Background Current guidelines recommend at least 24 hours of electrocardiographic (ECG) monitoring after an ischemic stroke to rule out atrial fibrillation. However, the most effective duration and type of monitoring have not been established, and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40% of cases (cryptogenic stroke). Detection of atrial fibrillation after cryptogenic stroke has therapeutic implications. Methods We conducted a randomized, controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor (ICM) is more effective than conventional follow-up (control) for detecting atrial fibrillation in patients with cryptogenic stroke. Patients 40 years of age or older with no evidence of atrial fibrillation during at least 24 hours of ECG monitoring underwent randomization within 90 days after the index event. The primary end point was the time to first detection of atrial fibrillation (lasting >30 seconds) within 6 months. Among the secondary end points was the time to first detection of atrial fibrillation within 12 months. Data were analyzed according to the intention-to-treat principle. Results By 6 months, atrial fibrillation had been detected in 8.9% of patients in the ICM group (19 patients) versus 1.4% of patients in the control group (3 patients) (hazard ratio, 6.4; 95% confidence interval [CI], 1.9 to 21.7; P<0.001). By 12 months, atrial fib rillation had been detected in 12.4% of patients in the ICM group (29 patients) versus 2.0% of patients in the control group (4 patients) (hazard ratio, 7.3; 95% CI, 2.6 to 20.8; P<0.001). Conclusions ECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke. (Funded by Medtronic; CRYSTAL AF ClinicalTrials.gov number, NCT00924638.)

/pdf/cryptogenic-stroke-and-underlying-atrial-fibrillation-2h96wiclzs.pdf

Cryptogenic stroke and underlying atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

The Clinical Profile and Pathophysiology of Atrial Fibrillation Relationships Among Clinical Features, Epidemiology, and Mechanisms

Summary Background Among patients with atrial fibrillation, the risk of stroke is highest for those with a history of stroke; however, oral anticoagulants can lower the risk of recurrent stroke by two-thirds. No consensus has been reached about how atrial fibrillation should be investigated in patients with stroke, and its prevalence after a stroke remains uncertain. We did a systematic review and meta-analysis to estimate the proportion of patients newly diagnosed with atrial fibrillation after four sequential phases of cardiac monitoring after a stroke or transient ischaemic attack. Methods We searched PubMed, Embase, and Scopus from 1980 to June 30, 2014. We included studies that provided the number of patients with ischaemic stroke or transient ischaemic attack who were newly diagnosed with atrial fibrillation. We stratified cardiac monitoring methods into four sequential phases of screening: phase 1 (emergency room) consisted of admission electrocardiogram (ECG); phase 2 (in hospital) comprised serial ECG, continuous inpatient ECG monitoring, continuous inpatient cardiac telemetry, and in-hospital Holter monitoring; phase 3 (first ambulatory period) consisted of ambulatory Holter; and phase 4 (second ambulatory period) consisted of mobile cardiac outpatient telemetry, external loop recording, and implantable loop recording. The primary endpoint was the proportion of patients newly diagnosed with atrial fibrillation for each method and each phase, and for the sequential combination of phases. For each method and each phase, we estimated the summary proportion of patients diagnosed with post-stroke atrial fibrillation using random-effects meta-analyses. Findings Our systematic review returned 28 290 studies, of which 50 studies (comprising 11 658 patients) met the criteria for inclusion in the meta-analyses. The summary proportion of patients diagnosed with post-stroke atrial fibrillation was 7·7% (95% CI 5·0–10·8) in phase 1, 5·1% (3·8–6·5) in phase 2, 10·7% (5·6–17·2) in phase 3, and 16·9% (13·0–21·2) in phase 4. The overall atrial fibrillation detection yield after all phases of sequential cardiac monitoring was 23·7% (95% CI 17·2–31·0). Interpretation By sequentially combining cardiac monitoring methods, atrial fibrillation might be newly detected in nearly a quarter of patients with stroke or transient ischaemic attack. The overall proportion of patients with stroke who are known to have atrial fibrillation seems to be higher than previously estimated. Accordingly, more patients could be treated with oral anticoagulants and more stroke recurrences prevented. Funding Heart and Stroke Foundation of Canada, and Natural Science and Engineering Research Council of Canada.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422%2815%2970027-X.pdf

Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and meta-analysis

The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation

ASCO phenotyping (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes) assigns a degree of likelihood of causal relationship to every potential disease (1 for potentiall

/pdf/the-ascod-phenotyping-of-ischemic-stroke-updated-asco-55iudj9sb0.pdf

The ASCOD phenotyping of ischemic stroke (Updated ASCO Phenotyping).

Background: Despite use in clinical practice and major positive trials of thrombolysis, non-contrast computed tomography (NCCT) is not sensitive for identifying penumbral tissue in

Does Perfusion Computed Tomography Facilitate Clinical Decision Making for Thrombolysis in Unselected Acute Patients with Suspected Ischaemic Stroke

Background: Stroke in younger people is relatively common and frequently unexplained. While understanding of the causes of young stroke has improved, there remains uncertainty over the role of low-risk lesions such as a patent foramen ovale (PFO). The TOAST criteria are often used to describe stroke aetiology, but in younger people in whom PFOs are frequent, there is a very high proportion of cases attributed to cardiac embolism. The impact of using the newer A-S-C-O criteria on stroke aetiology was investigated. Methods: Consecutive patients with ischaemic stroke were investigated and categorised by the TOAST and ASCO1 criteria. Stroke aetiology was presented and compared by the different classification systems. Results: Of the 106 ischaemic stroke cases, by TOAST 6% were ‘large artery atheroma’, 11% ‘small vessel occlusion’, 28% ‘cardioembolic’, 22% ‘other determined cause’ and 33% ‘undetermined cause’. The vascular territory and associated causes are presented. With the ASCO1 criteria, there were more cases of unclassified stroke (51.9 vs. 34.0%; p Conclusion: Using the ASCO criteria, more patients fall into the undetermined group which more accurately reflects our current uncertainty regarding the pathogenic relevance of PFOs in this age group.

Towards understanding the cause of stroke in young adults utilising a new stroke classification system (A-S-C-O).

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 To the Editor: We read with interest the article by Larrue et al.1 We recently assessed the impact of newer stroke classification systems on stroke subtypes.2 We also agree with the conclusion regarding the contribution of atrial septal abnormalities to stroke in younger people.

Despite the thorough cardiac investigation, Larrue et al. report a relatively low proportion of patients with unexplained stroke with patent foramen ovale (PFO). Of 160 cases investigated, 67 (41.2%) had a PFO (24 isolated, 43 with an atrial septal aneurysm [ASA]). In our institution, of those with …

Etiologic investigation of ischemic stroke in young adults

Stroke in young adults is not a rare entity, and often provides difficult management decisions for neurologists. The knowledge gained from stroke in older adults does not transfer easily to this younger group given the different causes of stroke observed. Cardiac causes of stroke are common in this group, but often consist of low risk cardiac lesions such as a patent foramen ovale. Appropriate investigation should follow a stepwise approach to initially exclude higher risk pathology for recurrent stroke such as arterial dissection. Similarly, stepwise application of cardiac investigations will allow early identification of significant pathology, with investigation for abnormalities of the inter-atrial septum reserved for those with no other identified cause of stroke. Bubble contrast echo is now widely available, and with improved image quality may be performed with either transthoracic or transoesophageal echo, as well as with transcranial Doppler. Following this approach, patients can be best categorised by the expected rate of recurrent stroke, as informed by observational studies. Appropriate secondary prevention can then be tailored to the recurrence rate, with anticoagulation and possibly device closure reserved for those at highest risk of recurrence.

Stroke in younger patients: the heart of the matter

Ischemic stroke in younger people is common, and often remains unexplained. There is a well-documented association between unexplained stroke in younger people, and the presence of a patent foramen ovale. Therefore, in the absence of a clear cause of stroke, the heart is often assessed in detail for such lower risk causes of stroke. This usually involves imaging with a transesophageal echo, and investigation for a right-to-left shunt. An understanding of the anatomy of the atrial septum, and its associated abnormalities, is important for the stroke neurologist charged with decision making regarding appropriate secondary prevention. In this paper, we review the development and anatomy of the right heart with a focus on patent foramen ovale, and other associated abnormalities. We discuss how the heart can be imaged in the case of unexplained stroke, and provide examples. Finally, we suggest a method of investigation, in light of the recent European Association of Echocardiography guidance. Our aim is to provide the neurologist with an understanding on how the heart can be investigated in unexplained stroke, and the significance of abnormalities detected.

Toward understanding the atrial septum in cryptogenic stroke.

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