Effects of chronic neutral endopeptidase inhibition on the progression of left ventricular dysfunction and remodeling in dogs with moderate heart failure.

BACKGROUND: The diuretic actions of endogenously produced atrial natriuretic factor (ANF) may be beneficial in the treatment of chronic heart failure (CHF). Neutral endopeptidase (NEP) is the primary enzyme responsible for the degradation of ANF. The present study investigates the effects of long-term NEP inhibition on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure. METHODS: LV dysfunction was produced in 12 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LV ejection fraction (EF) was between 30-40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with the NEP inhibitor ecadotril (100 mg, once daily, n = 6) or to no therapy at all (control, n = 6). RESULTS: During the 3 months of follow-up, LV EF in control dogs decreased from 37 +/- 1% to 28 +/- 1% (P < 0.01) and LV end-diastolic volume (EDV) and end-systolic volume (ESV) increased (EDV: 72 +/- 3 vs. 84 +/- 5 ml, P < 0.01); ESV: 45 +/- 1 vs. 60 +/- 4 ml, P < 0.01). In dogs treated with ecadotril, LV EF (34 +/- 1% vs. 37 +/- 2%), EDV (79+/- 5 vs. 78+/- 6 ml) and ESV (52 +/- 3 vs. 49 +/- 4) remained essentially unchanged after 3 months of therapy. Histomorphometric measurements at the termination of the study showed that ecadotril was associated with significantly reduced cardiomyocyte hypertrophy compared to control. CONCLUSION: Early, long-term NEP inhibition with ecadotril prevents the progression of LV dysfunction and attenuates progressive LV remodeling in dogs with moderate heart failure.

Prediction of functional recovery of the left ventricle after coronary revascularization in patients with prior anterior myocardial infarction: a myocardial integrated backscatter study.

Cyclic variation (CV) of myocardial integrated backscatter (IBS), which reflects intrinsic contractile performance, can predict myocardial viability in patients with a reperfused acute myocardial infarction (MI), but the use of this method has not been validated for chronic left ventricular (LV) dysfunction. The aim of this study was to examine whether myocardial IBS was useful for predicting LV functional recovery after coronary revascularization in 17 patients with prior anterior MI and LV dysfunction (ejection fraction <50%). Within 24 h of the revascularization procedure (percutaneous transluminal coronary angioplasty or coronary stenting), IBS curves were obtained by placing the region of interest on the anterior wall on the short-axis IBS image. The patients had repeat left heart catheterization at 3 or 6 months after the revascularization procedure, and were grouped according to the patterns of the IBS curve within the anterior wall. In 8 patients (group A), the IBS curve had a synchronized pattern with the magnitude of CV > or = 3.5, and in the remaining 9 patients (group B), the curve had either an asynchronized pattern or the magnitude of CV was less than 3.5 dB even in the case of synchronized pattern, or both. At baseline, there were no significant differences in LV functional indices between the 2 groups. After the follow-up period, the LV end-systolic volume decreased (75 +/- 21 ml to 56 +/- 20ml, p = 0.05), LV ejection fraction increased (35 +/- 12% to 50 +/- 14%, p = 0.014), and LV end-diastolic pressure decreased (19 +/- 10 mmHg to 13 +/- 6 mmHg, p = 0.02) in group A, whereas only the LV ejection fraction increased (34 +/- 9% to 40 +/- 11%, p = 0.03) in group B; LV end-systolic volume (72 +/- 19 ml to 66 +/- 16 ml, p = 0.126) and LV end-diastolic pressure (18 +/- 12 mmHg to 14 +/- 8 mmHg, p = 0.184) showed no significant changes. In conclusion, IBS is valuable for predicting LV functional recovery after coronary revascularization in patients with LV dysfunction caused by a remote anterior MI. A large-scale study is be needed to establish these data.