Paroxysmal Atrial FibrillationCRIPTO-FASTNCT06542770
Atrial Anomalies Predict Silent Atrial Fibrillation Detected by Implantable Cardiac Monitor in Cryptogenic Stroke
A study testing Early implant of cardiac monitor in people with Paroxysmal Atrial Fibrillation and Cardiac Rhythm Disorder, run by Parc de Salut Mar at 1 site in Spain.
Trial summary
Cryptogenic stroke (CS) causes about 30% of admissions to a stroke unit. Silent paroxysmal atrial fibrillation (PAF) is believed to be the underlying cause of a significant proportion of patients. Read more about this study
- Who is it for?
- Ages 50 to 89 years
- Conditions the study is for
- Paroxysmal Atrial Fibrillation, Cardiac Rhythm Disorder, Left Atrial Dilatation
- What is being tested?
- Early implant of cardiac monitor
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2021to Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute ischemic stroke or transient ischemic attack (TIA) from January 2022 to July 2023
- Age between 50 and 89 years;
- Undetermined origin at hospital admission according to the SSS-TOAST criteria (2):
- Absence of major structural heart disease by cardiac ultrasound (normal global and segmental left ventricle contraction, absence of valvular/rheumatic disease, absence of intracardiac shunts)
- Absence of AF during 48h ECG-monitoring
- Absence of major anomalies in the supra-aortic trunks ultrasound.
Who cannot join
- Patients with a history of hemorrhagic stroke;
- Presence with prior atrial fibrillation or atrial flutter;
- Permanent contraindication or indication for OAC for other reasons;
- Recent (<1 month) major surgery or cardiac events;
- Presence of severe cardiac abnormalities;
- Patients with life expectancy <1 year or severe stroke (modified Rankin Scale > 4).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Subtle Ultrasound Atrial Anomalies Predicts the Early Diagnosis of Silent Atrial Fibrillation Detected by Implantable Cardiac Monitor in Patients With Cryptogenic Stroke. A Randomized Trial
Cryptogenic stroke (CS) causes about 30% of admissions to a stroke unit. Silent paroxysmal atrial fibrillation (PAF) is believed to be the underlying cause of a significant proportion of patients. The use of implantable cardiac monitors (ICM) early after the CS has demonstrated benefits in the diagnostic yield, but the indication for ICM in the current guidelines remains unclear. Atrial contraction strain (ACS) evaluated by cardiac ultrasound could be of help to select the patients more prone to suffer from silent PAF.
The purpose of this investigation is to conduct a randomized prospective unicentric study to evaluate the usefulness of ICM for early detection of silent PAF episodes in patients with CS. Clinical and ultrasound predictors of PAF occurrence (ACS) will be studied in order to define patients needing a closer follow-up.
Read the detailed description
Introduction
Cryptogenic stroke (CS) is a stroke in which etiology cannot be determined after a comprehensive evaluation and it is the cause of about 30% of admissions to a stroke unit. In these cases single antiplatelet therapy is recommended as a long term treatment. However, silent paroxysmal atrial fibrillation (PAF) is believed to be the underlying cause of a significant proportion of episodes, and it´s recognition merits urgency since carries to oral anticoagulation (OAC) and antiplatelet therapy cessation. According to guidelines, in order to detect PAF we need to monitor the patient´s ECG for at least 48h, although the longer the monitoring is, the better the diagnostic yield.
Previous research showed controversial results regarding the use of implantable cardiac monitors (ICM) in such patients when the ICM had been implanted late after the CS. On the other hand, studies with an early implant demonstrated a clear benefit in the diagnostic yield. To date, the strategy to search actively for PAF in patients with CS is still not well established, and even when internal loop recorders (ILR) are our best option to recognize paroxysmal arrhythmic events, guidelines are not clear about the cases in which they might be indicated. Some markers, such as age, cardiovascular risk factors, blood biomarkers or cardiac ultrasound characteristics have been related to a higher silent PAF detection. Recent data points at the use of left atrium atrial strain (LAS) to select the patients more prone to suffer from silent PAF.
It remains to be defined the usefulness of ILR implanted early after the CS in order to diagnose the presence of silent PAF, and the roll or ACS in such patients in order to predict those being at higher risk.
Methods
This is a randomized prospective unicentric study to evaluate the usefulness of ICM for early detection of silent PAF episodes in patients with CS. During the first 48 hours from admission, patients were randomized to receive standard care (Control Group) or early ICM implantation (Study Group) before discharge. A special effort will be made to search for the clinical and ultrasound atrial predictors of PAF occurrence in order to better define what patients need a closer follow-up.
Ultrasound evaluation
The following ultrasound atrial features will be studied to separate patients into two categories:
- LA dilatation: indexed volumen >32 ml/m2
- PALS (Peak atrial longitudinal strain) <21%
- PACS ( Peak atrial contraction strain ) <13%
- Atrial ejection fraction <55%
Patients will be considered as having a "normal" LA if none of the above mentioned characteristics is accomplished, in opposition to patients who accomplish at least one characteristic described above, which will be considered as "atrial cardiomyopathy" patients.
Patients will be immediately treated with antiplatelet treatment. OAC will be started if PAF is detected during admission. Whilst in the Stroke Unit, all patients will be continuously ECG-monitored for at least 48 h and will undergo a cardiac transthoracic echocardiogram with complete evaluation of strain parameters.
Demographic factors, vascular risk factors and comorbidities will be collected. Work-up during admission will include, at least, a complete neurological examination, 12-lead ECG, brain computed tomography (CT), blood test and neurovascular imaging (magnetic resonance angiography, angioCT and/or two-dimensional ultrasound of supra-aortic trunks and intracranial territory).
The diagnosis of CS will be revisited in all patients 3 months after the index episode, and those found to have any potential cause other than PAF will be additionally excluded. The study follows national and international principles (Declaration of Helsinki), and it was approved by the local ethics committee. All patients are required to sign the specific informed consent.
Strategies for PAF detection Since the prevalence of AF is higher in patients having LA anomalies, we will divide the total group into two categories before randomization, depending on the presence or absence of: LA dilatation, and/or impaired ACS. Then we will randomize all patients to Control Group or Study Group.
Control group: after discharge from the Stroke Unit, patients in the control group will be studied with daily ECGs whilst admitted at the hospital. Outpatient serial ECGs will be performed at the time of each visit at the Neurology Clinic 3, 6 and 12 months after the stroke, and every 6 months thereafter. Additional ECGs will be performed if patients had symptoms potentially related to PAF. Furthermore all patients will undergo a 72h-Holter-monitoring scheduled 1 month after discharge.
Study group: patients in the active study group will undergo an ICM implant 3-4 days after the stroke and prior to discharge. All devices (Abbott Jot) will be implanted subcutaneously under local anaesthesia in the left chest region and programmed with an specific algorithm for AF detection set at 30 seconds for detection. All patients will be included in remote monitoring system (Merlin), which will be programmed to send alerts in case of registering episodes qualifying for AF detection, and a monthly routine registration. All ICM recordings will be reviewed by a specialized cardiologist. Patients will be seen at the arrhythmia and the neurology outpatient clinics at 3, 6 and 12 months after the stroke, and every 6 months thereafter.
End-points and follow-up Primary clinical outcome: detection of AF at follow-up, which is defined by the presence of a confirmatory 12-leads ECG, or a registration lasting more than 30 seconds in, either the 72h-Holter-Monitoring, or in the ICM recording. In case of AF detection OAC will be initiated immediately.
Secondary clinical outcomes: ultrasounds predictors for AF occurrence: LA indexed volumen, maximum systolic global longitudinal strain (PALs), atrial contraction strain (PACs), atrial ejection fraction.
We also will search for stroke recurrences, defined as new neurological events recorded after hospital discharge and validated by a vascular neurologist.
Statistical analysis Results are reported as mean (SD), median (p25-p75) or frequency (%). Comparisons between groups were performed with the Student t test or chi-squared analysis. The association between clinical variables and the study end-points was evaluated using survival analysis methodology (Cox regression models). The Kaplan-Meier method was used to estimate the cumulative probability of PAF detection and stroke recurrence in both groups, and comparisons were made by the log-rank test. Significance was set at P < 0.05.
- Conditions
- Paroxysmal Atrial Fibrillation, Cardiac Rhythm Disorder, Left Atrial Dilatation, Cryptogenic Stroke
- Being tested
- Early implant of cardiac monitor
- Keywords
- Atrial strain. Implantable cardiac monitor
- Medical subject headings
- Atrial Fibrillation, Arrhythmias, Cardiac, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early implant of cardiac monitorDevice
ICM implant 3-4 days after the stroke and prior to discharge. All devices (Abbott Confirm or Jot) were implanted subcutaneously under local anaesthesia in the left chest region and programmed with an specific algorithm for AF detection set at 30 seconds for detection. All patients were included in remote monitoring system (Merlin), which was programmed to send alerts in case of registering episodes qualifying for AF detection, and a monthly routine registration. All ICM recordings were reviewed by a specialized cardiologist.
| Study group | Role | What they receive |
|---|---|---|
| Atrial cardiomyopathy by echocardiogram intervention | Experimental | Presence of Atrial cardiomyopathy is defined by echocardiogram if ANY of the following is present:
1. LA dilatation: indexed volumen >32 ml/m2
2. PALS (Peak atrial longitudinal strain) <21%
3. PACS ( Peak atrial contraction strain ) <13%
4. Atrial ejection fraction <55% Receives: Device: Early implant of cardiac monitor |
| Atrial cardiomyopathy by echocardiogram standard practice | No intervention | Presence of Atrial cardiomyopathy is defined by echocardiogram if ANY of the following is present: 1. LA dilatation: indexed volumen >32 ml/m2 2. PALS (Peak atrial longitudinal strain) <21% 3. PACS ( Peak atrial contraction strain ) <13% 4. Atrial ejection fraction <55% |
| Non atrial cardiomyopathy by echocardiogram intervention | Experimental | Absence of atrial cardiomyopathy is defined by echocardiogram if none of the characteristics bellow were accomplished.
1. LA dilatation: indexed volumen >32 ml/m2
2. PALS (Peak atrial longitudinal strain) <21%
3. PACS ( Peak atrial contraction strain ) <13%
4. Atrial ejection fraction <55% Receives: Device: Early implant of cardiac monitor |
| Non atrial cardiomyopathy by echocardiogram standard practice | No intervention | Absence of atrial cardiomyopathy defined by echocardiogram if none of the characteristics bellow were accomplished. 1. LA dilatation: indexed volumen >32 ml/m2 2. PALS (Peak atrial longitudinal strain) <21% 3. PACS ( Peak atrial contraction strain ) <13% 4. Atrial ejection fraction <55% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection atrial fibrilation at follow-up
defined by the presence of a confirmatory 12-leads ECG, or a registration lasting more than 30 seconds in, either the 72h-Holter-Monitoring, or in the ICM recording. In case of AF detection OAC was initiated immediately.
Measured: Up to 2 years follow-up (ICM and standard care practice)
Secondary outcomes (5)
LA indexed volume
LA indexed volume in ml/m2
Measured: Before Day 3 since the Criptogenic Stroke
Maximum Systolic Global Longitudinal Strain (PALs)
Maximum Systolic Global Longitudinal Strain (PALs) in %
Measured: Before Day 3 since the Criptogenic Stroke
Atrial Contraction Strain (PACs)
atrial contraction strain (PACs) in %
Measured: Before Day 3 since the Criptogenic Stroke
Atrial Ejection Fraction
Atrial ejection fraction in %
Measured: Before Day 3 since the Criptogenic Stroke
stroke recurrences
new neurological events recorded after hospital discharge and validated by a vascular neurologist
Measured: Up to 2 years follow-up (ICM and standard care practice)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2024
- Study start1 Jan 2021
- Primary completionSep 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized prospective parallel study
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ermengol Vallès, Parc de Salut Mar
- Investigators
- Ermengol Valles Gras, PhD, Principal investigator, Hospital del Mar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06542770
- Sponsor's protocol ID
- CRIPTO-FAST
- Acronym
- CRIPTO-FAST
- Status last verified
- Aug 2024
- First submitted
- 21 Jul 2024
- Last updated
- 7 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: All data from this study, including pseudoanonimized data from ultrasound exams and ECG signals from ICM will be available.
Publications
Andrew NE, Thrift AG, Cadilhac DA. The prevalence, impact and economic implications of atrial fibrillation in stroke: what progress has been made? Neuroepidemiology. 2013;40(4):227-39. doi: 10.1159/000343667. Epub 2013 Jan 24.
PubMed 23364221Sposato LA, Cipriano LE, Saposnik G, Ruiz Vargas E, Riccio PM, Hachinski V. Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol. 2015 Apr;14(4):377-87. doi: 10.1016/S1474-4422(15)70027-X. Epub 2015 Mar 4.
PubMed 25748102Rubiera M, Aires A, Antonenko K, Lemeret S, Nolte CH, Putaala J, Schnabel RB, Tuladhar AM, Werring DJ, Zeraatkar D, Paciaroni M. European Stroke Organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin. Eur Stroke J. 2022 Sep;7(3):VI. doi: 10.1177/23969873221099478. Epub 2022 Jun 3.
PubMed 36082257Cuadrado-Godia E, Benito B, Ois A, Valles E, Rodriguez-Campello A, Giralt-Steinhauer E, Cabrera S, Alcalde O, Jimenez-Lopez J, Jimenez-Conde J, Marti-Almor J, Roquer J. Ultra-early continuous cardiac monitoring improves atrial fibrillation detection and prognosis of patients with cryptogenic stroke. Eur J Neurol. 2020 Feb;27(2):244-250. doi: 10.1111/ene.14061. Epub 2019 Sep 18.
PubMed 31424609Klijn CJ, Paciaroni M, Berge E, Korompoki E, Korv J, Lal A, Putaala J, Werring DJ. Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation: A European Stroke Organisation guideline. Eur Stroke J. 2019 Sep;4(3):198-223. doi: 10.1177/2396987319841187. Epub 2019 Apr 9.
PubMed 31984228Pagola J, Juega J, Francisco-Pascual J, Bustamante A, Penalba A, Pala E, Rodriguez M, De Lera-Alfonso M, Arenillas JF, Cabezas JA, Moniche F, de Torres R, Montaner J, Gonzalez-Alujas T, Alvarez-Sabin J, Molina CA; Crypto-AF study group. Predicting Atrial Fibrillation with High Risk of Embolization with Atrial Strain and NT-proBNP. Transl Stroke Res. 2021 Oct;12(5):735-741. doi: 10.1007/s12975-020-00873-2. Epub 2020 Nov 13.
PubMed 33184686Albers GW, Bernstein RA, Brachmann J, Camm J, Easton JD, Fromm P, Goto S, Granger CB, Hohnloser SH, Hylek E, Jaffer AK, Krieger DW, Passman R, Pines JM, Reed SD, Rothwell PM, Kowey PR. Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report. J Am Heart Assoc. 2016 Mar 15;5(3):e002944. doi: 10.1161/JAHA.115.002944. No abstract available.
PubMed 27068633Rubio Campal JM, Garcia Torres MA, Sanchez Borque P, Navas Vinagre I, Zamarbide Capdepon I, Miracle Blanco A, Bravo Calero L, Saez Pinel R, Tunon Fernandez J, Serratosa Fernandez JM. Detecting Atrial Fibrillation in Patients With an Embolic Stroke of Undetermined Source (from the DAF-ESUS registry). Am J Cardiol. 2020 Feb 1;125(3):409-414. doi: 10.1016/j.amjcard.2019.10.050. Epub 2019 Nov 6.
PubMed 31780074Marks D, Ho R, Then R, Weinstock JL, Teklemariam E, Kakadia B, Collins J, Andriulli J, Hunter K, Ortman M, Russo AM. Real-world experience with implantable loop recorder monitoring to detect subclinical atrial fibrillation in patients with cryptogenic stroke: The value of p wave dispersion in predicting arrhythmia occurrence. Int J Cardiol. 2021 Mar 15;327:86-92. doi: 10.1016/j.ijcard.2020.11.019. Epub 2020 Nov 10.
PubMed 33186666Chorin E, Peterson C, Kogan E, Barbhaiya C, Aizer A, Holmes D, Bernstein S, Schole M, Duraiswami H, Spinelli M, Park D, Chinitz L, Jankelson L. Comparison of the Effect of Atrial Fibrillation Detection Algorithms in Patients With Cryptogenic Stroke Using Implantable Loop Recorders. Am J Cardiol. 2020 Aug 15;129:25-29. doi: 10.1016/j.amjcard.2020.05.027. Epub 2020 May 23.
PubMed 32600783Magnusson P, Lyren A, Mattsson G. Diagnostic yield of chest and thumb ECG after cryptogenic stroke, Transient ECG Assessment in Stroke Evaluation (TEASE): an observational trial. BMJ Open. 2020 Sep 24;10(9):e037573. doi: 10.1136/bmjopen-2020-037573.
PubMed 32973062Lumikari TJ, Putaala J, Kerola A, Sibolt G, Pirinen J, Pakarinen S, Lehto M, Nieminen T. Continuous 4-week ECG monitoring with adhesive electrodes reveals AF in patients with recent embolic stroke of undetermined source. Ann Noninvasive Electrocardiol. 2019 Sep;24(5):e12649. doi: 10.1111/anec.12649. Epub 2019 May 2.
PubMed 31045315Kalani R, Bernstein R, Passman R, Curran Y, Ruff I, Prabhakaran S. Factual Inaccuracies Contained in the Article Entitled "Low Yield of Mobile Cardiac Outpatient Telemetry after Cryptogenic Stroke in Patients with Extensive Cardiac Imaging". J Stroke Cerebrovasc Dis. 2017 Dec;26(12):3035. doi: 10.1016/j.jstrokecerebrovasdis.2017.09.018. Epub 2017 Oct 18. No abstract available.
PubMed 29054732Ziegler PD, Rogers JD, Ferreira SW, Nichols AJ, Richards M, Koehler JL, Sarkar S. Long-term detection of atrial fibrillation with insertable cardiac monitors in a real-world cryptogenic stroke population. Int J Cardiol. 2017 Oct 1;244:175-179. doi: 10.1016/j.ijcard.2017.06.039. Epub 2017 Jun 10.
PubMed 28624331Ziegler PD, Rogers JD, Ferreira SW, Nichols AJ, Sarkar S, Koehler JL, Warman EN, Richards M. Real-World Experience with Insertable Cardiac Monitors to Find Atrial Fibrillation in Cryptogenic Stroke. Cerebrovasc Dis. 2015;40(3-4):175-81. doi: 10.1159/000439063. Epub 2015 Aug 28.
PubMed 26314298
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subtle Ultrasound Atrial Anomalies Predicts the Early Diagnosis of Silent Atrial Fibrillation Detected by Implantable Cardiac Monitor in Patients With Cryptogenic Stroke. A Randomized Trial
- ClinicalTrials.gov ID
- NCT06542770
- Acronym / sponsor ID
- CRIPTO-FAST / CRIPTO-FAST
- Conditions
- Paroxysmal Atrial Fibrillation, Cardiac Rhythm Disorder, Left Atrial Dilatation, Cryptogenic Stroke
- Keywords
- Atrial strain. Implantable cardiac monitor
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 7 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cryptogenic stroke (CS) causes about 30% of admissions to a stroke unit. Silent paroxysmal atrial fibrillation (PAF) is believed to be the underlying cause of a significant proportion of patients. The use of implantable cardiac monitors (ICM) early after the CS has demonstrated benefits in the diagnostic yield, but the indication for ICM in the current guidelines remains unclear. Atrial contraction strain (ACS) evaluated by cardiac ultrasound could be of help to select the patients more prone to suffer from silent PAF.
The purpose of this investigation is to conduct a randomized prospective unicentric study to evaluate the usefulness of ICM for early detection of silent PAF episodes in patients with CS. Clinical and ultrasound predictors of PAF occurrence (ACS) will be studied in order to define patients needing a closer follow-up.
Detailed description
Introduction
Cryptogenic stroke (CS) is a stroke in which etiology cannot be determined after a comprehensive evaluation and it is the cause of about 30% of admissions to a stroke unit. In these cases single antiplatelet therapy is recommended as a long term treatment. However, silent paroxysmal atrial fibrillation (PAF) is believed to be the underlying cause of a significant proportion of episodes, and it´s recognition merits urgency since carries to oral anticoagulation (OAC) and antiplatelet therapy cessation. According to guidelines, in order to detect PAF we need to monitor the patient´s ECG for at least 48h, although the longer the monitoring is, the better the diagnostic yield.
Previous research showed controversial results regarding the use of implantable cardiac monitors (ICM) in such patients when the ICM had been implanted late after the CS. On the other hand, studies with an early implant demonstrated a clear benefit in the diagnostic yield. To date, the strategy to search actively for PAF in patients with CS is still not well established, and even when internal loop recorders (ILR) are our best option to recognize paroxysmal arrhythmic events, guidelines are not clear about the cases in which they might be indicated. Some markers, such as age, cardiovascular risk factors, blood biomarkers or cardiac ultrasound characteristics have been related to a higher silent PAF detection. Recent data points at the use of left atrium atrial strain (LAS) to select the patients more prone to suffer from silent PAF.
It remains to be defined the usefulness of ILR implanted early after the CS in order to diagnose the presence of silent PAF, and the roll or ACS in such patients in order to predict those being at higher risk.
Methods
This is a randomized prospective unicentric study to evaluate the usefulness of ICM for early detection of silent PAF episodes in patients with CS. During the first 48 hours from admission, patients were randomized to receive standard care (Control Group) or early ICM implantation (Study Group) before discharge. A special effort will be made to search for the clinical and ultrasound atrial predictors of PAF occurrence in order to better define what patients need a closer follow-up.
Ultrasound evaluation
The following ultrasound atrial features will be studied to separate patients into two categories:
- LA dilatation: indexed volumen >32 ml/m2
- PALS (Peak atrial longitudinal strain) <21%
- PACS ( Peak atrial contraction strain ) <13%
- Atrial ejection fraction <55%
Patients will be considered as having a "normal" LA if none of the above mentioned characteristics is accomplished, in opposition to patients who accomplish at least one characteristic described above, which will be considered as "atrial cardiomyopathy" patients.
Patients will be immediately treated with antiplatelet treatment. OAC will be started if PAF is detected during admission. Whilst in the Stroke Unit, all patients will be continuously ECG-monitored for at least 48 h and will undergo a cardiac transthoracic echocardiogram with complete evaluation of strain parameters.
Demographic factors, vascular risk factors and comorbidities will be collected. Work-up during admission will include, at least, a complete neurological examination, 12-lead ECG, brain computed tomography (CT), blood test and neurovascular imaging (magnetic resonance angiography, angioCT and/or two-dimensional ultrasound of supra-aortic trunks and intracranial territory).
The diagnosis of CS will be revisited in all patients 3 months after the index episode, and those found to have any potential cause other than PAF will be additionally excluded. The study follows national and international principles (Declaration of Helsinki), and it was approved by the local ethics committee. All patients are required to sign the specific informed consent.
Strategies for PAF detection Since the prevalence of AF is higher in patients having LA anomalies, we will divide the total group into two categories before randomization, depending on the presence or absence of: LA dilatation, and/or impaired ACS. Then we will randomize all patients to Control Group or Study Group.
Control group: after discharge from the Stroke Unit, patients in the control group will be studied with daily ECGs whilst admitted at the hospital. Outpatient serial ECGs will be performed at the time of each visit at the Neurology Clinic 3, 6 and 12 months after the stroke, and every 6 months thereafter. Additional ECGs will be performed if patients had symptoms potentially related to PAF. Furthermore all patients will undergo a 72h-Holter-monitoring scheduled 1 month after discharge.
Study group: patients in the active study group will undergo an ICM implant 3-4 days after the stroke and prior to discharge. All devices (Abbott Jot) will be implanted subcutaneously under local anaesthesia in the left chest region and programmed with an specific algorithm for AF detection set at 30 seconds for detection. All patients will be included in remote monitoring system (Merlin), which will be programmed to send alerts in case of registering episodes qualifying for AF detection, and a monthly routine registration. All ICM recordings will be reviewed by a specialized cardiologist. Patients will be seen at the arrhythmia and the neurology outpatient clinics at 3, 6 and 12 months after the stroke, and every 6 months thereafter.
End-points and follow-up Primary clinical outcome: detection of AF at follow-up, which is defined by the presence of a confirmatory 12-leads ECG, or a registration lasting more than 30 seconds in, either the 72h-Holter-Monitoring, or in the ICM recording. In case of AF detection OAC will be initiated immediately.
Secondary clinical outcomes: ultrasounds predictors for AF occurrence: LA indexed volumen, maximum systolic global longitudinal strain (PALs), atrial contraction strain (PACs), atrial ejection fraction.
We also will search for stroke recurrences, defined as new neurological events recorded after hospital discharge and validated by a vascular neurologist.
Statistical analysis Results are reported as mean (SD), median (p25-p75) or frequency (%). Comparisons between groups were performed with the Student t test or chi-squared analysis. The association between clinical variables and the study end-points was evaluated using survival analysis methodology (Cox regression models). The Kaplan-Meier method was used to estimate the cumulative probability of PAF detection and stroke recurrence in both groups, and comparisons were made by the log-rank test. Significance was set at P < 0.05.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Randomized prospective parallel study
| Arm | Type | Receives |
|---|---|---|
| Atrial cardiomyopathy by echocardiogram intervention | Experimental | Device: Early implant of cardiac monitorPresence of Atrial cardiomyopathy is defined by echocardiogram if ANY of the following is present: 1. LA dilatation: indexed volumen >32 ml/m2 2. PALS (Peak atrial longitudinal strain) <21% 3. PACS ( Peak atrial contraction strain ) <13% 4. Atrial ejection fraction <55% |
| Atrial cardiomyopathy by echocardiogram standard practice | No intervention | –Presence of Atrial cardiomyopathy is defined by echocardiogram if ANY of the following is present: 1. LA dilatation: indexed volumen >32 ml/m2 2. PALS (Peak atrial longitudinal strain) <21% 3. PACS ( Peak atrial contraction strain ) <13% 4. Atrial ejection fraction <55% |
| Non atrial cardiomyopathy by echocardiogram intervention | Experimental | Device: Early implant of cardiac monitorAbsence of atrial cardiomyopathy is defined by echocardiogram if none of the characteristics bellow were accomplished. 1. LA dilatation: indexed volumen >32 ml/m2 2. PALS (Peak atrial longitudinal strain) <21% 3. PACS ( Peak atrial contraction strain ) <13% 4. Atrial ejection fraction <55% |
| Non atrial cardiomyopathy by echocardiogram standard practice | No intervention | –Absence of atrial cardiomyopathy defined by echocardiogram if none of the characteristics bellow were accomplished. 1. LA dilatation: indexed volumen >32 ml/m2 2. PALS (Peak atrial longitudinal strain) <21% 3. PACS ( Peak atrial contraction strain ) <13% 4. Atrial ejection fraction <55% |
Who may qualify
- Ages
- 50 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Acute ischemic stroke or transient ischemic attack (TIA) from January 2022 to July 2023
- Age between 50 and 89 years;
- Undetermined origin at hospital admission according to the SSS-TOAST criteria (2):
Key exclusion criteria (6 listed)
- Patients with a history of hemorrhagic stroke;
- Presence with prior atrial fibrillation or atrial flutter;
- Permanent contraindication or indication for OAC for other reasons;
- Recent (<1 month) major surgery or cardiac events;
- Presence of severe cardiac abnormalities;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Early implant of cardiac monitorICM implant 3-4 days after the stroke and prior to discharge. All devices (Abbott Confirm or Jot) were implanted subcutaneously under local anaesthesia in the left chest region and programmed with an specific algorithm for AF detection set at 30 seconds for detection. All patients were included in remote monitoring system (Merlin), which was programmed to send alerts in case of registering episodes qualifying for AF detection, and a monthly routine registration. All ICM recordings were reviewed by a specialized cardiologist. | Device | Atrial cardiomyopathy by echocardiogram intervention, Non atrial cardiomyopathy by echocardiogram intervention |
Primary outcome
Detection atrial fibrilation at follow-up
Time frame: Up to 2 years follow-up (ICM and standard care practice)
defined by the presence of a confirmatory 12-leads ECG, or a registration lasting more than 30 seconds in, either the 72h-Holter-Monitoring, or in the ICM recording. In case of AF detection OAC was initiated immediately.
5 secondary outcomes
LA indexed volume
Time frame: Before Day 3 since the Criptogenic Stroke
Maximum Systolic Global Longitudinal Strain (PALs)
Time frame: Before Day 3 since the Criptogenic Stroke
Atrial Contraction Strain (PACs)
Time frame: Before Day 3 since the Criptogenic Stroke
Atrial Ejection Fraction
Time frame: Before Day 3 since the Criptogenic Stroke
stroke recurrences
Time frame: Up to 2 years follow-up (ICM and standard care practice)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2024.
- Background: PubMed 23364221Andrew NE, Thrift AG, Cadilhac DA. The prevalence, impact and economic implications of atrial fibrillation in stroke: what progress has been made? Neuroepidemiology. 2013;40(4):227-39. doi: 10.1159/000343667. Epub 2013 Jan 24.
- Background: PubMed 25748102Sposato LA, Cipriano LE, Saposnik G, Ruiz Vargas E, Riccio PM, Hachinski V. Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol. 2015 Apr;14(4):377-87. doi: 10.1016/S1474-4422(15)70027-X. Epub 2015 Mar 4.
- Background: PubMed 36082257Rubiera M, Aires A, Antonenko K, Lemeret S, Nolte CH, Putaala J, Schnabel RB, Tuladhar AM, Werring DJ, Zeraatkar D, Paciaroni M. European Stroke Organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin. Eur Stroke J. 2022 Sep;7(3):VI. doi: 10.1177/23969873221099478. Epub 2022 Jun 3.
- Background: PubMed 31424609Cuadrado-Godia E, Benito B, Ois A, Valles E, Rodriguez-Campello A, Giralt-Steinhauer E, Cabrera S, Alcalde O, Jimenez-Lopez J, Jimenez-Conde J, Marti-Almor J, Roquer J. Ultra-early continuous cardiac monitoring improves atrial fibrillation detection and prognosis of patients with cryptogenic stroke. Eur J Neurol. 2020 Feb;27(2):244-250. doi: 10.1111/ene.14061. Epub 2019 Sep 18.
- Background: PubMed 31984228Klijn CJ, Paciaroni M, Berge E, Korompoki E, Korv J, Lal A, Putaala J, Werring DJ. Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation: A European Stroke Organisation guideline. Eur Stroke J. 2019 Sep;4(3):198-223. doi: 10.1177/2396987319841187. Epub 2019 Apr 9.
- Background: PubMed 33184686Pagola J, Juega J, Francisco-Pascual J, Bustamante A, Penalba A, Pala E, Rodriguez M, De Lera-Alfonso M, Arenillas JF, Cabezas JA, Moniche F, de Torres R, Montaner J, Gonzalez-Alujas T, Alvarez-Sabin J, Molina CA; Crypto-AF study group. Predicting Atrial Fibrillation with High Risk of Embolization with Atrial Strain and NT-proBNP. Transl Stroke Res. 2021 Oct;12(5):735-741. doi: 10.1007/s12975-020-00873-2. Epub 2020 Nov 13.
- Background: PubMed 27068633Albers GW, Bernstein RA, Brachmann J, Camm J, Easton JD, Fromm P, Goto S, Granger CB, Hohnloser SH, Hylek E, Jaffer AK, Krieger DW, Passman R, Pines JM, Reed SD, Rothwell PM, Kowey PR. Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report. J Am Heart Assoc. 2016 Mar 15;5(3):e002944. doi: 10.1161/JAHA.115.002944. No abstract available.
- Background: PubMed 31780074Rubio Campal JM, Garcia Torres MA, Sanchez Borque P, Navas Vinagre I, Zamarbide Capdepon I, Miracle Blanco A, Bravo Calero L, Saez Pinel R, Tunon Fernandez J, Serratosa Fernandez JM. Detecting Atrial Fibrillation in Patients With an Embolic Stroke of Undetermined Source (from the DAF-ESUS registry). Am J Cardiol. 2020 Feb 1;125(3):409-414. doi: 10.1016/j.amjcard.2019.10.050. Epub 2019 Nov 6.
- Background: PubMed 33186666Marks D, Ho R, Then R, Weinstock JL, Teklemariam E, Kakadia B, Collins J, Andriulli J, Hunter K, Ortman M, Russo AM. Real-world experience with implantable loop recorder monitoring to detect subclinical atrial fibrillation in patients with cryptogenic stroke: The value of p wave dispersion in predicting arrhythmia occurrence. Int J Cardiol. 2021 Mar 15;327:86-92. doi: 10.1016/j.ijcard.2020.11.019. Epub 2020 Nov 10.
- Background: PubMed 32600783Chorin E, Peterson C, Kogan E, Barbhaiya C, Aizer A, Holmes D, Bernstein S, Schole M, Duraiswami H, Spinelli M, Park D, Chinitz L, Jankelson L. Comparison of the Effect of Atrial Fibrillation Detection Algorithms in Patients With Cryptogenic Stroke Using Implantable Loop Recorders. Am J Cardiol. 2020 Aug 15;129:25-29. doi: 10.1016/j.amjcard.2020.05.027. Epub 2020 May 23.
- Background: PubMed 32973062Magnusson P, Lyren A, Mattsson G. Diagnostic yield of chest and thumb ECG after cryptogenic stroke, Transient ECG Assessment in Stroke Evaluation (TEASE): an observational trial. BMJ Open. 2020 Sep 24;10(9):e037573. doi: 10.1136/bmjopen-2020-037573.
- Background: PubMed 31045315Lumikari TJ, Putaala J, Kerola A, Sibolt G, Pirinen J, Pakarinen S, Lehto M, Nieminen T. Continuous 4-week ECG monitoring with adhesive electrodes reveals AF in patients with recent embolic stroke of undetermined source. Ann Noninvasive Electrocardiol. 2019 Sep;24(5):e12649. doi: 10.1111/anec.12649. Epub 2019 May 2.
- Individual participant dataSharing planned: Yes. All data from this study, including pseudoanonimized data from ultrasound exams and ECG signals from ICM will be available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ermengol Valles Gras, PhD principal investigator
Hospital del Mar
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Early implant of cardiac monitor in people with Paroxysmal Atrial Fibrillation and Cardiac Rhythm Disorder, run by Parc de Salut Mar at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ermengol Valles Gras, PhD (932 48 3118, evalles@psmar.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detection atrial fibrilation at follow-up (time frame: Up to 2 years follow-up (ICM and standard care practice)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06542770, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2024.