Date of Award

January 2021

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Tariq Ahmad

Second Advisor

Eric J. Velazquez

Abstract

Abstract

BackgroundWith the recent data sharing of the Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) randomized control trial (RCT) through the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC), the opportunity has risen to investigate various risk factors for adverse events in patients with heart failure (HF), specifically heart failure with reduced ejection fraction (HFrEF). In this thesis we investigate the following: (1) the impact of depression on GDMT and outcomes in patients with HFrEF, (2) the impact of atrial fibrillation on patients with HFrEF, (3) and the effect of different BMI categories on patients with HFrEF. The purpose of this thesis was to investigate these risk factors and prove the value of post-hoc analysis of RCTs.

MethodsThe following methodology was used. (1) Patients were split into cohorts based on the presence of clinical depression and their outcomes, biomarkers, and quality of life outcomes were compared. (2) Patients were split into cohorts based on the presence of atrial fibrillation (AF) and their outcomes, GDMT, biomarkers, and quality of life outcomes were compared. (3) Patients were split into cohorts based on BMI categories and the clinical outcomes of patients were explored.

ResultsResults were as follows: (1) Patients with depression were found to have significantly higher rates of hospitalization despite similar GDMT. (2) Patients with atrial fibrillation were more likely to have hospitalizations specifically for heart failure and had worsening NT-proBNP over the course of the trial. (3) Patients with a BMI >35 had significantly higher rates of hospitalizations than other BMI categories after adjustment for confounding variables.

ConclusionsConclusions are as follows: (1) Patients with depression have worse outcomes and thereby there needs to be a concomitant focus on mental health in parallel to achievement of HF GDMT. (2) There is a pathological relationship between HFrEF and AF despite optimal HF medical treatment. (3) There is no evidence of the “obesity paradox” in HFrEF patients within the GUIDE IT trial in contrast to other studies.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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