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Cause of Death and the Impact of Implantable Cardioverter Defibrillators Among Patients with Diabetes Mellitus and Heart Failure

  • Author / Creator
    Sharma, Abhinav
  • Introduction: Diabetes and heart failure (HF) place a large burden on healthcare systems and are associated with increased risk for death, including sudden cardiac death (SCD). However, causes of death have not been fully explored and evidence for primary prevention implantable-cardioverter-defibrillators (ICD) -which reduces the risk of SCD- among patients with co-morbid diabetes and HF have not been well described.Objective: The objectives of this thesis was to i) describe the causes of death among patients with diabetes and established atherosclerotic cardiovascular disease (ASCVD); ii) describe the causes of death among patients with diabetes and HF with reduced ejection fraction (HFrEF) and iii) describe whether primary prevention ICD placement is associated with a reduction in the risk of all-cause death and sudden death among patients with diabetes and HFrEF.Research Design and Methods: Data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study were used to describe adjudicated cause of death among patients with type 2 diabetes and ASCVD. The combined Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial and Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) studies were used to describe adjudicated cause of death among patients with diabetes and HFrEF. To evaluate the association with ICD implantation and outcomes the following data was used: i) patient-level combined-analysis from four primary prevention HFrEF ICD trials (MADIT I, MADIT II, DEFINITE, and SCD-HeFT) and ii) real-world data from the Get With The Guidelines - HF registry (GWTG-HF; 2005-2014). The primary outcome was all-cause death and the secondary outcome was SCD.Results: In TECOS (n=14,671), there were 1084 deaths adjudicated as following: 530 CV (49% of deaths, 1.2 per 100 patient-years [PY]), 338 non-CV (31% of deaths, 0.77 per 100-PY), andIII216 unknown (20% of deaths, 0.49 per 100-PY). The most common CV death was sudden death (n=145, 27% of CV death) followed by acute myocardial infarction (MI)/stroke (n=113 [MI n=48; stroke=65], 21% of CV death) and HF death (n=63, 12% of CV death). The most common non-CV death was malignancy (n=154, 46% of non-CV death). Among patients with diabetes and HFrEF in the HF-ACTION/ASIAN-HF cohort (n=2,445 [39.5%, out of 6,182]), there were 527 deaths: 322 (61%; 7.38 per 100-PY) were cardiovascular (CV), 80 (15.1%; 1.83 per 100-PY) were non-CV, and 125 (23.7%; 2.87 per 100-PY) were unknown. Among CV causes of death, sudden death was the most common adjudicated cause of death (n=115, 35.7%), followed by HF death (104, 32.3%), ‘Other’ CV death (65, 20.2%), and MI/stroke death (38, 11.8%). In the four primary prevention ICD trials, of the 3,359 patients, 996 had diabetes (29.6%). In total, 280 patients with diabetes died. While ICDs were not associated with a reduced risk of all-cause death (hazard ratio [HR] 0.88, 95% CI 0.7-1.12), they were associated with a reduced risk of SCD (adjusted subdistribution HR 0.51 95% CI 0.33-0.81; p=0.004). In the GWTG-HF registry, 663 patients with diabetes received an ICD during the HF hospitalization or were prescribed an ICD at discharge. After propensity matching, ICD use, compared to those without an ICD, was associated with a reduced risk of all-cause death (adjusted HR 0.74, 95% CI 0.65- 0.83; p< 0.0001).Conclusion: Among patients with diabetes and ASCVD or HFrEF, SCD was the most common subcategory of CV death. The ICD trials demonstrated that in patients with diabetes and HFrEF, ICD implantation was associated with a reduced risk of SCD and observational data suggested an association with a reduced risk of all-cause death. Given the burden of SCD, these findings reinforce the guideline recommendations for ICD implantation in patients with diabetes.

  • Subjects / Keywords
  • Graduation date
    Spring 2020
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/r3-7ys6-x880
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.