Harnessing Investigative Genomics in Heart Failure

Abstract

which promised to resolve several thousand proteins in a failing heart. However, 2DGE was successful for the abundant and moderately expressed proteins; it struggled to identify proteins expressed at low levels. Nonetheless, first dimension separations combined with advances in mass spectrometry can provide an alternative for solving this issue. 8 In this era of genomics, new technologies and the information they generate have a wide range of potential applications in HF. Though there has not been wide spread use of genomics in everyday practice but there are many examples of how this is beginning to transform the way we look at diseases in terms of diagnosis, prognosis and treatment. The experience from oncology and other fields is helping cardiovascular medicine not only for investigating HF but the reciprocal nature of this can be clinically useful (for instance, predicting treatment responses) to drive laboratory investigations (teasing out the pathways in non-responders to treatments can be a focus of new drug discoveries). 9 As etiology of HF is far more complex than previously realized molecular assays such as gene based micro-arrays coupled with robust algorithm derived from newer bioinformatics tools will provide ample opportunities developing diagnostics and prognostics and also important therapeutics.10 State of the art technologies are currently available to study genetics of CVDs, including mutation screening; genome wide association studies (GWAS) and the recently developed NGS. Genetic mutations of ion channel genes can lead to inheritance of SCD. Thus, further refinement in technology may aid in the development of molecular assays for detecting mutations and single nucleotide polymorphisms (SNPs) which have been shown to be linked with left ventricular hypertrophy (LVH). Also, hypertension (HTN) and obesity are well-established independent contributors for LVH pathology, but they only explain half of the variance of left ventricular mass (LVM) in humans. Clinical evidence suggests that there is a genetic basis to the observed inter-individual variability in the susceptibility for the development of LVH. Given the substantial relationship between LVM and cardiovascular events, elucidating the genetic determinants of inter-individual differences in the susceptibility to LVH is of considerable public health importance because it promises to identify high-risk individuals for targeted intervention and may identify novel targets for improved prevention and treatment.Another cause of HF is the congenital heart defect (CHD), which is also a common cause of morbidity and mortality across countries representing a unique situation in both categorization and protocol management of HF. It remains unclear if the current guidelines for diagnosis and treatment of HF in adults can serve as a meaningful framework for these patients. Additionally, widely used conventional HF therapy of β-blockers and angiotensin converting enzyme (ACE) inhibitors has not demonstrated clear survival benefit and adequately powered a...