The Effect of HMG CoA Reductase Inhibitors on the Progression of Aortic Sclerosis: Review Article.

The risk factors and pathology for the development and progression of aortic stenosis are similar to those for arterial atherosclerosis. Statin therapy has been hypothesized to delay progression of aortic stenosis, but studies evaluating this hypothesis report conflicting results. We performed a systematic search and review of statin clinical trials of aortic stenosis progression to determine why there are apparent differences in trial results. We identified 137 reports related to clinical trials of statin therapy and aortic stenosis, 14 of which qualified for analysis. Eight of the nine observational studies reported benefit with statin therapy whereas all five randomized controlled trials (RCTs) reported no benefit. We conclude that there is insufficient evidence to recommend statin treatment for patients at risk of aortic stenosis. Treatment in early stages or studies with longer follow-up is required to conclusively evaluate this possibility.

Dysphagia screening and hospital-acquired pneumonia in patients with acute ischemic stroke: findings from Get with the Guidelines--Stroke.

BACKGROUND: National guidelines recommend dysphagia screening (DS) before oral intake in stroke patients to reduce hospital-acquired pneumonia (HAP). We examined the relationship between DS and HAP after ischemic stroke. METHODS: Get with the Guidelines-Stroke defines HAP as postadmission diagnosis of pneumonia requiring antibiotics, and DS as the use of bedside swallow screening prior to oral intake. Univariable and multivariable analyses examined the relationship between DS and HAP. RESULTS: Among 314,007 ischemic stroke patients at 1244 Get with the Guidelines-Stroke hospitals from 2003-2009 who were eligible for DS and had completed HAP data, a total of 216,372 (68.9%) underwent DS and a total of 17,906 (5.7%) developed HAP. When compared with patients without HAP, patients with HAP were older, had admission National Institutes of Health Stroke Scale (NIHSS) score (median NIHSS score: 10 versus 4), were more likely to undergo DS (75.5% versus 68.5%), and had increased length of stay and in-hospital mortality (12.4% versus 2.3%). In multivariable analyses, factors independently associated with a lower risk of HAP were female gender (odds ratio [OR] 0.84), dyslipidemia (OR 0.84), and hypertension (OR 0.94). DS was associated with a higher adjusted OR for HAP (OR 1.40), but the OR was greatly attenuated after adding NIHSS score to the model (OR 1.10). CONCLUSIONS: HAP occurs in 1 of 17 hospitalized stroke patients and is associated with a greater than 5-fold increase in mortality. DS did not occur in 31.1% of eligible patients, with increased screening among those with more severe strokes and those who developed HAP. The attenuation of the relationship between DS and HAP risk when controlling for NIHSS score suggests the association between screening and pneumonia is confounded by severity. Controlled trials are needed to determine DS effectiveness.

Risk of thrombolytic therapy for acute ischemic stroke in patients with current malignancy.

Little is known about the risk of thrombolysis in patients with malignancy, because these patients have been excluded from most clinical trials. We reviewed our acute ischemic stroke (AIS) database for clinical outcomes and complications in patients with current malignancy (CM) who received thrombolytic therapy. Consecutive AIS patients receiving thrombolysis between January 2003 and December 2006 were retrospectively abstracted in accordance with the American Stroke Association's Get With the Guidelines-Stroke definitions and charts were reviewed for history of malignancy. Patients with brain metastases did not receive tissue plasminogen activator (tPA). Stepwise logistic regression was used to identify independent predictors of in-hospital mortality. Of 308 AIS patients treated with thrombolytic therapy, 210 (68%) received intravenous (IV) tPA only, 41 (13%) received IV tPA plus intra-arterial therapy (IAT), and 57 (18%) received IAT only. Eighteen patients (5.8%) had a CM, and 26 patients (8.4%) had a remote history of malignancy. Patients with CM had a higher in-hospital mortality (38.9% vs 19.7 %; P=.05) and were more likely to have died due to worsening medical comorbidity (71.4% vs 9.6%; P < .001). The rate of symptomatic intracranial hemorrhage (ICH) was similar in the 2 groups (5.6% vs 2.7%; P=.47). In multivariate analysis, the only independent predictors of mortality were National Institutes of Health Stroke Scale score, history of hypertension, and smoking. CM was not independently associated with increased in-hospital mortality following thrombolysis. Mortality was attributable largely to medical comorbidities, not to symptomatic ICH. Our data suggest that thrombolysis may be a reasonable option for patients with malignancy who have acceptable medical comorbidities and performance status. Further research is warranted.

Remote supervision of IV-tPA for acute ischemic stroke by telemedicine or telephone before transfer to a regional stroke center is feasible and safe.

BACKGROUND AND PURPOSE: Because of a shortage of stroke specialists, many outlying or "spoke" hospitals initiate intravenous (IV) thrombolysis using telemedicine or telephone consultation before transferring patients to a regional stroke center (RSC) hub. We analyzed complications and outcomes of patients treated with IV tissue plasminogen activator (tPA) using the "drip and ship" approach compared to those treated directly at the RSC. METHODS: A retrospective review of our Get With the Guidelines Stroke (GWTG-Stroke) database from 01/2003 to 03/2008 identified 296 patients who received IV tPA within 3 hours of symptom onset without catheter-based reperfusion. GWTG-Stroke definitions for symptomatic intracranial (sICH), systemic hemorrhage, discharge functional status, and destination were applied. Follow-up modified Rankin Score was recorded when available. RESULTS: Of 296 patients, 181 (61.1%) had tPA infusion started at an outside spoke hospital (OSH) and 115 (38.9%) at the RSC hub. OSH patients were younger with fewer severe strokes than RSC patients. Patients treated based on telestroke were more frequently octogenarians than patients treated based on a telephone consult. Mortality, sICH, and functional outcomes were not different between OSH versus RSC and telephone versus telestroke patients. Among survivors, mean length of stay was shorter for OSH patients but discharge status was similar and 75% of patients walked independently at discharge. CONCLUSIONS: Outcomes in OSH "drip and ship" patients treated in a hub-and-spoke network were comparable to those treated directly at an RSC. These data suggest that "drip and ship" is a safe and effective method to shorten time to treatment with IV tPA.

Brugada syndrome, exercise, and exercise testing.

There are few data on the risk of exercise and the role of exercise stress testing in Brugada syndrome. We sought to address this deficiency using a systematic literature review. We identified 98 English-language articles possibly addressing exercise in Brugada syndrome by searching PubMed and Google Scholar from January 1990 through November 2013 using the keywords "Brugada syndrome," "exercise," "exercise testing," and "syncope" alone and in combinations. Abstracts were reviewed, and those articles pertaining to Brugada syndrome and exercise were reviewed in full. We identified 18 articles reporting on Brugada syndrome and exercise. This pool included 2 large studies of 93 and 50 Brugada subjects undergoing exercise testing, plus 16 case reports. There were no reports of exercise-related sudden death, but there were 4 cases of syncope after exercise. We identified 166 Brugada patients who underwent exercise testing. During exercise testing, there were 2 reports of ventricular tachycardia and 1 report of multiple ventricular extrasystoles. ST-segment elevation increased (ST augmentation) during the early recovery phase of exercise in 57% of patients. Exercise unmasked a Brugada electrocardiographic pattern in 5 patients. Exercise is associated with syncope and ST augmentation after exercise and may be helpful in unmasking Brugada syndrome. There are insufficient data on the risks of exercise in Brugada syndrome to make recommendations for exercise, but the observations that exercise can worsen the ST abnormalities in Brugada and produce ventricular arrhythmias suggest that patients with Brugada syndrome should be restricted from vigorous exercise.

Allergic acute coronary syndrome (Kounis syndrome).

Anaphylaxis rarely manifests as a vasospastic acute coronary syndrome with or without the presence of underlying coronary artery disease. The variability in the underlying pathogenesis produces a wide clinical spectrum of this syndrome. We present three cases of anaphylactic acute coronary syndrome that display different clinical variants of this phenomenon. The main pathophysiological mechanism of the allergic anginal syndromes is the inflammatory mediators released during a hypersensitivity reaction triggered by food, insect bites, or drugs. It is important to appropriately recognize and treat Kounis syndrome in patients with exposure to a documented allergen.

Association of Acute and Chronic Hyperglycemia With Acute Ischemic Stroke Outcomes Post-Thrombolysis: Findings From Get With The Guidelines-Stroke.

BACKGROUND: Hyperglycemia has been associated with adverse outcomes in patients with acute ischemic stroke (AIS) and may influence outcomes after tissue plasminogen activator (tPA). We sought to analyze the association of acute and chronic hyperglycemia on clinical outcomes in tPA-treated patients. METHODS AND RESULTS: We identified 58 265 AIS patients from 1408 sites who received tPA from 2009 to 2013 in Get With The Guidelines-Stroke. Acute hyperglycemia at admission was defined as a plasma glucose level >140 mg/dL. Chronic hyperglycemia was defined by plasma glycosylated hemoglobin (HbA1c) >6.5%. Post-tPA outcomes were analyzed using logistic regression. Blood glucose >140 mg/dL and HbA1c >6.5 were associated with worse clinical outcomes (symptomatic intracranial hemorrhage [sICH], life-threatening hemorrhage, and in-hospital mortality and length of stay) in diabetic and nondiabetic patients. Among patients with documented history of diabetes, increasing admission glucose up to 200 mg/dL was associated with increased adjusted odds ratio (aOR) of in-hospital mortality (aOR, 1.07) and sICH (aOR, 1.05) per 10 mg/dL increase in blood glucose. Increasing HbA1C to 8% was associated with increased odds of in-hospital mortality (aOR, 1.19) and sICH (aOR, 1.16) per 1% increase in HbA1c. Similar findings were observed in patients without a documented history of diabetes. There was no further increase in poor outcomes above the blood glucose level of 200 mg/dL or HbA1c >8. CONCLUSION: Acute and chronic hyperglycemia are both associated with increased mortality and worse clinical outcomes in AIS patients treated with tPA. Controlled trials are needed to determine whether acute correction of hyperglycemia can improve outcomes after thrombolysis.

Safety of full-dose intravenous recombinant tissue plasminogen activator followed by multimodal endovascular therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: The optimal management of stroke patients who fail treatment with intravenous recombinant tissue plasminogen activator (rt-PA) remains unknown. A study was undertaken to establish whether treatment with a standard intravenous t-PA dose (0.9 mg/kg) followed by multimodal endovascular therapy would have a similar safety profile to reduced dose (0.6 mg/kg) bridging therapy. METHODS: A retrospective analysis was performed of a prospectively collected database. All patients treated with full-dose t-PA and endovascular therapy were included. The primary safety endpoints included ECASS-III symptomatic intracranial hemorrhage (sICH) and ECASS parenchymal hematomas (PH). Secondary safety endpoints included severe systemic bleeding and 90-day mortality. Clinical efficacy endpoints included rates of recanalization (TICI 2-3), ambulation at hospital discharge and 90-day independent outcomes (mRS 0-2). RESULTS: 106 consecutive patients (mean age 69 ± 17 years; mean baseline NIH Stroke Scale 17.8 ± 4.8; 55% women; occlusion sites: MCA-M1 60.4%; MCA-M2 6.6%; ICA-T 19.8%; tandem cervical ICA+MCA-M1 7.5%; basilar artery 5.7%) were identified over a 10-year period. The sICH rate was 8.5% and the PH-1, PH-2 and subarachnoid hemorrhage rates were 2.8%, 8.5% and 2.8%, respectively. There were two (1.9%) severe groin hematomas. The recanalization rate was 66%. At hospital discharge, 41.4% of the patients were ambulatory. The rate of independent functional outcomes at 90 days was 24%; however, this sample is biased since nearly all deaths were captured but detailed 90-day functional outcomes were missing in 27 patients. The 90-day death rate was 32.4%. CONCLUSION: Combined treatment with full-dose intravenous rt-PA followed by multimodal endovascular therapy seems to be associated with similar rates of sICH to that of bridging therapy with reduced rt-PA dosage.

Hospital acquired pneumonia is linked to right hemispheric peri-insular stroke.

PURPOSE: Hospital acquired pneumonia (HAP) is a major complication of stroke. We sought to determine associations between infarction of specific brain regions and HAP. METHODS: 215 consecutive acute stroke patients with HAP (2003-2009) were carefully matched with 215 non-pneumonia controls by gender, then NIHSS, then age. Admission imaging and binary masks of infarction were registered to MNI-152 space. Regional atlas and voxel-based log-odds were calculated to assess the relationship between infarct location and the likelihood of HAP. An independently validated penalized conditional logistic regression model was used to identify HAP associated imaging regions. RESULTS: The HAP and control patients were well matched by gender (100%), age (95% within 5-years), NIHSS (98% within 1-point), infarct size, dysphagia, and six other clinical variables. Right hemispheric infarcts were more frequent in patients with HAP versus controls (43.3% vs. 34.0%, p = 0.054), whereas left hemispheric infarcts were more frequent in controls (56.7% vs. 44.7%, p = 0.012); there was no significant difference between groups in the rate of brainstem strokes (p = 1.0). Of the 10 most infarcted regions, only right insular cortex volume was different in HAP versus controls (20 vs. 12 ml, p = 0.02). In univariate analyses, the highest log-odds regions for pneumonia were right hemisphere, cerebellum, and brainstem. The best performing multivariate model selected 7 brain regions of infarction and 2 infarct volume-based variables independently associated with HAP. CONCLUSIONS: HAP is associated with right hemispheric peri-insular stroke. These associations may be related to autonomic modulation of immune mechanisms, supporting recent hypotheses of stroke mediated immune suppression.

Management of thrombolysis-associated symptomatic intracerebral hemorrhage.

BACKGROUND: Symptomatic intracerebral hemorrhage (sICH) is the most devastating complication of thrombolytic therapy for acute stroke. It is not clear whether patients with sICH continue to bleed after diagnosis, nor has the most appropriate treatment been determined. METHODS: We performed a retrospective analysis of our prospectively collected Get With the Guidelines-Stroke database between April 1, 2003, and December 31, 2007. Radiologic images and all procoagulant agents used were reviewed. Multivariable logistic regression was performed to identify factors associated with in-hospital mortality. RESULTS: Of 2362 patients with acute ischemic stroke during the study period, sICH occurred in 19 of the 311 patients (6.1%) who received intravenous tissue plasminogen activator and 2 of the 72 (2.8%) who received intra-arterial thrombolysis. In-hospital mortality was significantly higher in patients with sICH than in those without (15 of 20 [75.0]% vs 56 of 332 [16.9%], P < .001). Eleven of 20 patients (55.0%) received therapy for coagulopathy: 7 received fresh frozen plasma; 5, cryoprecipitate; 4, phytonadione (vitamin K(1)); 3, platelets; and 1, aminocaproic acid. Independent predictors of in-hospital mortality included sICH (odds ratio, 32.6; 95% confidence interval, 8.8-120.2), increasing National Institutes of Health Stroke Scale score (1.2; 1.1-1.2), older age (1.3; 1.0-1.7), and intra-arterial thrombolysis (2.9; 1.4-6.0). Treatment for coagulopathy was not associated with outcome. Continued bleeding (>33% increase in intracerebral hemorrhage volume) occurred in 4 of 10 patients with follow-up scans available (40.0%). CONCLUSIONS: In many patients with sICH after thrombolysis, coagulopathy goes untreated. Our finding of continued bleeding after diagnosis in 40.0% of patients suggests a powerful opportunity for intervention. A multicenter registry to analyze management of thrombolysis-associated intracerebral hemorrhage and outcomes is warranted.