Effect of If-Channel Inhibition on Hemodynamic Status and Exercise Tolerance in Heart Failure With Preserved Ejection Fraction

Kosmala, Wojciech; Holland, David J.; Rojek, Aleksandra; Wright, Leah; Przewlocka‐Kosmala, M.; Marwick, Thomas H.

doi:10.1016/j.jacc.2013.06.043

Cited by 170 publications

(96 citation statements)

References 38 publications

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“…Given plurality of HFpEF definitions in professional guidelines and in clinical trials,6, 10, 19, 20, 21, 22, 23, 24, 25 we sought to determine whether results would change significantly with variations of inclusion criteria. Thus, we modified case‐control definitions for exploratory sensitivity analyses: Inclusion criteria for the first set of sensitivity cohorts retained all specifications described above, but also required presence or absence of objective HF indicators (elevated n‐terminal prohormone of brain natriuretic peptide >400 pg/mL, loop diuretic use, or HF International Classification of Diseases, Ninth Revision code) and excluded all patients with major adverse cardiac events (defined as myocardial infarction consistent with the universal definition,26 percutaneous coronary intervention, or coronary artery bypass grafting) 1 month before sample collection.…”

Section: Methodsmentioning

confidence: 99%

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Hunter

Kelly

McGarrah

et al. 2016

JAHA

186

137

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BackgroundMetabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF).Methods and ResultsWe identified HFpEF cases, HFrEF controls, and no‐HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No‐HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long‐chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no‐HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance.ConclusionsWe identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.

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Section: Methodsmentioning

confidence: 99%

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Hunter

Kelly

McGarrah

et al. 2016

JAHA

186

137

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“…Тера-пия ивабрадином сопровождалась менее выраженным приростом ЧСС в ходе ФН, чем на фоне плацебо и была независимо связана с увеличением переноси-мости ФН (β=0,34, p=0,04) и повышением потребле-ния кислорода (β=0,32, p=0,007). В свою очередь, толерантность к ФН продемонстрировала независи-мую корреляцию с приростом E/e' во время ФН (β=0,32, p=0,007) [15]. В представленных нами случаях также продемонстрирован значимый прирост продол-жительности ВЭМ-теста на фоне терапии Коракса-ном ® , причем у пациентки 21 года толерантность к ФН при лечении ивабрадином оказалась выше, чем на фоне бисопролола.…”

Section: Discussionunclassified

Pulse Reduction in Management of Hypertrophic Cardiomyopathy (Two Clinical Cases)

Крылова¹,

Ковалевская²,

Потешкина³

et al. 2017

Russ J Cardiol

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“…This is due to the better diastolic filling times and lowering of HR during exercise (as this is when symptoms usually occur with HFpEF). This is of great interest considering the poor treatment options currently available for HFpEF [43,44]. Further research is thus required to give a better understanding and confirmation of these results.…”

Section: Ivabradine In the Treatment Of Hfmentioning

confidence: 97%

Ivabradine: Current and Future Treatment of Heart Failure

Thorup

Simonsen

Grimm

et al. 2017

Basic Clin Pharma Tox

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In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT 1 ) antagonists, b-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT 1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with b-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF.Heart failure (HF) affects people all over the world and is a major health concern. Nearly 5.8 million people in the USA are affected by HF, and one of nine US death certificates mention HF [1]. HF is more prevalent with increasing age and more men than women are affected, and the life-time risk of developing this condition is an estimated one in five.Current treatment strategies include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT 1 ) antagonists, b-adrenoceptor antagonists (BAA), aldosterone receptor antagonists, diuretics and digoxin, and only if the patient is severely affected, ivabradine or a combination of AT1 receptor antagonist and neprilysin inhibitor (ARNI) is added [2]. The principal aim of this MiniReview was to examine the literature regarding use of ivabradine and investigate the hypothesis that ivabradine may be a first choice of therapy when the resting heart rate (HR) is 70 bpm or higher.

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Effect of If-Channel Inhibition on Hemodynamic Status and Exercise Tolerance in Heart Failure With Preserved Ejection Fraction

Cited by 170 publications

References 38 publications

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Pulse Reduction in Management of Hypertrophic Cardiomyopathy (Two Clinical Cases)

Ivabradine: Current and Future Treatment of Heart Failure

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