Association of Dialysate Bicarbonate with Hemodynamic Instability and Arrhythmia

项目摘要/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， 额外的培训和必要的保护时间，以实现她成为独立诊所的目标 调查员。斯科夫纳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，通过追求继续正规的教学课程 通过哈佛催化剂和哈佛医学硕士进行生物统计学和研究设计方面的教育 临床研究计划、研究会议、领导力课程和培训的科学 负责任的研究行为。这些将是对她强有力的指导计划和机构支持的补充 并将建立在她之前接受的人类调查培训的基础上。 美国约有45万名患者接受维持性血液透析(HD)治疗 治疗终末期肾病。这些患者每年的死亡率约为20%，几乎 四分之一的死亡归因于心脏性猝死(SCD)。这位K23指导了职业发展 获奖建议(PA-20-206)，题为“透析液碳酸氢盐与血流动力学不稳定和 心律失常“的目的是调查透析中碳酸氢盐在透析中低血压和高血压中的作用。 导致心律失常，从而增加患SCD的风险。这项研究的目标是了解 透析液碳酸氢盐与血清pH和电解质相互作用影响血流动力学和心律失常 并确定个性化透析液处方如何降低血液动力学不稳定性、心律失常和 维持性HD患者的终末期SCD。 在目标1中，我们将使用大型透析组织Data来评估透析液中碳酸氢盐的含量 与透析中的低血压有关。在目标2中，来自用于监测的植入式环路记录器的数据 在透析(MID)研究中，将分析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、停搏和 有症状的心律失常)、QT间期延长和室性异位，是与SCD相关的参数。 目的3建议在44名维持性HD门诊患者中进行随机、对照、双盲、交叉试验，以 临床测定透析液中碳酸氢盐水平对透析期QT间期延长、室性异位的影响 严重的心律失常和透析中的低血压，以评估如何改进HD处方以 预防心律失常和血流动力学不稳定。 在此颁奖期间，斯科夫纳博士将利用她无与伦比的学术资源和 在布里格姆妇女医院接受指导，获得达到R01和/或R01所需的技能和专业知识 R03资金，使她能够继续其至关重要的研究，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.