Use Of Ivabradine Research Articles

Ranolazine therapy is associated with a reduced new diagnosis of diabetes mellitus in chronic coronary syndrome patients: the results of a real-world analysis of an Italian population

Abstract Background Ranolazine (Ran) is an anti-anginal drug acting as a late sodium current inhibitor at a cell membrane level. Some experimental and clinical studies showed an antihyperglycemic effect of the drug, possibly mediated by the increase of insulin secretion, the inhibition of glucagon release, and the protective action on beta-cell function. These effects, additive to the anti-anginal properties of Ran in patients with chronic coronary syndrome (CCS), could modulate and improve glucose metabolic balance. Indeed, data exploring at a population level the association of the drug with diabetes mellitus (DM) incidence are effectively lacking. Aims Aim of this study was to evaluate in CCS patients if the use of Ran, compared with other treatments (No-Ran), was associated with a lower incidence of DM in an Italian real-world clinical setting. Methods Patients included in the database of the National Health System were evaluated (N=6.1 million; about 10% of the Italian population); the recorded information concerned hospitalizations with the related diseases, clinical events, outpatient visits and drug therapy. Patients hospitalized for any cause and discharged with a diagnosis of angina between 2011 and 2020 (ICD-9-CM codes: 413-414) were included in the study after having proved the absence of DM in their medical history. Study population was divided into the Ran (at least one drug prescription) and in the No-Ran cohorts. The mean follow up was 4.3 years for the Ran and 5.0 years for the No-Ran cohorts, respectively. Results The study population included N=171,015 patients (mean age: 72 years, men: 66%). Among them, N=148,808 (No-Ran cohort) were treated with other therapies while N=22,207 (Ran cohort) received Ran. After propensity score matching, Ran (N=6,384) and No-Ran (N=25,536) cohorts did not differ for age, Charlson comorbidity index, use of aspirin and other antithrombotic agents, statins, beta-blockers, Ca-antagonists and nitrates. The incidence of a new diagnosis of DM during the follow-up period was 10.5 and 15.8% in the Ran and in the No-Ran cohorts, respectively (p<0.001). The Cox-regression analysis showed that Ran therapy was associated with a 30% risk reduction to present a new diagnosis of DM (HR=0.70, 95%CI: 0.64-0.76, p<0.001), independently of age, Charlson comorbidity index, heart failure, previous stroke, use of ivabradine, Ca-antagonists and nitrates. Conclusions This real-world study, performed in a whole subset of the Italian population, showed that, in the long-term, the incidence of a new DM diagnosis was lower in Ran users. This association could contribute to explain the benefits of the drug in patients with CCS.

Use of ivabradine in children with junctional ectopic tachycardia after pediatric cardiac surgery; two‐centre experience

AbstractIntroductionAlthough amiodarone is traditionally used in the treatment of postoperative junctional ectopic tachycardia (JET), the search for new treatments is ongoing. We present our experience with ivabradine at two medical centers.Materials and MethodsBetween January 2022 and January 2023, patients who developed JET after pediatric cardiac surgery were prospectively followed up and documented. The diagnosis of JET was made with the support of the electrophysiology team and treatment was based primarily on whether JET disrupted hemodynamics.ResultsThis study was conducted at two high‐volume centers, which record a total of 1130 pediatric cardiac surgeries within a year. The study recruited 26 patients with median heart rate 180 beats per minute, and 10 (38%) patients had impaired hemodynamics. Out of the 26 study participants, 14 (54%) cases were treated with ivabradine alone, 10 (38%) cases were treated with amiodarone + ivabradine, and 2 patients (8%) with high heart rates and prolonged junctional arrhythmia were treated with ivabradine and flecainide. The median time to ventricular rate control was 12 h, and the median time to sinus rhythm conversion was 55.5 h. No ivabradine‐related side effects were observed in any of the patients, and no patient experienced JET recurrence after discontinuing treatment.ConclusionIvabradine seems to be a safe and effective medical treatment that can be used as the primary treatment in patients with stable hemodynamics, as an adjunctive therapy to amiodarone in patients with impaired hemodynamics.

Optimizing heart failure therapy with enhanced medical management: focus on heart rate management

Heart failure (HF) is a significant global health issue, affecting over 60 million people worldwide, with its prevalence expected to rise due to aging populations and the increasing incidence of comorbidities like hypertension and diabetes. Despite therapeutic advances, including quadruple therapy with renin-angiotensin-system inhibitors, beta blockers (BB), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors, HF remains a condition with a poor prognosis, particularly for those with reduced ejection fraction (HFrEF), who are predominantly found in low- and middle-income countries like India. Elevated resting heart rate (HR) is a critical prognostic factor in HF, correlating strongly with cardiovascular mortality and morbidity. For every five-beat increase in HR, there is a 16% rise in cardiovascular mortality and HF hospitalization, emphasizing the need for effective HR management. However, challenges persist in optimizing HF treatment, such as the underutilization of BBs, despite their proven efficacy in reducing mortality. In India, the "double burden" of age-related and contemporary diseases complicates HF management further. Addressing unmet needs in HF care requires optimizing therapeutic strategies and improving treatment adherence, particularly in the context of HR control. Studies indicate that tailored approaches, including the use of BBs and ivabradine, could reduce HR and improve clinical outcomes. The ongoing challenges in accessing guideline-directed therapy and ensuring adherence highlight the need for comprehensive strategies to enhance patient outcomes, while personalized treatments and further research remain essential in navigating the complex landscape of HF management.

Research progress in the application of ivabradine in children with cardiovascular diseases

Ivabradine, as a specific If current inhibitor, has been widely used in the treatment of chronic heart failure in adults due to its ability to reduce heart rate without affecting myocardial contractility and blood pressure. It has also shown good effects in various types of tachyarrhythmias. However, the application of ivabradine in pediatric cardiovascular diseases still faces many limitations. This article reviews the current research progress on the use of ivabradine in treating pediatric cardiovascular diseases both domestically and internationally, aiming to provide guidance for pediatric cardiologists. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 782-788.

Feasibility of Short-Term Use of Ivabradine in Critical Ill Patients Who Have Atrial Fibrillation and Tachycardia.

Ivabradine is approved for heart rate reduction in patients with stable symptomatic heart failure (HF). The United States Food and Drug Administration and Taiwan Central Health Insurance Agency approved the use of ivabradine for patients with chronic stable HF with sinus rhythm, but it has not yet been approved for patients with acute decompensated HF or with atrial fibrillation (AF). To investigate whether short-term ivabradine use is feasible in critically ill patients with AF and rapid ventricular response (RVR). This study retrospectively analyzed 23 patients admitted to an intensive care unit with acute HF and AF-RVR who received ivabradine. All patients initially received a slow IV of amiodarone. Other medications for HF were prescribed according to current HF guidelines. The time taken for ivabradine to reduce HR to 80 beats per minute, referred to as "Time to 80," was measured in each patient. Overall, 69.6 % (16/23) of the patients had New York Heart Association functional class IV HF. In addition, 60.9% (14/23) of the patients required endotracheal intubation and ventilatory support, with more than half receiving vasopressor treatment to manage hypotension. Five patients died during the study period. The surviving patients had a significantly shorter "Time to 80" compared to those who did not survive (p = 0.037). Adding ivabradine to standard treatment might be feasible for critically ill patients with AF and tachycardia. The finding that surviving patients had a shorter "Time to 80" duration than those who did not survive may have clinical implications. However, further investigations are needed to assess its clinical utility.

Beyond quadruple therapy: the potential roles for ivabradine, vericiguat, and omecamtiv mecarbil in the therapeutic armamentarium.

Quadruple therapy is effective for patients with heart failure with reduced ejection fraction, providing significant clinical benefits, including reduced mortality. Clinicians are now in an era focused on how to initiate and titrate quadrable therapy in the early phase of the disease trajectory, including during heart failure hospitalization. However, patients with heart failure with reduced ejection fraction still face a significant "residual risk" of mortality and heart failure hospitalization. Despite the effective implementation of quadruple therapy, high mortality and rehospitalization rates persist in heart failure with reduced ejection fraction, and many patients cannot maximize therapy due to side effects such as hypotension and renal dysfunction. In this context, ivabradine, vericiguat, and omecamtiv mecarbil may have adjunct roles in addition to quadruple therapy (note that omecamtiv mecarbil is not currently approved for clinical use). However, the contemporary use of ivabradine and vericiguat is relatively low globally, likely due in part to the under-recognition of the role of these therapies as well as costs. This review offers clinicians a straightforward guide for bedside evaluation of potential candidates for these medications. Quadruple therapy, with strong evidence to reduce mortality, should always be prioritized for implementation. As second-line therapies, ivabradine could be considered for patients who cannot achieve optimal heart rate control (≥ 70bpm at rest) despite maximally tolerated beta-blocker dosing. Vericiguat could be considered for high-risk patients who have recently experienced worsening heart failure events despite being on quadrable therapy, but they should not have N-terminal pro-B-type natriuretic peptide levels exceeding 8000pg/mL. In the future, omecamtiv mecarbil may be considered for severe heart failure (New York Heart Association class III to IV, ejection fraction ≤ 30%, and heart failure hospitalization within 6months) when current quadrable therapy is limited, although this is still hypothesis-generating and requires further investigation before its approval.

Effect of the combined use of ivabradine and metoprolol in patients with acute myocardial infarction early after percutaneous coronary intervention: A randomized controlled study

ObjectiveTo investigate the effect and safety of the combined use of ivabradine and metoprolol in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). MethodsEighty patients with AMI were randomly divided into the ivabradine group and the control group. The ivabradine group was treated with ivabradine combined with metoprolol after PCI, while the control group was treated with metoprolol only. Both groups were treated continuously for 1 year. Echocardiography-derived parameters, heart rate, cardiopulmonary exercise testing (CPET) data, major adverse cardiac events (MACE) and myocardial markers were analyzed. The primary endpoint was the left ventricular ejection fraction (LVEF). The safety outcomes were blood pressure, liver and kidney function. ResultsThe LVEF was significantly higher in the ivabradine group than in the control group at 1 week, 3 months and 1 year after PCI. The heart rate of the ivabradine group was significantly lower than that of the control group at 1 week and 1month after PCI. The VO2max, metabolic equivalents, anaerobic threshold heart rate, peak heart rate, and heart rate recovery at 8 min of the ivabradine group were significantly higher than those of the control group at 1 year after PCI. Kaplan-Meier analysis demonstrated the one-year total incidence of MACE in the ivabradine group was significantly lower than that in the control group. The B-type natriuretic peptide of the ivabradine group was significantly lower than that of the control group on Day 2 and Day 3 after PCI. The high-sensitivity cardiac troponin I level of the ivabradine group was significantly lower than that of the control group on Day 5 after PCI. ConclusionEarly use of ivabradine in patients with AMI after PCI can achieve effective heart rate control, reduce myocardial injury, improve cardiac function and exercise tolerance, and may reduce the incidence of major adverse cardiac events. (Clinical research registration number: ChiCTR2000032731)

A randomized controlled trial of ivabradine in patients with acute myocardial infarction related cardiogenic shock.

. Acute myocardial infarction-related cardiogenic shock (AMI-CS) is often accompanied by tachycardia, which, in turn, increases myocardial oxygen consumption and hinders the use of ventricular assist devices, such as intra-aortic balloon pump. Evidence suggests that ivabradine may reduce heart rate (HR) without affecting other hemodynamic parameters. The aim of the present study was to determine the effect of ivabradine on reducing HR and changes in other hemodynamic parameters such as cardiac index (CI), in patients with AMI-CS and tachycardia. . A single-center, open label, randomized clinical trial included patients diagnosed with AMI-CS and tachycardia with >100 beats per minute (BPM). Heart rate, cardiac index, and other hemodynamic parameters measured by pulmonary flotation catheter were compared at 0, 6, 12, 24, and 48 hours after randomization. . A total of 12 patients were randomized; 6 received standard therapy, and 6 received ivabradine in addition to standard therapy. Baseline clinical characteristics were similar at randomization. A statistically significant lower heart rate was found at 12 hours (p=0.003) and 48 hours (p=0.029) after randomization, with differences of -23.3 (-8.2 to -38.4) BPM and -12.6 (-0.5 to -25.9) BPM, respectively. No differences in cardiac index, or any other evaluated hemodynamic parameters, length of hospital stay, nor mortality rate were noted between both groups. . The use of ivabradine in patients with AMI-CS was associated with a significant reduction in heart rate at 12 and 48 h, without affecting other hemodynamic parameters.

Impact of heart rate changes during hospitalization on outcome in heart failure with preserved ejection fraction.

The benefits of lowering heart rate (HR) in heart failure (HF) with preserved ejection fraction (HFpEF) patients are still a matter of debate. This study aimed to investigate the relationship between changes in HR during hospitalization and cardiovascular (CV) events and all-cause death in hospitalized HFpEF patients. Hospitalized HF patients between January 2017 and December 2021 were consecutively enrolled in a national, multicentred, and prospective registry database, the China Cardiovascular Association Database-HF Center Registry. HF patients with a left ventricular ejection fraction of ≥50% were defined as HFpEF patients. The study analysed admission/discharge HR, change in HR during hospitalization (∆HR), and ∆HR ratio (∆HR/admission HR). The patients were categorized into three groups: no HR dropping group (ΔHR ratio>0.0%), moderate HR dropping group (-15%<ΔHR ratio≤0.0%), and excessive HR dropping group (ΔHR ratio≤-15%). All patients were followed up for 12months. The primary endpoint was CV events (CV death or HF rehospitalization). The secondary endpoint was all-cause death. A total of 19510 HFpEF patients (9750 males, mean age 71.9±12.2years) were included, with 4575 in the no HR dropping group, 8434 in the moderate HR dropping group, and 6501 in the excessive HR dropping group. Excessive HR dropping during hospitalization was significantly associated with an increased risk of CV events (17.1%) compared with the no HR dropping group (14.5%, P<0.001) or the moderate HR dropping group (14.0%, P<0.001), although all-cause mortality was similar among the three groups. After adjusting for multiple confounding factors, excessive HR dropping remained an independent predictor of increased CV event risk [hazard ratio 1.197, 95% confidence interval (CI) 1.078-1.328]. Subgroup analysis revealed that the prognostic impact of excessive HR dropping on increased CV event risk remained in the subgroups of older age, New York Heart Association class IV, ischaemic HF, higher left ventricular ejection fraction, absence of chronic kidney disease, and use of beta-blockers or ivabradine. Independent determinants associated with excessive HR dropping during admission included use of beta-blockers [odds ratio (OR) 1.683, 95% CI 1.558-1.819], lower discharge diastolic blood pressure (OR 0.988, 95% CI 0.985-0.991), no pacemaker (OR 0.501, 95% CI 0.416-0.603), coexisting atrial fibrillation or atrial flutter (OR 1.327, 95% CI 1.218-1.445), and use of digoxin (OR 1.340, 95% CI 1.213-1.480). In hospitalized HFpEF patients, excessive HR dropping during hospitalization is associated with an increased risk of CV death or HF rehospitalization. These findings highlight the importance of HR monitoring and avoiding excessively slowing down HR in hospitalized HFpEF patients to reduce the risk of CV events.

Extended Use of Ivabradine in Heart Failure with Preserved Ejection Fraction and Inappropriate Sinus Tachycardia

Ivabradine has been used for over a decade in managing chronic coronary syndromes and heart failure (HF) with reducedejection fraction (HFrEF). HF with preserved ejection fraction (HFpEF) accounts for 50% of the total HF cases carrying equalmortality and morbidity risk as HFrEF. Increased heart rate (HR) in such cases has been shown to be associated with poorclinical outcomes. Clinical conditions like inappropriate sinus tachycardia (IST) manifest with elevated HR without anyspecific triggers. Beta-blockers have been the preferred treatment of choice for both HFpEF and IST but are often ineffective orpresent with side effects due to their negative ionotropic effects. Ivabradine, through its inhibitory action on funny current(Ifc), reduces HR without altering the inotropic mechanism. Few case reports and small case series have documented itsextended use and efficacy in reducing HR in these cardiac conditions. In this article, we present two cases who needed HRcontrol, one with HFpEF and another case of IST syndrome. Ivabradine was successfully used in both these cases to controlthe elevated HR.

Effect of ivabradine on structural and functional changes of myocardium and NT-proBNP levels in patients with stable coronary heart disease after coronary stenting.

Aim: To investigate the effect of ivabradine on the hemodynamics and contractility of the myocardium and the features of NT-pro-BNP production in patients with stable ischemic heart disease after endovascular revascularization of the myocardium depending on the number of affected coronary arteries during 12 months of therapy. Materials and Methods: The object of the study was 120 patients with stable coronary artery disease: angina pectoris of functional class III with heart failure IIA FC III with preserved and moderately reduced ejection fraction of the left ventricle, who underwent coronary artery stenting. The examined patients were randomized according to the number of affected coronary vessels and the method of treatment. Results: Ivabradine in patients with stable ischemic heart disease after 12 months of therapy had a significant beneficial effect on the structural and functional parameters of the myocardium (contributed to the reverse remodeling of the left ventricle), which did not depend on the number of stented coronary arteries (p<0.05). In patients with stented one coronary artery, all structural and functional indicators of the heart after 12 months of treatment reached the values of practically healthy individuals from the control group. The use of ivabradine in patients with stable ischemic heart disease with heart failure with preserved and intermediate ejection fraction of the left ventricle after coronary stenting made it possible to ensure the correction of a number of clinical and pathogenetic links of the disease, which generally contributed to the improvement of metric and volumetric parameters of the heart. Conclusions: Ivabradine made it possible to significantly increase the effectiveness of standard therapy, which was manifested by a faster recovery of the geometry and contractility of the left ventricle. Therefore, the use of ivabradine along with standard therapy was appropriate for such a contingent of patients. The management of patients with stable coronary heart disease should combine adequate (surgical and pharmacological) treatment of the underlying disease, further individual medication correction of symptoms and circulatory disorders inherent in coronary heart disease and heart failure.

Ivabradine in the Prevention, and Reduction in Size, of Perioperative Myocardial Injury in Patients Undergoing Orthopedic Surgery for Acute Fracture.

Perioperative myocardial injury is common after major noncardiac surgery and is associated with adverse outcomes. This study investigated the use of ivabradine in patients undergoing urgent surgery for fracture. This was a prospective, double-blind, placebo-controlled, randomized clinical trial. Participants were enrolled 1:1 into ivabradine or placebo arm, and study drug was commenced before operation and continued for 7 days or until discharge. High-sensitivity troponin I was measured daily using Abbott Alinity analyzer and assay, and heart rate data were obtained using continuous Holter monitoring. A total of 199 patients underwent acute orthopedic surgery, 98 in the ivabradine group and 101 in the placebo group. The mean age was 78.7 years (range, 77.5-79.9 years), with 68% women. The average heart rate was 5 to 11 beats per minute lower in the ivabradine group compared with the placebo group at all time points (P<0.001 for all). There was no statistically significant difference between the ivabradine and placebo groups in the number of patients who had perioperative myocardial injury: 28.6% versus 31.6% (P=0.71). In patients with perioperative myocardial injury, average peak troponin was 168.8 ng/L (±431.2 ng/L) in the ivabradine group and 2094.5 ng/L (±7201.9 ng/L) in the placebo group (P=0.16). There was no statistically significant difference between groups in 30-day mortality, blood pressure, stroke, or major adverse cardiovascular event. Starting ivabradine preoperatively in elderly patients requiring acute surgery for fracture did not result in a statistically significant difference in the incidence of perioperative myocardial injury. There was no statistically significant difference in morbidity, mortality, or adverse events between treatment groups. URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12616001634460p.

Physiological effects of ivabradine in heart failure and beyond.

Ivabradine is a pharmacologic agent that inhibits the funny current responsible for determining heart rate in the sinoatrial node. Ivabradine's clinical potential has been investigated in the context of heart failure since it is associated with reduced myocardial oxygen demand, enhanced diastolic filling, stroke volume, and coronary perfusion time; however, it is yet to demonstrate definitive mortality benefit. Alternative effects of ivabradine include modulation of the renin-angiotensin-aldosterone system, sympathetic activation, and endothelial function. Here, we review key clinical trials informing the clinical use of ivabradine and explore opportunities for leveraging its potential pleiotropic effects in other diseases, including treatment of hyperadrenergic states and mitigating complications of COVID-19 infection.

Association of ivabradin use with ventricular arrhythmias in heart failure patients

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Heart failure patients with reduced left ventricular function are at high risk for ventricular arrhythmias and sudden cardiac death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, provides heart rate reduction in sinus rhythm and angina control in chronic coronary syndromes. Purpose The effect of ivabradine on ventricular arrhythmias in heart failure patients has not been fully elucidated. In this study, we aimed to investigate the effect of ivabradine use on life-threatening arrhythmias and long-term mortality in heart failure patients. Methods In this retrospective study, 1639 patients with heart failure were included. Patients were divided into two groups as ivabradine users and non-users. Patients presenting with ventricular tachycardia, presence of ventricular extra systole and ventricular tachycardia in 24-hour rhythm monitoring, appropriate ICD shocks and long-term mortality outcomes were evaluated according to ivabradine use. Results After adjustment for clinical variables, admission with ventricular tachycardia had 3.0 higher rates in ivabradine non-users (95% CI: 1.5 – 10.2). According to the adjusted model for all variables, approximately 4.1 times more appropriate ICD shocks were observed in the ivabradine non-users than the users (95% CI: 1.8 – 9.6). Long-term mortality did not differ between these groups after adjustment for all covariates. Conclusion The use of ivabradine reduced the appropriate ICD discharge in heart failure patients with low ejection fraction. Ivabradine has a potential in the treatment of ventricular arrhythmias in heart failure patients.

Effect of Ivabradine in Controlling Heart Rate in Patients with Sepsis and Septic Shock: Randomized Control Trails

Background: Ivabradine is a selective inhibitor of (If) channels in the sinoatrial node and a pure bradycardic agent with no deleterious effect on other aspects of cardiac function nor on blood pressure. This study was conducted to evaluate the effect of Ivabradine on controlling tachycardia in sepsis patients as compared to placebo. Methods: A total of 100 patients admitted to the Medical Intensive Care Unit (MICU) were recruited in this randomized controlled trial. A total of 50 patients were randomly allocated to either Group A (the Ivabradine group) or Group B (the control group). Heart rate (HR) was recorded for all patients at baseline, 12, 24, 48, 72, 96, and 120 hours. Mean arterial pressure (MAP), ejection fraction (EF), and change in Norepinephrine (NE) dosage were recorded at baseline and post-intervention (120 hours). A mortality rate was recorded for both groups. Results: The patients had a mean age of 32.49 + 16.22 years. There were 56 males and 44 females in the study. Epilepsy (n = 12, 12%) and tetanus (n = 11, 11%) were the most common primary diagnosis. Ventilator Associated Pneumonia (n = 60) was found to be the most common infection. Patients in Group A (23.2 + 11.02 beats per minute) had a significantly greater heart rate reduction at 120 hours in mean heart rate as compared to Group B patients (8.92 + 30.46 beats per minute, p = 0.002). The increase in mean MAP for Group A (1.68 + 2.44 mm Hg) was also significantly greater than that for Group B (0.54 + 2.46 mm Hg, p = 0.022). There was no difference in the mean change in NE dosage between Groups A (0.63 + 0.25 units/minute) and B (-0.34 + 0.36 units/minute, p = 0.106). A significantly greater increase in EF was found for Group A (1.16 + 1.5%), in comparison to Group B (0.30 + 1.69 %, p = 0.009). There were 22 (44%) deaths reported in Group A as compared to 24 (48%, p = 0.688) in Group B. Conclusion:Ivabradine has a significantly greater effect on controlling heart rate as compared to placebo in sepsis patients. The use of Ivabradine should be included in clinical guidelines for managing sepsis patients in ICU settings. Doi: 10.28991/SciMedJ-2023-05-01-04 Full Text: PDF

Therapeutic Use and Molecular Aspects of Ivabradine in Cardiac Remodeling: A Review.

Cardiac remodeling can cause ventricular dysfunction and progress to heart failure, a cardiovascular disease that claims many lives globally. Ivabradine, a funny channel (If) inhibitor, is used in patients with chronic heart failure as an adjunct to other heart failure medications. This review aims to gather updated information regarding the therapeutic use and mechanism of action of ivabradine in heart failure. The drug reduces elevated resting heart rate, which is linked to increased morbidity and mortality in patients with heart failure. Its use is associated with improved cardiac function, structure, and quality of life in the patients. Ivabradine exerts several pleiotropic effects, including an antiremodeling property, which are independent of its principal heart-rate-reducing effects. Its suppressive effects on cardiac remodeling have been demonstrated in animal models of cardiac remodeling and heart failure. It reduces myocardial fibrosis, apoptosis, inflammation, and oxidative stress as well as increases autophagy in the animals. It also modulates myocardial calcium homeostasis, neurohumoral systems, and energy metabolism. However, its role in improving heart failure remains unclear. Therefore, elucidating its molecular mechanisms is imperative and would aid in the design of future studies.

Ivabradine in the Management of Pediatric Arrhythmias.

Ivabradine has recently been described as a treatment for arrhythmias of enhanced automaticity in the pediatric population. We present an illustrative case of an infant treated with ivabradine for atrial ectopic tachycardia and we review the available literature on this topic.

Heart rate control and haemodynamic improvement with ivabradine in cardiogenic shock patient on mechanical circulatory support.

Cardiogenic shock (CS) is a life-threatening condition due to primary cardiac dysfunction. First-line therapy involves drug administration (including inotropes and/or vasopressors) up to mechanical circulatory support. Tachycardia is a frequent compensatory mechanism in response to hypotension and low cardiac output or a side effect related to inotropic drugs. Ivabradine selectively acts on the IKf channel in the sinoatrial node to reduce sinus heart rate without affecting inotropism. Its use, in small non-randomized series of patients with CS without mechanical circulatory support, was safe and well tolerated. We present the use of ivabradine in six patients with CS undertaking veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and a matched cohort of selected patients with similar features who did not receive ivabradine. Data regarding haemodynamic and echocardiographic monitoring, oxygenation, renal function, mechanical circulatory support, inotropes, and vasopressors doses were collected before (t0), at 12 (t1), 24 (t2), and 48 (t3) h after ivabradine administration. Ivabradine administration led to a significant heart rate reduction of 20.83 [95% confidence interval (CI) -27.2 to -14.4] b.p.m. (<0.01). Echo-derived left ventricular native stroke volume (SV) significantly increased by +7.83 (95% CI 4.74-10.93) mL (P < 0.001) with a parallel reduction of VA-ECMO support [-170 (95% CI -225.05 to -114.95)]. Noradrenaline was down-titrated over the observation period in all patients (P = 0.016). A significant reduction in heart rate was observed after ivabradine administration. This was associated with a native ventricular SV improvement allowing the reduction of extracorporeal flow support and vasopressors administration.

Heart rate control and hemodynamic improvement with Ivabradine in cardiogenic shock patients on mechanical circulatory support

Abstract Background Cardiogenic shock (CS) is a life threatening condition due to primary cardiac dysfunction. First line therapy involves drug administration (including inotropes and/or vasopressors) up to mechanical circulatory support. Tachycardia is a compensatory mechanism in response to hypotension and low cardiac output or a side effect related to inotropic drugs. Ivabradine selectively acts on IKf channel in the sinoatrial node to reduce sinus heart rate without affecting inotropism. Its use in small non-randomized series of patients with CS was safe and well tolerated [1]. Methods We present the use of ivabradine in six patients with CS undertaking veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Data regarding haemodynamic and echocardiographic monitoring were collected before, at 12, 24 and 48 hours after ivabradine administration. Results Ivabradine was administered through naso-gastric tube with a median time of 23 hours [IQR 18–28] since VA-ECMO implantation at the starting dose of 2.5 mg twice a day. Haemodynamic and echocardiographic parameters are shown in table. Ivabradine was well tolerated and led to a significant reduction of heart rate after first administration (p&amp;lt;0.01) (Fig. 1, panel A). Echo-derived stroke volume increased significantly (p&amp;lt;0.001) (Fig. 1, panel B); so did cardiac index (p&amp;lt;0.001) and left ventricular cardiac power index (p 0.005) (Fig. 1, panel C). VA-ECMO rate pump and blood flow significantly decreased (respectively p 0.002, p 0.001). No significant changes were observed in arterial blood pressure (p&amp;gt;0.05). Norepinephrine was down-titrated in all patients (p 0.01). Patients presented with cardiac arrest died due to neurological injury whereas the others were weaned off VA-ECMO and discharged alive. Conclusions Ivabradine administration resulted in an effective reduction of heart rate leading to ventricular stroke volume allowing the reduction of extracorporeal flow support and vasopressors administration. Funding Acknowledgement Type of funding sources: None.

Ivabradine in heart failure patients with reduced ejection fraction and history of paroxysmal atrial fibrillation.

AimsIvabradine is indicated for heart failure (HF) patients with reduced ejection fraction (HFrEF), but limited data are available with regards to the use of ivabradine in those with a history of paroxysmal atrial fibrillation (AF). To assess the effect of ivabradine in HFrEF patients with paroxysmal AF, we analysed heart failure (HF) hospitalization and mortality from multiple‐centre registry database.Methods and resultsWe conducted a multicentre observational matched cohort study, and this study enrolled patient with symptomatic HFrEF from 1 January 2015 to 31 December 2018 who had a history of paroxysmal AF in Chang Gung Memorial Hospital medical database in Taiwan. A total of 2042 patients were eligible for the study, of whom 887 were prescribed with ivabradine and 1115 were not. The primary outcome, including HF hospitalization and cardiovascular death, and individual outcome during the 12 month observation period were analysed after inverse probability of treatment weighting. The ivabradine group had significantly lower mean heart rate after 12 months follow‐up than the non‐ivabradine group (P < 0.05). The primary outcome was significantly higher in the ivabradine group than the non‐ivabradine group after 12 months follow‐up (hazard ratio [HR] = 1.58; 95% confidence interval [CI], 1.26–2.00, P < 0.001). Moreover, the ivabradine group had a significantly higher event rate of HF hospitalization (HR = 1.56; 95% CI, 1.40–1.75, P < 0.001) and HF death (HR = 1.67; 95% CI, 1.14–2.44, P = 0.009) than the non‐ivabradine group.ConclusionsIvabradine treatment was associated with an increased risk of HF hospitalization in symptomatic HFrEF patients with a history of paroxysmal AF. Further prospective randomized studies are warranted.