PRIMARY PULMONARY HYPERTENSION

Definition:

1. Mean PAP >25mmHg at rest OR >30mmHg with exercise

2. No L-sided cardiac valvular, myocardial, congenital heart disease

3. No clinically significant respiratory, connective tissue or chronic thromboembolic disease.

Causes:

1. Familial(6%)- autosomal dominant, genetic anticipation.

2. Acquired idiopathic

3. Acquired with association- portal HTN, HIV, cocaine, appetite-suppressant

Epidemiology: 1-2 per million. 0.5-2% of pts with portal HTN or HIV have evidence of PHTN. Mean survival 2.5 yrs after dx. 95% 5yr survival if responsive to CaCB.

Pathophysiology:

1. Vasoconstriction- imbalance of prostacyclin/thromboxane, NO/endothelin (?primary or secondary).

2. Vascular remodeling- intimal and adventitial proliferation.

3. Thrombosis- injury to endothelium, abnormal fibrinolysis, platelet abnormalities

Diagnosis:

1. Sxs: dyspnea(60%), fatigability, angina, syncope, Raynaud’s(10%).

2. ECHO: rule out valvular, congenital, myocardial disease, estimate PA systolic pressure.

3. VQ: rule out PE. May be normal or reveal patchy defects.

4. PA-gram: useful when V/Q inconclusive. Generally safe.

5. Exercise testing: reduced MVO2, high VE, low AT, low max O2 pulse, increased Aa gradient. 6 minute walk test distance correlates with severity.

6. Serologies: low-titre +ANA common

7. Hemodynamics: PAP three or more times nml, elevated RAP, depressed CO, usually nml L-sided pressures.

Therapy:

1. Vasodilators- first test invasively with short acting agents, IF good response, switch to PO CaCB, IF poor response, consider longer trial of prostacyclin.

Drug	Rte	Dose	Notes/half-life
Prostacyclin (epoprostenol)	IV	2-20ng/kg/min	Side fx: jaw pain, erythema, diarrhea, arthralgias, Can cause pulm edema in veno-occl dz. Half life 3-5min.
Adenosine	IV	50-200mcg/kg/min	5-10sec
Nitric oxide	INH	5-80ppm	15-30sec
Nifedipine	PO	30-40mg/d	2-5hr
Diltiazem	PO	120-900mg/d	2-4.5hr

2. Transplant- higher morbidity and mortality than other indications.

3. Anticoagulation- target INR 2.0. Double 3 yr survival.

Rubin. NEJM. 336(2):111-117, 1997.