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

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.

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.