The etiology of ischemic stroke affects prognosis, outcome, and management. Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke. A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST). A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies. "Possible" and "probable" diagnoses can be made based on the physician9s certainty of diagnosis. The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria. The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients, first based only on clinical features and then after reviewing the results of diagnostic tests. The TOAST classification denotes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology. Using this rating system, interphysician agreement was very high. The two physicians disagreed in only one patient. They were both able to reach a specific etiologic diagnosis in 11 patients, whereas the cause of stroke was not determined in nine. The TOAST stroke subtype classification system is easy to use and has good interobserver agreement. This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke. Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke.

Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment

Background Atrial fibrillation, the most common sustained cardiac arrhythmia and a major cause of stroke, results from simultaneous reentrant wavelets. Its spontaneous initiation has not been studied. Methods We studied 45 patients with frequent episodes of atrial fibrillation (mean [±SD] duration, 344±326 minutes per 24 hours) refractory to drug therapy. The spontaneous initiation of atrial fibrillation was mapped with the use of multielectrode catheters designed to record the earliest electrical activity preceding the onset of atrial fibrillation and associated atrial ectopic beats. The accuracy of the mapping was confirmed by the abrupt disappearance of triggering atrial ectopic beats after ablation with local radio-frequency energy. Results A single point of origin of atrial ectopic beats was identified in 29 patients, two points of origin were identified in 9 patients, and three or four points of origin were identified in 7 patients, for a total of 69 ectopic foci. Three foci were in the right atrium...

https://www.nejm.org/doi/pdf/10.1056/NEJM199809033391003

Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins

Background and Purpose—The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audienc...

/pdf/guidelines-for-the-early-management-of-patients-with-acute-19udbft6e7.pdf

Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

The impact of nonrheumatic atrial fibrillation, hypertension, coronary heart disease, and cardiac failure on stroke incidence was examined in 5,070 participants in the Framingham Study after 34 years of follow-up. Compared with subjects free of these conditions, the age-adjusted incidence of stroke was more than doubled in the presence of coronary heart disease (p less than 0.001) and more than trebled in the presence of hypertension (p less than 0.001). There was a more than fourfold excess of stroke in subjects with cardiac failure (p less than 0.001) and a near fivefold excess when atrial fibrillation was present (p less than 0.001). In persons with coronary heart disease or cardiac failure, atrial fibrillation doubled the stroke risk in men and trebled the risk in women. With increasing age the effects of hypertension, coronary heart disease, and cardiac failure on the risk of stroke became progressively weaker (p less than 0.05). Advancing age, however, did not reduce the significant impact of atrial...

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.22.8.983

Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.

From 1950 to 1980, 3623 patients from Olmsted County, Minnesota, were found to have atrial fibrillation. Ninety-seven of these patients (2.7 percent), who were 60 years old or younger at diagnosis, had lone atrial fibrillation (atrial fibrillation in the absence of overt cardiovascular disease or precipitating illness), and their data were reviewed to determine the incidence of thromboemboli. Twenty of these patients (21 percent) had an isolated episode of atrial fibrillation, 56 (58 percent) had recurrent atrial fibrillation, and 21 (22 percent) had chronic atrial fibrillation. The total follow-up period was 1440 person-years, with a mean of 14.8 years per patient. The mean age at diagnosis was 44 years. Nineteen cardiovascular events occurred in 17 patients; 4 patients had strokes thought to be due to emboli from atrial fibrillation, and 4 had myocardial infarctions without overt evidence of previous coronary artery disease. The probability of survival at 15 years was 94 percent among the patients with lone atrial fibrillation. At 15 years, 1.3 percent of the patients had had a stroke on a cumulative actuarial basis. On an actuarial basis, there was no difference in survival or in survival free of stroke among the patients with the three types of lone atrial fibrillation (i.e., isolated, recurrent, and chronic). We conclude that lone atrial fibrillation in patients under the age of 60 at diagnosis is associated with a very low risk of stroke. This suggests that routine anticoagulation may not be warranted.

The natural history of lone atrial fibrillation. A population-based study over three decades.

Background and Purpose —There is scant population-based information on functional outcome, survival, and recurrence for ischemic stroke subtypes. Methods —We identified all residents of Rochester, Minnesota, with a first ischemic stroke from 1985 through 1989 using the resources of the Rochester Epidemiology Project medical records linkage system. After reviewing medical records and imaging studies, we assigned patients to 4 major ischemic stroke categories based on National Institute of Neurological Diseases and Stroke Data Bank criteria: large-vessel cervical or intracranial atherosclerosis with stenosis (ATH, n=74), cardioembolic (CE, n=132), lacunar (LAC, n=72), and infarct of uncertain cause (IUC, n=164). We used the Rankin disability score to assess functional outcome and the Kaplan-Meier product-limit method and Cox proportional hazards regression analysis with bootstrap validation to estimate rates and identify predictors of survival and recurrent stroke among these patients. Results —Rankin disabilities were different across stroke subtypes at the time of stroke and 3 months and 1 year later ( P =0.001). LAC was associated with milder deficits compared with other subtypes. Mean follow-up among the 442 patients in the cohort was 3.2 years. Estimated rates of recurrent stroke at 30 days were significantly different ( P P =0.0006; eg, risk ratio for ATH compared with CE=3.3, 95% CI 1.2 to 9.3) but not long term ( P =0.07). Four of 25 recurrent strokes within 30 days were procedure-related, each in patients with ATH. Five-year death rates were significantly different ( P P =0.018; eg, risk ratio for ATH compared with cardioembolic=0.47, 95% CI 0.29 to 0.77) but not 30-day survival ( P =0.2). Conclusions —Early recurrence rates for ischemic stroke caused by ATH are higher than those for other subtypes and higher than previous non–population-based studies have reported. Some of the increased risk of early recurrence among patients with ATH may be iatrogenic. Patients with LAC have better poststroke functional status than those with other subtypes. Survival is poorest among those with ischemic stroke with a cardiac source of embolism.

Ischemic Stroke Subtypes A Population-Based Study of Functional Outcome, Survival, and Recurrence

Background and Purpose—There is scant population-based information on functional outcome, survival, and recurrence for ischemic stroke subtypes. Methods—We identified all residents of Rochester, Minnesota, with a first ischemic stroke from 1985 through 1989 using the resources of the Rochester Epidemiology Project medical records linkage system. After reviewing medical records and imaging studies, we assigned patients to 4 major ischemic stroke categories based on National Institute of Neurological Diseases and Stroke Data Bank criteria: large-vessel cervical or intracranial atherosclerosis with stenosis (ATH, n=74), cardioembolic (CE, n=132), lacunar (LAC, n=72), and infarct of uncertain cause (IUC, n=164). We used the Rankin disability score to assess functional outcome and the Kaplan-Meier product-limit method and Cox proportional hazards regression analysis with bootstrap validation to estimate rates and identify predictors of survival and recurrent stroke among these patients. Results—Rankin disabili...

https://www.ahajournals.org/doi/pdf/10.1161/01.str.31.5.1062?frame=header

Ischemic Stroke subtypes: A population-based study of incidence and risk factors

Background and purpose Trends in stroke incidence and mortality are available from few sites worldwide. The unique nature of the medical care in patients from Rochester, Minn, has allowed the ascertainment of virtually all cases of stroke for community residents for the period dating from 1955. This study updates incidence rates, stroke mortality, radiological imaging availability, and prevalence for stroke and subtypes of stroke though 1989 and evaluates trends since 1955. Methods Medical records of all residents of Rochester with potential diagnosis of stroke during the 5-year period through December 31, 1989 were screened to determine whether the case met the criteria for stroke. The type of stroke was determined with the use of all available data. Average annual age- and sex-adjusted incidence rates for stroke and various types of stroke were calculated for 5-year periods from 1955 to 1989. Prevalence of stroke was also determined. Poisson regression was used to better clarify the dependence of stroke incidence on multiple variables. Cox proportional hazards modeling evaluated trends in short-term and long-term stroke survival. Results We found that 496 incidence cases of stroke occurred among Rochester residents during 1985 to 1989. The annual age- and sex-adjusted stroke incidence rates was 145 per 100 000 population, which was virtually unchanged from 1980 to 1984 and 13% higher than the rate determined in 1975 to 1979. Increasing incidence rates compared with the 1970s were noted in all groups aged older than 54 years and in both sexes. Survival after cerebral infarction was dependent on age and calendar year when trends dating from 1955 were evaluated. The annual incidence rate of intraparenchymal hemorrhage was twice that of subarachnoid hemorrhage. Conclusions Incidence rates for stroke have remained at a high rate than those determined in the 1970s. Although the occurrence of untreated hypertension has been reported to be stable or decreasing, the incidence rate of stroke is higher than those noted during the decline in stroke incidence during the 1960s and 1970s. In addition to the impact of radiological imaging, increased contribution of patients with ischemic heart disease, and the possible detection of milder cases of stroke, other factors, which are undefined, may be contributing to the increased stroke incidence rates detected over the last 10 years.

Stroke incidence, prevalence, and survival: secular trends in Rochester, Minnesota, through 1989.

The authors report the results of a long-term follow-up study of 130 patients with 161 unruptured intracranial saccular aneurysms. Their findings suggest that unruptured saccular aneurysms less than 10 mm in diameter have a very low probability of subsequent rupture. The mean diameter of the aneurysms that subsequently ruptured was 21.3 mm, compared with a diameter of 7.5 mm for aneurysms defined after rupture at the same institution. Part of the explanation for this discrepancy may be that the size of the filling compartment of the aneurysm decreases after rupture. There is also evidence from the present study that intracranial saccular aneurysms develop with increasing age of the patient and stabilize over a relatively short period, if they do not initially rupture, and that the likelihood of subsequent rupture decreases considerably if the initial stabilized size is less than 10 mm in diameter. Consequently, the critical size for aneurysm rupture is likely to be smaller if rupture occurs at the time of or soon after aneurysm formation. There seems to be a substantial difference in potential for growth and rupture between previously ruptured and unruptured aneurysms.

Jack P. Whisnant

Papers

The natural history of lone atrial fibrillation. A population-based study over three decades.

Ischemic Stroke Subtypes A Population-Based Study of Functional Outcome, Survival, and Recurrence

Ischemic Stroke subtypes: A population-based study of incidence and risk factors

Stroke incidence, prevalence, and survival: secular trends in Rochester, Minnesota, through 1989.

The significance of unruptured intracranial saccular aneurysms.