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Role of Amino Acids and Genetic Disorder in Pathogenesis of Heart Failure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03590522
Recruitment Status : Unknown
Verified January 2019 by Reham I El-mahdy, Assiut University.
Recruitment status was:  Not yet recruiting
First Posted : July 18, 2018
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Reham I El-mahdy, Assiut University

Study Description
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Brief Summary:
Heart failure (HF) is a continuously growing public health problem. The study aim to provide novel insights into the role of amino acids in pathogenesis of heart failure, to obtain a better understanding of cardiac ryanodine Receptor 2 role as an essential player in excitation-contraction coupling in pathogenesis of heart failure and clarify the potential value of these markers as targets for heart failure therapy

Condition or disease Intervention/treatment
Heart Failure Genetic: Ryanodine Receptor 2 gene expression

Detailed Description:

Heart failure (HF) is a continuously growing public health problem. Presently, almost 40 million people are affected by heart failure worldwide. According to World Health Organization (WHO), cardiovascular diseases are number one cause of deaths globally . In developed countries, the prevalence of heart failure is approximately 1-2% of the adult population. In Egypt, the prevalence of HF with preserved ejection fraction represents about 34.2 % while heart failure with reduced ejection fraction represents 65.8 % of total heart failure cases .

A broad range of cardiac diseases, inherited disorders, and systematic diseases can result in heart failure. The situation is even more complex, as heart failure can have mixed etiologies. Heart failure itself represents a final common pathway in response to genetic and/or environmental influences. A clear genetic identification can positively influence patient treatment and, thereby, improve prognosis. Besides, understanding the pathogenesis of genetically induced heart failure at it molecular level may lead to the development of specific individual heart failure therapies in the future.

The human heart uses large amounts of amino acids (AAs) as regulators of both myocardium protein turnover and energy metabolism, but uses few AAs as substrates for direct energy production .The heart's reliance on AAs increases during heart failure because of high myocardium anabolic activity and cardiomyocyte energy shortage. Anabolic activity of the ventricle wall is induced by both high levels of ventricular pressure and a myocardial substrate shift from fatty acid oxidation (FAOX) to glucose oxidation (GLUOX).

Various mechanisms may potentially be operating during CHF to impair arterial AAs, including inadequate protein-energy intake, body AA overconsumption, particularly in hyper metabolic states, increased remodeling activity of the heart and lung and finally, the development of pathogenic gut flora. Understanding arterial AA levels could be useful to understand whether heart anabolic activity and remaining heart capacity of energy production are being threatened by low AA s and furthermore may allow us to correct altered AAs through diet and/or supplementation of specific free AAs.

A reduction in essential AAs in CHF subjects, shows the disease severity-related decline of arterial levels of those non-essential (and essential methionine) AAs with the greatest impact on myocardium energetics, anti-oxidative capacity and myocardial protein remodeling.

Calcium cycling protein and heart failure Ca2+-dependent signaling is highly regulated in cardiomyocytes and determines the force of cardiac muscle contraction. Ca2+ cycling refers to the release and reuptake of intracellular Ca2+ that drives muscle contraction and relaxation in failing hearts. Ca2+ cycling is profoundly altered, resulting in impaired contractility and fatal cardiac arrhythmias. The key defects in Ca2+ cycling occur at the level of the sarcoplasmic reticulum (SR), a Ca2+ storage organelle in muscle. Defects in the regulation of Ca2+ cycling proteins including the ryanodine receptor 2 (RyR2) a cardiac Ca2+ release channel macromolecular complexes and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase2a (SERCA2a) contribute to heart failure.

Phosphorylation of the cardiac ryanodine receptor (RyR2) phospho-site S2808 has hallmark of heart failure (HF) and a critical mediator of the physiological fight or flight response of the heart. In support of this hypothesis, mice unable to undergo phosphorylation at RyR2-S2808 (S2808A) were significantly protected against HF and displayed a blunted response to adrenergic stimulation.

Study Design
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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Role of Amino Acids and Genetic Disorder in Pathogenesis of Heart Failure
Estimated Study Start Date : January 17, 2019
Estimated Primary Completion Date : March 28, 2019
Estimated Study Completion Date : March 30, 2019

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
Group I:
Thirty heart failure patients
 Genetic: Ryanodine Receptor 2 gene expression
Ryanodine Receptor 2 gene expression will be measured by real time PCR. In addition, amino acids analysis will be measured in plasma by amino acid analyzer.
Group II:
Twenty healthy controls
 Genetic: Ryanodine Receptor 2 gene expression
Ryanodine Receptor 2 gene expression will be measured by real time PCR. In addition, amino acids analysis will be measured in plasma by amino acid analyzer.


Outcome Measures
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Primary Outcome Measures :
  1. Decrease cardiac ryanodine Receptor 2 gene expression and change of amino acids levels in patients with heart failure. [ Time Frame: Baseline ]
    better understanding of cardiac ryanodine Receptor 2 role as an essential player in excitation-contraction coupling in pathogenesis of heart failure and the role of amino acids in pathogenesis of heart failure


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Heart failure patients
Criteria

Inclusion Criteria:

• According to American Heart Association, patients with manifestation of heart failure (dyspnea, edema in the feet, ankles, legs or abdomen, heart palpitations) as diagnosed by clinical examination, laboratory investigations and imaging techniques.

Exclusion Criteria:

  • Diabetic patients
  • Neurological disorders
  • Cancers.
  • Obese patient
  • Smokers
  • Patient with chest infection
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03590522


Contacts
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Contact: reham elmahdy +201002714637 rehamibrahimelmahdy@gmail.com

Sponsors and Collaborators
Assiut University
More Information
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Publications:

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Responsible Party: Reham I El-mahdy, Principal Investigator, Assiut University
ClinicalTrials.gov Identifier: NCT03590522    
Other Study ID Numbers: Heart failure
First Posted: July 18, 2018    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Reham I El-mahdy, Assiut University:
pathogenesis of heart failure
cardiac ryanodine Receptor 2
Amino acids
Additional relevant MeSH terms:
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Heart Failure
Genetic Diseases, Inborn
Heart Diseases
Cardiovascular Diseases