Ann IM 2005;143:282; Nejm 2004;351:1425; 1997;336:111 (primary type)

Cause:

WHO classifications types 1-5 (J Am Coll Cardiol 2004;43:55)

Primary types due to autosomal dominant gene in 6% (Nejm 2001;345:319) including ones assoc w HAT (Nejm 2001;345:325); maybe Kaposi sarcoma associated human herpes virus 8 (HHV-8)? (Nejm 2003;349:1113)

Secondary causes: COPD w hypoxia (most commonly), recurrent chronic pulmonary emboli (Nejm 2001;345:1465; Ann IM 1988;108:425), silicosis, sarcoid, CHF, mitral stenosis, L-to-R shunts, most of which worsen w vasodilator rx (Ann IM 1986;105:499), HIV infection and hereditary hemolytic anemias (Jama 2008;299:324), cocaine and/or iv drug use, cirrhosis, and fenfluramine-type anorexic drugs (Nejm 1996;335:609), collagen vascular diseases like scleroderma (Ann IM 2000;132:425) where >50% get pulm HT (Am J Med 1983;75:65)

Pathophys: (Nejm 2004;351:1655)

Vascular proliferation, vasoconstriction, and thrombosis all increase pulm vascular resistance. Excess platelet thromboxane A and deficient endothelial cell prostacyclin, nitric oxide, and enothelin production are associated w both primary and secondary pulmonary HT; cause or effect? Worsened by hypoxia, cocaine, and weight-loss drugs related to amphetamines.

In primary, female/male = 1.7:1; peak onset age 30-40 yr; associated w positive family hx

Onset over 1-3 yr

Table 16.4 Symptoms of Pulmonary HT

Si:P₂ A₂; RV heave; R-sided S₃; pulmonary systolic and diastolic murmur

Progressive; median survival is 2.8 yr; 68% survive 1 yr, 50% survive 3 yr, and 34% survive 5 yr, worse if mean PA pressure 85 mm Hg, mean RA pressure >20, or cardiac index <2 L/min/m² (Ann IM 1991;115:343). Even w prostacycline rx, still have 33% 3-yr mortality

Cor pulmonale, sudden death (7%)

Lab:

ABGs:Low pCO₂ often is the only abnormality; hypoxia later in course, 1st exertional, then at rest

NIL, cardiac echo: RH, tricuspid regurgitation, pulmonary artery HT

Rx:

of secondary types, rx the cause if possible; thrombectomy successful in chronic emboli patients even after yrs (Nejm 2001;345:1465); O₂ critical if hypoxic etiology

of primary type: avoid indomethacin and other prostaglandin inhibitors, which increase pressure (Ann IM 1982;97:480)

of both types: avoid iron deficiency (Jama 2009;302:1444)

• Warfarin anticoagulation increases survival (Nejm 1992;327:76)
• Vasodilator rx (Med Let 2007;49:87):
• Epoprostenol (Flolan), iv continuous pump infusions (Ann IM 2000;132:425, 500; 1999;130:740; 1990;112:485; Nejm 1998;338:273, 321; 1996;334:296; Med Let 1996;38:14); a prostacycline; $32 000/yr
• Iloprost (Ventavis) 2.5 µgm inh 6-12 × qd (Nejm 2002;347:322; 2000;342:1866; Ann IM 2000;132:435); a prostacycline; $91 000/yr
• Treprostinil (Remodulin) (Med Let 2002;44:80) 20 ngm/kg/min sc continuous; a prostacycline; $98 000/yr
• Bosentan (Tracleer), an endothelin-receptor antagonist (Med Let 2002;44:30; Nejm 2002;346:896, 933) 125 mg po bid after half dose 1st month; adv efffects: hepatotoxic, teratogenic; $60 000/yr
• Sildenafil (Revatio/Viagra) (Nejm 2005;353:2148; Med Let 2004;46:18; Ann IM 2002;136:515) 20-50 mg po tid; not clearly helpful, at least with idiopathic type and fibrosis; $10000/yr
• Ambrisentan (Letairis) 5-10 mg po daily; $60 000/yr
• Lung transplant