Gino Gialdini

Perioperative Atrial Fibrillation and the Long-term Risk of Ischemic Stroke

IMPORTANCE Clinically apparent atrial fibrillation increases the risk of ischemic stroke. In contrast, perioperative atrial fibrillation may be viewed as a transient response to physiological stress, and the long-term risk of stroke after perioperative atrial fibrillation is unclear. OBJECTIVE To examine the association between perioperative atrial fibrillation and the long-term risk of stroke. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using administrative claims data on patients hospitalized for surgery (as defined by surgical diagnosis related group codes), and discharged alive and free of documented cerebrovascular disease or preexisting atrial fibrillation from nonfederal California acute care hospitals between 2007 and 2011. Patients undergoing cardiac vs other types of surgery were analyzed separately. MAIN OUTCOMES AND MEASURES Previously validated diagnosis codes were used to identify ischemic strokes after discharge from the index hospitalization for surgery. The primary predictor variable was atrial fibrillation newly diagnosed during the index hospitalization, as defined by previously validated present-on-admission codes. Patients were censored at postdischarge emergency department encounters or hospitalizations with a recorded diagnosis of atrial fibrillation. RESULTS Of 1,729,360 eligible patients, 24,711 (1.43%; 95% CI, 1.41%-1.45%) had new-onset perioperative atrial fibrillation during the index hospitalization and 13,952 (0.81%; 95% CI, 0.79%-0.82%) experienced a stroke after discharge. At 1 year after hospitalization for cardiac surgery, cumulative rates of stroke were 0.99% (95% CI, 0.81%-1.20%) in those with perioperative atrial fibrillation and 0.83% (95% CI, 0.76%-0.91%) in those without atrial fibrillation. At 1 year after noncardiac surgery, cumulative rates of stroke were 1.47% (95% CI, 1.24%-1.75%) in those with perioperative atrial fibrillation and 0.36% (95% CI, 0.35%-0.37%) in those without atrial fibrillation. In a Cox proportional hazards analysis accounting for potential confounders, perioperative atrial fibrillation was associated with subsequent stroke both after cardiac surgery (hazard ratio, 1.3; 95% CI, 1.1-1.6) and noncardiac surgery (hazard ratio, 2.0; 95% CI, 1.7-2.3). The association was significantly stronger for perioperative atrial fibrillation after noncardiac vs cardiac surgery (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Among patients hospitalized for surgery, perioperative atrial fibrillation was associated with an increased long-term risk of ischemic stroke, especially following noncardiac surgery.

Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study

Background and Purpose— The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods— ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke severity. The efficacy outcome was disability at 90 days assessed by the modified Rankin Scale, dichotomized as favorable (score of 0–2) or unfavorable (score of 3–6). Safety outcomes were death and any intracranial bleeding. Results— Included in the analysis were 253 cases and 253 controls. Seventy-three cases (28.9%) had a favorable outcome as compared with 52 controls (20.6%; adjusted odds ratio (OR), 1.80; 95% confidence interval [CI], 1.03–3.15; P=0.037). A total of 104 patients died, 65 cases (25.7%) and 39 controls (15.4%; adjusted OR, 2.28; 95% CI, 1.36–3.22; P=0.001). There were more fatal bleedings (2.8% versus 0.4%; OR, 7.17; 95% CI, 0.87–58.71; P=0.068) in the cases than in the controls. Conclusions— In patients with stroke attributable to ICA occlusion, thrombolytic therapy results in a significant reduction in the proportion of patients dependent in activities of daily living. Increases in death and any intracranial bleeding were the trade-offs for this clinical benefit.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis

Background and Purpose— Silent brain infarction (SBI) on magnetic resonance imaging has been proposed as a subclinical risk marker for future symptomatic stroke. We performed a systematic review and meta-analysis to summarize the association between magnetic resonance imaging–defined SBI and future stroke risk. Methods— We searched the medical literature to identify cohort studies involving adults with SBI detected by magnetic resonance imaging who were subsequently followed up for incident clinically defined stroke. Study data and quality assessment were recorded in duplicate with disagreements in data extraction resolved by a third reader. Strength association between magnetic resonance imaging–detected SBI and future symptomatic stroke was measured by an hazard ratio. Results— The meta-analysis included 13 studies (14 764 subjects) with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% confidence interval, 2.24–3.86, P<0.001; Q=39.65, P<0.001). In the 8 studies of 10 427 subjects providing hazard ratio adjusted for cardiovascular risk factors, SBI was an independent predictor of incident stroke (hazard ratio, 2.08 [95% confidence interval, 1.69–2.56; P<0.001]; Q=8.99; P=0.25). In a subgroup analysis pooling 9483 stroke-free individuals from large population-based studies, SBI was present in ≈18% of participants and remained a strong predictor of future stroke (hazard ratio, 2.06 [95% confidence interval, 1.64–2.59]; P<0.01). Conclusions— SBI is present in ≈1 in 5 stroke-free older adults and is associated with a 2-fold increased risk of future stroke. Future studies of in-depth stroke risk evaluations and intensive prevention measures are warranted in patients with clinically unrecognized radiologically evident brain infarctions.

Magnetic resonance angiography detection of abnormal carotid artery plaque in patients with cryptogenic stroke.

Background Magnetic resonance imaging of carotid plaque can aid in stroke risk stratification in patients with carotid stenosis. However, the prevalence of complicated carotid plaque in patients with cryptogenic stroke is uncertain, especially as assessed by plaque imaging techniques routinely included in acute stroke magnetic resonance imaging protocols. We assessed whether the magnetic resonance angiography–defined presence of intraplaque high-intensity signal (IHIS), a marker of intraplaque hemorrhage, is associated with ipsilateral cryptogenic stroke. Methods and Results Cryptogenic stroke patients with magnetic resonance imaging evidence of unilateral anterior circulation infarction and without hemodynamically significant (≥50%) stenosis of the cervical carotid artery were identified from a prospective stroke registry at a tertiary-care hospital. High-risk plaque was assessed by evaluating for IHIS on routine magnetic resonance angiography source images using a validated technique. To compare the presence of IHIS on the ipsilateral versus contralateral side within individual patients, we used McNemar’s test for correlated proportions. A total of 54 carotid arteries in 27 unique patients were included. A total of 6 patients (22.2%) had IHIS-positive nonstenosing carotid plaque ipsilateral to the side of ischemic stroke compared to 0 patients who had IHIS-positive carotid plaques contralateral to the side of stroke (P=0.01). Stroke severity measures, diagnostic evaluations, and prevalence of vascular risk factors were not different between the IHIS-positive and IHIS-negative groups. Conclusions Our findings suggest that a proportion of strokes classified as cryptogenic may be mechanistically related to complicated, nonhemodynamically significant cervical carotid artery plaque that can easily be detected by routine magnetic resonance imaging/magnetic resonance angiography acute stroke protocols.

Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: the ICARO-2 study.

Background and Purposes: In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion. Methods: Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke – International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3–6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time. Results: A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0–1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9–11.1) and mortality or disability (OR 5.0; 95% CI 2.9–8.7) at 90 days. Conclusions: This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.

Safety Outcomes After Percutaneous Transcatheter Closure of Patent Foramen Ovale

Background and Purpose— We sought to evaluate the real-world rate of safety outcomes after patent foramen ovale (PFO) closure in patients with ischemic stroke or transient ischemic attack (TIA). Methods— We performed a retrospective cohort study using administrative claims data on all hospitalizations from 2005 to 2013 in New York, California, and Florida. Using International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified patients who underwent percutaneous transcatheter PFO closure within 1 year of ischemic stroke or TIA. Our outcome was an adverse event occurring during the hospitalization for PFO closure, defined as in prior studies as atrial fibrillation or flutter, cardiac tamponade, pneumothorax, hemothorax, a vascular access complication, or death. Crude rates were reported with exact confidence intervals. Results— We identified 1887 patients who underwent PFO closure after ischemic stroke or TIA. The rate of any adverse outcome during the hospitalization for PFO closure was 7.0% (95% confidence interval [CI], 5.9%–8.2%). Rates of adverse outcomes varied by age and type of preceding cerebrovascular event. In patients >60 years of age, the rate of adverse outcomes was 10.9% (95% CI, 8.6%–13.6%) versus 4.9% (95% CI, 3.8%–6.3%) in patients ⩽60 years of age. The rate of adverse outcomes was 9.9% (95% CI, 7.3%–12.5%) in patients with preceding ischemic stroke versus 5.9% (95% CI, 4.7%–7.1%) after TIA. Conclusions— Approximately 1 in 14 patients who underwent percutaneous transcatheter PFO closure after ischemic stroke or TIA experienced a serious periprocedural adverse outcome or death. The risk of adverse outcomes was highest in older patients and in those with preceding ischemic stroke.

Demographic Differences in Catheter Ablation After Hospital Presentation With Symptomatic Atrial Fibrillation.

Background Catheter ablation is increasingly used for rhythm control in symptomatic atrial fibrillation (AF), but the demographic characteristics of patients undergoing this procedure are unclear. Methods and Results We used data on all admissions at nonfederal acute care hospitals in California, Florida, and New York to identify patients discharged with a primary diagnosis of AF between 2006 and 2011. Our primary outcome was readmission for catheter ablation of AF, identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes. Cox regression models were used to assess relationships between demographic characteristics and catheter ablation, adjusting for Elixhauser comorbidities. We identified 397 612 eligible patients. Of these, 16 717 (4.20%, 95% CI 0.41 to 0.43) underwent ablation. These patients were significantly younger, more often male, more often white, and more often privately insured, with higher household incomes and lower rates of medical comorbidity. In Cox regression models, the likelihood of ablation was lower in women than men (hazard ratio [HR] 0.83; 95% CI 0.80 to 0.86) despite higher rates of AF-related rehospitalization (HR 1.23; 95% CI 1.21 to 1.24). Compared to whites, the likelihood of ablation was lower in Hispanics (HR 0.60; 95% CI 0.56 to 0.64) and blacks (HR 0.68; 95% CI 0.64 to 0.73), even though blacks had only a slightly lower likelihood of AF-related rehospitalization (HR 0.97; 95% CI 0.94 to 0.99) and a higher likelihood of all-cause hospitalization (HR 1.38; 95% CI 1.37 to 1.39). Essentially the same pattern existed in Hispanics. Conclusions We found differences in use of catheter ablation for symptomatic AF according to sex and race despite adjustment for available data on demographic characteristics and medical comorbidities.

Timing of Incident Stroke Risk After Cervical Artery Dissection Presenting Without Ischemia

Background and Purpose— Cervical artery dissection is a common cause of stroke in young people. The temporal profile of stroke risk after cervical artery dissection presenting without ischemia remains uncertain. Methods— We performed a crossover cohort study using administrative claims data on all emergency department visits and acute care hospitalizations from 2005 to 2011 in CA, 2006 to 2013 in NY, and 2005 to 2013 in FL. Using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified patients with a cervical artery dissection and no previous or concurrent stroke or transient ischemic attack diagnosis. We compared the risk of stroke in successive 2-week periods during the 12 weeks after dissection versus the corresponding 2-week period 1 year later. Absolute risk increases were calculated using McNemar test for matched data. In a sensitivity analysis, we limited our population to patients presenting with typical symptoms of cervical artery dissection. Results— We identified 2791 patients with dissection without ischemia. The absolute increase in stroke risk was 1.25% (95% confidence interval, 0.84–1.67%) in the first 2 weeks after dissection compared with the same time period 1 year later. The absolute risk increase was 0.18% (95% confidence interval, 0.02–0.34%) during weeks 3 to 4 and was no longer significant during the remainder of the 12-week postdissection period. Our findings were similar in a sensitivity analysis identifying patients who presented with typical symptoms of acute dissection. Conclusions— The risk of stroke after cervical artery dissection unaccompanied by ischemia at time of diagnosis seems to be limited to the first 2 weeks.

External Validation of the Cincinnati Prehospital Stroke Severity Scale

BACKGROUND The Cincinnati Prehospital Stroke Severity Scale (CPSSS) was recently developed to predict large-vessel occlusions (LVOs) in patients with acute ischemic stroke (AIS). In its derivation study, which consisted of patients enrolled in thrombolysis and endovascular therapy trials, the CPSSS had excellent discriminatory performance. We sought to externally validate the CPSSS in an independent cohort. METHODS Using our institutions prospective stroke registry, we calculated CPSSS scores for all patients diagnosed with AIS at Weill Cornell Medical Center in 2013 and 2014. The primary outcome was presence of LVO and the secondary outcome was a National Institutes of Health Stroke Scale (NIHSS) score of 15 or higher. Harrells c-statistic was calculated to determine the CPSSS scores discriminatory performance. Using the previously defined cut-point of 2 or higher (range 0-4), we evaluated the test properties of the CPSSS for predicting study outcomes. RESULTS Among 751 patients with AIS, 664 had vessel imaging and were included in the final analysis. Of these patients, 80 (14.2%) had LVOs and 117 (17.6%) had an NIHSS score of 15 or higher. The median CPSSS score was 0 (interquartile range 0-1) and 133 patients (20%) had scores of 2 or higher. c-statistic was .85 (95% confidence interval [CI] .81-.90) for predicting LVO and .94 (95% CI .92-.97) for predicting an NIHSS score of 15 or higher. Using a cut-point of 2 or higher, the CPSSS was 70.0% sensitive and 86.8% specific for predicting LVO, and 87.2% sensitive and 94.3% specific for predicting an NIHSS score of 15 or higher. CONCLUSIONS In a cohort of patients with AIS treated at a tertiary-care stroke center, the CPSSS had reasonable sensitivity and specificity for predicting LVO and severe stroke. Future studies should aim to prospectively validate the score in emergency responders.