Normal Perfusion Research Articles

Two-photon autofluorescence lifetime assay of rabbit photoreceptors and retinal pigment epithelium during light-dark visual cycles in rabbit retina

Two-photon excited fluorescence (TPEF) is a powerful technique that enables the examination of intrinsic retinal fluorophores involved in cellular metabolism and the visual cycle. Although previous intensity-based TPEF studies in non-human primates have successfully imaged several classes of retinal cells and elucidated aspects of both rod and cone photoreceptor function, fluorescence lifetime imaging (FLIM) of the retinal cells under light-dark visual cycle has yet to be fully exploited. Here we demonstrate a FLIM assay of photoreceptors and retinal pigment epithelium (RPE) that reveals key insights into retinal physiology and adaptation. We found that photoreceptor fluorescence lifetimes increase and decrease in sync with light and dark exposure, respectively. This is likely due to changes in all-trans-retinol and all-trans-retinal levels in the outer segments, mediated by phototransduction and visual cycle activity. During light exposure, RPE fluorescence lifetime was observed to increase steadily over time, as a result of all-trans-retinol accumulation during the visual cycle and decreasing metabolism caused by the lack of normal perfusion of the sample. Our system can measure the fluorescence lifetime of intrinsic retinal fluorophores on a cellular scale, revealing differences in lifetime between retinal cell classes under different conditions of light and dark exposure.

Novel Insights Into the Intratendinous Pressure Behavior of the Achilles Tendon in Athletes.

In contrast to other musculoskeletal tissues, the normal pressure behavior of the Achilles tendon is poorly understood. This study aimed to explore the normal intratendinous and perfusion pressures of the Achilles tendon at rest and during exercise, and investigate potential correlations with tendon load and morphology. Intratendinous and perfusion pressures of the Achilles tendon exhibit similarities to other musculoskeletal tissues and depend on tendon load and morphology. Observational study. Level 3. A total of 22 recreational athletes were enrolled. Demographics, activity level, and blood pressures were recorded. Achilles tendon thickness and echogenicity were assessed 25 mm proximal to the posterosuperior calcaneal border. In this region, intratendinous and perfusion pressures of the Achilles tendon were measured at rest and during isometric plantarflexion up to 50 N, using the microcapillary infusion technique. Linear mixed models were used to investigate the effects of plantarflexion force, tendon thickness, and echogenicity on intratendinous and perfusion pressures. At rest, intratendinous and perfusion pressures of the Achilles tendon were 43.8 ± 15.2 and 48.7 ± 18.4 mmHg, respectively. Intratendinous pressure increased linearly with plantarflexion force, reaching 101.3 ± 25.5 mmHg at 50 N (P < 0.01). Perfusion pressure showed an inverse relationship, dropping below 0 mmHg at 50 N (P < 0.01). Neither intratendinous nor perfusion pressures of the Achilles tendon correlated with tendon thickness or echogenicity. The normal intratendinous resting pressure of the Achilles tendon is higher than other musculoskeletal tissues, making it more susceptible to ischemia. During exercise, intratendinous pressure increases significantly to a level that lowers perfusion pressure, thereby compromising blood supply at already low plantarflexion forces. Given the potential role of ischemia in Achilles tendinopathy, our findings caution against intratendinous injections, as they may exacerbate high intratendinous resting pressure, and against prolonged postexercise tendon stretching, as the associated rise in intratendinous pressure may impair the required hyperemic response.

Prognostic value of myocardial flow reserve vs corrected myocardial flow reserve in patients without obstructive coronary artery disease

BackgroundMyocardial flow reserve (MFR) by positron emission tomography (PET) is a validated measure of cardiovascular risk. Elevated resting rate pressure product (RPP = heart rate x systolic blood pressure) can cause high resting myocardial blood flow (MBF), resulting in reduced MFR despite normal/near-normal peak stress MBF. When resting MBF is high, it is not known if RPP-corrected MFR (MFRcorrected) helps reclassify CV risk. We aimed to study this question in patients without obstructive coronary artery disease (CAD). MethodsWe retrospectively studied patients referred for rest/stress cardiac PET at our center from 2006 to 2020. Patients with abnormal perfusion (summed stress score >3) or prior coronary artery bypass grafting (CABG) were excluded. MFRcorrected was defined as stress MBF/corrected rest MBF where corrected rest MBF = rest MBF x 10,000/RPP. The primary outcome was major cardiovascular events (MACE): cardiovascular death or myocardial infarction. Associations of MFR and MFRcorrected with MACE were assessed using unadjusted and adjusted Cox regression. Results3276 patients were followed for a median of 7 (IQR 3–12) years. 1685 patients (51%) had MFR <2.0, and of those 366 (22%) had an MFR ≥2.0 after RPP correction. MFR <2.0 was associated with an increased absolute risk of MACE (HR 2.24 [1.79–2.81], P < 0.0001). Among patients with MFR <2.0, the risk of MACE was not statistically different between patients with an MFRcorrected ≥2.0 compared with those with MFRcorrected <2.0 (1.9% vs 2.3% MACE/year, HR 0.84 [0.63–1.13], P = 0.26) even after adjustment for confounders (P = 0.66). ConclusionsIn patients without overt obstructive CAD and MFR< 2.0, there was no significant difference in cardiovascular risk between patients with discordant (≥2.0) and concordant (<2) MFR following RPP correction. This suggests that RPP-corrected MFR may not consistently provide accurate risk stratification in patients with normal perfusion and MFR <2.0. Stress MBF and uncorrected MFR should be reported to more reliably convey cardiovascular risk beyond perfusion results.

Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia, and normal perfusion

BackgroundLV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. Methods and resultsOne hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). ConclusionsShape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

CT brain perfusion patterns and clinical outcome after successful cardiopulmonary resuscitation: A pilot study

AimCT perfusion is a valuable tool for evaluating cerebrovascular diseases, but its role in patients with hypoxic ischaemic encephalopathy is unclear. This study aimed to investigate 1) the patterns of cerebral perfusion changes that may occur early on after successful resuscitation, and 2) their correlation with clinical outcome to explore their value for predicting outcome. MethodsWe conducted a retrospective analysis of perfusion maps from patients who underwent CT brain perfusion within 12 h following successful resuscitation. We classified the perfusion changes into distinct patterns. According to the cerebral performance category (CPC) score clinical outcome was categorised as favourable (CPC 1–2), or unfavourable (CPC 3–5). ResultsA total of 87 patients were included of whom 33 had a favourable outcome (60.6% male, mean age 60 ± 16 years), whereas 54 exhibited an unfavourable outcome (59.3% male, mean age 60 ± 19 years). Of the patients in the favourable outcome group, 30.3% showed no characteristic perfusion changes, in contrast to the unfavourable outcome group where all patients exhibit changes in perfusion. Eighteen perfusion patterns were identified. The most significant patterns for prediction of unfavourable outcome in terms of their high specificity and frequency were hypoperfusion of the brainstem as well as coexisting hypoperfusion of the brainstem and thalamus. ConclusionThis pilot study identified various perfusion patterns in patients after resuscitation, indicative of circulatory changes associated with post-cardiac-arrest brain injury. After validation, certain patterns could potentially be used in conjunction with other prognostic markers for stratifying patients and adjusting personalized treatment following cardiopulmonary resuscitation. Normal brain perfusion within 12 h after resuscitation is predictive of favourable outcome with high specificity.

Experimental study on the preservation of amputated limb by low-temperature HTK preservation solution arterial perfusion

Objective: To evaluate the effect of HTK (Histidine-Tryptophan-Ketoglutarate solution) infusion on the protection and replantation of amputated limb. Methods: In experiment 1, the amputated limbs of male New Zealand white rabbits were preserved by different preservation methods, including low-temperature HTK solution perfusion group, low-temperature normal saline perfusion group, low-temperature preservation group and non-perfusion group at normal temperature. The homogenates of muscle tissue at different time points were collected for biochemical detection. H&amp;E (hematoxylin and eosin) staining was performed on muscle tissue. Bax, Bcl-2 protein immunohistochemical staining and Tunel method were used to detect apoptosis in muscle, nerve, and vascular tissues. The ultrastructure of cells was observed by transmission electron microscope. In experiment 2, the amputated limbs of rabbits were treated with HTK perfusion and cryopreservation without perfusion, respectively. The survival of rabbits and their limbs were observed, and detected by H&amp;E, TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) and scanning electron microscopy. Statistical analysis was performed using SPSS 22 (SPSS Inc., Chicago, IL, USA). χ2 test, student’s t-test, and ANOVA (Analysis of Variance) were used to compare the categorical and continuous variables. Results: Experiment 1: With the extension of disconnection time, there were statistical differences between the biochemical indexes of the HTK liquid perfusion group and those of the non-low temperature non-perfusion group, while some indexes of the other groups were different. Immunohistochemical staining of tissues (muscle, nerve, and blood vessel) in each group showed that the number of cells stained by anti-apoptotic protein BCL-2 in each group significantly increased with the extension of time, while the number of cells stained by pro-apoptotic protein BAX2 in each group significantly decreased. Tunel test showed that compared with other treatment groups, the apoptosis rate of the HTK liquid group was significantly decreased. Experiment 2: The survival rate of the experimental group was 60%, and that of the control group was only 30%. H&amp;E staining, the TUNEL method and scanning electron microscopy suggested that HTK infusion could reduce ischemia-reperfusion injury in muscle tissue. Conclusion: 1. Perfusion preservation of severed limbs at 4 ℃ can effectively reduce tissue damage caused by ischemia and hypoxia, and the effect is stronger than direct preservation. 2. HTK solution and normal saline were used for one-time perfusion of the severed limbs of rabbits, and the preservation effect of HTK solution was the best. 3. HTK solution was used for one-time perfusion of severed hind limbs of rabbits, which was refrigerated at 4 ℃ and then replanted (ischemia time was 3–5 h). Compared with the replanted limbs after cold storage alone, the survival rate was higher, and the postoperative ischemia and hypoxia injury of surviving limbs were less.

Novel indices representing heterogeneous distributions of myocardial perfusion imaging

IntroductionHeterogeneous distribution in myocardial perfusion images (MPI) obtained by scintigraphy is often observed in cardiac diseases with normal myocardial perfusion. However, quantitative assessments of such heterogeneity have not been established. We hypothesized that the heterogeneity in MPI can be quantitatively evaluated through histogram analysis, calculating the standard deviation (SD), the 95% bandwidth (BW95%), and entropy.MethodsWe examined resting 99mTc-MIBI images in 20 healthy subjects and 29 patients with cardiac disease who had none or very-mild reduced myocardial perfusion evaluated as a low summed rest score (0 to 4, the range of the studied healthy subjects). Two nuclear medicine specialists blindly divided them into two groups: non-heterogeneity or heterogeneity group, based solely on their visual assessments of heterogeneity on splash and polar maps generated from single-photon emission computed tomography (SPECT) images. The %uptake was determined by dividing the tracer count of each pixel by the tracer count of the pixel with the highest value in the LV myocardium. SD, BW95%, and entropy from histogram patterns were analyzed from the polar map data array of each %uptake. We investigated whether heterogeneity could be assessed using SD, BW95, and entropy in two groups classified by visual assessments. Additionally, we evaluated the area under the curve (AUC) to identify heterogeneity in the receiver operating characteristic curve analysis.ResultsBased solely on visual assessments, 11 (22%) and 38 (78%) cases were classified into the non-heterogeneity and heterogeneity groups, respectively. The non-heterogeneity group consisted of only healthy subjects, and all patients with cardiac disease were classified into the heterogeneity group. The cases in the heterogeneity group had significantly higher values of heterogeneity indices (SD, BW95%, and entropy) in %uptake than those in the non-heterogeneity group (p < 0.05 for all). The AUCs of the heterogeneity indices were sufficiently high (AUCs > 0.90 for all) in distinguishing cases with visually heterogeneous distribution or patients with cardiac disease.ConclusionsHeterogeneity in MPI can be evaluated using SD, BW95%, and entropy through histogram analysis. These novel indices may help identify patients with subtle myocardial changes, even in images that show preserved perfusion (345/350).

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

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

How to assess nonresponsiveness to vasodilator stress

Myocardial perfusion imaging (MPI) is a powerful tool for the functional assessment of ischemia in patients with suspected or known coronary artery disease (CAD). Given that the diagnostic accuracy and prognostic value of MPI and post-test management are highly dependent on achieving an adequate stress vasodilatory response, it is critical to identify those who may not have adequately responded to vasodilator pharmacological stress agents such as adenosine, dipyridamole, and regadenoson. Caffeine, a potent inhibitor of the adenosine receptor, is a compound that can affect vasodilatory hemodynamics, result in false negative studies, and potentially alter management in cases of inaccurate test results. Vasodilator non-responsiveness can be suspected by examining hemodynamics, quantitative positron emission tomography (PET) metrics such as myocardial flow reserve (MFR), and splenic response to stress. Quantitative MFR values of 1–1.2 should raise suspicion for nonresponsiveness in the setting of normal perfusion, along with the absence of a splenic switch off. Newer metrics, such as splenic response ratio, can be used to aid in the identification of potential nonresponders to pharmacologic vasodilators.

Goal-directed fluid therapy guided by plethysmographic variability index versus conventional liberal fluid therapy in neonates undergoing abdominal surgery: A prospective randomized controlled trial.

Intraoperative fluid therapy maintains normovolemia, normal tissue perfusion, normal metabolic function, normal electrolytes, and acid-base status. Plethysmographic variability index has been shown to predict fluid responsiveness but its role in guiding intraoperative fluid therapy is still elusive. The aim of the present study was to compare intraoperative goal-directed fluid therapy based on plethysmographic variability index with liberal fluid therapy in term neonates undergoing abdominal surgeries. A prospective randomized controlled study was conducted in a tertiary care centre, over a period of 18 months. A total of 30 neonates completed the study out of 132 neonates screened. Neonates with tracheoesophageal fistula, congenital diaphragmatic hernia, congenital heart disease, respiratory disorders, creatinine clearance <90 mL/min and who were hemodynamically unstable were excluded. Neonates were randomized to goal-directed fluid therapy group where the plethysmographic variability index was targeted at <18 or liberal fluid therapy group. Primary outcome was comparison of total amount of fluid infused intraoperatively in both the groups. Secondary outcomes included intraoperative and postoperative arterial blood gas parameters, biochemical parameters, use of vasopressors, number of fluid boluses, complications and duration of hospital stay. There was no significant difference in total intraoperative fluid infused [90 (84-117.5 mL) in goal-directed fluid therapy and 105 (85.5-144.5 mL) in liberal fluid therapy group (p = .406)], median difference (95% CI) -15 (-49.1 to 19.1). There was a decrease in serum lactate levels in both groups from preoperative to postoperative 24 h. The amount of fluid infused before dopamine administration was significantly higher in liberal fluid therapy group (58 [50.25-65 mL]) compared to goal-directed fluid therapy group (36 [22-44 mL], p = .008), median difference (95% CI) -22 (-46 to 2). In postoperative period, the total amount of fluid intake over 24 h was comparable in two groups (222 [204-253 mL] in goal-directed fluid therapy group and 224 [179.5-289.5 mL] in liberal fluid therapy group, p = .917) median difference (95% CI) cutoff -2 (-65.3 to 61.2). Intraoperative plethysmographic variability index-guided goal-directed fluid therapy was comparable to liberal fluid therapy in terms of total volume of fluid infused in neonates during perioperative period. More randomized controlled trials with higher sample size are required. Central Trial Registry of India (CTRI/2020/02/023561).

Abstract TMP53: MR-ASL Imaging Can Predict the Collaterals in Moyamoya Disease

Introduction: Digital subtraction angiography (DSA) is the gold standard investigation for the diagnosis and prognostication of moyamoya disease (MMD). Magnetic resonance arterial spin labelling (MR-ASL) is a newer non-invasive technique that can predict the perfusion reliably. Our study aims at prediction of collaterals with MR-ASL in addition to parenchymal perfusion deficit. Methodology: It is an observational single centre cohort study where consecutive MMD patients with both DSA and MR-ASL done within 3 months of each other were included in the study. Images were reviewed by 2 radiologists independently. MMD severity was graded using Suzuki staging and collaterals were graded using DSA and MR-ASL in 7 different regions [4 areas in basal ganglia level - basal ganglia, M1, A1 and P1], 3 areas at superficial cortical level above basal ganglia [M2, A2, P2]. DSA collateral grading used was: grade 0 - no collaterals visible (absence of any capillary blush) with perfusion deficit, grade 1 - mild to moderate collaterals with some perfusion deficit, grade 2 - extensive collaterals with no perfusion deficit, grade 3 - normal antegrade flow. Collateral grading used on MR-ASL was: grade 0 - no or minimal ASL signal; grade 1 - moderate ASL signal with arterial transit artefact (ATA), grade 2 - high ASL signal with ATA, grade 3 - normal perfusion without ATA. Results: Of the 46 MMD patients (males - 22), 92 hemispheres were included. 4 hemispheres were excluded as the patient underwent revascularisation in the corresponding hemisphere. Among the remaining 88 hemispheres, 7 were normal on angiography. At various Suzuki grades, the degree of collaterals graded on ASL changed according to Suzuki staging (p&lt;0.001). Whether collateral grading using ASL can predict the collaterals graded using DSA was tested using Cohen Kappa’s method, and it was found that MR-ASL can predict collaterals graded by DSA with very good agreement in all the regions studied (p&lt;0.001). Conclusion: MR-ASL is a simple, safe, effective and reproducible alternative for DSA in determining the collaterals and perfusion status in MMD patients without the untoward effects like contrast exposure.

Racial effects on masimo pulse oximetry: impact of low perfusion index

Purpose: Evaluate the SpO2-SaO2 difference between Black and White volunteer subjects having a low perfusion index (Pi) compared to those having a normal Pi. Methods: The Pi data were abstracted from electronic files collected on 7183 paired SpO2-SaO2 samples (3201 Black and 3982 White) from a recently reported desaturation study of 75 subjects (39 Black and 36 White) where SaO2 values were sequentially decreased from 100 to 70%. The Pi values from that dataset were divided into two groups (Pi ≤ 1 or Pi > 1) for analysis. A Pi value ≤ 1 was considered “low perfusion” and a Pi value > 1 was considered “normal perfusion”. Statistical calculations included values of bias (mean difference of SpO2-SaO2), precision (standard deviation of the difference), and accuracy (root-mean-square error [ARMS]). During conditions of low perfusion (Pi ≤ 1, range [0.1 to 1]), overall bias and precision were + 0.48% ± 1.59%, while bias and precision were + 0.19 ± 1.53%, and + 0.91 ± 1.57%, for Black and White subjects, respectively. Results: During normal perfusion (Pi > 1, range [1 to 12]), overall bias and precision were + 0.18% ± 1.34%, while bias and precision were -0.26 ± 1.37%, and − 0.12 ± 1.31%, for Black and White subjects, respectively. ARMS was 1.37% in all subjects with normal perfusion and 1.64% in all subjects with low perfusion. Conclusion: Masimo SET® pulse oximeters with RD SET® sensors are accurate for individuals of both Black and White races when Pi is normal, as well as during conditions when Pi is low. The ARMS for all conditions studied is well within FDA standards. This study was conducted in healthy volunteers during well-controlled laboratory desaturations, and results could vary under certain challenging clinical conditions.

Clinical phenotypes among patients with normal cardiac perfusion using unsupervised learning: a retrospective observational study

Myocardial perfusion imaging (MPI) is one of the most common cardiac scans and is used for diagnosis of coronary artery disease and assessment of cardiovascular risk. However, the large majority of MPI patients have normal results. We evaluated whether unsupervised machine learning could identify unique phenotypes among patients with normal scans and whether those phenotypes were associated with risk of death or myocardial infarction. Patients from a large international multicenter MPI registry (10 sites) with normal perfusion by expert visual interpretation were included in this cohort analysis. The training population included 9849 patients, and external testing population 12,528 patients. Unsupervised cluster analysis was performed, with separate training and external testing cohorts, to identify clusters, with four distinct phenotypes. We evaluated the clinical and imaging features of clusters and their associations with death or myocardial infarction. Patients in Clusters 1 and 2 almost exclusively underwent exercise stress, while patients in Clusters 3 and 4 mostly required pharmacologic stress. In external testing, the risk for Cluster 4 patients (20.2% of population, unadjusted hazard ratio [HR] 6.17, 95% confidence interval [CI] 4.64-8.20) was higher than the risk associated with pharmacologic stress (HR 3.03, 95% CI 2.53-3.63), or previous myocardial infarction (HR 1.82, 95% CI 1.40-2.36). Unsupervised learning identified four distinct phenotypes of patients with normal perfusion scans, with a significant proportion of patients at very high risk of myocardial infarction or death. Our results suggest a potential role for patient phenotyping to improve risk stratification of patients with normal imaging results. This work was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R35HL161195 to PS]. The REFINE SPECT database was supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health [R01HL089765 to PS]. MCW was supported by the British Heart Foundation [FS/ICRF/20/26002].

Association of Cerebral Hypoperfusion and Poor Collaterals with Cognitive Impairment in Patients with Severe Vertebrobasilar Artery Stenosis.

Effect of stenosis of vertebrobasilar artery (VBA) on cognitive function is elusive. To investigate association of cerebral hypoperfusion and poor collaterals with vascular cognitive impairment (VCI) in severe VBA stenosis patients. We consecutively enrolled patients with severe VBA stenosis confirmed by digital subtraction angiography who underwent computed tomographic perfusion (CTP) and cognitive assessments. Patients were divided into poor or good collaterals groups according to the collateral circulation status, and were grouped into different perfusion groups according to CTP. Cognitive function was measured by Montreal Cognitive Assessment (MoCA), Clock Drawing Test, Stroop Color Word Test, Trail Making Test, Digital Span Test, Auditory Verbal Learning Test, and Boston Naming Test scales. The association of cerebral perfusion and collaterals with VCI were explored. Among 88 eligible patients, VCI occurred in 51 (57.9%) patients experienced. Poor collateral was present in 73 (83.0%) patients, and hypoperfusion in 64 (72.7%). Compared with normal perfusion patients, the odds ratio with 95% confidence interval for VCI was 12.5 (3.7-42.4) for overall hypoperfusion, 31.0 (7.1-135.5) for multiple site hypoperfusion, 3.3 (1.0-10.5) for poor collaterals, and 0.1 (0-0.6) for presence of posterior communicating artery (PcoA) compensated for posterior cerebral artery (PCA) and basilar artery (BA). Additionally, decreased scores of cognitive function tests occurred in patients with decompensated perfusion or poor collaterals. Hypoperfusion and poor collaterals were positively associated with cognitive impairment in patients with severe VBA. However, PcoA compensated for the PCA and BA had a protective role in cognitive impairment development.

Assessment of Myocardial Perfusion in Patients with Type 2 Diabetes Mellitus With and Without Chronic Kidney Disease

We examined 75 patients with T2DM: the control group - patients without CKD (n=10) and the main group - patients with CKD (n=65). The main group was also divided into 2 groups according to estimated GFR (eGFR; in mL/min/1.73m2) by the CKD-EPI: eGFR≥60 (n=45) and eGFR<60 (n=20).MP imaging was performed using SPECT - AnyScan® SC - Mediso with technetium-99m sestamibi. The following scale was used to determine the SRS measure: 0 points - 70% or more, 1 point - 69-50%, 2 points - 49-30%, 3 points - 29-10%, 4 points - 9% and below in 17 segments of the polar map.The average age of patients in the control group was 54.3±9.14, and 30% were men. In the main group, the average age was 58.05±8.0, and 41.5% were men, and their average eGFR was 74.5±26.39 mL/min/1.73m2.70% of patients in the control group had SRS=0, i.e. normal myocardial perfusion at rest. The remaining 30% of patients had a minimally abnormal results (SRS=1-2). The number of patients with normal MP observed decreases when CKD occurs: 46.7% in the group with eGFR>60ml/min and 35% in patients with eGFR<60ml/min. In patients with CKD, not only the number of patients with decreased MP increases, we can observe that its severity also increases: the percentage of patients with the SRS=1-2 is 35.5% and 35%, SRS=3-4 in 15.6% and 10%, and SRS≥5 were 2.22% and 20%, in the groups of GFR>60 and GFR<60 respectively (p=0.041).

The Correlation of Inflammation, Oxidative Stress, and Hippocampal Perfusion in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is closely related to abnormal cerebral blood flow. Inflammation and oxidative stress have always been important factors in the pathophysiology of AF. It remains unknown whether inflammation and oxidative stress are correlated to hippocampal perfusion in patients with AF.Sixty-three patients with AF with normal hippocampal blood perfusion (NHBP) were compared to 71 patients with AF with abnormal hippocampal blood perfusion (AHBP) using a case-control study design. The serum levels of inflammation and oxidative stress were measured. The hippocampal perfusion was detected. (1) The serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and oxidized low-density lipoprotein (ox-LDL) were statistically higher in the AHBP group than in the NHBP group. In the AHBP subgroup analysis, the serum levels of hs-CRP and IL-6 were statistically higher in patients with persistent AF than those with paroxysmal AF. (2) The relative cerebral blood volume (rCBV), mean transit time (MTT), and the time-to-peak (TTP) were statistically higher in the AHBP group than in the NHBP group. Moreover, cerebral blood flow (rCBF) was statistically lower in the AHBP group than in the NHBP group. (3) relative cerebral blood volume (rCBV), rCBF, MTT, and TTP were passively associated with serum hs-CRP and IL-6; rCBV, rCBF, and MTT were positively associated with ox-LDL. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF after multivariate logistic regression analysis.Oxidative stress and inflammatory biomarkers were increased in patients with AF with AHBP, in which the serum levels of hs-CRP and IL-6 in the persistent AF group were statistically higher than those in the paroxysmal AF group. The serum levels of hs-CRP, IL-6, and ox-LDL were associated with AHBP in patients with AF.

Thrombotic Thrombocytopenic Purpura (TTP) Survivors Exhibit Impaired Stress Perfusion on Cardiac MRI

Introduction: Thrombotic thrombocytopenic purpura (TTP) survivors have increased rates of cardiovascular morbidity and mortality when compared with the general population. In this prospective pilot study, we sought to further characterize the long-term cardiovascular sequelae of TTP survivors through pharmacologic stress cardiac magnetic resonance imaging (CMR). Stress CMR has been increasingly utilized to detect clinical and subclinical structural and functional changes. A CMR biomarker of myocardial remodeling is extracellular volume (ECV); an increase in ECV may indicate the development of interstitial myocardial fibrosis. ECV was chosen for structural assessment as it has been implicated with diastolic dysfunction and other cardiac issues in other hematologic diseases, like sickle cell anemia. Methods: Adult patients (age ≥18 years of age) with TTP (immune-mediated or congenital) in the Ohio State University (OSU) TTP registry were prospectively consented and enrolled from March 2023 through July 2023 to undergo adenosine stress CMR at standard clinical dosing. All patients in the TTP cohort had confirmed diagnosis based on ADAMTS13 activity &amp;lt;15% during an acute episode and were in clinical remission at the time of CMR testing. Standard baseline and stress CMR parameters were obtained and compared with an age and sex matched control population, selected from patients without TTP who underwent identical stress CMR protocol for other indications and demonstrated normal stress perfusion. Patients in the control cohort predominantly had diagnoses of arrhythmia, stable angina, or heart failure. We collected data on patient demographics, details of TTP history, and underlying comorbidities. On CMR standard structural measurements were evaluated, and ECV was calculated (normal range 25.3 ± 3.5%). Perfusion was measured per standard protocols via global myocardial blood flow (MBF) as ml/min/g. Differences between the TTP and control populations were tested using the Fischer's exact test for categorical variables and Mann-Whitney U test for continuous variables. Results: A total of 10 TTP patients (9 immune-mediated, 1 congenital) were enrolled between March and July 2023. Median age at enrollment was 44.5 years (IQR 40.8-49.5) and 80% (8/10) were female. Patients were in documented clinical and ADAMTS13 activity remission with median ADAMTS13 activity of 68% (64.0-84.5), excluding the activity level of the congenital patient. Median time from initial diagnosis was 15 years (range 0.5 - 41 years) and median number of acute TTP episodes was 2 (IQR 1.0-4.5). Characteristics of the study (n= 10) and control cohort (n = 13) are summarized in Table 1. There were no significant differences in the TTP and control cohorts with respect to age, sex, race, and presence of hypertension or diabetes. Patients in the TTP cohort had significantly higher BMI (median 34.5 mg/m 2 vs 26.5 mg/m 2, p = .012), diastolic blood pressure (94 mmHg vs 82 mmHg, p = .003), and a lower rate of known cardiac disease (10% vs 85%, p&amp;lt;.001). Stress CMR showed reduced myocardial perfusion in TTP survivors: Nine out of 10 (90%) TTP survivors had evidence of structural or perfusion deficits on CMR. The median ECV in the TTP cohort (28.5%, 24.8 - 31.5) was increased compared with controls (26%, 23.5 - 27.5) though it did not reach significance (p = .08). There were no significant differences in median global MBF at rest in the TTP group (1.30, 1.16 - 1.37) compared with controls (1.18, 1.07 - 1.31, p = .210). However, TTP survivors had significantly reduced stress MBF (3.28, 2.21 - 3.53) vs controls (4.1, 3.88 - 4.22, p &amp;lt;.001) with adenosine. Reductions in quantitative stress perfusion in the TTP cohort was primarily noted in the subendocardium as shown in Figure 2. Conclusion: Asymptomatic structural changes and reduction in quantitative perfusion are common in TTP survivors. The study is ongoing to recruit more patients to ensure clinical significance and generalizability of these preliminary findings. Stress CMR may detect subclinical myocardial damage in TTP survivors who otherwise do not exhibit overt cardiovascular symptoms until a later time and may provide the basis to understand increased cardiovascular morbidity and mortality in this population.

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

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

The impact of coronary revascularization on coronary flow capacity assessed by serial transthoracic echocardiographic findings in patients with chronic coronary syndrome

Abstract Background Coronary flow capacity (CFC) integrates quantitative hyperaemic myocardial blood flow and coronary flow reserve (CFR) to comprehensively assess physiological severity of coronary artery disease. This study evaluated the effects of revascularization (PCI) on CFC assessed by serial transthoracic doppler echocardiography (TDE) examinations before and after elective PCI. Methods A total of 177 patients with chronic coronary syndrome underwent stress TDE examinations of left anterior descending arteries (LAD) before and after PCI to assess changes in CFC. Resting and hyperemic diastolic peak velocity (hDPV) was used to calculate CFR. Using previously reported thresholds for ischemia and normal perfusion, vessels were stratified in four CFC categories: severely reduced, moderately reduced, minimally reduced CFC, and normal flow. The association between CFC increase and pre-procedural TDE parameters was studied. Results After PCI, fractional flow reserve (FFR) values improved in all cases (0.70, (0.62 - 0.74), P &amp;lt; 0.001), although 74 cases (41.8%) showed CFC decrease. Pre-PCI lower FFR, lower resting Pd/Pa, lower CFR, and lower hDPV were significant predictors for CFC increase after PCI. Lower baseline CFC, particularly in ischemic CFC defined as a composite of moderately, and severely reduced CFC was a predictor of CFC increase (P &amp;lt; 0.01). On multivariable analysis, pre-PCI lower hDPV, and pre-PCI ischemic CFC were independent factors predicting CFC-improvement, while pre-PCI wire-based physiological data including FFR were not significantly associated with CFC improvement. Conclusions About a half of successful LAD PCI resulted in an increase in CFC. Preprocedural TDE-derived parameters including hDPV and CFC may help identification of lesions that benefit from revascularization with respect to an increase in coronary flow capacity. Further studies are needed to elucidate the effect of CFC improvement on prognosis.Effect of preprocedural CFC after PCI

Abstract 13074: Incremental Value of Abnormal Quantitative Myocardial Perfusion and Myocardial Infarction Using Cardiovascular Magnetic Resonance as Prognostic Markers in Type 2 Diabetes Mellitus

Introduction: Abnormal myocardial perfusion and MI are each associated with cardiovascular events in individuals with diabetes mellitus (DM). Hypothesis: We hypothesised that, in patients with T2DM, CMR determined quantitative myocardial perfusion and MI are independent predictors of major adverse cardiovascular and cerebrovascular events (MACCE) and that the presence of both offers incremental prognostic value. Methods: A prospective multicentre cohort of individuals with T2DM and healthy controls underwent stress CMR with inline quantitative myocardial perfusion and late gadolinium enhancement (LGE). Adjusted cox proportional hazard models (adjusted for age, sex, LVEF, LV end diastolic volume (LVEDV) and LV mass quantified associations between quantitative myocardial perfusion and MI with MACCE (composite of all-cause death, MI, stroke, heart failure hospitalisation and coronary revascularisation). Results: A total of 572 participants with T2DM from four centres and 52 healthy controls were followed for a median of 851 (IQR 765-935) days, during which 82 (14%) participants accrued at least one MACCE, including 25 (4%) deaths. Presence of either CMR pathology was associated with increased MACCE (normal quantitative myocardial perfusion and no MI: 7% MACCE; abnormal quantitative myocardial perfusion or MI: 13% MACCE (adjusted HR compared with normal 2.06 (95% CI 1.07-3.97, p=0.03)); and both abnormal quantitative myocardial perfusion and MI was associated with the highest event rate: 28% MACCE (adjusted HR compared with normal quantitative myocardial perfusion and no MI 4.55 (95% CI 2.32-8.90, p&lt;0.001)). Conclusion: In individuals with T2DM, the presence of either abnormal quantitative myocardial perfusion or MI is associated with MACCE and the presence of both offers strong incremental prognostic value.