Impact of a high-dose nitrate strategy on cardiac stress in acute heart failure: a pilot study

Background. Intravenous nitrate therapy has been shown to improve short-term outcome of acute heart failure patients treated in the intensive care unit. The potential of a noninvasive high-dose nitrate strategy in the Emergency Department and the general ward remains unknown. Methods. A total of 128 consecutive acute heart failure patients were either treated with standard therapy or high-dose sublingual and transdermal nitrates on top of standard of care treatment. Cardiac recovery, quantified by B-type natriuretic peptide (BNP) levels during the first 48 h, was the primary endpoint. Secondary endpoints ascertained the safety of the nitrate therapy. Results. The high nitrate group received higher doses of nitrates during the first 48 h compared to the standard therapy group [82.4 mg (46.2-120.6) vs. 20 mg (10-30) respectively, P < 0.001]. The amount of diuretics given in both groups was similar. BNP levels decreased in all patients (P < 0.0001). However, the BNP decrease was larger in the high-dose nitrate group (P < 0.0001). The larger decrease in BNP in the high-dose nitrate group was already apparent 12 h after the initiation of treatment. After 48 h BNP values decreased by an average of 29 +/- 4.9% in the high-dose nitrate strategy group compared to 15 +/- 5.4% during standard therapy. There was a strong trend towards fewer ICU admissions in the high-dose nitrate group [high-dose nitrates: 2 cases (4%) vs. standard therapy: 9 cases (13%); P = 0.06]. During the study period, no intergroup changes were observed in blood pressure, RIFLE classes of acute kidney injury or troponin T. In-hospital and 90-day outcome was similar amongst the two groups. Conclusions. A noninvasive high-dose nitrate strategy on top of standard therapy is safe and notably accelerates cardiac recovery in patients observed on the general ward.