Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL AF): design and rationale. Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke Cryptogenic stroke and underlying atrial fibrillation. Uncovering Atrial Fibrillation Beyond Short-Term Monitoring in Cryptogenic Stroke Patients: Three-Year Results From the Cryptogenic Stroke and Underlying Atrial Fibrillation Trial Unexpected low prevalence of atrial fibrillation in cryptogenic ischemic stroke: a prospective study Intermittent atrial fibrillation may account for a large proportion of otherwise cryptogenic stroke: a study of 30-day cardiac event monitors. A Structured Reading Algorithm Improves Telemetric Detection of Atrial Fibrillation After Acute Ischemic Stroke The BioMonitor 2 insertable cardiac monitor: Clinical experience with a novel implantable cardiac monitor. Total atrial conduction time to predict occult atrial fibrillation after cryptogenic stroke Atrial fibrillation in patients with cryptogenic stroke. Pilot Randomized Trial of Outpatient Cardiac Monitoring After Cryptogenic Stroke Atrial Premature Beats Predict Atrial Fibrillation in Cryptogenic Stroke: Results From the EMBRACE Trial Frequent Atrial Premature Beats Predict Paroxysmal Atrial Fibrillation in Stroke Patients: An Opportunity for a New Diagnostic Strategy Performance of a New Leadless Implantable Cardiac Monitor in Detecting and Quantifying Atrial Fibrillation Results of the XPECT Trial Prevalence and Risk Factors for Paroxysmal Atrial Fibrillation and Flutter Detection after Cryptogenic Ischemic Stroke. 96 hours ECG monitoring for patients with ischemic cryptogenic stroke or transient ischaemic attack Twenty-eight day Holter monitoring is poorly tolerated and insensitive for paroxysmal atrial fibrillation detection in cryptogenic stroke. Screening for asymptomatic atrial fibrillation while monitoring the blood pressure at home: trial of regular versus irregular pulse for prevention of stroke (TRIPPS 2.0). Noninvasive Cardiac Event Monitoring to Detect Atrial Fibrillation After Ischemic Stroke: A Randomized, Controlled Trial Prevalence of atrial fibrillation with insertable cardiac monitors in cryptogenic stroke: A single-center experience. Predictors of newly diagnosed atrial fibrillation in cryptogenic stroke: a cohort study. Embolic Strokes of Undetermined Source in the Athens Stroke Registry: A Descriptive Analysis Rationale and design of the Apixaban for the Reduction of Thrombo‐Embolism in Patients With Device‐Detected Sub‐Clinical Atrial Fibrillation (ARTESiA) trial
BACKGROUND Patients with atrial fibrillation ( AF ) are at increased risk for ischemic stroke . In patients who have suffered a stroke , screening for AF is routinely performed only for a short period after the stroke as part of the evaluation for possible causes . If AF is detected after an ischemic stroke , oral anticoagulation therapy is recommended for secondary stroke prevention . In 25 % to 30 % of stroke patients , the stroke mechanism can not be determined ( cryptogenic stroke ) . The incidence of paroxysmal AF undetected by short-term monitoring in patients with cryptogenic stroke is unknown , but has important therapeutic implication s on patient care . The optimum monitoring duration and method of AF detection after stroke are unknown . The purpose of this study is to evaluate the incidence of AF and time to AF detection in patients with cryptogenic stroke using an insertable cardiac monitor . STUDY DESIGN The CRYSTAL AF trial is a r and omized prospect i ve study to evaluate a novel approach to long-term monitoring for AF detection in patients with cryptogenic stroke . Four hundred fifty cryptogenic stroke patients ( by definition , without a history of AF ) will be enrolled at approximately 50 sites in Europe , Canada , and the United States . Patients will be r and omized in a 1:1 fashion to st and ard arrhythmia monitoring ( control arm ) or implantation of the subcutaneous cardiac monitor ( Reveal XT ; Medtronic , Inc , Minneapolis , MN ) ( continuous monitoring arm ) . OUTCOMES The primary end point is time to detection of AF within 6 months after stroke . The clinical follow-up period will be at least 12 months . Study completion is expected at the end of 2012 Background and aims Documentation of atrial fibrillation is required to initiate oral anticoagulation therapy for recurrent stroke prevention . Atrial fibrillation often goes undetected with traditional electrocardiogram monitoring techniques . We evaluated whether atrial fibrillation detection using continuous long-term monitoring with an insertable cardiac monitor is cost-effective for preventing recurrent stroke in patients with cryptogenic stroke , in comparison to the st and ard of care . Methods A lifetime Markov model was developed to estimate the cost-effectiveness of insertable cardiac monitors from a UK National Health Service perspective using data from the r and omized CRYSTAL-AF trial and other published literature . We also conducted scenario analyses ( CHADS2 score ) and probabilistic sensitivity analyses . All costs and benefits were discounted at 3.5 % . Results Monitoring cryptogenic stroke patients with an insertable cardiac monitor was associated with fewer recurrent strokes and increased quality -adjusted life years compared to the st and ard of care ( 7.37 vs 7.22 ) . Stroke-related costs were reduced in insertable cardiac monitor patients , but overall costs remained higher than the st and ard of care ( £ 19,631 vs £ 17,045 ) . The incremental cost-effectiveness ratio was £ 17,175 per quality -adjusted life years gained , compared to st and ard of care in the base-case scenario , which is below established quality -adjusted life years willingness-to-pay thresholds . When warfarin replaced non-vitamin-K oral anticoagulants as the main anticoagulation therapy , the incremental cost-effectiveness ratio was £ 13,296 per quality -adjusted life years gained . Conclusion Insertable cardiac monitors are a cost-effective diagnostic tool for the prevention of recurrent stroke in patients with cryptogenic stroke . The cost-effectiveness results have relevance for the UK and across value-based healthcare systems that assess costs relative to outcomes 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 implication s. METHODS We conducted a r and omized , 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 r and omization 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 fibrillation 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 Clinical Trials.gov number , NCT00924638 . ) Background —Atrial fibrillation ( AF ) can be a cause of previously diagnosed cryptogenic stroke . However , AF can be paroxysmal and asymptomatic , thereby making detection with routine ECG methods difficult . Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF , but its initiation is dependent on the detection of AF . Cryptogenic Stroke and Underlying Atrial Fibrillation ( CRYSTAL AF ) is the first r and omized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors ( ICM ) . Methods and Results — Patients with prior cryptogenic stroke were r and omized to control ( n=220 ) or ICM ( n=221 ) and followed for ⩽36 months . Cumulative AF detection rates in the ICM arm increased progressively during this period ( 3.7 % , 8.9 % , 12.4 % , and 30.0 % at 1 , 6 , 12 , and 36 months , respectively ) , but remained low in the control arm ( 3.0 % at 36 months ) . This result ed in oral anticoagulation prescription in 94.7 % of ICM patients with AF detected at 6 months , 96.6 % at 12 months , and 90.5 % at 36 months . Among ICM patients with AF detected , the median time to AF detection was 8.4 months , 81.0 % of first AF episodes were asymptomatic , and 94.9 % had at least 1 day with > 6 minutes of AF . Conclusions —Three-year monitoring by ICM in cryptogenic stroke patients demonstrated a significantly higher AF detection rate compared with routine care . Given the frequency of asymptomatic first episodes and the long median time to detection , these findings highlight the limitations of using traditional AF detection methods . The majority of patients with AF were prescribed oral anticoagulation therapy . Clinical Trial Registration — Clinical trials.gov ; Unique identifier : NCT00924638 Purpose Ischemic stroke is a frequent pathology with high rate of recurrence and significant morbidity and mortality . There are several causes of stroke , affecting prognosis , outcomes , and management , but in many cases , the etiology remains undetermined . We hypothesized that atrial fibrillation was involved in this pathology but underdiagnosed by st and ard methods . The aim of the study was to determine the incidence of atrial fibrillation in cryptogenic ischemic stroke by using continuous monitoring of the heart rate over several months . The secondary objective was to test the value of atrial vulnerability assessment in predicting spontaneous atrial fibrillation . Methods and results We prospect ively enrolled 24 patients under 75 years of age , 15 men and 9 women of mean age 49 years , who within the last 4 months had experienced cryptogenic stroke diagnosed by clinical presentation and brain imaging and presumed to be of cardioembolic mechanism . All causes of stroke were excluded by normal 12-lead ECG , 24-h Holter monitoring , echocardiography , cervical Doppler , hematological , and inflammatory tests . All patients underwent electrophysiological study . Of the patients , 37.5 % had latent atrial vulnerability , and 33.3 % had inducible sustained arrhythmia . Patients were secondarily implanted with an implantable loop recorder to look for spontaneous atrial fibrillation over a mean follow-up interval of 14.5 months . No sustained arrhythmia was found . Only one patient had non-significant episodes of atrial fibrillation . Conclusion In this study , symptomatic atrial fibrillation or AF with fast ventricular rate has not been demonstrated by the implantable loop recorder  in patients under 75 years with unexplained cerebral ischemia . The use of this device should not be generalized in the systematic evaluation of these patients . In addition , this study attests that the assessment of atrial vulnerability is poor at predicting spontaneous arrhythmia in such patients INTRODUCTION Despite extensive inpatient workup including telemetry monitoring , a significant proportion of stroke is classified as cryptogenic at hospital discharge . It is possible that a significant proportion of cryptogenic stroke is a result of intermittent atrial fibrillation ( AF ) . Thirty-day cardiac event monitors ( 30-DEM ) may increase the rate of AF detection compared with st and ard investigations that include a combination of electrocardiography , cardiac telemetry , and short-term Holter monitoring . METHODS Charts were review ed of patients who were admitted to a university stroke center or who were evaluated in the outpatient clinic during a 9-month period to determine whether the cause of stroke was cryptogenic . As a matter of protocol , such patients typically underwent 30-DEM and the results of such monitoring were documented along with the duration of inpatient cardiac monitoring if relevant . RESULTS In all , 218 patients with a diagnosis of ischemic stroke or transient ischemic attack were identified . Of the strokes , 36 ( 16.5 % ) were classified as cryptogenic . Twenty patients with cryptogenic stroke or transient ischemic attack were evaluated with 30-DEM . Four ( 20 % ) were found to have AF , and all 4 patients were treated with warfarin . CONCLUSION The 30-DEM changed the medical treatment of 20 % of patients with otherwise cryptogenic stroke because of the detection of intermittent AF despite no detection of AF on electrocardiography and inpatient telemetry monitoring in the majority of patients . Further prospect i ve studies of extended cardiac event monitors in the setting of cryptogenic stroke are warranted Background and Purpose — Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter ( AF ) . However , the condition remains underdiagnosed , because paroxysmal AF may be missed by diagnostic tests in the acute phase . In this study , the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data ( SEA-AF ) . Methods — Three hundred forty-six consecutive patients with acute ischemic stroke were prospect ively included and subjected to st and ard telemetric monitoring . In addition , telemetric data were separately analyzed following SEA-AF , consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration . Serial electrocardiograms  were conducted in 24-hour intervals . Results — Median effective telemetry monitoring time was 75.5 hours ( interquartile range 64–86 hours ) . Overall , AF was diagnosed in 119 of 346 patients ( 34.4 % ) . The structured reading algorithm was the most sensitive method to detected AF . Conventional telemetry and serial electrocardiographic assessment s were less effective . However , only 35 % of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring . Conclusions — Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessment s and st and ard telemetry without structured reading . The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessment s. Clinical Trial Registration — URL : www . clinical trials.gov . Unique identifier : NCT01177748 INTRODUCTION Implantable loop recorders ( ILR ) are leadless subcutaneous devices that allow cardiac monitoring for up to 3 years and are a valuable tool in the diagnosis of arrhythmias , cryptogenic stroke and unexplained syncope . The Biotronik BioMonitor 2 is a novel , insertable ILR allowing long-term continuous monitoring with wireless telemetry options . METHODS A single-center , prospect i ve , observational study investigating the reliability of sensing quality and detection performance in the BioMonitor 2 ILR , as well as post-implantation patient satisfaction . R-wave amplitude was recorded immediately post implantation and 1 day post implantation , followed by extensive patient instruction . Follow-up was scheduled after 3 months , or after an event . Data from the ILR were retrieved , with documentation of all episodes , R-wave amplitude and noise burden . The anatomical position of the ILR was determined 1 day post implantation and after 3 months . A patient question naire was conducted after 3 months . RESULTS 30 consecutive patients ( mean age 71 ± 12 years , 56 % male ) were analyzed . Indications for ILR implantation were : unexplained syncope ( n = 24 , 80 % ) , suspected atrial fibrillation ( n = 4 , 13 % ) , cryptogenic stroke ( n = 1 , 3 % ) and palpitations ( n = 1 , 3 % ) . Median time from skin cut to suture was 8 min . No complications occurred . Mean R-wave amplitude at implantation was 0.84 ± 0.32 mV , at day 1 post implantation 0.96 ± 0.31 mV , and after a mean follow-up of 85 ± 24 days 1.02 ± 0.47 mV ( p = 0.01 ) . The mean noise burden was 1.4 ± 2 % . CONCLUSION Implantation of the novel BioMonitor 2 ILR is fast and uncomplicated . Initial sensing values are good and improve over time Background Insertable cardiac monitor ( ICM ) increases the detection rate of occult atrial fibrillation ( AF ) after cryptogenic stroke . The aim of this study was to evaluate the prognostic significance of  total atrial conduction time ( TACT )  assessed by tissue Doppler imaging ( PA-TDI interval ) to predict AF presence in patients with cryptogenic stroke . Methods Ninety patients ( 57.7 ± 12.3 years , 48 % women ) after acute cryptogenic stroke and ICM implantation were prospect i ve recruited at four centers for continuous rhythm monitoring . In all patients , TACT was measured by PA-TDI interval via echocardiography . Patients were followed up ( 331 ± 186 days ) for detection of AF ( defined by episode lasting ≥30 s ) . Results AF was detected in 16 patients ( 18 % ) during follow-up ( 331 ± 186 days ) . The median period to AF detection was 30 days ( q1–q3 ; 16–62 days ) . Patients who exhibited occult AF were characterized by significantly longer PA-TDI intervals ( 154.7 ± 12.6 vs. 133.9 ± 9.5 ms , p < 0.0001 ) . The cut-off value of PA-TDI interval at 145 ms demonstrated sensitivity and specificity for AF detection of 93.8 and 90.5 % , respectively . In multivariate analysis , CHA2DS2–VASc score ( HR 1.96 per 1 point , p < 0.01 ) and longer PA-TDI interval ( HR 4.05 per 10 ms , p < 0.0001 ) were independent predictors of occult AF . Conclusion Our data suggest that measurement of TACT could help to predict future AF detection in patients with cryptogenic stroke . The clinical importance of prolonged rhythm monitoring or indication of direct anticoagulation therapy after cryptogenic stroke based on TACT should be further investigated BACKGROUND Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical . However , paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack ( TIA ) . METHODS We r and omly assigned 572 patients 55 years of age or older , without known atrial fibrillation , who had had a cryptogenic ischemic stroke or TIA within the previous 6 months ( cause undetermined after st and ard tests , including 24-hour electrocardiography [ ECG ] ) , to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder ( intervention group ) or a conventional 24-hour monitor ( control group ) . The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after r and omization . Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days . RESULTS Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients ( 16.1 % ) in the intervention group , as compared with 9 of 277 ( 3.2 % ) in the control group ( absolute difference , 12.9 percentage points ; 95 % confidence interval [ CI ] , 8.0 to 17.6 ; P<0.001 ; number needed to screen , 8) . Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients ( 9.9 % ) in the intervention group , as compared with 7 of 277 ( 2.5 % ) in the control group ( absolute difference , 7.4 percentage points ; 95 % CI , 3.4 to 11.3 ; P<0.001 ) . By 90 days , oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group ( 52 of 280 patients [ 18.6 % ] vs. 31 of 279 [ 11.1 % ] ; absolute difference , 7.5 percentage points ; 95 % CI , 1.6 to 13.3 ; P=0.01 ) . CONCLUSIONS Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older , paroxysmal atrial fibrillation was common . Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment , as compared with the st and ard practice of short- duration ECG monitoring . ( Funded by the Canadian Stroke Network and others ; EMBRACE Clinical Trials.gov number , NCT00846924 . ) Background and Purpose — Observational studies indicate that outpatient cardiac monitoring detects previously undiagnosed atrial fibrillation ( AF ) in 5 % to 20 % of patients with recent stroke . However , it remains unknown whether the yield of monitoring exceeds that of routine clinical follow-up . Methods — In a pilot trial , we r and omly assigned 40 patients with cryptogenic ischemic stroke or high-risk transient ischemic attack to wear a Cardionet mobile cardiac outpatient telemetry monitor for 21 days or to receive routine follow-up alone . After thorough investigation , we excluded patients with documented AF or other apparent stroke pathogenesis . We contacted patients and their physicians at 3 months and at 1 year to ascertain any diagnoses of AF or recurrent stroke or transient ischemic attack . Results — The baseline characteristics of our cohort broadly matched those of previous observational studies of monitoring after stroke . In the monitoring group , patients wore monitors for 64 % of the assigned days , and 25 % of patients were not compliant at all with monitoring . No patient in either study arm received a diagnosis of AF . Cardiac monitoring revealed AF in zero patients ( 0 % ; 95 % confidence interval , 0%–17 % ) , brief episodes of atrial tachycardia in 2 patients ( 10 % ; 95 % confidence interval , 1%–32 % ) , and nonsustained ventricular tachycardia in 2 patients ( 10 % ; 95 % confidence interval , 1%–32 % ) . Conclusions — In the first reported r and omized trial of cardiac monitoring after cryptogenic stroke , the rate of AF detection was lower than expected , incidental arrhythmias were frequent , and compliance with monitoring was suboptimal . Our findings highlight the challenges of prospect ively identifying stroke patients at risk for harboring paroxysmal AF and ensuring adequate compliance with cardiac monitoring . Clinical Trial Registration — URL : http:// clinical trials.gov . Unique Identifier : Background and Purpose — Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation ( AF ) . We sought to identify those most likely to have sub clinical AF . Methods — We prospect ively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm , without known AF , enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event ( EMBRACE ) trial . Participants underwent baseline 24-hour Holter ECG poststroke ; if AF was not detected , they were r and omly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder . Multivariable logistic regression assessed the association between baseline variables ( Holter-detected atrial premature beats [ APBs ] , runs of atrial tachycardia , age , and left atrial enlargement ) and subsequent AF detection . Results — Among 237 participants , the median baseline Holter APB count/24 h was 629 ( interquartile range , 142–1973 ) among those who subsequently had AF detected versus 45 ( interquartile range , 14–250 ) in those without AF ( P<0.001 ) . APB count was the only significant predictor of AF detection by 30-day ECG ( P<0.0001 ) , and at 90 days ( P=0.0017 ) and 2 years ( P=0.0027 ) . Compared with the 16 % overall 90-day AF detection rate , the probability of AF increased from < 9 % among patients with < 100 APBs/24 h to 9 % to 24 % in those with 100 to 499 APBs/24 h , 25 % to 37 % with 500 to 999 APBs/24 h , 37 % to 40 % with 1000 to 1499 APBs/24 h , and 40 % beyond 1500 APBs/24 h. Conclusions — Among older cryptogenic stroke or transient ischemic attack patients , the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent sub clinical AF . Those with frequent APBs have a high probability of AF and represent ideal c and i date s for prolonged ECG monitoring for AF detection . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00846924 Background and Purpose — For patients having suffered ischemic stroke , the current diagnostic strategies often fail to detect atrial fibrillation as a potential cause of embolic events . The aim of the study was to identify paroxysmal atrial fibrillation in stroke patients . We hypothesized that patients with frequent atrial premature beats ( APBs ) recorded in 24-hour ECG will show more often atrial fibrillation when followed by repeated long-term ECG recordings than patients without or infrequent APBs . Methods — 127 patients with acute ischemic stroke and without known AF were enrolled in a prospect i ve study to detect paroxysmal AF . Patients were stratified according to the number of APBs recorded in a 24-hour ECG ( ≥70 APBs versus < 70 APBs ) . Subsequently , they all underwent serial 7-day event-recorder monitoring at 0 , 3 , and 6 months . Results — Serial extended ECG monitoring  identified AF in 26 % of patients with frequent APBs but only in 6.5 % when APBs were infrequent ( P=0.0021 ) . A multivariate analysis showed that the presence of frequent APBs in the initial 24-hour ECG was the only independent predictor of paroxysmal AF during follow-up ( odds ratio 6.6 , 95 % confidence intervals 1.6 to 28.2 , P=0.01 ) . Conclusions — In patients with acute ischemic stroke , frequent APBs ( ≥70/24 hours ) are a marker for individuals who are at greater risk to develop or have paroxysmal AF . For such patients , we propose a diagnostic workup with repeated prolonged ECG monitoring to diagnose paroxysmal AF Background —Current methods for detecting atrial fibrillation ( AF ) have limited diagnostic yield . Continuous monitoring with automatic arrhythmia detection and classification may improve detection of symptomatic and asymptomatic AF and subsequent patient treatment . The study purpose was to quantify the performance of the first implantable leadless cardiac monitor ( ICM ) with dedicated AF detection capabilities . Methods and Results — Patients ( n=247 ) with an implanted ICM ( Reveal XT , Medtronic Inc , Minneapolis , Minn ) who were likely to present with paroxysmal AF were selected . A special Holter device stored 46 hours of subcutaneously recorded ECG , ICM markers , and 2 surface ECG leads . The ICM  automatic arrhythmia classification was compared with the core laboratory classification of the surface ECG . Of the 206 analyzable Holter recordings collected , 76 ( 37 % ) contained at least 1 episode of core laboratory classified AF . The sensitivity , specificity , positive predictive value , and negative predictive value for identifying patients with any AF were 96.1 % , 85.4 % , 79.3 % , and 97.4 % , respectively . The AF burden measured with the ICM was very well correlated with the reference value derived from the Holter ( Pearson coefficient=0.97 ) . The overall accuracy of the ICM for detecting AF was 98.5 % . Conclusions —In this ICM validation study , the dedicated AF detection algorithm reliably detected the presence or absence of AF and the AF burden was accurately quantified . The ICM is a promising new diagnostic and monitoring tool for the clinician to treat AF patients independently of symptoms . Long-term studies are needed to evaluate the clinical benefits of the technology . Clinical Trial Registration — clinical trials.gov Identifier NCT00680927 INTRODUCTION Long-term cardiac monitoring with implantable loop recorders ( ILRs ) has revealed occult paroxysmal atrial fibrillation and flutter ( PAF ) in a substantial minority of cryptogenic ischemic stroke ( CIS ) patients . Herein , we aim to define the prevalence , clinical relevance , and risk factors for PAF detection following early poststroke ILR implantation . MATERIAL S AND METHODS A retrospective study of CIS patients ( n = 100 , mean age 65.8 years ; 52.5 % female ) who underwent ILR insertion during , or soon after , index stroke admission . Patients were prospect ively followed by the study cardiac electrophysiologist who confirmed the PAF diagnosis . Univariate and multivariate analyses compared clinical , laboratory , cardiac , and imaging variables between PAF patients and non-PAF patients . RESULTS PAF was detected in 31 of 100 ( 31 % ) CIS patients , and anticoagulation was initiated in almost all ( 30 of 31 , 96.8 % ) . Factors associated with PAF detection include older age ( mean [ year ] 72.9 versus 62.9 ; P = .003 ) , white race ( odds ratio [ OR ] , 4.5 ; confidence interval [ CI ] , 1.8 - 10.8 ; P = .001 ) , prolonged PR interval ( PR > 175 ms ; OR , 3.3 ; CI , 1.2 - 9.4 ; P = .022 ) , larger left atrial ( LA ) diameter ( mean [ cm ] 3.7 versus 3.5 ; P = .044 ) and LA volume index ( mean [ cc/m2 ] ; 30.6 versus 24.2 ; P = .014 ) , and lower hemoglobin (Hb)A1c ( mean [ % ] 6.0 versus 6.4 ; P = .036 ) . Controlling for age , obesity ( body mass index > 30 kg/m2 ; OR , 1.2 ; CI , 1.1 - 1.4 ; P = .033 ) was independently associated with PAF detection . DISCUSSION PAF was detected with high prevalence following early postcryptogenic stroke ILR implantation and result ed in significant management changes . Older age , increased PR interval , LA enlargement , and lower HbA1c are significantly associated with PAF detection . Controlling for age , obesity is an independent risk factor . A larger prospect i ve study is warranted to confirm these findings Atrial fibrillation ( AF ) is intermittent in 30 % of patients with cardioembolic stroke and , therefore , might not be seen in a single st and ard ECG recording . The aim of this study was to evaluate if prolonged ECG monitoring ( 96 h ) finds episodes of intermittent AF beyond the 24 h ECG monitoring in patients with cryptogenic stroke or transient ischemic attack ( TIA ) . We prospect ively evaluated consecutive patients affected by cryptogenic stroke or TIA who had sinus rhythm on a 12-lead ECG on admission , and during ECG monitoring performed in the acute phase ( for at least 24 h ) . Patients had continuous 96 h Holter ECG monitoring within 30 days from stroke onset . 114 patients were included in the study ( mean age 63.1 ± 15.1 , 59 males ) .  AF was found in 29 patients ( 24.3 % ) . In 20 patients , AF was found in the first 24 h of recording , and in nine patients after 24 h. In addition , several other dysrhythmias such as supraventricular ectopic activity ( 33 ) , ventricular tachycardia ( 10 ) , sinus pause ( 4 ) and sinus-atrial block ( 1 ) were found . In patients with cryptogenic stroke or TIA , 96 h ECG monitoring detected a high rate of AF . One-third of AF was seen beyond 24 h of ECG monitoring This pilot study in a prospect i ve cohort of 20 cryptogenic stroke patients showed that a significant proportion has paroxysmal atrial fibrillation undetected by 24-h Holter monitoring . However , longer monitoring with 28-day Holter was poorly tolerated and still insufficiently sensitive for paroxysmal atrial fibrillation detection . Further studies are urgently needed to eluci date the optimal timing , method and duration of cardiac rhythm monitoring following ischaemic stroke Asymptomatic atrial fibrillation ( AF ) is a common cause of strokes . Physician screening for AF has been recommended . Home screening for AF may increase the likelihood of detecting asymptomatic AF in patients at risk for stroke because of AF . The aim of this study was to assess the feasibility and accuracy of screening for AF when taking home blood pressure ( BP ) measurements using an automatic AF-detecting BP monitor .  Subjects aged > 64 years or those with hypertension , diabetes , congestive heart failure , or previous stroke were enrolled by their primary physicians and given the AF-BP monitor and an electrocardiographic event monitor to use at home for 30 days . The AF-BP monitor reading was compared with the electrocardiographic reading to calculate the sensitivity and specificity of the device for detecting AF . A total of 160 subjects were enrolled , with 10 withdrawing , 1 excluded , and 10 with no AF-BP monitor logs or electrocardiographic recordings . Of the 139 subjects included , 14 had known AF . There was a total of 3,316 days with AF-BP monitor readings and electrocardiographic readings . On the basis of the initial daily AF-BP monitor readings , the AF-BP monitor demonstrated sensitivity of 99.2 % and specificity of 92.9 % for detecting AF . Two subjects with no histories of AF had AF-BP monitor readings of AF that were confirmed by the electrocardiographic monitor . One of these subjects was started on warfarin . In conclusion , home screening for asymptomatic AF while taking BP measurements can be performed accurately . This can be used to detect new AF , allowing treatment with anticoagulation to reduce the future risk for stroke Background and Purpose — Atrial fibrillation ( AF ) elevates risk of recurrent stroke but is incompletely identified by st and ard investigation after stroke , though detection rates correlate with monitoring duration . We hypothesized that 7 days of noninvasive cardiac-event monitoring early after stroke would accelerate detection of AF and thus uptake of effective therapy . Methods — We performed a pragmatic r and omized trial with objective outcome assessment among patients presenting in sinus rhythm with no AF history , within 7 days of ischemic stroke symptom onset . Patients were r and omized to st and ard practice investigations ( SP ) to detect AF , or SP plus additional monitoring ( SP-AM ) . AM comprised 7 days of noninvasive cardiac-event monitoring reported by an accredited cardiac electrocardiology laboratory . Primary outcome was detection of AF at 14 days . Results — One-hundred patients were enrolled from 2 centers . Within 14 days of stroke , sustained paroxysms of AF were detected in 18 % of patients undergoing SP-AM versus 2 % undergoing SP ( P<0.05 ) . Paroxysms of any- duration were detected in 44 % of patients undergoing SP-AM versus 4 % undergoing SP ( P<0.001 ) . These differences persisted at 90 days . Anticoagulant therapy was commenced within 14 days in 16 % of SP-AM patients versus none r and omized to SP ( P<0.01 ) . This difference persisted to 90 days ( 22 % versus 6 % ; P<0.05 ) . Conclusions — Routine noninvasive cardiac-event monitoring after acute stroke enhances detection of paroxysmal AF and early anticoagulation . Extended monitoring should be offered to all eligible patients soon after acute stroke . Guidelines on investigation for AF in stroke patients could be strengthened . Clinical Trial Registration — URL : http://www.controlled-trials.com/is rct n/. Unique identifier : IS RCT N97412358 BACKGROUND The use of insertable cardiac monitors ( ICM ) has increased the rate of detection of atrial fibrillation ( AF ) among cryptogenic stroke ( CS ) patients . We describe a single-center experience for AF detection among CS patients receiving ICMs upon discharge after the index stroke event and attempt to identify predictors for AF detection . METHODS From April 2014 to October 2017 , patients receiving ICMs for CS who underwent > 60 days of monitoring were review ed . Chronic underlying medical illnesses , presence of left atrial enlargement ( LAE ) on echocardiography , and PR interval on admission electrocardiogram were assessed as predictors of AF detection . RESULTS A total of 234 patients ( median age 72 [ 61 , 78 ] years , 45 % women ) met inclusion criteria and were followed for a median of 536 [ 282 , 848 ] days . Among studied patients , 68 patients ( 29 % ) were found to have AF at a median of 94.5 [ 16 , 239 ] days from ICM placement . CS patients with AF were significantly older ( p < 0.001 ) , and there was a significantly higher proportion of women ( p = 0.003 ) when compared to CS patients without AF . Neither presence of LAE nor prolonged PR interval was predictive of AF detection . CONCLUSION Almost one-third of CS patients monitored with an ICM were found to have previously undiagnosed AF . CS patients found to have AF were older and more commonly women . Prospect i ve studies are needed to better identify predictors for early AF among the broader population of all CS patients BACKGROUND AND PURPOSE A significant proportion of cryptogenic ischaemic strokes are due to paroxysmal atrial fibrillation ( AF ) . As paroxysmal AF appears to inexorably progress to persistent or permanent AF , this study with long-term follow-up was design ed to establish the profile of patients who developed AF after hospital discharge . METHODS All patients with cryptogenic ischaemic stroke over a 1-year period were included ( n = 164 ) . Patients were prospect ively followed up at the outpatient clinic . Information on long-term outcome included the presence of newly diagnosed AF ( NDAF ) . A specific NDAF assessment was performed at least 2 years after the index stroke using a structured telephone interview .  Baseline clinical , laboratory , and echocardiographic data of these patients were retrospectively recorded . Independent predictive factors were then used to produce a predictive grading score for NDAF , derived by logistic regression analysis . RESULTS With a median follow-up of 854 days , 22 cases of NDAF ( 13 % ) were observed . On multivariate analysis , factors associated with NDAF were age ≥72 years ( two points ) , history of coronary artery disease ( one point ) or stroke ( one point ) , and left atrial area ≥16 cm(2 ) ( two points ) ( total score ranging from 0 to 6 ) . Patients with a score ≤1 point did not have NDAF during follow-up . CONCLUSIONS In cryptogenic ischaemic stroke , the NDAF score can be used to target patients at high risk of developing AF after hospital discharge , as a score of 0 - 1 was highly predictive of the absence of NDAF during follow-up . These results need to be confirmed in prospect i ve studies Background and Purpose — A new clinical construct termed embolic stroke of undetermined source ( ESUS ) was recently introduced , but no such population has been described yet . Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospect i ve ischemic stroke registry using the proposed diagnostic criteria . Methods — The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients . ESUS was defined as a radiologically confirmed nonlacunar brain infa rct in the absence of ( a ) extracranial or intracranial atherosclerosis causing ≥50 % luminal stenosis in arteries supplying the ischemic area , ( b ) major-risk cardioembolic source , and ( c ) any other specific cause of stroke . Results — Among 2735 patients admitted between 1992 and 2011 , 275 ( 10.0 % ) were classified as ESUS . In the majority of ESUS ( 74.2 % ) , symptoms were maximal at onset . ESUS were of moderate severity ( median National Institute Health Stroke Scale score , 5 ) . The most prevalent risk factor was arterial hypertension ( 64.7 % ) , and 50.9 % of patients were dyslipidemic . Among potential causes of the ESUS , covert atrial fibrillation ( AF ) was the most prevalent : in 30 ( 10.9 % ) patients , AF was diagnosed during hospitalization for stroke recurrence , whereas in 50 ( 18.2 % ) patients AF was detected after repeated ECG monitoring during follow-up . Also , covert AF was strongly suggested in 38 patients ( 13.8 % ) but never recorded . Conclusions — About 10 % of patients with first-ever ischemic stroke met criteria for ESUS ; covert paroxysmal AF seems to be a frequent cause of ESUS Background Device‐detected sub clinical atrial fibrillation ( AF ) refers to infrequent , short‐lasting , asymptomatic AF that is detected only with long‐term continuous monitoring . Sub clinical AF is common and associated with an increased risk of stroke ; however , the risk of stroke with sub clinical AF is lower than for clinical AF , and very few patients with sub clinical AF alone have been included in large AF anticoagulation trials . The net benefit of anticoagulation in patients with sub clinical AF is unknown . Design ARTESiA is a prospect i ve , multicenter , double‐blind , r and omized controlled trial , recruiting patients with sub clinical AF detected by an implanted pacemaker , defibrillator , or cardiac monitor , and who have additional risk factors for stroke . Patients with clinical AF documented by surface electrocardiogram will be excluded from the study . Participants will be r and omized to receive either apixaban ( according to st and ard AF dosing ) or aspirin 81 mg daily . The primary outcome is the composite of stroke , transient ischemic attack with diffusion‐weighted magnetic resonance imaging evidence of cerebral infa rct ion , and systemic embolism . Approximately 4,000 patients will be enrolled from around 230 clinical sites , with an anticipated mean follow‐up of 36 months until 248 adjudicated primary outcome events have occurred . Summary ARTESiA will determine whether oral anticoagulation therapy with apixaban compared with aspirin reduces the risk of stroke or systemic embolism in patients with sub clinical AF and additional risk factors
When each device is compared incrementally , BioMonitor 2-AF dominates Reveal LINQ and Confirm RX .
BACKGROUND Cryptogenic stroke is a stroke for which no cause is identified after st and ard diagnostic tests .
Long-term implantable cardiac monitors may be better at diagnosing atrial fibrillation and provide an opportunity to reduce the risk of stroke recurrence with anticoagulants .
OBJECTIVES The objectives were to assess the diagnostic test accuracy , clinical effectiveness and cost-effectiveness of three implantable monitors [ BioMonitor 2-AF ™ ( Biotronik SE & Co. KG , Berlin , Germany ) , Confirm Rx ™ ( Abbott Laboratories , Lake Bluff , IL , USA ) and Reveal LINQ ™ ( Medtronic plc , Minneapolis , MN , USA ) ] in patients who have had a cryptogenic stroke and for whom no atrial fibrillation is detected after 24 hours of external electrocardiographic monitoring .