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The Impact of Genetic Polymorphism on the Echocardiographic Parameters and Cardiac Fibrosis Markers in Response to Empagliflozin Treatment Among Patients With Heart Failure

Active, not recruiting
Conditions
Heart Failure
Registration Number
NCT06503601
Lead Sponsor
Ain Shams University
Brief Summary

It is important to assess the implications of genetic variants of the TGF-β1 gene in patients with HFrEF and the association of this polymorphism with treatment response to SGLT2I. Therefore, by correlating the pharmacogenetics hand in hand with the mechanistic markers involved in the pathogenesis of HF, this can aid in the development of individualized, therapeutic strategies and improve the patient's drug response.

Detailed Description

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. According to the American heart association (AHA) over 19.1 million deaths worldwide in 2020 were attributed to CVD. Heart failure (HF) is considered one of the most frequent causes of hospitalization and the final stage of many heart disorders. It is associated with high rates of morbidity and mortality. Heart failure (HF) affects more than 5.8 million people in the USA and over 23 million people worldwide, making it a serious public health issue. According to the 2022 guidelines of American heart association (AHA) a variety of non-pharmacologic and pharmacologic are available to treat heart failure (HF) to prevent or reverse its symptoms. Nonpharmacologic treatments may involve dietary sodium and fluid restriction, proper physical activity, and attention to weight gain depending on the illness\'s severity. Pharmacologic treatments include the use of diuretics, vasodilators, inotropic agents, anticoagulants, beta blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), digoxin, nitrates, B-type natriuretic peptides (BNPs), I(f) inhibitors, angiotensin receptor-neprilysin inhibitors (ARNIs), soluble guanylate cyclase stimulators, sodium-glucose cotransporter-2 inhibitors (SGLT2Is), and mineralocorticoid receptor antagonists (MRAs). Recent study has shown that SGLT2I not only lowers blood sugar levels but also protects the kidney and heart, which can dramatically lower cardiovascular events, stall the advancement of renal failure, significantly raise patient quality of life, and lower medical costs for families and society. A study showed that Empagliflozin has cardio-renal protective effects as it reduced inflammatory and fibrotic markers, such as NF-κB, TGF-β1, and improved fibrosis. However, it was found that the variation in treatment response with SGLT2I may be due to the genetic polymorphism of TGF-β1 since this polymorphism may influence its expression. Therefore, it is important to assess the implications of genetic variants of the TGF-β1 gene in patients with HFrEF and the association of this polymorphism with treatment response to SGLT2I. Therefore, by correlating the pharmacogenetics hand in hand with the mechanistic markers involved in the pathogenesis of HF, this can aid in the development of individualized, therapeutic strategies and improve the patient's drug response.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
92
Inclusion Criteria
  • Heart failure patients NYHA class II to IV.
  • Treatment with beta blockers, MRAs, ACEIs in addition to empagliflozin.
  • Age of 18 years to 80 years.
  • Written informed consent of the subject to participate in the study.
Exclusion Criteria
  • Contraindication to empagliflozin: pregnancy, hypersensitivity, and severe renal impairment.
  • CABG or valve surgery within 3 months.
  • Mild-to-severe valvular stenosis or severe (grade III/IV) valvular regurgitation
  • Pregnant or nursing women.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Genetic polymorphism and echocardiographic parameters3-6 months

To detect association between a TGFβ1 gene polymorphism variants and echocardiographic outcome of patients with HFrEF in response to empagliflozin.

Secondary Outcome Measures
NameTimeMethod
Cardiac fibrosis biochemical markers3-6 months

• To detect association between serum TGFβ1, MMP-2 and TNF-α levels (cardiac fibrosis biochemical marker) and echocardiographic parameters of patients with HFrEF in response to empagliflozin

Trial Locations

Locations (1)

Ain shams university

🇪🇬

Cairo, Egypt

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