Changes in left ventricular geometry during antihypertensive treatment

Salvetti, Massimo; Paini, Anna; Bertacchini, Fabio; Stassaldi, Deborah; Aggiusti, Carlo; Rosei, Claudia Agabiti; Bassetti, Davide; Agabiti‐Rosei, Enrico; Muiesan, María Lorenza

doi:10.1016/j.phrs.2018.06.026

Cited by 33 publications

(32 citation statements)

References 74 publications

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“…Our results suggest that dronedarone produces inhibition of the NFATc4/ERK/AKT pathway and improvement of thiol-specific oxidative stress possibly secondary to the reduction of blood pressure. The SHR animal model has been used widely as an experimental model for LVH (Quintana-Villamandos et al, 2013;Zimmer et al, 2015;Lu et al, 2016;Zwadlo and Borlak, 2016;Salvetti et al, 2018). Ten-month-old male rats show a hypertension-related compensated LVH (Brooks et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…There have been several clinical and preclinical studies that link the chronic use of antihypertensive therapy to a regression in LVH (Degirmenci et al, 2014;Salvetti et al, 2018;Jekell et al, 2018). Our group previously demonstrated that esmolol, an endovenous and selective beta-blocking agent, produces early regression in LVH and vascular remodeling after 48 h of treatment in an experimental model of arterial hypertension (Quintana-Villamandos et al, 2013, 2016a via inhibition of AKT/NF-B and NFATc4 and reduction of oxidative stress (Quintana-Villamandos et al, 2018).…”

Section: Introductionmentioning

confidence: 96%

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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

2020

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Untreated chronic hypertension causes left ventricular hypertrophy, which is related to the occurrence of atrial fibrillation. Dronedarone is an antiarrhythmic agent recently approved for atrial fibrillation. Our group previously demonstrated that dronedarone produced an early regression of left ventricular hypertrophy after 14 days of treatment in an experimental study. In this study, we analyze the possible mechanisms responsible for this effect. Ten-month-old male spontaneously hypertensive rats (SHRs, n = 16) were randomly divided into therapy groups: SHR-D, which received dronedarone, and hypertensive controls, SHR, which received saline. Ten-month-old male Wistar Kyoto rats (WKY, n = 8), which also received a saline solution, were selected as normotensive controls. After 14 days of treatment, echocardiographic measurements of the left ventricle were performed, blood samples were collected for thiol-specific oxidative stress analysis, and the left ventricles were processed for western blot analysis. Dronedarone significantly lowered the left ventricular mass index and relative wall thickness compared with the SHR control group, and no differences were observed between the SHR-D group and the WKY rats. Interestingly, the SHR-D group showed significantly decreased levels of nuclear factor of activated T cells 4 (p-NFATc4), extracellular-signal-regulated kinase 1/2 (p-ERK1/2), and protein kinase B (p-AKT) compared with the hypertensive controls without statistical differences when compared with the WKY rats. Moreover, the SHR control group showed elevated thiolated protein levels and protein thiolation index (PTI) compared with the WKY rats. After treatment with dronedarone, both parameters decreased with respect to the SHR control group until reaching similar levels to the WKY rats. Our study suggests that dronedarone produces inhibition of the NFATc4/ERK/AKT pathway and improvement of thiol-specific oxidative stress possibly secondary to the reduction of blood pressure in an animal model of ventricular hypertrophy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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

2020

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“…RWT independently predicts cardiovascular events in patients with both hypertension and diabetes [19], and after myocardial infarction [20]. Specific classes of antihypertensive agents may affect RWT and LVMI selectively [21]. These associations and interventions have not been evaluated in ESKD patients or in KT candidates.…”

Section: Discussionmentioning

confidence: 99%

Pre-Transplant Left Ventricular Geometry and Major Adverse Cardiovascular Events After Kidney Transplantation

et al. 2019

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Background Preventing major adverse cardiovascular events (MACE) after kidney transplantation motivates pre-transplant cardiac evaluation that includes two-dimensional transthoracic echocardiography (TTE). The relationship of relative wall thickness (RWT) to left ventricular mass index (LVMI) in predicting post-transplant MACE is unclear. Material/Methods In this multi-ethnic Canadian single-center cohort study, we identified 1063 adults undergoing pre-transplant TTE within 1 year pre-transplant and with minimum 6 months of post-kidney transplant follow-up for MACE, defined as a composite of coronary revascularization, myocardial infarction, stroke, and cardiac death. Left ventricular hypertrophy (LVH, >131 g/m 2 in men and >100 g/m 2 in women) and increased RWT (>0.45) were a priori used to define normal (no LVH, normal RWT), concentric remodeling (no LVH, increased RWT), eccentric hypertrophy (LVH, normal RWT), and concentric hypertrophy (LVH, increased RWT). Results There were 134 MACE over 3577 patient-years of post-transplant follow-up. Both LVH (HR 1.58, p=0.022) and high RWT (HR 1.44, p=0.041) predicted MACE in multivariate survival regression analysis independently of common pre-transplant MACE risk factors. Concentric remodeling, concentric hypertrophy, and eccentric hypertrophy all increased the risk for MACE (4.44, 5.05, and 5.55 events per 100 patient-years, respectively) versus normal echocardiography (2.71 events per 100 patient-years, all p<0.05 for difference). In Cox interactive regression analysis, LVMI and RWT were independently associated with MACE (p=0.015, p=0.025) and significantly interacted (p=0.008). Conclusions LV geometric parameters beyond LVH alone can assist post-transplant prognostication in kidney transplant candidates.

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“…7 An interesting recently published meta-analysis that included 7684 hypertensive patients showed that reduction in LV mass was significantly greater with calcium channel blockers than with beta-blockers (P < 0.02) without other significant differences between antihypertensive classes. 5 However, the authors did not investigate the influence of different diuretics on LVH regression.…”

Section: Onists the Losartan Intervention For Endpoint Reduction Inmentioning

confidence: 99%

“…It has been demonstrated that LVH represents one of the most important predictors of cardiovascular events including myocardial infarction, stroke, cardiovascular mortality, and total mortality. 3,4 Numerous studies reported LVH regression after antihypertensive therapy, 5 which shows the great importance of this parameter. However, it has always been difficult to distinguish the influence of blood pressure reduction on LVH reduction from the impact of antihypertensive medication itself.…”

mentioning

confidence: 99%

Diuretics and left ventricular hypertrophy regression: The relationship that we commonly forget

Tadić

Cuspidi

2018

J of Clinical Hypertension

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Changes in left ventricular geometry during antihypertensive treatment

Cited by 33 publications

References 74 publications

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

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

Pre-Transplant Left Ventricular Geometry and Major Adverse Cardiovascular Events After Kidney Transplantation

Diuretics and left ventricular hypertrophy regression: The relationship that we commonly forget

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