Reversible Perfusion Defects Research Articles

CONTRAST STRESS ECHOCARDIOGRAPHY FINDINGS IN MYOCARDIAL BRIDGING COMPARED TO NORMAL CORONARY COURSE, WITH AND WITHOUT CORONARY ARTERY DISEASE

Abstract Background Myocardial bridging (MB) correlation with ischemia remains a diagnostic challenge. There is a lack of studies that have assessed MB using contrast stress echo and compared the findings with those in patients demonstrating a normal coronary course, with or without obstructive coronary artery disease (CAD). Methods We evaluated all consecutive patients who underwent contrast stress echocardiography and coronary computed tomography angiography (CCTA) due to suspected symptoms of CAD within 3 months in Parma Hospital. Coronary computed tomography angiography served as the reference standard for detecting MB and obstructive CAD. The patients were divided into 3 groups: (1) MB and no evidence of obstructive CAD (MB group, N = 64), (2) no evidence of obstructive CAD or MB (NoCAD group, N = 135), (3) obstructive CAD without MB (CAD group, N = 68). Results The coronary flow velocity reserve in the LAD (CFVR–LAD) was reduced in the MB and CAD groups, measuring 1.91 ± 0.21 and 1.82 ± 0.28, respectively, whereas it was 2.27 ± 0.34 in the NoCAD group (P < .001). The MB and CAD groups exhibited a higher prevalence of reversible myocardial perfusion defects (rMPDs) compared to the NoCAD group (57.8% vs 64.7% vs 3.7%, P < .001). Reversible wall motion abnormalities were frequently observed in the CAD group and rarely found in the MB and NoCAD groups (47.1% vs 18.8% vs 4.4%, P < .001). In multivariable analyses, the presence of MB was independently associated with reduced CFVR–LAD (odds ratio = 14.55; 95% CI, 6.84–30.93; P < .001) and the presence of rMPD (odds ratio = 37.96; 95% CI, 13.49–106.84; P < .001). Patients with deep MB (>2 mm depth) and very deep MB (≥5 mm depth) exhibited significantly greater CFVR–LAD reduction and rMPD than those with superficial MB. Conclusions Myocardial bridging is capable of inducing rMPD and reducing CFVR–LAD similar to obstructive CAD. The depth of the MB correlates with the abnormalities found in the stress echo evaluation. Contrast stress echo may serve as a valuable noninvasive tool for evaluating patients with MB.

Evaluation of Perfusion and Function in Cardiac Radionuclide Imaging in Cases of Heart Failure with Mid-Range Ejection Fraction

Objective: Heart failure with mid-range ejection fraction (HFmrEF) poses a significant clinical challenge due to its diverse etiology and variable prognosis. Patients with HFmrEF exhibit an intermediate level of left ventricular dysfunction, making their management and prognosis less well-defined compared to those with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Coronary artery disease (CAD) is a common underlying cause of HFmrEF and can further exacerbate myocardial dysfunction under stress conditions. In this study, we aimed to evaluate the change in left ventricular ejection fraction with stress in the presence of coronary artery disease in cases of heart failure with mid-range ejection fraction. Material and Methods: In this retrospective study, we included 507 patients diagnosed with coronary artery disease and an left ventricular ejection fraction (LVEF) of 41-49% measured by echocardiography. All patients underwent a treadmill exercise test using the Bruce protocol, with progressively increasing speed and incline. Myocardial perfusion was assessed using stress gated myocardial perfusion scintigraphy (MPS), and fixed and reversible defects were identified in cases of coronary artery disease. Cardiac scintigraphic images were acquired from the right anterior oblique to the left posterior oblique. We calculated post-stress LVEF and the percentage decrease in LVEF to evaluate cardiac function. Results: Resting LVEF was measured as 46 (43-50), while post-stress LVEF was 35 (25-47) in all patients. Myocardial perfusion was evaluated using stress gated MPS in all patients, with 200 (39.5%) patients showing both fixed and reversible perfusion defects. The rate of decrease in LVEF due to stress was significantly higher in patients with reversible perfusion defects (15.90 (6-30.43) vs. 28.26 (24-43.18), p: 0.0005). Post-stress LVEF was lower in patients with reversible perfusion defects (40 (31-47) vs. 33 (25-38), p: 0.0005). Conclusion: In cases of impaired left ventricular perfusion, quantitative calculations of LVEF may vary, and their reliability may decrease as the ejection fraction decreases under stress conditions. Clinicians should consider this variability in the follow-up of patients with heart failure and mid-range ejection fraction.

Radionuclide Imaging Findings in Iatrogenic Stress in Cases with Reduced Left Ventricular Ejection Fraction

Objective: This study aims to contribute to the existing literature by assisting in the selection of stress protocols for patients with reduced left ventricular ejection fraction (LVEF). We also aim to provide insights into patient follow-up based on changes in post-stress LVEF determined by echocardiography. Methods: Our retrospective study encompassed 487 patients initially diagnosed with coronary artery disease. Left ventricular function was assessed using echocardiography and myocardial perfusion scintigraphy. Among them, 250 patients with LVEF values within normal limits constituted Group-1, while 237 patients with LVEF values below 50% formed Group-2. Exercise stress testing was performed using a treadmill according to the Bruce protocol. For vasodilator stress testing, intravenous adenosine infusion at a rate of 140 μg/kg/min was administered for 6 minutes. Tc-99m-sestamibi was intravenously administered (8-12 mCi) for stress imaging and (24-36 mCi) for rest imaging. Results: The median age of all patients in the study was 64 (52-79) years, with 283 (58.1%) being male. Myocardial perfusion, assessed by myocardial perfusion scintigraphy, revealed a fixed perfusion defect in all patients. Reversible perfusion defects were observed in 172 (35.3%) patients. Among patients with reduced echo-LVEF values, those who underwent exercise stress testing showed significantly lower post-stress EF values compared to those who underwent vasodilator stress testing (35 (25-42) vs. 36 (30-47), p: 0.0005). Post-stress LVEF was notably lower in patients with reversible perfusion defects, indicating a higher rate of LVEF decrease due to stress (p: 0.0005). Conclusion: Left ventricular ejection fraction (LVEF) serves as a valuable metric for assessing left ventricular function. The findings from this study support its utility in guiding the selection of a suitable stress protocol and monitoring patients during iatrogenic cardiac stress applications.

Impaired myocardial flow reserve from 82-rubidium positron emission tomography predicts survival benefit from revascularization: a multicenter registry study

Abstract Background The identification of patients that may accrue prognostic benefit from revascularization is complex. Myocardial perfusion imaging (MPI) using 82-rubidium positron emission tomography (82Rb-PET) provides information on myocardial perfusion defects, calcium-score, left ventricular ejection fraction (LVEF), and myocardial flow reserve (MFR). Purpose To examine if MFR assessed by 82-Rb PET MPI identifies subgroups that benefit from revascularization. Methods We included 7462 all-comers suspected of coronary artery disease undergoing 82-Rb-PET MPI at three high-volume nuclear centers in Denmark between January 1, 2018, and August 20, 2020. Patients with reversible perfusion defects <5%, eGFR <30 mL/min/1.73m2, receiving dialysis, left ventricular ejection fraction <35%, and those that died within 90 days of their index 82Rb-PET MPI were excluded. Revascularization was defined as percutaneous coronary intervention (PCI) or coronary artery bypass-graft surgery (CABG) within 90 days of MPI. Patients were followed for major adverse cardiac events (MACE), a composite of all-cause death, acute coronary syndromes, ischemic stroke, or heart failure, and all-cause mortality until July 9, 2022. We analyzed each outcome according to revascularization and MFR (<2 vs. ≥2) using the Kaplan-Meier estimator and proportional hazards Cox regressions adjusted for patient and 82Rb-PET characteristics, including any perfusion defects, using inverse probability weighting. Results A total of 1805 patients were included (mean age 69 (SD 10.6), 29.8% females, 27% diabetes), of whom 902 (50%) had MFR <2. The median follow-up was 35.9 months. A total of 480 were revascularized. 58 experienced a MACE; 36 died. Revascularization was associated with a significantly lower risk of all-cause mortality and MACE among patients with MFR<2, whereas there was no survival benefit from revascularization among those with normal MFR (figure 1). After adjustment, HR for revascularization for MACE in the MFR<2 group was 0.51 (95%CI 0.33-0.78) versus 1.19 (95%CI 0.64-2.20) in the MFR>=2 group (p for interaction 0.042) and for All-cause mortality 0.48 (95%CI 0.30-0.77) in the MFR<2 group versus 1.01 (95%CI 0.43-2.39) in the MFR>=2 group (p for interaction 0.28). Results were independent of the extent of reversible perfusion defect, consistent across several subgroups, and independent of the mode of revascularization (CABG or PCI), figure 2. Conclusion In this observational study, revascularization was associated with improved prognosis, specifically among patients with impaired MFR, whereas among patients with normal MFR, there was no prognostic benefit. Impaired MFR may identify patients with prognostic benefit from revascularization. This novel hypothesis should be tested in a randomized controlled trial.Kaplan MeierForest plot

Non-Invasive Assessment of Myocardial Perfusion Abnormality in Type 2 Diabetic Patients Without Symptoms of Coronary Artery Disease by SPECT-MPI

Introduction: Coronary artery disease (CAD) is the most common chronic macrovascular complication of diabetes mellitus. Diabetic patients have a high incidence of silent ischemia and MI due to autonomic neuropathy. SPECT imaging is a well-established, non-invasive procedure that offers perfusion and functional information for diagnosis and risk stratification, facilitating the early detection of CAD. Objective: To detect myocardial perfusion abnormality by SPECT-MPI in type 2 diabetic patients without symptoms of CAD. Methods: A total of eighteen diabetic patients with no history of typical CAD, with or without risk factors, underwent gated SPECT-MPI using 99mTc-sestaMIBI. A single-day stress–rest protocol with adenosine was done in each patient. Result: Six out of eighteen patients (33.3%) showed abnormal scans suggestive of myocardial ischemia or infarction. Four of these patients had reversible perfusion defects, one had a fixed perfusion defect, and one had a mixed defect. Among these patients, single vessel territory was involved in three patients, and three patients had involvement in double vessel territories. Regarding the summed stress score (SSS) value, most of the patients (four) had mild risk, whereas moderate and severe risk of a future cardiac event were observed in one patient each. In addition, two patients had left ventricular dysfunction (EF< 45%). Five patients with normal MPI and two patients with abnormal myocardial perfusion scans had high transient ischemic dilatation (TID). Risk factors such as male sex, hypertension, hyperlipidemia, obesity, and family history of CAD were not significantly correlated with abnormal scans. But abnormal scans were significantly related to a longer duration of diabetes (P = 0.038). Conclusion: This study showed that despite being asymptomatic, a considerable portion of diabetic patients had perfusion abnormalities, not just ischemia but also infarctions. Moreover, some of these patients are at high risk for future cardiac events as assessed by SSS, TID, and LVEF. Bangladesh J. Nuclear Med. 25(2): 110-116, 2022

Machine learning to predict hemodynamically significant CAD based on traditional risk factors, coronary artery calcium and epicardial fat volume.

We sought to establish an explainable machine learning (ML) model to screen for hemodynamically significant coronary artery disease (CAD) based on traditional risk factors, coronary artery calcium (CAC) and epicardial fat volume (EFV) measured from non-contrast CT scans. 184 symptomatic inpatients who underwent Single Photon Emission Computed Tomography/Myocardial Perfusion Imaging (SPECT/MPI) and Invasive Coronary Angiography (ICA) were enrolled. Clinical and imaging features (CAC and EFV) were collected. Hemodynamically significant CAD was defined when coronary stenosis severity ≥ 50% with a matched reversible perfusion defect in SPECT/MPI. Data was randomly split into a training cohort (70%) on which five-fold cross-validation was done and a test cohort (30%). The normalized training phase was preceded by the selection of features using recursive feature elimination (RFE). Three ML classifiers (LR, SVM, and XGBoost) were used to construct and choose the best predictive model for hemodynamically significant CAD. An explainable approach based on ML and the SHapley Additive exPlanations (SHAP) method was deployed to generate individual explanation of the model's decision. In the training cohort, hemodynamically significant CAD patients had significantly higher age, BMI and EFV, higher proportions of hypertension and CAC comparing with controls (P all < .05). In the test cohorts, hemodynamically significant CAD had significantly higher EFV and higher proportion of CAC. EFV, CAC, diabetes mellitus (DM), hypertension, and hyperlipidemia were the highest ranking features by RFE. XGBoost produced better performance (AUC of 0.88) compared with traditional LR model (AUC of 0.82) and SVM (AUC of 0.82) in the training cohort. Decision Curve Analysis (DCA) demonstrated that XGBoost model had the highest Net Benefit index. Validation of the model also yielded a favorable discriminatory ability with the AUC, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 0.89, 68.0%, 96.8%, 94.4%, 79.0% and 83.9% in the XGBoost model. A XGBoost model based on EFV, CAC, hypertension, DM and hyperlipidemia to assess hemodynamically significant CAD was constructed and validated, which showed favorable predictive value. ML combined with SHAP can offer a transparent explanation of personalized risk prediction, enabling physicians to gain an intuitive understanding of the impact of key features in the model.

Incremental value of epicardial fat volume on predicting obstructive coronary artery disease with myocardial ischemia

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm3 and (105.18±31.16)cm3, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.

Contrast Stress Echocardiography Findings in Myocardial Bridging Compared to Normal Coronary Course, With and Without Coronary Artery Disease

Myocardial bridging (MB) correlation with ischemia remains a diagnostic challenge. There is a lack of studies that have assessed MB using contrast stress echo and compared the findings with those in patients demonstrating a normal coronary course, with or without obstructive coronary artery disease (CAD). We evaluated all consecutive patients who underwent contrast stress echocardiography and coronary computed tomography angiography (CCTA) due to suspected symptoms of CAD within 3months in Parma Hospital. Coronary computed tomography angiography served as the reference standard for detecting MB and obstructive CAD. The patients were divided into 3 groups: (1) MB and no evidence of obstructive CAD (MB group, N=64), (2) no evidence of obstructive CAD or MB (NoCAD group, N=135), (3) obstructive CAD without MB (CAD group, N=68). The coronary flow velocity reserve in the LAD (CFVR-LAD) was reduced in the MB and CAD groups, measuring 1.91±0.21 and 1.82±0.28, respectively, whereas it was 2.27±0.34 in the NoCAD group (P<.001). The MB and CAD groups exhibited a higher prevalence of reversible myocardial perfusion defects (rMPDs) compared to the NoCAD group (57.8% vs 64.7% vs 3.7%, P<.001). Reversible wall motion abnormalities were frequently observed in the CAD group and rarely found in the MB and NoCAD groups (47.1% vs 18.8% vs 4.4%, P<.001). In multivariable analyses, the presence of MB was independently associated with reduced CFVR-LAD (odds ratio= 14.55; 95% CI, 6.84-30.93; P<.001) and the presence of rMPD (odds ratio= 37.96; 95% CI, 13.49-106.84; P<.001). Patients with deep MB (>2 mm depth) and very deep MB (≥5 mm depth) exhibited significantly greater CFVR-LAD reduction and rMPD than those with superficial MB. Myocardial bridging is capable of inducing rMPD and reducing CFVR-LAD similar to obstructive CAD. The depth of the MB correlates with the abnormalities found in the stress echo evaluation. Contrast stress echo may serve as a valuable noninvasive tool for evaluating patients with MB.

The Role of Myocardial Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events at 1 Year Follow-Up: A Single Center's Experience.

Myocardial perfusion imaging via single-photon emission computed tomography (SPECT MPI) is a well-established method of diagnosing coronary artery disease (CAD). The purpose of this study was to assess the role of SPECT MPI in predicting major cardiovascular events. The study population was composed of 614 consecutive patients (mean age: 67 years, 55% male) referred for SPECT MPI due to symptoms of stable CAD. The SPECT MPI was performed using a single-day protocol. We conducted a follow-up on all patients at 12 months via a telephone interview. The majority of our patients (78%) presented findings suggestive of reversible ischemia, fixed defects or both. Extensive perfusion defects were found in 18% of the population, while LV dilation was found in 7%. During the 12-month follow-up, 16 deaths, 8 non-fatal MIs and 20 non-fatal strokes were recorded. There was no significant association of SPECT findings with the combined endpoint of all-cause death, non-fatal MI and non-fatal stroke. The presence of extensive perfusion defects was an independent predictor of mortality at 12 months (HR: 2.90, 95% CI: 1.05, 8.06, p = 0.041). In a high-risk patient population with suspected stable CAD, only large reversible perfusion defects in SPECT MPI were independently associated with mortality at 1 year. Further trials are needed to validate our findings and refine the role of SPECT MPI findings in the diagnosis and prognosis of cardiovascular patients.

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.

230 ANOMALOUS ORIGIN OF LEFT CIRCUMFLEX ARTERY FROM RIGHT SINUS OF VALSALVA: A RARE CASE BUT WITH GREAT CLINICAL RELEVANCE

Abstract Introduction The anomalous connection of the left circumflex artery (LCx) to the right coronary artery (RCA) or sinus is the most frequent coronary artery (CA) anomaly. Among them, only those with an interarterial course are regarded as hidden conditions at risk of myocardial ischemia (MI) and sudden cardiac death (SCD). We report an uncommon of anomalous origin of LCx from the right sinus of Valsalva and a retroaortic path causing MI. Case presentation A 61-year-old man presented to the emergency department complaining palpitations and chest discomfort for an hour. He only had history of hypertension. Physical examination was unremarkable. The ECG demonstrated atrial flutter with a 2:1 conduction ratio and a ventricular rate of 157 bpm and ST segment depression in leads V4-6. Transthoracic echocardiography did not reveal segmental kinetic anomalies but a five-chamber apical view showed a “RAC sign”, typical of anomalous retroaortic course of the left coronary artery. The patient was treated with intravenous infusion of amiodarone. He restored sinus rhythm and symptoms regressed completely, but the ECG taken after conversion showed flattened T waves in leads V5-6 and negative T waves in I and aVL. Cardiac enzymes had transient increase. After the acute episode ended the patient underwent cardiac computed tomography angiography (CTA) with evidence of anomalous origin of LCx from the right sinus with a retroaortic course. A coronary angiography excluded obstructive atherosclerotic coronary lesions. Nuclear myocardial perfusion imaging revealed reversible small subsegmental perfusion defects in mid inferolateral wall and apical lateral wall. We established a medical treatment with beta-blocker. Discussion Our patient had anomalous connection of the LCx branch to the right sinus of Valsalva with a retroaortic course. Although this anomaly is usually considered benign, cases of association with SCD and MI have been reported. The factor responsible for this pathogenicity could be high orifice, ostial stenosis, slit-like/fish-mouth-shaped orifice and acute-angle take-off. As cardiac CTA did not reveal any of these characteristics, we hypothesized that the increased cardiac output and expansion of the great vessels during tachycardia could cause compression of the retroaortic segment or angling at its origin and generate ischemia. Repolarization abnormalities at ECG are well documented during supraventricular tachycardia as a response to pacing-induced stress. These changes are usually diffused and disappear after conversion to sinus rhythm. In this case they appeared hours later, accompanied by cardiac enzyme buildup. As the epicardial coronary arteries did not show any pathology, we suggest that the patient had transient ischemia due to LCx anomaly. We confirmed it by myocardial perfusion imaging. As for the management of this anomaly in adults, surgery is recommended as class IC in patients with typical angina symptoms who present with evidence of stress-induced myocardial ischemia in a matching territory or high-risk anatomy. Our patient has never had clear manifestations of angina. All these elements together with the age of our patient motivated us to use a conservative approach. Conclusions We report a case of anomalous origin of LCx from right sinus of Valsalva causing transient myocardial ischemia in a patient that has always been asymptomatic. This anomaly has been and continues to be considered benign, nevertheless we suggest to judge the clinical significance of this kind of CA anomaly on a case-by-case integrated approach.

Prognostic implications of myocardial perfusion imaging by 82-rubidium positron emission tomography in male and female patients with angina and no perfusion defects.

Myocardial perfusion imaging with 82-rubidium positron emission tomography (82Rb-PET) is increasingly used to assess stable coronary artery disease (CAD). We aimed to evaluate the prognostic value of 82Rb-PET-derived parameters in patients with symptoms suggestive of CAD but no significant reversible or irreversible perfusion defects. Among 3726 consecutive patients suspected of stable CAD who underwent 82Rb-PET between January 2018 and August 2020, 2175 had no regional perfusion defects. Among these patients, we studied the association of 82Rb-PET-derived parameters with a composite endpoint of all-cause mortality, hospitalization for unstable angina pectoris, acute myocardial infarction, heart failure, or ischaemic stroke. During a median follow up of 1.7 years (interquartile range 1.1-2.5 years), there were 148 endpoints. Myocardial blood flow (MBF) reserve (MFR), MBF during stress, left ventricular ejection fraction (LVEF), LVEF-reserve, heart rate reserve, and Ca score were associated with adverse outcomes. In multivariable Cox model adjusted for patient and 82Rb-PET characteristics, MFR < 2 (hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.24-2.48), LVEF (HR 1.38 per 10% decrease, 95% CI 1.24-1.54), and LVEF-reserve (HR 1.19 per 5% decrease, 95% CI 1.07-1.31) were significant predictors of endpoints. Results were consistent in subgroups defined by gender, history of ischaemic heart disease, low LVEF, and atrial fibrillation. MFR, LVEF, and LVEF-reserve derived from 82Rb-PET provide prognostic information on cardiovascular outcomes in patients with no perfusion defects. This may aid in identifying patients at risk and might provide an opportunity for preventive interventions.

PSAT008 Pheochromocytoma Management: Considerations for Cardiac Stress Testing

Abstract Introduction Pheochromocytomas, though rare, can have dire consequences and should be treated with timely surgical resection. Left untreated, there is high risk for developing cardiomyopathy, hemorrhagic stroke, pulmonary edema, etc. However, the resection itself has a high risk for hemodynamic instability and cardiac complications. We present a case of pheochromocytoma in a patient with multiple comorbidities who required pre-op cardiac clearance and discuss the considerations for appropriate stress test selection. Case A 60-year-old male with PMH of HTN, T2DM, CKD, OSA, and PAD s/p bilateral LE amputations was incidentally found to have a 6×5×5cm left adrenal mass on CT A/P done after a motor vehicle accident. MRI confirmed 6.6cm left adrenal mass. Lab testing showed elevated plasma fractionated catecholamines with free metanephrines 2246 (&amp;lt;57 pg/mL), free normetanephrines 1014 (&amp;lt;148 pg/mL), total metanephrines 3260 (&amp;lt;4-fold ULN of MN+NMN), aldosterone 11 (&amp;lt;28 ng/dL), plasma renin activity 0.28 (0.25-5.82 ng/mL/h), post-DST cortisol 2.7 (&amp;lt;2.0 ng/dL; 2-10 is equivocal), and chromogranin A 1449 (&amp;lt;311 ng/mL). 24-hour urine showed metanephrines 4114 (90-315 mcg/24H), normetanephrines 1174 (122-676 mcg/24H), and total metanephrines 5288 (224-832 mcg/24H). I-123 MIBG scan confirmed suspicion for pheochromocytoma. BP was elevated despite doxazosin 4mg BID, lisinopril 20mg daily, amlodipine 10mg daily, and carvedilol 37.5mg BID. He was referred to urology who planned for surgical resection pending cardiac clearance. Cardiology requested stress test to assist with pre-op risk stratification given multiple cardiac risk factors. Exercise stress test was not possible due to h/o LE amputations. Dobutamine stress test was initially recommended as this is the default testing modality at our institution but after multi-disciplinary discussion, regadenoson stress test was later selected due to concern for catecholamine surge and pheochromocytoma crisis with dobutamine use. Stress test was completed without complications and showed small reversible perfusion defect. Cardiac clearance was obtained for semi-urgent surgery. Patient tolerated left adrenalectomy and pathology confirmed pheochromocytoma. BP is now well-controlled on carvedilol 25mg BID alone. Discussion Cardiac stress testing with an underlying pheochromocytoma requires thoughtful decision making. Case reports describe cardiogenic shock, hypertensive crisis, or even death after exercise or dobutamine stress testing, possibly secondary to catecholamine surge resulting in pheochromocytoma crisis. Dobutamine is a synthetic catecholamine that stimulates both β and α1 receptors to increase inotropy and chronotropy, whereas regadenoson is a selective α2a receptor agonist that increases coronary vasodilation. In pheochromocytoma patients who require pre-op cardiac clearance, it is important to consider mechanism of action of various stress test modalities to avoid potential complications or consequent fatalities related to hemodynamic instability. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Coronary microvascular disease assessed by 82Rb-PET-CT is an independent prognostic marker of all-cause mortality

Abstract Background Coronary microvascular disease (CMD) is a major contributor to e.g. heart failure and angina pectoris, as well as being associated with an increased risk of adverse events. CMD is diagnosed by reduced myocardial blood flow reserve (MBFR), preferably by Positron emission tomography myocardial perfusion CT (PET-CT). Purpose We aim to determine whether reduced MBFR is associated with an increased hazard of all-cause mortality independently of the extent of perfusion defects in patients suspected of obstructive coronary artery disease. Method We conducted a multicenter study of all patients referred for 82Rubidium PET-CT imaging between January 2018 and August 2020. Rest and stress examinations were performed using standard imaging protocols. Percentage of perfusion defects were calculated based on summed rest- and difference score. CMD was defined as MBFR ≤2. Patients were followed for all-cause mortality through national registries with no loss to follow-up. Results Among the 7156 patients studied, 61.8% were men, median age was 69 [61–76 IQR] years, 14.1% had LVEF ≤40%, 58.4% had a previous diagnosis of ischemic heart disease (IHD), 20.1% had atrial fibrillation and 38.9% had MBFR ≤2. A total of 571 (7.8) deaths were observed, more frequently in MBFR ≤2 compared to MBFR &amp;gt;2 (4.2% vs 13.2%, p&amp;lt;0.001). MBFR was significantly associated with reversible hypoperfusion (r2=−0.33, p&amp;lt;0.0001). In Kaplan-Meier estimation MBFR ≤2 was significantly associated to all-cause mortality in the overall population as well as in clinically relevant subgroups defined by the extent of reversible and/or irreversible perfusion defects (p&amp;lt;0.05 for all, fig. 1). In multivariate Cox-analysis adjusting for age, sex, Charlson's Co-morbidity index, eGFR, LVEF and LVEF-reserve and stratifying by diabetes, MBFR ≤2 remained a robust predictor of all-cause mortality with a HR 1.73, 95% CI: 1.62–2.19, p&amp;lt;0.0001 (fig. 2). No interaction was found between MBFR and reversible hypoperfusion. In subgroup analysis including only patients with no reversible perfusion defects (n=3095), MBFR ≤2 was still strongly associated with a HR of 2.00, 95% CI: 1.29–3.11, p&amp;lt;0.001 for all-cause mortality. Conclusion MBFR ≤2 is a robust predictor of all-cause mortality independently of the extent of reversible- and/or irreversible perfusion defects. Information of MBFR should be incorporated in the clinical risk stratification of patients being investigated for ischemia. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Research Committee, Bispebjerg &amp; Frederiksberg University Hospital, scientific scholarship

Myocardial blood flow reserve assessed by 82Rb-PET-CT is associated with small-vessel disease in the kidney and brain

Abstract Background Coronary microvascular dysfunction (CMD) may be linked to small-vessel disease in other vascular beds as a part of multisystem disorder. However, there are limited data in support of this. Purpose We aim to determine whether reduced myocardial blood flow reserve (MBFR) is associated with an increased hazard of small-vessel disease in the kidneys and brain. Method We conducted a multicenter study of all patients consecutively referred for 82Rubidium-Positron emission tomography (82Rb-PET) myocardial perfusion CT imaging between January 2018 and August 2020. CMD was defined as MBFR ≤2. Patients were followed through national registries using ICD-10 codes with no loss to follow-up for microvascular events (ME) defined as chronic kidney disease, stroke, affective disorders, and dementia. Despite the heterogeneity of outcomes, they all play a crucial role in ME, with vascular dementia, affective disorders, and both ischemic and hemorrhagic strokes being major contributors to cerebral ME. Results Among the 7156 patients studied, 61.8% were men, median age was 69 [61–76 IQR] years, 14.1% had LVEF ≤40%, 58.4% had a previous diagnosis of ischemic heart disease (IHD) and 20.1% had atrial fibrillation. 38.9% had MBFR ≤2. MBFR was significantly associated with eGFR at baseline (r2=0.22, p&amp;lt;0.0001). After multivariable adjustment for demographics, cardiovascular risk factors, LVEF and reversible perfusion defects, MBFR remained significantly associated with eGFR, also in patients with no perfusion defects (β=0.039, 95% Cl 0.03–0.05, p&amp;lt;0.001 in all patients and β=0.039, 95% Cl 0.02–0.05, p&amp;lt;0.001, in patients with ≤5% reversible- and ≤5% irreversible hypoperfusion). During follow-up, a total of 677 (9.5%) ME were observed (480 (6.7%) cerebral ME and 197 (2.7%) renal ME). ME was more frequent in patients with MBFR ≤2 compared to MBFR &amp;gt;2 (11.2% vs. 5.5%, p&amp;lt;0.001). In crude analysis MBFR ≤2 was significantly associated with ME (p&amp;lt;0.0001, Fig. 1) as well as renal- and cerebral ME (both p&amp;lt;0.001). Similar results were found in subgroup analysis of patients with diabetes, normal kidney function (eGFR ≥60) or no perfusion defects, respectively (Fig. 1). After multivariate adjusting for demographics, IHD, cardiovascular risk factors, Charlson's Comorbidity index, atrial fibrillation and stratifying by chronic kidney disease stages, MBFR remained a significant predictor of ME (HR 1.43, 95% CI 1.15–1.78, p&amp;lt;0.001, fig. 2). In subgroup analysis including only patients with no reversible perfusion defects, MBFR ≤2 was associated with a HR of 2.04, 95% CI 1.43–2.91, p&amp;lt;0.0001 for ME. Conclusion This is the first larger cohort study relating CMD to microvascular outcome in the kidneys and brain. We conclude that CMD is an independent predictor of cerebral and renal ME. Data support the hypothesis that CMD is part of a systemic vascular disorder. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Research Committee, Bispebjerg &amp; Frederiksberg University Hospital, scientific scholarship

Safety and Efficacy of Regadenoson for Pediatric Stress Perfusion Cardiac MRI with Quantification of Myocardial Blood Flow.

Myocardial stress perfusion magnetic resonance imaging is a non-invasive tool to assess for myocardial ischemia and viability. Pediatric myocardial stress perfusion MRI can be challenging due to multiple intravenous lines, sedation, inadequate breath holding, fast heart rates, and complex anatomy. We performed a retrospective analysis in 39 children to evaluate safety and efficacy of regadenoson, a coronary vasodilator administered via a single intravenous line (6–10 mcg/kg), with respiratory motion correction (MOCO) and semi-quantitative blood flow analysis. Stress response data and adverse events were recorded, and image quality compared between native and MOCO reconstructions, assessing for perfusion deficits. Semi-quantitative analysis compared myocardial perfusion reserve index (MPRI) between patients who had a focal perfusion defect, patients who had undergone an orthotopic heart transplant, and non-transplant patients with no focal defects. Stress perfusion was completed in 38/39 patients (median age 15 years with a 41 ± 27% rise in heart rate (p < 0.005). Fifteen out of thirty-eight had transient minor side effects with no major adverse events. MOCO image quality was better than non-MOCO (4.63 vs. 4.01 at rest, p < 0.005: 4.41 vs. 3.84 at stress, p < 0.005). Reversible perfusion defects were seen in 4/38 patients with lower segmental mean MPRI in the area of the perfusion defect, nearing statistical significance when compared to non-transplant patients with no defects (0.78 ± 0.22 vs. 0.99 ± 0.36, p = 0.07). The global MPRI of the 16 patients who had undergone orthotopic heart transplant was significantly lower than the non-transplant patients (0.75 ± 0.22 vs. 0.92 ± 0.23, p = 0.03). Regadenoson is a safe and effective coronary vasodilator for pediatric stress perfusion MRI with MOCO producing better image quality and allowing for semi-quantitative assessment of perfusion deficits that correlate with qualitative assessment.

Long-term Survival Benefit From Revascularization Compared With Medical Therapy in Patients With or Without Diabetes Undergoing Myocardial Perfusion Single Photon Emission Computed Tomography.

To explore the long-term association of survival benefit from early revascularization with the magnitude of ischemia in patients with diabetes compared with those without diabetes using a large observational cohort of patients undergoing single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). Of 41,982 patients who underwent stress and rest SPECT-MPI from 1998 to 2017, 8,328 (19.8%) had diabetes. A propensity score was used to match 8,046 patients with diabetes to 8,046 patients without diabetes. Early revascularization was defined as occurring within 90 days after SPECT-MPI. The percentage of myocardial ischemia was assessed from the magnitude of reversible myocardial perfusion defect on SPECT-MPI. Over a median 10.3-year follow-up, the annualized mortality rate was higher for the patients with diabetes compared with those without diabetes (4.7 vs. 3.6%; P < 0.001). There were significant interactions between early revascularization and percent myocardial ischemia in patients with and without diabetes (all interaction P values <0.05). After adjusting for confounding variables, survival benefit from early revascularization was observed in patients with diabetes above a threshold of >8.6% ischemia and in patients without diabetes above a threshold of >12.1%. Patients with diabetes receiving insulin had a higher mortality rate (6.2 vs. 4.1%; P < 0.001), but there was no interaction between revascularization and insulin use (interaction P value = 0.405). Patients with diabetes, especially those on insulin treatment, had higher mortality rate compared with patients without diabetes. Early revascularization was associated with a mortality benefit at a lower ischemic threshold in patients with diabetes compared with those without diabetes.

Incremental value of epicardial fat volume to coronary artery calcium score and traditional risk factors for predicting myocardial ischemia in patients with suspected coronary artery disease

BackgroundEpicardial fat volume (EFV) has been reported to be associated with coronary artery disease (CAD). CAD is the leading cause of myocardial ischemia and myocardial ischemia is closely related to major adverse cardiovascular events. We hypothesized that EFV could provide incremental value to traditional risk factors and coronary artery calcium score (CACS) in predicting myocardial ischemia in Chinese patients with suspected CAD. MethodsWe retrospectively studied 204 Chinese patients with suspected CAD who underwent single-photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) combined with computed tomography (CT). Pericardial contours were manually defined, and EFV was automatically calculated. A reversible perfusion defect with summed difference score (SDS) ≥ 2 was defined as myocardial ischemia. ResultsThe myocardial ischemia group had higher EFV than normal MPI group (137.80 ± 34.95cm3 vs. 106.63 ± 29.10 cm3, P < .001). In multivariable logistic regression analysis, high EFV was significantly associated with myocardial ischemia [odds ratio (OR): 8.30, 95% CI: 3.72-18.49, P < .001]. Addition of EFV to CACS and traditional risk factors could predict myocardial ischemia more effectively, with larger AUC .82 (P < .001), positive net reclassification index .14 (P = .04) and integrated discrimination improvement .14 (P < .001). The bootstrap resampling method (times = 500) was used to internally validation and calculate the 95% confidence interval (CI) of the AUC (95% CI .75-.87). The calibration curve for the probability of myocardial ischemia demonstrated good agreement between prediction and observation. ConclusionsIn Chinese patients with suspected CAD, EFV was significantly associated with myocardial ischemia, and improved prediction of myocardial ischemia above traditional risk factors and CACS.

Myocardial perfusion imaging failed to improve patient risk classification compared with the revised cardiac risk index for early cardiac complications after major non-cardiac surgery.

Myocardial perfusion imaging (MPI) is frequently used for cardiac risk assessment before major non-cardiac surgery, but its ability to improve patient risk classification beyond simple clinical assessment is unknown. To explore the prognostic utility of MPI above a simple clinical risk calculator, the revised cardiac risk index (RCRI). A retrospective cohort study of at-risk patients who underwent MPI before major non-cardiac surgery in a tertiary hospital was conducted. Major adverse cardiac events (MACE) was defined as any myocardial infarction, acute pulmonary oedema, ventricular arrhythmia or cardiac death within 30 days of surgery. We analysed the predictive value of MPI for MACE using multivariable logistic regression and categorical net reclassification index. MACE occurred in 47 (7.4%) cases from 635 surgical procedures in 629 patients. MPI-identified medium or large-sized reversible perfusion defects (P = 0.02; odds ratio 2.9; 95% confidence interval 1.1-7.1) and RCRI score two or more (P = 0.03; odds ratio 2.3; 95% confidence interval 1.1-4.8) were significantly associated with MACE after adjusting for age, coronary revascularisation, surgical priority, need for general anaesthesia, left ventricular ejection fraction (LVEF) and fixed perfusion defects. MPI risk factors (LVEF, reversible perfusion and fixed perfusion defects) did not improve risk classification above baseline risk factors (age, RCRI and surgical priority). MPI risk factors are weak predictors for early cardiac complications after major non-cardiac surgery and failed to improve patient risk classification beyond essential assessment using age, RCRI and surgical priority. Clinicians should consider alternative risk assessment strategies because of MPI's poor prognostic utility and its associated time and financial costs.

Comparison of left ventricle mechanical dyssynchrony parameters in ischemic and non-ischemic patients using 13N-NH3 PET/CT

Background-AimThe relationship between perfusion pattern and stress-induced changes in Left Ventricular Mechanical Dyssynchrony (LVMD) has been previously described with controversial results using stress-rest perfusion imaging studies. The aim of this study was to assess the relationship between perfusion pattern and stress-induced changes in LVMD usingo regadenoson/rest13N-NH3 PET/CT. MethodsThere were 74 patients who underwent stress-rest 13N-NH PET/CT from January 2014 to October 2018 excluding patients with left bundle branch block, ventricular pacing and myocardial necrosis. The patients were divided into those with reversible perfusion defects at stress (Ischemic group, n = 18) and patients without reversible perfusion defects (non-ischemic group, n = 56). The LVMD parameters included: phase standard deviation (PSD) and phase histogram bandwidth (PHB), after stress and at rest. The ΔPSD (post-stressPSD-restPSD) and ΔPHB (post-stressPHB—restPHB) were calculated to measure stress-induced changes in LVMD. ResultsThere were no significant differences in LVMD parameters between post-stress and at rest in both groups. The PSD post-stress, ΔPSD and PHB post-stress were significantly higher in the ischemic group. ConclusionsUsing a vasodilator as a stress, the PSD and PHB post-stress and ΔPSD were significantly higher in the ischemic patients than the non-ischemic group, while there were no significant differences in each cohort between stress and rest indices.