Impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic perfusion defect and myocardial flow reserve.

PURPOSE: We evaluated the impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic total perfusion defect (ITPD) and myocardial flow reserve (MFR) as assessed by 82Rb positron emission tomography (PET)/computed tomography (CT) imaging. METHODS: The study included 102 patients referred to 82Rb PET/CT myocardial perfusion imaging before and after coronary revascularization. All patients were followed for the occurrence of cardiovascular events (cardiac death, nonfatal myocardial infarction, repeated revascularization, and heart failure) after the second imaging study. RESULTS: During a median follow-up of 20 months, 21 events occurred. The clinical characteristics were comparable between patients with and without events. In the overall study population, after revascularization, there was a significant reduction (P < 0.001) of ITPD, while hyperemic myocardial blood flow (MBF) (P < 0.01) and MFR (P < 0.05) significantly improved. Event rate was higher in patients with ITPD (P < 0.005) or MFR (P < 0.001) worsening compared to those with unchanged or improved ITPD or MFR. At Cox univariable analysis, ITPD and MFR worsening resulted in predictors of events (both P < 0.05). Patients with worsening of both ITPD and MFR had the worst event-free survival (log-rank 32.9, P for trend < 0.001). CONCLUSIONS: In patients with stable CAD, worsening of ITPD and MFR after revascularization procedures is associated with higher risk of cardiovascular events. Follow-up MPI with 82Rb PET/CT may improve risk stratification in patients submitted to coronary revascularization.

Lutetium [177Lu]-DOTA-TATE in gastroenteropancreatic-neuroendocrine tumours: rationale, design and baseline characteristics of the Italian prospective observational (REAL-LU) study.

PURPOSE: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [177Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [177Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. METHODS: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [177Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [177Lu]Lu-DOTA-TATE for GEP-NETs in Italy. RESULTS: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [177Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. CONCLUSION: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. STUDY REGISTRATION: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1.

Late-onset mucopolysaccharidosis type IIIA mimicking Usher syndrome.

Mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo syndrome type A) is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the SGSH gene encoding N-sulfoglucosamine sulfohydrolase, an enzyme involved in the degradation of heparan sulfate. MPS IIIA is typically characterized by neurocognitive decline and hepatosplenomegaly with childhood onset. Here, we report on a 53-year-old male subject initially diagnosed with Usher syndrome for the concurrence of retinitis pigmentosa and sensorineural hearing loss. Clinical exome sequencing identified biallelic missense variants in SGSH, and biochemical assays showed complete deficiency of sulfamidase activity and increased urinary glycosaminoglycan excretion. Reverse phenotyping revealed left ventricle pseudo-hypertrophy, hepatosplenomegaly, bilateral deep white matter hyperintensities upon brain MRI, and decreased cortical metabolic activity by PET-CT. On neuropsychological testing, the proband presented only partial and isolated verbal memory deficits. This case illustrates the power of unbiased, comprehensive genetic testing for the diagnosis of challenging mild or atypical forms of MPS IIIA.

Prognostic value of myocardial perfusion imaging by cadmium zinc telluride single-photon emission computed tomography in patients with suspected or known coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: Aim of this study was to define the prognostic value of stress myocardial perfusion imaging by cadmium zinc telluride (CZT) single-photon emission computed tomography (SPECT) for prediction of adverse cardiovascular events in patients with known or suspected coronary artery disease (CAD). METHODS AND RESULTS: Studies published until November 2022 were identified by database search. We included studies using stress myocardial perfusion imaging by CZT-SPECT to evaluate subjects with known or suspected CAD and providing primary data of adverse cardiovascular events. Total of 12 studies were finally included recruiting 36,415 patients. Pooled hazard ratio (HR) for the occurrence of adverse events was 2.17 (95% confidence interval, CI, 1.78-2.65) and heterogeneity was 66.1% (P = 0.001). Five studies reported data on adjusted HR for the occurrence of adverse events. Pooled HR was 1.69 (95% CI, 1.44-1.98) and heterogeneity was 44.9% (P = 0.123). Seven studies reported data on unadjusted HR for the occurrence of adverse events. Pooled HR was 2.72 (95% CI, 2.00-3.70). Nine studies reported data useful to calculate separately the incidence rate of adverse events in patients with abnormal and normal myocardial perfusion. Pooled incidence rate ratio was 2.38 (95% CI, 1.39-4.06) and heterogeneity was 84.6% (P < 0.001). The funnel plot showed no evidence of asymmetry (P = 0.517). At meta-regression analysis, we found an association between HR for adverse events and presence of angina symptoms and family history of CAD. CONCLUSIONS: Stress myocardial perfusion imaging by CZT-SPECT is a valuable noninvasive prognostic indicator for adverse cardiovascular events in patients with known or suspected CAD.

Combined evaluation of CAC score and myocardial perfusion imaging in patients at risk of cardiovascular disease: where are we and what do the data say.

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.

External validation and update of the J-ACCESS model in an Italian cohort of patients undergoing stress myocardial perfusion imaging.

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.

Prediction of outcome by 82Rb PET/CT in patients with ischemia and nonobstructive coronary arteries.

BACKGROUND: The purpose of this study was to assess the prognostic value of cardiac 82Rb 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 82Rb 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 82Rb PET/CT is able to identify those at higher risk of cardiac events.

Impact of COVID-19 infection on short-term outcome in patients referred to stress myocardial perfusion imaging.

PURPOSE: We assessed the impact of COVID-19 infection on cardiovascular events in patients with suspected or known coronary artery disease (CAD) referred to stress single-photon emission computed tomography myocardial perfusion imaging (MPS). METHODS: A total of 960 consecutive patients with suspected or known CAD were submitted by referring physicians to stress MPS for assessment of myocardial ischemia between January 2018 and June 2019. All patients underwent stress-optional rest MPS. Perfusion defects were quantitated as % of LV myocardium and expressed as total perfusion defect (TPD), representing the defect extent and severity. A TPD ≥ 5% was considered abnormal. RESULTS: During a mean follow-up of 27 months (range 4-38) 31 events occurred. Moreover, 55 (6%) patients had a COVID-19 infection. The median time from index MPS to COVID-19 infection was 16 months (range 6-24). At Cox multivariable analysis, abnormal MPS and COVID-19 infection resulted as independent predictors of events. There were no significant differences in annualized event rate in COVID-19 patients with or without abnormal MPS (p = 0.56). Differently, in patients without COVID-19, the presence of abnormal MPS was associated with higher event rate (p < .001). Patients with infection compared to those without had a higher event rate in the presence of both normal and abnormal TPD. CONCLUSION: In patients with suspected or known CAD, the presence of COVID-19 infection during a short-term follow-up was associated with a higher rate of cardiovascular events.

Regional myocardial perfusion imaging in predicting vessel-related outcome: interplay between the perfusion results and angiographic findings.

BACKGROUND: Despite myocardial perfusion imaging (MPI) by cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera is largely used in the diagnosis and risk stratification of patients with suspected or known coronary artery disease (CAD), no data are available on the prognostic value of a regional MPI evaluation. We evaluated the prognostic value of regional MPI by the CZT camera in predicting clinical outcomes at the vessel level in patients with available angiographic data. METHODS AND RESULTS: Five hundred and forty-one subjects with suspected or known CAD referred to 99mTc-sestamibi gated CZT-SPECT cardiac imaging and with available angiographic data were studied. Both regional total perfusion deficit (TPD) and ischemic TPD (ITPD) were calculated separately for each vascular territory (left anterior descending, left circumflex, and right coronary artery). The outcome end points were cardiac death, target vessel-related myocardial infarction, or late coronary revascularization. The prevalence of CAD ≥ 50%, regional stress TPD, and regional ITPD was significantly higher in vessels with events as compared to those without (both P < 0.001). The receiver operating characteristics area under the curve for regional ITPD for the identification of vessel-related events was 0.81 (95% confidence interval 0.75-0.86). An ITPD value of 2.0% provided the best trade-off for identifying the vessel-related event. At multivariable analysis, both CAD ≥ 50% and ITPD ≥ 2.0% resulted in independent predictors of events. CONCLUSIONS: Regional myocardial perfusion assessed by the CZT camera demonstrated good reliability in predicting vessel-related events in patients with suspected or known CAD.

Prognostic value of myocardial perfusion imaging in patients with chronic kidney disease: A systematic review and meta-analysis.

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.

Simultaneous assessment of myocardial perfusion and adrenergic innervation in patients with heart failure by low-dose dual-isotope CZT SPECT imaging.

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 123I/99mTc-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 123I-metaiodobenzylguanidine (MIBG)/99mTc-sestamibi gated CZT-SPECT cardiac imaging. Perfusion and innervation total defect sizes and perfusion/innervation mismatch size (defined by 123I-MIBG defect size minus 99mTc-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) 123I-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, 123I-MIBG washout rate (WR) correlated with perfusion/innervation mismatch (P < .05). CONCLUSIONS: In patients with HF, a simultaneous low-dose dual-isotope 123I/99mTc-acquisition protocol is feasible and could have important clinical implications.

A machine learning-based approach to directly compare the diagnostic accuracy of myocardial perfusion imaging by conventional and cadmium-zinc telluride SPECT.

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.

Diagnostic value of clinical risk scores for predicting normal stress myocardial perfusion imaging in subjects without coronary artery calcium.

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 82Rb 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.

Prognostic value of heart rate reserve in patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging.

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 χ2 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.

Effect of changes in perfusion defect size during serial stress myocardial perfusion imaging on cardiovascular outcomes in patients treated with primary percutaneous coronary intervention after myocardial infarction.

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 < .01) in patients with worsening of PDS compared to those with unchanged or improved PDS. Moreover, patients with remodeling had a higher (P < .001) event rate compared to those without. At Cox analysis, worsening of PDS and remodeling resulted independent predictors of events (both P < .01). Patients with both worsening of PDS and remodeling had the worst event-free survival (P <.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.

Incremental value of 18F-FDG cardiac PET imaging over dobutamine stress echocardiography in predicting myocardial ischemia in patients with suspected coronary artery disease.

BACKGROUND: To assess the incremental value of 18F-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 82Rb and DSE followed by cardiac 18F-FDG PET imaging. 18F-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 18F-FDG PET over DSE in detecting ischemia at 82Rb PET cardiac imaging was assessed by the likelihood ratio chi-square and net reclassification index. RESULTS: On 82Rb-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 18F-FDG PET (uptake score of 2 in ≥ 1 segment). 18F-FDG PET resulted as statistically significant predictor of ischemia on 82Rb-PET. The addition of 18F-FDG PET to DSE increased the likelihood of ischemia on 82Rb-PET (P < .05). 18F-FDG PET was able to reclassify the probability of stress-induced myocardial ischemia on both patient and vessel analyses. CONCLUSION: 18F-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 18F-FDG PET after dobutamine stress test.

External validation of the CRAX2MACE model in an Italian cohort of patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging.

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 (χ2 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 (χ2 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.

Effects of the COVID-19 pandemic on myocardial perfusion imaging for ischemic heart disease.

PURPOSE: We assessed the effects of the COVID-19 pandemic on myocardial perfusion imaging (MPI) for ischemic heart disease during the lockdown imposed by the Italian Government. METHODS: We retrospectively reviewed the number and the findings of stress single-photon emission computed tomography (SPECT)-MPI performed between February and May 2020 during the COVID-19 pandemic at the University of Napoli Federico II. The number and the findings of stress SPECT-MPI studies acquired in the corresponding months of the years 2017, 2018, and 2019 were also evaluated for direct comparison. RESULTS: The number of stress SPECT-MPI studies performed during the COVID-19 pandemic (n = 123) was significantly lower (P < 0.0001) compared with the mean yearly number of procedures performed in the corresponding months of the years 2017, 2018, and 2019 (n = 413). Yet, the percentage of abnormal stress SPECT-MPI studies was similar (P = 0.65) during the pandemic (36%) compared with the mean percentage value of the corresponding period of the years 2017, 2018, and 2019 (34%). CONCLUSION: The number of stress SPECT-MPI studies was significantly reduced during the COVID-19 pandemic compared with the corresponding months of the previous 3 years. The lack of difference in the prevalence of abnormal SPECT-MPI studies between the two study periods strongly suggests that many patients with potentially abnormal imaging test have been missed during the pandemic.

Prognostic value of coronary vascular dysfunction assessed by rubidium-82 PET/CT imaging in patients with resistant hypertension without overt coronary artery disease.

PURPOSE: The identification of coronary vascular dysfunction may enhance risk stratification in patients with resistant hypertension (RH). We evaluated if impaired coronary vascular function, assessed by rubidium-82 (82Rb) positron emission tomography/computed tomography (PET/CT) imaging, is associated with increased cardiovascular risk in patients with hypertension without overt coronary artery disease (CAD). METHODS: We studied 517 hypertensive subjects, 26% with RH, without overt CAD, and with normal stress-rest myocardial perfusion imaging at 82Rb PET/CT. The outcome end points were cardiac death, nonfatal myocardial infarction, coronary revascularization, and admission for heart failure. RESULTS: Over a median of 38 months (interquartile range 26 to 50), 21 cardiac events (4.1% cumulative event rate) occurred. Patients with RH were older (p < 0.05) and had a higher prevalence of left ventricular hypertrophy (p < 0.001), a lower hyperemic myocardial blood flow (MBF), and myocardial perfusion reserve (MPR) (both p < 0.001) compared to those without. Conversely, coronary artery calcium content and baseline MBF were not different between patients with and without RH. At univariable Cox regression analysis, age, RH, left ventricular ejection fraction, coronary artery calcium score, and reduced MPR were significant predictors of events. At multivariable analysis, age, RH, and reduced MPR (all p < 0.05) were independent predictors of events. Patients with RH and reduced MPR had the highest risk of events and the major risk acceleration over time. CONCLUSION: The findings suggest that the assessment of coronary vascular function may enhance risk stratification in patients with hypertension.

Prognostic value of coronary flow reserve in patients with suspected or known coronary artery disease referred to PET myocardial perfusion imaging: A meta-analysis.

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.