Ischemic Episodes Research Articles

Effect of Antiplatelet Activity of Aspirin on Chronic Kidney Disease

Background and aim: Individual differences in the pharmacological responsiveness to aspirin are considerable. A higher likelihood of ischemic episodes is linked to aspirin's inadequate antiplatelet actions. It has been hypothesized that chronic kidney disease (CKD) influences the pharmacologic reaction to antiplatelet drugs. The elevated chance of fatality and cardiovascular problems in CKD sufferers has already been found to be largely explained by high on-treatment platelets response (HTPR) to clopidogrel. This research aimed to examine at how aspirin affects blood clotting in CKD sufferers. Method: We performed cross-sectional research on 120 people in Medical center of Lahore taking aspirin regularly. The thromboxane production generated by AAI was used to gauge the pharmacologic reaction to aspirin. Result: Individuals with poor kidney functioning were more likely to experience HTPR to aspirin (48% vs. 23%; odds ratio, 3.17; 95% confidence interval [CI], 1.35-7.42; P = 0.007). When compared to individuals with healthy or mildly diminished kidney performance, those with mild or serious CKD had lower pharmacokinetic responsiveness to aspirin (91; interquartile ranged [IQR], 281 ng mL-1; differential in medians, 56; CI, 6-110 ng mL-1; P = 0.012). Remaining thromboxane production and glomerular filtration rate were both associated by bivariate Pearson correlation analysis (R = 0.312; R2 = 0.093; P = 0.001). Individuals with CKD were usually old age and being women. Women and aged were not significant predictors of the connection, according to multivariate linear regression analyses (R = 0.313; R2 = 0.081; P = 0.002 and P = 0.006) respectively. Conclusion: Aspirin pharmacological reaction is associated with kidney function. Individuals who have CKD are more likely to have aspirin's antiplatelet action compromised. To evaluate the therapeutic significance of this data and look into the best antithrombotic strategy for CKD individuals, additional research is required. Keywords: Chronic kidney disease, platelets, treatment, aspirin, cardiovascular

Effects of RIPC on the Metabolome in Patients Undergoing Vascular Surgery: A Randomized Controlled Trial.

Background: remote ischemic preconditioning (RIPC) is a phenomenon in which short episodes of ischemia are applied to distant organs to prepare target organs for more prolonged ischemia and to induce protection against ischemia-reperfusion injury. This study aims to evaluate whether preoperatively performed RIPC affects the metabolome and to assess whether metabolomic changes correlate with heart and kidney injury markers after vascular surgery. Methods: a randomized sham-controlled, double-blinded trial was conducted at Tartu University Hospital. Patients undergoing elective open vascular surgery were recruited and RIPC was applied before operation. Blood was collected preoperatively and 24 h postoperatively. The metabolome was analyzed using the AbsoluteIDQ p180 Kit. Results: final analysis included 45 patients from the RIPC group and 47 from the sham group. RIPC did not significantly alter metabolites 24 h postoperatively. There was positive correlation of change in the kynurenine/tryptophan ratio with change in hs-troponin T (r = 0.570, p < 0.001), NT-proBNP (r = 0.552, p < 0.001), cystatin C (r = 0.534, p < 0.001) and beta-2-microglobulin (r = 0.504, p < 0.001) only in the RIPC group. Conclusions: preoperative RIPC did not significantly affect the metabolome 24 h after vascular surgery. The positive linear correlation of kynurenine/tryptophan ratio with heart and kidney injury markers suggests that the kynurenine–tryptophan pathway can play a role in RIPC-associated cardio- and nephroprotective effects.

Diagnostic quality assessment for low-dimensional ECG representations

There have been several attempts to quantify the diagnostic distortion caused by algorithms that perform low-dimensional electrocardiogram (ECG) representation. However, there is no universally accepted quantitative measure that allows the diagnostic distortion arising from denoising, compression, and ECG beat representation algorithms to be determined. Hence, the main objective of this work was to develop a framework to enable biomedical engineers to efficiently and reliably assess diagnostic distortion resulting from ECG processing algorithms. We propose a semiautomatic framework for quantifying the diagnostic resemblance between original and denoised/reconstructed ECGs. Evaluation of the ECG must be done manually, but is kept simple and does not require medical training. In a case study, we quantified the agreement between raw and reconstructed (denoised) ECG recordings by means of kappa-based statistical tests. The proposed methodology takes into account that the observers may agree by chance alone. Consequently, for the case study, our statistical analysis reports the “true”, beyond-chance agreement in contrast to other, less robust measures, such as simple percent agreement calculations. Our framework allows efficient assessment of clinically important diagnostic distortion, a potential side effect of ECG (pre-)processing algorithms. Accurate quantification of a possible diagnostic loss is critical to any subsequent ECG signal analysis, for instance, the detection of ischemic ST episodes in long-term ECG recordings.

The Impact of a Modified Anaesthetic Protocol on Animal Survival and the Characteristics of Ventricular Arrhythmias in the Course of Acute Myocardial Infarction in a Domestic Pig Model.

Acute myocardial infarction (MI) is one of the most common causes of death in humans in highly developed countries. Among its most frequent complications affecting the patient's prognosis are cardiac arrhythmias: ventricular tachycardia (VT) and ventricular fibrillation (VF). The study aimed to characterise arrhythmias in 19 pigs subjected to experimentally induced MI obtained by occlusion of the proximal left anterior descending (LAD) coronary artery using an angioplasty balloon. The anaesthetic protocol was modified to reduce mortality by including procedures stabilising haemodynamic disorders which develop during episodes of ischaemia and arrhythmia. During 30 min of experimentally induced ischaemia, the heart rhythm was recorded using a 12-lead ECG. The time, frequency, and type of arrhythmias were analysed. Ventricular arrhythmias were found in 94.74% of the treated pigs. The most common were ventricular premature complexes, reported in 88.89% of pigs with arrhythmia. Ventricular tachycardia was recorded in 66.67% and ventricular fibrillation in 50% of pigs with arrhythmias. Myocardial infarction due to proximal LAD occlusion is characterised by a high incidence of ventricular arrhythmias, especially VT and VF. Because of the high survival rate, this MI porcine model may serve as a model for research on acute ischaemic ventricular arrhythmias in humans. Additionally, it reduces the total number of animals required for testing while yielding meaningful results, which is in line with the 3R principle.

A clinical case of mechanical recanalization of recurrent cerebral embolism in the hyperacute period of ischemic stroke with hemorrhagic transformation

Currently, there is no single algorithm for the treatment of acute tandem occlusion of the internal carotid artery (ICA) and middle cerebral artery (MCA). The article presents the clinical case of ischemic stroke, which developed 10 days after the first ischemic episode with hemorrhagic transformation. As reperfusion therapy, thrombectomy from the M1 segment of the left MCA and simultaneous stenting of the left ICA were performed. The use of dual antiplatelet therapy at a loading dose in this clinical case was justified by the risk of stent thrombosis, but this increased the risk of recurrent hemorrhagic transformation. Follow-up of the patient for 90 days after this vascular event showed a favorable clinical outcome without hemorrhagic complications. The presented clinical case is extremely rare and shows one of the possible approaches in the management of patients with tandem lesions of the brachiocephalic arteries with a history of intracranial hemorrhagic complications. To develop a unified algorithm for managing acute tandem occlusion in recurrent ischemic strokes, more observations are needed.

A murine model of ischemia–reperfusion: the perfusion with leptin promotes the apoptosis-related relocation of mitochondrial proteins Bax and cytochrome c

BackgroundLeptin exerts both protective and deleterious effects on the heart; the first occurs under hypoxia- or ischemia-associated damage, the second is a pro-hypertrophic factor on cardiomyocytes. Therefore, leptin could represent a link between obesity and cardiovascular diseases. The study aimed to investigate the effect of leptin—the same concentration that is frequently measured in obesity and induces cardiac hypertrophy—on murine hearts following an episode of ischemia–reperfusion; moreover, we evaluated the heart's performance, hypertrophy, and activation of apoptosis. Rat hearts were perfused continuously with or without 3.1 nM leptin for one h before and 1 h after an episode of ischemia. Cardiac performance was evaluated, homogenates and mitochondria were prepared for western blot analysis of cardiac actin, leptin receptor, STAT3, pSTAT3, and apoptosis-related proteins Bax, Bcl-2, cytochrome c, and caspase 3.ResultsLeptin worsened heart recovery after ischemia (p < 0.05 Control vs IR + Lep of Heart Perform, Fig. 2). Although no hypertrophic response was observed, leptin induced the migration of Bax to the mitochondria and the release of cytochrome c into the cytosol (p < 0.05 Control vs IR + Lep, Fig. 5), essential events in the intrinsic/mitochondrial apoptosis.ConclusionsOur results indicate that the presence of leptin for 1 h before and after the ischemic insult reduces heart recovery and amplifies apoptotic signaling through the mitochondrial pathway.

Vasopressor Administration via Peripheral Intravenous Access for Emergency Department Stabilization in Septic Shock Patients.

Septic shock is commonly treated in the emergency department (ED) with vasopressors. Prior data have shown that vasopressor administration through a peripheral intravenous line (PIV) is feasible. To characterize vasopressor administration for patients presenting to an academic ED in septic shock. Retrospective observational cohort study evaluating initial vasopressor administration for septic shock. ED patients from June 2018 to May 2019 were screened. Exclusion criteria included other shock states, hospital transfers, or heart failure history. Patient demographics, vasopressor data, and length of stay (LOS) were collected. Cases were grouped by initiation site: PIV, ED placed central line (ED-CVL), or tunneled port/indwelling central line (Prior-CVL). Of the 136 patients identified, 69 were included. Vasopressors were initiated via PIV in 49%, ED-CVL in 25%, and prior-CVL in 26%. The time to initiation was 214.8 minutes in PIV and 294.7 minutes in ED-CVL (p = 0.240). Norepinephrine predominated all groups. No extravasation or ischemic complications were identified with PIV vasopressor administration. Twenty-eight-day mortality was 20.6% for PIV, 17.6% for ED-CVL, and 61.1% for prior-CVL. Of 28-day survivors, ICU LOS was 4.44 for PIV and 4.86 for ED-CVL (p = 0.687), while vasopressor days were 2.26 for PIV and 3.14 for ED-CVL (p = 0.050). Vasopressors are being administered via PIVs for ED septic shock patients. Norepinephrine comprised the majority of initial PIV vasopressor administration. There were no documented episodes of extravasation or ischemia. Further studies should look at the duration of PIV administration with potential avoidance of central venous cannulation altogether in appropriate patients. Kilian S, Surrey A, McCarron W, Mueller K, Wessman BT. Vasopressor Administration via Peripheral Intravenous Access for Emergency Department Stabilization in Septic Shock Patients. Indian J Crit Care Med 2022;26(7):811-815.

Examining the Role of the Linker in Bitopic N6-Substituted Adenosine Derivatives Acting as Biased Adenosine A1 Receptor Agonists.

The adenosine A1 receptor is a therapeutic target based on its ability to provide cardioprotection during episodes of myocardial ischemia and reperfusion injury. However, the clinical translation of A1R agonists has been hindered by dose-limiting adverse effects (bradycardia and hypotension). Previously, we demonstrated that the bitopic agonist VCP746 (1), consisting of an adenosine pharmacophore linked to an allosteric moiety, can stimulate cardioprotective A1R signaling effects in the absence of unwanted bradycardia. This study maps the structure-activity relationships of 1 through modifications to the linker moiety. Derivatives differing in the flexibility, length, and nature of the linker were assessed, which revealed that the linker is tolerant of several modifications including added rigidity. Ligands featuring 1,4-disubstituted 1,2,3-triazoles were the most biased of the novel analogues but also displayed sub-nanomolar potency in a cAMP accumulation assay at the A2BR. To our knowledge, 10 is the most potent A2BR agonist published to date.

Neuroimaging in acute ischemic stroke: Trends, disparities, and clinical impact

IntroductionClinical studies over the past decade expanded the eligibility criteria for endovascular therapy, with advanced imaging selection and new devices leading to higher rates of good outcomes. Herein, we explore the current trends in neuroimaging, associated factors, and impact on treatment and clinical outcomes. Materials and MethodsThis is a retrospective study of consecutive acute ischemic stroke patients, admitted to a comprehensive stroke center from 2016 to 2020. Patient characteristics, including age, sex, race, arrival method, admission National Institutes of Health Stroke Scale score and last known well to arrival time; imaging and treatment utilization; and discharge outcome by modified Rankin Scale and disposition were extracted from medical records. Trend and multivariable logistic regression analyses were performed, and trends were stratified by patient characteristics. ResultsOf 4,125 acute ischemic stroke episodes, 15.1% received intravenous thrombolysis only, and 7.5% received endovascular thrombectomy from 2016 to 2020. Neuroimaging utilization trends significantly increased for computed tomography angiography (CTA) (48.7% to 75.2%, p < 0.001) and computed tomography perfusion (CTP) (0.26% to 32.9%, p < 0.001), and decreased for magnetic resonance angiography (MRA) (43.2% to 24.7%, p < 0.001). These trends held after adjusting for patient characteristics. Endovascular thrombectomy and intravenous thrombolysis were significantly more common in patients with CTA and CTP (p < 0.0001), and these treatments were associated with good clinical outcomes after controlling for patient characteristics. ConclusionWe found significantly increased trends in CTA and CTP imaging, which were associated with endovascular thrombectomy and intravenous thrombolysis utilization, in acute ischemic stroke patients from 2016 to 2020.

Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke.

Nitrones are encouraging drug candidates for the treatment of oxidative stress-driven diseases such as acute ischemic stroke (AIS). In a previous study, we found a promising quinolylnitrone, QN23, which exerted a neuroprotective effect in neuronal cell cultures subjected to oxygen–glucose deprivation and in experimental models of cerebral ischemia. In this paper, we update the biological and pharmacological characterization of QN23. We describe the suitability of intravenous administration of QN23 to induce neuroprotection in transitory four-vessel occlusion (4VO) and middle cerebral artery occlusion (tMCAO) experimental models of brain ischemia by assessing neuronal death, apoptosis induction, and infarct area, as well as neurofunctional outcomes. QN23 significantly decreased the neuronal death and apoptosis induced by the ischemic episode in a dose-dependent manner and showed a therapeutic effect when administered up to 3 h after post-ischemic reperfusion onset, effects that remained 11 weeks after the ischemic episode. In addition, QN23 significantly reduced infarct volume, thus recovering the motor function in a tMCAO model. Remarkably, we assessed the antioxidant activity of QN23 in vivo using dihydroethidium as a molecular probe for radical species. Finally, we describe QN23 pharmacokinetic parameters. All these results pointing to QN23 as an interesting and promising preclinical candidate for the treatment of AIS.

Capabilities of long-term ECG monitoring in patients with myocardial infarction: the longer, the better?

Background. In modern cardiology, 24-hour electrocardiogram (ECG) monitoring has a high diagnostic value, but this method has a number of disadvantages in detecting episodes of unstable life-threatening arrhythmias. An increase in ECG monitoring duration allows expanding the possibilities of diagnosing life-threatening arrhythmias.Objective. To study the possibilities of long-term ECG monitoring (48–120 hours) in the detection of life-threatening arrhythmic events and parameters of myocardial electrical instability in patients with ST-segment elevation myocardial infarction (STEMI).Design and methods. The study included 71 STEMI patients. All patients from the 4th day of STEMI underwent multi-day ECG monitoring in 3 leads using a telemetric ECG recording complex with an average recording duration of 90.4 ± 30.2 hours. The analysis of episodes of myocardial ischemia, rhythm and conduction disturbances, turbulence and heart rate variability, late ventricular potentials and dispersion of the QT interval within 5 days was carried out.Results. Long-term monitoring allowed detecting high-grade ventricular extrasystoles. Analysis of episodes of myocardial ischemia in the postinfarction period revealed significant differences in the data of 120h-ECG monitoring in comparison with 24h-ECG. Multiday ECG monitoring made it possible to detect dysfunction of the autonomic regulation of cardiac activity in patients 2 times more often.Conclusion. A comprehensive assessment of the possibilities of multi-day ECG monitoring is a promising direction in predicting severe arrhythmias in patients in the postinfarction period.

Alzheimer's Disease Connected Genes in the Post-Ischemic Hippocampus and Temporal Cortex.

It is considered that brain ischemia can be causative connected to Alzheimer’s disease. In the CA1 and CA3 regions of the hippocampus and temporal cortex, genes related to Alzheimer’s disease, such as the amyloid protein precursor (APP), β-secretase (BACE1), presenilin 1 (PSEN1) and 2 (PSEN2), are deregulated by ischemia. The pattern of change in the CA1 area of the hippocampus covers all genes tested, and the changes occur at all post-ischemic times. In contrast, the pattern of gene changes in the CA3 subfield is much less intense, does not occur at all post-ischemic times, and is delayed in time post-ischemia relative to the CA1 field. Conversely, the pattern of gene alterations in the temporal cortex appears immediately after ischemia, and does not occur at all post-ischemic times and does not affect all genes. Evidence therefore suggests that various forms of dysregulation of the APP, BACE1 and PSEN1 and PSEN2 genes are associated with individual neuronal cell responses in the CA1 and CA3 areas of the hippocampus and temporal cortex with reversible cerebral ischemia. Scientific data indicate that an ischemic episode of the brain is a trigger of amyloidogenic processes. From the information provided, it appears that post-ischemic brain injury additionally activates neuronal death in the hippocampus and temporal cortex in an amyloid-dependent manner.

P2X7 Receptors in Astrocytes: A Switch for Ischemic Tolerance.

A sub-lethal ischemic episode (preconditioning [PC]) protects neurons against a subsequent lethal ischemic injury. This phenomenon is known as ischemic tolerance. PC itself does not cause brain damage, but affects glial responses, especially astrocytes, and transforms them into an ischemia-resistant phenotype. P2X7 receptors (P2X7Rs) in astrocytes play essential roles in PC. Although P2X7Rs trigger inflammatory and toxic responses, PC-induced P2X7Rs in astrocytes function as a switch to protect the brain against ischemia. In this review, we focus on P2X7Rs and summarize recent developments on how astrocytes control P2X7Rs and what molecular mechanisms they use to induce ischemic tolerance.

DETERMINING THE ASSOCIATION OF PERSONALITY TRAITS WITH PAIN PERCEPTION THRESHOLD IN THE CASE OF DUMP ISCHEMIA INDUCED BY PHYSICAL STRESS TEST

The aim of the study was to determine the association of personality character traits with the pain perception threshold in the case of dumb ischemia induced by cold stress test. Materials: We examined 58 patients on the basis of the therapeutic clinic of the Georgian Patriarchate. Patients were divided into three groups: Group I - with various somatic pathologies, Group II with unstable angina and Group III - Persons obsessed with neurocirculatory dystonia. Methods: I. Characteristic features of patients were studied using the Eysenck Questionnaire: This questionnaire assesses the degree of extroversion and introversion and the level of neuroticism. II - Determination of pain perception threshold by heat method, standard cold test. Cold test was performed on 8 patients of group I, 10 patients of group II and 7 patients of group III. Discussion: It has finally been established that under conditions of the same degree of occlusion of the coronary arteries, both painful and painless episodes of ischemia can occur. Our study showed that patients with asymptomatic ischemia detected by physical stress test showed an increase in pain perception threshold after treatment with anaprilin and isosorbide dinitrate. Treatment with diltiazem does not affect the pain perception threshold. Conclusion: According to our study, patients who have dumb ischemia are prone to introversion and low neuroticism. This tendency is best seen from the contrast between personality traits and pain threshold. Patients with episodes of asymptomatic ischemia and a high threshold for pain perception respond to cold-induced sympathetic stimulation with a weakened hemodynamic response, in contrast to those with health and unstable angina pectoris.

ST Segment Elevation

Abstract As the earliest indirect sign of an acute coronary occlusion arriving against non-operative collateral heart vessels, the unabating ST segment elevation accounts for the acute coronary syndrome asking for mandatory and immediate reperfusion therapy. The geography of the ST segment elevations usually enables one to identify the culprit artery and to guess its likely occlusion site, as pivotal pieces of the necessary vital risk forecasting, along with somehow expected occurring arrhythmias. Aside from the classical ST segment elevation myocardial infarction (STEMI) pattern, a handful of distinctive non-ST elevation appearances of the acute coronary occlusion also need imperative reperfusion therapy, thus qualifying themselves as STEMI equivalents. The early forthcoming of ST elevation during an acute transmural ischaemic episode, as well as the wide availability of the electrocardiogram, make it an invaluable diagnostic tool. Yet many confounding factors are able to limit the diagnostic sensibility of ST elevation (as for example its customary absence in the conventional leads in some cases of circumflex artery occlusion, or the casual mutual cancellation of the transmural ST vectors from opposite ventricular walls), the accuracy of the electrocardiographic localisation of the occlusion site (due to coronary anatomic variants, concomitant new or old coronary lesions elsewhere, previous coronary artery bypass grafts), as well as its specificity for transmural ischaemia (by virtue of a well-known manifold of non-ischaemic causes). While the STEMI patient must be offered undelayed reperfusion therapy, the non-ischaemic ST elevation one should be kept away from the haemorrhagic risk of a useless invasive procedure.

Blocking Mitochondrial Zn2+ Accumulation after Ischemia Reduces Mitochondrial Dysfunction and Neuronal Injury.

Zn2+ is an important contributor to ischemic brain injury, and recent studies support the hypothesis that mitochondria are key sites of its injurious effects. In murine hippocampal slices (both sexes) subjected to oxygen glucose deprivation (OGD), we found that Zn2+ accumulation and its entry into mitochondria precedes and contributes to the induction of acute neuronal death. In addition, if the ischemic episode is short (and sublethal), there is ongoing Zn2+ accumulation in CA1 mitochondria after OGD that may contribute to their delayed dysfunction. Using this slice model of sublethal OGD, we have examined Zn2+ contributions to the progression of changes evoked by OGD and occurring over 4-5 h. We detected progressive mitochondrial depolarization occurring from ∼2 h after ischemia, a large increase in spontaneous synaptic activity between 2 and 3 h, and mitochondrial swelling and fragmentation at 4 h. Blockade of the primary route for Zn2+ entry, the mitochondrial Ca2+ uniporter (with ruthenium red [RR]) or Zn2+ chelation shortly after OGD withdrawal substantially attenuated the mitochondrial depolarization and the changes in synaptic activity. RR also largely reversed the mitochondrial swelling. Finally, using an in vivo rat (male) asphyxial cardiac arrest model of transient global ischemia, we found that ∼8 min asphyxia induces considerable injury of CA1 neurons 4 h later that is associated with strong Zn2+ accumulation within many damaged mitochondria. These effects were substantially attenuated by infusion of RR on reperfusion. Our findings highlight mitochondrial Zn2+ accumulation after ischemia as a possible target for neuroprotective therapy.SIGNIFICANCE STATEMENT Brain ischemia is a leading cause of mortality and long-term disability that still lacks effective treatment. After transient ischemia, delayed death of neurons occurs in vulnerable brain regions. There is a critical need to understand mechanisms of this delayed neurodegeneration which can be targeted for neuroprotection. We found progressive and long-lasting mitochondrial Zn2+ accumulation to occur in highly vulnerable CA1 neurons after ischemia. Here we demonstrate that this Zn2+ accumulation contributes strongly to deleterious events occurring after ischemia, including mitochondrial dysfunction, swelling, and structural changes. We suggest that this mitochondrial Zn2+ entry may constitute a promising target for development of therapeutic interventions to be delivered after termination of an episode of transient global ischemia.

P373 INCIDENCE OF EMBOLIC EVENTS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY AND ATRIAL ARRYTHMIAS

Abstract Background Atrial arrythmias (AA) are well–known major complications in HCM patients. Nevertheless, there are only a few studies investigating clinical features of HCM patients with AA who experienced embolic events (EVs). Methods We retrospectively collected clinical data from patients with HCM and atrial fibrillation or flutter followed at our Cardiology Department. The aim of this study was to assess the occurrence of EVs during long–term follow up. Results Among 702 HCM patients, 126 had AA: 79% AF (56% paroxysmal, 23% chronic), 6% AFL, 15 % both AF and AFL. Among those, 21 (16.7%) patients experienced at least one ischemic episode since HCM diagnosis and overall 29 ischemic events occurred (17 strokes, 11 TIAs, 1 lower limb embolism). 5 ischemic events occurred in 3 patients for whom no certain correlation with AA could be detected as the events occurred before the AA–diagnosis was performed. Therefore, they were excluded from the analysis. In the remaining 18 patients, age at first embolic event was 72 ± 5 years old. The mean CHA2DS2VASc score was 1.82 ± 1.16. We registered 24 EVs (15 strokes, 8 TIAs, 1 lower limb embolism) at a follow–up of 6.8 ± 5 years: in 5 (all &amp;gt;70 years old) the diagnosis of AA was done at the moment of the first EV, in 13 the embolism occurred at a mean time of 6.3 ± 4.5 years after the diagnosis of AA. Among the patients with previously diagnosed AA, in 8 the embolism happened despite proper anticoagulation (2 NOACs, 6 VKA), 2 were not in therapeutic range, 1 had temporary NOAC withdrawal for surgery and 2 started anticoagulation only after the embolic event occurred. 5 out of 18 patients (28%) had permanent neurological impairment and 1 patient died of stroke. The independent predictors of the first embolic event in patients with a previous diagnosis of AA were female sex (p = 0.017) and inappropriate anticoagulation (p = 0.002). CHA2DS2VASc score (1.85 ± 1.19 in EVs vs 1.81 ± 1.16 in no EVs) was not a predictor of embolism (p = 0.167). Conclusions In our cohort of HCM patients with AA, embolic events are frequent regardless of CHA2DS2VASc score. Therefore, anticoagulation should be started immediately after the first arrhythmic episode as recommended by most recent guidelines.

Percutaneous transluminal angioplasty and stenting for vertebral artery stenosis.

Vertebral artery stenosis (narrowing of the vertebral artery) is an important cause of posterior circulation ischaemic stroke. Medical treatment (MT) e.g. controlling risk-factors and drug treatment, surgery, and endovascular treatment (ET) are the prevailing treatment strategies for symptomatic vertebral artery stenosis. ET consist s of percutaneous transluminal angioplasty (balloon catheter through the skin), with or without stenting. However, optimal management of people with symptomatic vertebral artery stenosis has not yet been established. To assess the safety and efficacy of percutaneous transluminal angioplasty, with or without stenting, combined with MT, compared to MT alone, in people with episodes of cerebral ischaemia due to vertebral artery stenosis. We searched the Cochrane Stroke Group, MEDLINE, Embase, BIOSIS, and two other indexes in Web of Science, China Biological Medicine Database, Chinese Science and Technique Journals Database, China National Knowledge Infrastructure and Wanfang Data, as well as ClinicalTrials.gov trials register and the World Health Organization (WHO) International Clinical Trials Registry Platform to 23 July 2021. We included all randomised controlled trials (RCTs) that compared ET plus MT with MT alone in treating people aged 18 years or over with symptomatic vertebral artery stenosis. We included all types of ET modalities (e.g. angioplasty alone, balloon-mounted stenting, and angioplasty followed by placement of a self-expanding stent). MT included risk factor control, antiplatelet therapy, lipid-lowering therapy, and individualised management for people with hypertension or diabetes. Two review authors independently screened potentially eligible studies, extracted data, and assessed trial quality and risk of bias. We applied the GRADE approach to assess the certainty of evidence. The primary outcomes were 30-day post-randomisation death/stroke (short-term outcome) and fatal/non-fatal stroke after 30 days post-randomisation to completion of follow-up (long-term outcome). MAIN RESULTS: We included three RCTs with 349 participants with symptomatic vertebral artery stenosis with a mean age of 64.4 years. The included RCTs were at low risk of bias overall. However, all included studies had a high risk of performance bias because blinding of the ET was not feasible. There was no significant difference in 30-day post-randomisation deaths/strokes between ET plus MT and MT alone (risk ratio (RR) 2.33, 95% confidence interval (CI) 0.77 to 7.07; 3 studies, 349 participants; low-certainty evidence). There were no significant differences between ET plus MT and MT alone in fatal/non-fatal strokes in the territory of the treated vertebral artery stenosis after 30 days post-randomisation to completion of follow-up (RR 0.51, 95% CI 0.26 to 1.01; 3 studies, 349 participants; moderate-certainty evidence), ischaemic or haemorrhagic stroke during the entire follow-up period (RR 0.77, 95% CI 0.44 to 1.32; 3 studies, 349 participants; moderate-certainty evidence), death during the entire follow-up period (RR 0.78, 95% CI 0.37 to 1.62; 3 studies, 349 participants; low-certainty evidence), and stroke or transient ischaemic attack (TIA) during the entire follow-up period (RR 0.65, 95% CI 0.39 to 1.06; 2 studies, 234 participants; moderate-certainty evidence). This Cochrane Review provides low- to moderate-certainty evidence indicating that there are no significant differences in either short- or long-term risks of stroke, death, or TIA between people with symptomatic vertebral artery stenosis treated with ET plus MT and those treated with MT alone.

Stroke in sickle cell disease in association with bilateral absence of the internal carotid arteries. Case report

BackgroundCongenital absence of the internal carotid artery (ICA) is a highly infrequent congenital incidence and occurs in less than 0.01% of the population; bilateral absence is exceedingly rare, diagnosed below 10% of the unilateral absence of the ICA. Sickle cell disease (SCD) is a serious disorder and carries a high risk of stroke.Case presentationWe present a five-year-old child with SCD who experienced an ischemic stroke episode with epileptic seizures. Neuroimaging revealed the agenesis of both ICAs. The frequency, embryology, and collateral pathway of the vascular anomaly as the clinical presentation, of this rare hematologic disease, are discussed.ConclusionsSickle cell disease (SCD) carries a high risk of stroke. Congenital absence of ICA occurs in less than 0.01% of the population; bilateral absence is diagnosed below 10% of the unilateral absence of the ICA.

Myocardial injury, troponin release, and cardiomyocyte death in brief ischemia, failure, and ventricular remodeling.

Troponin released from irreversibly injured myocytes is the gold standard biomarker for the rapid identification of an acute coronary syndrome. In acute myocardial infarction, necrotic cell death is characterized by sarcolemmal disruption in response to a critical level of energy depletion after more than 15 min of ischemia. Although troponin I and T are highly specific for cardiomyocyte death, high-sensitivity assays have demonstrated that measurable circulating levels of troponin are present in many normal subjects. In addition, transient as well as chronic elevations have been demonstrated in many disease states not clearly associated with myocardial ischemia. The latter observations have given rise to the clinical concept of myocardial injury. This review will summarize evidence supporting the notion that circulating troponin levels parallel the extent of myocyte apoptosis in normal ventricular remodeling and in pathophysiological conditions not associated with infarction or necrosis. It will review the evidence that myocyte apoptosis can be accelerated by diastolic strain from elevated ventricular preload and systolic strain from dyskinesis after brief episodes of ischemia too short to cause a critical level of myocyte energy depletion. We then show how chronic, low rates of myocyte apoptosis from endogenous myocyte turnover, repetitive ischemia, or repetitive elevations in left ventricular diastolic pressure can lead to significant myocyte loss in the absence of neurohormonal stimulation. Finally, we posit that the differential response to strain-induced injury in heart failure may determine whether progressive myocyte loss and heart failure with reduced ejection fraction or interstitial fibrosis and heart failure with preserved ejection fraction become the heart failure phenotype.