Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial

Fontenla, Adolfo; Tamargo, Juan; Salgado, Ricardo; López‐Gil, María; Mejía, Elena; Matía, Roberto; Toquero, Jorge; Montilla, Isabel; Rajjoub, Ez-Alddin; García-Fernández, Francisco Javier; Miracle, Ángel; Rey, Juan-Ramón; Bueno, Héctor

doi:10.1016/j.hrthm.2023.02.012

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…The observed PR shortening following ivabradine administration might indicate an increased activity of the sympathetic nervous system. In cases of atrial fibrillation, ivabradine reduced the average or minimum ventricular rate but did not affect the maximum ventricular rate, indicating that ivabradine could not suppress atrioventricular conduction during heightened sympathetic nerve activity compared with vagal nerve activity [5]. Therefore, patients who did not exhibit PR interval prolongation following ivabradine administration may indicate over-activity of the sympathetic nerve.…”

Section: Clinical Perspectivementioning

confidence: 96%

“…Recent experimental literature demonstrated that I f is expressed also on the atrioventricular node [3]. Previous clinical trials have demonstrated the utility of ivabradine in reducing heart rate during atrial fibrillation, instead of sinus tachycardia [4,5]. In experimental models, ivabradine reduced atrioventricular conduction in a rate-dependent manner [6].…”

Section: Introductionmentioning

confidence: 99%

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PR Interval as a Novel Therapeutic Target of Ivabradine Therapy—Prognostic Impact of Ivabradine-Induced PR Prolongation in Heart Failure Patients

Yamamoto,

Kataoka,

Imamura

et al. 2024

JCM

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Background: Ivabradine reduces heart rate by inhibiting the “funny current” expressed on the sinoatrial node and improves mortality and morbidity in patients with systolic heart failure and sinus tachycardia. The funny current is known to be expressed also on the atrioventricular node according to experimental studies. However, the impact of ivabradine on PR interval remained unknown. Methods: Patients with a left ventricular ejection fraction of less than 50% who received 1 month of ivabradine were screened. Electrocardiographic and echocardiographic data, particularly concerning heart rate, the PR interval, and trans-mitral flow pattern, were collected at baseline and 1-month follow-up. The primary endpoint was defined as the composite of cardiovascular death and hospital readmission for worsening heart failure following ivabradine administration. Results: In the cohort of 29 enrolled patients (median age: 66 years, 62% male), the median baseline heart rate was 86 beats per minute and the median PR interval was 168 milliseconds. Following ivabradine administration, a significant decrease of 20 beats per minute in the heart rate and a significant increase of 24 milliseconds in the PR interval were observed. The truncated interval of the A-wave, detected in the trans-mitral flow, consistently demonstrated a negative correlation with the PR interval both before and after the administration of ivabradine. During a median of 1.8 years of follow-up, six patients reached the primary endpoint. A combination of heart rate reduction and PR prolongation following ivabradine administration, both of which were independent factors associated with the primary endpoint (p < 0.05 for both), was associated with greater freedom from the primary endpoint compared with either/neither of them (p = 0.002). Conclusions: Ivabradine seems to prolong PR interval, which is a novel surrogate marker of favorable clinical outcomes in patients with systolic heart failure. This effect may be associated with the dynamics of the trans-mitral flow pattern, in conjunction with heart rate and the PR interval. Clinical implications of PR interval-guided ivabradine therapy remains the future concern.

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Section: Clinical Perspectivementioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

PR Interval as a Novel Therapeutic Target of Ivabradine Therapy—Prognostic Impact of Ivabradine-Induced PR Prolongation in Heart Failure Patients

Yamamoto,

Kataoka,

Imamura

et al. 2024

JCM

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“…A retrospective study demonstrated an average reduction in ventricular rate from 105 to 89 beats per minute in individuals with permanent atrial fibrillation following ivabradine administration [52]. In another translational clinical trial, ivabradine produced a moderate reduction in heart rate for patients with permanent atrial fibrillation [53]. This heart-rate reduction was primarily attributed to the inhibition of the funny current in the atrioventricular node.…”

Section: Future Considerationsmentioning

confidence: 99%

Clinical Implications of Ivabradine in the Contemporary Era

Imamura

2024

Medicina

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Ivabradine is a recently introduced inhibitor of the If ion channel, which exhibits the capacity to reduce heart rate while preserving hemodynamic stability. At present, ivabradine finds its clinical indication in patients suffering from heart failure with reduced ejection fraction and maintaining a relative sinus rhythm refractory to beta-blockers. To optimize heart rate control, it is recommended to pursue an aggressive up-titration of ivabradine. This approach may ameliorate tachycardia-induced hypotension by incrementally enhancing cardiac output and allow further up-titration of agents aimed at ameliorating heart failure, such as beta-blockers. Both the modulation of heart rate itself and the up-titration of agents targeting heart failure lead to cardiac reverse remodeling, consequently culminating in a subsequent reduction in mortality and morbidity. A novel overlap theory that our team proposed recently has emerged in recent times. Under trans-mitral Doppler echocardiography, the E-wave and A-wave closely juxtapose one another without any overlapping at the optimal heart rate. Employing echocardiography-guided ivabradine for heart-rate modulation to minimize the overlap between the E-wave and A-wave appears to confer substantial benefits to patients with heart failure. This approach facilitates superior cardiac reverse remodeling and yields more favorable clinical outcomes when compared to those patients who do not receive echocardiography-guided care. The next pertinent issue revolves around the potential expansion of ivabradine’s clinical indications to encompass a broader spectrum of diseases. It is imperative to acknowledge that ivabradine may not yield clinically significant benefits in patients afflicted by heart failure with preserved ejection fraction, acute heart failure, sepsis, or stable angina. An important fact yet to be explored is the clinical applicability of ivabradine in patients with atrial fibrillation, a concern that beckons future investigation. In this review, the concept of overlap theory it introduced, along with its application to expand the indication of ivabradine and the overlap theory-guided optimal ivabradine therapy.

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“…62 Ivabradine might be used to control ventricular rate in AF patients and to treat atrial tachycardia. 63,64 Additionally, it shows benefits in the prevention of postoperative AF. 65 There have also been various preclinical experiments supporting the anti-AF properties of ivabradine.…”

Section: Ivabradinementioning

confidence: 99%

Drug-induced AF: Arrhythmogenic Mechanisms and Management Strategies

Li,

Lin,

2024

Arrhythm Electrophysiol Rev

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AF is a prevalent condition that is associated with various modifiable and unmodifiable risk factors. Drug-induced AF, despite being commonly under-recognised, can be relatively easy to manage. Numerous cardiovascular and non-cardiovascular agents, including catecholaminergic agents, adenosine, anti-tumour agents and others, have been reported to induce AF. However, the mechanisms underlying drug-induced AF are diverse and not fully understood. The complexity of clinical scenarios and insufficient knowledge regarding drug-induced AF have rendered the management of this condition complicated, and current treatment guidelines follow those for other types of AF. Here, we present a review of the epidemiology of drug-induced AF and highlight a range of drugs that can induce or exacerbate AF, along with their molecular and electrophysiological mechanisms. Given the inadequate evidence and lack of attention, further research is crucial to underscore the clinical significance of drug-induced AF, clarify the underlying mechanisms and develop effective treatment strategies for the condition.

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Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial

Cited by 11 publications

References 22 publications

PR Interval as a Novel Therapeutic Target of Ivabradine Therapy—Prognostic Impact of Ivabradine-Induced PR Prolongation in Heart Failure Patients

PR Interval as a Novel Therapeutic Target of Ivabradine Therapy—Prognostic Impact of Ivabradine-Induced PR Prolongation in Heart Failure Patients

Clinical Implications of Ivabradine in the Contemporary Era

Drug-induced AF: Arrhythmogenic Mechanisms and Management Strategies

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