Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction

Kuno, Toshiki; Ueyama, Hiroki; Fujisaki, Tomohiro; Briasouli, Artemis; Takagi, Hisato; Briasoulis, Αlexandros

doi:10.1016/j.amjcard.2020.01.009

Cited by 32 publications

(33 citation statements)

References 23 publications

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“…Neurohormonal activation is less prominent in HFpEF, rather than in HFm-rEF or HFrEF. Furthermore, a large proportion of trial patients had already taken RAAS blocker (20% to 86% of the study population) and beta-blocker (55% to 80% of the study population) at enrollment [71], because of their comorbidities including CAD and arrhythmia and their neurohormonal system might be stabilized. Thus, it might leave a little room for the additional benefit from another RAAS inhibitor.…”

Section: Traditional Pharmacological Strategies Of Hf: Blockade Of Thmentioning

confidence: 99%

Heart failure with preserved ejection fraction: insights from recent clinical researches

Kim

Park

2020

Korean J Intern Med

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Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for nearly half of the cases of HF and its incidence might be increasing with the aging society. Patients with HFpEF present with significant symptoms, including exercise intolerance, impaired quality of life, and have a poor prognosis as well as frequent hospitalization and increased mortality compared with HF with reduced ejection fraction. The concept of HFpEF is still evolving and may be a virtual complex rather than a real systemic disorder. Thus, beyond solely targeting cardiac abnormalities management strategies need to be extended, such as left ventricular diastolic dysfunction. In this review, we examine new diagnostic algorithms, pathophysiology, current management status, and ongoing trials based on heterogeneous pathophysiology and etiology in HFpEF.

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Section: Traditional Pharmacological Strategies Of Hf: Blockade Of Thmentioning

confidence: 99%

Heart failure with preserved ejection fraction: insights from recent clinical researches

Kim

Park

2020

Korean J Intern Med

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“…However, drugs targeting systolic dysfunction are not usually considered as effective in the management of DD, thereby necessitating the need to develop drugs that specifically target DD, especially in the setting of obesity [34,35]. In this regard, obesity-induced DD is associated with multiple abnormalities, including inappropriate activation of tissue renin-angiotensin-aldosterone system (RAAS) [24,36,37], as well as, normal or subnormal responses to ANP in the early stages of the disease or enhanced ANP responsiveness at later stages [23]. Sac/val is a first-in-class approved ARNi, that simultaneously provides Ang II type I receptor blockade and NP inhibition.…”

Section: Discussionmentioning

confidence: 99%

Sacubitril/valsartan Inhibits Obesity-associated Diastolic Dysfunction through Suppression of Ventricular-vascular Stiffness

Aroor

Mummidi

López-Alvarenga

et al. 2021

Preprint

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Objective: Both cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes and serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan monotherapy.Methods: Sixteen week-old male Zucker Obese rats (ZO; n=64) were assigned randomly to 4 different groups: Group 1: saline control (ZOC); Group 2: sacubitril/valsartan (sac/val; 68 mg•kg-1•day-1; ZOSV); Group 3: valsartan (31 mg•kg-1•day-1; ZOV) and Group 4: hydralazine, an anti-hypertensive drug (30 mg•kg-1•day-1; ZOH). Six Zucker Lean (ZL) rats that received saline only (Group 5) served as lean controls (ZLC). Drugs were administered daily for 10 weeks by oral gavage.Results: Sac/val improved echocardiographic parameters of impaired left ventricular (LV) stiffness in untreated ZO rats, without altering the amount of food consumed or body weight gained. In addition to improving DD, sac/val also decreased aortic stiffness and reversed impairment of nitric oxide-induced vascular relaxation seen in ZO rats. However, sac/val had no impact on LV hypertrophy. Notably, sac/val was more effective at ameliorating DD compared to val. Although, hydralazine was as effective as sac/val in improving these parameters, it adversely affected LV mass index. Further, proteomics revealed distinct effects of sac/val, including marked suppression of Notch-1 by both valsartan and sac/val suggesting that cardiovascular protection afforded by both share some common mechanisms; however, sac/val increased IL-4 which is increasingly been recognized for its cardiovascular protection, possibly contributing, in part, to more favorable effects of sac/val over val alone in improving obesity associated DD.Conclusions: These studies suggest that sac/val is superior to val in reversing obesity-associated DD. It is an effective drug combination to blunt progression of asymptomatic DD and vascular stiffness to HFpEF development in a preclinical model of obesity-associated prediabetes.

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“…RAAS is a central system that regulates blood vessel tension, blood volume, and cardiovascular function. RAAS also plays an indispensable part in the pathogenesis of heart failure [33]. Many studies have confirmed that AngII, ALD, and PRA, the main ingredients in RAAS, significantly increased among heart failure [34][35][36].…”

Section: Discussionmentioning

confidence: 99%

The protective effects of liguzinediol on congestive heart failure induced by myocardial infarction and its relative mechanism

Chen

Zhang

et al. 2020

Chin Med

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Background: Heart failure (HF) is one of the most common causes of cardiovascular diseases in the world. Currently, the drugs used to treat HF in the clinic may cause serious side effects. Liguzinediol, 2, 5-dimethyl-3, 6-dimethylpyrazine, is a compound synthesized after the structural modification of ligustrazine (one active ingredient of Szechwan Lovage Rhizome). We aimed to observe the effects of liguzinediol on preventing HF and explore the related mechanisms. Methods: The ligation of left anterior descending coronary artery was operated to established the myocardial infarction (MI) model in Sprague-Dawley rats. Cardiac functions were recorded by echocardiography and hemodynamics. The changes in the Renin-Angiotensin-Aldosterone System (RAAS), inflammation, and oxidative stress were detected by radioimmunoassay and Elisa kits. Western blot and real-time PCR were applied to determine the expressions of the TGF-β1/Smads pathway. Results: Firstly, liguzinediol enhanced the systolic and diastolic functions of the heart in MI rats. Liguzinediol improved ventricular remodeling by reducing myocardial cell necrosis, as well as reducing collagen deposition and myocardial fibrosis. Then, liguzinediol suppressed the activation of RAAS, inhibited the synthesis of pro-inflammation factors, and reduced oxidative stress. In the end, liguzinediol also down-regulated the expressions of the TGF-β1/Smads pathway. Conclusions: Liguzinediol could alleviate HF caused by MI in rats, and the protective effect was associated with the regulation of the TGF-β1/Smads pathway.

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Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction

Cited by 32 publications

References 23 publications

Heart failure with preserved ejection fraction: insights from recent clinical researches

Heart failure with preserved ejection fraction: insights from recent clinical researches

Sacubitril/valsartan Inhibits Obesity-associated Diastolic Dysfunction through Suppression of Ventricular-vascular Stiffness

The protective effects of liguzinediol on congestive heart failure induced by myocardial infarction and its relative mechanism

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