Reversible Ischemia Research Articles

Cardiac troponin T and NT-proBNP for detecting myocardial ischemia in suspected chronic coronary syndrome

BackgroundElevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear. MethodsPatients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples. ResultsWe included 430 patients (25% female) aged 64 ± 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73–294) versus 87 (44–192) ng/L and 10 (6–13) versus 7 (4–11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%–73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (≤5 ng/L cTnT and ≤ 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%. ConclusioncTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.

Reversible Ischaemia Without Infarction Presenting as Progressive Hemichorea (P10-10.010)

Reversible Ischaemia Without Infarction Presenting as Progressive Hemichorea (P10-10.010)

Inpatient myocardial perfusion imaging characteristics of patients admitted with suspected type 2 myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background ESC defines a type 1 myocardial infarction (T1MI) as "MI caused by atherosclerotic coronary artery disease and usually precipitated by atherosclerotic plaque disruption" and type 2 myocardial infarction (T2MI) as "ischaemic myocardial injury in the context of a mismatch between oxygen supply and demand". In practice it can be difficult to differentiate between MI types and the role of myocardial perfusion imaging (MPI) in making this distinction remains unclear. Purpose To establish whether suspected T2MI has different characteristics on MPI compared to suspected T1MI. Methods All inpatient MPI scans at our institution between 01/03/2018 and 28/02/2020 were retrospectively reviewed. Patients were excluded if they had a previous diagnosis of coronary artery disease, an invasive coronary angiogram prior to MPI, or a maximal troponin T &amp;lt; 14ng/l. Diagnoses were categorised based on review of scan request information. Echocardiography images were reviewed if within 30 days of MPI. Results 58 patients were included: 28 with suspected type 2 MI and 30 with suspected type 1 MI (mean age 70 vs. 75). There was no statistically significant difference in maximal troponin T between groups (T2MI 394.0 ng/l, T1MI 415.6 ng/l; p=0.90). 50% T2MI patients and 53% T1MI patients had a territorial defect on MPI (fully reversible defect 25% vs. 17%, partially reversible defect 7% vs. 33%, irreversible defect 14% vs. 3% for T2MI vs T1MI respectively). 25% T2MI patients had an area &amp;gt;10% LV myocardium volume showing reversibility, compared with 33% T1MI (p=0.49). Both groups had similar proportions of left ventricular (LV) impairment (both had 65% of patients with normal LV ejection fraction) and prevalence of regional wall motion abnormalities ((RWMA) 39% for T2MI, 35% for T1MI, p=0.76) on echocardiography. Conclusions A clinically significant proportion of the suspected T2MI group had territorial ischaemia. Additionally, both patient groups demonstrated similar proportion of patients with reversible ischaemia and of LV systolic dysfunction. Therefore differentiation between T2MI and T1MI can be challenging both clinically and with MPI. Prospective studies are required to establish the optimal methods for making the distinction between types of MI.

The Effect of Presurgical and Postsurgical Topical Tacrolimus on Pedicled Flap Survival in Rats: A Pilot Study.

Our previous rodent studies demonstrated significantly decreased full-thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared with petroleum jelly. Histologically, we found that topical tacrolimus was correlated with increased vascular growth in areas more susceptible to ischemic damage. The purpose of this study was to investigate the potential benefits of pretreatment with tacrolimus. By applying tacrolimus in advance of raising the dorsal skin flaps, we hoped to increase vascularity and thus increase the overall viability of the flaps. Twenty Sprague-Dawley rats were initially randomized to 4 groups based on timing of tacrolimus treatment (presurgical/postsurgical treatment): control/control (C/C), control/tacrolimus (C/T), tacrolimus/control (T/C), and tacrolimus/tacrolimus (T/T). Treatments consisted of 0.2 g of the control (topical petroleum jelly) and 0.1% topical tacrolimus to the rat dorsum twice per day. After 7 days of presurgical treatment, a cranially based dorsal skin flap measuring 3 × 10 cm was created. Two rats perished during surgery and were excluded for further analysis. Each rat was treated for a further 7 days and sacrificed. Two blinded reviewers marked the total skin flap area as well as areas of viable tissue, reversible ischemia, and full-thickness necrosis. Percentage areas were calculated using Fiji/ImageJ, and statistical analysis was performed in R. The average viable areas for C/C, C/T, T/C, and T/T were 31.4%, 31.9%, 35.6%, and 22.6%, respectively. The average reversible ischemic area for C/C, C/T, T/C, and T/T was 53.1%, 54.0%, 54.1%, and 71.5%, respectively. The average necrotic area for C/C, C/T, T/C, and T/T was 15.4%, 14.0%, 10.2%, and 5.9%, respectively. For areas of reversible ischemia, T/T arm had higher areas compared with C/T (P = 0.004) and T/C (P = 0.044). There was no significance between treatment arms for areas of viable and necrotic tissue. We observed higher areas of reversible ischemia for continuous tacrolimus treatment compared with only pre-tacrolimus application or post-tacrolimus application. This suggests that tacrolimus application before and after surgical insult may be associated with improved ischemic survival of the skin. Although we did not observe decreased areas of necrosis for tacrolimus treatment compared with control, this was likely due to the limited number of rats available in each arm to reach significance. Further study is needed to fully elucidate the encouraging trends that were observed.

Combination of myocardial perfusion imaging, left ventricle function parameters and coronary artery calcium score in risk evaluation in patients with diabetes mellitus.

Myocardial perfusion imaging (MPI) can be challenging in some cases of multi vessel involvement. Our aim was to examine specific group of patients with diabetes mellitus (DM), who did not have significant reversible ischaemia diagnosed on perfusion study itself, and asses additional value of functional parameters obtained from gated acquisition and added information from coronary artery calcium score (CACS). One hundred and seventy eight patients with a history of DM, with summed difference score (SDS)≤1, were included in the study. All patients underwent gated acquisition with recording of functional parameters and CACS evaluation. During the follow-up, cardiac events (CE) were recorded. During the median follow-up of 20.3 months there were 23 CE encountered. Optimal cut-off value for CACS to predict CE was found at 1427, higher values were significantly related to CE (P<0.001). Low stress left ventricular ejection fraction (LVEF) <45% and induced stress LVEF drop for 5% were also more frequent in CE group (P=0.001, P=0.008). Multivariable Cox analysis revealed low stress LVEF (P=0.001, HR=4.48, 95%CI 1.79-11.22), stress induced LVEF drop (P=0.017, HR 3.13, 95%CI 1.22-8.01) and high CACS (P<0.001, HR 10.52, 95%CI 4.32-25.63) as significant predictors of CE. Low stress LVEF under 45%, post-stress LVEF drop for more than 5% and CACS more than or equal to 1427 are significant predictors of CE in patients with DM, who did not have reversible ischemia detected on MPI single photon emission computed tomography (SPECT).

Chapter 22 - Neuromonitoring during descending aorta procedures

Thoraco-abdominal aneurysm (TAA) repair carries a significant risk of spinal cord infarction. The latter results from irreversible changes in the spinal cord arterial network, e.g., sacrifice of the segmental arteries. Intra-operative neurophysiology with somatosensory and especially motor evoked potential (SEP and MEP respectively) monitoring, has emerged as an effective tool to assess the efficiency of the collateral blood flow, detect reversible spinal cord ischemia and guide the peri-operative multidisciplinary management to prevent postoperative paraplegia. The main roles of such monitoring include diagnosis of spinal cord vs peripheral limb ischemia, titration of mean arterial pressure during aortic clamping, the guidance of selective re-implantation of critical segmental arteries, and management of hemodynamics in the immediate postoperative period. In addition, manipulation of the aortic arch and proximal descending aorta, adds the risk of cerebral infarction from both low flow state and/or thromboembolic events. As such, EEG monitoring may be a useful add-on for either assessment of the efficiency of cerebral cooling as a neuroprotective method and/or for detection and treatment of reversible cerebral ischemia. This chapter presents the multimodality approach to open TAA monitoring as a versatile tool for the prevention of devastating postoperative neurologic deficits.

Correlation between quantification of myocardial area at risk and ischemic burden at cardiac computed tomography

PurposeThis study aims to investigate the correlation between myocardial area at risk at coronary computed tomography angiography (CCTA) and the ischemic burden derived from myocardial computed tomography perfusion (CTP) by using the 17-segment model. MethodsForty-two patients with chest pain complaints who underwent a combined CCTA and CTP protocol were identified. Patients with reversible ischemia at CTP and at least one stenosis of ≥ 50% at CCTA were selected. Myocardial area at risk was calculated using a Voronoi-based segmentation algorithm at CCTA and was defined as the sum of all territories related to a ≥ 50% stenosis as a percentage of the total left ventricular (LV) mass. The latter was calculated using LV contours which were automatically drawn using a machine learning algorithm. Subsequently, the ischemic burden was defined as the number of segments demonstrating relative hypoperfusion as a percentage of the total amount of segments (=17). Finally, correlations were tested between the myocardial area at risk and the ischemic burden using Pearson’s correlation coefficient. ResultsA total of 77 coronary lesions were assessed. Average myocardial area at risk and ischemic burden for all lesions was 59% and 23%, respectively. Correlations for ≥ 50% and ≥ 70% stenosis based myocardial area at risk compared to ischemic burden were moderate (r = 0.564; p < 0.01) and good (r = 0.708; p < 0.01), respectively. ConclusionThe relation between myocardial area at risk as calculated by using a Voronoi-based algorithm at CCTA and ischemic burden as assessed by CTP is dependent on stenosis severity.

Оценка перфузии и диастолической функции у больных с микрососудистой стенокардией, по данным перфузионной гибридной томосцинтиграфии (С-ОФЭКТ/КТ) миокарда

Objective. To study the correlation between quantitative perfusion parameters and the diastolic function in patients with microvascular angina according to the single-photon emission computed tomography with 99mTc. Material and methods. The study included 17 patients, each of whom underwent selective coronary angiography (CAG) and ECG-synchronized C-SPECT/CT of myocardium with 99mTc-technetril at rest and in combination with exercise testing on bicycle ergometer (ergonometer Anaerobic Test). Verification of ischemia was performed using C-SPECT/CT with 99mTc-technetril at rest (r) and with ergonometer Anaerobic Test (s) according to a 2-day protocol. Quantitative perfusion indices (QPI) and DF were assessed by 17 segmental LV model: rExtent/sExtent, area of perfusion impairment (PI); SRS, SSS, severity of NP; rTPD/sTPD, total perfusion deficit; SDS, stress-induced (reversible) ischemia index; iTPD, ischemic perfusion deficit; PFR, peak LV volume filling rate; MFR/3, avg. LV filling rate in the first/3 of diastole; TTPF, time from the beginning of diastole to the peak LV filling level; PFR2, peak LV filling volume rate during the 2nd peak. Results. The present study revealed a diastolic dysfunction in patients with microvascular angina and increased diastolic filling disturbances during myocardial ischemia with exercise. When comparing the perfusion and diastolic function, a direct link between the prevalence and the intensity of perfusion dysfunction at rest and stress-induced ischemia and temporary parameters and inverse correlation - with speed parameters of diastole was revealed. Conclusion. Patients with microvascular angina show signs of left ventricular dysfunction. The conducted correlational analysis revealed the existence of interconnection between perfusion and diastolic function.

Abstract 11473: Renal and Cardiac Effects of Remote Ischemic Preconditioning in Children Undergoing Cardiopulmonary Bypass Surgery

Introduction: Children undergoing cardiac surgery are at risk for AKI and cardiac dysfunction affecting outcome. Improved surgical techniques and post-operative care allow better outcomes in complex repairs and at-risk patients. Opportunity exists in further protecting multiple end organ function with remote ischemic preconditioning (RIPC) given promising but mixed data in adults and children. Hypothesis: A non-invasive technique of inducing reversible lower extremity ischemia with inflation of pressure cuff lessens renal and myocardial injury. Methods: A single center randomized, placebo controlled, double blinded trial of RIPC in children undergoing cardiac surgery of RACHS-1 category 2 or greater. RIPC was performed in the operating room after anesthesia and before sternotomy. Pre-specified end points are change in creatinine, eGFR, development of AKI, B-type natriuretic peptide and Troponin I at 6, 12, 24, 48, 72 hours post separation from bypass. Secondary end points included select clinical outcomes. Results: There were 45 in the RIPC and 39 patients in the control group: age was 3.5 and 3.8 years, respectively; 57 patients below 1 year of age; 35 patients below 1 month of age. There was no difference between groups in creatinine, cystatin C, eGFR at each time points. There was a trend for a larger rate of decrease, especially for cystatin C (p=0.042) in the RIPC group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of RIPC group (p=0.094). Adjusting for baseline creatinine, the odds ratio for AKI in in RIPC compared to control group was 0.31 (p=0.037). Adjusted for clinical characteristics, the odds ratio was 0.34 (p=0.056). Peak troponin occurred at 6 hrs. Compared to control, the RIPC group had a lower troponin at 6 hrs (p=0.140). However, no difference in other analyses of troponin and B-type natriuretic peptides between the groups. Length of stay, all-cause mortality, systolic function by echocardiography and composite clinical end points of advanced renal and heart failure were not different between groups. Conclusions: There is suggestion of RIPC delivering renal protection in an at-risk pediatric population. Additional larger, higher risk population studies will be required to fully determine its efficacy.

Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis

Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. Stryker Neurovascular.

Late thrombectomy for ischaemic stroke

Patients with ischaemic stroke tend to delay seeking professional help compared with patients with acute myocardial infarction with ST elevation (STEMI). Moreover, for patients with STEMI, a diagnosis of ongoing ischaemia can be made with an electrocardiogram in the ambulance. The situation is vastly different for a patient who has had a stroke. Those with cortical infarcts—the case for most patients—are often not aware of their acute deficit, or they cannot communicate because of language problems. Moreover, patients with cerebral ischaemia do not have pain, as patients with STEMI do. They also typically do not wake up when a stroke occurs during sleep. Notification of the stroke to emergency services often depends on the alertness of partners and bystanders, and it should not be surprising that patients have delays in presenting to the emergency room, typically 3–4 h later than patients with a STEMI. 1 Al'Aref SJ Wong SC Swaminathan RV et al. Analysis of reperfusion time trends in patients with ST-elevation myocardial infarction across New York State from 2004 to 2012. Int J Cardiol. 2017; 232: 140-146 Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar , 2 de Havenon A Alexander MD Nogueira RG et al. Duration of symptomatic stroke and successful reperfusion with endovascular thrombectomy for anterior circulation large vessel occlusive stroke. J Neurointerv Surg. 2021; 01 (neurintsurg-2020-016961.) Google Scholar In patients arriving after more than 6 h from onset, diagnosis of ongoing ischaemia caused by intracranial large vessel occlusion has to be made with CT angiography and perfusion imaging, which further adds to the delay. Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysisThese findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6–24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6–24 h time window. Full-Text PDF

Prognostic implication of myocardial perfusion and contractile reserve in end-stage renal disease: A direct comparison of myocardial perfusion scintigraphy and dobutamine stress echocardiography

BackgroundWe aimed to compare the prognostic value of myocardial perfusion scintigraphy (MPS) and dobutamine stress echocardiography (DSE) in patients with end-stage renal disease (ESRD) without known coronary artery disease. MethodsTwo-hundred twenty-nine ESRD patients who applied for kidney transplantation at our centre were prospectively evaluated by MPS and DSE. The primary endpoint was a composite of myocardial infarction (MI) or all-cause mortality. The secondary endpoint included MI or coronary revascularization (CR) not triggered by MPS or DSE at baseline. ResultsMPS detected reversible ischemia in 31 patients (13.5%) and fixed perfusion defects in 13 (5.7%) patients. DSE discovered stress-induced wall motion abnormalities (WMAs) in 28 (12.2%) and at rest in 18 (7.9%) patients. MPS and DSE results agreed in 85.6% regarding reversible defects (κ = 0.358; P < .001) and in 90.8% regarding fixed defects (κ = 0.275; P < .001). Coronary angiography detected relevant stenosis > 50% in only 15 of 38 patients (39.5%) with pathological findings in MPS and/or DSE. At a median follow-up of 8 years and 10 months, the primary endpoint occurred in 70 patients (30.6%) and the secondary endpoint in 24 patients (10.5%). The adjusted Cox hazard ratios (HRs) for the primary endpoint were 1.77 (95% CI 1.02-3.08; P = .043) for perfusion defects in MPS and 1.36 (95% CI 0.78-2.37; P = ns) for WMA in DSE. The secondary endpoint was significantly correlated with the findings of both modalities, MPS (HR 3.21; 95% CI 1.35-7.61; P = .008) and DSE (HR 2.67; 95% CI 1.15-6.20; P = .022). ConclusionPerfusion defects in MPS are a stronger determinant of all-cause mortality, MI and the need for future CR compared with WMAs in DSE. Given the complementary functional information provided by MPS vs DSE, results are sometimes contradictory, which may indicate differences in the underlying pathophysiology.

The associations of serum homoarginine to long-term prognosis in patients with chronic coronary syndrome and non-obstructive coronary artery disease

Abstract Background Although generally at lower risk than those with obstructive CAD, patients with non-obstructive CAD (NOCAD) are heterogeneous concerning long-term prognosis. Notably, reversible ischemia due to vascular dysfunction is a frequent finding in NOCAD patients (1). The endogenous, non-proteinogenic amino acid homoarginine (hArg) increases the availability of nitric oxide (NO) and thereby the NO-dependent vasodilatation (2). Several studies have reported a strong inverse relation between serum hArg levels and cardiovascular disease (CVD) risk among patients with obstructive CAD. However, the prognostic implications of serum hArg levels in NOCAD patients have not been explored previously. Purpose We evaluated serum hArg as a predictor of long-term risk of CVD mortality among patients with NOCAD. Methods 1046 patients with chronic coronary syndrome (CCS) underwent elective coronary angiography during 2000–2004, with the findings of NOCAD. Serum hArg was measured by liquid chromatography-tandem mass spectrometry in samples that had been frozen and stored at −80°C. The association of serum hArg to CVD mortality risk was visualized in a generalized additive regression plot and further explored using Cox regression. The models included age, sex, body mass index, hypertension, diabetes, smoking status, serum LDL cholesterol and estimated glomerular filtration rate as independent covariables. We evaluated model discrimination and risk classification by calculating C-statistics and net reclassification improvement (NRI &amp;gt;0), respectively. Results Median (25th-75th percentiles) age at inclusion was 57 (51–65) years, 48.5% were women and median (25th-75th percentiles) level of serum hArg was 1.87 (1.47–2.38) μmol/L. During median (25th- 75th percentiles) 14.1 (13.2–15.4) years of follow-up 5.7% of the patients died from CVD. The multivariable adjusted hazard ratio (95% confidence interval) per SD increment of (log transformed) hArg was 0.53 (0.40–0.70) in relation to CVD mortality. The multivariable model without biomarker provided a C- statistics for CVD mortality of 0.79 which increased to 0.82 by the addition of serum-hArg to the model (Δ area =0.03, P=0.01). Further, serum hArg provided a high NRI (95% CI) of 0.53 (0.40–0.70), P&amp;lt;0.001. Conclusion We demonstrated a strong inverse relationship between serum hArg and long-term risk of CVD mortality among patients with NOCAD. Our study adds to previous literature linking low hArg with vascular dysfunction and adverse CVD prognosis. The potential clinical usefulness of serum hArg measurements for the identification of a high-risk phenotype in NOCAD warrants further evaluation. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): The Western Norway Regional Health Authority

COVID-19 COAGULOPATHY SECONDARY TO ACTIVATING PLATELET ANTIBODIES

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coagulopathies have been extensively reported in COVID-19 patients (1). CASE PRESENTATION: A 58-year old female presented to the emergency department (ED) with 2-weeks history of shortness of breath. A nasopharyngeal swab was positive for SARS-CoV-2. She was treated and discharged on room air. D-dimer (DD) and platelet (plt) count at the time of discharge were within normal. Six days after discharge she presented to the ED with severe abdominal and right leg pain. Lower extremity pulses were present by doppler but hard to palpate. Laboratory tests showed elevated DD (27,820 ng/ml) and elevated plt (530 x109/L), table-1. Computed tomography scan (fig-1) of the abdomen and pelvis showed multiple wedge-shape infarcts in the liver, spleen, and right kidney and acute thrombosis of the right common iliac artery. Acute deep vein thrombosis in the lower and upper extremities were excluded by US. Duplex US of the right lower extremity showed ankle brachial index of 0.2. The patient was admitted and started on heparin therapy. On day 2, plt count dropped to 127 x 109/L. The 4T score was 5, heparin was stopped and argatroban was started. Serotonin release assay was sent and showed no inhibition with high dose heparin. However, non-heparin dependent anti-platelet activating antibodies (class I HLA antibodies) were detected. Anti-platelet factor-4 was negative and patient was restarted back on heparin. Thrombophilia and autoimmune work up were negative. Patient was discharged on low-molecular weight heparin. Plt count was 179 x109/L before discharge. DISCUSSION: Recent study published by Bilaloglu showed that 533 (16.0%) COVID-19 patients had at least one thrombotic evet during hospitalization. Of all 3334 patients, only 32 (1.0%) had acute limb ischemia, upper extremity arterial thrombosis, renal, and splenic infarcts, and portal vein thrombosis (2). In another case series, 4 of the reported 7 cases developed progressive irreversible lower limb ischemia. Two patients presented with lower limb ischemia and the other two developed severe thrombosis after 4 and 15 days respectively. Of the reported lab values, two patients had D-dimer levels more than 20,000 ng/ml and the same two were thrombocytopenic (1). Interestingly, our patient had reversible limb ischemia as shown by the repeated duplex US done after discharge. Nicolai and colleagues reported that plts hyperactivation and possible immuno-thrombosis may play a role in the pathogenesis of coagulopathy among severe COVID-19 patients (3). In our case, patient had hypercoagulability secondary to activating anti-platelets antibodies, a novel finding that can help understanding the pathogenesis of COVID-19 induced hypercoagulability. CONCLUSIONS: COVID-19 associated coagulopathy can be un-predictable. Activating anti-plt antibodies may play a role in the pathogenesis of COVID-19 coagulopathy. REFERENCE #1: Kashi M, Jacquin A, Dakhil B, et al. Severe arterial thrombosis associated with Covid-19 infection. Thromb Res 2020;192:75-7. REFERENCE #2: Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. JAMA 2020. REFERENCE #3: Nicolai L, Leunig A, Brambs S, et al. Immunothrombotic Dysregulation in COVID-19 Pneumonia is Associated with Respiratory Failure and Coagulopathy. Circulation 2020. DISCLOSURES: No relevant relationships by Bahaa Abdelghaffar, source=Web Response No relevant relationships by hamed daw, source=Web Response No relevant relationships by Tariq Kewan, source=Web Response No relevant relationships by Talha Saleem, source=Web Response

Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke.

Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk. We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S2TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario. Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%–1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk. Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment.

Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial.

BackgroundSodium–glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial (The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk.Methods and ResultsWe randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add‐on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium‐82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate‐pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08–2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, −0.18 to 0.21) or placebo groups: 0.06 (95% CI, −0.15 to 0.27), with no treatment effect −0.05 (95% CI, −0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium‐82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A1c by 0.76% (95% CI, 1.0–0.5; P<0.001) and increased hematocrit by 1.69% (95% CI, 0.7–2.6; P<0.001).ConclusionsEmpagliflozin did not improve MFR among patients with type 2 diabetes mellitus and high cardiovascular disease risk. The present study does not support that short‐term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials.RegistrationURL: https://clinicaltrialsregister.eu/; Unique identifier: 2016‐003743‐10.

Stress Echocardiography Audit

Background: Stress echocardiography is a very useful diagnostic and prognostic test in the evaluation of significant coronary artery disease (CAD) causing inducible myocardial ischemia. Stress echocardiography has higher sensitivity and specificity as compared to exercise stress electrocardiography, and therefore, the guidelines recommend opting for the former modality over the latter. There are data suggesting that the incidence of major cardiac events is &lt;1% within 12 months of a negative stress echocardiogram showing no reversible ischemia. The present audit was performed to assess the predictive accuracy of stress echocardiography at our center for major cardiac events during the first year of the test. Methods: Data for all patients referred for stress echocardiography between March 10, 2015 and December 31, 2018 were captured. All patients were contacted after 1 year to evaluate for any cardiac event (cardiac death, nonfatal myocardial infarction, need for revascularization or hospital admission related to acute coronary syndrome, and/or heart failure). Analysis was performed using the standard statistical definitions. Results: Baseline information was available for 1205 patients (mean age 59 years, 60% males). Of these, 416 (34.4%) had documented CAD; 223 (18.4%) underwent stress echocardiography for chest pain evaluation, whereas 273 (22.6%) underwent the test for preoperative assessment before a noncardiac surgery. Dobutamine stress echocardiography was the modality in 1145 (95.0%) patients; ultrasound contrast was used in 1154 (95.8%) patients. One-year event rates were available for 1024 patients. Stress echocardiography was normal in 1009 (98.5%) of these patients, eight of whom had a cardiac event during the subsequent year, yielding a negative predictive value (NPV) of 99.2%. The test was abnormal in 15 (1.5%) patients, but two of them were later found to have normal coronary arteries, yielding a positive predictive value (PPV) of 86.7%. The NPV and PPV were thus both at par or even higher than most other centers. The incidence of complications during stress echocardiography was extremely low. Conclusions: This audit shows that stress echocardiography at our center has an excellent safety as well as accuracy for predicting major adverse cardiac events during the subsequent year. Stress echocardiography could thus obviate the need for coronary angiogram and even revascularization in many patients. Our findings also reinforce the value of stress echocardiography as a greatly useful preoperative test for cardiac fitness in patients undergoing a major noncardiac surgery.

Pneumatosis intestinalis and portal venous gas in mechanical small bowel obstruction: Is it worrisome?

PurposeThe purpose of this study was to evaluate the clinical significance of pneumatosis intestinalis (PI) and portal venous gas (PVG) in patients with mechanical small bowel obstruction (SBO), using surgical findings or clinical follow-up as standard of reference. Materials and methodsFourteen patients with mechanical SBO associated with PI and PVG were retrospectively included. There were 7 men and 7 women with a mean age of 59±19 (SD) (range: 25–93 years). CT examinations were reviewed by two radiologists to confirm the diagnosis of mechanical SBO and make a description of PI. Interobserver agreement was calculated. The reference standard was intraoperative appearance of the bowel wall (10/14; 71%) or the recovery of a normal bowel function in patients who were managed conservatively (4/14; 29%). ResultsAmong the 10 patients who underwent surgery, a normal appearance of the bowel in association with PI on CT was found intraoperatively in 8/10 (80%) patients and a reversible ischemia in the remaining 2/10 (20%) patients. The four patients who were managed conservatively recovered normal bowel function. Two patients died within two weeks following SBO. ConclusionPI and PVG are not specific signs of bowel necrosis in mechanical SBO.

The Effect of Topical Tacrolimus on Pedicled Flap Survival: A Histological Analysis.

Our previous rodent study demonstrated significantly decreased full-thickness necrosis in pedicled dorsal skin flaps with topical tacrolimus as compared with petroleum jelly. The pathophysiology of tissue necrosis involves lymphatic congestion, followed by venous congestion and ultimately arterial insufficiency. Topical tacrolimus has been shown to increase growth of lymphatic collateral vessels and decrease lymphedema, potentially obviating one contributor to necrosis. The purpose of this study was to investigate the vascular and histological differences between these 2 groups to identify the etiology of our research findings. A 3 × 10-cm cranially based dorsal skin flap was raised and reinset on 22 Sprague Dawley rats. They were randomized to receive 0.2 g of either topical petroleum jelly or topical 0.1% tacrolimus ointment daily to the flaps. The rats were killed 7 days postoperatively. Two blinded reviewers marked the total flap area as well as areas of viable tissue, reversible ischemia, and necrotic tissue. Full-thickness biopsies of each area were taken from 2 randomly chosen animals in each group. Paraffin-embedded tissue was sectioned to generate hematoxylin and eosin-stained slides. Representative images of each area of the flap were taken less than 40× magnification using light microscopy. Arteries, veins, and lymphatics in the dermal layer were quantified under blinded conditions by a trained pathologist and calculated per cross-sectional area using Fiji software. The average area of the dorsal flaps in the control and tacrolimus groups was 22.5 and 23.9 cm2, respectively. Total necrotic area was significantly lower in rats receiving topical tacrolimus as compared with controls (P = 0.015). In the control cohort, average total number of vessels was 12.5, 6, and 0, in the areas of viable tissue, reversible ischemia, and necrosis, respectively. In the tacrolimus cohort, average total number of vessels increased was 20, 11.5, and 5.4, in the areas of viable tissue, reversible ischemia, and necrosis, respectively. On a histological level, topical tacrolimus is correlated with increased vascular growth in areas most susceptible for ischemic damage as compared with topical control. Future work is needed to investigate vascular biomarkers and increase the power of our study.

The Peptide Drug ACTH(4–7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain

The Peptide Drug ACTH(4–7)PGP (Semax) Suppresses mRNA Transcripts Encoding Proinflammatory Mediators Induced by Reversible Ischemia of the Rat Brain