Benefits gained from modulationg the heart rate
　　First of all， heart rate has been defined as a risk factor in both the general population and in patients with cardiovascular disease and particularly coronary artery disease. This refers to elevated heart rate， in particular above 80 bpm at rest， is associated with increased subsequent mortality. This has been an intriguing factor to try to handle and treat and has been one of the rationales for initiating beta-blocker therapy in the trials that were done in the eighties. There have been reports about the association between the degree of reduced heart rate and the degree of reduced risk. All that is fine， but it has not been possible to determine if heart rate is the factor or if it is the confounder that has also been influenced by beta-blockade.
　　Secondly， other mechanisms have been proposed and experimentally observed. For example， if you reduce heart rate by vagal stimulation， it could also be associated with a decrease in the incidence of ventricular fibrillation in the experimental setting. So the autonomic balance could be another trigger or important factor in reducing heart rate.
　　With respect to heart failure， which I have been interested in since the seventies， when we observed the effects of beta-blockers in the late seventies in chronic heart failure， we speculated that the reason why a reduced heart rate would show a net benefit could be that rate-limiting enzymes producing ATP could be harmfully influenced by elevated heart rate. By reducing them， these enzymes had enough time to produce energy and that is why myocardial function is improved in those patients.
　　Once again， it’s speculation but has been supported by some experimental studies concerning heart rate. However we hadn’t been able to study the effects of beta-blockers in this context until it became possible with the advent of a direct heart rate lowering agent， ivabradine， which has no other known cardiovascular effect at the doses we use. Consequently， we conducted a trial called SHIFT published last year， to show that there was a relationship between a reduction in heart rate using ivabradine and improved outcomes. That has been a very important step in the understanding of heart rate. The role of other ways of modulating heart rate， for example， by increasing vagal stimulation， remain to be seen in this context but there could be additional benefits.
　　Treating asymptomatic arrhythmias in patients with heart failure
　　In general， we know that arrhythmias increase risk and in particular ventricular arrhythmias. In the majority of cases， we have no good techniques of reducing the risk using pharmacological agents. For atrial fibrillation， it is better to prevent it. We have presented at the Gothenburg Heart Failure Congress a study where we have managed to reduce the incidence of atrial fibrillation in mild systolic failure by eplerenone data from the EMPHASIS trial. Otherwise， once you have atrial fibrillation， the best strategy is to prevent thromboembolism by anticoagulation and， to some extent， by heart rate control. In atrial fibrillation surprisingly， the importance of heart rate modulation has not really been proven.
　　心率调节的获益
　　心率现已作为普通人群和心血管疾病患者，尤其是冠状动脉疾病患者的一项危险因素，心率增加，尤其是静息心率＞80 bpm，与死亡率升高相关。已有报道显示，心率降低的程度与风险降低的程度相关。实验室研究表明，通过刺激迷走神经，减慢心率，可能使室颤的发生率降低。因此，自主神经的平衡可能是另一种减慢心率的重要触发因素。据推测，减慢心率可使限速酶有足够时间产生ATP，进而改善患者的心肌功能。2010年发布的SHIFT试验显示，服用伐布雷定可减慢心率，改善预后。其他方式如刺激迷走神经调节心率仍有待观察，可能会带来额外的益处。
　　HF患者无症状心律失常的心率调节
　　通常，心律失常增加发生心血管事件的风险，尤其是室性心律失常。在大多数病例中，我们无降低风险的良好策略。对于房颤，应以预防为主。在哥德堡HF会议上，我们发布了EMPHASIS试验。结果显示，依普利酮可降低轻度收缩性HF患者房颤的发生率。否则，一旦出现房颤，最好的方法是抗凝预防血栓，并在一定程度上控制心率。然而，心率调节对房颤的重要性并未得到证实。