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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.

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BACKGROUND: Coronary computed tomography angiogram (CCTA) is a crucial tool for diagnosing CAD, but its impact on altering preventive medications is not well-documented. This systematic review aimed to compare changes in aspirin and statin therapy following CCTA and functional stress testing in patients with suspected CAD, and in those underwent CCTA when stratified by the presence/absence of plaque. RESULTS: Eight studies involving 42,812 CCTA patients and 64,118 cardiac stress testing patients were analyzed. Compared to functional testing, CCTA led to 66 â€‹% more changes in statin therapy (pooled RR, 95 â€‹% CI [1.28-2.15]) and a 74 â€‹% increase in aspirin prescriptions (pooled RR, 95 â€‹% CI [1.34-2.26]). For medication modifications based on CCTA results, 13 studies (47,112 patients with statin data) and 11 studies (12,089 patients with aspirin data) were included. Patients with any plaque on CCTA were five times more likely to use or intensify statins compared to those without CAD (pooled RR, 5.40, 95 â€‹% CI [4.16-7.00]). Significant heterogeneity remained, which decreased when stratified by diabetes rates. Aspirin use increased eightfold after plaque detection (pooled RR, 8.94 [95 â€‹% CI, 4.21-19.01]), especially with obstructive plaque findings (pooled RR, 9.41, 95 â€‹% CI [2.80-39.02]). CONCLUSION: In conclusion, CCTA resulted in higher changes in statin and aspirin therapy compared to cardiac stress testing. Detection of plaque by CCTA significantly increased statin and aspirin therapy.

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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.

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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.

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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.

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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.

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BACKGROUND: The utility of performing early myocardial revascularization among patients presenting with inducible myocardial ischemia and low left ventricular ejection fraction (LVEF) is currently unknown. OBJECTIVES: In this study, we sought to assess the relationship between stress-induced myocardial ischemia, revascularization, and all-cause mortality (ACM) among patients with normal vs low LVEF. METHODS: We evaluated 43,443 patients undergoing stress-rest single-photon emission computed tomography myocardial perfusion imaging from 1998 to 2017. Median follow-up was 11.4 years. Myocardial ischemia was assessed for its interaction between early revascularization and mortality. A propensity score was used to adjust for nonrandomization to revascularization, followed by multivariable Cox modeling adjusted for the propensity score and clinical variables to predict ACM. RESULTS: The frequency of myocardial ischemia varied markedly according to LVEF and angina, ranging from 6.7% among patients with LVEF ≥55% and no typical angina to 64.0% among patients with LVEF <45% and typical angina (P < 0.001). Among 39,883 patients with LVEF ≥45%, early revascularization was associated with increased mortality risk among patients without ischemia and lower mortality risk among patients with severe (≥15%) ischemia (HR: 0.70; 95% CI: 0.52-0.95). Among 3,560 patients with LVEF <45%, revascularization was not associated with mortality benefit among patients with no or mild ischemia, and was associated with decreased mortality among patients with moderate (10%-14%) (HR: 0.67; 95% CI: 0.49-0.91) and severe (≥15%) (HR: 0.55; 95% CI: 0.38-0.80) ischemia. CONCLUSIONS: Within this cohort, early myocardial revascularization was associated with a significant reduction in mortality among both patients with normal LVEF and severe inducible myocardial ischemia and patients with low LVEF and moderate or severe inducible myocardial ischemia.

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BACKGROUND: The utility of cardiac stress testing depends on the prevalence of myocardial ischemia within candidate populations. However, a comprehensive assessment of the factors influencing frequency of myocardial ischemia within contemporary populations referred for stress testing has not been performed. METHODS: We assessed 19,690 patients undergoing nuclear stress testing from a multicenter registry. The chi-square test was used to assess the relative importance of features for predicting myocardial ischemia. RESULTS: In the overall cohort, LVEF, male gender, and rest total perfusion deficit (TPD) were the top three predictors of ischemia, followed by CAD status, age, typical angina, and CAD risk factors. Myocardial ischemia was observed in 13.6 % of patients with LVEF > 55 %, in 26.2 % of patients with LVEF 45 %-54 %, and in 48.3% among patients with LVEF < 45 % (P < 0.001). A similar pattern was noted for rest TPD (P < 0.001). Men had a threefold higher frequency of ischemia versus women (25.8 % vs. 8.4%, P < 0.001). Although the relative ranking of ischemia predictors varied among centers, LVEF and/or rest TPD were among the two most potent predictors of myocardial ischemia within each center. CONCLUSION: The prevalence of myocardial ischemia varied markedly according to clinical and imaging characteristics. LVEF and rest TPD are robust predictors of myocardial ischemia.

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BACKGROUND: The frequency of inducible myocardial ischemia has declined in contemporary stress test cohorts, suggesting a need to re-evaluate its optimal use. To-date, however, a comprehensive analysis of the most potent predictors of myocardial ischemia among cardiac stress test patients has not been conducted. METHODS: We assessed 27,615 patients referred for stress-rest SPECT myocardial perfusion imaging between January 1, 2004 and December 31, 2017. Chi-square analysis was used to ascertain the most potent predictors of ischemia. RESULTS: Among our cohort, CAD status (presence/absence of known CAD), rest left ventricular ejection fraction (LVEF), and typical angina were the most potent predictors of ischemia. The frequency of ischemia was only 6.6% among patients with an LVEF > 55% but 38.1% for patients with LVEF < 45% (P < 0.001). The frequency of myocardial ischemia was fourfold higher among patients with known CAD vs no known CAD (28.0% vs 6.5%, P < 0.001) and approximately threefold higher among patients with typical angina vs patients with atypical symptoms (P < 0.001). CONCLUSIONS: The frequency of myocardial ischemia varies markedly according to the common clinical parameters and is particularly high among patients with known CAD, low LVEF, and typical angina. These observations may be used to develop more cost-effective strategies for referring patients for cardiac stress testing.

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BACKGROUND: Patients with myocardial ischemia in the absence of obstructive coronary artery disease (CAD) often experience anginal complaints and are at risk of cardiac events. Stress-related psychological factors and acute negative emotions might play a role in these patients with suspect coronary microvascular dysfunction (CMD). METHODS AND RESULTS: 295 Patients (66.9 ± 8.7 years, 46% women) undergoing myocardial perfusion single-photon-emission computed tomography (MPI-SPECT), were divided as follows: (1) a non-ischemic reference group (n = 136); (2) patients without inducible ischemia, but with a history of CAD (n = 62); (3) ischemia and documented CAD (n = 52); and (4) ischemia and suspect CMD (n = 45). These four groups were compared with regard to psychological factors and acute emotions. Results revealed no differences between the groups in psychological factors (all P > .646, all effect sizes d < .015). State sadness was higher for patients with suspect CMD (16%) versus the other groups (P = .029). The groups did not differ in the association of psychological factors or emotions with anginal complaints (all P values > .448). CONCLUSION: Suspect CMD was not associated with more negative psychological factors compared to other groups. State sadness was significantly higher for patients with suspect CMD, whereas no differences in state anxiety and other psychological factors were found.

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Regadenoson myocardial perfusion imaging (MPI) is a widely used screening study for patients with an intermediate pretest probability of coronary artery disease (CAD). Via selective agonism of the adenosine A2A receptor, regadenoson can induce coronary steal, revealing stenotic vessel territory through transient ischemia. Common side effects of this medication include chest pain, shortness of breath, nausea, vomiting, atrioventricular block, seizure, and allergic reactions. Here we present a case of severe shivering and chest tightness after the administration of regadenoson, along with a physiologic explanation and treatment.

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(1) Background: Both cerebral vascular disorders and cognitive decline increase in incidence with age. The role of cerebral vascular disease and hemodynamic changes in the development of cognitive deficits is controversial. The objective of this study was to assess the cardiovascular response during cardiac stress testing in neurologically asymptomatic individuals who developed cognitive impairment several years after previous cardiac stress testing. (2) Methods: This was a retrospective cohort study of patients who underwent cardiac stress testing between January 2001 and December 2010. Patients were followed up until May 2015, and we selected those who developed cognitive dysfunction including dementia, mild cognitive impairment, and subjective cognitive decline, after the stress test. Heart rate and blood pressure both at rest and at peak exercise, and the mean R-R interval at rest were recorded. For each patient who developed cognitive impairment, we selected one matched control who did not show cognitive decline by the end of the follow-up period. (3) Results: From the cohort of 7224 patients, 371 developed cognitive impairment; of these, 186 (124 men) met the inclusion criteria, and 186 of the other patients were selected as matched controls. During follow-up, cognitive impairment appeared 6.2 ± 4.7 years after the cardiac stress test. These patients who had subsequently developed cognitive impairment had significantly lower at-rest systolic, diastolic, and mean blood pressure than controls (p < 0.05). Further, compared with controls, their maximum heart rate was significantly higher at peak exercise. (4) Conclusion: The results from this study suggest that differences in cardiovascular response to stress might be present in individuals who develop cognitive decline. These findings challenge the possibility of assessing blood pressure and heart rate variability at rest and during cardiac stress as potential risk factors associated with cognitive impairment.

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BACKGROUND: Negative emotions have been linked to ischemic heart disease, but existing research typically involves self-report methods and little is known about non-verbal facial emotion expression. The role of ischemia and anginal symptoms in emotion expression was examined. METHODS: Patients undergoing cardiac stress testing (CST) using bicycle exercise or adenosine with myocardial perfusion imaging were included (N = 256, mean age 66.8 ± 8.7 year., 43% women). Video images and emotion expression (sadness, anxiety, anger, and happiness) were analyzed at baseline, initial CST , maximal CST, recovery. Nuclear images were evaluated using SPECT. RESULTS: Ischemia (N = 89; 35%) was associated with higher levels of sadness (p = .017, d = 0.34) and lower happiness (p = .015, d = 0.30). During recovery, patients with both ischemia and anginal symptoms had the highest sadness expression (F (3,254) = 3.67, p = .013, eta2 = 0.042) and the lowest happiness expression (F (3, 254) = 4.19, p = .006, eta2 = .048). CONCLUSION: Sadness and reduced happiness were more common in patients with ischemia. Also, anginal symptoms were associated with more negative emotions.

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BACKGROUND: The prevalence of myocardial ischemia is associated with anxiety. State and trait anxiety are more common in younger women compared to men, and high anxiety levels could affect hemodynamic reactivity during cardiac stress testing. The aim is to examine whether anxiety plays a role in gender differences in patients ≤ 65 and > 65 years in hemodynamic reactivity and ischemia during cardiac stress testing. METHODS AND RESULTS: Included were 291 patients (66.8 ± 8.7 years, 45% women) with suspect ischemia undergoing myocardial perfusion single-photon emission computed tomography (MPI-SPECT). Primary outcomes were semi-quantitative summed difference score (SDS) and summed stress score (SSS), as continuous indicators of myocardial ischemia. Analyses were stratified by age. Trait anxiety was measured using a validated questionnaire (GAD-7) and state anxiety using facial expression analyses software. Overall, trait and state anxiety were not associated with the prevalence of ischemia (N = 107, 36%). A significant interaction was found between gender and trait anxiety in women ≤ 65 years for SDS (F(1,4) = 5.73, P = .019) and SSS (F(1,10) = 6.50, P = .012). This was not found for state anxiety. CONCLUSION: SDS and SSS were significantly higher in women younger than 65 years with high trait anxiety. This interaction was not found in men and women over 65 years.

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BACKGROUND AND AIMS: Patients with suspected coronary artery disease who undergo stress SPECT myocardial perfusion imaging (MPI) and require pharmacologic stress are at substantially increased mortality risk compared to those who can exercise. However, the mechanisms underlying this increased risk are not well delineated. To test whether increased atherosclerotic burden accounts for this increased risk, we assessed the association between coronary artery calcium (CAC) scores and mortality risk among patients undergoing exercise versus pharmacologic SPECT MPI. METHODS: We assessed all-cause mortality in 2,151 patients, followed for 12.2 ± 3.4 years, after undergoing stress-rest SPECT-MPI and CAC scanning within 3 months of each other. Patients were divided according to their mode of stress testing (exercise or pharmacologic). We further employed propensity analysis to create a subgroup of exercise and pharmacologic subgroups with comparable age, symptoms, and coronary risk factors. RESULTS: Despite greater age and worse clinical profiles, pharmacologic and exercise patients had similar CAC scores. However, the hazard ratio (95% CI) for mortality was substantially greater among pharmacologic patients: 2.39 (1.83-3.10). For each level of CAC abnormality, pharmacologic patients had >2-fold increased risk adjusted hazard ratio for all-mortality risk (p < 0.05 for each CAC level). Among propensity-matched exercise versus pharmacologic patients, the same findings were observed. CONCLUSIONS: Among patients referred for stress-rest SPECT-MPI and CAC scoring, pharmacologic patients have substantially increased mortality risk compared to exercise patients, despite having comparable levels of coronary atherosclerosis.

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Cardiovascular disease is the leading cause of death for individuals with end-stage renal disease. Due to concern about cardiac fitness, international guidelines support screening algorithms based on clinical risk factors for people with kidney failure who wish to consider kidney transplantation surgery. The stated aim of cardiac screening is to identify asymptomatic kidney transplantation candidates with potentially significant pathology that either allows risk stratification or facilitates intervention. This will enable some to proceed toward kidney transplant listing while others will be denied kidney transplantation due to perceived risks. The ultimate aim is to attenuate the risk for peri- or early postoperative cardiovascular mortality after kidney transplantation while maximizing the utility of scarce donor organs. However, heterogeneous recommendations for cardiac screening from international professional and/or society guidelines reflect the lack of evidence base to support published advice. Currently established screening strategies lack evidence for efficacy, incur substantial expense, and can be associated with significant risk for harm. In this Perspective article, the argument is made that current cardiac screening algorithms for asymptomatic kidney transplantation candidates are overzealous, counterproductive, and not in the best interests of the majority of people living with kidney failure and should be abolished.

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Due to a marked temporal decline in inducible myocardial ischemia over recent decades, most diagnostic patients now referred for cardiac stress testing have nonischemic studies. Among nonischemic patients, however, long-term risk is heterogeneous and highly influenced by a variety of clinical parameters. Herein, we review 8 factors that can govern long-term clinical risk: coronary risk factor burden; patient symptoms; exercise capacity and exercise test responses; the need for pharmacologic stress testing; autonomic function; musculoskeletal status; subclinical atherosclerosis; and psychosocial risk. To capture the clinical benefit provided by both assessing myocardial ischemia and these additional parameters, the authors propose that a cardiac stress tests report have an additional component beyond statements as to the likelihood of obstructive coronary artery disease and/or magnitude of ischemia. This added component could be a comment section designed to make referring physicians aware of aspects of long-term risk that may influence clinical management and potentially lead to changes in the intensity of risk factor management, frequency of follow-up, need for further testing, or other management decisions. In this manner, the increasingly frequent normal stress test result might more commonly influence treatment recommendations and even patient behavior, thus leading to improvement in patient outcomes even in the setting of normal stress test results.

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Evaluation of cardiac function during periods of stress is of key importance for the perioperative setting. Non-invasive hemodynamic monitors provide markers of cardiac function. This pilot study sought to evaluate the ability of a non-invasive hemodynamic monitor to detect cardiac stress during formal stress echocardiography testing. The primary goal was to compare the change in hemodynamic values during the pre/during/post phases of stress echocardiography testing in patients who had results negative versus positive for myocardial ischemia. Adult patients scheduled for outpatient cardiac stress testing were screened. Only patients scheduled for stress-echocardiography testing were consented. Patients with history of arrhythmias were excluded. During the testing, patients wore a cuff-based hemodynamic sensor (Nexfin system, Edwards Lifesciences). Data from the hemodynamic sensor were compared to the findings of the stress study. A total of 37 patients were enrolled, with 31 patients included for analysis. Five patients had stress studies positive for coronary ischemia. Comparison of the hemodynamic variables between patients who had a positive stress study versus negative showed a significant reduction in the percentage change in dP/dt and stroke volume from baseline (p < 0.05). This pilot study indicates that patients who have abnormal stress echocardiograms also have significantly reduced values from a noninvasive hemodynamic monitor. Further evaluation of the clinical utility of this technology, to assist in the care of patients at risk for cardiac ischemia, should be carried out.

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