Dronedarone produces early regression of myocardial remodelling in structural heart disease

Abstract

Background and aimsLeft ventricular hypertrophy (LVH) in hypertension is associated with a greater risk of sustained supraventricular/atrial arrhythmias. Dronedarone is an antiarrhythmic agent that was recently approved for the treatment of atrial fibrillation. However, its effect on early regression of LVH has not been reported. We tested the hypothesis that short-term administration of dronedarone induces early regression of LVH in spontaneously hypertensive rats (SHRs).MethodsTen-month-old male SHRs were randomly assigned to an intervention group (SHR-D), where animals received dronedarone treatment (100 mg/kg) for a period of 14 days, or to a control group (SHR) where rats were given vehicle. A third group with normotensive control rats (WKY) was also added. At the end of the treatment with dronedarone we studied the cardiac anatomy and function in all the rats using transthoracic echocardiogram, cardiac metabolism using the PET/CT study (2-deoxy-2[18F]fluoro-D-glucose) and cardiac structure by histological analysis of myocyte size and collagen content.ResultsThe hypertensive vehicle treated SHR rats developed the classic cardiac pattern of hypertensive cardiomyopathy as expected for the experimental model, with increases in left ventricular wall thickness, a metabolic shift towards an increase in glucose use and increases in myocyte and collagen content. However, the SHR-D rats showed statistically significant lower values in comparison to SHR group for septal wall thickness, posterior wall thickness, ventricular mass, glucose myocardial uptake, size of left ventricular cardiomyocytes and collagen content. All these values obtained in SHR-D rats were similar to the values measured in the normotensive WKY control group.ConclusionThe results suggest by three alternative and complementary ways (analysis of anatomy and cardiac function, metabolism and histological structure) that dronedarone has the potential to reverse the LVH induced by arterial hypertension in the SHR model of compensated ventricular hypertrophy.

The protective effect of dronedarone on the structure and mechanical properties of the aorta in hypertensive rats by decreasing the concentration of symmetric dimethylarginine (SDMA)

“…Our results are consistent with other studies that describe a decrease in blood pressure and heart rate associated with the administration of this drug [11]. Our group has previously demonstrated that dronedarone produces a regression of LVH in hypertensive rats after two weeks of treatment [14]. However, the impact of this drug on the remodeling of the elastic arteries (e.g.…”

“…Dronedarone produces a reduction in the risk of stroke [10] and acute coronary syndrome [11] that may be related to reduced heart rate and arterial blood pressure [12,13]. Our group has previously demonstrated that dronedarone produces regression of left ventricular hypertrophy (LVH) in hypertensive rats after two weeks of treatment (resulting in reduced left ventricular mass, changes in the cardiomyocytes and collagen of the left ventricle, and an improvement in cardiac metabolism) [14]. However, the impact of this drug on vascular remodeling has not yet been studied.…”

Impact of a Multichannel Blocker in Attenuating Intramyocardial Artery Remodeling in Hypertensive Rats through Increased Nitric Oxide Bioavailability

“…Functional and structural alterations of the coronary circulation have been well documented in left ventricular hypertrophy [1]. In a preclinical study, we show that short-term treatment (two weeks) with dronedarone has the potential to reverse the left ventricular hypertrophy induced by arterial hypertension in the SHR model of compensated ventricular hypertrophy [10]. In this context, we found it of interest to assess the impact of dronedarone in attenuating intramyocardial artery remodeling.…”

“…Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation [7, 8]; however it is avoided in patients with unstable chronic heart failure [9]. In a preclinical study, we previously analyzed early regression of left ventricular hypertrophy following short-term use of antiarrhythmic agents and we found that dronedarone produces regression of left ventricular hypertrophy after two weeks of treatment [10]. However, its effect on intramyocardial artery remodeling has not been analyzed to date.…”

Inhibition of the NFATc4/ERK/AKT Pathway and Improvement of Thiol-Specific Oxidative Stress by Dronedarone Possibly Secondary to the Reduction of Blood Pressure in an Animal Model of Ventricular Hypertrophy

“…However, it may worsen the clinical status of hemodynamically unstable patients or those with moderate to severe ventricular dysfunction ( Kober et al, 2008 ). Our group previously demonstrated that dronedarone produced regression of LVH after only 14 days of treatment in a preclinical study ( Quintana-Villamandos et al, 2017 ). In the present study, we aim to analyze the possible mechanisms responsible for this effect.…”