New Therapy for Inappropriate Sinus Tachycardia

Abstract & Commentary

By John P. DiMarco, MD, PhD Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville Dr. DiMarco receives grant/research support from Medtronic, is a consultant for Medtronic, Novartis, and St. Jude, and is a speaker for Boston Scientific.

Source: Calo L, et al. Efficacy of ivabradine administration in patients affected by inappropriate sinus tachycardia. Heart Rhythm. 2010;7:1318-1323

Inappropriate sinus tachycardia (IST) is a nonparoxysmal arrhythmia characterized by either a continuous sinus tachycardia or intermittent periods of inappropriately rapid sinus rates. It occurs most frequently in women, many of whom are health care workers. In this paper, Calo and associates from Rome, Italy, report the effects of the novel If current blocker, ivabradine, in a small group of patients with IST. The authors identified 18 patients with IST characterized by recurrent palpitations and physical stress intolerance. Secondary causes of sinus tachycardia and significant structural heart disease were excluded. All patients had failed trials with either beta adrenergic blockers and/or nondihydropyridine calcium-channel blockers. At baseline, each patient underwent physical examination, a resting ECG, a 24-hour ambulatory ECG (AECG), and a symptom-limited exercise test. The same panel of tests was repeated at three and six months follow-up during ivabradine therapy. This was an observational, uncontrolled study. The starting dose of ivabradine was 5 mg twice daily, and the dose could be titrated up to 7.5 mg twice daily at the three-month follow-up in patients with persistent symptoms, or could be lowered to 2.5 mg twice daily if side effects developed.

Sixteen patients successfully completed the study. One patient stopped ivabradine because of the development of phosgenes, an ocular toxicity seen with ivabradine, and one patient was noncompliant with the protocol. The final group included 14 women and two men, with a mean age of 41 + 14 years. At baseline, the mean heart rate on resting ECG was 107 + 7 bpm. During 24-hour AECG, the mean, maximal, and minimal heart rates were 98 + 5 bpm, 151 + 21 bpm, and 62 + 4 bpm, respectively. The maximum heart rate during exercise testing was 157 + 24 bpm. This heart rate was achieved despite relatively low workloads, with 75% of the patients only reaching workloads of ≤ 75 watts. During ivabradine therapy, the mean resting heart rate at three months had declined to 85 + 5 bpm, and it declined further at six months to 72 + 5 bpm. Similar magnitude heart-rate reductions were noted by ambulatory ECG. The mean 24-hour heart rate decreased to 76 + 8 bpm after three months and to 68 + 4 bpm after six months. Similar changes also were noted in maximum heart rate at both three and six months. The minimum heart rate also declined to 52 + 5 bpm at three months and 50 + 6 bpm at six months. During exercise, similar percentage reductions in maximum heart rate were observed at both follow-up time points. The maximum workload achieved during exercise increased in all patients, with 75% now reaching workloads over 100 watts. Symptoms had completely resolved in 12 of 16 patients by the three-month time point and in all 16 patients at six months.

The authors conclude that ivabradine offers a new pharmacologic option for patients with IST.

Commentary

Inappropriate sinus tachycardia can have several different presentations. Some patients are persistently tachycardic and do not have normal heart rates even during sleep. Others may have marked variability in heart rate during normal activities, swinging between periods of bradycardia and tachycardia unpredictably. Some other patients, such as those with the postural orthostatic tachycardia syndrome, have other manifestations of autonomic nervous system dysfunction.

Patients with inappropriate sinus tachycardia are often quite difficult to manage. Many do not respond to beta-adrenergic blockers or calcium-channel blockers. Although catheter ablation may be attempted, successful long-term results are difficult to achieve. I have had true success with ablation only in those patients who present with continuous tachycardia. In this paper, the authors present preliminary evidence that ivabradine may be successful in patients with IST. Ivabradine is an If channel blocker with little or no effect on other cardiac ion channels. Although ivabradine is available for general use in Europe for the treatment of angina, unfortunately, it is not now available in the United States. Clearly, larger randomized trials of ivabradine in patients with IST are needed to prove its value, but the data here suggest that it may be uniquely helpful in this group of patients.