Effect of Genetic Polymorphism on the Clinical Outcome of Patients With Heart Failure (SNPs)

Effect of Genetic Polymorphism on the Clinical Outcome, Echocardiographic Parameters and Cardiac Biomarkers of Patients With Heart Failure

Heart failure (HF) is one the most common cause of hospitalization and represents the end stage of a variety of heart conditions; it is associated with significant morbidity and mortality.The pathophysiology of HF is centered on increased activity in the adrenergic and renin-angiotensin-aldosterone systems (RAAS), which leads to vasoconstriction and fluid restriction with further deleterious effect on cardiac function. Β-blockers, angiotensin converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) and aldosterone antagonists reduce activity in these pathways and have shown prognostic benefit, thus are the foundation of HF therapy.There is a growing body of evidence that variation in proteins within the sympathetic axis and RAAS influence drug response thus increasingly pharmacogenetics of HF research is being sought as a way to optimize HF treatment and advance new drug development in this area.

Study Overview

• Status: Completed
• Conditions: Heart Failure

Detailed Description

In the past decade there has been considerable progress in cardiovascular pharmacogenetics and pharmacogenomics. Although drug response variation in Heart Failure is likely multifactorial, pharmacogenetic variation may partially account for therapeutic failure contributing to the remaining high mortality in HF. Identifying novel gene variants affecting treatment response may reveal unrecognized pathways and new potential therapeutic targets. Few studies to date have attempted to assess the extent to which variation in drug response was exclusively due to genetic factors and therefore expounding the likely clinical benefit of using pharmacogenetics to guide HF therapy. One of the prerequisites to bridging this gap is to consider likely trial designs and criteria that will lead to a consensus upon using pharmacogenetics-based variants to guide therapy in clinical practice.

Another area gaining momentum is tailoring medication in response to biomarker levels as there is considerable evidence for the relationship between remodeling and fibrosis markers levels and worse prognosis in those with HF. Moreover,investigation into the proteomics of HF may also reveal variation that can be used to guide HF therapy hand-in-hand with biomarkers and pharmacogenomics, which would facilitate bridging the gap of genotype and phenotype. Disparity between genotype and phenotype may also account for the inconsistent results with current SNPs, further appreciation of this relationship would be a significant step forward.

• Study Type: Observational
• Enrollment (Actual): 246

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • National Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Heart Failure Patients with reduced Ejection Fraction

Description

Inclusion Criteria:

• Heart failure patients NYHA class II to IV.
• Left ventricular ejection fraction (LVEF) < 45%
• Written informed consent of the subject to participate in the study.
• Newly diagnosed patients who will be treated with BBs and ACEIs/or ARBs.
• Patients who are candidate for add-on treatment with Spironolactone / Eplerenone.
• Age of 18 years to 80 years.

Exclusion Criteria:

• Contraindication to SGLT2i.
• Contraindication to Spironolactone / Eplerenone.
• Patients who received previous treatment with Spironolactone / Eplerenone.
• Sig CAD, CABG, PCI, or valve surgery within 3 months.
• Mild-to-severe valvular stenosis or severe (grade III/IV) valvular regurgitation
• Pregnant or nursing women.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cohort B; Heart Failure patients who are candidate for add-on treatment with Spironolactone / Eplerenone.
Cohort A; Newly diagnosed Heart Failure patients who will be treated with beta blockers (BB) and Angiotensin converting enzyme inhibitors (ACEIs)/or Angiotensin receptor blockers (ARBs) /or Angiotensin receptor neprilysin inhibitors (ARNI) and sodium glucose transporter 2 inhibitor (SGLT2i) for the first time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RAAS genes and Clinical Outcome	Association between RAAS genetic polymorphism and clinical response, in-terms of change in LVEF among patients with heart failure	6 months
Adrenergic receptors genes and Clinical Outcome	Association between Adrenergic receptors genetic polymorphism and clinical response in terms of change in LVEF among patients with heart failure.	6 months
Cardiac Fibrosis genes and Clinical Outcome	Association between Cardiac Fibrosis genes genetic polymorphism and clinical response in terms of change in LVEF among patients with heart failure.	6 months
Reno-protective effect and gene polymorphism	Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal response in-terms of change in GFR among patients with heart failure.	6 months
RAAS genes and Biomarkers	Association between RAAS genetic polymorphism and Cardiac biomarkers among patients with heart failure.	6 months
Adrenergic receptors genes and Biomarkers	Association between Adrenergic receptors genetic polymorphism and Cardiac biomarkers among patients with heart failure.	6 months
Cardiac Fibrosis genes and Clinical Outcome	Association between Cardiac Fibrosis genes genetic polymorphism and Cardiac biomarkers among patients with heart failure.	6 months
Other Gene polymorphisms and Renal biomarkers	Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal biomarkers among patients with heart failure.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients' mortality	Potential interaction between these target genes polymorphism and the 1 Year patients' mortality.	12 months

Collaborators and Investigators

• Sponsor: Ain Shams University
• Collaborators: Misr International University; National Heart Institute
• Investigators: Study Director: Mona F. Schaalan, PhD, Misr International University; Principal Investigator: Neven M. Sarhan, PhD, Misr International University; Study Chair: Bassem Zarif, MD, National Heart Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Actual): April 10, 2024
• Study Completion (Actual): June 14, 2024

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (Actual): April 21, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Heart Failure; Genetic Polymorphism; Remodeling; RAAS; Cardiac Fibrosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: SGLT2i-MRAs-ARNI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No