Reverse Remodeling and Current Medical Therapy in Heart Failure with Reduced Ejection Fraction

Maki, Hisataka; Takeda, Norihiko

doi:10.1536/ihj.20-034

Cited by 3 publications

(10 citation statements)

References 16 publications

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“…Although existing clinical drugs, device therapies and adjuvant treatments can delay the progression of heart failure, the overall prognosis of patients with heart failure is still very poor. Myocardial remodeling is a major component of heart injury and is a pathophysiological process that occurs when cardiovascular disease progresses to heart failure ( Aimo et al, 2019 ; Maki and Takeda, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Farrerol prevents Angiotensin II-induced cardiac remodeling in vivo and in vitro

Wang

et al. 2023

Front. Pharmacol.

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Cardiovascular disease has become the primary disease that threatens human health and is considered the leading cause of death. Cardiac remodeling, which is associated with cardiovascular disease, mainly manifests as cardiac hypertrophy, fibrosis, inflammation, and oxidative stress. Farrerol plays an important role in treating conditions such as inflammation, endothelial injury and tumors, and we speculated that Farrerol may also play an important role in mitigating cardiac hypertrophy and remodeling. We established a model of myocardial remodeling using Angiotensin II (Ang II) with concurrent intraperitoneal injection of Farrerol as an intervention. We used cardiac ultrasound, immunohistochemistry, Immunofluorescence, Wheat Germ Agglutinin, Dihydroethidium, Western Blot, qPCR and other methods to detect the role of Farrerol in cardiac remodeling. The results showed that Farrerol inhibited Ang II-induced cardiac hypertrophy; decreased the ratio of heart weight to tibia length in mice; reduced inflammation, fibrosis, and oxidative stress; and reduced the size of cardiomyocytes in vivo. Farrerol inhibited Ang II-induced cardiomyocyte hypertrophy, levels of oxidative stress, and the proliferation and migration of fibroblast in vitro. Our results revealed that Farrerol could inhibit Ang II-induced cardiac remodeling. Farrerol may therefore be a candidate drug for the treatment of myocardial remodeling.

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Section: Introductionmentioning

confidence: 99%

Farrerol prevents Angiotensin II-induced cardiac remodeling in vivo and in vitro

Wang

et al. 2023

Front. Pharmacol.

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“…In patients with heart failure and low or reduced ejection fraction, reverse myocardial remodeling or reverse remodeling is generally described as increased left ventricular ejection fraction (LVEF) and reduced LV diameter or volume (Choi et al, 2013;Maki and Takeda, 2020). Reverse cardiac remodeling occurs in approximately 30% of patients with nonischemic dilated cardiomyopathy (NIDCM) (Choi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…LV reverse remodeling correlates with long-term prognosis in patients hospitalized with decompensated HFrEF and LVEF <40% at hospital discharge (Abe et al, 2020;Maki and Takeda, 2020). After 4 months of follow-up, LVEF normalizes or recovers to midrange in nearly 60% of patients.…”

Section: Introductionmentioning

confidence: 99%

“…These changes are associated with significantly lower cardiac event rates and all-cause mortality and correlate with younger age, absence of atrial fibrillation, smaller LV diastolic diameter, and higher LVEF at first discharge (Abe et al, 2020). In previous clinical trials of HFrEF, patients receiving betablockers, angiotensin converting enzyme inhibitors (ACEIs), angiotensin II type 1 receptor blockers (ARBs), or ivabradine, LVEF has improved by 2-12% over the course of 5-20 months (Tardif et al, 2011;Sze and Daubert, 2018;Maki and Takeda, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…While LV reverse remodeling is critically important in HF management, the factors that predict reverse remodeling, as well as the underlying molecular processes, remain to be elucidated (Maki and Takeda, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation

et al. 2021

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Background: Reverse remodeling is a clinically relevant endpoint in heart failure with reduced ejection fraction (HFrEF). Rho-kinase (ROCK) signaling cascade activation correlates with cardiac remodeling and left ventricular (LV) systolic dysfunction in HFrEF patients. Cardiac resynchronization therapy (CRT) is effective in HFrEF, especially when there is a left bundle block, as this treatment may stimulate reverse remodeling, thereby improving quality of life and prolonging survival for patients with this severe condition. Here, we evaluate the hypothesis that ROCK activation is reduced after effective CRT in HFrEF.Methods: ROCK activation in circulating leukocytes was evaluated in 28 HFrHF patients, using Western blot (myosin light chain phosphatase subunit 1 phosphorylation, MYPT1p/t), before and three months after initiation of CRT. LV systolic function and remodeling were assessed by echocardiography.Results: Three months after CRT, LV ejection fraction increased an average of 14.5% (p < 0.001) in 13 patients (responders), while no change was observed in 15 patients (non-responders). End-systolic diameter decreased 16% (p < 0.001) in responders, with no change in non-responders. ROCK activation in PBMCs decreased 66% in responders (p < 0.05) but increased 10% in non-responders (NS). LV end-diastolic diameter was also 5.2 mm larger in non-responders vs. responders (p = 0.058). LV ejection fraction, systolic diameter, and ROCK activation levels were similar in both groups at baseline.Conclusion: In HFrEF patients, 3 months of effective CRT induced reverse myocardial remodeling, and ROCK activation was significantly decreased in circulating leukocytes. Thus, decreased ROCK activation in circulating leukocytes may reflect reverse cardiac remodeling in patients with heart failure.

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Cardiac reverse remodelling by imaging parameters with recent changes to guideline medical therapy in heart failure

Kodsi,

Makarious,

Gan

et al. 2023

ESC Heart Failure

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Recently established heart failure therapies, including sodium glucose co‐transporter 2 inhibitors, angiotensin‐neprilysin inhibitors, and cardiac resynchronization therapy, have led to both clinical and structural improvements. Reverse remodelling describes the structural and functional responses to therapy and has been shown to correlate with patients' clinical response, acting as a biomarker for treatment success. The introduction of these new therapeutic agents in addition to advances in non‐invasive cardiac imaging has led to an expansion in the evaluation and the validation of cardiac reverse remodelling. Methods including volumetric changes as well as strain and myocardial work have all been shown to be non‐invasive end‐points of reverse remodelling, correlating with clinical outcomes. Our review summarizes the current available evidence on reverse remodelling in heart failure by the non‐invasive cardiac imaging techniques, in particular transthoracic echocardiography.

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Reverse Remodeling and Current Medical Therapy in Heart Failure with Reduced Ejection Fraction

Cited by 3 publications

References 16 publications

Farrerol prevents Angiotensin II-induced cardiac remodeling in vivo and in vitro

Farrerol prevents Angiotensin II-induced cardiac remodeling in vivo and in vitro

Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation

Cardiac reverse remodelling by imaging parameters with recent changes to guideline medical therapy in heart failure

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