following may be observed:
- Poor appetite
- Poor growth
- Nausea
- Vomiting
- Lethargy
- Sweating
- Tachypnea
- Tachycardia
If infants have a patent foramen ovale, they may also present with cyanosis either at rest or with exercise because of a concomitant right-to-left shunt. In infants and children without the atrial level pop-off, syncope can be a presenting symptom that is somewhat ominous. Older children and adolescents tend to present with exertional dyspnea and chest pain. These are the typical symptoms in adults.
Physical
The physical examination findings are typical of the findings of pulmonary hypertension.
- Typically, the pulmonic component of the second heart sound is accentuated.
- A right ventricular heave with or without chest wall distortion may be noted as a result of right ventricular hypertrophy and/or dysfunction.
- Tricuspid regurgitation is common.
- Clinical signs of right heart failure, such as hepatomegaly, peripheral edema, and acrocyanosis, are rare in infants but can be observed in older children and adults.
Causes
- The exact pathogenesis and pathophysiology of idiopathic pulmonary artery hypertension (IPAH) are unclear. The mechanism that is most widely accepted is that of pulmonary vasoconstriction. Many studies suggest that individuals who are predisposed may be exposed to certain stimuli that initiate the characteristic vascular lesions.
- Various triggers, such as high altitude, hypoxemia, drugs, toxins, sympathetic tone, and autoimmune disorders, can cause pulmonary vasoconstriction in susceptible individuals.
- Other studies also invoke an imbalance of vasoactive mediators favoring vasoconstriction as important in the pathophysiology of IPAH. Factors such as thromboxane, arachidonate metabolites, and prostacyclin and other endothelial factors have been invoked.
- In addition, coagulation abnormalities may occur, supported by the finding of microthrombi in the pulmonary vascular bed, noted at the time of lung biopsy, autopsy, or in explanted lungs at the time of lung transplantation. Whether this is a primary or secondary finding is unknown.
More on Pulmonary Hypertension, Idiopathic |
 Overview: Pulmonary Hypertension, Idiopathic |
| Differential Diagnoses & Workup: Pulmonary Hypertension, Idiopathic |
| Treatment & Medication: Pulmonary Hypertension, Idiopathic |
| Follow-up: Pulmonary Hypertension, Idiopathic |
| References |
| Next Page » |
References
Barst R, Long W, Gersony W. Long-term vasodilator treatment improves survival in children with primary pulmonary hypertension. Cardiol Young. 1993;3 (S1):89.
Atz AM, Wessel DL. Sildenafil ameliorates effects of inhaled nitric oxide withdrawal. Anesthesiology. Jul 1999;91(1):307-10. [Medline].
Atz AM, Adatia I, Lock JE, Wessel DL. Combined effects of nitric oxide and oxygen during acute pulmonary vasodilator testing. J Am Coll Cardiol. Mar 1999;33(3):813-9. [Medline].
Atz AM, Adatia I, Wessel DL. Rebound pulmonary hypertension after inhalation of nitric oxide. Ann Thorac Surg. Dec 1996;62(6):1759-64. [Medline].
Atz AM, Lefler AK, Fairbrother DL, et al. Sildenafil augments the effect of inhaled nitric oxide for postoperative pulmonary hypertensive crises. J Thorac Cardiovasc Surg. Sep 2002;124(3):628-9. [Medline].
Barst R. Primary pulmonary hypertension in children. In: Rubin LJ, Lenfant C, Rich S, eds. Primary Pulmonary Hypertension. New York, NY: Marcel Dekker; 1997:179-225.
Barst RJ. Pharmacologically induced pulmonary vasodilatation in children and young adults with primary pulmonary hypertension. Chest. Apr 1986;89(4):497-503. [Medline].
Barst RJ, McGoon M, McLaughlin V, et al. Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol. Jun 18 2003;41(12):2119-25. [Medline].
Barst RJ, Rubin LJ, McGoon MD, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med. Sep 15 1994;121(6):409-15. [Medline]. [Full Text].
Boucek MM, Edwards LB, Keck BM, et al. The Registry of the International Society for Heart and Lung Transplantation: Sixth Official Pediatric Report--2003. J Heart Lung Transplant. Jun 2003;22(6):636-52. [Medline].
de Hoyos AL, Patterson GA, Maurer JR, et al. Pulmonary transplantation. Early and late results. The Toronto Lung Transplant Group. J Thorac Cardiovasc Surg. Feb 1992;103(2):295-306. [Medline].
Kerstein D, Levy PS, Hsu DT, et al. Blade balloon atrial septostomy in patients with severe primary pulmonary hypertension. Circulation. Apr 1 1995;91(7):2028-35. [Medline]. [Full Text].
Kinsella JP, Neish SR, Shaffer E, Abman SH. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet. Oct 3 1992;340(8823):819-20. [Medline].
Rashid A, Ivy D. Severe paediatric pulmonary hypertension: new management strategies. Arch Dis Child. Jan 2005;90(1):92-8. [Medline]. [Full Text].
Rich S, Brundage BH, Levy PS. The effect of vasodilator therapy on the clinical outcome of patients with primary pulmonary hypertension. Circulation. Jun 1985;71(6):1191-6. [Medline].
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].
Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. Mar 21 2002;346(12):896-903. [Medline].
Rubin LJ, Mendoza J, Hood M, et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med. Apr 1 1990;112(7):485-91. [Medline].
Thoele D, Barst R, Gersony W. Physiologic-based management of primary pulmonary hypertension in children and young adults. J Am Coll Cardiol. 1993;2:402A.
Further Reading
Keywords
idiopathic pulmonary hypertension, idiopathic pulmonary artery hypertension, IPAH, elevation of pulmonary artery pressure, primary pulmonary hypertension, collagen vascular disease, congenital heart disease, portal hypertension, HIV, Gaucher disease, hereditary hemorrhagic telangiectasia, veno-occlusive disease, chronic obstructive lung disease, interstitial lung disease, sleep-disordered breathing, alveolar hypoventilation, neonatal lung disease, alveolar-capillary dysplasia, pulmonary embolism, right ventricular failure, pulmonary vasoconstriction, patent foramen ovale, tricuspid regurgitation
