Use of ivabradine for treatment of junctional ectopic tachycardia in post congenital heart surgery

Cardiac surgeries especially involving crux of the heart as performed in tetralogy of Fallot (TOF) and pulmonary stenosis are mainly responsible for junctional ectopic tachycardia (JET). Diversified antiarrhythmic agents have been used in an impressive way to treat JET but showed suboptimal efficacy and varied associated adverse effects. But, ivabradine has proved as final crusader for its treatment. We report our initial experience of 4 cases in last 6 months with ivabradine in the management of postoperative JET. Encouraged by various reports and our increasing experience with ivabradine in heart failure population, we have moved to ivabradine as the first drug of choice for postoperative JET. Bradycardia was the only significant adverse effect in our series. The availability of atrial and ventricular pacing wires or at least transvenous temporary pacing should be ensured before starting ivabradine.     

La ivabradina induce cardioprotección previniendo la degradación de la matriz extracelular inducida por shock cardiogénico

Introduction and objectivesIvabradine reduces heart rate by blocking the I(f) current and preserves blood pressure and stroke volume through unknown mechanisms. Caveolin-3 protects the heart by forming protein complexes with several proteins, including extracellular matrix (ECM)-metalloproteinase-inducer (EMMPRIN) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HN4), a target of ivabradine. We hypothesized that ivabradine might also exert cardioprotective effects through inhibition of ECM degradation.MethodsIn a porcine model of cardiogenic shock, we studied the effects of ivabradine on heart integrity, the levels of MMP-9 and EMMPRIN, and the stability of caveolin-3/HCN4 protein complexes with EMMPRIN.ResultsAdministration of 0.3 mg/kg ivabradine significantly reduced cardiogenic shock-induced ventricular necrosis and expression of MMP-9 without affecting EMMPRIN mRNA, protein, or protein glycosylation (required for MMP activation). However, ivabradine increased the levels of the caveolin-3/LG-EMMPRIN (low-glycosylated EMMPRIN) and caveolin-3/HCN4 protein complexes and decreased that of a new complex between HCN4 and high-glycosylated EMMPRIN formed in response to cardiogenic shock. We next tested whether caveolin-3 can bind to HCN4 and EMMPRIN and found that the HCN4/EMMPRIN complex was preserved when we silenced caveolin-3 expression, indicating a direct interaction between these 2 proteins. Similarly, EMMPRIN-silenced cells showed a significant reduction in the binding of caveolin-3/HCN4, which regulates the I(f) current, suggesting that, rather than a direct interaction, both proteins bind to EMMPRIN.ConclusionsIn addition to inhibition of the I(f) current, ivabradine may induce cardiac protection by inhibiting ECM degradation through preservation of the caveolin-3/LG-EMMPRIN complex and control heart rate by stabilizing the caveolin-3/HCN4 complex.     

伊伐布雷定对糖尿病伴冠心病患者的效果观察

目的 探讨伊伐布雷定对糖尿病伴冠心病患者的效果观察。方法 选择2018年1月至2019年1月本院收治的糖尿病伴冠心病患者90例,采用随机数字表法分为两组,各45例。对照组采用常规治疗,观察组在对照组基础上服用伊伐布雷定。对比两组临床疗效、心功能指标、炎性因子、血液流变学指标。结果 治疗后,观察组总有效率97.78%高于对照组80.00%,差异具有统计学意义（P<0.05）。观察组心率（71.63±3.21）次/min及氨基末端脑钠肽前体（NT-proBNP）（755.48±346.42）ng/L水平、空腹血糖( FPG)（6.55±1.14）mmol/L、糖化血红蛋白( HbA1c)（6.13±1.08）%、餐后2 h 血糖(2hPG)（7.14±0.52）mmol/L、肿瘤坏死因子-α（TNF-α）（0.81±0.21）ng/L、白介素-6（IL-6）（7.42±1.21）ng/L、血清超敏C反应蛋白（hs-CRP）（1.24±0.54）mg/L水平、全血黏度（33.92±1.13）mpa?s、血浆黏度（1.35±0.09）mpa?s、血浆纤维蛋白原（2.01±0.03）g/L低于对照组心率（84.06±3.54）次/min、NT-proBNP（1598.14±309.34）ng/L水平、FPG（7.95±1.02）mmol/L、HbA1c（7.12±1.23）%、2hPG（7.87±0.76）mmol/L、TNF-α（1.06±0.28）ng/L、IL-6（9.24±1.52）ng/L、hs-CRP（1.67±0.72）mg/L水平、全血黏度（38.10±1.18）mpa?s、血浆黏度（1.58±0.13）mpa?s、血浆纤维蛋白原（2.64±0.16）g/L;且观察组左心室射血分数（LVEF）（50.69±4.98）%、左心室收缩末期内径（LVESD）（45.70±4.70）mm、左心室舒张末期内径（LVEDD）（45.20±3.81）mm、6 min步行距离（422.67±70.54）m高于对照组LVEF（46.72±5.38）%、LVESD（50.52±5.20）mm、LVEDD（49.40±4.03）mm水平、6 min步行距离（322.04±53.12）m,差异具有统计学意义（P<0.05）。结论 伊伐布雷定有助于糖尿病伴冠心病患者降低NT-proBNP水平、改善心功能指标、降低炎性因子水平和血液流变学指标,改善患者临床疗效,提高患者生活质量,有助于患者转归。     

盐酸伊伐布雷定对单硝酸异山梨酯在比格犬体内的药动学影响

目的 研究盐酸伊伐布雷定对单硝酸异山梨酯在比格犬体内的药动学影响.方法 采用HPLC法测定单硝酸异山梨酯单独给药或联合盐酸伊伐布雷定给药后不同时间比格犬体内的血药浓度,采用非房室模型计算单硝酸异山梨酯药动学参数.结果 单硝酸异山梨酯单独给药及与盐酸伊伐布雷定联合使用后,在比格犬体内单硝酸异山梨酯的主要药动学参数差异无统计学意义(P<0.05).单硝酸异山梨酯联合盐酸伊伐布雷定给药相对单硝酸异山梨酯单独给药的生物利用度为100%.结论 盐酸伊伐布雷定与单硝酸异山梨酯联合用药后对单硝酸异山梨酯在比格犬体内的药动学过程无影响.     

Elevated Heart Rate in Cardiovascular Diseases: A Target for Treatment?

Heart rate is a major determinant of myocardial oxygen consumption and of cardiac work, and thus reduction of heart rate may represent an important strategy for the treatment of patients with a wide range of cardiac disorders. In addition, several experimental lines of research point to high heart rate as an important risk factor for atherosclerosis and, thus, pharmacologic heart rate reduction could prevent or retard the development of atherosclerotic plaques and increase survival. Today, in patients with acute or chronic coronary syndromes or with congestive heart failure, reducing heart rate is a generally accepted treatment modality. Up to now, no human study has been performed to demonstrate the efficacy and the risk-benefit ratio of cardiac slowing in patients without cardiac disorders. However, recent retrospective analyses of the INternational VErapamil-SR/trandolapril STudy and the Paris Prospective Study 1 provided promising results. Treatment of high heart rate in healthy subjects appears to be premature, but in clinical conditions such as hypertension or diabetes, the reduction of elevated heart rate appears a desirable additional goal of therapy.     

Effect of ivabradine on cardiac arrhythmias: Antiarrhythmic or proarrhythmic?

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Effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction: A pilot test

Objective

To investigate the effect of early use of ivabradine on left ventricular remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI).

Methods

A total of 66 STEMI patients with sinus rhythm and the resting heart rate ≥80 bpm after successful emergency PCI were included. The patients in the test group were treated with ivabradine combined with metoprolol at 12 hr after PCI, while the control group was given only metoprolol orally. Their resting heart rate was controlled to <70 bpm at discharge and followed for 180 days. Heart rate and blood pressure were measured regularly. Echocardiogram was performed. N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity troponin T, high sensitivity troponin I, and high sensitivity C-reactive protein were measured. The major adverse cardiovascular events during hospitalization and follow-up period were recorded.

Results

Compared with the control group, the heart rate of the test group decreased significantly (p < .05). Compared with the control group, the left ventricular end-diastolic volume and left ventricular end-systolic volume were significantly decreased while left ventricular ejection fraction was significantly increased in the test group at 90 days after operation. NT-proBNP of the test group was significantly lower than that of the control group at 7 days after operation (p < .05).

Conclusion

For STEMI patients, early use of ivabradine combined with standard therapy such as β-blocker after successful reperfusion can achieve effective heart rate control, with great safety and tolerance. But the effect of ivabradine on left ventricular remodeling is uncertain.