title: Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic concept.
abstract: Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate.
authors: Cardiology Division, University of Vermont College of Medicine, Burlington, Vermont.
authors: Franziska J
authors: FJ
authors: Klein
authors: Cardiology Division, University of Vermont College of Medicine, Burlington, Vermont.
authors: Stephen
authors: S
authors: Bell
authors: Cardiology Division, University of Vermont College of Medicine, Burlington, Vermont.
authors: K Elisabeth
authors: KE
authors: Runte
authors: Cardiology Division, University of Vermont College of Medicine, Burlington, Vermont.
authors: Robert
authors: R
authors: Lobel
authors: Biostatistics Unit, University of Vermont College of Medicine, Burlington, Vermont; and.
authors: Takamuru
authors: T
authors: Ashikaga
authors: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
authors: Lilach O
authors: LO
authors: Lerman
authors: Cardiology Division, University of Vermont College of Medicine, Burlington, Vermont.
authors: Martin M
authors: MM
authors: LeWinter
authors: Cardiology Division, University of Vermont College of Medicine, Burlington, Vermont; markus.meyer@uvmhealth.org.
authors: Markus
authors: M
authors: Meyer
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004548:Elasticity; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure; D006339:Heart Rate / Q000502:physiology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology*; D008026:Ligation; D009206:Myocardium / Q000473:pathology*; D012077:Renal Artery / Q000601:surgery; D013318:Stroke Volume; D013552:Swine; D013556:Swine, Miniature; D020257:Ventricular Remodeling
keywords: heart rate; hypertrophy; pacemaker; remodeling