Normal Myocardial Perfusion Imaging Research Articles

Prognostic Value of Coronary Flow Capacity by 82Rb PET in Patients With Suspected Coronary Artery Disease and Normal Myocardial Perfusion at Semiquantitative Imaging Analysis.

Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and myocardial flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. We assessed the prognostic value of CFC derived from 82Rb positron emission tomography/computed tomography in patients with suspected coronary artery disease and normal myocardial perfusion imaging. We studied 1967 patients with suspected coronary artery disease and normal myocardial perfusion at the semiquantitative analysis of stress/rest cardiac 82Rb positron emission tomography/computed tomography imaging. Coronary artery calcium scores were calculated and categorized into 3 groups: 0, 0.1 to 99.9, and ≥100. Patients were classified as having myocardial steal, severely reduced CFC, moderately reduced CFC, mildly reduced CFC, minimally reduced CFC, or normal flow using previously defined thresholds. The outcome end points were myocardial infarction and cardiac death, whichever occurred first. During a mean time of 41±27 months, 49 events occurred (2.5% cumulative event rate, with an annualized event rate of 0.5% person-years). At multivariable Cox analysis, coronary artery calcium score categories and impaired CFC resulted as independent predictors of events (both P<0.001). The annualized event rate was higher in patients with impaired CFC compared with those with normal CFC (P<0.05). Kaplan-Meier analysis showed that patients with impaired CFC were at the highest risk of events. In patients with suspected coronary artery disease and normal myocardial perfusion, impaired CFC is associated with a higher risk of cardiac events. Evaluating CFC can help identify patients' candidates for additional therapies to prevent future events.

Left Ventricular Wall Motion as an Additional Valuable Parameter in Diabetic Patients with Normal Myocardial Perfusion Imaging.

Gated SPECT is an established technique for assessment of left ventricular function in cardiovascular disease patients. However, there is little information about the influence of diabetes mellitus on gated SPECT parameters. This study was established to assess gated SPECT parameters in Diabetes Mellitus (DM) and non-diabetes mellitus (non-DM) patients with normal Myocardial Perfusion Imaging (MPI). In this analytical cross-sectional study, 314 patients (157 DM, 157 non-DM) with normal MPI were enrolled. Prevalence of risk factors for CAD like hypertension (HTN), and dyslipidemia were found to be significantly higher (p <0.01) in DM patients compared to non-DM. No statistically significant difference was observed among the TID, ESV, EDV, PFR, TTPF, and Wall Thickness (WT) parameters between DM and non-DM patients. Wall motion (Wm) in DM patients was significantly higher compared to non-DM patients. (3.9 ± 0.51 vs. 2.69 ± 0.48 for DM and non-DM patients, respectively, p-value:0.01). Also, there was no significant difference in Wm in the two groups with and without HTN. This shows the independent effect of DM on the Wm. This study believes that the Wm parameter should be noted for the early diagnosis or prevention of heart disease in DM patients. These findings can indicate the gradual changes in the movements of the left ventricle and the beginning of the progression of diabetic cardiomyopathy.

Prognostic value of modified coronary flow capacity by rubidium-82 pet/ct in patients with suspected cad and normal myocardial perfusion imaging

Prognostic value of modified coronary flow capacity by rubidium-82 pet/ct in patients with suspected cad and normal myocardial perfusion imaging

Association of epicardial fat volume with subclinical myocardial damage in patients with type 2 diabetes mellitus.

In type 2 diabetes mellitus (T2DM) patients, left ventricular systolic dyssynchrony (LVSD) with normal left ventricular ejection fraction (LVEF) and normal myocardial perfusion could referred to as subclinical myocardial damage, which is difficult to diagnose at an early stage. Epicardial adipose tissue, a distinctive heart-specific visceral fat, is closely related to various cardiovascular diseases. The objective of this study was to investigate the correlation between epicardial fat volume (EFV) and subclinical myocardial damage in T2DM patients. This retrospective cross-sectional study included 117 T2DM patients with normal myocardial perfusion by single photon emission computed tomography-computed tomography (SPECT-CT) and normal LVEF by echocardiography. The study was conducted from January 2018 to December 2022. Patient data were collected through electronic medical records including basic patient information, medical history, laboratory tests, and medication data. The EFV was quantified through a non-contrast CT scan. Quantitative indicators of LVSD including phase standard deviation (PSD) and phase histogram bandwidth (PBW) were obtained through phase analysis of the gated rest myocardial perfusion imaging (MPI). Additionally, 83 healthy individuals at the same time were selected to gain the reference threshold of LVSD indicators (13.1° for PSD and 37.6° for PBW). Univariate and multivariable logistic regression models were performed to analyze factors influencing LVSD. A generalized additive model (GAM) was applied to explore the relationship between EFV and LVSD. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of EFV for LVSD. Among all patients, 32 (27.4%) patients had LVSD. Compared with the non-LVSD group, the body mass index (BMI) and EFV were higher in the LVSD group (25.83±2.66 vs. 23.94±3.13 kg/m2; 142.41±44.17 vs. 108.01±38.24 cm3, respectively, both P<0.05). Multivariate regression analysis revealed that EFV was independently associated with LVSD [odds ratio (OR) =1.19; 95% confidence interval (CI): 1.06-1.34; P=0.003]. Age, BMI, incidence of hypertension, and LVSD were increased with tertiles of EFV (all P<0.05). The GAM indicated a linear association between EFV and LVSD. The ROC curve analysis concluded that the area under the curve (AUC) of EFV for predicting subclinical myocardial damage in T2DM patients was 0.732 (95% CI: 0.633-0.831, P<0.001), with the optimal threshold of 122.26 cm3, sensitivity of 71.9%, and specificity of 69.4%. EFV is an independent risk factor for LVSD in T2DM patients with normal LVEF and normal MPI, which could potentially serve as a novel imaging marker and a potential therapeutic target for subclinical myocardial damage.

Major adverse cardiovascular events in patients with ECG changes during dipyridamole infusion as a myocardial stress agent and normal MPI among filipino patients at a tertiary hospital

Abstract Introduction There is paucity and conflicting results of data regarding the prognostic significance of ST-segment depression during vasodilator stress testing in patients with normal myocardial perfusion imaging (MPI). It is even less well studied in minorities such as Filipino population. Purpose This study aims to determine the major adverse cardiovascular events (MACE) in patients with ECG changes during dipyridamole infusion as a myocardial stress agent and normal myocardial perfusion imaging. Methodology We performed a cross-sectional retrospective analysis of 266 adult patients aged 18 years and above who underwent dipyridamole MPI. Patients with abnormal baseline ECG, patients subjected to tests other than the Dipyridamole VST and those with missing clinical, electrocardiogram, or myocardial perfusion Imaging data were excluded. The primary endpoint was the composite MACE: of all-cause mortality, nonfatal MI, stroke, hospitalization because of heart failure, and revascularization. Results Among 226 included patients (mean age ‘61.11 + 10.72’ years; 58% women), those with ST segment depression &amp;gt;0.5mm were more likely to have MACE (OR 281.12; 95% CI 37.59 to 2101.82, p-value &amp;lt;0.001), female patients were more likely to have MACE compared to male patients (OR 2.1839; 95% CI 1.1373 to 4.1936; p-value 0.019), and patients with atypical type of chest pain were likely to have MACE (OR 2.1767; CI 1.1844 to 4.0003; p-value 0.012). During follow-up of 3 years, a total of 55 patients had MACE. All-cause mortality occurred in 3 patients, non-fatal MI in 40 patients, Hospitalization due to heart failure in 5 patients, stroke in 6 patients, and revascularization in 1 patient. Conclusion Dipyridamole-induced ischemic ST depression is more common in women, and is associated with increased risk for future cardiac events compared with similar patients without ECG evidence of ischemia. Ischemic ECG changes during dipyridamole MPI should warrant further evaluation and follow up, even when perfusion images are reassuring.

Epicardial fat volume, an independent risk factor for major adverse cardiovascular events, had an incremental prognostic value to myocardial perfusion imaging in Chinese populations with suspected or known coronary artery disease with a normal left ventricular ejection fraction.

Most coronary artery disease (CAD) patients with a normal left ventricular ejection fraction (LVEF) experience a poor prognosis. Single-photon emission computerized tomography (SPECT)-myocardial perfusion imaging (MPI), a routine examination, is useful in assessing risk and predicting major adverse cardiovascular events (MACEs) in populations with suspected or known CAD. SPECT/CT is a "one-stop shop" examination, which, through non-contrast CT, can produce attenuation correction for MPI and obtain information on coronary artery calcium (CAC) and epicardial fat volume (EFV) simultaneously. This study aims to investigate the predictive and incremental value of EFV to MPI for MACE in Chinese populations with suspected or known CAD with a normal LVEF. We retrospectively studied 290 suspected or known CAD inpatients with a normal LVEF who underwent SPECT/CT between February 2014 and December 2017. Abnormal MPI was defined as a summed stress score ≥4 or summed difference score ≥2. EFV and CAC were calculated using non-contrast CT. The end date of follow-ups was in February 2022. The follow-up information was obtained from the clinical case notes of the patients or reviews of telephone calls. MACE was defined as cardiac death, late coronary revascularization ≥3 months after MPI, non-fatal myocardial infarction, angina-related rehospitalization, heart failure, and stroke. During the 76-month follow-up, the event rate was 32.0% (93/290). Univariate and multivariate Cox regression analyses concluded that high EFV (>108.3 cm3) [hazard ratio (HR): 3.3, 95% CI: 2.1-5.2, P < 0.000] and abnormal MPI (HR: 1.8, 95% CI: 1.1-2.8, P = 0.010) were independent risk factors for MACE. The event-free survival of patients with high EFV was significantly lower than that of the low EFV group (log-rank test P < 0.001). In the subgroup with normal MPI, high EFV was associated with reduced event-free survival (log-rank P < 0.01), with a higher annualized event rate (8.3% vs. 1.9%). Adding high EFV to MPI could predict MACEs more effectively, with a higher concordance index (0.56-0.69, P < 0.01), higher global chi square (7.2-41.4, P < 0.01), positive integrated discrimination improvement (0.10, P < 0.01), and net reclassification index (0.37, P < 0.01). In Chinese populations with suspected or known CAD with normal LVEF, high EFV was an independent risk factor for MACE after adjusting for traditional risk factors, CAC and MPI. In subgroups with normal MPI, EFV could also improve risk stratification. Adding EFV to MPI had an incremental value for predicting MACE.

Optimizing stress-only myocardial perfusion imaging: a clinical prediction model to improve patient selection.

Stress-only single photon emission computed tomography myocardial perfusion imaging (MPI) offers numerous advantages in terms of improved workflow, cost and radiation reduction but is currently not widely utilized due to challenges in selecting appropriate patients for this technique. Data from 5959 individuals were used to derive (N = 4018) and validate (N = 1941) a binomial logistic regression model to predict normal stress MPI studies (stress total perfusion deficit < 4%, ejection fraction ≥ 50%). Model performance was analyzed using receiver operator characteristic curves. A simplified point-scoring system was developed and its impact on imaging workflow was assessed. Significant predictors of abnormal vs. normal stress MPI included male sex, age > 65 years, cardiomyopathy, congestive heart failure, myocardial infarction, angina, and pharmacological stress. The final model and simplified scoring system were associated with areas under the curve of 0.81 (95% CI 0.79-0.83) and 0.80 (95% CI 0.79-0.82) in the validation group, respectively. Use of the scoring system was estimated to result in a decrease of 56.5% in the number of non-contributory imaging studies acquired with minimal patient rescheduling. A prediction tool derived from simple clinical information can identify candidates for stress-only MPI studies with a beneficial impact on departmental workflow.

SPECT for risk stratification in patients with advanced liver disease

BackgroundPatients with advanced liver disease (ALD) have unique hemodynamics including high resting cardiac output and low systemic vascular resistance which may reduce the sensitivity of pharmacological myocardial perfusion imaging (MPI). MPI is frequently ordered for patients with ALD if liver transplantation is being considered. Because of the limited data on effectiveness of MPI in the ALD population, we conducted this cohort study focused on cardiac outcomes after pharmacological MPI. MethodsWe conducted a cohort study comparing normal versus abnormal MPI among 454 patients with ALD between 1/1/2011 and 06/01/2021 at a single tertiarycare academic medical center. Abnormal MPI was defined as summed stress score > 2 on LVEF < 40 %. The primary outcome was to compare the frequency of major adverse cardiovascular events (MACEs) among ALD patients with and without abnormal MPI. Secondary outcome included individual components of MACE analyzed by chi square. Kaplan-Meier survival curves and a logistic-regression model of associations with MACE were also performed. ResultsIn this cohort, 58 patients were observed to have an abnormal MPI. Baseline characteristics between the groups were similar, except prior coronary disease, which was more common among the abnormal MPI group (risk ratio 2.07, 95 % confidence interval 1.30–3.30, P = 0.003). MACE was more common in the group with abnormal MPI (n = 24, 41.4 % versus normal MPI n = 104, 26.3 %, P < .001). No difference in MACE was observed when stratified by liver disease type. In the logistic regression model, diabetes mellitus, stage 3 chronic kidney disease, and summed stress score >2 were retained as being associated with MACE. ConclusionsOur data suggest that MPI remains an effective test for identifying ALD patients at higher risk of mortality and cardiac events. Further study is needed to understand whether a strategy of routine MPI for liver transplant candidates effectively improves long term survival.

The incremental value of coronary artery calcium score in predicting long-term prognosis and defining the warranty period of normal adenosine stress-only myocardial perfusion imaging using CZT SPECT.

Normal stress-only (SO) myocardial perfusion imaging (MPI) using SPECT reduces imaging time and radiation dose with a good prognosis. However, the long-term prognostic value of combining coronary artery calcium score (CACS) with SO MPI to determine the warranty period remains unknown. Hence, we assessed the incremental prognostic value of CACS and its impact on the warranty period of normal SO MPI using SPECT. We retrospectively included 1375 symptomatic patients without a history of coronary artery disease (CAD) and a normal SO MPI using adenosine who underwent simultaneous CAC scoring. Annual major adverse cardiac events (MACE) rates were calculated for CACS categories: 0, 1-399, 400-999, and ≥1000. The mean age was 60.0 ± 11.8 years (66.9% female) with a median follow-up of 10.3 [IQR 9.6-10.9] years. The warranty period for annual MACE rate for normal SO SPECT extended the total follow-up time in years. MACE rate categorized by CAC categories demonstrated an increase in MACE rates with increasing CACS; CACS 0 and CACS 1-399 were associated with a 10-year warranty period, CACS 400-999 had a warranty period of 4 years and no warranty period could be given for CACS≥1000 (5.9 % at 1 year). CACS as an adjunct to normal pharmacological SO MPI provides additional prognostic information and aids in determining a warranty period.

Association between Cardiovascular Risk Factors and High-Risk Features in Myocardial Perfusion Imaging: A Multicenter Study.

Myocardial perfusion imaging (MPI) is a noninvasive method with acceptable sensitivity and specificity in diagnosing coronary artery disease (CAD) in moderate-risk patients, including those with CAD risk factors. The present cross-sectional, prospective study was conducted on 4886 patients from April 2020 through March 2023 at Chamran and Tehran Heart Center hospitals. A questionnaire regarding anthropometric variables, demographic characteristics, CAD risk factors, and MPI findings was designed. Totally, 2179 patients (44.6%) had abnormal MPI. Patients with abnormal MPI were significantly older than those with normal MPI. Older age (OR, 1.64; 95% CI, 1.2 to 1.72; P<0.001), diabetes mellitus (DM) (OR, 1.36; 95% CI, 1.1 to 1.48; P=0.012), hypertension (OR, 1.24; 95% CI, 1.04 to 1.37; P=0.032), and dyslipidemia (OR, 1.54; 95% CI, 1.25 to 1.8; P<0.001) were associated with abnormal MPI independently. Patients with more CAD risk factors were more likely to have abnormal MPI. Thus, in patients without or at most with 1 risk factor and those with 8 CAD risk factors, the likelihood of abnormal MPI was 3.7% and 76.2%, respectively. The frequency of left ventricular dilation and right ventricular prominence was significantly higher in patients with older age (P<0.001 and P=0.043, respectively), dyslipidemia (P<0.001 and P=0.007, respectively), DM (P<0.001 and P<0.001, respectively), and hypertension (P=0.048 and P=0.057, respectively). Individuals with CAD risk factors, especially those with older age, DM, hypertension, or dyslipidemia, require meticulous attention during CAD evaluation, particularly via MPI.

P150 STRESS–REST DYNAMIC–CT MYOCARDIAL PERFUSION IMAGING IN THE MANAGEMENT OF MYOCARDIAL BRIDGING: A “ONE–STOP SHOP” EXAM

Abstract Myocardial bridging (MB) is a congenital anomaly characterized by intramyocardial coronary course that can cause coronary compression during systole and can lead to myocardial ischemia. The improvement in computed tomography (CT) scanner technology has increased the detection of MB during coronary–CT (cCT) exam but the assessment of their functional significance is often challenging. Tha stress–rest myocardial perfusion imaging (MPI) single–photon emission CT (SPECT) is often required to decide patient’s management after anatomical evaluation with cCT or Invasine Coronary Angiography (ICA). However, SPECT has long acquisition protocols, poor spatial resolution, and the anatomical/Functional protocols expose patients to significant radiation doses. Thus, dynamic–CT MPI after cCGT can represent a valid alternative. We report the cases of seven patients in which we detected MBs during cCT exam and we evaluated their functional significance using a stress–rest dynamic–CT MPI to decide the correct patient’s management. Three patients showed reversible perfusion defect in the left anterior descending (LAD) territory segments involved with MB and they were referred for treatment. The remnants four patients with MB in the LAD revealed normal MPI and they were conservatively managed. In all patients the results of the stress perfusion were completely overlapping, but the study with SPECT after anatomical evaluation required a longer process. The cCT and stress–rest dynamic–CT MPI allowed to detect and to evaluate the functional significance and to decide the management of MB in a “one–stop shop” exam.

Transient ischaemic dilation ratio thresholds in patients with zero coronary calcium score undergoing exercise or dipyridamole stress SPECT myocardial perfusion imaging using a cadmium-zinc-telluride camera.

Transient ischaemic dilation (TID) is a marker of underlying extensive coronary artery disease (CAD) during myocardial perfusion imaging (MPI). The cut-off for a normal TID ratio (TIDr) value is often derived from a cohort of individuals with no apparent CAD. Varying criteria have been used to define the absence of CAD. We aim to derive TIDr cut-offs using patients with normal MPI and coronary artery calcium (CAC) score of zero, and compare the TIDr obtained from different software packages. We studied 232 patients with zero CAC and normal MPI undergoing exercise or dipyridamole stress using either a 1- or 2-day protocol. All patients were scanned in the supine position with a cadmium-zinc-telluride camera. TIDr was automatically generated using quantitative perfusion SPECT (QPS) software initially, and subsequently using Myometrix for comparison. The TIDr cut-offs calculated using the mean + 2 standard deviation were 1.29 and 1.24 for the 1- and 2-day protocol groups, respectively. In patients undergoing a 2-day protocol, dipyridamole stress resulted in significantly higher mean TIDr when compared to exercise stress (1.07 ± 0.13 vs. 1.01 ± 0.12, P = 0.035). Myometrix-derived TIDr were also significantly lower compared to QPS-derived values for most protocols except for 2-day exercise stress. This study is the first to derive TIDr threshold values using a normal population defined by zero CAC and normal MPI. TIDr was found to vary depending on stress modality, protocol as well as the software used.

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA

BackgroundA significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients. MethodsConsecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke). ResultsOf all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030). ConclusioncaIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes. Graphical abstract▪

Abstract 11488: Comparative Effectiveness of PET and SPECT Myocardial Perfusion Imaging for Identification of Low-Risk Patients With Cardiometabolic Disease

Introduction: The epidemiology of coronary artery disease (CAD) has shifted, with increasing cardiometabolic (CM) disease and decreasing obstructive CAD in patients referred for myocardial perfusion imaging (MPI). Coronary microvascular dysfunction, defined as impaired coronary flow reserve (CFR) by positron emission tomography (PET), has emerged as a key mediator of risk. Our objective was to assess whether CFR provides additive value to identify low-risk CM disease patients compared with single-photon emission computed tomography (SPECT) MPI. Methods: We retrospectively studied patients with CM disease (obesity, diabetes, or chronic kidney disease (CKD) stage ≥3) and without known CAD referred for PET or SPECT MPI at our center from 2006 to 2020. Annualized all-cause and cardiac mortality was determined from death certificates, and propensity-matched low-risk PET and SPECT patients were compared using Poisson and Cox regression. Results: CM disease was prevalent in consecutive MPI referrals without CAD including obesity (N=8869), diabetes (N=4896) and CKD (N=3555), and higher among PET MPI (p &lt;0.001). Prevalence of summed stress score (SSS) &gt;3 reflecting obstructive CAD was low (12%, 15% and 16%). Conversely, prevalence of CFR &lt;2 was high (52%, 61% and 69%), reflecting impaired myocardial perfusion. In adjusted hazard analysis, normal MPI was associated with lower risk of all-cause and cardiac death (p &lt;0.001). Normal PET (SSS ≤3 and CFR &gt;2) was associated with lower all-cause death compared to normal SPECT (Figure, A). Normal PET and SPECT identified low-risk (&lt;1%/year cardiac death) patients with obesity and diabetes, however those with CKD remained moderate-risk (1-3%/year) (Figure, B). Conclusion: CM disease is common among patients without CAD referred for MPI. Normal PET and SPECT MPI identify a low-risk group for obesity and diabetes, but not CKD. PET with CFR has additive prognostic utility to identify low-risk individuals compared to SPECT.

Abstract 12386: The Prevalence of Coronary Microvascular Dysfunction Among Patients With Low Pretest Probability of Coronary Artery Disease

Introduction: Coronary microvascular dysfunction (CMD) is an underdiagnosed cause of chest pain. The 2021 AHA/ACC guidelines do not advocate for testing in patients with chest pain and low pretest probability (PTP &lt;15%) of coronary artery disease (CAD). The prevalence of CMD among patients with low pretest probability is not known. We sought to estimate the prevalence of CMD among patients with chest pain and a low pretest probability of CAD. Methods: We reviewed all the patients referred to positron emission tomography myocardial perfusion imaging (PET-MPI) from May 2011 to January 2022. Patients with chest pain and low PTP of CAD who had normal PET-MPI were included in the analysis. Rest and peak myocardial blood flows (MBF) were measured. Coronary flow reserve (CFR) was calculated as a ratio of peak/rest MBF. CMD was defined as CFR of &lt;2. Results: 1873 patients (age 53.7 ± 9.3 years, 23.6% males) with low PTP and normal PET-MPI were included in the analysis. 372 (20%) patients had MVD. Patients with CMD had lower use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, aspirin, and statin. Diabetes, hypercholesterolemia, and hypertension did not predict CMD. However, female gender (OR: 1.7 95%CI: 1.1- 2.6, p=0.016), age (OR: 1.02 95%CI: 1.00 - 1.04, p=0.023) and BMI (OR: 1.04 95%CI: 1.02 - 1.07, p=0.001) were associated with higher likelihood of MVD. Conclusions: Coronary Microvascular Dysfunction is common among patients with chest pain, low PTP of CAD, and normal myocardial perfusion imaging. Females are more likely to have CMD. Further studies are needed to verify the prognostic value of this population.

Unsupervised machine learning improves risk stratification of patients with visual normal SPECT myocardial perfusion imaging assessments

Abstract Background Unsupervised machine learning has the potential to identify new cardiovascular phenotypes and more accurately assess individual risk in an unbiased fashion. Purpose We aimed to use unsupervised learning to identify, analyze, and risk-stratify subgroups of patients with normal perfusion by visual interpretation on single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Methods We included consecutive patients with visual normal clinical assessment (summed stress score of 0) from the multicenter (9 sites), REFINE SPECT registry. We considered 23 clinical, 17 image-acquisition, and 26 imaging variables. Optimal dimensionality reduction (Uniform Manifold Approximation and Projection), clustering (Gaussian Mixture Model), and number of clusters were selected to maximize the silhouette coefficient (how similar a patient is to those in their own cluster compared to other clusters). Risk stratification for all-cause mortality (ACM) and major adverse cardiac events (MACE) was assessed within these clusters and compared to risk stratification by quantitative ischemia (&amp;lt;5%, 5–10%, &amp;gt;10%) using Kaplan-Meier curves and Cox Proportional-Hazards analysis. Results In total, 17,527 (of 30,351) patients in the registry had visually normal perfusion, 49.7% female, median age of 64 [55, 72] years. There were 1,138 ACM events and 2,091 MACE events with a median follow-up of 4.1 [2.9, 5.7] years. Unsupervised learning provided better risk stratification for both ACM and MACE compared to quantitative ischemia (Figure). Notably, the high-risk cluster by unsupervised learning had a hazard ratio (HR) of 9.5 (95% confidence interval [CI]: 7.7–11.7) compared to 1.4 (95% CI: 1.1–1.9) for quantitative ischemia &amp;gt;10%. The high-risk cluster had proportionally more women (45% [low-risk], 51% [medium-risk], 57% [high-risk], all p&amp;lt;0.001), higher body mass indices (26.9, 27.4, 29.6, all p&amp;lt;0.001), prevalence of diabetes (17%, 22%, 33%, all p&amp;lt;0.001), and abnormal rest ECGs (30%, 43%, 64%, p&amp;lt;0.001); with lower rates of family history of coronary artery disease (40%, 33%, 24%, p&amp;lt;0.001). Patients in the low-risk cluster were more likely to undergo exercise stress (100%, 38%, 0%, all p&amp;lt;0.001), had lower rest peak systolic blood pressure (130, 131, 140 mmHg, all p&amp;lt;0.001), and higher stress peak systolic blood pressure (164, 150, 131 mmHg, all p&amp;lt;0.001). Patients in the high-risk cluster had higher left ventricular mass (129, 135.45, 143.9 g, all p&amp;lt;0.001) and stress volume (57, 59, 66 ml, all p&amp;lt;0.001). Conclusion Unsupervised learning identified new phenotypic clusters for SPECT MPI patients with visual normal assessments which provided improved risk stratification for ACM and MACE compared to SPECT ischemia. Such individualized risk assessment may allow better targeted management of patients with visually normal perfusion. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Research reported in this publication was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL089765. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Transient ischemic dilation or transient RV visualization in patients with normal SPECT stress myocardial perfusion imaging: Correlation with CT coronary artery calcium scoring and coronary angiography

BackgroundAncillary findings on MPI, such as transient ischemic dilation (TID) and transient right ventricular visualization (TRV), are recognized as markers of extensive CAD and predictive of adverse outcomes. They usually occur in association with stress-induced regional MPI abnormalities. However, the clinical significance of these ancillary markers in the presence of normal stress MPI is incompletely understood. MethodsFrom a cohort of 564 consecutive patients referred for clinical SPECT stress MPI, 44 patients had normal stress SPECT MPI and either TID (n = 28) or TRV (n = 16). These imaging findings were correlated with CT coronary calcium (CAC), CT coronary angiography (CTA), and invasive coronary angiography (ICA) in patients with severe CAC ≥ 1000 HU. TID and TRV were quantified as stress/rest ratios. Severe CAD was defined as > 70% luminal stenosis on CTA or ICA. ResultsThe median TID ratio was 1.23, with a range of 1.13–1.48; the median TRV ratio was 1.30, with a range of 1.20–1.48. Of 44 patients with TID or TRV, only 9 patients (20.5%) had severe obstructive > 70% CAD by angiography (6 of 28 patients (21.5%) with TID and 3 of 16 patients (19%) with TRV). Severe multi-vessel CAD occurred in only 2 of 44 patients (4.5%). In contrast, of 9 patients with CAC > 1000 HU, 6 (67%) had severe obstructive CAD. ConclusionIn patients with normal stress SPECT MPI and TID or TRV, the incidence of severe obstructive CAD was relatively low and predominantly single-vessel CAD. These findings do not support the concept that TID or TRV with normal stress MPI is predictive of high-risk CAD.

Clinical impact of quantitative [15O] H2O PET/CT myocardial perfusion imaging on decision-making regarding invasive management of coronary artery disease

BackgroundThis study was performed to determine the impact of oxygen-15-labeled water ([15O] H2O) positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging (MPI) on referral for invasive coronary angiography (ICA) and revascularization. MethodsThis study involved 57 patients who underwent [15O] H2O PET/CT MPI for evaluation of coronary artery disease (CAD). Data of referral for ICA and revascularization, clinical symptoms, and cardiac events within 6 months after MPI were assessed. Logistic regression was used to determine the predictors for referral and revascularization. The diagnostic values of hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) were calculated. ResultsNormal and abnormal MPI findings were observed in 18 (32%) and 39 (68%) patients, respectively. The referral rate was significantly different between the normal and abnormal MPI groups (5.6% and 48.7%, respectively; P = .002). Revascularization rate of abnormal MPI group was 40.0%. There were significant differences of hyperemic MBF and CFR between patients with and without referral. Hyperemic MBF was significant predictor for referral (OR 15.24, 95% CI 3.39-68.55, P < .005) and revascularization (OR 28.57, 95% CI 3.08-265.33, P < .005). Conclusion[15O] H2O PET/CT MPI showed a clinical impact on decision-making regarding invasive procedure for management of CAD.

The prognostic and diagnostic implications of surveillance serial myocardial perfusion imaging in asymptomatic renal transplant candidates

BackgroundThe utility of serial SPECT myocardial perfusion imaging (MPI) for CAD surveillance in asymptomatic ESRD patients awaiting kidney transplantation (KT) is uncertain. Methods and ResultsWe retrospectively investigated 700 asymptomatic KT candidates with ≥ 2 pre-transplant SPECT-MPIs (mean interval, 20 ± 13 months). Worsening MPI was defined as total perfusion deficit increase (ΔTPD) > 5%. High clinical risk was defined as ≥ 3 AHA/ACC KT risk factors. The primary outcome was major adverse cardiac events (MACE) of cardiac death or myocardial infarction. The initial MPI was normal in 462 (66%) subjects. On repeat MPI, ΔTPD > 5% was observed in 82 (12%) subjects, and the incidence increased with increasing time gap between MPIs (P = .006). During a mean follow-up of 16 ± 8 months, there were 119 (17%) MACEs. In the entire cohort, ΔTPD > 5% was not significantly associated with MACE (HR = 1.38; P = .210). ΔTPD > 5% was associated with increased MACE rate among patients with normal initial MPI (HR = 2.30; P = .005), but not among those with abnormal initial MPI (P = .260). There was a significant interaction between ΔTPD > 5% and initial MPI normalcy status in predicting MACE (interaction P = .018), such that the predictive value of ΔTPD is dependent on the initial MPI normalcy. Among subjects with normal initial MPI, ΔTPD > 5% was significantly associated with MACE only if the sum of KT risk factors was ≥ 3 (HR = 2.26; P = .016). Among 123 patients who underwent coronary angiography, ΔTPD > 5% was associated with a higher prevalence of obstructive CAD when the initial MPI was normal and the sum of KT risk factors was ≥ 3. ConclusionAmong patients with ESRD waitlisted for KT, new/worsening MPI abnormalities are expected. On serial surveillance, ΔTPD > 5% is associated with MACE and obstructive CAD among those with a normal initial MPI and ≥ 3 AHA/ACC KT risk factors.

Implications of transient ischemic dilatation and impaired left ventricular ejection fraction reserve in patients with normal stress myocardial perfusion imaging and elevated coronary artery calcium.

Guidelines recommend stress only (SO) myocardial perfusion imaging (MPI) without follow-up rest imaging if perfusion and left ventricular ejection fraction (LVEF) are normal. However additional rest imaging may show transient ischaemic dilation (TID) and/or impaired LVEF reserve (iLVEFr) suggestive of 'balanced ischemia'. Concurrent coronary artery calcium (CAC) scoring helps to identify subclinical atherosclerosis. The safety of SO MPI when CAC is elevated is unclear. We aim to assess the incidence and outcomes of TID and iLVEFr amongst stress/rest MPIs with normal SO images and elevated CAC. Retrospective analysis of normal stress/rest MPIs performed between 1 March 2016 to 31 January 2017 with concurrently measured CAC >300. Cases were stratified by presence of TID and/or iLVEFr. Major adverse cardiac events (MACE, defined as cardiac death, non-fatal myocardial infarction and revascularization) within 24 months were compared. There were 230 cases included of which 43 (18.7%) had TID and/or iLVEFr. Presence of TID and/or iLVEFr was associated with higher 24-month MACE (23.3 vs. 8.6%, p = 0.013), driven by more elective revascularizations (18.6 vs. 4.3%, p = 0.001). Cardiac death and non-fatal myocardial infarction rates were similar. TID and/or iLVEFr significantly predicted overall MACE after multivariate analysis (OR 2.933 [1.214 - 7.087], p = 0.017). TID and/or iLVEFr is seen in the minority of normal stress MPI with elevated CAC, and is associated with higher 24-month MACE, driven by higher elective revascularizations. Overall cardiac death and non-fatal myocardial infarction rates were low and not significantly different between both groups.