Association of Dialysate Bicarbonate with Hemodynamic Instability and Arrhythmia

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PROJECT SUMMARY/ABSTRACT This mentored career development award will provide Dr. Katherine Scovner with the resources, additional training and protected time necessary to achieve her goal of becoming an independent clinical investigator. Dr. Scovner has completed her master’s degree in Public Health and will continue to benefit from her outstanding institutional support and resources through the pursuit of didactic courses for continued formal education in biostatistics and study design through Harvard Catalyst and the Harvard Master of Medical Sciences in Clinical Investigation program, research conferences, leadership courses and training in the responsible conduct of research. These will complement her strong mentoring plan and institutional support and will build upon her prior training in human investigation. Approximately 450,000 patients in the United States are treated with life-sustaining hemodialysis (HD) for end-stage renal disease. These patients experience mortality rates of around 20% per year with nearly a quarter of their mortality attributed to sudden cardiac death (SCD). This K23 Mentored Career Development Award proposal (PA-20-206), entitled “Association of Dialysate Bicarbonate with Hemodynamic Instability and Arrhythmia,” aims to investigate the role that dialysate bicarbonate plays in intradialytic hypotension and in causing cardiac rhythms which increase the risk for SCD. The goal of this research is to understand how dialysate bicarbonate interacts with serum pH and electrolytes to impact hemodynamics and cardiac rhythms and to identify how individualized dialysate prescriptions may reduce hemodynamic instability, arrhythmia and ultimately SCD in maintenance HD patients. In Aim 1, we will use data a large dialysis organization to assess how dialysate bicarbonate is associated with intradialytic hypotension. In Aim 2, data from implanted loop recorders used in the Monitoring in Dialysis (MiD) study will be analyzed to investigate the associations of serum and dialysate bicarbonate with clinically significant arrhythmias (defined as sustained ventricular tachycardia, bradycardia, asystole and symptomatic arrhythmias), QTc prolongation and ventricular ectopy, parameters that are associated with SCD. Aim 3 proposes a randomized, controlled, double-blind, cross-over trial in 44 maintenance HD outpatients to measure how dialysate bicarbonate levels affect intradialytic QTc prolongation, ventricular ectopy, clinically significant arrhythmias and intradialytic hypotension to assess how HD prescriptions might be improved to prevent cardiac dysrhythmia and hemodynamic instability. During this award period, Dr. Scovner will employ her unsurpassed academic resources and mentorship at Brigham and Women’s Hospital to acquire the skills and expertise required to attain R01 and/or R03 funding, allowing her to continue her critically important research and to train future clinical investigators.