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, Raynaudís(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.