Downward myocardial creep during stress PET imaging is inversely associated with mortality.

PURPOSE: The myocardial creep is a phenomenon in which the heart moves from its original position during stress-dynamic PET myocardial perfusion imaging (MPI) that can confound myocardial blood flow measurements. Therefore, myocardial motion correction is important to obtain reliable myocardial flow quantification. However, the clinical importance of the magnitude of myocardial creep has not been explored. We aimed to explore the prognostic value of myocardial creep quantified by an automated motion correction algorithm beyond traditional PET-MPI imaging variables. METHODS: Consecutive patients undergoing regadenoson rest-stress [82Rb]Cl PET-MPI were included. A newly developed 3D motion correction algorithm quantified myocardial creep, the maximum motion at stress during the first pass (60 s), in each direction. All-cause mortality (ACM) served as the primary endpoint. RESULTS: A total of 4,276 patients (median age 71 years; 60% male) were analyzed, and 1,007 ACM events were documented during a 5-year median follow-up. Processing time for automatic motion correction was < 12 s per patient. Myocardial creep in the superior to inferior (downward) direction was greater than the other directions (median, 4.2 mm vs. 1.3-1.7 mm). Annual mortality rates adjusted for age and sex were reduced with a larger downward creep, with a 4.2-fold ratio between the first (0 mm motion) and 10th decile (11 mm motion) (mortality, 7.9% vs. 1.9%/year). Downward creep was associated with lower ACM after full adjustment for clinical and imaging parameters (adjusted hazard ratio, 0.93; 95%CI, 0.91-0.95; p < 0.001). Adding downward creep to the standard PET-MPI imaging model significantly improved ACM prediction (area under the receiver operating characteristics curve, 0.790 vs. 0.775; p < 0.001), but other directions did not (p > 0.5). CONCLUSIONS: Downward myocardial creep during regadenoson stress carries additional information for the prediction of ACM beyond conventional flow and perfusion PET-MPI. This novel imaging biomarker is quantified automatically and rapidly from stress dynamic PET-MPI.

Comparative predictors of mortality among patients referred for stress single-photon emission computed tomography versus positron emission tomography myocardial perfusion imaging.

BACKGROUND: There is currently little information regarding the usage and comparative predictors of mortality among patients referred for single-photon emission computed tomography (SPECT) versus positron emission tomography (PET) myocardial perfusion imaging (MPI) within multimodality imaging laboratories. METHODS: We compared the clinical characteristics and mortality outcomes among 15,718 patients referred for SPECT-MPI and 6202 patients referred for PET-MPI between 2008 and 2017. RESULTS: Approximately two-thirds of MPI studies were performed using SPECT-MPI. The PET-MPI group was substantially older and included more patients with known coronary artery disease (CAD), hypertension, diabetes, and myocardial ischemia. The annualized mortality rate was also higher in the PET-MPI group, and this difference persisted after propensity matching 3615 SPECT-MPI and 3615 PET-MPI patients to have similar clinical profiles. Among the SPECT-MPI patients, the most potent predictor of mortality was exercise ability and performance, including consideration of patients' mode of stress testing and exercise duration. Among the PET-MPI patients, myocardial flow reserve (MFR) was the most potent predictor of mortality. CONCLUSIONS: In our real-world setting, PET-MPI was more commonly employed among older patients with more cardiac risk factors than SPECT-MPI patients. The most potent predictors of mortality in our SPECT and PET-MPI groups were variables exclusive to each test: exercise ability/capacity for SPECT-MPI patients and MFR for PET-MPI patients.

Is typical angina still prognostically important? The influence of "treatment bias" upon prognostic assessments.

BACKGROUND: Since typical angina has become less frequent, it is unclear if this symptom still has prognostic significance. METHODS: We evaluated 38,383 patients undergoing stress/rest SPECT myocardial perfusion imaging followed for a median of 10.9 years. After dividing patients by clinical symptoms, we evaluated the magnitude of myocardial ischemia and subsequent mortality among medically treated versus revascularized subgroups following testing. RESULTS: Patients with typical angina had more frequent and greater ischemia than other symptom groups, but not higher mortality. Among typical angina patients, those who underwent early revascularization had substantially greater ischemia than the medically treated subgroup, including a far higher proportion with severe ischemia (44.9% vs 4.3%, P < 0.001) and transient ischemic dilation of the LV (31.3% vs 4.7%, P < 0.001). Nevertheless, the revascularized typical angina subgroup had a lower adjusted mortality risk than the medically treated subgroup (HR = 0.72, 95% CI: 0.57-0.92, P = 0.009) CONCLUSIONS: Typical angina is associated with substantially more ischemia than other clinical symptoms. However, the high referral of patients with typical angina patients with ischemia to early revascularization resulted in this group having a lower rather than higher mortality risk versus other symptom groups. These findings illustrate the need to account for "treatment bias" among prognostic studies.

Use of a Single-item Exercise Questionnaire Predicts Prognostic Risk among Patients undergoing Stress PET-MPI.

BACKGROUND: Exercise activity reduces mortality and favorably influences mediators of risk, including myocardial flow reserve (MFR) and chronotropic responsiveness. Comprehensive research regarding the relationship between exercise activity, MFR, and chronotropic response to pharmacological stress, as assessed by heart rate response (HRR) among patients undergoing PET myocardial perfusion imaging (MPI) has not been performed. Thus, we aimed to evaluate the relationship between exercise activity as assessed by a practical single-item questionnaire, MFR and HRR, and longitudinal clinical risk. METHODS: We studied outpatients who underwent pharmacological stress rubidium-82. PET-MPI and answered a self-reported one-item exercise activity questionnaire (0-10 scale) at the time of PET-MPI. HRR was calculated by the following equation: (stress HR-rest HR)/rest HR*100 (%). The primary outcome was death or myocardial infarction. RESULTS: Of 1,686 patients, 221 (13%) patients had hard events during our mean follow up of 3.8 years. Patients were divided into four groups: no/minimal exercise (n=551), low exercise (n=468), moderate exercise (n=485), and high exercise (n=182) based on the questionnaire. MFR and HRR increased with exercise activity in a stepwise manner. By Cox analysis adjusted for clinical and PET-MPI variables including MFR and HRR, exercise activity was independently associated with hard events (HR [95%CI] per activity scale, 0.95 [0.91-0.99]; p=0.028). CONCLUSIONS: Patients with higher exercise activity assessed by a practical single-item questionnaire had higher MFR and HRR. Exercise activity was an independent predictor of hard events in patients undergoing PET-MPI. Because of its ease of use, this single-item questionnaire should be applied among patients undergoing stress MPI.

Decline in typical angina among patients referred for cardiac stress testing.

OBJECTIVE: To evaluate temporal trends in the prevalence of typical angina and its clinical correlates among patients referred for stress/rest SPECT myocardial perfusion imaging (MPI). PATIENTS AND METHODS: We evaluated the prevalence of chest pain symptoms and their relationship to inducible myocardial ischemia among 61,717 patients undergoing stress/rest SPECT-MPI between January 2, 1991 and December 31, 2017. We also assessed the relationship between chest pain symptom and angiographic findings among 6,579 patients undergoing coronary CT angiography between 2011 and 2017. RESULTS: The prevalence of typical angina among SPECT-MPI patients declined from 16.2% between 1991 and 1997 to 3.1% between 2011 and 2017, while the prevalence of dyspnea without any chest pain increased from 5.9 to 14.5% over the same period. The frequency of inducible myocardial ischemia declined over time within all symptom groups, but its frequency among current patients (2011-2017) with typical angina was approximately three-fold higher versus other symptom groups (28.4% versus 8.6%, p < 0.001). Overall, patients with typical angina had a higher prevalence of obstructive CAD on CCTA than those with other clinical symptoms, but 33.3% of typical angina patients had no coronary stenoses, 31.1% had 1-49% stenoses, and 35.4% had ≥ 50% stenoses. CONCLUSIONS: The prevalence of typical angina has declined to a very low level among contemporary patients referred for noninvasive cardiac tests. The angiographic findings among current typical angina patients are now quite heterogeneous, with one-third of such patients having normal coronary angiograms. However, typical angina remains associated with a substantially higher frequency of inducible myocardial ischemia compared to patients with other cardiac symptoms.

Increasing frequency of dyspnea among patients referred for cardiac stress testing.

OBJECTIVE: To assess the frequency, change in prevalence, and prognostic significance of dyspnea among contemporary patients referred for cardiac stress testing. PATIENTS AND METHODS: We evaluated the prevalence of dyspnea and its relationship to all-cause mortality among 33,564 patients undergoing stress/rest SPECT-MPI between January 1, 2002 and December 31, 2017. Dyspnea was assessed as a single-item question. Patients were divided into three temporal groups. RESULTS: The overall prevalence of dyspnea in our cohort was 30.2%. However, there was a stepwise increase in the temporal prevalence of dyspnea, which was present in 25.6% of patients studied between 2002 and 2006, 30.5% of patients studied between 2007 and 2011, and 38.7% of patients studied between 2012 and 2017. There was a temporal increase in the prevalence of dyspnea in each age, symptom, and risk factor subgroup. The adjusted hazard ratio for mortality was higher among patients with dyspnea vs those without dyspnea both among all patients, and within each chest pain subgroup. CONCLUSIONS: Dyspnea has become increasingly prevalent among patients referred for cardiac stress testing and is now present among nearly two-fifths of contemporary cohorts referred for stress-rest SPECT-MPI. Prospective study is needed to standardize the assessment of dyspnea and evaluate the reasons for its increasing prevalence.

Development and validation of ischemia risk scores.

BACKGROUND: The likelihood of ischemia on myocardial perfusion imaging is central to physician decisions regarding test selection, but dedicated risk scores are lacking. We derived and validated two novel ischemia risk scores to support physician decision making. METHODS: Risk scores were derived using 15,186 patients and validated with 2,995 patients from a different center. Logistic regression was used to assess associations with ischemia to derive point-based and calculated ischemia scores. Predictive performance for ischemia was assessed using area under the receiver operating characteristic curve (AUC) and compared with the CAD consortium basic and clinical models. RESULTS: During derivation, the calculated ischemia risk score (0.801) had higher AUC compared to the point-based score (0.786, p < 0.001). During validation, the calculated ischemia score (0.716, 95% CI 0.684- 0.748) had higher AUC compared to the point-based ischemia score (0.699, 95% CI 0.666- 0.732, p = 0.016) and the clinical CAD model (AUC 0.667, 95% CI 0.633- 0.701, p = 0.002). Calibration for both ischemia scores was good in both populations (Brier score  < 0.100). CONCLUSIONS: We developed two novel risk scores for predicting probability of ischemia on MPI which demonstrated high accuracy during model derivation and in external testing. These scores could support physician decisions regarding diagnostic testing strategies.

Mortality risk among patients undergoing exercise versus pharmacologic myocardial perfusion imaging: A propensity-based comparison.

BACKGROUND: The increased risk associated with pharmacologic versus exercise testing is obscured by the higher prevalence of clinical risk factors among pharmacologic patients. Thus, we assessed comparative mortality in a large risk factor-matched group of exercise versus pharmacologic patients undergoing stress/rest SPECT myocardial perfusion imaging (MPI). METHODS: 39,179 patients undergoing stress/rest SPECT-MPI were followed for 13.3 ± 5.0 years for all-cause mortality (ACM). We applied propensity-matching to create pharmacologic and exercise groups with similar risk profiles. RESULTS: In comparison to exercise patients, pharmacologic patients had an increased risk-adjusted hazard ratio for ACM for each level of ischemia: increased by 3.8-fold (95%CI 3.5-4.1) among nonischemic patients, 2.5-fold (95%CI 2.0-3.2) among mildly ischemic patients, and 2.6-fold (95%CI 2.1-3.3) among moderate/severe ischemic patients. Similar findings were observed among a propensity-matched cohort of 10,113 exercise and 10,113 pharmacologic patients as well as in an additional cohort that also excluded patients with noncardiac co-morbidities. CONCLUSIONS: Patients requiring pharmacologic stress testing manifest substantially heightened clinical risk at each level of myocardial ischemia and even when myocardial ischemia is absent. These findings suggest the need to study the pathophysiological drivers of increased risk in association with pharmacologic testing and to convey this risk in clinical reports.

Simultaneous Tc-99m PYP/Tl-201 dual-isotope SPECT myocardial imaging in patients with suspected cardiac amyloidosis.

INTRODUCTION: Assessment of myocardial uptake of Tc-99m-pyrophosphate (Tc-99m PYP) is pivotal in distinguishing transthyretin-associated cardiac amyloidosis (ATTR) from light chain amyloid (AL). It is often difficult to differentiate myocardial uptake from blood pool radioactivity with planar imaging or SPECT. We studied whether simultaneous dual-isotope Tc-99m PYP/Tl-201 SPECT improves assessment of Tc-99m PYP uptake compared to single-isotope SPECT. METHODS: Simultaneous Tc-99m PYP/Tl-201 dual-isotope SPECT was acquired in 112 patients studied for possible cardiac amyloidosis. Visual interpretation was performed by two observers on single-isotope followed by dual-isotope SPECT. Heart-to-contralateral lung ratio (H/CL) of myocardial counts quantified by single-isotope and dual-isotope SPECT was compared between ATTR, AL, and no amyloidosis groups. RESULTS: In 112 patients (39 ATTR and 26 AL patients, and 47 no amyloidosis), a lower proportion of no amyloidosis and AL patients were classified visually as equivocal with dual-isotope SPECT compared to single-isotope SPECT (2% vs 19%, P = 0.02 and 8% vs 35%, P = 0.04, respectively). H/CL measurements with single-isotope and dual-isotope were lower in AL and no amyloidosis patients vs ATTR patients (P < 0.05). Interobserver agreement of visual assessment was improved with dual-isotope SPECT (P = 0.03). AUCs for detection of ATTR by visual assessment and H/CL quantification were higher with dual-isotope (0.94 and 0.95, respectively) compared to single-isotope SPECT (0.84, P = 0.001 and 0.92, P = 0.02). CONCLUSION: Tc-99m PYP/Tl-201 SPECT improves visual differentiation of ATTR and AL amyloidosis compared to single-isotope SPECT. Visual assessment and H/CL quantitation with dual-isotope SPECT provide similar discrimination between patients with ATTR and AL amyloidosis.

Predictors of high-risk coronary artery disease in subjects with normal SPECT myocardial perfusion imaging.

BACKGROUND: While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in patients with high-risk coronary artery disease (CAD) by invasive coronary angiography (ICA).The predictors of high-risk CAD in patients with normal SPECT-MPI have not been described. METHODS: We studied 580 patients (age 64 ± 12 years, 49% men) without known CAD who underwent stress-gated SPECT-MPI [exercise (41%) or vasodilator (59%)] <2 months before ICA and had summed stress score (SSS) <4. High-risk CAD was defined as 3 vessels with ≥70% stenosis, 2 vessels with ≥70% stenosis including proximal left anterior descending, or left main with ≥50% stenosis. Obstructive non-high-risk CAD was defined by the presence of a ≥70% stenosis but without having other high-risk criteria. Tenfold cross-validated receiver operating characteristic (ROC) estimates were obtained to assess the predictors of high-risk CAD. RESULTS: Forty-two subjects (7.2%) had high-risk CAD and 168 (29.0%) had obstructive non-high-risk CAD. Variables associated with high-risk CAD were pretest probability of CAD ≥66% (Odds ratio [OR] 3.63, 95% CI 1.6-8.3, P = .002), SSS > 0 (OR 7.46, 95% CI 2.6-21.1, P < 0.001), and abnormal TID (OR 2.16, 95% CI 1.0-4.5, P = 0.044). When substituted for TID, EF change was also predictive of high-risk CAD (OR 0.93, 95% CI 0.9-1.0, P = 0.023). The prevalence of high-risk CAD increased as the number of these predictors increased. In a sub-analysis of patients in whom quantitative total perfusion deficit (TPD) was available, TPD > 0 was also a predictor of high-risk CAD (OR 6.01, 95% CI 1.5-22.2, P = 0.011). CONCLUSION: Several clinical, stress, and SPECT-MPI findings are associated high-risk CAD among patients with normal SPECT-MPI. Consideration of these factors may improve the overall assessment of the likelihood of high-risk CAD in patients undergoing stress SPECT-MPI.

Prediction of revascularization after myocardial perfusion SPECT by machine learning in a large population.

OBJECTIVE: We aimed to investigate if early revascularization in patients with suspected coronary artery disease can be effectively predicted by integrating clinical data and quantitative image features derived from perfusion SPECT (MPS) by machine learning (ML) approach. METHODS: 713 rest (201)Thallium/stress (99m)Technetium MPS studies with correlating invasive angiography with 372 revascularization events (275 PCI/97 CABG) within 90 days after MPS (91% within 30 days) were considered. Transient ischemic dilation, stress combined supine/prone total perfusion deficit (TPD), supine rest and stress TPD, exercise ejection fraction, and end-systolic volume, along with clinical parameters including patient gender, history of hypertension and diabetes mellitus, ST-depression on baseline ECG, ECG and clinical response during stress, and post-ECG probability by boosted ensemble ML algorithm (LogitBoost) to predict revascularization events. These features were selected using an automated feature selection algorithm from all available clinical and quantitative data (33 parameters). Tenfold cross-validation was utilized to train and test the prediction model. The prediction of revascularization by ML algorithm was compared to standalone measures of perfusion and visual analysis by two experienced readers utilizing all imaging, quantitative, and clinical data. RESULTS: The sensitivity of machine learning (ML) (73.6% ± 4.3%) for prediction of revascularization was similar to one reader (73.9% ± 4.6%) and standalone measures of perfusion (75.5% ± 4.5%). The specificity of ML (74.7% ± 4.2%) was also better than both expert readers (67.2% ± 4.9% and 66.0% ± 5.0%, P < .05), but was similar to ischemic TPD (68.3% ± 4.9%, P < .05). The receiver operator characteristics areas under curve for ML (0.81 ± 0.02) was similar to reader 1 (0.81 ± 0.02) but superior to reader 2 (0.72 ± 0.02, P < .01) and standalone measure of perfusion (0.77 ± 0.02, P < .01). CONCLUSION: ML approach is comparable or better than experienced readers in prediction of the early revascularization after MPS, and is significantly better than standalone measures of perfusion derived from MPS.

Quantitative high-efficiency cadmium-zinc-telluride SPECT with dedicated parallel-hole collimation system in obese patients: results of a multi-center study.

BACKGROUND: Obesity is a common source of artifact on conventional SPECT myocardial perfusion imaging (MPI). We evaluated image quality and diagnostic performance of high-efficiency (HE) cadmium-zinc-telluride parallel-hole SPECT MPI for coronary artery disease (CAD) in obese patients. METHODS AND RESULTS: 118 consecutive obese patients at three centers (BMI 43.6 ± 8.9 kg·m(-2), range 35-79.7 kg·m(-2)) had upright/supine HE-SPECT and invasive coronary angiography > 6 months (n = 67) or low likelihood of CAD (n = 51). Stress quantitative total perfusion deficit (TPD) for upright (U-TPD), supine (S-TPD), and combined acquisitions (C-TPD) was assessed. Image quality (IQ; 5 = excellent; < 3 nondiagnostic) was compared among BMI 35-39.9 (n = 58), 40-44.9 (n = 24) and ≥45 (n = 36) groups. ROC curve area for CAD detection (≥50% stenosis) for U-TPD, S-TPD, and C-TPD were 0.80, 0.80, and 0.87, respectively. Sensitivity/specificity was 82%/57% for U-TPD, 74%/71% for S-TPD, and 80%/82% for C-TPD. C-TPD had highest specificity (P = .02). C-TPD normalcy rate was higher than U-TPD (88% vs 75%, P = .02). Mean IQ was similar among BMI 35-39.9, 40-44.9 and ≥45 groups [4.6 vs 4.4 vs 4.5, respectively (P = .6)]. No patient had a nondiagnostic stress scan. CONCLUSIONS: In obese patients, HE-SPECT MPI with dedicated parallel-hole collimation demonstrated high image quality, normalcy rate, and diagnostic accuracy for CAD by quantitative analysis of combined upright/supine acquisitions.

Long-term mortality following normal exercise myocardial perfusion SPECT according to coronary disease risk factors.

BACKGROUND: While normal exercise myocardial perfusion imaging (SPECT-MPI) is a robust predictor of low short-term clinical risk, there is increasing interest in ascertaining how clinical factors influence long-term risk following SPECT-MPI. METHODS: We evaluated the predictors of outcome from clinical data obtained at the time of testing in 12,232 patients with normal exercise SPECT-MPI studies. All-cause mortality (ACM) was assessed at a mean of 11.2 ± 4.5 years using the Social Security Death Index. RESULTS: The ACM rate was 0.8%/year, but varied markedly according to the presence of CAD risk factors. Hypertension, smoking, diabetes, exercise capacity, dyspnea, obesity, higher resting heart rate, an abnormal ECG, LVH, atrial fibrillation, and LVEF < 45% were all predictors of increased mortality. Risk factors were synergistic in predicting mortality: annualized age and gender-adjusted ACM rates ranged from only 0.2%/year among patients exercising for >9 minutes having none of three significant risk factors (among hypertension, diabetes, and smoking) to 1.6%/year among patients exercising <6 minutes and having ≥ 2 of these three risk factors. The age and gender-adjusted hazard ratio for mortality was increased by 7.3 (95% confidence interval 5.5-9.7) in the latter patients compared to those patients who exercised >9 minutes and had no significant risk factors (P < .001). CONCLUSIONS: Long-term mortality risk varies markedly in accordance with baseline CAD risk factors and functional capacity among patients with normal exercise SPECT-MPI studies. Further study is indicated to determine whether the prospective characterization of both short-term and long-term risks following the performance of stress SPECT-MPI leads to improved clinical management.

Two-position supine/prone myocardial perfusion SPECT (MPS) imaging improves visual inter-observer correlation and agreement.

OBJECTIVES: We aimed to compare the inter-observer agreement between two experienced readers using supine vs combined supine/prone myocardial perfusion SPECT (MPS) in a large population. METHODS: 1,181 consecutive patients without known coronary artery disease (CAD) undergoing rest (201)Tl/stress (99m)Tc-sestamibi MPS studies were evaluated. Visual reads were performed in two consecutive steps, with readers scoring the stress supine perfusion images during step 1 and rescoring the images using both supine/prone data during step 2. Visual summed stress scores (SSS) of two readers including regional scores in different vascular territories were compared. RESULTS: The specificity for both readers improved using combined supine/prone imaging (reader 1: 92% vs 86% [P = .0002], reader 2: 88% vs 72% [P < .0001]). The inter-observer correlation for SSS (0.90 vs 0.84, P < .0001) and inter-observer agreement for combined supine/prone reading (bias = 1.0, 95% confidence interval (CI) 0.9-1.2 vs bias = 3.1, 95% CI 2.8-3.4, P < .0001) were significantly better as compared to supine-only reading. The overall correlation between SSS scores for two readers improved with supine/prone imaging for both genders, as well as in the left anterior descending and right coronary territories. CONCLUSION: The inter-observer correlation and agreement significantly improve using two-position supine/prone vs supine-only imaging.

The lack of ethnic and racial diversity among patients undergoing coronary artery calcium scanning.

BACKGROUND: While coronary artery calcium (CAC) CAC scanning has become increasingly used as a tool for primary cardiovascular disease prevention, there has been little study regarding its comparative utilization among ethnic and racial minorities. METHODS: We contrasted the temporal trends in the ethnoracial composition for 73,856 out-patients undergoing stress/rest radionuclide myocardial perfusion imaging (MPI) between 1991 and 2020 and 32,906 undergoing CAC scanning between 1998 and 2020. Both groups were divided into those below and above 65 years. Initial medical insurance claims were used to identify which patients self-paid for SPECT-MPI and CAC studies. RESULTS: Among stress-MPI patients <65 years, the prevalence of White patients declined from 85.5% to 54.0% over the temporal span of our study while the prevalence of Blacks increased from 7.2% to 15.1% and that of Hispanics from 2.3 to 21.6%. Increasing ethnoracial diversification was also noted for SPECT-MPI patients ≥65 years. By contrast, over four-fifths of CAC studies were performed in White patients in each temporal period among both younger and older patients. Among CAC patients <65 years, over 95% of studies were self-paid by patients. For CAC patients ≥65 years, nearly two-third of studies were first submitted to Medicare, but there was no difference in the ethnoracial composition in this group versus initial self-paying patients. CONCLUSIONS: While the ethnoracial diversity of patients undergoing SPECT-MPI markedly increased at our Institution over recent decades, CAC scanning has been disproportionately and consistently utilized by self-paying White patients. These findings highlight the need to make CAC scanning more available among ethnoracial minorities.

Automated Motion Correction for Myocardial Blood Flow Measurements and Diagnostic Performance of 82Rb PET Myocardial Perfusion Imaging.

Motion correction (MC) affects myocardial blood flow (MBF) measurements in 82Rb PET myocardial perfusion imaging (MPI); however, frame-by-frame manual MC of dynamic frames is time-consuming. This study aims to develop an automated MC algorithm for time-activity curves used in compartmental modeling and compare the predictive value of MBF with and without automated MC for significant coronary artery disease (CAD). Methods: In total, 565 patients who underwent PET-MPI were considered. Patients without angiographic findings were split into training (n = 112) and validation (n = 112) groups. The automated MC algorithm used simplex iterative optimization of a count-based cost function and was developed using the training group. MBF measurements with automated MC were compared with those with manual MC in the validation group. In a separate cohort, 341 patients who underwent PET-MPI and invasive coronary angiography were enrolled in the angiographic group. The predictive performance in patients with significant CAD (≥70% stenosis) was compared between MBF measurements with and without automated MC. Results: In the validation group (n = 112), MBF measurements with automated and manual MC showed strong correlations (r = 0.98 for stress MBF and r = 0.99 for rest MBF). The automatic MC took less time than the manual MC (<12 s vs. 10 min per case). In the angiographic group (n = 341), MBF measurements with automated MC decreased significantly compared with those without (stress MBF, 2.16 vs. 2.26 mL/g/min; rest MBF, 1.12 vs. 1.14 mL/g/min; MFR, 2.02 vs. 2.10; all P < 0.05). The area under the curve (AUC) for the detection of significant CAD by stress MBF with automated MC was higher than that without (AUC, 95% CI, 0.76 [0.71-0.80] vs. 0.73 [0.68-0.78]; P < 0.05). The addition of stress MBF with automated MC to the model with ischemic total perfusion deficit showed higher diagnostic performance for detection of significant CAD (AUC, 95% CI, 0.82 [0.77-0.86] vs. 0.78 [0.74-0.83]; P = 0.022), but the addition of stress MBF without MC to the model with ischemic total perfusion deficit did not reach significance (AUC, 95% CI, 0.81 [0.76-0.85] vs. 0.78 [0.74-0.83]; P = 0.067). Conclusion: Automated MC on 82Rb PET-MPI can be performed rapidly with excellent agreement with experienced operators. Stress MBF with automated MC showed significantly higher diagnostic performance than without MC.

Self-reported exercise activity influences the relationship between coronary computed tomography angiographic finding and mortality.

AIM: Recent studies suggest that the application of exercise activity questionnaires, including the use of a single-item exercise question, can be additive to the prognostic efficacy of imaging findings. This study aims to evaluate the prognostic efficacy of exercise activity in patients undergoing coronary computed tomography angiography (CCTA). METHODS AND RESULTS: We assessed 9772 patients who underwent CCTA at a single center between 2007 and 2020. Patients were divided into 4 groups of physical activity as no exercise (n â€‹= â€‹1643, 17%), mild exercise (n â€‹= â€‹3156, 32%), moderate exercise (n â€‹= â€‹3542, 36%), and high exercise (n â€‹= â€‹1431,15%), based on a single-item self-reported questionnaire. Coronary stenosis was categorized as no (0%), non-obstructive (1-49%), borderline (50-69%), and obstructive (≥70%). During a median follow-up of 4.64 (IQR 1.53-7.89) years, 490 (7.6%) died. There was a stepwise inverse relationship between exercise activity and mortality (p â€‹< â€‹0.001). Compared with the high activity group, the no activity group had a 3-fold higher mortality risk (HR: 3.3, 95%CI (1.94-5.63), p â€‹< â€‹0.001) after adjustment for age, clinical risk factors, symptoms, and statin use. For any level of CCTA stenosis, mortality rates were inversely associated with the degree of patients' exercise activity. The risk of all-cause mortality was similar among the patients with obstructive stenosis with high exercise versus those with no coronary stenosis but no exercise activity (p â€‹= â€‹0.912). CONCLUSION: Physical activity as assessed by a single-item self-reported questionnaire is a strong stepwise inverse predictor of mortality risk among patients undergoing CCTA.

10-year experience of utilizing a stress-first SPECT myocardial perfusion imaging.

BACKGROUND: Despite its potential benefits, the utilization of stress-only protocol in clinical practice has been limited. We report utilizing stress-first single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: We assessed 12,472 patients who were referred for SPECT-MPI between 2013 and 2020. The temporal changes in frequency of stress-only imaging were assessed according to risk factors, mode of stress, prior coronary artery disease (CAD) history, left ventricular function, and symptom status. The clinical endpoint was all-cause mortality. RESULTS: In our lab, stress/rest SPECT-MPI in place of rest/stress SPECT-MPI was first introduced in November 2011 and was performed more commonly than rest/stress imaging after 2013. Stress-only SPECT-MPI scanning has been performed in 30-34% of our SPECT-MPI studies since 2013 (i.e.. 31.7% in 2013 and 33.6% in 2020). During the study period, we routinely used two-position imaging (additional prone or upright imaging) to reduce attenuation and motion artifact and introduced SPECT/CT scanner in 2018. The rate of stress-only study remained consistent before and after implementing the SPECT/CT scanner. The frequency of stress-only imaging was 43% among patients without a history of prior CAD and 19% among those with a prior CAD history. Among patients undergoing treadmill exercise, the frequency of stress-only imaging was 48%, while 32% among patients undergoing pharmacologic stress test. In multivariate Cox analysis, there was no significant difference in mortality risk between stress-only and stress/rest protocols in patients with normal SPECT-MPI results (p = 0.271). CONCLUSION: Implementation of a stress-first imaging protocol has consistently resulted in safe cancellation of 30% of rest SPECT-MPI studies.

Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA.

There is a preponderance of evidence that, in the setting of an acute coronary syndrome, an invasive approach using coronary revascularization has a morbidity and mortality benefit. However, recent stable ischemic heart disease (SIHD) randomized clinical trials testing whether the addition of coronary revascularization to guideline-directed medical therapy (GDMT) reduces death or major cardiovascular events have been negative. Based on the evidence from these trials, the primary role of GDMT as a front line medical management approach has been clearly defined in the recent SIHD clinical practice guideline; the role of prompt revascularization is less precisely defined. Based on data from observational studies, it has been hypothesized that there is a level of ischemia above which a revascularization strategy might result in benefit regarding cardiovascular events. However, eligibility for recent negative trials in SIHD has mandated at most minimal standards for ischemia. An ongoing randomized trial evaluating the effectiveness of randomization of patients to coronary angiography and revascularization as compared to no coronary angiography and GDMT in patients with moderate-severe ischemia will formally test this hypothesis. The current review will highlight the available evidence including a review of the published and ongoing SIHD trials.

Comparison of coronary artery calcium scores among patients referred for cardiac imaging tests.

BACKGROUND: While coronary artery calcium (CAC) can now be evaluated by multiple imaging modalities, there is presently scant study regarding how CAC scores may vary among populations of varying clinical risk. METHODS: We evaluated the distribution of CAC scores among three patient groups: 18,941 referred for CAC scanning, 5101 referred for diagnostic coronary CT angiography (CCTA), and 3307 referred for diagnostic positron emission tomography (PET) myocardial perfusion imaging (MPI). We assessed the relationship between CAC score and myocardial ischemia, obstructive coronary artery disease (CAD), and all-cause mortality across imaging modalities. RESULTS: Within each age group, the frequency of CAC abnormalities were relatively similar across testing modalities, despite an annualized mortality rate which varied from 0.5%/year among CAC patients to 3.8%/year among PET-MPI patients (p < 0.001). Among CCTA and PET-MPI patients, a zero CAC score was common, occurring in ~70% of patients <50 years, ~40% of patients 50-59 years, and ~ 25% of patients 60-69 years. Among CCTA patients, zero CAC was associated with a normal coronary angiogram with high frequency, ranging from 92.2% among patients <50 years to 87.9% among patients ≥70 years. Among PET-MPI patients, zero CAC was associated with a very low frequency of inducible ischemia across all age groups, ranging from 1.5% among patients <50 years to 0.9% among patients ≥70 years. CONCLUSIONS: In our study, relatively similar CAC scores were noted among patients varying markedly in mortality risk. Clinically, zero CAC scores predicted both a low likelihood of obstructive CAD and inducible myocardial ischemia in all age groups and were observed with high frequency across diagnostic testing modalities.