Search

Advances in the prevention and treatment of cardiovascular disease (CVD) over the last decades have led to a marked reduction in mortality for CVD. Nevertheless, atherosclerosis leading to coronary artery disease and stroke remains one of the most common causes of death in the world. The usefulness of imaging tests in the early identification of disease led to identify subjects at major risk of poor outcomes, suggesting risk factor modification. The aim of this article is to analyze the state of art of combined imaging in patients at risk of CVD referred to MPI evaluation, to highlight the present and potential features able to provide incremental prognostic information to help clinicians in patient management and to reduce adverse events., (© 2023. The Author(s).)

Background: Cardiovascular risk models are based on traditional risk factors and investigations such as imaging tests. External validation is important to determine reproducibility and generalizability of a prediction model. We performed an external validation of t the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS) model, developed from a cohort of patients undergoing stress myocardial perfusion imaging., Methods: We included 3623 patients with suspected or known coronary artery disease undergoing stress single-photon emission computer tomography (SPECT) myocardial perfusion imaging at our academic center between January 2001 and December 2019., Results: In our study population, the J-ACCESS model underestimated the risk of major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and severe heart failure requiring hospitalization) within three-year follow-up. The recalibrations and updated of the model slightly improved the initial performance: C-statistics increased from 0.664 to 0.666 and Brier score decreased from 0.075 to 0.073. Hosmer-Lemeshow test indicated a logistic regression fit only for the calibration slope (P = .45) and updated model (P = .22). In the update model, the intercept, diabetes, and severity of myocardial perfusion defects categorized coefficients were comparable with J-ACCESS., Conclusion: The external validation of the J-ACCESS model as well as recalibration models have a limited value for predicting of three-year major adverse cardiac events in our patients. The performance in predicting risk of the updated model resulted superimposable to the calibration slope model., (© 2023. The Author(s).)

Background: The purpose of this study was to assess the prognostic value of cardiac 82 Rb positron emission tomography (PET)/computed tomography (CT) imaging in patients with myocardial ischemia of nonobstructive coronary arteries (INOCA)., Methods: We retrospectively evaluated 311 INOCA patients who underwent rest stress 82 Rb PET/CT. Cardiac end points were cardiac death, myocardial infarction, or late coronary revascularization. A parametric survival model was also used to identify how the variables influenced time to event., Results: During a median follow-up of 37 months (range 6-108), 23 (7%) cardiac events occurred. In patients with events total perfusion defect (TPD) was higher and myocardial flow reserve (MFR) lower compared to those without events (both P < .001). At multivariable Cox analysis, increased TPD (i.e., ≥ 5%) and reduced MFR (i.e., < 2) were predictors of events (both P < .001). At Weibull survival analysis, the highest probability of cardiac events and risk acceleration were observed in patients with both increased TPD and reduced MFR. Annualized event rate was higher in patients with reduced MFR compared to those with preserved MFR (P < .001)., Conclusion: In patients with INOCA, the combined evaluation of myocardial perfusion and coronary vascular function by 82 Rb PET/CT is able to identify those at higher risk of cardiac events., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: In patients with heart failure (HF) sequential imaging studies have demonstrated a relationship between myocardial perfusion and adrenergic innervation. We evaluated the feasibility of a simultaneous low-dose dual-isotope 123 I/ 99m Tc-acquisition protocol using a cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera., Methods and Results: Thirty-six patients with HF underwent simultaneous low-dose 123 I-metaiodobenzylguanidine (MIBG)/ 99m Tc-sestamibi gated CZT-SPECT cardiac imaging. Perfusion and innervation total defect sizes and perfusion/innervation mismatch size (defined by 123 I-MIBG defect size minus 99m Tc-sestamibi defect size) were expressed as percentages of the total left ventricular (LV) surface area. LV ejection fraction (EF) significantly correlated with perfusion defect size (P < .005), innervation defect size (P < .005), and early (P < .05) and late (P < .01) 123 I-MIBG heart-to-mediastinum (H/M) ratio. In addition, late H/M ratio was independently associated with reduced LVEF (P < .05). Although there was a significant relationship (P < .001) between perfusion and innervation defect size, innervation defect size was larger than perfusion defect size (P < .001). At multivariable linear regression analysis, 123 I-MIBG washout rate (WR) correlated with perfusion/innervation mismatch (P < .05)., Conclusions: In patients with HF, a simultaneous low-dose dual-isotope 123 I/ 99m Tc-acquisition protocol is feasible and could have important clinical implications., (© 2022. The Author(s).)

Background: Prevention and development of diagnostic and therapeutic techniques reduced morbidity and mortality for coronary artery disease (CAD). In this context, the cardiovascular risk assessment for major adverse cardiac events (MACE) at 2-year (CRAX2MACE) model for prediction of 2-year major adverse cardiac events was developed. We performed an external validation of this model., Methods: We included 1003 patients with suspected CAD undergoing stress-rest single-photon emission computed tomography myocardial perfusion imaging at our academic center between March 2015 and April 2019., Results: Considering the occurrence of MACE (death from any cause, acute myocardial infarction, or late coronary revascularization), for the CRAX2MACE model the area under the receiver operating characteristic curve was 0.612 and the Brier score was 0.061. The Hosmer-Lemeshow test estimated a non-optimal fit (χ 2 28, P < .001). Considering only hard events (cardiac death, acute myocardial infarction), the external validation of the CRAX2MACE model revealed a Brier score of 0.053 and an area under the receiver operating characteristic curve of 0.621. Hosmer-Lemeshow test was calculated by deciles and showed a poor fit (χ 2 31, P < .001)., Conclusion: CRAX2MACE model had a limited value for predicting 2-year major adverse cardiovascular events in an external validation cohort of patients with suspected CAD., (© 2021. American Society of Nuclear Cardiology.)

Background: To assess the incremental value of 18 F-fluorodeoxyglucose (FDG) cardiac positron emission tomography (PET) over dobutamine stress echocardiography (DSE) in predicting myocardial ischemia in patients with suspected coronary artery disease (CAD)., Methods: Forty-one patients with suspected CAD underwent within 7 days apart rest-stress cardiac PET with 82 Rb and DSE followed by cardiac 18 F-FDG PET imaging. 18 F-FDG images were scored on a 0 (no discernible uptake) to 2 (intense uptake) scale. Logistic regression analysis was performed to identify predictors of stress-induced ischemia. The incremental value of 18 F-FDG PET over DSE in detecting ischemia at 82 Rb PET cardiac imaging was assessed by the likelihood ratio chi-square and net reclassification index., Results: On 82 Rb-PET imaging, myocardial ischemia (ischemic total perfusion defect ≥ 5%) was detected in 20 (49%) patients. Inducible ischemia was found in 22 (54%) patients on DSE (biphasic or worsening response pattern in ≥ 1 segment) and in 21 (51%) patients on 18 F-FDG PET (uptake score of 2 in ≥ 1 segment). 18 F-FDG PET resulted as statistically significant predictor of ischemia on 82 Rb-PET. The addition of 18 F-FDG PET to DSE increased the likelihood of ischemia on 82 Rb-PET (P < .05). 18 F-FDG PET was able to reclassify the probability of stress-induced myocardial ischemia on both patient and vessel analyses., Conclusion: 18 F-FDG PET performed after dobutamine stress test may provide incremental value to DSE in the evaluation of myocardial ischemia. These results suggest that stress-induced myocardial ischemia can be imaged directly using 18 F-FDG PET after dobutamine stress test., (© 2021. American Society of Nuclear Cardiology.)

Background: We evaluated the prognostic value of changes in perfusion defect size (PDS) on serial MPS in patients treated with primary percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI)., Methods: We enrolled 112 patients treated with primary PCI after AMI who underwent two stress MPS within 1 month and after 6 months. Improvement in PDS was defined as a reduction ≥5%. Remodeling was defined as an increase in left ventricular (LV) end-diastolic volume index ≥20%. Cardiac events included cardiac death, nonfatal MI, unstable angina, repeated revascularization, and heart failure., Results: During a median follow-up of 86 months, 22 events occurred. Event rate was higher (P &lt; .01) in patients with worsening of PDS compared to those with unchanged or improved PDS. Moreover, patients with remodeling had a higher (P &lt; .001) event rate compared to those without. At Cox analysis, worsening of PDS and remodeling resulted independent predictors of events (both P &lt; .01). Patients with both worsening of PDS and remodeling had the worst event-free survival (P &lt;.001)., Conclusion: In patients treated with primary PCI after AMI, worsening of PDS and remodeling are associated to higher risk of events at long-term follow-up. Gated stress MPS improves risk stratification in these patients., (© 2021. American Society of Nuclear Cardiology.)

Background: Chronotropic incompetence is common in patients with cardiovascular disease and is associated with increased risk of adverse events. We assessed the incremental prognostic value of heart rate reserve (HRR) over stress myocardial perfusion single-photon emission computed tomography (MPS) findings in patients with suspected coronary artery disease (CAD)., Methods: We studied 866 patients with suspected CAD undergoing exercise stress-MPS as part of their diagnostic program. The primary study endpoint was all-cause mortality. All patients were followed for at least 5 years. HRR was calculated as the difference between peak exercise and resting HR, divided by the difference of age-predicted maximal and resting HR and expressed as percentage., Results: During 7 years follow-up, 61 deaths occurred, with a 7% cumulative event rate. Patients experiencing death were older (P < .001), and had a higher prevalence of male gender (P < .001) and diabetes (P < .05). Patients with event also had lower values of HRR (65% ± 27% vs 73% ± 18%, P < .0001) and higher prevalence of stress-induced myocardial ischemia (25% vs 8%, P < .0001). Male gender, HRR and stress-induced ischemia were independent predictors of all-cause mortality (all P < .01). HRR improved the prognostic power of a model including clinical data and MPS findings, increasing the global χ 2 from 66 to 82 (P < .005)., Conclusions: Chronotropic incompetence has independent and incremental prognostic value in predicting all-cause mortality in patients with suspected CAD undergoing exercise stress-MPS. Hence, the evaluation of HRR may further improve patients' risk stratification., (© 2021. The Author(s).)

Background: We evaluated the performance of conventional (C) single-photon emission computed tomography (SPECT) and cadmium-zinc-telluride (CZT)-SPECT in a large cohort of patients with suspected or known coronary artery disease (CAD) and compared the diagnostic accuracy of the two systems using machine learning (ML) algorithms., Methods and Results: A total of 517 consecutive patients underwent stress myocardial perfusion imaging (MPI) by both C-SPECT and CZT-SPECT. In the overall population, an excellent correlation between stress MPI data and left ventricular (LV) functional parameters measured by C-SPECT and by CZT-SPECT was observed (all P < .001). ML analysis performed through the implementation of random forest (RF) and k-nearest neighbors (NN) algorithms proved that CZT-SPECT has greater accuracy than C-SPECT in detecting CAD. For both algorithms, the sensitivity of CZT-SPECT (96% for RF and 60% for k-NN) was greater than that of C-SPECT (88% for RF and 53% for k-NN)., Conclusions: MPI data and LV functional parameters obtained by CZT-SPECT are highly reproducible and provide good correlation with those obtained by C-SPECT. ML approach showed that the accuracy and sensitivity of CZT-SPECT is greater than C-SPECT in detecting CAD., (© 2020. American Society of Nuclear Cardiology.)

Background: We evaluated if risk scores commonly used to predict the absence of significant stenosis at coronary computed tomography (CT) angiography are useful to predict a normal stress myocardial perfusion imaging (MPI) study., Methods: Our cohort included a total of 1422 consecutive patients with zero coronary artery calcium score (ZCS) who underwent 82 Rb PET/CT for evaluation of suspected coronary artery disease (CAD). Predictive models were constructed as reported by Genders et al. and Alshahrani et al., and the probability of abnormal summed stress score (SSS) and of reduced myocardial perfusion reserve (MPR) based on these risk scores was assessed., Results: In the overall population, the prevalence of abnormal SSS was 0.10 and the prevalence of reduced MPR was 0.17 (both P < .001).The observed frequencies of abnormal SSS and reduced MPR vs the probabilities predicted by the Genders and Alshahrani models were above the diagonal identity line, highlighting an underestimation of the observed occurrence by these models. The areas under the receiver operating characteristic curve of the Genders and Alshahrani models indicated lack of discriminative ability for predicting abnormal SSS (0.547 and 0.527) and reduced MPR (0.509 and 0.538). The Hosmer-Lemeshow test revealed that both models underestimated the observed occurrence of abnormal SSS and reduced MPR., Conclusions: Available models were unable to identify among patients with ZCS those with a low probability of a normal stress MPI study. Thus, an optimal approach to rule out from MPI patients without detectable coronary calcium still needs to be improved., (© 2020. American Society of Nuclear Cardiology.)

Background: We performed a systematic review and meta-analysis to investigate the prognostic value of stress myocardial perfusion single-photon emission computed tomography (MPS) in predicting adverse cardiovascular events in patients with chronic kidney disease (CKD)., Methods: Studies published from inception until July 2020 were identified by PubMed and Embase databases search. Studies were included if they evaluated CKD patients referred for stress MPS, providing data on adjusted hazard ratio (HR) for the occurrence of adverse events. For studies providing only non-adjusted HR, the univariable risk estimate was included in the analysis. Pooled HR and 95% confidence interval (CI) were estimated using a random effects model to compare patients with abnormal and normal MPS. Whenever possible, incidence rate ratio (IRR) was also calculated and pooled., Results: Sixteen eligible studies were identified including 7834 patients with a follow-up range from 1 to 4.4 years. Eleven articles included patients with end-stage renal disease (IV-V CKD stage), 3 articles with III-V CKD stage and 2 articles with I-V CKD stage. The pooled HR for the occurrence of adverse events was 2.02 (95% CI 1.68-2.42) and heterogeneity was 34%. Among the included studies, 5 reported the HR for the occurrence of hard events, with a pooled HR of 2.36 (95% CI 1.77-3.13). A total of 8 studies reported data useful to calculate the IRR in patients with normal and abnormal perfusion. The pooled IRR was 2.37 (95% CI 1.63-3.47) and heterogeneity was 60%. At meta-regression analysis, we found an association between HR for adverse events and age, hypertension and smoking, while no significant association was found between HR for hard events and demographic and clinical variables., Conclusions: In patients with CKD an abnormal myocardial perfusion at stress MPS is associated with adverse cardiovascular events., (© 2021. American Society of Nuclear Cardiology.)

Background: Chronotropic response to pharmacological stress test is blunted in patients with autonomic neuropathy. The relationship between heart rate (HR) changes during pharmacological stress test and cardiac autonomic dysfunction has not been fully investigated. We assessed the potential interplay between HR response (HRR) and myocardial innervation in patients with suspected or known coronary artery disease (CAD)., Methods and Results: We studied 71 patients with suspected or known CAD referred to pharmacological stress myocardial perfusion imaging and 123 I metaiodobenzylguanidine ( 123 I-MIBG) cardiac scintigraphy. HRR was calculated as the maximum percent change from baseline according to the formula: (peak HR - rest HR)/rest HR × 100. 123 I-MIBG heart-to-mediastinum (H/M) ratio was calculated and a late H/M ratio < 1.6 was considered abnormal. HRR progressively decreased with decreasing late H/M ratio (P for trend = 0.02) and a significant correlation between HRR and late H/M ratio (P = 0.03) was observed. The addition of HRR to a model including age, diabetes, known CAD, left ventricular ejection fraction, and stress-induced ischemia added incremental value in predicting an abnormal late H/M ratio, increasing the global chi-square from 8.09 to 13.8 (P = 0.02)., Conclusions: The relationship between HRR and cardiac sympathetic innervation in patients with suspected or known CAD confirms a strong interplay between cardiac response to stress tests and cardiac autonomic activation. This finding suggests that HRR may be used as a surrogate for assessing cardiac sympathetic function., (© 2020. American Society of Nuclear Cardiology.)

Background: We measured myocardial blood flow (MBF) and perfusion reserve (MPR) by dynamic CZT-SPECT and 82 Rb-PET in patients with suspected or known coronary artery disease (CAD) and compared the accuracy of the two methods in predicting obstructive CAD., Methods: Twenty-five patients with available coronary angiography data underwent 99m Tc-sestamibi CZT-SPECT and 82 Rb-PET cardiac imaging. Stress and rest MBF and MPR were calculated by both methods and compared. Diagnostic accuracies of CZT-SPECT and PET were also assessed using a receiver-operator-characteristic curve., Results: CZT-SPECT yielded similar baseline MBF, but higher hyperemic MBF and MPR values compared to PET. There was a modest correlation between the two methods for MPR (r = 0.56, P < .01). MPR by CZT-SPECT showed a good ability in identify a reduced MPR by PET, with an area under the curve of 0.85. A MPR cut-off of 2.5 was identified by CZT-SPECT for detection of abnormal MPR by PET, with a sensitivity, specificity and accuracy of 86%, 73% and 80%. The area under the curve for the identification of obstructive CAD by regional MPR were 0.83 for CZT-SPECT and 0.84 for PET (P = .90). At CZT-SPECT, a regional MPR of 2.1 provided the best trade-off between sensitivity and specificity for identifying obstructive CAD. Diagnostic accuracy of CZT-SPECT and PET using respective cut-off values was comparable (P = .62)., Conclusion: Hyperemic MBF and MPR values obtained by CZT-SPECT are higher than those measured by 82 Rb-PET imaging, with a moderate correlation between the two methods. CZT-SPECT shows good diagnostic accuracy for the identification of obstructive CAD. These findings may encourage the use of this new technique to a better risk stratification and patient management., (© 2020. American Society of Nuclear Cardiology.)

Background: The frequency of abnormal stress SPECT myocardial perfusion imaging (MPS) decreased over the past decades despite an increase in the prevalence of cardiovascular risk factors. These findings strengthen the need to develop more effective strategies for appropriately referring patients with suspected coronary artery disease (CAD) to cardiac imaging. The aim of this study was to develop pretest assessment models for predicting abnormal stress MPS., Methods: We included 5,601 consecutive patients with suspected CAD, who underwent stress MPS at our academic center. Two different models were considered: a basic model including age, gender, and anginal symptoms; and a clinical model including also diabetes, hypertension, hypercholesterolemia, smoking, and family history of CAD., Results: In patients with abnormal MPS, the basic model classified more than 75% of patients as intermediate risk, whereas only 23% were incorrectly classified as low risk. In patients with normal MPS, 45% were correctly classified as low risk and none as high risk. Basic and clinical models had a limited discriminating capacity (area under the receiver operating characteristic curve 0.644 for basic model and 0.647 for clinical model) between individuals with and without abnormal stress MPS. The decision curve analysis demonstrates a high net benefit across a range of threshold probabilities from ~ 15% to ~30% for both models., Conclusions: A pretest risk stratification based on traditional cardiovascular risk factors has a limited value for predicting an abnormal stress MPS in patients with suspected CAD. However, selecting a proper threshold probability enhances the appropriateness of referral to stress MPS., (© 2019. American Society of Nuclear Cardiology.)

Background: We assessed the prognostic value of structural abnormalities and coronary vasodilator function in diabetic patients referred to a PET/CT for suspected coronary artery disease (CAD)., Methods: We studied 451 diabetics and 451 nondiabetics without overt CAD and normal myocardial perfusion. Myocardial blood flow (MBF) was computed from the dynamic rest and stress imaging. Myocardial flow reserve (MFR) was defined as ratio of hyperemic to baseline MBF and was considered reduced when < 2., Results: During a mean follow-up of 44 months 33 events occurred. Annualized event rate (AER) was higher in diabetic than nondiabetic patients (1.4% vs 0.3%, P < .001). Diabetic patients with reduced MFR had higher AER compared to those with preserved MFR (3.3% vs 0.4%, P  < .001). At Cox analysis, age, BMI and reduced MFR were independent predictors of events in diabetic patients. Patients with diabetes and reduced MFR had lower event-free survival compared to nondiabetic patients and MFR < 2 (P < .001). Event-free survival was similar in patients with diabetes and normal MFR and those without diabetes and reduced MFR., Conclusions: Diabetic patients with reduced MFR had higher AER and lower event-free survival compared to those with preserved MFR and to nondiabetic patients., (© 2021. The Author(s).)

Background: We performed a meta-meta-analysis to evaluate the prognostic value of coronary flow reserve (CFR) assessed by cardiac positron emission tomography (PET) imaging in patients with suspected or known coronary artery disease (CAD)., Methods: Studies published until April 2019 were identified by database search. We included studies if they evaluated CFR by PET providing data on adjusted hazard ratio (HR) for the occurrence of adverse events. Annualized event rates were calculated and the incidence rate ratios with 95% confidence interval (CI) were estimated to compare patients with impaired and preserved CFR., Results: We identified 13 eligible articles including 11,867 patients with a follow-up ranging from 0.6 to 7.1 years. The HR for the occurrence of major adverse cardiac events (MACE) was reported in 11 studies and pooled HR was 1.93 (95% CI 1.65-2.27). The HR for the occurrence of hard events was reported in 5 studies and pooled HR was 3.11 (95% CI 1.88-5.14). Six studies reported data useful to calculate separately the incidence rate of MACE in patients with preserved and impaired CFR and pooled IRR was 2.26 (CI 95% 1.79-2.85). Three studies reported data useful to calculate separately the incidence rate of hard events in patients with preserved and impaired CFR and pooled IRR was 4.12 (CI 95% 3.08-5.51). At meta-regression analysis, we found an association between HR for MACE and gender, diabetes and hypertension, while no significant association was found between HR for hard events and demographic and clinical variables., Conclusion: In patients with suspected or known CAD, an impaired CFR is associated with adverse cardiovascular events. However, the large heterogeneity in study population underlines the need for further investigations to maximize the prognostic role of CFR.

Background: Breast attenuation may impact the diagnostic accuracy of stress myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT). We compared the performance of conventional (C)-SPECT and cadmium-zinc-telluride (CZT)-SPECT systems in women with low-intermediate likelihood of coronary artery disease (CAD)., Methods and Results: A total of 109 consecutive women underwent stress-optional rest MPI by both C-SPECT and CZT-SPECT. In the overall study population, a weak albeit significant correlation between total perfusion defect (TPD) measured by C-SPECT and CZT-SPECT was observed (r = 0.38, P < .001) and at Bland-Altman analysis the mean difference in TPD (C-SPECT minus CZT-SPECT) was 2.40% (P < .001). Overall concordance of semi-quantitative diagnostic performance between C-SPECT and CZT-SPECT was observed in 52 (48%) women with a κ value of 0.09. Normalcy rate was significantly higher using CZT-SPECT compared to C-SPECT (P < .001). Machine learning analysis performed through the implementation of J48 algorithm proved that CZT-SPECT has higher sensitivity, specificity, and accuracy than C-SPECT., Conclusions: In women with low-intermediate likelihood of CAD, there is a poor concordance of diagnostic performance between C-SPECT and CZT-SPECT, and CZT-SPECT allows better normalcy rate detection compared to C-SPECT.

Background: We performed a meta-analysis to compare the diagnostic performance of conventional SPECT (C-SPECT) and cadmium-zinc-telluride (CZT)-SPECT systems in detecting angiographically proven coronary artery disease (CAD)., Methods: Studies published between January 2000 and February 2018 were identified by database search. We included studies assessing C-SPECT or CZT-SPECT as a diagnostic test to evaluate patients for the presence of CAD, defined as at least 50% diameter stenosis on invasive coronary angiography. A study was eligible regardless of whether patients were referred for suspected or known CAD., Results: We identified 40 eligible articles (25 C-SPECT and 15 CZT-SPECT studies) including 7334 patients (4997 in C-SPECT and 2337 in CZT-SPECT studies). The pooled sensitivity and specificity were 85% and 66% for C-SPECT and 89% and 69% for CZT-SPECT imaging studies. The area under the curve was slightly higher for CZT-SPECT (0.89) compared to C-SPECT (0.83); accordingly, the summary diagnostic OR was 17 for CZT-SPECT and 11 for C-SPECT. The accuracy of the two tests slightly differs between C-SPECT and CZT-SPECT (chi-square 11.28, P < .05). At meta-regression analysis, no significant association between both sensitivity and specificity and demographical and clinical variables considered was found for C-SPECT and CZT-SPECT studies., Conclusions: C-SPECT and CZT-SPECT have good diagnostic performance in detecting angiographic proven CAD, with a slightly higher accuracy for CZT-SPECT. This result supports the use of the novel gamma cameras in clinical routine practices also considering the improvements in acquisition time and radiation exposure reduction.

Background: The frequency of abnormal stress single-photon emission computed tomography myocardial perfusion imaging (MPS) has decreased over the past decades despite an increase in the prevalence of cardiovascular risk factors. This study evaluated the temporal trend of abnormal stress MPS and its relationship with risk factors in a cohort of Italian subjects., Methods: We included all patients who underwent clinically indicated stress MPS at our academic center between January 2006 and December 2017. Patients were assessed for change in demographics, clinical symptoms, risk factors, and frequency of abnormal and ischemic MPS., Results: A total of 8,886 stress MPS studies were performed (3,350 abnormal). Age, male gender, diabetes, smoking, and angina were independent predictors of abnormal MPS. There was a slight decline in the frequency of abnormal (from 39 to 36%, P < 0.05) and ischemic (from 25 to 22%, P < 0.01) MPS during the study period, while the percentage of patients with hypertension, hypercholesterolemia, smoking, and angina increased. The Cochran-Mantel-Haenszel test indicates that the likelihood of having an abnormal MPS did not change over time for age, diabetes, smoking, and a history of coronary artery disease (CAD), increased for hypertension and hypercholesterolemia and decreased for male compared to female gender., Conclusions: In our cohort of Italian subjects, there was a slight temporal decline in the frequency of abnormal and ischemic MPS despite an increase over time in the prevalence of many cardiac risk factors. These results strengthen the need to develop more effective strategies for appropriately referring patients to cardiac imaging procedures.

Diabetes represents a worldwide increasing problem and cardiovascular disease is the most common cause of death in diabetic patients. Pathophysiology that links diabetes to cardiovascular disease is a complex and multifactorial phenomenon evolving over time and involving both large blood vessels (macrovasculature) and small blood vessels (microvasculature). Myocardial perfusion imaging (MPI) imaging by both single-photon emission computer tomography and positron emission tomography with different specific tracers has become an indispensable tool for discriminating normal from diseased myocardial tissues and left ventricular function and monitoring myocardial blood flows, leading to the evaluation of almost overall physiologic consequences of the macro- and microvascular impairment involved in diabetic patients. This review will provide an overview of the role of MPI in the diagnosis and risk assessment of patients with diabetes and suspected or known CAD.

Cardiac amyloidosis is a restrictive infiltrative cardiomyopathy burdened by high mortality. The two more common forms are immunoglobulin light-chain amyloidosis and transthyretin-related amyloidosis with different prognoses and treatments. However, distinguishing between them is challenging. Appropriate utilization of the different available imaging techniques in the evaluation of patients with known or suspected cardiac amyloidosis is mandatory. We report two cases with cardiac amyloidosis of different etiology and with distinct imaging patterns. In the first case, the negative 99m Tc-diphosphonate imaging was useful to support the diagnosis of cardiac amyloid light-chain; the second case emphasized the utility of whole-body scintigraphy in recognizing transthyretin-related cardiac amyloidosis and the potential role of cadmium-zinc-telluride SPECT imaging for the evaluation of segmental distribution of cardiac disease. Both cases support the growing interest in looking for noninvasive methods to type cardiac amyloidosis in the place of invasive myocardial biopsy highlighting both possibilities and limitations of available imaging techniques in diagnosis and treatment monitoring.

Background: A normal stress myocardial perfusion single-photon emission computed tomography (MPS) is associated with a good clinical outcome. New iterative algorithms, such as wide beam reconstruction (WBR), which improve image interpretation with half-dose or half-time acquisition, have been proposed for cardiac MPS. The aim of this study was to assess the long-term predictive value of a low-dose normal stress-only MPS with WBR using conventional Anger camera in patients with known or suspected coronary artery disease (CAD)., Methods and Results: A total of 2106 patients with known or suspected CAD and normal perfusion at half-dose stress-only MPS protocol were followed for a mean of 6.6 ± 2.7 years. MPS data were reconstructed with WBR iterative algorithm. End-point events were cardiac death or nonfatal myocardial infarction. Noncardiac death was considered the competing event. During follow-up, 149 cardiac events occurred with an annualized event rate of 1.2%. Independent predictors of cardiac events at Cox analysis were age, male gender, diabetes mellitus, previous myocardial infarction and the need for pharmacologic stress testing. At Fine-Gray analysis the cumulative incidence of cardiac events progressively increases with age and in the presence of diabetes for any combination of gender and stress type. Survival tree analysis confirmed that long-term prognosis considerably varies according of risk factors profile., Conclusions: Low-dose normal stress-only WBR MPS has a reliable long-term prognostic value in patients with suspected or known CAD. This finding supports the introduction of such a method into clinical practice with a consistent dose optimization in the interest of patients and exposed staff.

Background: We evaluated the warranty period of a normal stress myocardial perfusion single-photon emission computed tomography (MPS) in hypertensive patients., Methods and Results: A total of 471 consecutive hypertensive patients with suspected coronary artery disease and normal perfusion at stress MPS were followed for a mean of 76 ± 21 months. Endpoint events were cardiac death or nonfatal myocardial infarction. With Cox analysis, age (hazard ratio 1.1, P < .005) and stress test type (hazard ratio 2.7, P < .005) were independent predictors of events. With parametric Weibull analysis, patients ≤60 years old undergoing exercise stress test remained at low risk for the entire length of follow-up, while the highest probability of events and the major risk acceleration were observed in those > 60 years old who underwent pharmacologic stress test. In patients undergoing exercise test, peak systolic blood pressure (BP; hazard ratio 1.1, P < .005) emerged as predictor of events, and only subjects with peak systolic BP < 160 mmHg remained at low risk for the entire length of follow-up. In contrast, for patients with peak systolic BP ≥180 mmHg, the time to achieve a cumulative cardiac risk level of 3% was 18 months., Conclusions: In hypertensive patients, the warranty period of a normal stress MPS varies according to stress type and peak systolic BP. A normal stress MPS can be considered reassuring in subjects ≤60 years old who performed exercise stress test and a peak systolic BP < 160 mmHg.

Background: Coronary artery calcium (CAC) can be used to estimate vascular age in adults, providing a convenient transformation of CAC from Agatston units into a year's scale. We investigated the role of coronary vascular age in predicting stress-induced myocardial ischemia in subjects with suspected coronary artery disease (CAD)., Methods: A total of 717 subjects referred to CAC scoring and 82 Rb PET/CT stress-rest myocardial perfusion imaging for suspected CAD were studied. CAC score was measured according to the Agatston method and coronary vascular age by equating estimated CAD risk for chronological age and CAC using the formula 39.1 + 7.25 × ln(CAC + 1)., Results: Stress-induced ischemia was present in 105 (15%) patients. Mean chronological age, CAC score, and coronary vascular age were higher (all P < .001) in patients with ischemia compared to those without. At incremental analysis, the global Chi square increased from 41.26 to 68.77 (P < .001) when chronological age was added to clinical variables. Including vascular age in the model, the global Chi square further increased from 68.77 to 106.38 (P < .001). Adding chronological age to clinical data, continuous net reclassification improvement (cNRI) was 0.57, while adding vascular age to clinical data and chronological age cNRI was 0.62. At decision curve analysis, the model including vascular age was associated with the highest net benefit compared to the model including only clinical data, to the model including chronological age and clinical data, and to a strategy considering that all patients had ischemia. The model including vascular age also showed the largest reduction in false-positive rate without missing any ischemic patients., Conclusions: In subjects with suspected CAD, coronary vascular age is strongly associated with stress-induced ischemia. The communication of a given vascular age would have a superior emotive impact improving observance of therapies and healthier lifestyles.

Background: Left ventricular (LV) remodeling is associated with adverse cardiovascular events. We evaluated the added prognostic value of LV shape index (SI) assessed by gated single-photon emission tomography (SPECT) in patients without known coronary artery disease (CAD)., Methods and Results: We studied 674 patients with normal myocardial perfusion and normal LV ejection fraction (EF) on stress gated SPECT imaging. An automated software program was used to calculate end-diastolic and end-systolic LVSI. An LVSI ≤ 0.54 at end-systole was considered normal. Follow-up was 96% complete with a median follow-up of 37 months. During follow-up, 25 events occurred (3.8% cumulative event rate). Event-free survival was lower in patients with abnormal end-systolic LVSI (P < .001). Age (P = .021), diabetes (P = .048), and end-systolic LVSI (P < .001) were independent predictors of events. LVSI added prognostic information increasing the global chi-square of the model including age and diabetes from 15.15 to 25.97 (P < .001). The effect of diabetes on hazard ratio increased with increasing values of end-systolic LVSI. The probability of events at 48 months predicted by Weibull analysis progressively increased with increasing values of end-systolic LVSI and was higher in patients with diabetes as compared to those without. Decision curve analyses indicate that the model including end-systolic LVSI resulted in an increased net benefit between 5% and 30% threshold probability, indicating superior estimation of outcomes at low threshold probability levels., Conclusions: The evaluation of LVSI may identify patients with early-stage LV remodeling and at higher risk of adverse cardiac events, even in the presence of normal myocardial perfusion.

The concept of warranty period, the duration of time during which the patient's risk remains low, is appealing. However, some points remain to be resolved before its translation in the clinical arena. Methodological issues should be standardized in order to compare the results of studies in different patient populations. Also, the definition of a "normal" study should always take into consideration the history of prior revascularization, the achieved level of exercise, and the stressor used. The promise of warranty can be questioned by the patient's baseline demographic and clinical characteristics and may also be influenced by life-style modification in the course of the follow-up. The "warranty period" concept should shift from data reflecting the time to a cardiac event to the development of ischemia, given an opportunity for intervention before a cardiac event occurs. In this context, clarify the role of serial imaging can be extremely useful, in particular to evaluate if and when retesting a patient after a normal scan.

Background: We compared the long-term prognostic value of coronary artery calcium (CAC) scanning, coronary computed tomographic angiography (CCTA), and stress single-photon emission computed tomography myocardial perfusion imaging (MPI) in patients with suspected coronary artery disease (CAD)., Methods and Results: A total of 164 patients were studied. CAC score was measured according to the Agatston method and patients were categorized into 3 groups (0, 1-300, and >300). The following events were recorded: cardiac death, nonfatal infarction, and unstable angina requiring revascularization. Follow-up was 95% complete during a mean period of 82 ± 34 months. During follow-up, 22 events occurred (14% cumulative event rate). Event-free survival decreased with worsening of CAC score category (P < .001) and it was worse (P < .001) in patients with significant CAD (≥50% stenosis) and in those with stress-induced ischemia (summed difference score >2). At multivariable analysis, CAC (P = .001) and ischemia (P = .012) were independent predictors of events. MPI data added prognostic information to a model including clinical variables, CAC and CCTA findings, increasing the global Chi-square from 36.2 to 41.9 (P = .013). The decision curve analyses in patients with CAC score >0 indicate that the prognostic model including MPI resulted in a higher net benefit across a wide range of decision threshold probabilities., Conclusions: CAC and MPI, but not CCTA, are independent predictors of cardiac events. Stress MPI appears to improve risk stratification over clinical variables, CAC scanning and CCTA findings.

Background: Diabetes mellitus induces structural and functional cardiac alterations that can result in heart failure. Left ventricular (LV) shape is a dynamic component of cardiac geometry influencing its contractile function. However, few data are available comparing LV shape index in diabetic and nondiabetic patients without overt coronary artery disease after balancing for coronary risk factors., Methods: We studied 1168 patients with normal myocardial perfusion and normal LV ejection fraction on stress gated single-photon emission computed tomography (SPECT) imaging. To account for differences in baseline characteristics between diabetic and nondiabetic patients, we created a propensity score-matched cohort considering clinical variables, coronary risk factors, and stress type., Results: Before matching, diabetic patients were older, had higher prevalence of male gender and coronary risk factors, and higher end-diastolic and end-systolic LV shape index. After matching, all clinical characteristics were comparable between diabetic and nondiabetic patients, but diabetic patients still had higher end-diastolic and end-systolic LV shape index (both P < .001). At multivariable linear regression analysis, diabetes was a strong predictor of end-systolic LV shape index in the overall study population and in the propensity-matched cohort., Conclusions: Diabetic patients have higher values of LV shape index compared to nondiabetic patients also after balancing clinical characteristics by propensity score analysis. Shape indexes assessment by gated SPECT may be useful for identifying early LV remodeling in patients with diabetes.

Background: We assessed the relationship between coronary artery calcium (CAC) score, myocardial blood flow (MBF) and coronary flow reserve (CFR) in patients undergoing hybrid 82 Rb positron emission tomography (PET)/computed tomography (CT) imaging for suspected CAD. We also evaluated if CAC score is able to predict a reduced CFR independently from conventional coronary risk factors., Methods: A total of 637 (mean age 58 ± 13 years) consecutive patients were studied. CAC score was measured according to the Agatston method and patients were categorized into 4 groups (0, 0.01-99.9, 100-399.9, and ≥400). Baseline and hyperemic MBF were automatically quantified. CFR was calculated as the ratio of hyperemic to baseline MBF and it was considered reduced when <2., Results: Global CAC score showed a significant inverse correlation with hyperemic MBF and CFR (both P < .001), while no correlation between CAC score and baseline MBF was found. At multivariable logistic regression analysis age, diabetes and CAC score were independently associated with reduced CFR (all P < .001). The addition of CAC score to clinical data increased the global chi-square value for predicting reduced CFR from 81.01 to 91.13 (P < .01). Continuous net reclassification improvement, obtained by adding CAC score to clinical data, was 0.36., Conclusions: CAC score provides incremental information about coronary vascular function over established CAD risk factors in patients with suspected CAD and it might be helpful for identifying those with a reduced CFR.

Treadmill exercise electrocardiogram (ECG) is one of the most commonly used noninvasive tests for the assessment of ischemic heart disease (IHD). Sex-specific challenges in diagnostic and prognostic tests methods for IHD outlined the importance of pretest probability evaluation and referral bias using risk-prediction charts available for both asymptomatic and symptomatic women. Accordingly, exercise ECG has been indicated as the initial test for the symptomatic women at intermediate risk of IHD who has a normal resting ECG and is capable of maximal exercise. However, the difficulties of using exercise testing for diagnosing IHD in women have led to an initial speculation that stress imaging may be preferred to standard stress testing. This editorial analyzed a large body of evidence on the diagnostic and prognostic powers of treadmill ECG and exercise myocardial perfusion imaging (MPI) according to new advanced imaging technologies.

Background: Transient ischemic dilation (TID) of the left ventricle during stress myocardial perfusion SPECT (MPS) has been shown to be a useful marker of severe coronary artery disease (CAD). However, investigations in diabetic patients with available coronary angiographic data are still limited. We evaluated the incremental diagnostic value of TID in identifying the presence of angiographically severe CAD in diabetic patients., Methods and Results: TID ratio values were automatically derived from rest-stress MPS in 242 diabetic patients with available coronary angiography data. A cutoff of ≥1.19 was considered to represent TID. Severe CAD (≥70% stenosis in the proximal left anterior descending artery or the left main artery, or ≥90% stenosis in two or three vessels) was identified in 69 (29%) patients. At multivariate analysis, the best independent predictors of severe CAD were summed stress score and TID (both P < .001). At incremental analysis, the addition of TID improved the power of a model including clinical data and summed stress score, increasing the global χ(2) value from 14.3 to 28.2 (P < .01). The best cutoff of summed stress score for identifying patients with severe CAD was ≥8. When the TID ratio was considered in patients with summed stress score between 3 and 7, the sensitivity for diagnosing severe CAD significantly improved from 71% to 77% (P < .05). In the overall study population, the net reclassification improvement by adding TID to a model including clinical data and summed stress score in the prediction of severe CAD was 0.40 (P < .005)., Conclusions: TID ratios obtained from rest-stress MPS provide incremental diagnostic information to standard perfusion analysis for the identification of severe and extensive CAD in diabetic patients.

Context: Congenital hypothyroidism (CH) is a common endocrine disorder with an incidence of 1:3000- 4000 newborns. In 80-85% of cases, CH is caused by defects in thyroid organogenesis, resulting in absent, ectopically located, and/or severely reduced gland, all conditions indicated as "thyroid dysgenesis" (TD). A higher prevalence of congenital heart diseases has been documented in children with CH compared to the general population. This association suggests a possible pathogenic role of genes involved in both heart and thyroid development. Among these, it can be included Isl1, a transcription factor containing a LIM homeodomain that is expressed in both thyroid and heart during morphogenesis., Objective: In the present study, we investigate the role of ISL1 in the pathogenesis of TD., Settings and Patients: By single stranded conformational polymorphism, we screened for mutations the entire ISL1 coding sequence in 96 patients with TD and in 96 normal controls., Results: No mutations have been found in patients and controls., Conclusion: Our data indicate that, despite the relevant role of ISL1 in thyroid and heart morphogenesis, mutations in its coding region are not associated with TD in our group of patients.

Aim: In 80-85% of cases, congenital hypothyroidism is associated with thyroid dysgenesis (TD), but only in a small percentage of cases mutations in thyroid transcription factors (NKX2.1, PAX8, FOXE1, and NKX2.5) have been associated with the disease. Several studies demonstrated that the activity of the transcription factors can be modulated by the interaction with other proteins, such as coactivators and co-repressors, and TAZ (transcriptional co-activator with PDZ-binding motif or WWTR1) is a co-activator interacting with both NKX2.1 and PAX8. In the present study we investigate the role of TAZ in the pathogenesis of TD., Material and Methods: By Single Stranded Conformational Polymorphism, we screened the entire TAZ coding sequence for mutations in 96 patients with TD and in 96 normal controls., Results: No mutations were found in patients and controls, but we found several polymorphisms in both groups. No significant differences could be demonstrated in the prevalence of the mutations between patients and controls., Conclusions: Our data indicate that TAZ mutations are not a cause of TD in the series of patients studied.