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Management of ventricular arrhythmia in structural heart disease is complicated by the toxicity of the limited antiarrhythmic options available. In others, proarrhythmia and deleterious hemodynamic and noncardiac effects prevent practical use. This necessitates new thinking in therapeutic agents for ventricular arrhythmia in structural heart disease. Ivabradine, a funny current (I f ) inhibitor, has proven safety in heart failure, angina, and inappropriate sinus tachycardia. Although it is commonly known that funny channels are primarily expressed in the sinoatrial node, atrioventricular node, and conducting system of the ventricle, ivabradine is known to exert effects on metabolism, ion homeostasis, and membrane electrophysiology of remodeled ventricular myocardium. This review considers novel concepts and evidence from clinical and experimental studies regarding this paradigm, with a potential role of ivabradine in ventricular arrhythmia., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Inappropriate sinus tachycardia (IST) is debilitating despite available treatment. Off-label use of ivabradine for IST prompted this systematic analysis of existing data quality and sample size estimates for adequately powered studies., Objective: To determine clinical efficacy of ivabradine in IST from pooled prospective studies., Methods: Analysis included ivabradine studies for IST participants without structural heart disease and with follow-up of ≥2 weeks. Heart rate and symptom reduction with ivabradine were estimated based on results of subjective change in symptoms assessed by various data instruments used in each study. Studies were assessed for quality using validated checklists. Sample sizes were calculated based on the magnitude of symptom reduction encountered after treatment with ivabradine., Results: Nine studies met criteria, culminating in 145 patients pooled. Most patients were women (≥70%). Studies were small and not adequately powered, and all reported a decrease in maximum or mean resting heart rate or both, with complete or considerable amelioration of symptoms with ivabradine. Most studies had moderate quality with excellent consistency of study quality and narrow limits of agreement between the quality checklists. Sample size estimates for adequately powered studies with various placebo effects and comparisons with β-blockade are reported., Conclusions: Ivabradine effectively reduces heart rate and symptoms in IST, but no study was adequately powered to account for the expected placebo effect on symptoms. A multicenter, randomized, placebo-controlled, active, comparative study with a β-blocker is needed for confirmation. This is especially relevant given the ivabradine's potential teratogenic effect, as many IST patients are females of childbearing potential., (Published by Elsevier Inc.)

Background: Inappropriate sinus tachycardia (IST) is characterized by an elevated heart rate (HR) at rest and an exaggerated HR response to physical activity or emotional stress. Beta-blockers and calcium channel blockers are the first-line therapy but sometimes are poorly tolerated due to side effects., Objective: The purpose of this study was to evaluate the efficacy and safety of ivabradine, a selective inhibitor of the I(f) current of the sinoatrial node, in patients affected by IST., Methods: Eighteen consecutive symptomatic patients (2 men and 16 women; mean age 45 +/- 15 years) affected by IST were enrolled in the study. Every patient underwent resting ECG, 24-hour Holter ECG, and exercise ECG at baseline and at 3-month and 6-month follow-up., Results: Sixteen patients (14 women; mean age 41 +/- 14 years) completed the study. Holter ECG assessment showed a significant reduction of medium HR (P <.001) and maximal HR (P <.001, basal vs 3-6 months; P = .02, 3 vs 6 months). Minimal HR slightly decreased at 3 months and then stabilized (P = .49, 3 vs 6 months) despite an increased drug dose. Stress test showed a significant decrease at rest (P <.001) and maximal HR (P <.05), suggesting an increased tolerance to physical stress, which was confirmed by a progressive increase of maximal load reached (>100 W) during stress test at 3 months (75%) and 6 months (85%). One patient was excluded because of phosphenes despite dose lowering, and another patient did not complete the protocol., Conclusion: Ivabradine could represent an effective and safe alternative to calcium channel blockers and beta-blockers for treatment of IST., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

A 28-year-old male presented with thyrotoxic periodic paralysis. On admission to hospital the serum potassium level was 1.4 mmol/l. The ECG showed classical features of hypokalaemia. In addition, sino-atrial block with Wenckebach conduction was also present. With the normalization of the serum potassium, the ECG became completely normal and showed no evidence of any arrhythmia.

We describe a case of cardiomyopathy resulting from a tachycardia of high-right atrial origin indistinguishable from sinus tachycardia. The symptoms and angiographic appearances improved dramatically with beta blockade.

From 1979 to 1989, 18 patients were seen in the Electrophysiology Service, Duke University Medical Center, with automatic atrial tachycardia. There were 8 male and 10 female patients with a mean age of 28.1 +/- 2.9 years. Electrophysiological mapping localized automatic foci to right atrial sites (14 patients) and left atrial sites (4 patients). Depending on origin of the focus, patients were further diagnosed as having either chronic ectopic atrial tachycardia or inappropriate sinus tachycardia. Of the 15 patients with chronic ectopic atrial tachycardia, 6 responded to medical treatment; in 9, the tachycardia was not adequately controlled. Six of them were referred for surgical intervention. All 3 patients with inappropriate sinus tachycardia underwent operative therapy. In the surgical group of patients with chronic ectopic atrial tachycardia, all 6 had a tachycardia-induced cardiomyopathy with ejection fractions ranging from 14% to 27% (mean ejection fraction, 21% +/- 2.7%). Surgical techniques used (alone or in combination) included an isolation procedure in 1 patient, cryoablation in 4 patients, and excision of atrial appendages or portions of atrial free walls in 7. Normal sinus rhythm developed in all surgical patients except 1 patient who had intractable congestive heart failure preoperatively and died of this condition and stroke. The overall success rates for medical and surgical therapy were 33.3% and 88.9%, respectively (p less than 0.01). Long-term follow-up was possible for 7 (87.5%) of 8 patients 3 to 7 years after operation. All patients with chronic ectopic atrial tachycardia were cured, but only 1 of 3 patients with inappropriate sinus tachycardia was in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of intravenous (IV) amiodarone (300 mg) on heart rate was investigated in 22 patients with acute myocardial infarction (18) or ischemia (4) and sinus tachycardia. There were 11 men and 11 women (age range, 48 to 83 years; mean, 63.5). Amiodarone IV slowed the mean heart rate from 109 +/- 14 beats/min to 94 +/- 15 beats/min (p less than 0.0005). There was a linear correlation between the initial heart rate (preamiodarone) and the final heart rate (postamiodarone), (r = 0.6930, p less than 0.0005). Most of the patients with initial heart rates higher than the mean maintained relatively high heart rates (above the mean), while most patients with lower initial heart rates showed low heart rates (below the mean) after amiodarone administration. Patients in Killip class 1 showed a significant reduction in heart rate after receiving amiodarone, from a mean of 105 +/- 10 to 88 +/- 11 beats/min (p less than 0.01). Patients in Killip class 2 also had reduced heart rates (118 +/- 14 to 81 +/- 39 beats/min), but these changes were not statistically significant. Of the three patients in Killip class 3 to 4, the heart rate slowed by 10 beats/min in one, while in the remaining two no changes were observed. There were no significant side effects from the administration of amiodarone.