Rationale and design for the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study

Abstract

BackgroundSudden cardiac death occurs commonly in the end-stage renal disease population receiving dialysis, with 25% dying of sudden cardiac death over 5 years. Despite this high risk, surprisingly few prospective studies have studied clinical- and dialysis-related risk factors for sudden cardiac death and arrhythmic precursors of sudden cardiac death in end-stage renal disease.Methods/DesignWe present a brief summary of the risk factors for arrhythmias and sudden cardiac death in persons with end-stage renal disease as the rationale for the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, a prospective cohort study of patients recently initiated on chronic hemodialysis, with the overall goal to understand arrhythmic and sudden cardiac death risk. Participants were screened for eligibility and excluded if they already had a pacemaker or an automatic implantable cardioverter defibrillator. We describe the study aims, design, and data collection of 574 incident hemodialysis participants from the Baltimore region in Maryland, U.S.A.. Participants were recruited from 27 hemodialysis units and underwent detailed clinical, dialysis and cardiovascular evaluation at baseline and follow-up. Cardiovascular phenotyping was conducted on nondialysis days with signal averaged electrocardiogram, echocardiogram, pulse wave velocity, ankle, brachial index, and cardiac computed tomography and angiography conducted at baseline. Participants were followed annually with study visits including electrocardiogram, pulse wave velocity, and ankle brachial index up to 4 years. A biorepository of serum, plasma, DNA, RNA, and nails were collected to study genetic and serologic factors associated with disease.DiscussionStudies of modifiable risk factors for sudden cardiac death will help set the stage for clinical trials to test therapies to prevent sudden cardiac death in this high-risk population.

Electrocardiographic predictors of mortality and sudden cardiac death in patients with end stage renal disease on hemodialysis

“…It remains unclear if ECG abnormalities in ESRD are mechanistically related to SCD, or if they are simply electrophysiological markers of more advanced cardiovascular disease such as severe fibrosis or LVH. Large, prospective studies with carefully adjudicated SCD [41] are needed to determine associations between ECG parameters and SCD, and to determine the optimal time to measure these parameters (pre-dialysis, during dialysis, or after dialysis) as a hemodialysis session itself can have significant effects on the ECG; fluid loss and resulting increases in total body impedance [31,42] usually result in increased amplitude of the entire P-QRS-T complex [14,30]. …”

Electrophysiologic Substrate and Risk of Mortality in Incident Hemodialysis

“…Details of the study protocol have been described previously. 11 Briefly, ESRD patients were eligible for enrollment if they (1) were 18 years of age or older, (2) had started hemodialysis within 6 months of enrollment, and (3) were English speakers. Exclusion criteria were (1) diagnosed active cancer other than nonmelanoma skin cancer, (2) implanted pacemaker or implantable cardioverter defibrillator, and (3) pregnancy or nursing.…”

“…Detailed medical history, family history, and dialysis laboratories were collected as previously described. 11 Average levels of serum albumin, creatinine, calcium, magnesium, and potassium were calculated using values from routine dialysis laboratory blood work during 90 days before the study clinic visit. Intradialytic weight change was calculated as the difference between postdialysis weight and predialysis weight and averaged using values during 90 days before the study visit.…”

“…10 The goal of this study is to determine and compare the association of spatial QRS-T angle and late potentials on SAECG with mortality in a large prospective cohort of patients on incident hemodialysis. 11 Evaluations of electrophysiologic markers specifically in an incident rather than prevalent dialysis population may yield more promising targets for interventions to decrease risk of mortality, which is highest in the first few months on dialysis.…”

Frailty and Cognitive Function in Incident Hemodialysis Patients

“…This study (ancillary to the Predictors of Arrhythmic and Cardiovascular Risk in ESRD [PACE] trial; R01DK072367) (15,16) was an in-person assessment of frailty and other factors in patients who had initiated hemodialysis at 27 free-standing dialysis centers in Baltimore, Maryland, and six surrounding counties (17). Although all participants were hemodialysis initiates (within 6 months), participants were not necessarily enrolled on their first day of hemodialysis; 95% were enrolled within the first month of dialysis.…”