Should Ivabradine be First-Line Therapy for Inappropriate Sinus Tachycardia?

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_f) 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_f 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_f 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.