Title : Predictive value of metabolomic profiling in diagnosis & prognosis of rheumatic valvular heart disease
Abstract:
Introduction: Diseases of the heart valves constitute a major cause of cardiovascular morbidity and mortality worldwide with an enormous burden on healthcare resources(1). The dominant form of heart disease in the developing nations is Rheumatic heart disease (RHD)(2). The prevalence of RHD has greatly decreased in developed nations; however, increasing life expectancy and atherosclerotic risk factors have increased the risk of acquiring age-related degenerative valvular heart disease (VHD). Although the patterns of valve disease differ among these nations, the burden of valvular heart disease continues unabated across the globe.
Cardiac Metabolism: Metabolism is the transformation of a substrate to product. The Human heart, for example pumps 7200 liters of blood each day against an average mean arterial pressure of 100mmHg. In the same time period, the human heart consumes > 20 grams of carbohydrates (glucose and lactate) and >30 grams of fat (fatty acids and triacylglycerols), as energy providing substrates, whereas it uses 35 liters of oxygen to support the oxidative phosphorylation of ADP to ATP. In humans, the heart is responsible for around 10% of whole-body fuel consumption. The relative contribution of fat and carbohydrate to energy provision for the heart is 70% and 30% respectively, but it varies with physiological state (11).
Materials And Methods: 2D Echocardiography was done as per the 2004 WHO guidelines for 2D echo for RHD, in Department of Cardiology (as a part of clinical diagnosis and evaluation). During surgery, valvular heart tissues were collected and stored in -80 degree Celsius. All the samples were subjected to Mass spectrometric analysis for metabolomic profiling at Bio-analytics Facility, Centralized Core Research Facility (CCRF). Sampling was done for healthy controls after ruling out any symptoms of cardiac illness by a questionnaire, Sampling of the diseased were done after confirming the diagnosis on 2D ECHO according to the 2004 WHO criteria for RHD.
Results: The study population was 36 in total (18 healthy controls and 18 patients). The mean age was 28.3 years (SD 5.3) in healthy controls and the mean age in study group was years (SD16.5). Gender - The study population consisted of 9 males and 9 females. Histopathology Of the Valves - Fibrosis was present in 16 valve specimens, Dystrophic Calcification was present in 8 valve specimens, Neovascularisation was found in 7 specimens, Aschoff bodies were noted in 1 specimen.
Discussion: Rheumatic heart disease (RHD) is an immune mediated inflammatory disease of the cardiac valves. The disease is caused by the aberrant immune reaction triggered by the group A beta-haemolytic streptococcus at the cardiac valve surface1. Worldwide, estimated cases were 33.4 million and India is reported to contribute 40-50% of the global case burden (3). Although, genome-based studies have revealed various genes associated with RHD but the disease pathogenesis is still not well understood.
Conclusion: Rheumatic heart disease is an immune mediated inflammatory disease of heart valves and tissues. The lack of specific prognostic and diagnostic biomarkers is the bottleneck in the diagnosis and treatment of rheumatic heart disease. Omics approach such as metabolomics can give valuable information regarding the selection of potential biomarkers for the planning of the type and timing of intervention in economical and accessible manner. The current study attempted to use metabolomics to find the potential biomarkers in blood in rheumatic heart disease. The study further attempted to use valve tissue metabolomics for biomolecular snapshot of the prognosis of the disease. The study found metabolic pathway derangement related to inflammation, lipid metabolism, amino acid metabolism and oxidative stress dysregulation. Findings of the current study could lead to the development of pharmacological intervention for the dysregulated pathways.
