Absence Of Ischemia Research Articles

The incremental value of exercise ECG to myocardial perfusion SPECT for prediction of cardiac events

Abstract Background Both myocardial perfusion SPECT (MPS) and exercise ECG (Ex-ECG) are known to carry prognostic information in patients with chronic coronary syndrome (CCS). However, it is not fully understood if combining MPS and Ex-ECG results improves risk prediction. Current guidelines no longer recommend Ex-ECG for diagnostic evaluation of CCS, but adding Ex-ECG results to MPS could be of incremental prognostic importance. Purpose The study aimed to assess the incremental prognostic value of Ex-ECG to MPS results in patients with CCS. Methods A single-center study of 908 consecutive patients with CCS (age 63±9 years, 49% male) who underwent a MPS with Ex-ECG. Subjects were followed for five years. The clinical endpoint was a composite of cardiovascular death (CV), acute myocardial infarction (AMI), unstable angina and unplanned PCI. National registry data and electronic medical charts were used for end point allocation. Results Combining the findings of MPS and Ex-ECG resulted in concordant evidence of ischemia in 72 patients (8%) or absence of ischemia in 634 patients (70%). Dis-concordant results were found in 202 patients (22%; MPS−/Ex-ECG+, n=126 and MPS+/Ex-ECG−, n=76). During follow-up 95 composite cardiac events occurred (CV deaths n=6, AMI n=27, unstable angina n=34 and unplanned PCI n=28). Kaplan-Meier curves display an increased risk of cardiac events in patients with any combination of abnormal stress test results (Figure 1). In a multivariable regression model (adjusting for age, sex, smoking, known IHD, diabetes, dyslipidaemia and exercise capacity) MPS was the strongest predictor of cardiac events regardless of Ex-ECG results (MPS+/Ex-ECG−, Hazard ratio (HR) = 3.0, p=0.001 or MPS+/Ex-ECG+, HR=4.0, p<0.001). However, an abnormal Ex-ECG almost doubled the risk of event in subjects with a normal MPS (MPS−/Ex-ECG+, HR=1.9, p=0.04). Conclusions Combining the results from MPS and Ex-ECG in patients with chronic coronary syndrome lead to an improved prediction of future cardiac events. Even though MPS is the stronger predictor, there is an incremental prognostic value of adding data from Ex-ECG to MPS, especially in patients with normal MPS findings. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swedish Heart and Lung Foundation, Region of Scania

Predictors of Stress-Delta High-Sensitivity Troponin T in Emergency Department Patients Undergoing Stress Testing.

Background and objective Elevations in high-sensitivity troponin T (hs-TnT) are frequently observed following extreme physical exercise. In light of this, we sought to determine whether specific clinical characteristics are associated with this phenomenon in patients undergoing cardiac exercise tolerance testing (ETT). Methods We conducted a retrospective analysis of a prospectively collected biospecimen repository of 257 patients undergoing a stress echocardiogram forpossible acute coronary syndrome (ACS). Ischemic electrocardiogram (ECG) changes during ETT and the presence or absence of ischemia on imaging were determined by a board-licensed cardiologist. N-terminalpro-brain natriuretic peptide (NT-proBNP) and hs-TnT assays were obtained immediately before and two hours following ETT. We developed linear regression models including several clinical characteristics to predict two-hour stress-delta hs-TnT. Variable selection was performed using theleast absolute shrinkage and selection operator (LASSO). Results The mean age of the patients was 52 years [standard deviation (SD): 11.4]; 125 (48.6%) of them were men, and 88 (34.2%) were African-American. Twenty-two patients (8.6%) had ischemia evident on echocardiography, and 31 (12.1%) had ischemic ECG changes during exercise. The mean baseline hs-TnT was 5.6 ng/L (SD: 6.4) and the mean two-hour hs-TnT was 7.1 ng/L (SD: 10.2). Age and ischemic ECG changes were associated with two-hour stress-delta hs-TnT values. Conclusions Based on our findings, ischemic changes in stress ECG and age were associated with an increase in hs-TnT levels following exercise during a stress echo.

Successful Treatment of Paraplegia Caused by Venous Hypertension Secondary to Extensive Iliocaval Deep Venous Thrombosis in the Absence of Phlegmasia Cerulea Dolens

Paraplegia is known to complicate extensive iliocaval and lower extremity deep vein thrombosis (DVT) in rare instances. The most common pathophysiology is ischemia from severe venous hypertension in phlegmasia cerulea dolens. Less understood, however, is paresis or paraplegia in the absence of ischemia. We present a case of paraplegia in extensive iliocaval and lower extremity DVT without ischemia, which was successfully treated by percutaneous pharmacomechanical therapy.

Thrombolytic tPA-induced hemorrhagic transformation of ischemic stroke is mediated by PKCβ phosphorylation of occludin

AbstractThe current standard of care for moderate to severe ischemic stroke is thrombolytic therapy with tissue plasminogen activator (tPA). Treatment with tPA can significantly improve neurologic outcomes; however, thrombolytic therapy is associated with an increased risk of intracerebral hemorrhage (ICH). The risk of hemorrhage significantly limits the use of thrombolytic therapy, and identifying pathways induced by tPA that increase this risk could provide new therapeutic options to extend thrombolytic therapy to a wider patient population. Here, we investigate the role of protein kinase Cβ (PKCβ) phosphorylation of the tight junction protein occludin during ischemic stroke and its role in cerebrovascular permeability. We show that activation of this pathway by tPA is associated with an increased risk of ICH. Middle cerebral artery occlusion (MCAO) increased phosphorylation of occludin serine 490 (S490) in the ischemic penumbra in a tPA-dependent manner, as tPA−/− mice were significantly protected from MCAO-induced occludin phosphorylation. Intraventricular injection of tPA in the absence of ischemia was sufficient to induce occludin phosphorylation and vascular permeability in a PKCβ-dependent manner. Blocking occludin phosphorylation, either by targeted expression of a non-phosphorylatable form of occludin (S490A) or by pharmacologic inhibition of PKCβ, reduced MCAO-induced permeability and improved functional outcome. Furthermore, inhibiting PKCβ after MCAO prevented ICH associated with delayed thrombolysis. These results show that PKCβ phosphorylation of occludin is a downstream mediator of tPA-induced cerebrovascular permeability and suggest that PKCβ inhibitors could improve stroke outcome and prevent ICH associated with delayed thrombolysis, potentially extending the window for thrombolytic therapy in stroke.

Repetitive Preload Elevation in Swine with Chronic Coronary Artery Disease Promotes Pro‐Fibrotic Gene Expression and Transmural Fibrosis in Remote Non‐Ischemic Myocardium

ObjectiveUsing implantable telemetry, we recently found that transient elevations in preload are common in swine with multi‐vessel coronary artery disease (CAD), presumably as a result of intermittent demand‐induced regional myocardial ischemia. Based on prior evidence that repetitive preload elevation can lead to interstitial fibrosis and myocardial stiffening in the absence of ischemia, the present study was designed to compare temporal changes in pro‐fibrotic gene expression and transmural variability in interstitial fibrosis in ischemic vs. non‐ischemic areas of the left ventricle (LV) in a porcine model of chronic CAD.MethodsA total of 20 juvenile swine were instrumented with fixed 1.5 mm constrictors on the proximal left anterior descending (LAD) and left circumflex (LCx) coronary arteries and followed for up to 3‐months, during which coronary stenosis severity progressed to >90 % (LAD: 93±2 %; LCx: 91±3 %). Expression of fibronectin (FN1) and lysyl oxidase like‐2 (LOXL‐2) was assessed in ischemic (LAD) and non‐ischemic (RCA) regions of the LV via quantitative PCR 1‐month (n=4) or 3‐months (n=8) after instrumentation and compared to normal controls (n=8). Post‐mortem quantification of interstitial fibrosis was performed on picrosirius red‐stained tissue samples from ischemic and non‐ischemic regions (n=16), with an automated classifier‐based approach to compare regional transmural variability in collagen content to that of normal controls (n=11). Flash‐frozen tissue samples from a sub‐set of animals with CAD (n=4) and normal controls (n=4) were subjected to uniaxial tensile testing to assess passive subendocardial stiffness.ResultsOne month after instrumentation, FN1 expression was 2.5±0.9‐fold higher than control in the ischemic region and 2.7±0.7‐fold higher than control in the non‐ischemic region of the LV (both p<0.05). LOXL2 expression was also significantly higher in the ischemic (2.2 ± 0.6‐fold higher than control) and non‐ischemic (2.4 ± 0.3‐fold higher than control) regions of the LV at this timepoint. Two months later, pro‐fibrotic gene expression had normalized but a significant elevation in interstitial collagen content was observed throughout the LV of animals with CAD (Figure; left panel). Interestingly, subendocardial fibrosis was particularly prominent in the non‐ischemic RCA territory, which coincided with a significant increase in subendocardial passive stiffness in this region (Figure; right panel).ConclusionsIn a porcine model of chronic CAD, repetitive preload elevation is associated with transient changes in pro‐fibrotic gene expression that ultimately lead to transmural fibrosis that is particularly prominent in non‐ischemic areas of the LV. Regional transmural variability in collagen content coincides with changes in the passive stiffness of non‐ischemic myocardium, suggesting that repetitive preload elevation may contribute to fibrosis‐mediated diastolic dysfunction in patients with chronic CAD.

Preservation of Right Ventricular Contractility After Transient Phenylephrine‐Induced Pressure Overload in Swine

ObjectiveWe have previously demonstrated that a transient phenylephrine (PE)‐induced rise in systemic arterial blood pressure leads to reversible left ventricular (LV) systolic dysfunction in the absence of ischemia (i.e., “stretch‐induced stunning”). However, the extent to which this phenomenon occurs in the right ventricle (RV) is unclear. Accordingly, the present study was designed to assess changes in pulmonary artery (PA) pressure and RV function during and after systemic administration of PE in swine.MethodsClosed‐chest propofol‐anesthetized swine (n=5) were instrumented with a Swan‐Ganz catheter and an admittance catheter for continuous measurement of PA pressure, RV pressure, and RV volume (ADV500; Transonic SciSense, Inc.). Ventricular end‐diastolic and end‐systolic volumes were assessed by multi‐detector computed tomography with iodinated contrast (1 mL/kg at 4 mL/s) before, during, and 30‐minutes after transient pressure overload elicited by a 1‐hour intravenous infusion of PE (18 mg/hour). Load‐independent RV systolic function was derived from RV pressure‐volume loops collected during inferior vena cava occlusion at baseline and 30 min after PE.ResultsPE elicited a significant rise in PA pressure (27±1/14±1 to 43±1/23±31mmHg; p<0.05) and RV pressure (25±2/3±1 to 44±2/8±2 mmHg; p<0.05) that normalized 30‐minutes after the end of the infusion period (PA: 28±1/11±1 mmHg; RV: 29±5/4±2 mmHg). This was accompanied by a significant increase in RV end‐diastolic and end‐systolic volumes and decrease in RV ejection fraction that tended to persist 30‐minutes after cessation of PE (Table; top panel). However, load‐dependent (dP/dtmax) and load‐independent (ESPVR and PRSW) parameters of RV systolic function were preserved after PE‐induced TPO (Table; bottom panel).ConclusionsDespite causing a significant rise in RV preload volume and pressure, transient PE‐induced pressure overload is not associated with RV contractile dysfunction during the post‐infusion period. The absence of stretch‐induced stunning in the RV may be linked to inherent differences in compliance relative to the LV as well as a diminished pressor response to PE in the pulmonary vs. systemic circulation.

The diagnostic and prognostic value of near-normal perfusion or borderline ischemia on stress myocardial perfusion imaging

BackgroundData on the diagnostic and prognostic value of subtle abnormalities on myocardial perfusion imaging (MPI) are limited. Methods and resultsIn a retrospective single-center cohort of patients who underwent regadenoson SPECT-MPI, near-normal MPI was defined as normal left ventricular ejection fraction (LVEF ≥ 50%) and a summed stress score (SSS) of 1-3 vs SSS = 0 in normal MPI. Borderline ischemia was defined as normal LVEF, SSS = 1-3, and a summed difference score (SDS) of 1 vs SDS = 0 in the absence of ischemia. Coronary angiography data within 6 months from MPI were tabulated. Patients were followed for cardiac death (CD), myocardial infarction (MI), coronary revascularization (CR), and Late CR (LCR) [> 90 days post MPI]. Among 6,802 patients (mean age, 62 ± 13 years; 42% men), followed for a mean of 2.5 ± 2.1 years, 4,398 had normal MPI, 2,404 had near-normal MPI, and 972 had borderline ischemia. Among patients who underwent angiography within 6 months, obstructive (≥ 70% or left main ≥ 50%) CAD was observed at higher rates among subjects with near-normal MPI (33.5% vs 25.5%; P = .049) and those with borderline ischemia (40.5% vs 25.8%; P = .004). During follow-up, 158 (2.3%) CD/MI, 246 (3.6%) CR, and 150 (2.2%) LCR were observed. Near-normal MPI (SSS = 1-3), compared to normal MPI (SSS = 0), was not associated with a significant difference in the risk of the composite endpoint of CD/MI (Hazard ratio [HR], 1.21; 95% confidence interval [CI], .88-1.66; P = .243) or LCR (HR 1.28; CI .93-1.78; P = .130), but was associated with a significant increase in the risk of CR (HR 1.91; CI 1.49-2.46; P < .001). Borderline ischemia (SDS = 1), compared to no ischemia (SDS = 0), was not associated with a significant difference in the risk of CD/MI [HR 1.09; CI .70-1.69; P = .693], but was associated with a significant increase in the risk of CR (HR 5.62; CI 3.08-10.25; P < .001) and LCR (HR 2.98; CI 1.36-6.53; P = .006). ConclusionNear-normal MPI and borderline ischemia on SPECT-MPI provide no significant prognostic information in predicting hard cardiac events but are associated with higher rates of obstructive angiographic CAD and coronary revascularizations.

Relationship Between the Severity of Exercise Induced Ischaemia and the Prevalence of Exercise Induced Calf Symptoms During Treadmill Testing With Transcutaneous Oximetry

It was hypothesised that there is a linear relationship between the severity of exercise induced calf ischaemia and the prevalence of calf claudication on a treadmill until a plateau is reached. It was expected that no pain would be present in the absence of ischaemia and all severely ischaemic calves would be symptomatic. This was a retrospective analysis of a cross sectional acquired database recording. Transcutaneous oxygen pressure (TcPO2) on the chest and on each calf was used to evaluate calf ischaemia during treadmill tests with simultaneous recording of calf pain in 7 884 subjects (15 768 calves). The minimum value of calf changes from rest minus chest changes from rest (DROPm) was calculated. Regression analyses were used to determine the correlation between the proportion of exercise induced symptoms present in the calves and each unit of DROPm values. Analysis was repeated after objective determination of the cutoff point between the linear increase and the plateau. A linear relationship was found between the degree of ischaemia and the proportion of symptomatic calves for DROPm values ranging from 0 mmHg to-28 mmHg (proportion=-0.014 × DROPm+ 0.32, r= 0.961, p <.001). For DROPm values lower than-28 mmHg (severe ischaemia), on average one of three limbs remained asymptomatic. The biphasic relationship between DROPm and prevalence of symptoms persists after exclusion of patients with diabetes mellitus, exercise induced hypoxaemia, and no evidence of lower extremity arterial disease (LEAD). The relationship between exercise induced pain and ischaemia is biphasic with a linear increase in the proportion of symptomatic limbs with ischaemia severity, until a plateau is reached for the more severely ischaemic limbs. The presence of exercise related calf symptoms should not automatically be reported as indicating the presence of LEAD; and the absence of exercise induced symptoms is not proof that ischaemia does not occur during exercise.

Treatment options for dialysis access steal syndrome.

Vascular access-induced limb ischemia is a known complication of arteriovenous fistulas and grafts. Many techniques have been adopted to prevent steal in high-risk patients and to treat steal in cases of moderate ischemia not controlled with conservative management. A major factor guiding treatment is access flow volume. Management is different when ischemia is combined with the excessive flow in contrast to the combination with normal flow. We describe the most popular techniques encountered in the English literature as a part of a stepwise approach to treating dialysis access steal syndrome. In absence of ischemia, when cardiac issues emerge due to extreme access flow volumes, some of these techniques are also used to decrease flow and protect the heart. Patient’s history, focused clinical examination, color duplex ultrasound examination, pulse oximetry and an angiogram are essential tools to approach this entity.

Using ultra-widefield red channel images to improve the detection of ischemic central retinal vein occlusion.

To examine the usefulness of red channel fundus imaging to detect the ischemic status in eyes with central retinal vein occlusion (CRVO). Ultra-widefield (UWF) fundus images were obtained from 42 eyes with CRVO. Twenty-one eyes were ischemic, and 21 eyes were non-ischemic. Rubeosis was found in 11 ischemic eyes. UWF images were split into red and green channels using ImageJ software. Both the color and red channel images were used to predict the presence or absence of ischemia when examined by masked graders. The sensitivity and specificity of UWF imagings for the detection of ischemia were calculated in Group A (total 42 eyes), Group B (32 eyes excluding non-rubeotic ischemic CRVO) and Group C (31 eyes excluding rubeotic ischemic CRVO), respectively. Moreover, a linear mixed model was conducted to investigate the relationship between the type of images and the accuracy of prediction in each group. No significant difference in the sensitivity of color fundus imaging was seen between Group A and Group B. By contrast, a significant difference in the sensitivity of red channel imaging was seen between Group A and Group B (p = 0.031). The accuracies of the predictions were not associated with the type of image in Group A and Group B, but were significantly associated in Group C (p = 0.026). UWF red channel imaging enabled more accurate detection of the ischemic status, compared with color fundus images, especially in non-rubeotic CRVO eyes.

Ischemic signs on the post-resuscitation ECG in absence of STEMI is associated with lower survival. A COACT trial's sub-study

Abstract Background The recently published Coronary Angiography after Cardiac arrest (COACT) trial found that urgent coronary angiography did not improve 90-day survival in out-of-hospital cardiac arrest (OHCA) patients without STEMI. The prognostic value of signs of ischemia on the ECG in absence of STEMI, is yet to be determined. Purpose To assess whether ischemic ECG patterns such as ST-depression and T-wave inversion are predictors for survival after OHCA in patients without STEMI. Methods In the COACT trial, patients with return of spontaneous circulation after OHCA with initial shockable rhythm and absence of ST-segment elevation were included. In this sub-study, the first post-resuscitation ECG recorded at the hospital was analysed for signs of ischemia. Ischemia was defined as ST-depression or T-wave inversion &amp;gt;1mm in ≥2 contiguous leads, or both. Primary endpoint was 90-day survival. Secondary endpoints included angiographic outcomes and left ventricular function assessed by cardiac magnetic resonance imaging or echocardiography. Results In total, 552 patients were included in the COACT trial. For this sub-study, 510 OHCA-patients had an ECG available for assessment of whom 340 patients (66.7%) had signs of ischemia on the ECG and 170 patients (33.3%) were without signs of ischemia. Patients with signs of ischemia were significantly older (p=0.003) and more frequently had a history of CAD (p=0.009). Left ventricular ejection fraction was lower in those with signs of ischemia (p=0.007). The number of acute thrombotic occlusions did not differ between groups (p=0.34). Patients with signs of ischemia had a significantly worse 90-day survival compared to patients that showed no signs of ischemia (HR 1.51 (95% CI 1.08–2.12); log-rank p=0.02). Furthermore, larger ST-depression was found to be associated with worse survival (log-rank p=0.01). Neurologic injury was the most common cause of death and its incidence did not differ between the groups (p=0.77). Conclusion Signs of ischemia in absence of STEMI on the post-resuscitation ECG is a predictor for worse survival. Furthermore, a correlation was found between the sum of ST-depression and lower survival rate. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Research grants of Netherlands Heart institue, Biotronic, AstraZeneca Survival plot signs of ischemia on ECGSurvival plot sum of ST-depression

Prognostic Value of Stress Cardiac Magnetic Resonance in Patients With Known Coronary Artery Disease

ObjectivesThis study sought to determine whether stress cardiac magnetic resonance (CMR) provides clinically relevant risk reclassification in patients with known coronary artery disease (CAD) in a multicenter setting in the United States. BackgroundDespite improvements in medical therapy and coronary revascularization, patients with previous CAD account for a disproportionately large portion of CV events and pose a challenge for noninvasive stress testing. MethodsFrom the Stress Perfusion Imaging in the United States (SPINS) registry, we identified consecutive patients with documented CAD who were referred to stress CMR for evaluation of myocardial ischemia. The primary outcome was nonfatal myocardial infarction (MI) or cardiovascular (CV) death. Major adverse CV events (MACE) included MI/CV death, hospitalization for heart failure or unstable angina, and late unplanned coronary artery bypass graft. The prognostic association and net reclassification improvement by ischemia for MI/CV death were determined. ResultsOut of 755 patients (age 64 ± 11 years, 64% male), we observed 97 MI/CV deaths and 210 MACE over a median follow-up of 5.3 years. Presence of ischemia demonstrated a significant association with MI/CV death (HR: 2.30; 95% CI: 1.54-3.44; P < 0.001) and MACE (HR: 2.24 ([95% CI: 1.69-2.95; P < 0.001). In a multivariate model adjusted for CV risk factors, ischemia maintained strong association with MI/CV death (HR: 1.84; 95% CI: 1.17-2.88; P = 0.008) and MACE (HR: 1.77; 95% CI: 1.31-2.40; P < 0.001) and reclassified 95% of patients at intermediate pretest risk (62% to low risk, 33% to high risk) with corresponding changes in the observed event rates of 1.4% and 5.3% per year for low and high post-test risk, respectively. ConclusionsIn a multicenter cohort of patients with known CAD, CMR-assessed ischemia was strongly associated with MI/CV death and reclassified patient risk beyond CV risk factors, especially in those considered to be at intermediate risk. Absence of ischemia was associated with a <2% annual rate of MI/CV death. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891)

Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial.

The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

Metabolic derangements are associated with impaired glucose delivery following traumatic brain injury.

Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements.Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited. Eighteen volunteers were excluded for age over 60 years (n = 11), movement-related artefact (n = 3) or physiological instability during imaging (n = 4). We measured cerebral blood flow, blood volume, oxygen extraction fraction, and 18F-FDG transport into the brain (K1) and its phosphorylation (k3). We calculated oxygen metabolism, 18F-FDG influx rate constant (Ki), glucose metabolism and the oxygen/glucose metabolic ratio. Lesion core, penumbra and peri-penumbra, and normal-appearing brain, ischaemic brain volume and k3 hotspot regions were compared with plasma and microdialysis glucose in patients.Twenty-six head injury patients, median age 40 years (22 male, four female) underwent 34 combined 18F-FDG and oxygen-15 PET at early, intermediate, and late time points (within 24 h, Days 2–5, and Days 6–12 post-injury; n = 12, 8, and 14, respectively), and were compared with 20 volunteers, median age 43 years (15 male, five female) who underwent oxygen-15, and nine volunteers, median age 56 years (three male, six female) who underwent 18F-FDG PET.Higher plasma glucose was associated with higher microdialysate glucose. Blood flow and K1 were decreased in the vicinity of lesions, and closely related when blood flow was <25 ml/100 ml/min. Within normal-appearing brain, K1 was maintained despite lower blood flow than volunteers. Glucose utilization was globally reduced in comparison with volunteers (P < 0.001). k3 was variable; highest within lesions with some patients showing increases with blood flow <25 ml/100 ml/min, but falling steeply with blood flow lower than 12 ml/100 ml/min. k3 hotspots were found distant from lesions, with k3 increases associated with lower plasma glucose (Rho −0.33, P < 0.001) and microdialysis glucose (Rho −0.73, P = 0.02). k3 hotspots showed similar K1 and glucose metabolism to volunteers despite lower blood flow and oxygen metabolism (P < 0.001, both comparisons); oxygen extraction fraction increases consistent with ischaemia were uncommon.We show that glucose delivery was dependent on plasma glucose and cerebral blood flow. Overall glucose utilization was low, but regional increases were associated with reductions in glucose availability, blood flow and oxygen metabolism in the absence of ischaemia. Clinical management should optimize blood flow and glucose delivery and could explore the use of alternative energy substrates.

Hybrid cardiac imaging-guided optimal management of right anomalous coronary artery origin from the opposite sinus with interarterial course (R-ACAOS): a case report

BackgroundDetermining the optimal management of right anomalous coronary artery from the opposite sinus (R-ACAOS) with an interarterial course (IAC) in middle-aged adults remains elusive. Hybrid cardiac imaging combining non-invasive and invasive approaches to identify high-risk anatomic features, as well as functional testing to assess potential ischaemic status by dynamic compression, can guide therapeutic decisions.Case summaryA 65-year-old female was newly diagnosed with R-ACAOS with IAC, accompanied by suspected angina and two syncope episodes. She was initially considered as non-specific chest pain based on negative treadmill test (TMT) taken 10 years earlier. An anomaly of R-ACAOS with IAC travelling between the aorta and pulmonary artery was detected by coronary computed tomography angiography with a severe stenosis at the ostium, but with little evidence of atherosclerotic plaque. Exercise test (TMT) and single-photon emission computed tomography (SPECT) results were negative. Invasive imaging revealed a luminal area stenosis of 45% at the ostial right coronary artery, and a slit-like orifice anatomical feature, with a minimal lumen area of 5.81 mm2 at diastole determined by intravascular ultrasound. Based on hybrid cardiac imaging results and previous data from a case series, conservative management was recommended with strenuous exercise restrictions. The patient fared well during 12 months of follow-up after discharge.DiscussionHybrid cardiac imaging-guided conservative management including exercise restriction appears justifiable in such middle-aged adults with R-ACAOS accompanied by suspected angina in absence of ischaemia in stress-induced tests (TMT or SPECT), despite high-risk anatomical features of an IAC and slit-like orifice being present.

Effect of myocardial ischemia in diabetic and non-diabetic patients: long-term follow-up of MASS registry

Abstract Background Prognostic role of ischemia has been debated. The association with diabetes mellitus (DM) seems to add risks of cardiovascular events. We aimed to assess whether ischemia confers additional risks in diabetic population. Methods A single-center, prospective study including subjects with multivessel coronary artery disease who underwent surgery, percutaneous intervention or medical therapy. They were stratified according to presence of ischemia and DM. Primary endpoint was defined as death or myocardial infarction (MI). Secondary endpoint was death. Results We enrolled 1001 patients with conclusive stress tests: 790 (79%) with ischemia and 211 (21%) without ischemia. Mean follow-up was 8.7 years (IQR 4.04–10.07). The primary outcome occurred in 228 (28.9%) patients with ischemia and 64 (30.3%) without ischemia (p=0.60). Event rate among those with negative stress test, with or without DM, was similar (p=0.96 and p=0.60 respectively). Among those with ischemia, 145 (35.6%) with DM presented the combined event compared to 83 (21.7%) without DM (HR: 1.39; 95% CI 1.06–1.83, p=0.01). Death occurred in 117 diabetic and 65 (17%) in non-diabetic subjects (HR: 1.49, 95% CI: 2.03, p=0.01). Conclusion Overall, the presence or absence of ischemia was not related to death or MI. However, subset of patients with DM and ischemia revealed increased risk of death and cardiovascular events irrespective of treatment strategy. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Zerbini Foundation

Abstract 265: Systemic Inflammation and Cardiac Macrophage Infiltration Accompany Stretch-induced Myocardial Injury in Swine Subjected to Transient Pressure Overload

Objective: Transient pressure overload (TPO) elicits stretch-induced myocyte injury in the absence of ischemia or infarction, but the extent to which this is associated with inflammation is unclear. The present study was designed to assess immune activation after TPO in swine and compare the inflammatory cytokine profile to that observed after myocardial infarction (MI). Methods: Swine received a brief infusion of phenylephrine (18 mg/hr iv; 30-60 min) to induce TPO and were studied for 1 hr (n=5), 3 hr (n=6), or 24 hr (n=6) before analysis of myocardial macrophage gene expression (CD68) via qPCR. Serial blood sampling was performed to assess neutrophil and monocyte counts as well as circulating cardiac troponin I (cTnI), IL-6, TNF-α, and CRP. Cytokine levels were compared to those from a separate group (n=5) subjected to a 60 min LAD occlusion to produce MI. Results: TPO increased circulating cTnI (from 20±5 ng/L to 340±58 ng/L at 3 hr and 1520±616 ng/L at 24 hr; p&lt;0.01) without evidence of infarction. Compared with controls (n=6), swine subjected to TPO exhibited increased CD68 gene expression at 1, 3, and 24 hr ( A ). This was accompanied by a rise in peripheral blood neutrophils and monocytes ( B ) as well as an elevation in circulating IL-6, TNF-α, and CRP that was comparable to that observed after MI ( C ). Conclusion: Myocyte injury following TPO elicits mobilization of neutrophils and monocytes and a rise in circulating inflammatory cytokines comparable to that observed after MI. This is accompanied by an increase in cardiac macrophages and may be an important mechanism by which repetitive episodes of TPO lead to interstitial fibrosis and diastolic dysfunction without anatomic hypertrophy.

Adhesive Small Bowel Obstruction: Predictive Radiology to Improve Patient Management.

Adhesive small bowel obstruction (SBO) remains one of the leading causes of emergency room visits and is still associated with high morbidity and mortality rates. Because the management of adhesive SBO has shifted from immediate surgery to nonoperative treatment in the absence of ischemia, it is crucial to rapidly detect or predict strangulation, which requires emergent surgery. CT is now established as the best imaging technique for the initial assessment of patients suspected of having adhesive SBO. CT helps confirm the diagnosis of mechanical SBO, locate the site of obstruction, establish the cause, and detect complications. This article is a review of the role of imaging in answering specific questions to help predict the management needs of each individual patient. It includes (a) an update on the best CT signs for predicting ischemia and a need for bowel resection; (b) a discussion of the CT features that help differentiate open-loop from closed-loop obstruction and a single adhesive band from matted adhesions and how these differences can influence the management; and (c) a review of the main CT predictors of the success or failure of nonoperative management in adhesive SBO.

Clinical and Imaging Features of Contrast-Induced Neurotoxicity After Neurointerventional Surgery

Contrast-induced neurotoxicity (CIN) is an infrequent complication of endovascular procedures, and its understanding remains poor. We aimed to study and characterize the clinical and imaging features of a case series of CIN after neurointerventional surgery. We reviewed all neuroendovascular consecutive procedures from September 2014 to November 2018. CIN was defined as new onset of neurologic deficits that occurred postoperatively after excluding other conditions. All demographic, clinical, procedural, and radiologic data were retrospectively analyzed and collected. Eleven cases of CIN in 1587 patients were identified out of 2510 procedures. The median age was 76 years (interquartile range [IQR], 65-81). The most common comorbidity was hypertension (82%). Median procedure time was 100 minutes (IQR, 80-130.5 minutes). All patients showed wide variability in intraprocedural blood pressure (BP) recordings with fluctuations from the baseline BP. Systolic BP ranged from 83 mm Hg below the patient baseline to 80 mm Hg above baseline. The median symptom onset was 4 hours (IQR, 0.8-9.5 hours). The CIN signs and symptoms presented gradually, initially with encephalopathy and later with focal signs. All patients had an initial computed tomography scan, which showed ipsilateral cerebral edema in 82% of patients. Two had contrast enhancement. Complete resolution of CIN symptoms was obtained in a median time of 3 days (IQR, 2.5-3 days). CIN should be considered in the context of the progressive onset of neurologic deficits after neuroendovascular procedures. A distinct imaging pattern of ipsilateral hemisphere edema in the absence of ischemia is usually identified. Variability in procedural BP might be a predisposing factor.

Stress-delta B-type Natriuretic Peptide Levels as a Test for Inducible Myocardial Ischemia: A Systematic Review and Meta-Analysis.

BackgroundCardiac ischemia induces myocardial dysfunction and ventricular wall stretch, which causes the release of B-type natriuretic peptide (BNP) into the bloodstream. However, it is unclear whether inducible ischemia produces a significant change in BNP levels (“stress delta-BNP”). The objective of this study was to determine the utility of stress-delta BNP levels and its precursor NT-proBNP for detecting inducible myocardial ischemia during cardiac stress testing.MethodsWe conducted a systematic review and meta-analysis. We searched PubMed, EMBASE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Ovid. Studies examining the changes in levels of BNP and its precursor, N-terminal pro-B-type natriuretic peptide (NT-proBNP), after an exercise cardiac stress test were included. Two reviewers independently analyzed titles and abstracts. s that did not provide enough information regarding eligibility criteria were kept for full-text evaluation. The same two reviewers also performed data extraction for analyses. Any disagreement was resolved by a consensus and, if it persisted, by a third reviewer adjudication. We report the median and mean values in studies in the order of sample size.ResultsA total of 15 studies met the inclusion criteria. Nine studies reported results in medians and six studies reported results in means. Of the nine studies, five assessed BNP alone, three assessed NT-proBNP, and one assessed both. Due to the non-normal distribution of results in these studies, they could not be meta-analyzed. Of the six studies that reported results in means, three assessed BNP and three assessed NT-proBNP. The standardized difference between normal and ischemic patients' stress-delta BNP values was -0.39 (95% confidence interval (CI): -0.61; -0.17) in a fixed-effects model and -0.73 (95% CI: -1.72; 0.28) in the random-effects model with high heterogeneity (I^2 = 94%, Q test P = 0.001). For NT-proBNP, the meta-analysis model showed no significant difference between the stress-delta test for ischemic and normal patients (standardized mean difference (SMD): -0.02, 95% CI: -0.31; 0.28). Patients without inducible ischemia appeared to have a lower baseline BNP and NT-proBNP compared to patients with inducible ischemia by stress testing. Although some studies report higher stress-delta BNP in the ischemic group, this pattern was not seen consistently across studies. There was high heterogeneity across studies which was not robust to sensitivity analysis. A random-effects model failed to find statistically significant differences in stress-delta BNP or NT-proBNP.ConclusionsWe failed to find a relationship between stress-delta BNP or NT-proBNP and the presence or absence of ischemia. This may be due to high heterogeneity in the underlying studies.