Neurocardiac Interactions Evaluated by Anatomic and Physiologic MRI Assessment

Mental stress ischemia occurs when a psychosocial or mental stressor triggers an imbalance
between the supply and demand for oxygen by cardiac myocytes. Epidemiological studies
indicate that mental stress ischemia is common, occurring in 20-25% of patients with coronary
artery disease (CAD) and portends a poor prognosis. The underlying mechanisms are thought to
involve stress-induced activation of the sympathetic nervous system and associated effects on
cardiovascular function. But how neurobiological and cardiovascular factors interact to
generate mental stress ischemia is unknown. Furthermore, patients with major depressive
disorder, bipolar disorder, and other stress-related psychiatric conditions have elevated
rates of cardiovascular co-morbidities, including sudden cardiac death, yet mental stress
ischemia has not been studied extensively in these psychiatric populations. The purpose of
project is to answer fundamental questions about the mechanisms underlying mental stress
ischemia in patients with coronary artery disease, mood disorders, or both, and to identify
potential biomarkers and psychosocial risk factors associated with this condition.

To achieve this goal, investigators will use cutting-edge cardiovascular and functional
neuroimaging tools to study mental stress ischemia in a carefully controlled laboratory
setting in subjects recruited from four patient populations: 1) patients who recently
sustained a myocardial infarction; 2) patients undergoing non-emergent invasive coronary
angiography (with and without known coronary artery disease); 3) patients with a diagnosis of
major depressive disorder; and 4) patients with a diagnosis of bipolar 1 or bipolar 2
disorder.

Inclusion Criteria for Cardiac Subjects:

1. Male and female subjects, ages 50 years or more

2. Able to provide informed consent. Must be fluent english speakers.

3. Known coronary artery disease (CAD) as defined by prior PCI, CABG, prior MI, prior
abnormal stress test or invasive coronary angiography (ICA)

4. Patients that are hemodynamically stable

Exclusion Criteria for Cardiac subjects:

1. Evidence of ongoing myocardial infarction or homonymic instability

2. Positive pregnancy test or unknown pregnant state at the time of enrollment for all
women of child-bearing potential

3. Known contraindications to cardiovascular CT angiography with intravenous contrast (A)
Known allergies (B) Renal dysfunction (GFR < 30ml/min) (C) Contraindications to
beta-blockers or nitroglycerin or adenosine (D) Irregular heart rate not controlled by
administration of beta-blockers

4. Patients with contraindications to MRI scans (A) Non-MR compatible device or material
implant (B) Known allergies to gadolinium containing contrast agent (C) Renal
dysfunction (GFR < 30 ml/min)

Inclusion Criteria for Psychiatric Subjects

1. Male and female subjects, ages 50 years or more

2. Must be fluent English-speakers due to the design of the mental stress tasks. Able to
provide informed consent.

3. Subjects who are stable and meet DSM-V criteria for a diagnosis of major depressive
disorder, bipolar 1 disorder, or bipolar 2 disorder, as assessed in an initial
screening interview by phone and confirmed by a structured clinical interview on the
first day of the study.

Exclusion Criteria for Psychiatric Subjects:

1. Subjects with a history of seizure disorder, stroke, Parkinson's disease, any form of
dementia, or head injury resulting in loss of consciousness will be excluded from this
study.

2. Contraindications to MRI be assessed during the screening interview and again using
the NY-Presbyterian Hospital MRI Checklist prior to scanning and will also serve as
exclusion criteria. They include claustrophobia; a history of metal implants
(including braces, orthopedic implant, cochlear implant, implanted cardiac pacemaker,
implanted cardioverter defibrillator, and ocular implant); weight over 250 pounds
(owing to the size of the MR scanner bore); and women who are currently pregnant or
breastfeeding.

3. Subjects who indicate that there is a chance that they may be pregnant will be asked
to take a pregnancy test. They will be informed of the potential for false positive
results due to diet, vitamins, and supplements, or over-the-counter medications. A
positive pregnancy test will necessitate exclusion from the study, and the results
will be disclosed to the participant.

4. Patients who are currently being treated with a beta blocker or daily (standing)
benzodiazepines will be excluded, unless, in the judgment of the prescribing
physician, the dose can be withheld on the morning of the each study session, due to
the potential for these medications to mask neurobiological and cardiovascular
responses to mental stress.

5. Investigators will also assess for additional psychiatric exclusion criteria during
the screening interview and structured clinical interview: patients with bipolar 1
disorder who are currently manic; patients with any mood disorder currently
complicated by hallucinations, delusions, or other psychotic features; patients with
active suicidal ideation; and patients meeting DSM-V criteria for a co-morbid
substance abuse disorder within the last 12 months will all be excluded. Other
psychiatric co-morbidities will be permitted.

Subjects who meet both the psychiatric and cardiac inclusion criteria will also be enrolled
in the study.