Beneficial neurohumoral profile in left ventricular systolic dysfunction following acute myocardial infarction
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The goal of our study was to determine the effects of combined renin-angiotensin-aldosterone system (RAAS) blocking therapy, including a selective aldosterone inhibitor eplerenone, on neurohumoral profile in patients with left ventricular (LV) systolic dysfunction following an acute myocardial infarction (MI). We also assessed the effect of multiple neuroendocrine inhibitors therapy on renal function and explored the interaction between changes in renal function and heart failure markers.
Our study incorporated 74 patients aged between 39 and 86 (mean 64.5 +/- 11.4) with established acute MI and reduced left ventricular ejection fraction (EF ≤ 40%). The additive effect of eplerenone (25–50 mg/d) on top of the standard heart failure regimen on plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), renin and aldosterone were assessed at study entry and at six months. Renal function was determined by creatinine and estimated glomerular filtration rate (eGFR), calculated using the Cockcroft-Gault formula. The changes in LV volumes and systolic function were assessed by a transthoracic echocardiography at baseline and at the end of follow-up.
Following 6 months of combined RAAS blocking therapy, incorporating aldosterone inhibitor eplerenone, plasma levels of NT-proBNP (−77.7%, p= 0.001) and renin (−52.2%, p= 0.083) decreased. As expected, an increase in aldosterone levels was observed (+36.8%, p= 0.758). A mild decline in eGFR (−2,0 ml/min, p= 0.028) was observed, with potassium levels increasing slightly, but remaining within the normal range (4.28 vs. 4.48 mmol/L, p= 0.028). We found that baseline creatinine correlated with measures characterising myocardial function (NT-proBNP, LVEF). The highest correlation was with NT-proBNP at baseline (r = 0.537, p <0.001). Logistic regression models for prediction of significant left ventricular ejection fraction improvement (LVEF after 6 months-LVEF at baseline ≥5%) did not demonstrate that renal function measurements are suitable for this purpose.
A combined heart failure regimen, including aldosterone inhibitor eplerenone, in patients with left ventricular systolic dysfunction following acute MI decreases circulating levels of natriuretic peptides and renin and increases levels of aldosterone. The reduction in NT-proBNP is related to improvement of left ventricular systolic function and possibly to improved LV compliance and reduction of LV-filling pressures, whereas the increase in aldosterone levels could reflect activated feedback mechanisms of RAAS. A mild reduction in eGFR can be expected in the course of HF therapy in post-MI patients with normal baseline renal function. A severe hyperkalemia can be prevented by close monitoring of renal function and potassium levels. Our findings suggest, that there is a direct linear relationship between renal function and markers of myocardial function early post-MI, which is no longer present after six months. Cardio-renal correlation is best reflected by raw values of creatinine.
KeywordsHeart failure Left ventricular systolic dysfunction Renin-angiotensin-aldosterone system NT-proBNP Eplerenone
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