Canadian SCAD Study

Background:

Spontaneous coronary artery dissection (SCAD) is an under-diagnosed and poorly understood
condition that frequently affects young women without conventional cardiovascular (CV) risk
factors, and can result in myocardial infarction (MI), cardiac arrest, and death. This
condition has been inadequately researched, with no prospective studies evaluating management
strategies, assessing the presence and impact of predisposing and precipitating causes, or
assessing its effects on short- and long-term CV prognosis. Furthermore, many people
presenting with MI due to SCAD have been mis-diagnosed due to the limitations of the current
"gold-standard" diagnostic test (coronary angiography) for this condition, resulting in
erroneous diagnoses such as atherosclerosis, microvascular dysfunction, Takotsubo
cardiomyopathy, coronary artery spasm, or "normal" coronary arteries. As such, clinicians are
uncertain about how to diagnose, investigate and manage patients with SCAD, and similarly,
patients are uncertain about how this condition will affect their subsequent lifestyle and
long-term cardiac prognosis. Therefore, we propose a large prospective multicenter Canadian
SCAD cohort study to ascertain the natural history according to predisposing arteriopathies
and treatment strategy on long-term CV outcomes. The design of this study will secondarily
improve the diagnosis of SCAD on coronary angiography by participating clinicians, and
provide guidance on investigating predisposing conditions.

Preliminary Data:

We have enrolled 170 NA-SCAD patients in our registry at Vancouver General Hospital. We
discovered a very strong association between NA-SCAD and fibromuscular dysplasia (FMD), with
~80% of these NA-SCAD patients diagnosed with concomitant FMD. Of patients who underwent
coronary angioplasty/stenting, successful and durable results occurred in only 33%. Of
patients treated medically, those who had repeat coronary angiograms all showed angiographic
healing.

Primary Objective:

1. To evaluate the overall natural history of NA-SCAD: (a) the overall in-hospital and
long-term CV outcomes with NA-SCAD, (b) the prevalence and effects of predisposing
arteriopathies on in-hospital and long-term CV outcomes, (c) the prevalence and impact
of precipitating stressors on in-hospital and long-term CV events.

Secondary Objectives:

2. To evaluate the in-hospital and long-term outcomes of conservative therapy and
revascularization in patients with NA-SCAD.

3. To evaluate the presenting angiographic patterns of NA-SCAD.

4. To assess the incidence of spontaneous arterial healing with conservative medical
therapy alone in NA-SCAD patients undergoing repeat angiography.

Hypotheses:

1. We hypothesize that NA-SCAD patients have a high risk of long-term recurrent CV events
and FMD, as the most frequently observed predisposing condition confers lower subsequent
risk compared to other arteriopathies, such as peripartum SCAD, with regards to CV
outcomes. We hypothesize that precipitating stressors are common preceding the SCAD
event in >50% of cases.

2. We hypothesize that NA-SCAD patients have a high risk of long-term CV events, and that
patients who undergo revascularization have worse CV outcomes.

3. We hypothesize that the most common angiographic NA-SCAD pattern is diffuse stenosis.

4. We hypothesize that conservative medical therapy is associated with high rates of
spontaneous healing.

Methodology:

Prospective Canadian observational cohort study enrolling 750 consecutive patients presenting
with MI (NSTEMI or STEMI) due to NA-SCAD. Both women and men will be included. Rigorous
coronary angiographic criteria with supplementary intracoronary imaging (reviewed by core
laboratory) will be used for SCAD diagnosis. Detailed baseline demographics, targeted history
for predisposing and precipitating factors, and screening laboratory tests will be performed.
Patients will be prospectively followed for 3 years for CV events.

Significance:

This study will have significant impacts on the diagnosis, investigation, and management of
NA-SCAD. Our diagnostic algorithm will help establish guidelines on SCAD diagnosis on
coronary angiogram, which is currently elusive. Our rigorous clinical and laboratory
screening will elucidate the prevalence of predisposing arteriopathies, which will help
establish guidelines on investigation of SCAD patients. Knowledge of CV outcomes and natural
history of NA-SCAD, especially stratified to predisposing arteriopathies, will establish
prognosis, risk stratification, and management guidelines.

Knowledge Translation:

Our results will be disseminated to clinicians and patients through publications in
scientific journals, physician scientific presentations, Healthy Heart Programs, patient
educational sessions, educational website, and public media. Results from this study will
help establish national and international guidelines on the diagnosis, investigation and
management of NA-SCAD.

Inclusion Criteria:

1. Patients admitted with troponin-positive ACS (NSTEMI or STEMI)

2. Documented NA-SCAD on coronary angiogram (including diagnosis with OCT or IVUS)

Exclusion Criteria:

1. Patients with troponin-negative ACS

2. Patients with typical atherosclerotic coronary artery disease in other coronary
arterial segments with diameter stenosis ≥50%