Effects of nisoldipine therapy on myocardial perfusion and neuro-hormonal status in patients with severe ischaemic left ventricular dysfunction

The effects of nisoldipine on regional myocardial perfusion and neuro-hormonal status were assessed in a double-blind, placebo-controlled study of 32 patients. All patients had ischaemic left ventricular dysfunction, with a left ventricular ejection fraction between 25% and 35%; per protocol, they were stratified according to concomitant use of ACE inhibitors. After baseline measurements at rest, including single photon emission computed tomography (SPECT) with Tc-MIBI, plasma neuro-hormones (norephinephrine, renin, arginine vasopressin, atrial natriuretic peptide) and echocardiography, the patients were randomized to nisoldipine (core coat tablet, 20 mg once daily; n=16) or placebo (n=16). Measurements were repeated after 8 weeks. SPECT data were analysed qualitatively (visual comparison by blinded observer) and quantitatively to derive an index of hypoperfusion representing the percentage of the left ventricular mass with Tc-MIBI activity below normal. At baseline, all patients had left ventricular areas with reduced Tc-MIBI uptake and 29 patients also had increases in plasma neuro-hormones. With nisoldipine, the extent of hypoperfusion (quantitative analysis) was reduced in 8114 patients vs only 2114 patients with placebo (P=0.046, 2-tailed test). The benefit of nisoldipine was similar in patients with or without ACE inhibitor therapy and was also confirmed by the visual analysis of the data. Further, none of the neuro-hormones examined was significantly modified by nisoldipine. Thus, chronically underperfused areas are present at rest in patients with ischaemic left ventricular dysfunction, and nisoldipine significantly improved Tc-MIBI uptake in these areas without evidence of detrimental changes in plasma neuro-hormones. The improved perfusion of such ‘hibernating areas’ could explain some of the beneficial changes in left ventricular function observed with nisoldipine in larger studies.