Long-Term Risk of Arterial Thrombosis After Intracerebral Hemorrhage: MUCH-Italy.

BACKGROUND: The identification of patients surviving an acute intracerebral hemorrhage who are at a long-term risk of arterial thrombosis is a poorly defined, crucial issue for clinicians. METHODS: In the setting of the MUCH-Italy (Multicenter Study on Cerebral Haemorrhage in Italy) prospective observational cohort, we enrolled and followed up consecutive 30-day intracerebral hemorrhage survivors to assess the long-term incidence of arterial thrombotic events, to assess the impact of clinical and radiological variables on the risk of these events, and to develop a tool for estimating such a risk at the individual level. Primary end point was a composite of ischemic stroke, myocardial infarction, or other arterial thrombotic events. A point-scoring system was generated by the ß-coefficients of the variables independently associated with the long-term risk of arterial thrombosis, and the predictive MUCH score was calculated as the sum of the weighted scores. RESULTS: Overall, 1729 patients (median follow-up time, 43 months [25th to 75th percentile, 69.0]) qualified for inclusion. Arterial thrombotic events occurred in 169 (9.7%) patients. Male sex, diabetes, hypercholesterolemia, atrial fibrillation, and personal history of coronary artery disease were associated with increased long-term risk of arterial thrombosis, whereas the use of statins and antithrombotic medications after the acute intracerebral hemorrhage was associated with a reduced risk. The area under the receiver operating characteristic curve of the MUCH score predictive validity was 0.716 (95% CI, 0.56-0.81) for the 0- to 1-year score, 0.672 (95% CI, 0.58-0.73) for the 0- to 5-year score, and 0.744 (95% CI, 0.65-0.81) for the 0- to 10-year score. C statistic for the prediction of events that occur from 0 to 10 years was 0.69 (95% CI, 0.64-0.74). CONCLUSIONS: Intracerebral hemorrhage survivors are at high long-term risk of arterial thrombosis. The MUCH score may serve as a simple tool for risk estimation.

Statin use and long-term risk of recurrent intracerebral haemorrhage: the MUCH-Italy.

BACKGROUND: Whether statin use after spontaneous intracerebral haemorrhage (ICH) increases the risk of recurrent ICH is uncertain. METHODS: In the setting of the Multicentric Study on Cerebral Haemorrhage in Italy we followed up a cohort of 30-day ICH survivors, consecutively admitted from January 2002 to July 2014, to assess whether the use of statins after the acute event is associated with recurrent cerebral bleeding. RESULTS: 1623 patients (mean age, 73.9±10.3 years; males, 55.9%) qualified for the analysis. After a median follow-up of 40.5 months (25th to 75th percentile, 67.7) statin use was not associated with increased risk of recurrent ICH either in the whole study group (adjusted HR, 0.99; 95% CI 0.64 to 1.53) or in the subgroups defined by haematoma location (deep ICH, adjusted HR, 0.74; 95% CI 0.35 to 1.57; lobar ICH, adjusted HR, 1.09; 95% CI 0.62 to 1.90), intensity of statins (low-moderate intensity statins, adjusted HR, 0.93; 95% CI 0.58 to 1.49; high-intensity statins, adjusted HR, 1.48; 95% CI 0.66 to 3.31) and use of statins before the index event (adjusted HR, 0.66; 95% CI 0.38 to 1.17). CONCLUSIONS: Statin use appears to be unrelated to the risk of ICH recurrence.

Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

Cryptogenic stroke as a working diagnosis: the need for an early and comprehensive diagnostic work-up.

In the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study, the causes of ischemic stroke were identified in 43% of cryptogenic stroke patients monitored with implantable cardiac monitor (ICM), but one-third of these patients had non-cardioembolic causes. These results suggest the need for an early and comprehensive diagnostic work-up before inserting an ICM.

Increased Arterial Stiffness is a Predictor of Delayed Ischaemic Stroke After Subarachnoid Haemorrhage.

BACKGROUND: Subarachnoid haemorrhage (SAH) accounts for 5-10% of strokes and its prognosis may be influenced by different complications, including delayed cerebral ischaemia (DCI). The pathophysiology of DCI is complex and still unknown. Many different mechanisms may contribute to the occurrence of DCI. Arterial stiffness (AS), a well-known risk factor for cardiovascular events, also associated with the development and rupture of cerebral aneurysms, may represent a novel contributing risk factor. The aim of our study was to investigate a possible link between AS and DCI after SAH. METHOD: Fifty-nine (59) patients with SAH (age [mean±standard deviation], 62±12 years) underwent neuroimaging examination, and 24-hour heart rate and blood pressure monitoring, including AS index (ASI) measurement. RESULTS: Of 59 patients, DCI occurred in 12. ASI was significantly higher in patients with DCI than in patients without it (0.70±0.1 vs 0.62±0.1; p=0.03). ASI was a significant predictor for DCI (odds ratio [for an increase of 0.20 points in ASI], 5.99; 95% confidence interval, 1.23-29.22; p=0.03). CONCLUSIONS: Arterial stiffness index is a simple and inexpensive tool that is able to predict the risk of DCI in patients with SAH. This marker can impact on intensive care unit monitoring, early recognition, and treatment, contributing to optimal acute management of patients with SAH.

Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation.

BACKGROUND AND PURPOSE: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. METHODS: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. RESULTS: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). CONCLUSIONS: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.

Anticoagulation After Stroke in Patients With Atrial Fibrillation.

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Single-center experience using the 3MAX or 4MAX reperfusion catheter for the treatment of acute ischemic stroke with distal arterial occlusions in patients not eligible for intravenous fibrinolysis.

BACKGROUND: In acute stroke, distal cerebrovascular occlusions can be linked to severe clinical symptoms, and treatment by mechanical thrombectomy may have an important clinical impact. When intravenous fibrinolytic therapy is firmly contraindicated, it remains the only treatment option. METHODS: A total of 42 patients with isolated distal arterial occlusions and absolute contraindication for intravenous fibrinolytic therapy were retrospectively included. Mechanical thrombectomy was performed using Penumbra 4MAX or 3MAX aspiration catheters. When aspiration alone did not result in successful revascularization, a stent retriever was added. RESULTS: Direct thromboaspiration was the first treatment option in all patients. 16.7% of cases required the additional use of a stent retriever. A TICI score ≥ 2b reperfusion at the end of the procedure was obtained in 76.2% and a Rankin Score of 2 or less at 90 days in 45.7%. Two hemorrhagic complications were observed. CONCLUSIONS: Direct thromboaspiration appears a safe technique in acute isolated distal arterial occlusions. In a cohort of patients with absolute contraindication for intravenous fibrinolytic therapy, a significant percentage achieved good revascularization.

Inflammation and Atrial Electrical Remodelling in Patients With Embolic Strokes of Undetermined Source.

BACKGROUND: About one third of ischaemic strokes are classified as embolic strokes of undetermined source (ESUS). A silent atrial fibrillation (AF) may play a pathogenic role in these strokes and P wave dispersion (PWD), representing an electrocardiographic (ECG) predictor for paroxysmal AF, thereby a potential marker of covert cardioembolism, was found to be increased in cryptogenic stroke. Furthermore, current evidence links AF to inflammation: inflammatory markers, such as high-sensitive C-reactive protein (hsCRP), have been related to the development and persistence of AF, possibly by promoting atrial remodelling. The aim of this study was to evaluate whether a relationship between PWD and hsCRP in patients with ESUS exists, in order to highlight a possible role for inflammation in the atrial electric remodelling, that predisposes to AF. METHODS: We enrolled 174 patients (91 males, 83 females; mean age 69±13years) with ESUS. All patients underwent neuroimaging examination, arterial ultrasound examination, echocardiography and ECG. P wave dispersion and hsCRP were measured in all subjects. RESULTS: A significant positive correlation was found between hsCRP and PWD (Spearman r: 0.35, p<0.0001). In patients with high PWD (>40 msec; n=102), hsCRP was three-fold higher than in patients with normal PWD (≤40 msec; n=72)(1.57±2.9 vs 0.42±0.4mg/dl, p=0.0005). CONCLUSIONS: Our results show increased hsCRP levels in cryptogenic stroke patients with high PWD. These findings provide support for the hypothesis that systemic inflammation plays a role in a fraction of patients with ESUS, by increasing AF risk via atrial electric remodelling.

Electrocardiographic Predictors of Silent Atrial Fibrillation in Cryptogenic Stroke.

BACKGROUND: Prolonged screening for the presence of atrial fibrillation (AF) is recommended after cryptogenic stroke (CS) and different electrocardiographic markers of atrial cardiopathy have been proposed as tools to identify patients at high-risk for AF. AIM: The aim of this study was to evaluate the relationship between different electrocardiographic parameters and in-hospital AF occurrence after acute CS. METHOD: In total, 222 patients with CS underwent 12-lead resting electrocardiogram (ECG) at admission and 7-day in-hospital ECG monitoring in order to evaluate the possible occurrence of silent AF. At admission, the following indices were evaluated: maximum and minimum P-wave duration (P max and P min), P-wave dispersion (PWD), P-wave index, P-wave axis, atrial size. Patients were dichotomised into two groups according to the detection of AF during 7-day in-hospital ECG monitoring and a logistic regression model was constructed to determine the predictors of AF. RESULTS: Atrial fibrillation was detected in 44 patients. Those in the AF group had a significantly higher PWD, P-wave index, PR interval, and greater frequency of abnormal P-wave axis than those in the no AF group. The following variables were found to be the main predictors for AF: age (odds ratio [OR] 1.41 for 5 years, 95% confidence interval [CI] 1.15-1.72), PWD (OR 1.92 for 10ms, 95% CI 1.45-2.55), abnormal P-wave axis (OR 3.31, 95% CI 1.49-7.35). CONCLUSIONS: In CS, high PWD and abnormal P-wave axis are independent predictors of AF, representing useful tools to identify patients at high-risk of AF.

Stroke in Pregnancy and Review of Current Literature: Arterial Spin-Labeling MRI Can Identify the Presence and Intensity of Collateral Circle.

Diagnosis and treatment of acute ischemic stroke is challenging during pregnancy. We present a diagnostic strategy in a pregnant woman with suspect of acute stroke. We perform magnetic resonance with arterial spin labeling sequence, an X-ray and contrast medium safe perfusion technique. Arterial spin labeling can detects collateral vessels in patient with acute ischemic stroke. Demonstrating collateral vessels is relevant for better understanding prognosis and for improving the diagnostic assessment in pregnancy.

Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

BACKGROUND AND PURPOSES: This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. METHODS: The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. RESULTS: The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. CONCLUSIONS: In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.

Neuroimaging of Takayasu Arteritis in a Patient with Ulcerative Rectocolitis.

BACKGROUND: Takayasu arteritis (TA), also known as aortoarteritis and pulseless disease, is an autoimmune, idiopathic, large-vessel vasculitis that primarily affects the aorta and its major branches, the coronary arteries, and the pulmonary arteries. METHODS: This is a peculiar clinical and radiological pattern of TA in a young female Caucasian. Her medical history included diagnosis of ulcerative rectocolitis at the age of 14. Because of the occurrence of anemia and exacerbation of rectocolitis, she had started infliximab associated with low doses of cortisone and mesalazine. Three months before admission, therapy with infliximab was discontinued because of the onset of fever, sore throat, and the increase in the neck pain. Imaging is crucial to achieve a proper diagnosis and the main differential diagnosis of this setting is arterial dissection. Magnetic resonance angiography (MRA) and color Doppler sonography (CDS) have been able to demonstrate rare but possible arteriovenous fistula in TA patients. This is the first report on arteriovenous fistula of cervical venous plexus in TA patients. CONCLUSION: (1) TA has to be suspected in young woman with neck pain, even without neurological symptoms. (2) Magnetic resonance imaging and CDS can depict wall thickening and abnormal caliber in the involved vessels. (3) MRA and CDS are able to demonstrate rare but possible arteriovenous fistula in TA patients. (4) Rectocolitis therapy could be a trigger factor of wall vessel involvement.

Double ophthalmic arteries arising from the internal carotid artery: a case report of a hidden second ophthalmic artery.

A case of double ophthalmic arteries arising from the internal carotid artery with unique features is reported. This case was discovered following in the course of time the progress of a thrombosis of the anterior cavernous sinus associated with a low-flow direct arteriovenous fistula of the superior ophthalmic vein. At different time points, the same patient underwent four angiographic studies and one computerized tomography with contrast medium. Angiographies showed that the double internal carotid artery origin of the ophthalmic artery was detectable only within a short range of time. To the best of our knowledge, this case is unique as it demonstrates that a second ophthalmic artery may lie hidden, showing itself only under particular hemodynamic requirements.

Elevated Interleukin-6 Levels Are Associated With an Increased Risk of QTc Interval Prolongation in a Large Cohort of US Veterans.

BACKGROUND: Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects. METHODS AND RESULTS: An observational study using the Veterans Affairs Informatics and Computing Infrastructure was performed. Participants were US veterans who had an ECG and were tested for IL-6. Descriptive statistics and univariate and multivariate regression analyses were performed to study the relationship between IL-6 and QTc prolongation risk. Study population comprised 1085 individuals, 306 showing normal (<5 pg/mL), 376 moderately high (5-25 pg/mL), and 403 high (>25 pg/mL) IL-6 levels. Subjects with elevated IL-6 showed a concentration-dependent increase in the prevalence of QTc prolongation, and those presenting with QTc prolongation exhibited higher circulating IL-6 levels. Stepwise multivariate regression analyses demonstrated that increased IL-6 level was significantly associated with a risk of QTc prolongation up to 2 times the odds of the reference category of QTc (e.g. QTc >470 ms men/480 ms women ms: odds ratio, 2.28 [95% CI, 1.12-4.50] for IL-6 >25 pg/mL) regardless of the underlying cause. Specifically, the mean QTc increase observed in the presence of elevated IL-6 was quantitatively comparable (IL-6 >25 pg/mL:+6.7 ms) to that of major recognized QT-prolonging risk factors, such as hypokalemia and history of myocardial infarction. CONCLUSIONS: Our data provide evidence that a high circulating IL-6 level is a robust risk factor for QTc prolongation in a large cohort of US veterans, supporting a potentially important arrhythmogenic role for this cytokine in the general population.

Advanced Atrioventricular Block in Athletes: Prevalence and Role of Anti-Ro/Sjögren Syndrome-Related Antigen A Antibodies.

BACKGROUND: Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes. METHODS AND RESULTS: A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression. CONCLUSIONS: Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.