Depression and Heart Failure Disease Progression

There are over five million Americans living with heart failure (HF), and another 670,000 new
cases being diagnosed each year. HF is a characteristically unstable condition that is the
most costly diagnosis in the Medicare population and is the most common cause for
hospitalization. The instability of HF disease is reflected in short-term fluctuations of the
HF disease biomarker, B-Type Natriuretic Peptide (BNP). Patient self-management behaviors are
important for minimizing HF disease instability. Depression is often comorbid with HF, and
elevated depressive symptoms are associated with a marked increase in adverse clinical
outcomes. For both depressed and non-depressed HF patients, worsening depressive symptoms
mark a substantially increased risk of cardiovascular hospitalization or death. Despite the
risk associated with depressive symptoms, the nature of their association with a worsening HF
disease trajectory and adverse clinical outcomes is poorly understood.

Converging evidence suggests that the association between depressive symptoms and accelerated
HF disease progression may involve multiple behavioral and pathophysiological pathways. This
study proposes an innovative, prospective bio-behavioral monitoring study of 220 HF patients
that is designed to address the issue of how depressive symptoms and their bio-behavioral
manifestations are implicated in worsening HF disease. Using home-monitoring biotechnology,
we propose to track fluctuations in HF disease severity using biweekly assessments of BNP
over a 16-week period. Symptoms of depression and HF-related health behaviors also will be
assessed biweekly via concurrent monitoring. This biweekly bio-behavioral monitoring will be
framed by comprehensive baseline and 4-month assessments of depression, HF disease severity,
and pathophysiological mechanisms that have been related to the presence of depressive
symptoms and implicated in the progression of HF disease. Clinical outcomes also will be
assessed over a subsequent average 3-year follow-up period. This study will create a unique
data structure that will allow us to use contemporary statistical methods that will serve to
elucidate causal associations between depressive symptoms, self-management health behaviors,
pathophysiological processes, and HF disease progression and clinical outcomes. The study
findings are expected to yield important advances in our understanding of why depressive
symptoms may be particularly detrimental in the presence of HF and will help to inform the
design of future clinical trials.

Inclusion Criteria:

- Men or women aged 21 years or older

- Heart Failure of at least 3-months duration

- Left ventricular Ejection Fraction (EF) ≤ 45% by left ventricular angiography, nuclear
wall motion study, or echocardiography, Or

- Preserved ejection fraction with either: Hospitalization within the previous 12 months
with management of heart failure as a major component of the care provided; or
Elevated natriuretic peptide level (NT-proBNP ≥ 360 pg/ml or BNP ≥ 100 pg/ml) within 6
months of enrollment.

- Undergoing treatment with a stable medication regimen.

Exclusion Criteria:

- Myocardial Infarction (MI), within 1 month of enrollment

- Percutaneous Transluminal Coronary Angioplasty(PTCA), Coronary Artery Bypass Graft
(CABG) within 3 month of enrollment

- HF due to correctable cause or condition such as uncorrected primary valvular disease

- Alcohol or drug abuse within 12 months

- Illness such as malignancies that are associated with a life-expectancy of < 12 months

- Current pregnancy

- Inability to provide informed consent