Renin-angiotensin system inhibitor exerts prognostic effects in HFpEF patients with low baseline chloride level

Shirotani, Shota; Jujo, Kentaro; Takada, Takuma; Abe, Takuro; Kishihara, Makoto; Watanabe, S; Endo, Natsumi; Fujita, Hiroko; Murasaki, Satoshi; Yamaguchi, Junichi

doi:10.1016/j.ijcard.2022.11.049

Cited by 3 publications

(1 citation statement)

References 32 publications

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“…We acknowledge that our considerations are in contrast with the results of major trials that failed to show any significant efficacy of RAAS inhibition in HFpEF, but they are still consistent with recent data showing improved outcomes with RAAS inhibition in a subset of patients with HFpEF with a phenotype of RAAS activation. 10…”

Section: Discussionmentioning

confidence: 99%

Atrial Septal Defect, Pulmonary Arterial Hypertension, and Diastolic Left Heart Failure: When 3 Players Come into the Game

Rutz,

Aubert,

Beghetti

et al. 2024

Circ: Heart Failure

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Section: Discussionmentioning

confidence: 99%

Atrial Septal Defect, Pulmonary Arterial Hypertension, and Diastolic Left Heart Failure: When 3 Players Come into the Game

Rutz,

Aubert,

Beghetti

et al. 2024

Circ: Heart Failure

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The association between serum chloride and mortality in ICU patients with heart failure: The impact of bicarbonate

Tan,

Liu,

Hong

2024

International Journal of Cardiology

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Metabolic Syndrome Nonalcoholic Steatohepatitis Male Mouse With Adeno‐Associated Viral Renin as a Novel Model for Heart Failure With Preserved Ejection Fraction

Shi,

Perez‐Bonilla,

Chen

et al. 2024

JAHA

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Background Heart failure with preserved ejection fraction (HFpEF) currently accounts for more than half of patients with HF, with limited approved evidence‐based therapies. HFpEF is a complex multifactorial disease associated with hypertension, obesity, diabetes, and renal dysfunction. In addition to our limited understanding of HFpEF pathophysiology, the development of new therapies is partially hindered by the existing translationally relevant preclinical HFpEF models. Methods and Results Here, we report the development of a novel 2‐hit HFpEF male mouse model through adding hypertensive stress from the activation of the renin‐angiotensin‐aldosterone system with adeno‐associated viral‐renin (AAV‐renin), to the metabolic syndrome nonalcoholic steatohepatitis (MSNASH, formerly FATZO) mouse (MSNASH+AAV‐renin). To further demonstrate model translatability, MSNASH+AAV‐renin mice were then treated with approved HFpEF therapies sacubitril/valsartan or a combination of sacubitril/valsartan and empagliflozin. We found that the MSNASH+AAV‐renin mouse model demonstrates clinically relevant features of human HFpEF, including preserved ejection fraction, cardiac hypertrophy, left atrial enlargement, diastolic dysfunction, elevated natriuretic peptides, inflammation, and low exercise capacity. We also demonstrate that treatment with approved HFpEF therapies sacubitril/valsartan and the combination of sacubitril/valsartan with empagliflozin improves the cardiac phenotypes of HFpEF in this model. Conclusions The MSNASH+AAV‐renin model faithfully represents a severe cardiometabolic HFpEF phenogroup that can be used as a new tool for HFpEF preclinical research and drug discovery.

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Renin-angiotensin system inhibitor exerts prognostic effects in HFpEF patients with low baseline chloride level

Cited by 3 publications

References 32 publications

Atrial Septal Defect, Pulmonary Arterial Hypertension, and Diastolic Left Heart Failure: When 3 Players Come into the Game

Atrial Septal Defect, Pulmonary Arterial Hypertension, and Diastolic Left Heart Failure: When 3 Players Come into the Game

The association between serum chloride and mortality in ICU patients with heart failure: The impact of bicarbonate

Metabolic Syndrome Nonalcoholic Steatohepatitis Male Mouse With Adeno‐Associated Viral Renin as a Novel Model for Heart Failure With Preserved Ejection Fraction

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