Brain Natriuretic Peptide and PPH

The August 22, 2000 issue of Circulation reports that follow-up serum levels of brain natriuretic peptide (BNP) are the best diagnostic predictor of mortality from PPH.   In a study of 60 patients with NYHA Class II, III and IV PPH, nearly all of which were on prostacyclin therapy, baseline and follow-up levels of BNP were a better predictor of mortality (20 out of the 60 patients died within four years) than any invasively measured cardiopulmonary hemodynamic measurement, ventilation measurements and echocardiographic dimensional measurements of heart size.

The study by Dr. Noritoshi Nagaya and colleagues from the National Cardiovascular Center in Osaka, Japan, is striking in its demonstration that follow-up BNP provided an almost fail-safe indication of patient responsiveness to prostacyclin therapy.  Those patients whose BNP levels stayed below 180 pg/mL achieved nearly 100% survival over four years, while those patients whose BNP levels exceeded this threshold all died within three years.  In a similar, though somewhat less striking vein, those patients whose baseline BNP levels were below 150 pg/mL achieved a nearly 80% survival rate over 4 years, while those patients whose baseline BNP levels exceeded this threshold had only a 50% survival rate over 4 years.

Dr. Nagaya noted that “BNP is secreted predominantly from cardiac ventricles through a constitutive pathway and is affected by the degree of myocardial stretch, damage, and ischemia in the ventricle.”  However, BNP is much more sensitive to such heart damage than other measures because survival was not nearly so well correlated with right atrial pressure or ventricle deformity as a result of pressure overload as it was with BNP levels.

It is well-known that many patients are refractory to prostacyclin therapy, although this is generally not known for some period of months.   Dr. Nagaya’s research provides strong support for assessing patients BNP levels regularly in the first three months of prostacyclin therapy, and to promptly arrange for alternative therapy (such as continuous nitric oxide inhalation and/or lung transplantation) in the event that a fall in BNP levels is not shown.  In addition, any patient presenting with BNP levels in excess of 150 pg/mL should be listed for lung transplantation immediately, as Dr. Nagaya’s research shows that such patients are less likely to respond to prostacyclin therapy.