Heart Rate Reduction for 12 Months With Ivabradine Reduces Left Ventricular Mass in Cardiac Allograft Recipients

Doesch, Andreas O.; Ammon, K.; Konstandin, Mathias; Celik, Sultan; Kristen, Arnt V.; Frankenstein, Lutz; Buss, Sebastian J.; Hardt, Stefan; Sack, Falk–Udo; Katus, Hugo A.; Dengler, Thomas J.

doi:10.1097/tp.0b013e3181b4e0f5

Cited by 30 publications

(52 citation statements)

References 12 publications

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“…However, its impact on mortality was not assessed. A further study of the same group exposed that selective reduction in HR with ivabradine in patients with symptomatic sinus tachycardia led to a significant reduction in left ventricle hypertrophy [20].…”

Section: Discussionmentioning

confidence: 99%

Impact of basal heart rate on long-term prognosis of heart transplant patients

et al. 2013

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Section: Discussionmentioning

confidence: 99%

Impact of basal heart rate on long-term prognosis of heart transplant patients

et al. 2013

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“…Despite the limitations of our study model, such as the basal conditions, absence of neuronal influence, and fixed compliance, we believe that this experimental model mimics to some extent the human transplanted heart, a condition for which IVA has been shown to be beneficial for the control of HR (16,27).…”

Section: Cihr Author Manuscriptmentioning

confidence: 99%

Ivabradine reduces heart rate while preserving metabolic fluxes and energy status of healthy normoxic working hearts

Lauzier

Vaillant

Gélinas

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Heart rate reduction (HRR) is an important target in the management of patients with chronic stable angina. Most available drugs for HRR, such as β-blockers, have adverse effects, including on cardiac energy substrate metabolism, a well-recognized determinant of cardiac homeostasis. This study aimed at 1) testing whether HRR by ivabradine (IVA) alters substrate metabolism in the healthy normoxic working heart and 2) comparing the effect of IVA with that of the β-blocker metoprolol (METO). This was assessed using our well-established model of ex vivo mouse heart perfusion in the working mode, which enables concomitant evaluation of myocardial contractility and metabolic fluxes using 13 C-labeled substrates. Hearts were perfused in the absence (controls; n = 10) or presence of IVA (n = 10, 3 μM) with or without atrial pacing to abolish HRR in the IVA group. IVA significantly reduced HR (35 ± 5%) and increased stroke volume (39 ± 9%) while maintaining similar cardiac output, contractility, power, and efficiency. Effects of IVA on HR and stroke volume were reversed by atrial pacing. At the metabolic level, IVA did not impact on substrate selection to citrate formation, rates of glycolysis, or tissue levels of high-energy phosphates. In contrast, METO, at concentrations up to 40 μM, decreased markedly cardiac function (flow: 25 ± 6%; stroke volume: 30 ± 10%; contractility: 31 ± 9%) as well as glycolysis (2.9-fold) but marginally affected HR. Collectively, these results demonstrate that IVA selectively reduces HR while preserving energy substrate metabolism of normoxic healthy working mouse hearts perfused ex vivo, a model that mimics to some extent the denervated transplanted heart. Our results provide the impetus for testing selective HRR by IVA on cardiac substrate metabolism in pathological models.Address for reprint requests and other correspondence: C. Des Rosiers, Laboratory of Intermediary Metabolism, Montreal Heart Institute, Research Center, 5000 Bélanger St., Rm. 5350, Montreal, QC, Canada, H1T 1C8 (christine.des.rosiers@umontreal.ca CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptKeywords substrate metabolism; isolated working heart; ivabradine; β-blockers Heart rate reduction (HRR) is an important target in the management of patients with ischemic heart disease, a major cause of morbidity and mortality in developed countries (for reviews, see Refs. 6 and 45). Given their well-described beneficial effects on cardiovascular outcomes after myocardial infarction and in heart failure, β-blockers remain the first line treatment for many patients with ischemic heart disease (5, 12, 28). However, even new classes of β-blockers exhibit undesirable side effects on cardiac energy substrate metabolism (4, 28), which is now a well-recognized determinant of energy production, redox status, contractile function, ion fluxes, and oxygen consumption as well as hypertrophy development and progression to heart failure (33, 41).Specifically, acute administration of β-blockers to the isolated perfu...

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“…In acute heart failure due to myocarditis: In a few cases [65], ivabradine was administered as an adjuvant off-label to patients with acute heart failure and multiorgan failure due to myocarditis; it has proven to be beneficial in supporting hemodynamic stabilization [66]. Furthermore, in cardiac allograft recipients, ivabradine showed a reduction of left ventricular mass index by significant heart rate reduction [85]. In the current case, TTC symptoms recovered during ivabradine use; however, a causal relation between ivabradine and left ventricular recovery cannot be proven as the recovery of TTCinduced left ventricular dysfunction may occur spontaneously; however, the condition-related symptoms showed good clinical response.…”

Section: Ivabradine Use In Different Disordersmentioning

confidence: 99%

Ivabradine in Takotsubo cardiomyopathy

Saïd¹

2017

IJCC

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Abstract:AIM: The aim of this review is to present a case report of Takotsubo cardiomyopathy and to review the current literature. The second aim is to describe the role of ivabradine in the management of Takotsubo cardiomyopathy when intolerance for beta blockers occurs. MATERIALS: Case report and literature review of Takotsubo cardiomyopathy. RESULTS: A 52-year-old Caucasian female presented with Takotsubo cardiomyopathy triggered by severe emotional stress. Dmission electrocardiogram mimicked acute ST-segment elevation myocardial infarction , coronary angiography excluded significant coronary stenosis and left ventriculogram showed a typical Takotsubo cardiomyopathy apical ballooning appearance. Due to beta blocker intolerance, "off-label" treatment with ivabradine was initiated because of symptomatic sinus tachycardia. Echocardiography revealed normalization of the ejection fraction at outpatient follow-up. In the recent literature, ivabradine has been used in the management of different entities such as stable angina pectoris, congestive heart failure, inappropriate sinus tachycardia syndrome, postural tachycardia syndrome and Takotsubo cardiomyopathy. CONCLUSION: Takotsubo cardiomyopathy may be induced by witnessing a robbery. The patient was intolerant for beta blockers and had a favorable response to treatment with ivabradine. Ivabradine may be an alternative choice in cases where there is an intolerance of beta blockers. We present an exceedingly rare case of Takotsubo cardiomyopathy induced by uncommon severe emotional stress, catching her colleague stealing money from the cash register, which was associated with sinus tachycardia in a female patient with intolerance for beta blockers. The patient responded well to treatment with oral ivabradine. The literature is briefly reviewed

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Heart Rate Reduction for 12 Months With Ivabradine Reduces Left Ventricular Mass in Cardiac Allograft Recipients

Abstract: Heart rate reduction with ivabradine is effective and safe in heart transplant recipients. After 12 months, significant effects on LVMI were observed. Therefore, ivabradine may offer a beneficial effect on left ventricular remodelling in HTX patients.

Cited by 30 publications

References 12 publications

Impact of basal heart rate on long-term prognosis of heart transplant patients

Impact of basal heart rate on long-term prognosis of heart transplant patients

Ivabradine reduces heart rate while preserving metabolic fluxes and energy status of healthy normoxic working hearts

Ivabradine in Takotsubo cardiomyopathy

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