Primary Pulmonary Hypertension Disease

DESCRIPTION

Pulmonary arterial hypertension of unknown cause, where secondary causes have been ruled out. Three pathologic subtypes have been identified: (1) thrombotic (56%), (2) plexogenic (28%), (3) veno-occlusive (16%).

System(s) affected: Pulmonary, Cardiovascular
Genetics: 7% familial; autosomal dominant with variable expression and "genetic anticipation"
Incidence/Prevalence in USA: 1-2 cases/million. 1% of all causes of cor pulmonale at autopsy. 0.5-2% of patients with portal hypertension or HIV
Predominant age: Mean age 34-36 years; second incidence peak in males 50-59 years
Predominant sex: Female > Male (3:1)

SIGNS AND SYMPTOMS

Loud P2 (> 80%)
Right ventricular lift (> 80%)
Dyspnea (> 75%)
Murmur of tricuspid insufficiency (50-80%)
Increased jugular venous pressure (50-80%)
Right ventricular S4 (50-80%)
Chest pain (> 50%)
Fatigue (> 50%)
Palpitations (< 50%)
Syncope; dizziness (< 50%)
Cough (< 50%)
Raynaud's phenomenon (< 10%)
Hepatomegaly (< 50%)
Pulmonic ejection click (< 50%)
Right ventricular S3 (< 50%)
Murmur of pulmonic insufficiency (< 50%)
Lower extremity edema (< 50%)
Superficial thrombophlebitis (5%)

CAUSES

Unknown; possible pulmonary arteriolar hyperactivity and vasoconstriction; occult thromboembolism; possible autoimmune (high frequency antinuclear antibodies)
In Europe, reports of PPH associated with anorectic agent aminorex fumarate in late 1960's; tainted rapeseed oil
HIV positive patients may have an increased incidence of primary pulmonary hypertension
Anorectic agents (fenfluramine and dexfenfluramine)
Amphetamines

RISK FACTORS

Female sex

LABORATORY

ANA positive (1/3 of patients)

Drugs that may alter lab results: Hydralazine, procainamide, isoniazid, etc.
Disorders that may alter lab results: Many other diseases, e.g., lupus, scleroderma

PATHOLOGICAL FINDINGS

Medial hypertrophy and arterial thrombosis are common in all subtypes
Plexogenic pulmonary arteriopathy (30-70%): laminar "onion skin" intimal proliferation, focal medial disruption, aneurysmal dilatation
Microthromboemboli (20-50%)
Veno-occlusive disease (10-15%)

SPECIAL TESTS

ECG: right ventricular hypertrophy and right axis deviation
Pulmonary function testing: arterial hypoxemia, reduced diffusion capacity, hypocapnia
V/Q scan: must rule out proximal pulmonary artery emboli
Exercise test: reduced maximal O2 consumption, high minute ventilation, low anaerobic threshold, reduced maximal oxygen pulse, increased DO2A-a. Correlation to severity of disease with 6 minute walk test.

IMAGING

Chest x-ray: enlarged central pulmonary arteries with pulmonary arterial branches attenuated. Right ventricular enlargement a late finding. If increased interstitial markings, consider lung parenchymal disease or veno-occlusive disease.
Echo-Doppler: right ventricular enlargement and overload; important to rule out underlying cardiac disease such as atrial septal defect with secondary pulmonary hypertension or mitral stenosis
Ultra fast CT: sensitivity probably equal to pulmonary angiogram with lower contrast dose

DIAGNOSTIC PROCEDURES

Chest x-ray, pulmonary function tests, arterial blood gases, and V/Q scan should be done
Cardiac catheterization: right heart catheterization is necessary to measure pulmonary artery pressures and hemodynamics; rule out underlying cardiac disease and response to vasodilator therapy
Pulmonary angiography: should be done if segmental or larger defect on V/Q scan. Caution in pulmonary hypertension as can lead to hemodynamic collapse; use low osmolar agents, subselective angiograms.
Lung biopsy: not recommended

APPROPRIATE HEALTH CARE

Medical therapy is first line and primarily palliative; health care is guided by clinical status
Hospitalization with invasive monitoring is needed to screen vasodilator responsiveness and initiate vasodilator therapy
There is a national registry established by the National Heart, Lung, and Blood Institute

GENERAL MEASURES

Primary modalities are oxygen supplementation, vasodilators, anticoagulants, and treatment of heart failure (e.g., diuretics)
Oxygen supplementation is indicated for rest, exercise, or nocturnal hypoxemia
The acute response to vasodilators may improve survival; hydralazine, calcium channel blockers and prostacyclin

SURGICAL MEASURES

Surgical procedures - patients with documented large vessel thromboembolic disease should be considered for pulmonary thrombectomy
Heart-lung or lung transplantation is an option for appropriate patients when medical therapy has failed
Blade-balloon atrial septostomy

ACTIVITY

Restricted; exercise worsens pulmonary vascular resistance

DIET

Low salt with heart failure

PATIENT EDUCATION

Need to discuss prognosis; options such as transplantation
Avoidance of pregnancy

PREVENTION/AVOIDANCE

None

POSSIBLE COMPLICATIONS

Thromboembolism, heart failure, sudden death

EXPECTED COURSE AND PROGNOSIS

Mean survival 2-3 years from time of diagnosis, 75% mortality at 5 years, although survival is quite variable as learned from the NIH registry.
Mean age at diagnosis 34 years
Mode of death:
- Right heart failure 63%
- Indeterminate 15%
- Pneumonia 7%
- Sudden death 7%
- Cardiac death 5%
Poor prognostic factors:
- PaO2 < 63%
- RA pressure > 20 mm Hg
- Cardiac index < 2 L/min/m2
- Mean pulmonary arterial (PA) pressure > 85 mm Hg
- New York Heart Association (NYHA) class 3 or 4
- Raynaud's phenomenon

ASSOCIATED CONDITIONS

Portal hypertension
Systemic lupus erythematosus
HIV
Raynauds

AGE-RELATED FACTORS

Pediatric: N/A
Geriatric: N/A
Others: N/A

PREGNANCY

Must be avoided; high mother and fetal wastage

OTHER NOTES

N/A

ABBREVIATIONS

V/Q = ventilation/perfusion

Clinical Investigations

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