The current paradigm for heart failure in the general population does not adequately describe the spectrum of cardiac disease in patients with end-stage renal disease (ESRD). Most patients with ESRD have normal left ventricular ejection fraction and mildly impaired diastolic function, as measured by conventional echocardiographic methods. This information suggests that most patients with ESRD have low risk for heart failure. In fact, patients on dialysis have an extremely high rate of heart failure and cardiovascular mortality. We believe that modern methods of echocardiography will capture a broader range of systolic and diastolic function in this population, and thus provide better insight into cardiac function and risk. Another challenge in studying heart failure in this population is the impact tha hemodialysis-related changes in volume status have on cardiac function.
The aim of this study is to collect echocardiographic data with consistent timing relative to hemodialysis, using two novel methods. Ventricular chamber elastance (stiffness) is a novel parameter that can be calculated non-invasively using quantitative analysis of conventional echocardiographic images, and is thought to be independent of loading conditions. Speckle tracking echocardiography is a state-of-the-art imaging and analysis modality that captures incremental deformation of individual cardiac segments during systole and diastole and thus is a measure of intrinsic myocardial mechanics as opposed to global cardiac chamber measurements (such as ejection fraction) that depend on ventricular volumes. Echocardiography will be performed in an ESRD cohort that is being recruited as part of a K23 Award focused on vascular dysfunction in ESRD. We will study 200 participants on hemodialysis; patients will be studied the day after their first dialysis session of the week. Twenty of the patients will also be studied on a dialysis day, directly before and after dialysis, to test the hypothesis that novel echo parameters will vary les during dialysis than traditional, volume-dependent parameters. We will rigorously adjudicate heart failure hospitalizations distinct from hospitalizations due to medical non-compliance or missed dialysis. We will compare the performance of novel and conventional echocardiography for predicting two-year heart failure hospitalizations and overall mortality.

Public Health Relevance

Although patients with end-stage renal disease (ESRD) suffer high morbidity and mortality due to heart failure, we lack diagnostic guidelines for the use of echocardiography in these patients. We will compare the performance of traditional and novel methods for predicting heart failure hospitalizations and mortality in this high-risk population. W anticipate that our data will lead to larger studies aimed at defining and optimizing echocardiographic assessment of cardiac function in ESRD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
1R03DK104013-01A1
Application #
8969309
Study Section
Special Emphasis Panel (ZDK1-GRB-G (M2))
Program Officer
Rankin, Tracy L
Project Start
2015-08-01
Project End
2017-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
$73,843
Indirect Cost
$15,228
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Guajardo, Isabella; Ayer, Amrita; Johnson, Alexander D et al. (2018) Sex differences in vascular dysfunction and cardiovascular outcomes: The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study. Hemodial Int 22:93-102
Dubin, Ruth F (2018) Application of echocardiographic data in patients with chronic kidney disease. Curr Opin Nephrol Hypertens 27:283-288
Dubin, Ruth F; Judd, Suzanne; Scherzer, Rebecca et al. (2018) Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study. Kidney Int Rep 3:1183-1192
Dubin, Ruth F; Deo, Rajat; Bansal, Nisha et al. (2017) Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort. Clin J Am Soc Nephrol 12:60-68
Dubin, Ruth F; Guajardo, Isabella; Ayer, Amrita et al. (2016) Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease. Hypertension 68:913-20