If inhibition in the atrioventricular node by ivabradine causes rate-dependent slowing of conduction and reduces ventricular rate during atrial fibrillation

Verrier, Richard L.; Bonatti, Rodolfo; Silva, Ana F.G.; Batatinha, Júlio Américo Pereira; Nearing, Bruce D.; Liu, Gongxin; Rajamani, Sridharan; Zeng, Dewan; Belardinelli, Luiz

doi:10.1016/j.hrthm.2014.08.007

Cited by 64 publications

(61 citation statements)

References 26 publications

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“…One such possibility is stimulation of the pacemaker current, I f [26]. Though I f density is lower in the atrioventricular node than in the sinus node, the I f blocker ivabradine does prolong the PR interval at clinical doses [27]. Thus, an agonist effect on I f might be expected to change both HR and PR.…”

Section: Discussionmentioning

confidence: 99%

Moxifloxacin Increases Heart Rate in Humans

Mason

Moon

2017

Antibiotics

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(1) Background: We assessed the effect of moxifloxacin on heart rate, and reviewed the heart rate effects of other antibiotics; (2) Methods: A total of 335 normal volunteers had 12-lead electrocardiograms recorded at multiple time points before and during treatment with moxifloxacin and with placebo in seven consecutive, thorough QT studies of crossover design; (3) Results: The average baseline heart rate across the seven studies was 61.5 bpm. The heart rate after moxifloxacin dosing was analyzed at five time points shared by all seven studies (hours 1, 2, 3, 12 and 24). The maximum mean heart rate (HR) increase for the seven studies combined was 2.4 bpm (95% CI 1.6, 3.3) at hour 2. The range of mean maximum increases among the seven studies was 2.1 to 4.3 bpm. For the seven studies combined, the increase was statistically significant at all but the 24 h time point. The maximum observed individual increase in HR was 36 bpm and the mean maximum increase was 30 ± 4.1 bpm by time point and 8 ± 6.9 bpm by subject. Many antibiotics increase HR, some several-fold more than moxifloxacin. However, clinicians and clinical investigators give little attention to this potential adverse effect in the medical literature; (4) Conclusions: The observed moxifloxacin-induced increase in HR is large enough to be clinically relevant, and it is a potentially important confounder in thorough QT studies using moxifloxacin as an active control. More attention to heart rate effects of antibiotics is warranted.

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Section: Discussionmentioning

confidence: 99%

Moxifloxacin Increases Heart Rate in Humans

Mason

Moon

2017

Antibiotics

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“…Yamazaki et al evidenced that zatebardine, an If current inhibitor, decreased both intrinsic AV rate and the increase in junctional rate in response to sympathetic nerve stimulation in anesthetized dog hearts [28] . The administration of Ivabradine (0.1 mg/kg IV bolus) slowed ventricular rate (from 240 ± 21 to 211 ± 25 bpm) and increased A-H interval in a rate-dependent fashion [29] . The administration of Ivabradine and dronedarone, both inhibitors of the If current at AV node level, reduced ventricular rate during AF in pigs by 39.5% (from 200 ± 14.6 to 121 ± 20.1 bpm) and 22% respectively [26] .…”

Section: If Current In the Atrioventricular Nodementioning

confidence: 98%

“…The expression of all HCN channel mRNA (HCN1-4) is higher in the SA node than AV node [26] , and the most important isoform, HCN4, shows level of expression 6 times higher in the SA node compared to the AV node. Recent studies clarified the role of If current in AV node by demonstrating that the inhibition of this current slows the AV node conduction in animals and humans [26][27][28][29][30] . Yamazaki et al evidenced that zatebardine, an If current inhibitor, decreased both intrinsic AV rate and the increase in junctional rate in response to sympathetic nerve stimulation in anesthetized dog hearts [28] .…”

Section: If Current In the Atrioventricular Nodementioning

confidence: 99%

Heart Rate Control in Non-Paroxysmal Atrial Fibrillation. A New Indication for Ivabradine?

Caminiti

Cacciapuoti

Fossati

et al. 2017

Journal of Cardiology and Therapy

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stable angina and chronic heart failure in sinus rhythm. According to very preliminary data, ivabradine shows heart rate lowering proprieties in non-paroxysmal AF when used alone or in association to other heart rate lowering drugs. Interestingly, studies suggest that this seems to translate into clinical benefits such as improvement of exercise tolerance and ejection fraction. However, new trials are needed to confirm the effectiveness and safety of ivabradine in nonparoxysmal AF. INTRODUCTIONAtrial fibrillation (AF) is the most common cardiac arrhythmia and its incidence and prevalence increase with age. Although by itself it is a non-fatal arrhythmia, it is often associated with a considerable comorbidity and an increased risk of stroke and heart failure. Patients with AF have significantly poorer quality of life than healthy controls, experiencing a variety of symptoms including lethargy, palpitations, dyspnoea, chest tightness, sleeping difficulties, and psychosocial distress [1] . These symptoms are often related to an uncontrolled ventricular rate and they can be significantly improved by the administration of drugs aimed to establish heart rate (HR) control. In the setting of non-paroxysmal AF, rate-control is an integral part of the management of AF patients as underlined by the most recent guidelines [2] . In such patients, HR control is usually obtained by using drugs which prolong atrioventricular (AV) node refractoriness such as β-blockers, nondihydropyridine calcium channel blockers, and digoxin. These drugs can be used alone or in combination for resistant AF. In clinical practice the choice of drug and target HR depends on patient characteristics and comorbidities but the decision can be particularly challenging in elderly frail subjects with multiple comorbidities. Diltiazem and verapamil may have negative inotropic effects in patients ABSTRACTAtrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with poor quality of life and high rate of hospitalization in elderly frail patients. In patients with non-paroxysmal AF, optimizing heart rate is often the main goal but available drugs fail to reach heart rate control in about 30% of cases and this often happens because their doses can not be implemented due to side effects. Ivabradine is a pure heart rate lowering agent acting through the inhibition of If current in the sinus atrial cells, and it is widely used for patients with

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“…28 Verrier et al 28 demonstrated that ivabradine exerts a marked rate-dependent slowing of atrioventricular node conduction during AF, reflected in an increase in A-H interval that was inversely correlated with ventricular rate. This study provides significant preclinical evidence that ivabradine may have a role in AF rate control.…”

Section: Rate Control Ivabradinementioning

confidence: 99%