Methods

Study protocol
All patients included in the study were part of ongoing prospective dedicated database [9]. The study was approved by the Ethical Committee “Carlo Romano,” University of Naples Federico II, and all patients were informed and signed a written consent to participate to this study.

Clinical definitions
As part of the baseline examination, clinical teams collected information on traditional cardiovascular risk factors, including age, gender, chest pain, smoking history, family history of CAD, diabetes, hypertension, and known CAD. Chest pain was classified according to the American College of Cardiology/American Heart Association 2002 guideline update on exercise testing [10]. Patients were considered as having diabetes if they were receiving treatment with oral hypoglycemic drugs or insulin. A family history of premature CAD was defined as a diagnosis of CAD in a first-degree relative prior to or at 55 years of age. Hypertension was defined as a blood pressure > 140/90 mmHg or use of anti-hypertensive medication. Hyperlipidemia was defined as total cholesterol level > 6.2 mmol/L or treatment with cholesterol lowering medication. Smoking history was defined as prior or current tobacco use. A patient was considered to have known CAD at the time of imaging based on a provided history of previously diagnosed atherosclerotic coronary disease, history of myocardial infarction (chest pain or equivalent symptom complex, positive cardiac biomarkers, or typical electrocardiographic changes), history of percutaneous coronary intervention, or history of coronary artery bypass grafting.

Myocardial perfusion imaging
Patients underwent stress-optional rest 99mTc sestamibi-gated stress SPECT-MPI by physical exercise or dipyridamole stress test, according to the recommendations of the European Association of Nuclear Medicine [11]. During the pandemic, pharmacological stress was preferred to exercise stress test and criteria to prioritize patients were implemented, according to the recommendations of the American Society of Nuclear Cardiology and Society of Nuclear Medicine and Molecular Imaging [4]. Decisions were made based on clinical judgment on expected benefit to guide management, on the urgency of the test, and in discussion with the referring clinician. SPECT-MPI was performed as scheduled: (1) for evaluation of ischemia in moderate- to high-risk patients considered for urgent coronary revascularization, (2) in patients with intermediate pretest CAD likelihood or when suspicion of CAD was high but coronary angiography had greater risk, and (3) for evaluation of ischemia in moderate- to high-risk patients in whom surgical procedure was urgent and revascularization was an option. On the other hand, the test was postponed by 2–4 months for evaluation of ischemia follow-up when there was no urgent revascularization plan.
At peak exercise, or 4 min after completion of dipyridamole infusion, a bolus of 155 MBq of 99mTc-sestamibi was intravenously injected [12, 13]. For stress imaging studies, recordings were obtained by cadmium-zinc telluride (CZT)-SPECT (D-SPECT, Spectrum Dynamics, Caesarea, Israel) system using 9 pixilated CZT crystal detector columns mounted vertically spanning a 90° geometry [14]. Each of the columns consists of 1024 (16 × 64) 5-mm thick CZT crystal elements (2.46 × 2.46 mm). Square hole tungsten collimators are fitted to each of the detectors, which are shorter than conventional low-energy, high-resolution collimators, yielding significantly better geometric speed. Data were acquired focusing on the heart by the detectors rotating in synchrony and saved in list mode. Images were obtained with the patient in a semi-recumbent position. A 10-s pre-scan acquisition was performed to identify the location of the heart and to set the angle limits of scanning for each detector (region of interest-centric scanning). Using the myocardial count rate from the pre-scan acquisition, the time per projection was set to target the recording of 1000 myocardial kcounts. For rest-optional images, a second intravenous bolus of 370 MBq of 99mTc-sestamibi was injected followed by rest imaging recording. The duration of the scans was less than 10 min for stress and 4 min for rest. Summed and gated projections were reconstructed with an iterative maximum likelihood expectation maximization algorithm using 7 and 4 iterations, respectively [15].

Imaging interpretation
An automated software program (e-soft, 2.5, QGS/QPS, Cedars-Sinai Medical Center, Los Angeles, CA) was used to calculate the scores incorporating both the extent and severity of perfusion defects, using standardized segmentation of 17 myocardial regions [16]. The summed stress score (SSS), representing the total abnormal myocardium (i.e., necrotic and ischemic tissue), was obtained by adding the scores of the 17 segments of the stress images. A SSS > 3 was considered abnormal [17]. A similar procedure was applied to the resting images to calculate the summed rest score and the summed difference score. Total perfusion defect reflecting a combination of both severity and extent of myocardial defect was also calculated and categorized according to the presence of ≥ 10% of abnormal myocardium.

Statistical analysis
Continuous data are expressed as mean ± standard deviation and categorical data as percentage. Student’s t test and χ2 test were used to compare the differences in continuous and categorical variables, respectively. Poisson regression was used to compare the number of SPECT-MPI test performed during the lockdown and those during the corresponding time interval of the previous 3 years. Multivariable logistic regression analysis for predicting abnormal SPECT-MPI was performed for lockdown period and corresponding period of previous 3 years. Two-tailed P values < 0.05 were considered significant. Statistical analysis was performed with R software version 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria).