Association of Dialysate Bicarbonate with Hemodynamic Instability and Arrhythmia

项目总结/摘要 这个指导职业发展奖将为凯瑟琳斯科夫纳博士提供资源， 额外的培训和保护时间，以实现她成为一个独立的临床医生的目标。 调查员Scovner博士已完成公共卫生硕士学位，并将继续受益于 她杰出的机构支持和资源，通过追求教学课程，继续正式 通过哈佛Catalyst和哈佛医学硕士进行生物统计学和研究设计教育 临床研究计划中的科学，研究会议，领导力课程和培训 负责任地进行研究。这些将补充她强大的辅导计划和机构支持 并将以她之前接受的人体调查训练为基础 美国约有45万患者接受维持生命的血液透析（HD）治疗 治疗终末期肾病这些患者每年的死亡率约为20%， 四分之一的死亡归因于心脏性猝死（SCD）。K23的职业发展 获奖提案（PA-20-206），标题为“透析液Bicycline与血液动力学不稳定的相关性， 心律失常”，旨在研究透析液碳酸氢盐在透析中低血压和透析后低血压中的作用。 导致心律失常从而增加SCD的风险。这项研究的目的是了解 透析液碳酸氢盐与血清pH值和电解质相互作用，影响血液动力学和心律 并确定个性化透析液处方如何减少血液动力学不稳定性、心律失常和 最终在维持性HD患者中发生SCD。 在目标1中，我们将使用大型透析组织的数据来评估透析液碳酸氢盐 与透析中低血压相关。在目标2中，监测中使用的植入式回路记录器的数据 将分析透析（MiD）研究中的血清和透析液碳酸氢盐与 临床上显著的心律失常（定义为持续性室性心动过速、心动过缓、心搏停止和 症状性心律失常）、QTc延长和室性异位，与SCD相关的参数。 目的3提出了一项在44名维持性HD门诊患者中进行的随机、对照、双盲、交叉试验， 临床上测量透析液碳酸氢盐水平如何影响透析中QTc延长、心室异位 严重心律失常和透析中低血压，以评估如何改善HD处方， 预防心律失常和血流动力学不稳定。 在此期间，Scovner博士将利用她无与伦比的学术资源， 在布里格姆妇女医院的指导，以获得获得R 01和/或 R 03资金，使她能够继续她至关重要的研究，并培训未来的临床研究人员。

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.