Potential Biological Markers of Atrial Fibrillation: A Chance to Prevent Cryptogenic Stroke

Stroke affects millions of people all over the world, causing death and disability. The most frequent type of this disease is ischemic stroke, which can be caused by different factors. In approximately 25 percent of cases, no obvious cause can be found. Recent observations have shown that paroxysmal atrial fibrillation could be responsible for a significant number of cryptogenic stroke events. Short- or long-lasting ECG monitoring could help with the diagnosis of transient arrhythmias. Unfortunately, these techniques either are expensive or require good patient compliance. An alternative option is the identification of biological markers that are specific for atrial fibrillation and can be used to predict arrhythmia. In this review, we give a summary of the recent advances in the research of arrhythmia markers. Based on their structure and function, we differentiated four groups of biomarkers: markers of inflammation, markers of fibrosis, markers with hormonal activity, and other markers. In spite of intensive researches, the optimal biological marker is still not available, but there are some promising markers, like NT-proBNP/BNP.

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P3859Long-term noninvasive ecg monitoring in atrial fibrillation detection in patients after cryptogenic stroke

European Heart Journal ◽

10.1093/eurheartj/ehy563.p3859 ◽

2018 ◽

Vol 39 (suppl_1) ◽

Author(s):

V Bulkova ◽

P Jansky ◽

D Kovarikova ◽

H Alfredova ◽

V Dlugosova ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cryptogenic Stroke ◽

Ecg Monitoring ◽

Atrial Fibrillation Detection

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Abstract 14972: Sub-clinical Atrial Fibrillation in Elderly Primary Care Patients Without Clinical Atrial Fibrillation

Circulation ◽

10.1161/circ.132.suppl_3.14972 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Jeff S Healey ◽

Stuart J Connolly ◽

Veena Manja ◽

Yan Liu ◽

Kim D Simek ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Primary Care ◽

Coronary Disease ◽

Cryptogenic Stroke ◽

Left Ventricular ◽

Ecg Monitoring ◽

High Background ◽

Non Invasive ◽

History Of

Introduction: Sub-clinical AF has been reported in 10% of pacemaker patients (≥ 6 minutes, with 3 months of monitoring) and 16% of patients following cryptogenic stroke (≥ 30 seconds, with 1 month of monitoring). It is unknown how common sub-clinical AF is among other patient groups, including the elderly. These data are needed to give context to the detection of sub-clinical AF in clinical practice. Methods: We prospectively investigated the prevalence of sub-clinical AF among individuals ≥ 80 years, without known AF or symptoms of arrhythmia, attending primary care clinics. Subjects had a history of hypertension and at least one of the following: diabetes, BMI ≥ 30, sleep apnea, smoking, coronary disease, heart failure or left ventricular hypertrophy. Patients were recruited from 7 Ontario family practice clinics (n=119) and one general medicine clinic (n=10). Patients underwent 30 days of continuous, non-invasive ambulatory ECG monitoring using a device with automatic AF detection (Vitaphone 3100). The primary outcome was a composite of atrial flutter (AFL) or AF ≥ 6 minutes in duration. Those without AF were invited to complete an additional 30 days of monitoring. Results: Of 129 patients screened and consented, 100 patients initiated monitoring for an average monitoring duration of 36± 21 days. The mean (SD) age was 84 ± 3 years and systolic blood pressure was 138 ± 17 mmHg; 50% had coronary disease, 28% had diabetes and 6% had heart failure. Only 4% had a history of prior stroke. Thirty days of monitoring was completed by 57% of patients and 31% completed an additional 30 days. AFL or AF ≥ 30 seconds duration was documented in 19/100 patients; ≥ 6 minutes in 15; ≥ 30 minutes in 12; ≥ 6 hours in 8 and ≥ 24 hours in 2. Shorter episodes of atrial tachycardia lasting less than 30 seconds were observed in 47 patients. Conclusions: In this prospective, outpatient study, using non-invasive ECG monitoring, we found AFL or AF ≥ 6 minutes in 15% of elderly individuals with stroke risk factors. This high background prevalence of AFL/AF among elderly patients suggests a possible role for AF screening in this population; but also should be taken into consideration when interpreting the prevalence of AFL/AF in other populations.

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Cost-Effectiveness of Extended Electrocardiogram Monitoring for Atrial Fibrillation After Stroke

Stroke ◽

10.1161/strokeaha.120.029340 ◽

2020 ◽

Vol 51 (7) ◽

pp. 2244-2248 ◽

Cited By ~ 3

Author(s):

Derek S. Chew ◽

Elissa Rennert-May ◽

Eldon Spackman ◽

Daniel B. Mark ◽

Derek V. Exner

Keyword(s):

Atrial Fibrillation ◽

Cost Effectiveness ◽

Standard Care ◽

Cryptogenic Stroke ◽

Cost Utility ◽

Economic Evaluations ◽

Ecg Monitoring ◽

The Cost ◽

Monitoring Devices ◽

Rhythm Monitoring

Background and Purpose: Management of cryptogenic stroke involves the identification of modifiable risk factors, such as atrial fibrillation (AF). Extended rhythm monitoring increases AF detection rates but at an increased device cost compared with conventional Holter monitoring. The objective of the study was to identify and synthesize the existing literature on the cost-effectiveness of prolonged rhythm monitoring devices for AF detection in cryptogenic stroke. Methods: We conducted a systematic review of available economic evaluations of prolonged ECG monitoring for AF detection following cryptogenic stroke compared with standard care. Results: Of the 530 unique citations, 8 studies assessed the cost-utility of prolonged ECG monitoring compared with standard care following cryptogenic stroke. The prolonged ECG monitoring strategies included 7-day ambulatory monitoring, 30-day external loop recorders or intermittent ECG monitoring, and implantable loop recorders. The majority of cost-utility analyses reported incremental cost-effectiveness ratios below $50 000 per QALY gained; and two studies reported a cost-savings. Conclusions: There is limited economic literature on the cost-effectiveness of extended ECG monitoring devices for detection of atrial fibrillation in cryptogenic stroke. In patients with cryptogenic stroke, extended ECG monitoring for AF detection may be economically attractive when traditional willingness-to-pay thresholds are adopted. However, there was substantial variation in the reported ICERs. The direct comparison of cost-effectiveness across technologies is limited by heterogeneity in modeling assumptions.

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COST-EFFECTIVENESS OF EXTENDED ECG MONITORING FOR DETECTION OF OCCULT ATRIAL FIBRILLATION IN PATIENTS WITH CRYPTOGENIC STROKE

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(20)30942-6 ◽

2020 ◽

Vol 75 (11) ◽

pp. 315 ◽

Cited By ~ 1

Author(s):

Derek Chew ◽

Elissa Rennert-May ◽

F Russell Quinn ◽

Eldon Spackman ◽

Braden Manns ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cost Effectiveness ◽

Cryptogenic Stroke ◽

Ecg Monitoring

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Sensitive Detection of Atrial Fibrillation in Acute Stroke Patients by Short-Term Bedside Electrocardiography Monitoring Software Analysis

Cerebrovascular Diseases ◽

10.1159/000485193 ◽

2018 ◽

Vol 45 (1-2) ◽

pp. 54-60

Author(s):

Linda Sarah Ross ◽

Markus Bettin ◽

Simon Kochhäuser ◽

Martin Ritter ◽

Jens Minnerup ◽

...

Keyword(s):

Atrial Fibrillation ◽

Acute Stroke ◽

Predictive Value ◽

Cryptogenic Stroke ◽

Ecg Monitoring ◽

Stroke Patients ◽

Software Analysis ◽

Diagnostic Work ◽

Work Up ◽

Diagnostic Work Up

Background: Atrial fibrillation (AF) is an important cause of stroke. Continuous electrocardiography (ECG) monitoring with software-based analysis algorithms has been suggested to enhance the AF detection rate. We investigated the ability of stroke risk analysis (SRA) in the detection of AF in acute stroke patients. Methods: Consecutive stroke patients numbering 1,153 were screened. Patients with cardioembolic stroke related to AF (n = 296, paroxysmal n = 63, persistent n = 233) and patients with cryptogenic stroke (n = 309) after standard diagnostic work-up (bedside ECG monitoring, ultrasound, transesophageal echocardiography, 24 h Holter ECG) received SRA during their stay at the Stroke Unit. Determination of AF risk by SRA in the patients with AF and in the patient group with cryptogenic stroke was assessed and compared. Results: Median SRA monitoring analysis time was 16 h (range 2–206 h, interquartile range 10–36). In AF patients, SRA also detected a possible or definitive AF in 98%. The overall sensitivity of SRA to detect possible or definitive AF in patients with proven AF by standard diagnostic work up and cryptogenic stroke was 98%, specificity 27%, positive predictive value 56%, and the negative predictive value (NPV) was 92%. Area under ROC curve was 0.622. Conclusion: SRA was found to be highly sensitive to detect possible or definitive AF in clinical routine within a short monitoring time. However, low specificity and poor accuracy do not allow diagnosing AF by SRA alone, but with the high NPV compared to current diagnostic standard, it is a valid diagnostic tool to rule out AF. Thereby, SRA is a contribution to clarify stroke etiology.

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What after cryptogenic stroke – NOAC for everyone or ICM for some?

In a good rythm ◽

10.5604/01.3001.0013.0505 ◽

2019 ◽

Vol 4 (49) ◽

pp. 25-27

Author(s):

Michał Karliński

Keyword(s):

Atrial Fibrillation ◽

Therapeutic Strategy ◽

Randomized Trials ◽

Significant Proportion ◽

Cryptogenic Stroke ◽

Ecg Monitoring ◽

Optimal Model ◽

Common Cause ◽

Current Thinking ◽

Economic Considerations

Atrial fibrillation (AF) is by far the most common cause of stroke with cardiovascular etiology. It is commonly believed that a significant proportion of ischemic strokes of an unknown cause are in fact also embolic (ESUS). This leads to consideration that patients after ESUS are potential candidates for chronic NOAC treatment. However, the therapeutic strategy constructed in such a simple way has been verified negatively in recent randomized trials. It is uncertain whether the pharmaceutical industry will be interested in continuing research in a subpopulation of ESUS patients with a particularly high risk of AF. However, it is now possible to strive for extended ECG monitoring aimed at detecting paroxysmal AF that is not detected by standard post-stroke diagnostic workup. In both scenarios, pragmatic and economic considerations make it necessary to develop a method of proper patients selection. The discussed analysis of data collected during the CRYSTAL-AF study, discussed by me, allows to better understand the imperfection of the current thinking about ESUS and provides information that may development the creation of an optimal model for dealing with this group of patients.

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Applicability of a Novel Wearable Wireless Electrocardiogram Monitoring Device (Spyder) for Arrhythmia Detection in Patients with Suspected Cardiac Arrhythmias

Cardiology Research and Practice ◽

10.1155/2021/8496351 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Do Van Chien ◽

Nguyen Thanh Binh ◽

Nguyen Dung ◽

Pham Truong Son

Keyword(s):

Atrial Fibrillation ◽

Supraventricular Tachycardia ◽

Cardiac Arrhythmias ◽

Cryptogenic Stroke ◽

Premature Ventricular Contraction ◽

Monitoring Device ◽

Ecg Monitoring ◽

Monitoring Methods ◽

New Device ◽

Recurrent Atrial Fibrillation

Introduction. In clinical practice, many cardiovascular symptoms can be caused by arrhythmias that are not detected by electrocardiography (ECG) or 24–48 h Holter ECG monitoring. Aims. To describe the efficacy and applicability of a new device (Spyder) in detecting cardiac arrhythmias with midterm ECG monitoring. Methods. A descriptive, prospective study was performed on 26 consecutive patients who underwent midterm ECG monitoring with the novel ECG patch device (Spyder). The study was conducted over a 6-month period from August 2020 to February 2021. Results. Twenty-six patients (mean age, 57.8 ± 12.5 years; men, 77%) wearing a Spyder wireless ECG-monitoring device were recruited. The mean wearing time was 84 hours. The main indications for using the device were detection of recurrent atrial fibrillation after radiofrequency ablation (30.7%) and screening for atrial fibrillation after cryptogenic stroke (23.1%). All ECG monitor recordings obtained during the study period were of good quality. The device detected 12 episodes of atrial fibrillation in eight patients, one episode of ventricular tachycardia, one supraventricular tachycardia event, one case of paroxysmal third-degree atrioventricular block, and five cases of frequent premature ventricular contraction. The time to detection of the first episodes of atrial fibrillation and ventricular and supraventricular tachycardia was 28.8 and 47 hours, respectively. Conclusions. The new wearable wireless ECG-monitoring device (Spyder) is a feasible and effective method for the detection of cardiac arrhythmias.

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606 Predictive value of left atrial and left ventricular strain for the detection of atrial fibrillation in patients with cryptogenic stroke

European Heart Journal Supplements ◽

10.1093/eurheartj/suab127.003 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Gabriella Bufano ◽

Francesco Radico ◽

Carolina Maria D’Angelo ◽

Francesca Pierfelice ◽

Maria Vittoria De Angelis ◽

...

Keyword(s):

Atrial Fibrillation ◽

Predictive Value ◽

Left Atrial ◽

Longitudinal Strain ◽

Cryptogenic Stroke ◽

Left Ventricular ◽

Volume Index ◽

Lv Function ◽

Ecg Monitoring ◽

Echocardiographic Parameters

Abstract Aims Cryptogenic stroke (CS) is associated with high rate of recurrences and adverse outcomes at long-term follow-up, especially in light of its unknown etiology that often leads to ineffective secondary prevention. In such scenario, asymptomatic misdiagnosed atrial fibrillation (AF) episodes could play an important pathophysiological role. Some studies have pointed left atrial (LA) and left ventricular (LV) systolic and diastolic dysfunction as surrogate markers of AF. The aim of this study was to evaluate the relationship between echocardiographic parameters of LA and LV function, and the occurrence of AF revealed by continuous electrocardiogram (ECG) monitoring in a cohort of CS patients. Methods and results This is a single-centre prospective cohort study. Seventy-two CS patients with continuous ECG monitoring with insertable cardiac monitor (ICM) underwent transthoracic echocardiography (TTE). TTE was focused on LA and LV function, including both standard and longitudinal strain-derived parameters. All detected AF episodes lasting more than 2 min were considered. Patients with and without AF were homogeneous in all baseline characteristics, except for CHA2DS2-VASc score, which was significantly higher in AF group, and prevalence of hypercholesterolaemia, that was significantly higher in no-AF group. ICM revealed AF in 23 patients (32%), on average 196 days after ICM implantation. Among echocardiographic parameters, LV ejection fraction (LVEF, P = 0.007), LA end systolic area (LAES area, P = 0.006), LA volume index (LAVI, P = 0.008), total LA emptying fraction (LATEF, P = 0.013), E velocity (P = 0.042), pulmonary veins AR duration (P = 0.01), septal and median TDI E/e′ (respectively, P = 0.045 and P = 0.039), peak atrial longitudinal strain (PALS) in 4-chamber and in 2-chamber view (respectively, P < 0.001 and P = 0.011), peak atrial contraction strain (PACS, P < 0.001), LA conduit strain (P = 0.005), and LV longitudinal strain (LVLS, P = 0.001) were significantly associated to the occurrence of AF, suggesting worst atrial function in AF group. Furthermore, multivariable regression analysis revealed that PACS and LV strain were the only echocardiographic parameters independently associated with AF [confidence interval (CI) 95%: 0.48–0.90, P = 0.005 and CI 95%: 0.46–0.95, P = 0.041 respectively]. Conclusions In a cohort of CS patients, continuous ECG monitoring with ICM revealed subclinical AF episodes in about one-third of patients. In such population, LA and LV strain analysis add predictive value for occurrence of AF over clinical and morpho-functional echocardiographic parameters. Impaired booster pump strain and LVLS strain are strong and independent predictors of AF.

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Predictors of atrial fibrillation in patients with cryptogenic stroke and fifteen-days electrocardiographic monitoring. Preliminary results of the DECRYPTORING study

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.121 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

A Vera Sainz ◽

A Cecconi ◽

P Martinez Vives ◽

A Ximenez Carrillo ◽

C Aguirre ◽

...

Keyword(s):

Atrial Fibrillation ◽

Left Atrial ◽

Retrospective Studies ◽

Cryptogenic Stroke ◽

P Value ◽

Ecg Monitoring ◽

Funding Sources ◽

Electrocardiographic Monitoring ◽

3D Volume ◽

Funding Acknowledgements

Abstract Funding Acknowledgements Type of funding sources: None. onbehalf DECRYPTORING study Introduction Cryptogenic stroke (CS) represents up to 30% of all stroke types. In one third of CS, atrial fibrillation (AF) is identified as the underlying cause. Predictors of AF in the setting of CS have been described, however these findings were based on retrospective studies and with maximum ECG monitoring of 72 hours. To overcome these limitations, we designed the prospective Decryptoring study whose objective is to create a comprehensive predictive model for AF in patients with CS. Methods From April 2019, 41 consecutive patients with a CS and age > 60 years were included. On admission, a transthoracic echocardiogram with 3D volume and left atrial (LA) strain was performed. All patients were monitored with a 15-day ECG-Holter after discharge. Patients were classified according to AF detection. Results AF was detected in 9 patients (22%). Patients with AF were older (75.9 ± 8 vs. 81.9 ± 4.3 years, p = 0.041). There was no difference in T-troponin levels. NTproBNP was higher in the group with AF (350 ± 586 pg / ml vs. 1084 ± 1416 pg / ml, p = 0.018). Regarding LA strain, patients with AF presented reservoir LA strain (25.5 ± 8.2% vs 17.4 ± 4.3%; p = 0.006) and conduct LA strain (12 ± 5.2% vs 7.2 ± 1.5%; p = 0.01) lower than patients without AF. There were no differences in contraction LA strain or other echocardiographic variables. The risk of developing AF was higher in patients with NTproBNP> 165 pg / ml (OR 11.3 [95% CI 1.2-102.9] p = 0.031), LA reservoir strain <19.1% (OR 7.7 [IC 95 % 1.5-40.0] p = 0.016) and LA conduct strain <9.1% (OR 7.8 [95% CI 1.3-45.0] p = 0.022) (Table). Conclusions This prospective study, demonstrates that high NTproBNP, low reservoir LA strain and low conduct LA strain are associated with underlying AF in patients with cryptogenic stroke. No AF (n = 32) AF (n = 9) P value Age (years) 75.9 ± 8 81.9 ± 4.3 p = 0.041 NTPROBNP (pg/ml) 350 ± 586 1084 ± 1416 P = 0.018 LA indexed diastolic volume (ml/m2) 30 ± 11.8 33.8 ± 9.8 P = 0.35 LA EF (%) 45 ± 16.7 45 ± 12.8 P = 1 Reservoir LA strain (%) 25.5± 8.2 17.4± 4.3 P = 0.006 Conduct LA strain (%) 12 ± 5.2 7.2 ± 1.5 P = 0.01 Contraction LA strain (%) 13.5 ±5.3 10.2± 3.9 P = 0.10 NTPROBNP > 165 pg/ml 12 (41%) 8 (89%) OR 11.3 [IC 95% 1.2-102.9]; p = 0.031 Reservoir LA strain <19.1% 6 (20%) 6 (67%) OR 7.7 [IC 95% 1.5-40.0]; p = 0.016 Conduct LA strain <9.1% 9 (31%) 7 (78%) OR 7.8 [IC 95% 1.3-45.1]; p = 0.022

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Supraventricular Runs in 7-Day Holter Monitoring Are Related to Increased Incidence of Atrial Fibrillation in a 3-Year Follow-Up of Cryptogenic Stroke Patients Free from Arrhythmia in a 24 h-Holter

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8070081 ◽

2021 ◽

Vol 8 (7) ◽

pp. 81

Author(s):

Andrzej Kułach ◽

Milena Dewerenda ◽

Michał Majewski ◽

Anetta Lasek-Bal ◽

Zbigniew Gąsior

Keyword(s):

Atrial Fibrillation ◽

Cryptogenic Stroke ◽

Holter Monitoring ◽

Ecg Monitoring ◽

Stroke Patients ◽

Long Term Monitoring ◽

In Cis ◽

Term Monitoring

Introduction: Silent atrial fibrillation (AF) is a common cause of cryptogenic ischemic stroke (CIS). The 24-h-Holter is insufficient to reveal an occult arrhythmic cause of stroke and the strategy to select the patients for long-term monitoring is missing. Objectives: The aim of the study was to evaluate 7-day-Holter monitoring to identify cases with the arrhythmic cause of stroke in CIS patients in whom 24-h-Holter was free from arrhythmia, and to assess the relation between supraventricular (SV) runs in baseline Holter and the incidence of AF in a 3-year follow-up period. Methods: 78 patients (aged 60 ± 9 years, 45 males) with CIS and no arrhythmic findings in 24-h-Holter were enrolled. All patients had 7-day-Holter monitoring after stroke and were followed up for 36 months, and then 7-day Holter was repeated. We assessed SV runs (≥5 QRS) in the initial 7-day Holter and analyzed the relation of the findings with clinical characteristics of novel AF episodes revealed early after stroke and during a 3-year follow-up. Results: Baseline 7-day-Holter revealed SV runs in 36% of patients and AF in 9% of cases. During a 3-year follow-up, 8 additional cases were confirmed, both in standard care and in repeated Holter (a total of 19% of AF cases). There was no difference with regard to CHADS2VASc score (3.6 ± 1.1 vs. 3.4 ± 1.5; p = NS) and left atrium parameters between patients with SV runs and the non-arrhythmic group. Patients with SV runs had a higher incidence of AF both after stroke and in a 3-year follow-up (46% vs. 4%, RR 11.6, p < 0.001). In 8 cases, patent foramen ovale was detected during follow-up. Conclusions: A strategy of baseline 7-day-Holter monitoring after stroke allows for disclosing SV runs in every third case and AF in 9% of stroke survivors. Patients with SV runs have a higher incidence of AF (RR 11.6, p < 0.001) and should be considered for extended continuous ECG monitoring.

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