scholarly journals Abnormal calcium homeostasis in heart failure with preserved ejection fraction is related to both reduced contractile function and incomplete relaxation: an electromechanically detailed biophysical modeling study

2015 ◽  
Vol 6 ◽  
Author(s):  
Ismail Adeniran ◽  
David H. MacIver ◽  
Jules C. Hancox ◽  
Henggui Zhang
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Calcium Homeostasis ◽  
Contractile Function ◽  
Preserved Ejection Fraction ◽  
Biophysical Modeling ◽  
Modeling Study

scholarly journals Myocardial hypertrophy and its role in heart failure with preserved ejection fraction

2015 ◽  
Vol 119 (10) ◽  
pp. 1233-1242 ◽  
Author(s):  
Frank R. Heinzel ◽  
Felix Hohendanner ◽  
Ge Jin ◽  
Simon Sedej ◽  
Frank Edelmann
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Clinical Evidence ◽  
Mechanical Load ◽  
Contractile Function ◽  
Surrogate Marker ◽  
Left Ventricular ◽  
Structural Abnormality ◽  
Preserved Ejection Fraction

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load, and cytokines associated with arterial hypertension, chronic kidney disease, diabetes, and other comorbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood, but may include extracellular matrix changes, vascular dysfunction, as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound comorbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training, on the other hand, in clinical trials improved exercise tolerance and diastolic function, but did not reduce LVH. Thus current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF.

scholarly journals RV Contractile Function and its Coupling to Pulmonary Circulation in Heart Failure With Preserved Ejection Fraction

2017 ◽  
Vol 10 (10) ◽  
pp. 1211-1221 ◽  
Author(s):  
Marco Guazzi ◽  
Debra Dixon ◽  
Valentina Labate ◽  
Lauren Beussink-Nelson ◽  
Francesco Bandera ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Pulmonary Circulation ◽  
Contractile Function ◽  
Preserved Ejection Fraction

Clinical and treatment perspectives for heart failure with preserved ejection fraction

2016 ◽  
Author(s):  
◽  
Jessica Ann Hiemstra
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Contractile Function ◽  
Pressure Overload ◽  
The United States ◽  
Calcium Handling ◽  
Swine Model ◽  
Preserved Ejection Fraction ◽  
Novel Treatment ◽  
Hormone Status

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Heart failure with preserved ejection fraction (HFpEF) currently represents half of the ~6 million heart failure patients in the United States, and is increasing at a rate of ~1% per year. Conventional treatments commonly used for heart failure with reduced ejection fraction (HFrEF) patients have proven ineffective for HFpEF, highlighting the critical need for development of novel treatment options for this HF sub-population. Further, population studies have repeatedly found HFpEF to disproportionally effect women 2:1 over the age of sixty-five compared to men. Therefore the purpose of my dissertation was two-fold: (1) To examine novel treatment perspectives testing pharmacological interventions for treatment of heart failure with preserved ejection fraction; and (2) A clinical perspective examining mechanisms responsible for the increased prevalence of HFpEF in women. A novel miniature swine model displaying key characteristics of HFpEF was used to assess both of these aims. Aim one evaluated the efficacy of three different pharmacological treatments. The first drug cyclospsorine, aimed at inhibiting cylophilin D and preventing mitochondria permeability transition and the second drug tadalafil, aimed at inhibiting phosphodiesterase 5 and preserving cyclic guanine monophosphate (cGMP) both were ineffective in treating HFpEF. However, the third drug tested, saxagliptin; a dipeptidyl-peptidase 4 inhibitor, aimed at preserving cGMP, improved both cellular and functional cardiovascular outcomes in our mini-swine HFpEF model. This study highlighted the potential benefit of saxagliptin's for treatment of HFpEF, which currently lacks any viable therapeutic options. The purpose of the second aim was to evaluate HFpEF from a clinical prospective, in effort to uncover what mechanisms actually lead to the development of HFpEF. We hypothesized female sex hormones would protect against pressure overload-induced cardiomyocyte calcium handling and contractile abnormalities, thus preserving overall cardiomyocyte function. In contrast to our hypothesis, our results found regardless of hormone status, compromised cardiomyocyte excitation-contraction coupling (ECC) was evident by impaired calcium release and reuptake in parallel with diminished contractile function. Cardiomyocyte dysfunction was associated with distinct alterations to the protein levels and phosphorylation state of important calcium handling and contractile proteins. Our results show impaired cardiomyocyte function contributes to pressure-overload HF regardless of hormone status in a translational model with potential relevance to human HFpEF. While important advances have been made in our understanding of the haemodynamic and cellular pathophysiology HFpEF as well as contributing mechanisms associated with the disease, further research is urgently required to determine how to better target these abnormalities to reduce the substantial burden of morbidity and mortality in this form of HF, which is reaching epidemic proportions.

scholarly journals Etiology-Dependent Impairment of Diastolic Cardiomyocyte Calcium Homeostasis in Heart Failure With Preserved Ejection Fraction

2021 ◽  
Vol 77 (4) ◽  
pp. 405-419 ◽  
Author(s):  
Michael Frisk ◽  
Christopher Le ◽  
Xin Shen ◽  
Åsmund T. Røe ◽  
Yufeng Hou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Calcium Homeostasis ◽  
Preserved Ejection Fraction

Acute heart failure with preserved ejection fraction and long-term Readmisions

2008 ◽  
Vol 7 ◽  
pp. 62-63
Author(s):  
J NUNEZ ◽  
L MAINAR ◽  
G MINANA ◽  
R ROBLES ◽  
J SANCHIS ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Acute Heart Failure ◽  
Preserved Ejection Fraction

Galectin-3 in Heart Failure – Linking Fibrosis, Remodelling and Progression

2010 ◽  
Vol 6 (2) ◽  
pp. 33 ◽  
Author(s):  
Christopher R deFilippi ◽  
G Michael Felker ◽  
◽  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Stratification ◽  
Cardiac Fibrosis ◽  
The Elderly ◽  
Preserved Ejection Fraction ◽  
Heart Failure Patients ◽  
Large Populations ◽  
Galectin 3

For many with heart failure, including the elderly and those with a preserved ejection fraction, both risk stratification and treatment are challenging. For these large populations and others there is increasing recognition of the role of cardiac fibrosis in the pathophysiology of heart failure. Galectin-3 is a novel biomarker of fibrosis and cardiac remodelling that represents an intriguing link between inflammation and fibrosis. In this article we review the biology of galectin-3, recent clinical research and its application in the management of heart failure patients.

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