Clinical Evaluation of the CADence Device in Detection of Coronary Artery Diseases
Clinical Evaluation of the CADence Device in Detection of Coronary Artery Diseases
This is a multi-center, prospective, non-randomized, double-blinded trial to evaluate the
 sensitivity and specificity of the CADence device in detecting the existence of clinically
 significant coronary artery disease as determined by either standard or CT angiography.
This is a multi-center, prospective, non-randomized, double-blinded, trial to evaluate the
 performance of the CADence in detecting the existence of at least one major coronary artery
 with clinically significant stenosis in a subject is defined as the presence of at least one
 lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid
 Left anterior Descending, proximal Left Circumflex, mid Left Circumflex , proximal Right
 Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1,
 Obtuse Margin 2, and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis
 in the Left Main coronary arteries.

 Consented subjects will be evaluated with the CADence device and then undergo nuclear stress
 testing followed by either computed tomography or standard coronary angiography. The maximum
 expected timeframe between CADence and computed tomography Angiography or standard
 angiography is 6 weeks.

 This is a double-blinded study. All physicians and subjects will be masked to the diagnostic
 results of the CADence until completion of CADence, nuclear stress, computed tomography or
 standard coronary angiogram testing for the subjects. Patient care will not be based on the
 CADence results.

 Study participation will conclude after the computed tomography angiography or standard
 coronary angiography procedure.

 computed tomograph or standard coronary angiography are considered acceptable clinical
 reference standards in this study and are gold standards for detection of coronary artery
 disease. The experimental unit of this study is the subject. Existence of clinically
 significant coronary artery disease in a subject is defined as the presence of at least one
 lesion with ≥ 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid
 Left anterior Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right
 Coronary Artery, mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1,
 Obtuse Margin 2, and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis
 in the Left Main coronary arteries.

 The study required sample size is 826 but may enroll up to 1,300 subjects. The sensitivity
 and specificity of the CADence are expected to be 80% and 73% respectively. Observed
 sensitivity and specificity will be compared to nuclear stress literature-based performance
 standards of 83% and 80% respectively using one sample non-inferiority binomial tests with a
 non-inferiority margin of 15 percentage points. Sample size requirements are 109 subjects
 with the presence of at least one lesion with ≥ ≥ 70% diameter stenosis anywhere in the
 proximal Left anterior Descending, mid Left anterior Descending, proximal Left Circumflex,
 mid Left Circumflex, proximal Right Coronary Artery, mid Right Coronary Artery, distal Right
 Coronary Artery and Obtuse Margin 1, Obtuse Margin 2, and Ramus Intermedius if segment
 diameter >2.5 mm or ≥50% diameter stenosis in the Left MAIN coronary arteries. to test the
 sensitivity hypothesis and 268 subjects without the presence of at least one lesion with ≥
 70% diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior
 Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery,
 mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2,
 and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis in the Left MAIN
 coronary arteries. to test the specificity hypothesis. It was assumed that 15 percent of
 enrolled subjects would be found to have the presence of at least one lesion with ≥ 70%
 diameter stenosis anywhere in the proximal Left anterior Descending, mid Left anterior
 Descending, proximal Left Circumflex, mid Left Circumflex, proximal Right Coronary Artery,
 mid Right Coronary Artery, distal Right Coronary Artery and Obtuse Margin 1, Obtuse Margin 2,
 and Ramus Intermedius if segment diameter >2.5 mm or ≥50% diameter stenosis in the Left Main
 coronary arteries. In order to accrue 109 subjects with significant Coronary Artery Disease
 as defined in the protocol, 826 subjects must be enrolled. Sample sizes provide 85% power
 with alpha of 0.05 for each statistical test.
Subjects clinically indicated for nuclear stress test and who satisfy all the inclusion and
 exclusion criteria are eligible for participation.

 Inclusion criteria:

 Age 22 years or older Willing and able to give informed consent Clinical indication for
 nuclear stress test evaluation Chest pain syndrome

 Two or more coronary artery disease risk factors as defined by:

 1. Dyslipidemia: low-density lipoprotein (LDL) >130 mm/dL or high-density lipoprotein
 (HDL) <35 mm/dL or on treatment for dyslipidemia

 2. Hypertension: blood pressure >140 millimeter of mercury (mmHg) systolic, >90 mmHg
 diastolic or on blood pressure altering treatment

 3. Obesity: body mass index (BMI)>28

 4. Current cigarette smoking

 5. Diabetes: Type 1 or 2

 6. Family history: coronary disease in a first or second degree relative

 Exclusion criteria:

 Body Mass Index (BMI)<18.5 or BMI >40

 Known coronary disease as defined as:

 Prior bypass surgery or coronary stenting Q-wave infarction on a past electrocardiogram
 (EKG) (>0.01 sec Q-wave duration in two adjacent leads)

 Presence of pacemaker/defibrillator Presence of artificial valve Presence of obvious
 cyanotic or pre-diagnosed congenital heart defect and coarctation of the aorta Presence
 murmurs including valve lesions, ventricular septal defects, and arteriovenous (AV)
 fistulae.

 Presence of moderate or severe valve disease as defined by >1/6 heart murmur on physical
 diagnosis Left Ventricular Assist Device (LVAD) Presence of scars on the site thorax areas
 Participation in trial within 30 days prior to collecting CADence data except participation
 in registry studies Asthma with wheezing Inability to lie flat in the supine position Acute
 coronary syndrome with elevated cardiac biomarkers (troponin (TP)>3x upper limit of normal
 (ULN) or creatine kinase MB (CKMB) >3x ULN) Heart Transplant Current cocaine use (within
 the past 24 hours, as reported by subject) Chronic Obstructive Pulmonary Disease (COPD)
 Contraindication to computed tomography (CT) angiography

 -  Renal failure with glomerular filtration rate (GFR)<50 (angio risk)

 -  Iodinated contrast allergy

 -  Elevated heart rate which cannot be controlled sufficiently to achieve a good computed
 tomography angiogram

 -  Body weight >350lbs.

 -  Sinus rhythm rate greater than 100 beats per minute at screening.

 -  Atrial fibrillation with average heart rate of greater than 70 beats per minute on
 resting screening electrocardiogram (ECG).