Renal Dysfunction and Heart Failure with Preserved Ejection Fraction

Ananthram, Manjula; Gottlieb, Stephen S.

doi:10.1016/j.hfc.2021.03.005

Cited by 15 publications

(9 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…181,182 Conventional thinking supports a cardiocentric origin for cardiorenal syndrome, driven by hemodynamic dysfunction and poor forward flow or renal venous congestion leading to renal hypoperfusion, activation of the renin-angiotensin-aldosterone system, and arginine and vasopressin hypersecretion. 183–185 However, renal dysfunction in HFpEF (including metabolic, electrolyte, and systemic impairments) contributes to a systemic proinflammatory state, diminished nitric oxide bioavailability and endothelial dysfunction, which can promote cardiomyocyte stiffening, cardiac hypertrophy, and interstitial fibrosis by crosstalk between the endothelium and cardiomyocyte compartments. 6,186…”

Section: Current Models Of the Major Hfpef Phenogroupsmentioning

confidence: 99%

Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models

Roh

Hill

Singh

et al. 2022

Circulation Research

View full text Add to dashboard Cite

Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest challenges facing cardiovascular medicine today. Despite being the most common form of heart failure worldwide, there has been limited success in developing therapeutics for this syndrome. This is largely due to our incomplete understanding of the biology driving its systemic pathophysiology and the heterogeneity of clinical phenotypes, which are increasingly being recognized as distinct HFpEF phenogroups. Development of efficacious therapeutics fundamentally relies on robust preclinical models that not only faithfully recapitulate key features of the clinical syndrome but also enable rigorous investigation of putative mechanisms of disease in the context of clinically relevant phenotypes. In this review, we propose a preclinical research strategy that is conceptually grounded in model diversification and aims to better align with our evolving understanding of the heterogeneity of clinical HFpEF. Although heterogeneity is often viewed as a major obstacle in preclinical HFpEF research, we challenge this notion and argue that embracing it may be the key to demystifying its pathobiology. Here, we first provide an overarching guideline for developing HFpEF models through a stepwise approach of comprehensive cardiac and extra-cardiac phenotyping. We then present an overview of currently available models, focused on the 3 leading phenogroups, which are primarily based on aging, cardiometabolic stress, and chronic hypertension. We discuss how well these models reflect their clinically relevant phenogroup and highlight some of the more recent mechanistic insights they are providing into the complex pathophysiology underlying HFpEF.

show abstract

Section: Current Models Of the Major Hfpef Phenogroupsmentioning

confidence: 99%

Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models

Roh

Hill

Singh

et al. 2022

Circulation Research

View full text Add to dashboard Cite

show abstract

“…Cell stresses, including oxidative stress, endoplasmic reticulum (ER) stress, AGE buildup, inflammation, and histone and chromosomal abnormalities, all contribute to the etiology of DKD ( Sakashita et al., 2021 ). Chronic renal dysfunction is related to increased hospitalization and death in HFpEF ( Ananthram and Gottlieb, 2021 ). Consequently, T2D, kidney dysfunction, and HF are suggested to form a ‘vicious circle’ ( Yamazaki et al., 2021 ).…”

Section: Pathophysiology Of Hfpef In T2dmentioning

confidence: 99%

Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes mellitus: from pathophysiology to therapeutics

Abudureyimu

Luo

Wang

et al. 2022

Journal of Molecular Cell Biology

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2D) is a devastating metabolic abnormality featured by insulin resistance, hyperglycemia, and hyperlipidemia. T2D provokes unique metabolic changes and compromises cardiovascular geometry and function. Meanwhile, T2D increases the overall risk for heart failure (HF) and acts independent of classical risk factors including coronary artery disease, hypertension, and valvular heart diseases. The incidence of HF is extremely high in patients with T2D and is manifested as heart failure with preserved, reduced, and midrange ejection fraction (HFpEF, HFrEF, and HFmrEF, respectively), all of which significantly worsen the prognosis for T2D. HFpEF is seen in approximately half of HF cases and is defined as a heterogenous syndrome with discrete phenotypes, in particularly in close association with metabolic syndrome. Nonetheless, management of HFpEF in T2D remains unclear, largely due to the poorly defined pathophysiology behind HFpEF. Here, in this review, we will summarize findings from multiple preclinical and clinical studies as well as recent clinical trials, mainly focusing on the pathophysiology, potential mechanisms, and therapies of HFpEF in T2D.

show abstract

“…The opposite is also true: increased filling pressures and reduced cardiac output increase central venous pressure, leading to reduced renal flow and consequent worsening of renal function. 16 The good outcomes of SGLT2 studies, with improvement of renal function and HF, promote the possibility of a joint treatment for these conditions for the populations in question.…”

Section: The Importance Of Controlling Comorbidities In Hfpefmentioning

confidence: 99%

The Importance of Controlling Comorbidities in HFpEF and How They Influence Disease Evolution

Hoffmann¹,

Durães²,

Erzinger³

2022

ABC: Heart Failure &Amp; Cardiomyopathy

View full text Add to dashboard Cite

Renal Dysfunction and Heart Failure with Preserved Ejection Fraction

Cited by 15 publications

References 100 publications

Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models

Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models

Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes mellitus: from pathophysiology to therapeutics

The Importance of Controlling Comorbidities in HFpEF and How They Influence Disease Evolution

Contact Info

Product

Resources

About