The study included 1,011 consecutive male and female patients who were referred for an exercise nuclear stress test at New York Methodist Hospital. All patients were referred for evaluation of chest pain (CP), dyspnea or other associated risk factors for CAD by their primary care physician or cardiologist. Patients with resting ECG's unsuitable for stress interpretation were excluded (pathologic Q waves, left bundle branch block (LBBB), left ventricular hypertrophy with strain pattern (LVH), Wolff-Parkinson-White (WPW) syndrome, or other significant (≥1 mm) downward displacement of the ST segment) 
. Additionally, patients who did not reach a minimum of 85% predicted maximal heart rate during the exercise stress test were excluded from data analysis to standardize and ensure sufficient myocardial stress.
All patients underwent a thorough history and physical exam with data collected on presenting symptoms, past medical history, cardiac risk factors, as well as medications. The baseline ECG's were analyzed by a certified exercise physiologist prior to undergoing the stress test. All patients were instructed to hold their beta-blockers and calcium channel blockers for 24 hours prior to the stress test.
The study was approved by the Institutional Review Board (IRB) of New York Methodist hospital. An informed consent was not required because the study data was obtained and analyzed anonymously. The IRB of New York Methodist Hospital specifically waived the need for consent.
SPECT 201Tl and Tc-99m Imaging
The gold standard for the diagnosis of ischemia was myocardial single photon emission computed tomography (SPECT) imaging. Initial resting myocardial SPECT images were acquired while the patient was in a supine position with shoulders flexed to 180°, using a GE Millennium MyoSIGHT rotating gamma camera (General Electric Company, Milwaukee, WI). Resting images were performed after receiving thallium (201Tl) (predetermined using a weight-based algorithm) for patients weighing less than 300 lbs using the following parameters: 201Tl dosing up to 4mcI; imaging time: 18 min; 36 views/ 30 sec per view; matrix 64×64; circular; Collimator: LEHR. Patients weighing greater than 300 lbs underwent resting images with technetium (Tc-99m), but followed the same parameters with the exception of a dosing rate of 12–15mcI.
Stress imaging for patients less than 300 lbs was performed with Tc-99m and used the following parameters: Tc-99m dosing range 30–40mcI; imaging time: 15 min; 36 views/25 sec per view; matrix 64×64; circular; 16 frames/RR interval. Again, the same parameters were used for patients weighing over 300 lbs, only the dosing ranged from 35–40mcI.
Treadmill Exercise Testing
All treadmill testing was conducted using either the Bruce or Modified Bruce protocols (GE Medical Systems CASE Stress System Version 5 with Series 2000 Marquette Treadmill, General Electric Company, Milwaukee, WI). End points of exercise were predetermined according to absolute and relative indications for terminating exercise testing 
. One minute prior to peak exercise, patients received Tc-99m (weight based) and were imaged 15 to 20 min post exercise. All 12 leads of the standard ECG were monitored and used for analysis. ST measurements were assessed visually 80 msec post J-point during exercise and recovery with the PR segments used as the baseline. The criteria for determining a positive exercise ST-segment response were as follows: ≥1.0 mm horizontal or downsloping depression 80 msec post J-point for at least 3 consecutive beats 
Image Interpretation & Heart Size Criteria
The horizontal and vertical planes and the short-axis views were reviewed to detect the presence of defects. A 17-segment semi-quantitative method was utilized for visual interpretation of perfusion defects 
. In addition, a semi-quantitative scoring system using the five-point model was utilized to assess myocardial perfusion (0–4: 0
normal perfusion; 1
mild reduction in counts; 2
moderate reduction in counts; 3
severe reduction in counts; 4
absent uptake) 
. An image was considered positive for ischemia if there was ≥1 segment perfusion defect seen at stress which was not seen at rest.
The left ventricular cavity size was determined by a computer algorithm that assesses the left ventricular cavitary borders and computes the size of the cavity in milliliters (mL). An end diastolic cavitary size less than 65 mL was used as a cutoff for small vs. normal cavitary size. This cut off was determined prior to initiation of the study by doing a retrospective analysis of data consisting of 200 consecutive patients to determine the smallest (20%) ventricular cavitary size in our patient population. The first 200 patients were performed on the same clinical grounds as the patients in our current study, using the new GE scanner and computer database system. This population was selected as it best estimated the population that we analyzed in the current study.
The diagnostic accuracy of the ECG with nuclear imaging as the reference standard was determined by calculating sensitivity, specificity, and predictive values 
. Associations between demographic data and between ECG outcome (false positive versus no false positive) and heart size (small versus normal) were analyzed using the Chi square test for independence, with a Yates continuity correction. A multivariate analysis was performed to assess which pertinent variables (diabetes, age, body mass index (BMI), hypertension, coronary artery disease, and gender) were significantly associated with a false positive test. Both a C statistic and Goodness of fit were performed to assess the validity of the multivariate analysis.
Two-tailed significance was accepted at p<0.05 and all statistical analyses were conducted using SPSS® for Windows software, release 17.0 (SPSS Inc., Chicago, IL).