Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.

AIMS: Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE). METHODS AND RESULTS: We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% [relative risk (RR) 0.75, 95% confidence interval (CI) 0.61-0.92; P = 0.005], myocardial infarction by 22% (RR 0.78, 95% CI 0.64-0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34-0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66-0.90; P < 0.001). We observed no difference in all-cause death (RR 1.08, 95% CI 0.71-1.62; P = 0.73), with a lower incidence of cardiovascular death (RR 0.82, 95% CI 0.55-1.23; P = 0.34) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38, 95% CI 0.99-1.92; P = 0.060). CONCLUSION: Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.

Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial.

BACKGROUND: Inflammation plays a crucial role in clinical manifestations and complications of acute coronary syndromes (ACS). Colchicine, a commonly used treatment for gout, has recently emerged as a novel therapeutic option in cardiovascular medicine owing to its anti-inflammatory properties. We sought to determine the potential usefulness of colchicine treatment in patients with ACS. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial involving 17 hospitals in Australia that provide acute cardiac care service. Eligible participants were adults (18-85 years) who presented with ACS and had evidence of coronary artery disease on coronary angiography managed with either percutaneous coronary intervention or medical therapy. Patients were assigned to receive either colchicine (0.5 mg twice daily for the first month, then 0.5 mg daily for 11 months) or placebo, in addition to standard secondary prevention pharmacotherapy, and were followed up for a minimum of 12 months. The primary outcome was a composite of all-cause mortality, ACS, ischemia-driven (unplanned) urgent revascularization, and noncardioembolic ischemic stroke in a time to event analysis. RESULTS: A total of 795 patients were recruited between December 2015 and September 2018 (mean age, 59.8±10.3 years; 21% female), with 396 assigned to the colchicine group and 399 to the placebo group. Over the 12-month follow-up, there were 24 events in the colchicine group compared with 38 events in the placebo group (P=0.09, log-rank). There was a higher rate of total death (8 versus 1; P=0.017, log-rank) and, in particular, noncardiovascular death in the colchicine group (5 versus 0; P=0.024, log-rank). The rates of reported adverse effects were not different (colchicine 23.0% versus placebo 24.3%), and they were predominantly gastrointestinal symptoms (colchicine, 23.0% versus placebo, 20.8%). CONCLUSIONS: The addition of colchicine to standard medical therapy did not significantly affect cardiovascular outcomes at 12 months in patients with ACS and was associated with a higher rate of mortality. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615000861550.

Epidemiology of COVID-19 Infection in Hospitalized End-Stage Kidney Disease Patients in a Predominantly African-American Population.

BACKGROUND: End-stage kidney disease patients on dialysis are particularly susceptible to COVID-19 infection due to comorbidities, age, and logistic constraints of dialysis making social distancing difficult. We describe our experience with hospitalized dialysis patients with COVID-19 and factors associated with mortality. METHODS: From March 1, 2020, to May 31, 2020, all dialysis patients admitted to 4 Emory Hospitals and tested for COVID-19 were identified. Sociodemographic information and clinical and laboratory data were obtained from the medical record. Death was defined as an in-hospital death or transfer to hospice for end-of-life care. Patients were followed until discharge or death. RESULTS: Sixty-four dialysis patients with COVID-19 were identified. Eighty-four percent were African-American. The median age was 64 years, and 59% were males. Four patients were on peritoneal dialysis, and 60 were on hemodialysis for a median time of 3.8 years, while 31% were obese. Fever (72%), cough (61%), and diarrhea (22%) were the most common symptoms at presentation. Thirty-three percent required admission to intensive care unit, and 23% required mechanical ventilation. The median length of stay was 10 days, while 11 patients (17%) died during hospitalization and 17% were discharged to a temporary rehabilitation facility. Age >65 years (RR 13.7, CI: 1.9-100.7), C-reactive protein >100 mg/dL (RR 8.3, CI: 1.1-60.4), peak D-dimer >3,000 ng/mL (RR 4.3, CI: 1.03-18.2), bilirubin >1 mg/dL (RR 3.9, CI: 1.5-10.4), and history of peripheral vascular disease (RR 3.2, CI: 1.2-9.1) were associated with mortality. Dialysis COVID-19-infected patients were more likely to develop thromboembolic complications than those without COVID-19 (RR 3.7, CI: 1.3-10.1). CONCLUSION: In a predominantly African-American population, the mortality of end-stage kidney disease patients admitted with COVID-19 infection was 17%. Age, C-reactive protein, D-dimer, bilirubin, and history of peripheral vascular disease were associated with worse survival.

Utility of Zwolle Risk Score in Guiding Low-Risk STEMI Discharge.

BACKGROUND: Despite emerging evidence suggesting that selected patients presenting with ST-segment elevation myocardial infarction (STEMI) treated successfully with primary percutaneous coronary intervention (PPCI) may be considered for early discharge, STEMI patients are typically hospitalised longer to monitor for serious complications. METHODS: We assessed the feasibility of identifying low-risk STEMI patients in our institution for early discharge using the Zwolle risk score (ZRS). We evaluated consecutive STEMI patients who underwent successful PPCI within the period 1 January 2016 to 31 December 2017. Low-risk was defined as ZRS≤3. Demographic, angiographic characteristics, length of stay (LOS), and 30-day major adverse cardiovascular events (MACE) defined as cardiac death, stroke, congestive cardiac failure, and non-fatal myocardial infarction, were recorded. RESULTS: There were 183 STEMI patients in our study cohort (mean age 62.0±12.2 years, 77.0% male). The median ZRS was 2 (interquartile range 1-4) with 132 (72.1%) patients classified as low-risk. The overall 30-day MACE and mortality rates were 10.4% and 3.3% respectively. None of the 35 (26.5%) low-risk patients who were discharged within 72 hours experienced MACE at 30 days. Low-risk STEMI patients had significantly shorter median LOS (86.3 vs. 93.2 hours, p=0.002), lower 30-day MACE (4.5% vs. 25.5%, p<0.0001) and mortality (0% vs. 11.8%, p<0.0001) compared to high-risk group (ZRS>3). Receiver operating characteristic (ROC) curve analyses for ZRS in predicting 30-day MACE and mortality yielded C-statistics of 0.79 (95%CI 0.68-0.90, p<0.0001) and 0.98 (95%CI 0.95-1.00, p<0.0001) respectively. CONCLUSION: Low-risk STEMI patients stratified by Zwolle risk score, who were treated successfully with PPCI, experienced low 30-day MACE and mortality rates, indicating that early discharge may be safe in these patients. Larger studies are warranted to evaluate the safety of ZRS-guided early discharge of STEMI patients, as well as the economic and psychological impacts.

Elevated Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio Predicts Long-Term Mortality in High-Risk Patients.

BACKGROUND: Elevated triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been utilised as a predictor of outcomes in patients with adverse cardiometabolic risk profiles. In this study, we examined the prognostic value of elevated TG/HDL-C level in an Australian population of patients with high clinical suspicion of coronary artery disease (CAD) presenting for coronary angiography. METHODS: Follow-up data was collected for 482 patients who underwent coronary angiography in a prospective cohort study. The primary endpoint was all-cause mortality and the secondary endpoint was a major adverse cardiac event (MACE). Patients were stratified into two groups according to their baseline TG/HDL-C ratio, using a TG/HDL-C ratio cut point of 2.5. RESULTS: The mean follow-up period was 5.1 ± 1.2 years, with 49 all-cause deaths. Coronary artery disease on coronary angiography was more prevalent in patients with TG/HDL-C ratio ≥2.5 (83.6% vs. 69.4%, p = 0.03). On the Kaplan-Meier analysis, patients with TG/HDL-C ratio ≥2.5 had worse long-term prognosis (p = 0.04). On multivariate Cox regression adjusting for established cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was an independent predictor of long-term all-cause mortality (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.04-4.20, p = 0.04). On multivariate logistic regression adjusting for known cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was strongly associated with an increased risk of long-term MACE (odds ratio [OR] 2.72, 95% CI 1.42-5.20, p = 0.002). CONCLUSIONS: Elevated TG/HDL-C ratio is an independent predictor of long-term all-cause mortality and is strongly associated with an increased risk of MACE.

Generalized Safety and Efficacy of Simplified Intravenous Thrombolysis Treatment (SMART) Criteria in Acute Ischemic Stroke: The MULTI SMART Study.

BACKGROUND: Common intravenous recombinant tissue plasminogen activator (IV rt-PA) exclusion criteria may substantially limit the use of thrombolysis. Preliminary data have shown that the SMART (Simplified Management of Acute stroke using Revised Treatment) criteria greatly expand patient eligibility by reducing thrombolysis exclusions, but they have not been assessed on a large scale. We evaluated the safety and efficacy of general adoption of SMART thrombolysis criteria to a large regional stroke network. METHODS: Retrospective analysis of consecutive patients who received IV thrombolysis within a regional stroke network was performed. Patients were divided into those receiving thrombolysis locally versus at an outside hospital. The primary outcome was modified Rankin Scale score (≤1) at discharge and the main safety outcome was symptomatic intracranial hemorrhage (sICH) rate. RESULTS: There were 539 consecutive patients, and 50.5% received thrombolysis at an outside facility. Ninety percent of the patients possessed common conventional IV rt-PA contraindications. There were no significant differences between local and network treated patients in favorable outcome (45.4% versus 37.4%; odds ratio [OR], .72; P > .09), mortality (9% versus 14%; OR, 1.6; P > .07), or sICH rate (2.6% versus 5.1%; OR, 2.0; P = .13). Multivariate analysis showed no association between receiving IV rt-PA at an outlying spoke hospital and higher rate of sICH or worse outcome at discharge. CONCLUSIONS: Generalized application of SMART criteria is safe and effective. Widespread application of these criteria could substantially increase the proportion of patients who might qualify for treatment.

Description of symptom course in a telemedicine monitoring clinic for acute symptomatic COVID-19: a retrospective cohort study.

OBJECTIVE: Describe the disease course in a cohort of outpatients with COVID-19 and evaluate factors predicting duration of symptoms. DESIGN: Retrospective cohort study. SETTING: Telemedicine clinic at a large medical system in Atlanta, Georgia. PARTICIPANTS: 337 patients with acute COVID-19. Exclusion criteria included intake visit more than 10 days after symptom onset and hospitalisation prior to intake visit. MAIN OUTCOME MEASURES: Symptom duration in days. RESULTS: Common symptoms at intake visit are upper respiratory (73% cough, 55% loss of smell or taste, 57% sinus congestion, 32% sore throat) and systemic (66% headache, 64% body aches, 53% chills, 30% dizziness, 36% fever). Day of symptom onset was earliest for systemic and upper respiratory symptoms (median onset day 1 for both), followed by lower respiratory symptoms (day 3, 95% CI 2 to 4), with later onset of gastrointestinal symptoms (day 4, 95% CI 3 to 5), when present. Cough had the longest duration when present with median 17 days (95% CI 15 to 21), with 42% not resolved at final visit. Loss of smell or taste had the second longest duration with 14 days (95% CI 12 to 17), with 38% not resolved at final visit. Initial symptom severity is a significant predictor of symptom duration (p<0.01 for multiple symptoms). CONCLUSIONS: COVID-19 illness in outpatients follows a pattern of progression from systemic symptoms to lower respiratory symptoms and persistent symptoms are common across categories. Initial symptom severity is a significant predictor of disease duration for most considered symptoms.

Use of a Telemedicine Risk Assessment Tool to Predict the Risk of Hospitalization of 496 Outpatients With COVID-19: Retrospective Analysis.

BACKGROUND: Risk assessment of patients with acute COVID-19 in a telemedicine context is not well described. In settings of large numbers of patients, a risk assessment tool may guide resource allocation not only for patient care but also for maximum health care and public health benefit. OBJECTIVE: The goal of this study was to determine whether a COVID-19 telemedicine risk assessment tool accurately predicts hospitalizations. METHODS: We conducted a retrospective study of a COVID-19 telemedicine home monitoring program serving health care workers and the community in Atlanta, Georgia, with enrollment from March 24 to May 26, 2020; the final call range was from March 27 to June 19, 2020. All patients were assessed by medical providers using an institutional COVID-19 risk assessment tool designating patients as Tier 1 (low risk for hospitalization), Tier 2 (intermediate risk for hospitalization), or Tier 3 (high risk for hospitalization). Patients were followed with regular telephone calls to an endpoint of improvement or hospitalization. Using survival analysis by Cox regression with days to hospitalization as the metric, we analyzed the performance of the risk tiers and explored individual patient factors associated with risk of hospitalization. RESULTS: Providers using the risk assessment rubric assigned 496 outpatients to tiers: Tier 1, 237 out of 496 (47.8%); Tier 2, 185 out of 496 (37.3%); and Tier 3, 74 out of 496 (14.9%). Subsequent hospitalizations numbered 3 out of 237 (1.3%) for Tier 1, 15 out of 185 (8.1%) for Tier 2, and 17 out of 74 (23%) for Tier 3. From a Cox regression model with age of 60 years or older, gender, and reported obesity as covariates, the adjusted hazard ratios for hospitalization using Tier 1 as reference were 3.74 (95% CI 1.06-13.27; P=.04) for Tier 2 and 10.87 (95% CI 3.09-38.27; P<.001) for Tier 3. CONCLUSIONS: A telemedicine risk assessment tool prospectively applied to an outpatient population with COVID-19 identified populations with low, intermediate, and high risk of hospitalization.

In-hospital 'CODE STEMI' improves door-to-balloon time in patients undergoing primary percutaneous coronary intervention.

OBJECTIVE: Reducing time to reperfusion for ST-segment elevation myocardial infarction (STEMI) is essential in improving outcomes. Consequently, numerous strategies have been employed to reduce median door-to-balloon time (DTBT). METHODS: CODE STEMI is an ED physician-activated STEMI notification system. On activation, an announcement is made over the hospital's public announcement (PA) system. We prospectively analysed all in-hours STEMI patients who had primary percutaneous coronary intervention (PPCI) Pre-CODE STEMI (2014) and after CODE STEMI was implemented (2015). The primary end-points were median DTBT and the proportion of STEMI patients achieving a DTBT ≤90 min. The secondary end-points were in-hospital outcomes, and a composite of major adverse cardiac events (MACE) and hospital readmission rates at 30 days and 12 months. RESULTS: There were 41 and 42 patients in Pre-CODE STEMI and CODE STEMI groups respectively. Baseline characteristics were similar. DTBT was significantly reduced by 22.1 min from 67.1 ± 34.9 min Pre-CODE STEMI to 45.0 ± 22.7 min (P = 0.001) in the CODE STEMI group. Door-to-door time (DTDT) was also reduced from 46.3 ± 30.9 min to 29.4 ± 23.3 min (P = 0.006). A greater proportion of CODE STEMI patients achieved the target DTBT ≤90 min (95.2% vs 73.2%, P = 0.007). CODE STEMI patients had less systolic dysfunction measured by a left ventricle ejection fraction of ≤40% (10.0% vs 27.8%, P = 0.07). There were trends to lower in-hospital mortality rates (4.8% vs 9.8%, P = 0.43), MACE at 30 days and 12 months (4.8% vs 9.8%, P = 0.43; 11.9% vs 22.0%, P = 0.25). CONCLUSION: The novel in-hospital in-hours CODE STEMI notification system significantly reduced DTBT in patients undergoing PPCI.

Combination therapy with the advanced glycation end product cross-link breaker, alagebrium, and angiotensin converting enzyme inhibitors in diabetes: synergy or redundancy?

Blockade of advanced glycation end product (AGE) accumulation with alagebrium with concomitant angiotensin converting enzyme inhibition was tested for effects on renal function and on other postulated mediators of diabetic renal disease including the renin-angiotensin system, AGEs, mitochondrial and cytosolic oxidative stress, and intracellular signaling molecules. Sprague Dawley rats were rendered diabetic with streptozocin and followed consecutively for 32 wk with nondiabetic controls. Groups were treated with ramipril (1 mg/kg.d; wk 0-32); alagebrium (10 mg/kg.d; wk 16-32); or a combination of both. Although individual treatments had significant effects on albuminuria, no further improvements were seen with combination therapy. Changes in urinary vascular endothelial growth factor excretion mirrored those seen in albuminuria. Diabetes was associated with suppression of circulating angiotensin II in the context of increased circulating and renal levels of the AGE, carboxymethyllysine. All treatments attenuated circulating but not renal carboxymethyllysine levels. The renal gene expression of AGE receptor 1 and soluble receptor for advanced glycation end products were markedly reduced by diabetes and normalized with alagebrium. Diabetes induced renal mitochondrial oxidative stress, which was reduced with alagebrium. In the cytosol, both therapies were equally effective in reducing reactive oxygen species production. Increases in membranous protein kinase C activity in diabetes were attenuated by all treatments, whereas diabetes-associated increases in nuclear factor-kappaB p65 translocation remained unaltered by any therapy. It is evident that renin-angiotensin system blockade and AGE inhibition have specific effects. However, many of their downstream effects appear to be similar, suggesting that their renoprotective benefits may ultimately involve common pathways and key points of convergence, which could be important targets for new therapies in diabetic nephropathy.

High-Sensitivity C-Reactive Protein Is a Predictor of Coronary Microvascular Dysfunction in Patients with Ischemic Heart Disease.

BACKGROUND: Inflammation and microvascular dysfunction (MVD) are independently associated with adverse cardiovascular outcomes in patients with ischemic heart disease. This study aimed to assess the relationship between inflammation, MVD, and myocardial injury. METHODS: Coronary microvascular function was assessed in 74 patients undergoing percutaneous coronary intervention (PCI) using the index of microvascular resistance (IMR) by a pressure-temperature sensor-tipped wire. Serum high-sensitivity C-reactive protein (hsCRP) level was quantified by rate turbidimetry. Severe MVD was defined as IMR ≥ 30. Pearson correlation was computed to assess the relationships between hsCRP, troponin, and IMR of culprit vessel. Predictors of severe MVD were assessed by regression analysis. RESULTS: Acute coronary syndromes (ACSs) represented 49% of the total cohort. Study cohort was divided into low C-reactive protein (CRP) (hsCRP < 3 mg/L) and high CRP (hsCRP ≥ 3 mg/L) groups. There was higher representation of smokers (78 vs. 52%), diabetics (39 vs. 18%), and ACS (61 vs. 33%), as well as higher body mass index (29.4 ± 4.6 vs. 27.2 ± 4.1) in the high CRP group. Pre-PCI and post-PCI IMR were significantly elevated in the high CRP group compared to the low CRP group (pre-PCI IMR: 29.0 ± 13.9 vs. 17.4 ± 11.1, p < 0.0001; post-PCI IMR: 23.0 ± 16.8 vs. 15.5 ± 8.4, p = 0.02). Peak troponin levels were significantly raised in the high CRP group (9.96 ± 17.19 vs. 1.17 ± 3.00 µg/L, p = 0.002). There was a strong positive correlation between hsCRP and pre-PCI IMR (r = 0.85, p < 0.0001). Pre- and post-PCI IMR levels were correlated with peak troponin level (r = 0.45, p < 0.0001; r = 0.33, p = 0.005, respectively). Predictors of severe MVD include male gender (OR 3.0), diabetes (OR 3.7), smoking history (OR 4.0), ACS presentation (OR 8.5), and hsCRP ≥ 3 mg/L (OR 5.6). CONCLUSION: hsCRP is a significant predictor of MVD while MVD is associated with myocardial injury, supporting the central role of inflammation and MVD in the pathophysiology and complications of coronary artery disease. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN): 12617000648325. Universal Trial Number (UTN): U1111-1196-2246.

Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America.

BACKGROUND: Despite advances in medical, surgical, and critical care interventions, infective endocarditis remains a disease that is associated with considerable morbidity and mortality. The continuing evolution of antimicrobial resistance among common pathogens that cause infective endocarditis creates additional therapeutic issues for physicians to manage in this potentially life-threatening illness. METHODS AND RESULTS: This work represents the third iteration of an infective endocarditis "treatment" document developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It updates recommendations for diagnosis, treatment, and management of complications of infective endocarditis. A multidisciplinary committee of experts drafted this document to assist physicians in the evolving care of patients with infective endocarditis in the new millennium. This extensive document is accompanied by an executive summary that covers the key points of the diagnosis, antimicrobial therapy, and management of infective endocarditis. For the first time, an evidence-based scoring system that is used by the American College of Cardiology and the American Heart Association was applied to treatment recommendations. Tables also have been included that provide input on the use of echocardiography during diagnosis and treatment of infective endocarditis, evaluation and treatment of culture-negative endocarditis, and short-term and long-term management of patients during and after completion of antimicrobial treatment. To assist physicians who care for children, pediatric dosing was added to each treatment regimen. CONCLUSIONS: The recommendations outlined in this update should assist physicians in all aspects of patient care in the diagnosis, medical and surgical treatment, and follow-up of infective endocarditis, as well as management of associated complications. Clinical variability and complexity in infective endocarditis, however, dictate that these guidelines be used to support and not supplant physician-directed decisions in individual patient management.

Colchicine in cardiovascular disease: an ancient drug with modern tricks.

From the dark history of being a poison and purgative, colchicine has risen to become one of the few irrefutable positives in the history of pharmacology in the management of myriad inflammatory conditions. Colchicine exerts its action through binding to tubulin, which in turn affects several cellular processes and pathways modulating the inflammatory response. Despite narrow therapeutic-toxicity window and the most common complaint of gastrointestinal upset, its list of medicinal use is expanding in recent years as we continue to unravel the mystery of this ancient remedy. In this review, we summarise the history of colchicine use, discuss its pharmacokinetics and mechanism of actions, and examine the most up-to-date evidence of colchicine in the treatment of various cardiac conditions with a focus on cardiovascular disease.

Novel risk factors for acute coronary syndromes and emerging therapies.

Acute coronary syndromes represent not merely disrupted atherosclerotic plaques or luminal stenoses but rather a complex clinical syndrome. The traditional conception of pathogenesis and management of ACS has been challenged by numerous recent landmark ACS trials. Current prognostication models lack clinical precision and can be challenging to the clinicians in tailoring management strategies for individual patients. In this review we summarise the emerging evidence of novel risk factors (plaque phenotype, coronary blood flow, endothelial dysfunction, microvascular dysfunction, and inflammation) in predicting future events and outcomes in ACS population. As the search for miracle cure for ischaemic heart disease continues, one is hopeful that emerging therapeutic approaches targeting these novel risk factors will improve long-term outcomes of ACS.

Automated method for generating the arterial input function on perfusion-weighted MR imaging: validation in patients with stroke.

BACKGROUND AND PURPOSE: The choice of arterial input function (AIF) can have a profound effect on the blood flow maps generated on perfusion-weighted MR imaging (PWI). Automation of this process could substantially reduce operator dependency, increase consistency, and accelerate PWI analysis. We created an automated AIF identification program (auto-AIF) and validated its performance against conventional manual methods. METHODS: We compared the auto-AIF against manually derived AIFs from multisection PWIs of 22 patients with stroke. Time to peak, curve width, curve height, and voxel location determined with both techniques were compared. The time to maximum of the tissue residue function (Tmax) and cerebral blood flow (CBF) were computed on a per-pixel basis for each AIF. Spatial patterns of 528 map pairs were compared by computing Pearson correlation coefficients between maps generated with each method. RESULTS: All auto-AIF-derived PWI map parameters, including bolus peak, width, and height, were consistently superior to manually derived ones. Reproducibility of the auto-AIF-based Tmax maps was excellent (r = 1.0). Paired Tmax maps and CBF maps from both techniques were well correlated (r = 0.82). Time to identify the AIF was significantly shorter with the auto-AIF method than with the manual technique (mean difference, 72 seconds; 95% confidence interval: 54, 89 seconds). CONCLUSION: An automated program that identifies the AIF is feasible and can create reliably reproducible and accurate Tmax and CBF maps. Automation of this process could reduce PWI analysis time and increase consistency and may allow for more effective use of PWI in the evaluation of acute stroke.

Mechanical thrombectomy for acute stroke.

BACKGROUND AND PURPOSE: We evaluated a mechanical thrombectomy protocol to treat acute stroke and report the angiographic results and clinical outcomes. METHODS: Patients with anterior circulation strokes <8 hours and posterior circulation strokes <12 hours were treated at a single center over 10 months. Patients were excluded if they were candidates for intravenous tissue plasminogen activator (tPA). Treatment involved one of two mechanical thrombectomy devices. Retrieval was augmented by low-dose intra-arterial tPA if needed. Outcome was measured by using the Modified Rankin score. RESULTS: Ten patients were treated: five with anterior circulation strokes, four with posterior circulation strokes, and one with embolic strokes involving both circulations. Mean National Institutes of Health Stroke Scale score at presentation was 24.6 +/- 10.9. In eight patients (80%), revascularization was successful (Thrombolysis in Acute Myocardial Infarction score, 3). Mean time from symptom onset to initiation of the procedure was 6 hours (5.3 hours for anterior circulation and 7.0 hours for posterior circulation). Mean time for recanalization from the start of the procedure was 1.17 +/- 0.58 hours for the six anterior circulation strokes and 2.75 +/- 1.34 hours in the two posterior circulation strokes. Five patients died within 48 hours; all had posterior circulation strokes. Mean Modified Rankin score at 90 days was 1.4. CONCLUSION: In this small series, mechanical thrombectomy of acute stroke appeared to improve recanalization rates compared with intra-arterial thrombolysis. No hemorrhagic complications occurred. Further study is required to determine the role of these techniques.

Intracranial angioplasty without stenting for symptomatic atherosclerotic stenosis: long-term follow-up.

BACKGROUND AND PURPOSE: Angioplasty and stent placement have been reported for the treatment of intracranial stenosis. This study was undertaken to assess the efficacy and long-term clinical outcome of angioplasty without stent placement for patients with symptomatic intracranial stenosis. METHODS: A retrospective study was done to evaluate 36 patients with 37 symptomatic atherosclerotic intracranial stenosis who underwent primary balloon angioplasty. All patients had symptoms despite medical therapy. Thirty-four patients were available for follow-up ranging from 6 to 128 months. Mean follow-up was 52.9 months. RESULTS: Mean pretreatment stenosis was 84.2% before angioplasty and 43.3% after angioplasty. The periprocedural death and stroke rate was 8.3% (two deaths and one minor stroke). Two patients had strokes in the territory of angioplasty at 2 and 37 months after angioplasty. The annual stroke rate in the territory appropriate to the site of angioplasty was 3.36%, and for those patients with a residual stenosis of > or =50% it was 4.5%. Patients with iatrogenic dissection (n=11) did not have transient ischemic attacks or strokes after treatment. CONCLUSION: Results of long-term follow-up suggest that intracranial angioplasty without stent placement reduces the risk of further stroke in symptomatic patients.

Detection of diffusion-weighted MRI abnormalities in patients with transient ischemic attack: correlation with clinical characteristics.

BACKGROUND AND PURPOSE: Although diffusion-weighted MRI (DWI) has demonstrated clear superiority over other conventional imaging modalities in the detection of hyperacute cerebral ischemia, its value in the evaluation of patients with transient symptoms has received only limited attention. We assessed the utility of DWI in patients with transient ischemic attack (TIA) to further evaluate the usefulness of this technique in these individuals. METHODS: A retrospective analysis was performed on all patients entered in the Stanford Stroke Center database during 1997-2001 who were clinically diagnosed with a TIA and who had also undergone a DWI scan or=1 hour, 16 times more likely to have had motor deficits, and 25 times more likely to have had aphasia than patients with negative DWI scans. The combination of all 3 symptoms was 100% specific for an abnormality on DWI. In 7 of 16 cases (44%), a DWI abnormality was present on both DWI and conventional imaging (T2-weighted imaging or fluid-attenuated inversion recovery [FLAIR]). In all of these cases the DWI clarified the extent or acuity of the lesion (n=7) or identified additional lesions not detected by conventional imaging (n=9). CONCLUSIONS: In TIA patients, symptom duration >or=1 hour, motor deficits, and aphasia were each independently correlated with detecting an abnormality with DWI. DWI was also helpful in differentiating between chronic versus acute lesions. These data may be of value in identifying those TIA patients for whom MRI evaluation with DWI is of greatest clinical utility.