Effect of Genetic Polymorphism on the Clinical Outcome, Echocardiographic Parameters and Cardiac Biomarkers of Patients With Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 246
- 试验地点
- 1
- 主要终点
- RAAS genes and Clinical Outcome
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
RAAS genes and Clinical Outcome
时间窗: 6 months
Association between RAAS genetic polymorphism and clinical response, in-terms of change in LVEF among patients with heart failure
Adrenergic receptors genes and Clinical Outcome
时间窗: 6 months
Association between Adrenergic receptors genetic polymorphism and clinical response in terms of change in LVEF among patients with heart failure.
Cardiac Fibrosis genes and Clinical Outcome
时间窗: 6 months
Association between Cardiac Fibrosis genes genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Reno-protective effect and gene polymorphism
时间窗: 6 months
Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal response in-terms of change in GFR among patients with heart failure.
RAAS genes and Biomarkers
时间窗: 6 months
Association between RAAS genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Adrenergic receptors genes and Biomarkers
时间窗: 6 months
Association between Adrenergic receptors genetic polymorphism and Cardiac biomarkers among patients with heart failure.
Other Gene polymorphisms and Renal biomarkers
时间窗: 6 months
Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal biomarkers among patients with heart failure.
次要结局
- Patients' mortality(12 months)
研究者
Neven Sarhan
Lecturer of Clinical Pharmacy
Misr International University
