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      Heart rate reduction after ivabradine might be associated with reverse electrical remodeling in patients with cardiomyopathy and left bundle branch block

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          Abstract

          Left bundle branch block increases the risk of death in patients with chronic heart failure. We herein report four clinical cases of patients with chronic heart failure caused by nonischemic cardiomyopathy with left bundle branch block that occurred when adding ivabradine to optimal medical therapy, resulting in reverse electrical and mechanical remodeling. This phenomenon might be explained by the effect of ivabradine on reverse remodeling of the left ventricle with improvement of intraventricular conduction.

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          Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiography substudy

          Jean-Claude Tardif, Eileen O’Meara, Michel Komajda … (2011)
          Aims The SHIFT echocardiographic substudy evaluated the effects of ivabradine on left ventricular (LV) remodelling in heart failure (HF). Methods and results Eligible patients had chronic HF and systolic dysfunction [LV ejection fraction (LVEF) ≤35%], were in sinus rhythm, and had resting heart rate ≥70 bpm. Patients were randomly allocated to ivabradine or placebo, superimposed on background therapy for HF. Complete echocardiographic data at baseline and 8 months were available for 411 patients (ivabradine 208, placebo 203). Treatment with ivabradine reduced LVESVI (primary substudy endpoint) vs. placebo [−7.0 ± 16.3 vs. −0.9 ± 17.1 mL/m2; difference (SE), −5.8 (1.6), 95% CI −8.8 to −2.7, P< 0.001]. The reduction in LVESVI was independent of beta-blocker use, HF aetiology, and baseline LVEF. Ivabradine also improved LV end-diastolic volume index (−7.9 ± 18.9 vs. −1.8 ± 19.0 mL/m2, P= 0.002) and LVEF (+2.4 ± 7.7 vs. −0.1 ± 8.0%, P< 0.001). The incidence of the SHIFT primary composite outcome (cardiovascular mortality or hospitalization for worsening HF) was higher in patients with LVESVI above the median (59 mL/m2) at baseline (HR 1.62, 95% CI 1.03–2.56, P= 0.04). Patients with the largest relative reductions in LVESVI had the lowest event rates. Conclusion Ivabradine reverses cardiac remodelling in patients with HF and LV systolic dysfunction.
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            Beneficial effects of delayed ivabradine treatment on cardiac anatomical and electrical remodeling in rat severe chronic heart failure.

            Smail Messaoudi, Jane-Lise Samuel, Johnny Nehmé … (2009)
            We tested the hypothesis that heart rate (HR) reduction, induced by the selective hyperpolarization-activated current inhibitor ivabradine (Iva), might improve left ventricular (LV) function, structure, and electrical remodeling in severe post-myocardial infarction (MI) chronic heart failure (HF). MI was produced in adult male Wistar rats. After 2 mo, echocardiography was performed before the randomization into MI and MI + Iva (10 mg x kg(-1) x day(-1)) groups. After 3 mo of treatment, echocardiography and 24-h telemetry were recorded. Cardiac collagen, mRNA, and protein expressions of angiotensin-converting enzyme (ACE) and ANG II type 1 (AT(1)) receptor were quantified. As a result, at 2 mo post-MI, all rats displayed severe congestive HF signs (ejection fraction < 30%). At 5 mo post-MI, body and heart weights were similar in the MI and MI + Iva groups. LV ejection fraction and LV end-diastolic pressure were worsened in the MI group, whereas both were improved with Iva. Iva reduced HR by 10.4% (P < 0.03 vs. MI) and ventricular premature complexes by 89% (P < 0.03) and improved HR variability (standard deviation of the RR interval) by 22% (P < 0.05). There were no effects of Iva on PR, QRS, and QT durations. Interstitial fibrosis in the MI-remote LV was markedly reduced by Iva (4.0 +/- 0.1 vs. 1.8 +/- 0.1%, P < 0.005). Increases in ventricular gene and protein expressions of ACE and AT(1) receptor in MI were completely blunted by Iva. In conclusion, these data indicated that HR reduction by Iva prevents the worsening of LV dysfunction and remodeling that may be related to a downregulation of cardiac renin-angiotensin-aldosterone system transcripts. Such beneficial effects of Iva on cardiac remodeling open new clinical perspectives for the treatment of severe HF.
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              Reverse electrical remodeling by cardiac resynchronization therapy: prevalence and clinical impact.

              Frédéric Sebag, Raphael P Martins, Pascal Defaye … (2012)
              Cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) in patients with congestive heart failure, LV systolic dysfunction, and a wide QRS complex. Previous reports suggest that CRT may also induce electrical remodeling but the impact on clinical outcome remains unknown.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Int Med Res
                Journal ID (iso-abbrev): J. Int. Med. Res
                Journal ID (publisher-id): IMR
                Journal ID (hwp): spimr
                Title: The Journal of International Medical Research
                Publisher: SAGE Publications (Sage UK: London, England )
                ISSN (Print): 0300-0605
                ISSN (Electronic): 1473-2300
                Publication date (Electronic): 18 September 2018
                Publication date (Print): November 2018
                Volume: 46
                Issue: 11
                Pages: 4825-4828
                Affiliations
                [1-0300060518799566]Cardiovascular Center, Na Homolce Hospital, Roentgenova 2, Prague, Czech Republic, EU
                Author notes
                [*]Filip Málek, Cardiovascular Center, Na Homolce Hospital, Roentgenova 2, 150 30 Prague 5, Czech Republic, EU. Email: filip.malek@ 123456centrum.cz
                Article
                Publisher ID: 10.1177_0300060518799566
                DOI: 10.1177/0300060518799566
                PMC ID: 6259405
                PubMed ID: 30223689
                SO-VID: 96916b21-7c3b-4ed0-bf6b-fe225ec0a249
                Copyright © © The Author(s) 2018
                License:

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 26 June 2018
                Date accepted : 17 August 2018
                Funding
                Funded by: Ministry of Health, Czech Republic, FundRef ;
                Award ID: MH CZ - DRO (Nemocnice Na Homolce - NNH, 0002388
                Categories
                Subject: Case Reports

                Keywords: electrical remodeling,ivabradine,left bundle branch block,cardiomyopathy,chronic heart failure,intraventricular conduction
                Data availability:
                Keywords: electrical remodeling, ivabradine, left bundle branch block, cardiomyopathy, chronic heart failure, intraventricular conduction

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