Impaired Myocardial Perfusion Research Articles

Exploring the impact of recent COVID-19 infection on perfusion and functional parameters derived from gated myocardial perfusion imaging in patients undergoing evaluation for coronary artery disease.

This study seeks to evaluate how recent COVID-19 infection affects myocardial perfusion and functional parameters derived from gated myocardial perfusion imaging in patients undergoing evaluation for coronary artery disease. The goal is to enhance our understanding of COVID-19's influence on the cardiovascular system. Conducted at Farshchian Heart Hospital from 2022 to 2023, this case-control study enrolled patients suspected of coronary artery disease, stratified into two groups: those with confirmed COVID-19 infection within the past 6months (study group) and those without prior COVID-19 infection (control group). Employing a 2-day protocol, stress testing and gated SPECT MPI were performed. Statistical analysis included descriptive statistics, Chi-square test, Student's t test, and Mann-Whitney U test. Among the 86 patients included, 43 were in each group. Significantly higher summed stress core and summed difference score values were observed in the study group compared to the control group (p < 0.05). In addition, the study group exhibited significantly altered global left ventricular ejection fraction, end-diastolic volume, and end-systolic volume (p < 0.05). Non-perfusion findings, including transient ischemic dilation and transient right ventricular visualization, were more prevalent in the study group. Recent COVID-19 infection is associated with impaired myocardial perfusion and altered functional parameters as detected by MPI. These findings underscore the intricate interplay between COVID-19 and cardiovascular health, emphasizing the importance of comprehensive evaluation and management strategies to address cardiac complications in affected individuals. Further research is warranted to elucidate the underlying mechanisms and optimize patient care in the context of COVID-19-associated cardiovascular manifestations.

Association of cardiac mechanical dyssynchrony indices with data of dynamic single-photon emission computed tomography of the myocardium: the role of the time interval between the stress test and recording

Introduction. According to ECG-synchronized myocardial perfusion imaging (MPI) mechanical dyssynchrony (MD) is a sensitive marker of impaired myocardial perfusion. However, its direct comparison with indicators of myocardial blood flow reserve (MFR) according to single-photon emission computed tomography (SPECT) was not carried out. Traditional MPI protocols imply a long gap between stress test and image acquisition, during which stress-induced changes may pass. It is potentially possible to reduce the time interval down to 5 minutes.Aim: To investigate the relationship between early and delayed MD indices and the data of MFR by means of SPECT.Material and Methods. The study included 20 patients with suspected coronary heart disease, preserved left ventricular ejection fraction (&gt; 55%) and without obstructive coronary artery lesions (&lt; 50%) according to multislice computed coronary angiography. All patients underwent dynamic SPECT (dSPECT) according to a two-day rest/stress protocol. Gated MPI was performed 60 minutes after radiopharmaceutical administration. Myocardial blood flow and reserve, as well as phase histogram standard deviation (PSD, degree) and phase histogram bandwidth (HBW, degree) from 5 minutes after radiopharmaceutical administration were obtained from the dSPECT data by postprocessing. Perfusion data as well as MD indices (PSD, HBW) were obtained from delayed images. Based on dSPECT data, patients were divided into 2 groups: with preserved (MFR ≥ 2.0) and reduced (MFR &lt; 2.0) myocardial blood flow reserve.Results. Correlation analysis showed that MD indices on stress test in early scan had a stronger association with MFR (PSD ρ = –0.68, p &lt; 0.001; HBW ρ = –0.68, p = 0.001) compared to those in delayed scan (PSD ρ = –0.38, p = 0.019; HBW ρ = –0.44, p = 0.005). According to multivariate regression analysis, PSD on stress test at early scan was the only independent predictor of reduced MFR (OR 1.29 (1.1; 1.53)). Stress PSD &gt; 22° obtained at early scanning had a sensitivity of 81% and specificity of 87% (AUC = 0.86, p &lt; 0.001) in predicting of reduced MFR.Conclusion. Left ventricular mechanical dyssynchrony indices obtained by early post-stress gated MPI have a stronger association with myocardial blood flow reserve indices.

Fully automated quantitative stress perfusion cardiac MRI to assess myocardial perfusion in adult patients with convalescent Kawasaki disease and coronary aneurysms: an age and sex-matched analysis

Abstract Introduction Coronary aneurysms are a well-documented complication of childhood Kawasaki disease. They may persist into adulthood predisposing to impaired myocardial blood flow, symptoms, and adverse cardiovascular events. Preliminary reports suggest that Kawasaki disease may also be associated with coronary microvascular dysfunction. The effect of coronary involvement from Kawasaki disease on myocardial perfusion in convalescent asymptomatic adults has not been studied using fully automated inline quantitative perfusion MRI (CMR). Purpose To assess the effect of coronary artery abnormalities on quantitative myocardial perfusion in adult patients with convalescent Kawasaki disease compared to an age and sex-matched control cohort. Methods Retrospective single centre cohort analysis of adult patients with convalescent Kawasaki disease who have undergone fully automated inline quantitative myocardial stress perfusion CMR. All patients had coronary involvement during their acute childhood illness. An age and sex-matched group (n=14) with normal CMRs was selected for comparison. Rest MBF was corrected for heart rate by dividing by the scan heart rate and multiplying by the mean resting heart rate among all subjects. A per-vessel analysis was performed using a linear mixed effects model with pairwise comparisons to assess the effect of coronary abnormalities (normal, aneurysmal with or without thrombosis, revascularised) on myocardial perfusion reserve (MPR). Results 28 patients were included (14 Kawasaki; 14 controls). All patients in the Kawasaki cohort had assessment of coronary anatomy either by CT (93%) or invasive (7%) coronary angiography. A total of 84 vessels were analysed. Mean age and sex were well matched (Kawasaki: 27±6.2 years; 13 males : 1 female vs. controls: 27±6.4 years; 13 males : 1 female). In patients with Kawasaki disease, thrombosed aneurysmal arteries were associated with a significantly impaired MPR compared to normal (mean Δ: -0.817; P=0.003) and aneurysmal (mean Δ: -0.957; P&amp;lt;0.001) arteries. MPR in aneurysmal and revascularised arteries were not significantly different from normal arteries in patients with Kawasaki disease. There was no significant difference in MPR between normal coronary arteries in patients with Kawasaki compared to controls. Conclusions Thrombosis in coronary aneurysms was associated with a significant impairment of myocardial perfusion in adult patients with convalescent Kawasaki disease. There was no significant reduction in perfusion in territories supplied by normal or aneurysmal arteries which does not support coronary microvascular dysfunction in these patients. Further studies are needed to confirm these preliminary findings.

Reactive oxygen species mitigate perturbations in coronary microvascular tone in exercising swine with multiple risk factors

Abstract Background Multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) and dyslipidemia are known to induce inflammation and microvascular dysfunction contributing to impaired myocardial perfusion. We previously observed that a combination of DM, high fat diet (HFD) and CKD produced an increase in coronary microvascular tone in awake swine, resulting in perturbations in myocardial O2 balance. The increased microvascular tone was mediated by an impaired NO bioavailability and was accompanied by increased myocardial levels of reactive oxygen species (ROS) and increased circulating levels of endothelin (ET). Hypothesis: In the present study in swine, we tested the hypothesis that ROS scavenging and ET receptor blockade reduce coronary microvascular tone, improving myocardial O2 delivery and O2 balance in swine with DM+HFD+CKD. Methods DM (streptozotocin), HFD and CKD (renal artery embolization) were induced in 13 female swine (DM+HFD+CKD), while 11 healthy female swine on normal pig chow served as controls (Normal). After 6 months, the effects of ROS scavenging and ET receptor blockade on coronary microvascular tone were studied at rest and during graded treadmill exercise. Results 6 months of sustained hyperglycemia (18.1±1.0 in DM+HFD+CKD vs 8.5±0.6 mmol/l in Normal), hypercholesterolemia (12.3±2.0 vs 1.7±0.1 mmol/l) and renal dysfunction (plasma creatinine: 165±7 vs 119±3 µmol/l) were accompanied by systemic inflammation (TNF 52±5 vs 25±6 pg/ml), elevated ET plasma levels, (36±2 vs 29±2 pg/ml), and oxidative stress (myocardial PGF2a 12.9±0.8 vs 10.2±0.5 pg/mg protein, all P&amp;lt;0.05 by t-test). Surprisingly, in vivo ROS scavenging (TEMPOL+MPG) reduced myocardial O2 delivery (forcing an increased myocardial O2 extraction) in DM+HFD+CKD swine, indicative of a coronary microvascular constrictor response to ROS scavenging, implying a ROS-mediated vasodilator influence (Fig. A, B). In vitro experiments, using catalase in coronary small arteries, suggested a vasodilator role for hydrogen peroxide (H2O2) in DM+HFD+CKD but not in Normal swine. A switch from NO towards to H2O2 in the regulation of coronary microvascular tone was further supported by an increase in ceramide production (138±34 vs 45±4 nmol/ml, P&amp;lt;0.05) and increased activity of catalase in the myocardium (44±3 vs 31±4 nmol/min/mg, P&amp;lt;0.05) of DM+HFD+CKD vs Normal swine. Despite elevated ET plasma levels in DM+HFD+CKD swine, combined ETA/ETB receptor blockade with tezosentan did not affect myocardial O2 balance in either Normal or DM+HFD+CKD swine (Fig C, D). Conclusion In swine, 6 months exposure to multiple risk factors resulted in increased oxidative stress that paradoxically acted to mitigate perturbations in coronary microvascular tone via an H2O2-mediated coronary vasodilator influence. Despite an increase in circulating ET levels, we found no evidence for an increased ET-1 mediated coronary vasoconstrictor influence.

Dynamic perfusion SPECT for functional evaluation in symptomatic patients with myocardial bridging

BackgroundThe aim of this study was to investigate the feasibility and diagnostic value of myocardial flow reserve (MFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) in the functional evaluation of myocardial bridge (MB). MethodsFrom May 2017 to July 2021, patients with angiographically confirmed isolated MB on the left anterior descending artery (LAD) who underwent dynamic SPECT myocardial perfusion imaging were retrospectively included. The assessment of semiquantitative indices of myocardial perfusion (summed stress scores, SSS) and quantitative parameters (MFR) was performed. ResultsA total of 49 patients were enrolled. The mean age of the subjects was 61.0 ± 9.0 years. All of the patients were symptomatic, and 16 cases (32.7%) presented with typical angina. SPECT-derived MFR showed a borderline significantly negative correlation with SSS (r = 0.261, P = .070). There was a trend of higher prevalence of impaired myocardial perfusion defined as MFR < 2 than as SSS ≥ 4 (42.9% vs 26.5%; P = .090). ConclusionOur data support that SPECT MFR may be a useful parameter for the functional assessment of MB. In patients with MB, the use of dynamic SPECT could be a potential method for hemodynamic assessment.

Radiomics for the detection of diffusely impaired myocardial perfusion: A proof-of-concept study using 13N-ammonia positron emission tomography

AimThe current proof-of-concept study investigates the value of radiomic features from normal 13N-ammonia positron emission tomography (PET) myocardial retention images to identify patients with reduced global myocardial flow reserve (MFR). MethodsData from 100 patients with normal retention 13N-ammonia PET scans were divided into two groups, according to global MFR (i.e., < 2 and ≥ 2), as derived from quantitative PET analysis. We extracted radiomic features from retention images at each of five different gray-level (GL) discretization (8, 16, 32, 64, and 128 bins). Outcome independent and dependent feature selection and subsequent univariate and multivariate analyses was performed to identify image features predicting reduced global MFR. ResultsA total of 475 radiomic features were extracted per patient. Outcome independent and dependent feature selection resulted in a remainder of 35 features. Discretization at 16 bins (GL16) yielded the highest number of significant predictors of reduced MFR and was chosen for the final analysis. GLRLM_GLNU was the most robust parameter and at a cut-off of 948 yielded an accuracy, sensitivity, specificity, negative and positive predictive value of 67%, 74%, 58%, 64%, and 69%, respectively, to detect diffusely impaired myocardial perfusion. ConclusionA single radiomic feature (GLRLM_GLNU) extracted from visually normal 13N-ammonia PET retention images independently predicts reduced global MFR with moderate accuracy. This concept could potentially be applied to other myocardial perfusion imaging modalities based purely on relative distribution patterns to allow for better detection of diffuse disease.

A High De Ritis Ratio Predicts Poor Myocardial Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction.

Successful reperfusion of myocardial tissue is the goal of primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). We aimed to investigate the association between the De Ritis ratio (AST/ALT) and myocardial reperfusion in patients with STEMI who underwent pPCI. We retrospectively investigated 1236 consecutive patients who were hospitalized for STEMI and underwent pPCI. ST-segment resolution (STR) was defined as the return of the deviated ST-segment to baseline; poor myocardial reperfusion was defined as <70% STR. Patients were divided into 2 groups according to the median De Ritis ratio (.921); 618 patients (50%) were assigned to the De Ritis low group while 618 patients (50%) were assigned to the De Ritis high group. Stent size, neutrophil-to lymphocyte ratio (NLR), and the De Ritis ratio found to be associated with poor myocardial reperfusion (Odds ratio (OR) 1.45, 95% CI 1.07-1.98, P = .01, OR 1.22, 95% CI 1.01-1.48, P = .03 and OR 10.9, 95% CI 7.9-15, P < .001, respectively). A high De Ritis ratio was associated with poor myocardial reperfusion in STEMI patients who underwent pPCI. As an easily obtainable test in clinical practice, the De Ritis ratio may help identify patients at major risk for impaired myocardial perfusion.

Exploring the prospect of intrinsic wave propagation in evaluating myocardial stiffness among patients with type 2 diabetes.

Diabetes predisposes affected individuals to impaired myocardial perfusion and ischemia, leading to cardiac dysfunction. Increased myocardial stiffness is an independent and significant risk factor in diastolic dysfunction. This study sought to estimate myocardial stiffness in Type 2 diabetes (T2DM) patients using the intrinsic wave velocity propagation (IVP) along the longitudinal wall motion during late diastole and evaluate the value of IVP in assessing cardiac function and structure. 87 and 53 participants with and without T2DM (control group) were enrolled. Of the 87 T2DM patients (DM group), 43 were complicated with hypertension (DM + H group), and 44 were not (DM-H group). Ultrasound parameters were measured and analyzed, including color M-mode flow propagation velocity, global longitudinal systolic strain (GLS), and IVP. IVP was higher in the DM group than in the control group (1.62 ± 0.25 m/s and 1.40 ± 0.19 m/s, P < 0.001). After stratification for hypertension, IVP in both DM + H (1.71 ± 0.25 m/s) and DM-H (1.53 ± 0.20 m/s) groups were found to be significantly higher than that in the control group (1.40 ± 0.19 m/s); also, the difference of IVP between DM + H and DM-H group reached statistical significance. Moreover, IVP was significantly correlated with flow propagation velocity during early diastole (Pve) (r = -0.580, P < 0.001), flow propagation velocity during late diastole (Pva) (r = 0.271, P < 0.001), GLS (r = 0.330, P < 0.001), interventricular septal thickness at end-diastole (IVSd) (r = 0.321, P < 0.001), blood glucose (r = 0.246, P < 0.003), systolic blood pressure (r = 0.370, P < 0.001) and diastolic blood pressure (r = 0.389, P < 0.001). The results indicated the application potential of IVP in assessing the early detection of cardiac function changes noninvasively and sensitively. The correlation with myocardial stiffness warrants further studies to substantiate its potential clinical utility.

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Randomized Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Myocardial Perfusion and Function Among Persons With Human Immunodeficiency Virus (HIV)-Results From the MIRACLE HIV Study.

Increased renin angiotensin aldosterone system (RAAS) activity may contribute to excess cardiovascular disease in people with HIV (PWH). We investigated how RAAS blockade may improve myocardial perfusion, injury, and function among well-treated PWH. Forty PWH, on stable ART, without known heart disease were randomized to eplerenone 50 mg PO BID (n = 20) or identical placebo (n = 20) for 12 months. The primary endpoints were (1) myocardial perfusion assessed by coronary flow reserve (CFR) on cardiac PET or stress myocardial blood flow (sMBF) on cardiac MRI or (2) myocardial inflammation by extracellular mass index (ECMi) on cardiac MRI. Beneficial effects on myocardial perfusion were seen for sMBF by cardiac MRI (mean [SD]: 0.09 [0.56] vs -0.53 [0.68] mL/min/g; P = .03) but not CFR by cardiac PET (0.01 [0.64] vs -0.07 [0.48]; P = .72, eplerenone vs placebo). Eplerenone improved parameters of myocardial function on cardiac MRI including left ventricular end diastolic volume (-13 [28] vs 10 [26] mL; P = .03) and global circumferential strain (GCS; median [interquartile range 25th-75th]: -1.3% [-2.9%-1.0%] vs 2.3% [-0.4%-4.1%]; P = .03), eplerenone versus placebo respectively. On cardiac MRI, improvement in sMBF related to improvement in global circumferential strain (ρ = -0.65, P = .057) among those treated with eplerenone. Selecting for those with impaired myocardial perfusion (CFR <2.5 and/or sMBF <1.8), there was a treatment effect of eplerenone versus placebo to improve CFR (0.28 [0.27] vs -0.05 [0.36]; P = .04). Eplerenone prevented a small increase in troponin (0.00 [-0.13-0.00] vs 0.00 [0.00-0.74] ng/L; P = .03) without effects on ECMi (0.9 [-2.3-4.3] vs -0.7 [-2.2--0.1] g/m2; P = .38). CD4+ T-cell count (127 [-38-286] vs -6 [-168-53] cells/μL; P = .02) increased in the eplerenone- versus placebo-treated groups. RAAS blockade with eplerenone benefitted key indices and prevented worsening of myocardial perfusion, injury, and function among PWH with subclinical cardiac disease when compared with placebo. NCT02740179 (https://clinicaltrials.gov/ct2/show/NCT02740179?term=NCT02740179&draw=2&rank=1).

Myocardial Perfusion is Compromised in Patients with COPD and Associated with Reduced Functional Capacity

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of death worldwide and carries with it significant cardiovascular mortality. Arterial stiffness is a known risk factor for cardiovascular disease that contributes to worsening myocardial blood flow and limits functional capacity, a marker of disease prognosis and quality of life in COPD. Myocardial perfusion is decided by a careful balance between myocardial blood flow and workload and has been strongly associated with cardiovascular mortality. Despite the convincing relationship between COPD and cardiovascular disease, to date, studies investigating myocardial perfusion and its relationship to functional capacity in COPD remains unexplored. Purpose: This study sought to test the hypothesis that myocardial perfusion is reduced in COPD and associated to functional capacity. Methods: Ten patients with COPD (GOLD Stage II-IV) with no overt signs of cardiovascular disease or diagnosis and 10 demographically matched, apparently healthy controls participated in this study completing a comprehensive analysis of vascular function and functional capacity. Carotid femoral applanation tonometry was used to assess myocardial perfusion (subendocardial viability ratio (SEVR)) and arterial stiffness (Pulse Wave Velocity (PWV)). Functional Capacity was measured via six-minute walk test distance (6MWT) with dyspnea being measured on a 0-10 scale. Results: Patients with COPD exhibited significantly ( p=0.041) reduced myocardial perfusion (SEVR: ΔCOPD=131±19% vs. ΔControl=153±28%) and increased arterial stiffness (PWV: ΔCOPD=8±1 m/s vs. ΔControl=6±1 m/s, p=0.013) when compared to matched controls. Functional Capacity was significantly ( p&lt;0.001) reduced in patients with COPD (6MWT Distance: ΔCOPD=274±87 m vs. ΔControl=476±99 m) while exhibiting significantly ( p=0.02) increased post exercise dyspnea (ΔCOPD=3.1±2.4 vs. ΔControl=0.8±1.2 a.u.). Myocardial perfusion was strongly associated to 6MWT distance ( p=0.038; r=0.693) and arterial stiffness was negatively associated with dyspnea ( p=0.015; r=-0.850). Conclusion: Our data supports that patient with COPD exhibit poor myocardial perfusion that is associated to worse functional capacity, key component of quality of life and mortality in this population. This preliminary data highlights the importance of cardiovascular screening in COPD as it emphasizes how myocardial perfusion impairments may predict prognosis in this population even when no diagnosis of cardiovascular disease is present. Future studies are warranted to investigate if impaired myocardial perfusion plays a causational role in decreasing functional capacity and its potential as a therapeutic target. Supported by American Heart Association (18CDA34110323 PRM &amp; PRE905812 KC/PRM). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Reactive Oxygen Species Mitigate Perturbations in Coronary Microvascular Tone in Exercising Swine with Multiple Risk Factors

Multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) and dyslipidemia are known to induce inflammation and microvascular dysfunction contributing to impaired myocardial perfusion. We previously observed that a combination of DM, high fat diet (HFD) and CKD produced an increase in coronary microvascular tone in awake swine, resulting in perturbations in myocardial O 2 balance. The increased microvascular tone was mediated by an impaired NO bioavailability and was accompanied by increased myocardial levels of reactive oxygen species (ROS) and increased circulating levels of endothelin (ET). In the present study in swine, we tested the hypothesis that ROS scavenging and ET receptor blockade reduce coronary microvascular tone, improving myocardial O 2 delivery and O 2 balance in swine with DM+HFD+CKD. DM (streptozotocin), HFD and CKD (renal artery embolization) were induced in 13 female swine (DM+HFD+CKD), while 11 healthy female swine on normal pig chow served as controls (Normal). After 6 months, the effects of ROS scavenging and ET receptor blockade on coronary microvascular tone were studied at rest and during graded treadmill exercise. 6 months of sustained hyperglycemia (18.1±1.0 in DM+HFD+CKD vs 8.5±0.6 mmol/l in Normal), hypercholesterolemia (12.3±2.0 vs 1.7±0.1 mmol/l) and renal dysfunction (plasma creatinine: 165±7 vs 119±3 μmol/l) were accompanied by systemic inflammation (TNF 52±5 vs 25±6 pg/ml), elevated ET plasma levels, (36±2 vs 29±2 pg/ml), and oxidative stress (myocardial PGF2α 12.9±0.8 vs 10.2±0.5 pg/mg protein, all P&lt;0.05 by t-test). Surprisingly, i n vivo ROS scavenging (TEMPOL+MPG) reduced myocardial O 2 delivery (forcing an increased myocardial O 2 extraction) in DM+HFD+CKD swine, indicative of a coronary microvascular constrictor response to ROS scavenging, implying a ROS-mediated vasodilator influence. In vitro experiments, using catalase in coronary small arteries, suggested a vasodilator role for hydrogen peroxide (H 2 O 2 ) in DM+HFD+CKD but not in Normal swine. A switch from NO towards to H 2 O 2 in the regulation of coronary microvascular tone was further supported by an increase in ceramide production (138±34 vs 45±4 nmol/ml, P&lt;0.05) and increased activity of catalase in the myocardium (44±3 vs 31±4 nmol/min/mg, P&lt;0.05) of DM+HFD+CKD vs Normal swine. Despite elevated ET plasma levels in DM+HFD+CKD swine, combined ET A /ET B receptor blockade with tezosentan did not affect myocardial O 2 balance in either Normal or DM+HFD+CKD swine. Conclusion: In swine, 6 months exposure to multiple risk factors resulted in increased oxidative stress that paradoxically acted to mitigate perturbations in coronary microvascular tone via an H 2 O 2 -mediated coronary vasodilator influence. Despite an increase in circulating ET levels, we found no evidence for an increased ET mediated coronary vasoconstrictor influence. Funding: Grants 2017B018 ARENA-PRIME and 2020B008 RECONNEXT This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Circulating Ectonucleotidases Signal Impaired Myocardial Perfusion at Rest and Stress.

Background Ectonucleotidases maintain vascular homeostasis by metabolizing extracellular nucleotides, modulating inflammation and thrombosis, and potentially, myocardial flow through adenosine generation. Evidence implicates dysfunction or deficiency of ectonucleotidases CD39 or CD73 in human disease; the utility of measuring levels of circulating ectonucleotidases as plasma biomarkers of coronary artery dysfunction or disease has not been previously reported. Methods and Results A total of 529 individuals undergoing clinically indicated positron emission tomography stress testing between 2015 and 2019 were enrolled in this single-center retrospective analysis. Baseline demographics, clinical data, nuclear stress test, and coronary artery calcium score variables were collected, as well as a blood sample. CD39 and CD73 levels were assessed as binary (detectable, undetectable) or continuous variables using ELISAs. Plasma CD39 was detectable in 24% of White and 8% of Black study participants (P=0.02). Of the clinical history variables examined, ectonucleotidase levels were most strongly associated with underlying liver disease and not other traditional coronary artery disease risk factors. Intriguingly, detection of circulating ectonucleotidase was inversely associated with stress myocardial blood flow (2.3±0.8 mL/min per g versus 2.7 mL/min per g±1.1 for detectable versus undetectable CD39 levels, P<0.001) and global myocardial flow reserve (Pearson correlation between myocardial flow reserve and log(CD73) -0.19, P<0.001). A subanalysis showed these differences held true independent of liver disease. Conclusions Vasodilatory adenosine is the expected product of local ectonucleotidase activity, yet these data support an inverse relationship between plasma ectonucleotidases, stress myocardial blood flow (CD39), and myocardial flow reserve (CD73). These findings support the conclusion that plasma levels of ectonucleotidases, which may be shed from the endothelial surface, contribute to reduced stress myocardial blood flow and myocardial flow reserve.

Blood pressure, arterial waveform, and arterial stiffness during hemodialysis and their clinical implications in intradialytic hypotension.

This study included 152 hemodialysis patients (mean age, 69 years; 34.2% female) and investigated serial changes in blood pressure (BP) and arterial stiffness indices during hemodialysis using an oscillometric device, SphygmoCor XCEL, and examined whether assessment of the arterial waveform has clinical implications for the management of intradialytic hypotension (IDH). Measurement was performed every 30 min during hemodialysis, and the threshold defining IDH was systolic BP (SBP) decrease ≥40 mmHg or a requirement for antihypotensive medication in all patients and ≥ the 75th percentile of maximum SBP decrease during hemodialysis (≥34 mmHg) in the subgroup without antihypotensive medication (n = 98). In all patients, a 1-standard deviation (SD) increase in the baseline subendocardial viability ratio (SEVR), an index of myocardial perfusion, was an independent predictor of IDH (odds ratio [OR] 0.43, p < 0.001). In the subgroup analysis, a serial change in SBP and all arterial waveform indices, including the augmentation index, augmented pressure (AP), and SEVR, during hemodialysis were greater for IDH than for non-IDH patients (all p < 0.01 by 2-way repeated-measures ANOVA), with the exception of heart rate (p = 0.40) and diastolic pressure time index (p = 0.21). Diabetes (OR 4.08), a 1-SD increase in ultrafiltration rate (OR 2.07), fractional shortening (OR 0.45), baseline SEVR (OR 0.36) and the first 1-h percent change in AP (OR 0.52) were independent predictors of IDH (all p < 0.05). In conclusion, impaired myocardial perfusion and increased arterial stiffness, particularly poor arteriolar responsiveness to acute dialysis-related changes, are associated with IDH, and predialysis SEVR evaluation can complement screening for IDH.

Abstract 11377: Takotsubo Syndrome Among Patients With Spontaneous Coronary Artery Dissection: A Report of the ISCAD Registry

Introduction: Association of takotsubo syndrome (TTS) with spontaneous coronary artery dissection (SCAD) has been described previously. Characteristics and in-hospital prognosis of SCAD patients with concomitant TTS remain unclear. Methods: Patients with angiography-confirmed SCAD were selected from the iSCAD Registry and underwent core lab adjudication of left ventriculography (LVG) and coronary angiography including assessment of SCAD lesion characteristics, TIMI Flow Grade (TFG), and TIMI Myocardial Perfusion Grade (TMPG). Classic TTS was defined as wall motion abnormality (WMA) presenting as apical ballooning. TTS variants were defined as non-apical WMA discordant to dissected coronary territory with apical sparing. In-hospital event was defined as composite of recurrent myocardial infarction (MI), cerebrovascular accident, heart failure requiring diuretics, or new arrhythmia. Results: On blinded review of LVG from 216 patients, TTS was identified in 38 (17.6%) patients (classic, midventricular, and focal pattern: 86.8%, 2.6%, and 10.5%, respectively). There was no significant difference in age, cardiovascular risk factors, history of anxiety or depression, recreational substance use, emotional or physical stressors, extracoronary vascular abnormalities, peak troponin levels, or TFG of dissected arteries between TTS and non-TTS groups. TTS patients were more likely to present with ST-segment elevation MI (47.4% vs 27.5%; p=0.02), left anterior descending artery (LAD) involvement (89.5% vs 59.0%; p=0.0004), and TMPG &lt; 3 (68.4% vs 48.3%; p=0.02) compared to non-TTS patients. TTS patients had a greater risk of in-hospital events (32.4% vs 15.1%; p=0.01), mainly attributed to new arrhythmia (27.0% vs 6.5%; p=0.0009) and heart failure (11.4% vs 3.0%; p=0.03). Conclusion: Coexistence of TTS and SCAD was associated with ST-elevation MI, LAD involvement, impaired microvascular myocardial perfusion, and adverse in-hospital outcomes.

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.

Quantitative myocardial blood flow as a prognostic marker for cardiovascular outcomes in patients with Type 2 Diabetes Mellitus: a multicentre study

Abstract Introduction: Patients with Type 2 Diabetes Mellitus (T2DM) are at increased risk of cardiovascular disease, including epicardial coronary heart disease, silent myocardial infarction (MI), and coronary microvascular dysfunction (CMD) [1]. All of these can be assessed and quantified using cardiac magnetic resonance (CMR), including most recently quantitative myocardial blood flow (MBF). We aimed to determine the prognostic relevance of MBF in patients with T2DM and test the hypothesis that impaired stress MBF and myocardial perfusion reserve (MPR) have independent prognostic value over standard clinical and imaging parameters. Methods A 4-centre study of patients with T2DM who underwent quantitative perfusion assessment using CMR. Diagnosis of T2DM was based on Hba1c &amp;gt;48mmol/l or a known diagnosis of T2DM. Image analysis was performed automatically using an artificial intelligence approach deriving global MBF and MPR [2]. Cox proportional hazard models adjusting for comorbidities and CMR parameters sought associations between stress MBF and MPR with death and major adverse cardiovascular events (MACE), including MI, non-fatal stroke, heart failure hospitalisation and death. Results A total of 630 patients with T2DM were included with a median follow-up of 722 days (interquartile range 493) days. There were 27 (4.3%) deaths and 76 MACE events in 62 (12.1%) patients. Patient data was represented into groups depending on threshold stress MBF values of 1.94ml/g/min and MPR thresholds of 1.96 using validated data from invasive coronary physiology [3]. Patient demographics and CMR data are seen in table 1. Kaplan-Meier curves are seen in figure 1. Stress MBF was associated with mortality and MACE after adjusting for age, LV ejection fraction and HbA1c. The stress MBF adjusted hazard ratios for all cause death and death and MACE were 0.35 (95% CI, 0.13–0.95, P=0.04) and 0.54 (95% CI, 0.30–0.96, P=0.04), respectively. MPR was not significantly associated with death and MACE after adjusting for age, LV ejection fraction and HbA1c; hazard ratio for all cause death and death and MACE was 0.83 (95% CI, 0.41–1.69, P=0.60) and 0.81 (95% CI, 0.53–1.23, p=0.32) respectively. Conclusion In patients with T2DM, reduced stress MBF measured automatically inline using artificial intelligence quantification of cardiovascular magnetic resonance perfusion mapping provides a strong, independent predictor of adverse cardiovascular outcome. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): 1. REC ID 14/EE/0007 (Barts Heart Centre funding). 2. For PREDICT (Leicester data) ethical approval was provided by the UK Health Research Authority Research Ethics Committee (reference 17/WM/0192). 3. MATCH Study, Leeds - British Heart Foundation - 17/YH/0300. 4. LEAN-DM, Leeds - British Heart Foundation - 18/YH/01685. CEED, Leeds: British Heart Foundation - REC reference - 18/YH/0190

Radiomics-based analysis by machine learning techniques improves characterization of functionally significant coronary lesions

Abstract Background Computed Tomography Coronary Angiography (CTCA) is an effective non-invasive imaging modality for anatomo-functional assessment of coronary artery disease (CAD). Radiomics features have been used for diagnosis or outcome prediction, however, their potential value for characterizing flow limiting coronary lesions has not been explored. Purpose To assess whether application of novel radiomics and machine learning (ML) techniques on CTCA derived datasets improves characterization of functionally significant coronary lesions. Methods Consecutive patients with stable chest pain and intermediate pre-test likelihood for CAD, who underwent CTCA and PET-or SPECT-Myocardial Perfusion Imaging (MPI) respectively, were prospectively evaluated and included in the analysis. PET-MPI was considered abnormal when &amp;gt;1 contiguous segments showed both stress Myocardial Blood Flow ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or &amp;lt;1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively. Defect reversibility (DR) was defined as a summed difference score (SDS) between stress and rest images ≥2. CTCA and functional images were fused to assign each myocardial segment to the pertinent coronary territory. Stenosis severity, plaque characteristics and radiomic plaque features were assessed in the total length of the 3 main coronary vessels. In total, 1765 features were extracted from each vessel and a feature reduction and model creation pipeline was constructed [Figure 1]. Two separate datasets: a) coronary stenosis (≥50%) + plaque characteristics and b) coronary stenosis (≥50%) + plaque characteristics + radiomics were formulated and compared in terms of AUCs accordingly. Results A total of 292 coronary vessels (140 with corresponding PET-MPI data and 152 with SPECT MPI data) were analysed. Plaque burden and stenosis severity were the only independent predictors of impaired myocardial perfusion on PET-MPI, with an AUC = 0.749, (95% CI: 0.658–0.826). Stenosis severity, kurtosis, contrast, interquartile range and entropy were predictors of an abnormal PET-MPI result and their combination resulted in an AUC = 0.854, (95% CI: 0.775–0.914). The difference between the 2 models was statistically significant (p-diff: 0.02, 95% CI: 0.0165–0.194). Stenosis severity was the only predictor of a DR on SPECT-MPI, AUC = 0.624 (95% CI: 0.542–0.702). Small Dependence High Gray Level Emphasis, Cluster Prominence, Region Length, wavelet Median and square Median were predictors of a positive SPECT result, with AUC = 0.816, (95% CI: 0.745–0.875). The difference between the two models was statistically significant (p-diff: 0.006, 95% CI: 0.152–0.329) Conclusion Radiomic futures can be combined with anatomical and morphological characteristics of coronary lesions in CTCA imaging and provide valuable complementary information for characterizing functionally significant coronary lesions. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2022 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR)

Intracoronary pharmacological therapy versus aspiration thrombectomy in STEMI (IPAT-STEMI): A systematic review and meta-analysis of randomized trials.

BackgroundThrombus load in STEMI patients remains a challenge in practice. It aggravates coronary obstruction leading to impaired myocardial perfusion, worsened cardiac function, and adverse clinical outcomes. Various strategies have been advocated to reduce thrombus burden.ObjectivesThis meta-analysis aimed to evaluate the effectiveness of intracoronary-administered thrombolytics or glycoprotein IIb/IIIa inhibitors (GPI) in comparison with aspiration thrombectomy (AT) as an adjunct to percutaneous coronary intervention (PCI) among patients presenting with ST-segment elevation myocardial infarction (STEMI).MethodsA comprehensive literature search for randomized trials that compared intracoronary-administered thrombolytics or GPI with AT in STEMI patients who underwent PCI, was conducted using various databases (e.g., MEDLINE, EMBASE, CENTRALE). Primary outcome was procedural measures (e.g., TIMI flow grade 3, TIMI myocardial perfusion grade (TMPG) 3, Myocardial blush grade (MBG) 2/3, ST-segment resolution (STR)).ResultsTwelve randomized trials enrolled 1,466 patients: 696 were randomized to intracoronary-administered pharmacological interventions and 553 to AT. Patients randomized to PCI alone were excluded. Thrombolytics significantly improved TIMI flow grade 3 (odds ratio = 3.71, 95% CI: 1.85–7.45), complete STR (odds ratio = 3.64, 95% CI: 1.60–8.26), and TMPG 3 (odds ratio = 5.31, 95% CI: 2.48–11.36). Thrombolytics significantly reduced major adverse cardiovascular events (MACE) (odds ratio = 0.29, 95% CI: 0.13–0.65) without increasing bleeding risk. Trial sequential analysis assessment confirmed the superiority of thrombolytics for the primary outcome. Intracoronary GPI, either alone or combined with AT, did not improve procedural or clinical outcomes.ConclusionsCompared with AT, intracoronary-administered thrombolytics significantly improved myocardial perfusion and MACE in STEMI patients.

Additive Effects of Obesity on Myocardial Microcirculation and Left Ventricular Deformation in Essential Hypertension: A Contrast-Enhanced Cardiac Magnetic Resonance Imaging Study.

ObjectiveThe combination of hypertension and obesity is a major cause of cardiovascular risk, and microvascular changes and subclinical dysfunction should be considered to illustrate the underlying mechanisms and early identification, thereby developing targeted therapies. This study aims to explore the effect of obesity on myocardial microcirculation and left ventricular (LV) deformation in hypertensive patients by cardiac magnetic resonance (CMR).MethodsThis study comprised 101 hypertensive patients, including 54 subjects with a body mass index (BMI) of 18.5–24.9 kg/m2 and 47 subjects with a BMI ≥25 kg/m2, as well as 55 age- and sex-matched controls with a BMI of 18.5–24.9 kg/m2. Myocardial perfusion indicators [upslope, time to maximum signal intensity (TTM), maximum signal intensity (Max SI)] and LV strains [radial, circumferential, and longitudinal global peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR)] were measured.ResultsUpslope was numerically increased in obese patients but statistically decreased in non-obese patients compared with controls. Longitudinal PS deteriorated significantly and gradually from controls to non-obese and obese hypertensive patients. Longitudinal PSSR and PDSR were significantly decreased in obese hypertensive patients compared with the other two groups. BMI was associated with upslope (β = −0.136, P < 0.001), Max SI (β = −0.922, P < 0.001), longitudinal PSSR (β = 0.018, P < 0.001), and PDSR (β = −0.024, P = 0.001). Myocardial perfusion was independently associated with longitudinal PSSR (TTM: β = 0.003, P = 0.017) and longitudinal PDSR (upslope: β = 0.067, P = 0.020) in hypertension.ConclusionObesity had adverse effects on microvascular changes and subclinical LV dysfunction in hypertension, and BMI was independently associated with both myocardial perfusion and LV deformation. Impaired myocardial perfusion was independently associated with subclinical LV dysfunction in hypertension.