Acute myocardial infarction is mostly caused by acute vascular occlusion due to coronary atherosclerotic plaque rupture and secondary thrombosis, inducing myocardial ischemia, hypoxia and necrosis, which can lead to serious complications, including malignant arrhythmia, heart failure, cardiogenic shock and sudden cardiac death [9]. At present, emergency PCI can quickly open the occluded vessels and restore myocardial blood flow perfusion, but the mortality of myocardial infarction in China has not been decreased to an ideal level [10]. An accelerated heart rate is significantly associated with AMI mortality. The possible mechanisms are as follows [11–13]: increased heart rate can shorten the ventricular diastole and lead to coronary artery hypoperfusion, affecting myocardial blood supply; increased heart rate leads to excessive myocardial oxygen consumption and imbalance of oxygen supply and consumption, which further aggravates myocardial ischemia. At the same time, increased heart rate is often accompanied by excessive activation of sympathetic nerves and elevated catecholamine levels, which can directly induce vascular endothelial injury and myocardial remodeling. Therefore, heart rate should be strictly controlled after PCI to improve the prognosis of patients with myocardial infarction.
Metoprolol is the most commonly used β-blocker in clinical practice and can slow heart rate, reduce myocardial oxygen consumption, decrease catecholamine levels, and inhibit myocardial remodeling. However, long-term and massive use may produce side effects such as negative inotropy, negative conduction, asthma and hypotension [14]. Ivabradine is a highly selective If current inhibitor that can inhibit the sinus node rhythm and thus slow the heart rate. Moreover, the drug can reduce the heart rate without affecting the atrioventricular conduction time and myocardial contractility [15].
In this study, cardiac function was evaluated by echocardiography. LVEF was significantly higher in the ivabradine group than in the control group at 1 week, 3 months and 1 year after PCI, and the difference between the two groups was more significant at 1 year. This suggests that early use of ivabradine can better improve left ventricular systolic function, and the longer the follow-up time, the more significant and sustainable its effect on improving cardiac function will be found. Gerbaud et al. [16] used cardiac magnetic resonance to evaluate myocardial remodeling, and they found that ivabradine added to basic drug therapy could significantly improve left ventricular remodeling in STEMI patients after successful PCI. Xu et al. [17] found that LVEF in the ivabradine group was significantly higher than that in the control group at 3 months after PCI, but there was no significant difference in LVEF between the two groups at 6 months after PCI. It was found that the heart rate of the ivabradine group was significantly lower than that of the control group at 1 week after PCI, suggesting that early use of ivabradine can control the heart rate faster and better. However, the heart rate of the two groups further decreased and tended to be consistent at 3 months and 1 year after PCI, indicating that ivabradine combined with metoprolol had better heart rate control than metoprolol alone in the early stage, but this effect gradually disappeared in the longer follow-up. The early control of heart rate in the ivabradine group may be the fundamental reason for reducing cardiac load and improving myocardial remodeling.
CPET is an important noninvasive method to evaluate cardiopulmonary function and aerobic exercise capacity. Peak oxygen uptake is a strong predictor of exercise capacity in patients with cardiac insufficiency and is closely related to the prognosis of patients [18]. Studies have shown that every 1 ml/(min•kg) increase in peak oxygen uptake can reduce all-cause mortality by approximately 10% [19]. This study found that VO2max, METs, AT heart rate, and peak heart rate were significantly higher in the ivabradine group than in the control group at 1 year after PCI, suggesting that ivabradine can significantly improve the cardiopulmonary function and exercise tolerance of patients. Heart rate recovery (HRR) after an exercise test is affected by the cardiac sympathetic nerve and vagus nerve, which can reflect the regulatory ability of the cardiac autonomic nerve. Delayed or abnormal heart rate recovery is an independent risk factor for predicting cardiovascular disease mortality and can predict the prognosis of patients with ischemic heart disease [20, 21]. The HRR value of the ivabradine group was significantly higher than that of the control group, which may be related to the significant inhibition of sinoatrial node autonomic rhythm by ivabradine. In this study, patients in both groups were followed up for 1 year, and no cardiac death occurred. The proportion of recurrent angina and heart failure in the ivabradine group was lower than that in the control group, which was consistent with the results of the SHIFT study [22]. Meanwhile, the total incidence of MACE at 1 year after PCI in the ivabradine group was significantly lower than that in the control group, which was because ivabradine combined with β-blockers can more significantly reduce the heart rate, increase the coronary flow reserve, and improve vascular endothelial function, thereby reducing the incidence of myocardial ischemia and heart failure and improving the long-term prognosis of patients.
BNP is a reliable indicator for predicting the prognosis of myocardial infarction and is positively correlated with the onset of heart failure in AMI patients [23, 24]. This study found that the BNP of the ivabradine group after PCI was lower than that of the control group, and the difference was statistically significant on Days 2 and 3 after PCI, suggesting that ivabradine can reduce the occurrence of early heart failure after myocardial infarction, probably because it can slow the heart rate earlier and improve cardiac function. This study found that the TnI of the ivabradine group was lower than that of the control group from Day 1 to Day 5 after PCI, and there was a statistically significant difference between the two groups on Day 5 after PCI, suggesting that ivabradine can significantly reduce the degree of myocardial injury in patients, which may be related to its ability to reduce heart rate, myocardial oxygen consumption and myocardial infarction area. Studies have shown that ivabradine can improve myocardial blood supply by increasing coronary artery reserve and thus reduce myocardial infarction area, and this effect is independent of its effect on heart rate reduction [25]. In addition, ivabradine can inhibit oxidative stress, reduce cardiomyocyte inflammation and protect cardiomyocyte viability [26]. It can thicken the ventricular wall of the infarcted area, inhibit infarct expansion, and protect the contractile function and synchrony of the distal viable myocardium [27].
Limitations
This study is a prospective, single-center randomized controlled study with a small sample size, which may lead to bias in the results. It still needs to be further verified by multicenter and large-sample studies. The lack of placebo and blinding may also have affected the objectivity of the results.