Original ArticleEffects of mineralocorticoid receptor antagonist eplerenone on cardiac sympathetic nerve activity and left ventricular remodeling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction
Introduction
Since the Epleronone Post-acute myocardial infarction Heart failure Efficacy and SUrvival Study (EPHESUS)1 reported the effectiveness of mineralocorticoid receptor antagonist (MRA) eplerenone in the treatment of acute myocardial infarction with left ventricular (LV) dysfunction, this agent has often been used in these patients. Aldosterone is well known to bind to mineralocorticoid receptors to regulate sodium and water reabsorption.2 Moreover, aldosterone displays both myocardial and renal effects that can have profound implications for LV remodeling,3 or abnormal cardiac sympathetic nerve activity (CSNA).4 In the EPHESUS trial, the eplerenone was demonstrated to reduce mortality in patients with acute myocardial infarction,1 and the beneficial outcome in the EPHESUS was shown to be associated with the suppression of cardiac collagen synthesis, and prevention of LV remodeling by this agent.5
Myocardial imaging with 123I-metaiodobenzylguanidine (MIBG), an analog of norepinephrine, is useful for detecting abnormalities in the myocardial adrenergic nervous system in patients with acute myocardial infarction.6 The myocardial ischemic area and cardiac 123I-MIBG defect size are correlated in patients undergoing reperfusion therapy for these patients.7 This imaging modality has been reported to be useful for predicting the adverse cardiac events in patients with ST-segment elevation myocardial infarction (STEMI).8 Furthermore, previous studies reported that aldosterone inhibition normalizes autonomic neural control in failing human heart,9 and attenuates enhanced CSNA in animal models of heart failure.10 These favorable effects were associated with the increased myocardial uptake of norepinephrine mediated by aldosterone blockade.4 Therefore, adding MRA to the standard therapy may normalize CSNA, i.e., improve 123I-MIBG uptake in failing human heart. However, to our knowledge, no studies have examined the effects of eplerenone on CSNA evaluated by 123I-MIBG scintigraphy in patients with STEMI.
Accordingly, we performed using our previously reported data,8 to evaluate the hypothesis that mineralocorticoid receptor antagonist eplerenone improves CSNA in patients undergoing primary percutaneous coronary intervention (PCI) following their first STEMI.
Section snippets
Patient Population
The consecutive patients admitted to our institution for STEMI were considered the study population. This study was sub-analysis using our previous database.8 The diagnosis of STEMI was made on the basis of chest pain > 30 minutes in duration, ST-segment elevation > 2 mm in two electrocardiographic leads, and more than threefold increase in serum creatine phosphokinase activity. In the acute phase, all patients were treated in standard fashion, including primary PCI. Patients were excluded from
Clinical Characteristics
No significant differences were observed in the clinical characteristics or cardiac medications were found between the two groups. Age, gender, culprit coronary artery, risk factors, recanalization time, and peak creatine phosphokinase concentrations in the acute phase were similar for both groups (Table 1). No differences were observed in the in-hospital medications (except eplerenone) and clinical follow-up of the two study groups. There were no differences in medication dose (all, P = NS),
Discussion
The findings of this study demonstrate for the first time that the addition of eplerenone to standard therapy can improve CSNA and prevent LV remodeling in patients with a first STEMI, as compared to standard conventional therapy alone. This agent can also suppress cardiac collagen synthesis during the acute to subacute phase of STEMI, following primary PCI.
Aldosterone promotes retention of sodium, loss of magnesium and potassium, myocardial and vascular fibrosis,3 baroreceptor dysfunction,20
New Knowledge Gained
While it is known that the cardioprotective treatments can improve CSNA evaluated by 123I-MIBG scintigraphy in patients with STEMI, we have shown that MRA have similar effects. Therefore, MRA treatment may be effective for reducing the incidence of cardiac events for these patients.
Conclusion
The TDS, H/M ratio, and WR determined by cardiac 123I-MIBG scintigraphy were better by use of eplerenone, as compared with the standard conventional therapy. Three weeks after treatment, LV parameters in the eplerenone group more favorable than those in the conventional therapy group. These findings indicate that administration of eplerenone can improve CSNA and prevent LV remodeling in patients with a first STEMI.
Funding
The authors have indicated they have no financial conflicts of interest.
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