Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiography substudy
TL;DR: Ivabradine reverses cardiac remodelling in patients with HF and LV systolic dysfunction and patients with the largest relative reductions in LVESVI had the lowest event rates.
Abstract: 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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TL;DR: The remodelling processes in atherosclerosis, vascular and myocardial ischaemia-reperfusion injury, and heart failure are characterised, and potential avenues for innovative therapeutic approaches are drawn attention, including conditioning and metabolic strategies.
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TL;DR: In this brief review, the effects of heart rate on the heart, arterial system and survival will be discussed.
Abstract: It has long been known that life span is inversely related to resting heart rate in most organisms. This association between heart rate and survival has been attributed to the metabolic rate, which is greater in smaller animals and is directly associated with heart rate. Studies have shown that heart rate is related to survival in apparently healthy individuals and in patients with different underlying cardiovascular diseases. A decrease in heart rate due to therapeutic interventions may result in an increase in survival. However, there are many factors regulating heart rate, and it is quite plausible that these may independently affect life expectancy. Nonetheless, a fast heart rate itself affects the cardiovascular system in multiple ways (it increases ventricular work, myocardial oxygen consumption, endothelial stress, aortic/arterial stiffness, decreases myocardial oxygen supply, other) which, in turn, may affect survival. In this brief review, the effects of heart rate on the heart, arterial system and survival will be discussed.
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Abstract: Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF)....
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TL;DR: The effect of ivabradine on outcomes is greater in patients with heart rate ≥75 bpm with heart rates achieved <60 bpm or heart rate reductions >10 bpm predicting best risk reduction, which emphasize the importance of identification of high-risk HF patients by high heart rates and their treatment withheart rate-lowering drugs such as ivABradine.
Abstract: We analysed the effect of ivabradine on outcomes in heart failure (HF) patients on recommended background therapies with heart rates ≥75 bpm and 10 bpm. None of the endpoints was significantly reduced in the 10 bpm. Ivabradine was tolerated similarly in both groups. The effect of ivabradine on outcomes is greater in patients with heart rate ≥75 bpm with heart rates achieved 10 bpm predicting best risk reduction. Our findings emphasize the importance of identification of high-risk HF patients by high heart rates and their treatment with heart rate-lowering drugs such as ivabradine.
203 citations
Cites result from "Effects of selective heart rate red..."
...Consistent with these conclusions, heart rate reduction with ivabradine has been shown to reduce remodelling of the failing heart [15], associated with a reversal of the HF-associated phenotype of the failing myocyte [16, 17]....
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TL;DR: An update on the associations between heart rate and cardiovascular outcomes in various conditions, the experimental effects of heart rate reduction with ivabradine, and the potential new indications in cardiovascular disease is provided.
150 citations
Cites background or result from "Effects of selective heart rate red..."
...Mechanistically, beneficial left ventricular reverse remodeling occurred with ivabradine treatment compared with placebo.(62) In addition to the direct beneficial effect of myocardial performance and energy balance, unloading of the left ventricle may occur with heart rate slowing because it has been shown to improve ventricular arterial coupling, potentially an effect of arterial stiffness and afterload....
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...These results were confirmed by clinical studies in, showing increases in left ventricular ejection fraction and reductions in left ventricular volumes after treatment with ivabradine, forming a pathophysiologic basis for ivabradine as a disease-modifying therapy , improving cardiac mechanical performance.(62) Patients with heart rates >70 bpm were included in the SHIFT (Systolic Heart Failure Treatment with the If-inhibitor Ivabradine trial) study....
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References
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TL;DR: Members of the Chamber Quantification Writing Group are: Roberto M. Lang, MD, Fase, Michelle Bierig, MPH, RDCS, FASE, Richard B. Devereux,MD, Frank A. Flachskampf, MD and Elyse Foster, MD.
Abstract: Members of the Chamber Quantification Writing Group are: Roberto M. Lang, MD, FASE, Michelle Bierig, MPH, RDCS, FASE, Richard B. Devereux, MD, Frank A. Flachskampf, MD, Elyse Foster, MD, Patricia A. Pellikka, MD, Michael H. Picard, MD, Mary J. Roman, MD, James Seward, MD, Jack S. Shanewise, MD, FASE, Scott D. Solomon, MD, Kirk T. Spencer, MD, FASE, Martin St John Sutton, MD, FASE, and William J. Stewart, MD
10,834 citations
TL;DR: This document reviews the technical aspects on how to perform quantitative chamber measurements of morphology and function, which is a component of every complete echocardiographic examination.
Abstract: Quantification of cardiac chamber size, ventricular mass and function ranks among the most clinically important and most frequently requested tasks of echocardiography. Over the last decades, echocardiographic methods and techniques have improved and expanded dramatically, due to the introduction of higher frequency transducers, harmonic imaging, fully digital machines, left-sided contrast agents, and other technological advancements. Furthermore, echocardiography due to its portability and versatility is now used in emergency rooms, operating rooms, and intensive care units. Standardization of measurements in echocardiography has been inconsistent and less successful, compared to other imaging techniques and consequently, echocardiographic measurements are sometimes perceived as less reliable. Therefore, the American Society of Echocardiography, working together with the European Association of Echocardiography, a branch of the European Society of Cardiology, has critically reviewed the literature and updated the recommendations for quantifying cardiac chambers using echocardiography. This document reviews the technical aspects on how to perform quantitative chamber measurements of morphology and function, which is a component of every complete echocardiographic examination.
4,014 citations
"Effects of selective heart rate red..." refers methods in this paper
...All measurements were made according to the recommendations of the American Society of Echocardiography (ASE) and the European Association of Echocardiography.(8) Each assessment was analysed for at least three consecutive cycles (or at least five in case of atrial fibrillation), avoiding post-ectopic beats....
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...All measurements were made according to the recommendations of the American Society of Echocardiography (ASE) and the European Association of Echocardiography.8 Each assessment was analysed for at least three consecutive cycles (or at least five in case of atrial fibrillation), avoiding post-ectopic beats....
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TL;DR: Left ventricular end-diastolic and end-systolic volume and ejection fraction data provide support for the beneficial effects of therapeutic agents such as angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents on the remodeling process.
2,215 citations
TL;DR: In this article, the effect of heart rate reduction by the selective sinus-node inhibitor ivabradine on outcomes in heart failure was evaluated in a randomized, double-blind, placebo-controlled, parallel-group study.
2,039 citations
TL;DR: In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose- related reductions in mortality and hospitalization rate and was generally well tolerated.
Abstract: Background We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a “third-generation” β-blocking agent with vasodilator properties, in chronic heart failure. Methods and Results Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, ...
1,280 citations