Khan Asif, Ling Joanne, Parikh Valay K, Bekheit Soad
Department of Cardiology, Northwell, New Hyde Park, New York, USA.
Pacing Clin Electrophysiol. 2025 Jul;48(7):725-732. doi: 10.1111/pace.15214. Epub 2025 Jun 2.
Inappropriate sinus tachycardia (IST) is a rare syndrome characterized by a persistent daytime resting heart rate (HR) >100 beats per minute, a mean 24-h HR of >90 beats per minute, with P wave morphology and axis characteristics similar to that of sinus rhythm. IST is associated with symptomatic palpitation described as an abrupt transient acceleration of HR at rest or minimal activity and is often associated with multiple psychosomatic symptoms. Self-sustained contractile activity, i.e., pace-making, is the basic physiological process characterizing the sinus node. The funny current (I) initially described in sinus node myocytes is a mixed Na/K cation channel that is slowly activated upon the hyperpolarization of the sinoatrial node's myocytes. This inward current generates repetitive activity responsible for the rhythmic pacemaker activity. The higher the activation of I current, the steeper will be phase 4 hence greater the frequency of action potential firing, i.e., HR. Dysfunctional funny channels have been identified as playing a critical role in the development of IST, alongside the external influences stemming from modulatory actions of the autonomic nervous and humoral systems. Beta-blockers and calcium channel blockers are current first-line therapies that often require high doses, but are usually inefficient and poorly tolerated. Ivabradine has been shown to have unique properties of blocking I current at low concentration with a use-dependent way, which manifests as a slowly progressing accumulation of the drug during repetitive channel activation/deactivation cycles. Thus, unlike beta-blockers, Ivabradine, in smaller doses, results in a more substantial blocking effect at higher tachycardic rates and, therefore, more successful in the treatment of IST. The current literature review, which includes a small number of patients, has shown that Ivabradine lowered basal, mean, and maximal HR and was associated with symptomatic improvement. We have described the unique and specific mechanism of action, along with its safety profile, which supports Ivabradine's role as the first-line therapy for the resolution of IST.
不适当窦性心动过速（IST）是一种罕见综合征，其特征为白天静息心率（HR）持续>100次/分钟，24小时平均心率>90次/分钟，P波形态和电轴特征与窦性心律相似。IST与静息或轻微活动时HR突然短暂加速的症状性心悸相关，且常伴有多种心身症状。自我维持的收缩活动，即起搏，是窦房结的基本生理过程。最初在窦房结心肌细胞中描述的“funny电流（I）”是一种混合的Na/K阳离子通道，在窦房结心肌细胞超极化时缓慢激活。这种内向电流产生负责节律性起搏活动的重复活动。I电流的激活越高，4期就越陡峭，因此动作电位发放频率越高，即心率越高。功能失调的“funny通道”已被确定在IST的发生中起关键作用，同时还有来自自主神经和体液系统调节作用的外部影响。β受体阻滞剂和钙通道阻滞剂是目前的一线治疗方法，通常需要高剂量，但往往效果不佳且耐受性差。伊伐布雷定已被证明具有在低浓度下以使用依赖方式阻断I电流的独特特性，这表现为在重复的通道激活/失活周期中药物缓慢进展性蓄积。因此，与β受体阻滞剂不同，小剂量的伊伐布雷定在较高的心动过速心率下会产生更显著的阻断作用，因此在治疗IST方面更成功。目前包括少数患者的文献综述表明，伊伐布雷定降低了基础、平均和最大心率，并与症状改善相关。我们已经描述了其独特而具体的作用机制及其安全性，这支持伊伐布雷定作为解决IST的一线治疗药物的作用。
