Abstract
Background
Cryptogenic stroke (CS) remains a significant cause of morbidity. Failure to identify the underlying pathology increases the rate of recurrence. Atrial fibrillation (AF) seems to be responsible for a substantial proportion of CS. Thus, there is an unmet need to identify and properly treat those with silent AF.
Purpose
To investigate the association between left atrial strain and newly diagnosed AF in CS patients.
Objectives
We searched major electronic databases for articles assessing the relationship between either peak left atrial longitudinal (PALS) or peak contractile (PACS) strain—quantified using speckle tracking echocardiography—and the incidence of occult AF during the diagnostic work-up of CS patients.
Results
Eleven studies (two thousand and eighty-one patients) were analyzed. Incidence of occult AF was 19%. Both PALS and PACS were significantly lower in patients with newly diagnosed AF (MD − 8.6%, 95%CI − 10.7 to − 6.4, I2 86.4% and MD − 5.5, 95%CI − 6.8 to − 4.2, I2 80.8%). According to the diagnostic accuracy meta-analysis, PALS < 20% present 71% (95%CI 47–87%) sensitivity and 71% (95%CI 60–81%) specificity for the diagnosis of occult AF, assuming a prevalence of 20%. The corresponding values for PACS < 11% are 83% (95%CI 57–94%) and 78% (95%CI 56–91%).
Conclusion
Both PALS and PACS are significantly lower in patients with CS and silent AF. It seems that the cut-off values mentioned above could help physicians in identifying patients who may benefit more from prolonged rhythm monitoring. More studies are needed to confirm these findings.
Graphical Abstract
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Data availability
Data are available upon reasonable request.
References
GBD 2019 Stroke Collaborators (2019) Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 20:795–820
Girotra T, Lekoubou A, Bishu KG, Ovbiagele B (2020) A contemporary and comprehensive analysis of the costs of stroke in the United States. J Neurol Sci 15(410):116643
Friberg L, Rosenqvist M, Lindgren A, Terént A, Norrving B, Asplund K (2014) High prevalence of atrial fibrillation among patients with ischemic stroke. Stroke 45(9):2599–2605
Saver JL (2016) Cryptogenic stroke. N Engl J Med 375:e26
Ko D, Dai Q, Flynn DB, Bosch NA, Helm RH, Monahan KM, Andersson C, Anderson CD, Walkey AJ (2022) Meta-analysis of randomized clinical trials comparing the impact of implantable loop recorder versus usual care after ischemic stroke for detection of atrial fibrillation and stroke risk. Am J Cardiol 1(162):100–104
Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, Vaid H, O’Donnell M, Laupacis A, Côté R, Sharma M, Blakely JA, Shuaib A, Hachinski V, Coutts SB, Sahlas DJ, Teal P, Yip S, Spence JD, Buck B, Verreault S, Casaubon LK, Penn A, Selchen D, Jin A, Howse D, Mehdiratta M, Boyle K, Aviv R, Kapral MK, Mamdani M, EMBRACE Investigators and Coordinators (2014) Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 370(26):2467–2477
Gorenek B, Bax J, Boriani G, Chen SA, Dagres N, Glotzer TV, Healey JS, Israel CW, Kudaiberdieva G, Levin LÅ, Lip GYH, Martin D, Okumura K, Svendsen JH, Tse HF, Botto GL, ESC Scientific Document Group (2017) Device-detected subclinical atrial tachyarrhythmias: definition, implications and management-an European Heart Rhythm Association (EHRA) consensus document, endorsed by Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE). Europace 19(9):1556–1578
Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU (2001) Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke 32(12):2735–2740
Pagola J, Pagola C, Juega J, González-Alujas T, Alvarez-Sabin J, Molina CA (2020) The role of echocardiography screening at the stroke unit. Front Neurol 11(11):1003
Jordan K, Yaghi S, Poppas A, Chang AD, Mac Grory B, Cutting S, Burton T, Jayaraman M, Tsivgoulis G, Sabeh MK, Merkler AE, Kamel H, Elkind MSV, Furie K, Song C (2019) Left atrial volume index is associated with cardioembolic stroke and atrial fibrillation detection after embolic stroke of undetermined source. Stroke 50(8):1997–2001
Badano LP, Kolias TJ, Muraru D, Abraham TP, Aurigemma G, Edvardsen T, D’Hooge J, Donal E, Fraser AG, Marwick T, Mertens L, Popescu BA, Sengupta PP, Lancellotti P, Thomas JD, Voigt JU, Industry representatives; Reviewers: This document was reviewed by members of the 2016–2018 EACVI Scientific Documents Committee (2018) Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur Heart J Cardiovasc Imaging 19(6):591–600
Huber MP, Pandit JA, Jensen PN, Wiggins KL, Patel RB, Freed BH, Bertoni AG, Shah SJ, Heckbert SR, Floyd JS (2022) Left atrial strain and the risk of atrial arrhythmias from extended ambulatory cardiac monitoring: MESA. J Am Heart Assoc 11(21):e026875
Anagnostopoulos I, Kousta M, Kossyvakis C, Lakka E, Paraskevaidis NT, Schizas N, Deftereos S, Giannopoulos G (2022) The role of left atrial peak systolic strain in atrial fibrillation recurrence after catheter ablation. A systematic review and meta-analysis. Acta Cardiol 77(6):536–544
Hauser R, Nielsen AB, Skaarup KG, Lassen MCH, Duus LS, Johansen ND, Sengeløv M, Marott JL, Jensen G, Schnohr P, Søgaard P, Møgelvang R, Biering-Sørensen T (2021) Left atrial strain predicts incident atrial fibrillation in the general population: the Copenhagen City Heart Study. Eur Heart J Cardiovasc Imaging 23(1):52–60
Mac Grory B, Flood SP, Apostolidou E, Yaghi S (2019) Cryptogenic stroke: diagnostic workup and management. Curr Treat Options Cardiovasc Med 21(11):77
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62(10):e1–e34
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd (1993) Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24(1):35–41
Hart RG, Diener HC, Coutts SB et al (2014) Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 13(4):429–438
National Institutes of Health (2014) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed 20 Dec 2022
Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634
Ryan R. Cochrane Consumers and Communication Review Group. Heterogeneity and subgroup analyses in Cochrane Consumers and Communication Group reviews: planning the analysis at protocol stage. https://cccrg.cochrane.org/sites/cccrg.cochrane.org/files/public/uploads/heterogeneity_subgroup_analyses_revising_december_1st_2016.pdf. Accessed 15 Dec 2022
Schneider A, Linde K, Reitsma JB, Steinhauser S, Rücker G (2017) A novel statistical model for analyzing data of a systematic review generates optimal cut-off values for fractional exhaled nitric oxide for asthma diagnosis. J Clin Epidemiol 92:69–78
Pathan F, Sivaraj E, Negishi K, Rafiudeen R, Pathan S, D’Elia N, Galligan J, Neilson S, Fonseca R, Marwick TH (2018) Use of atrial strain to predict atrial fibrillation after cerebral ischemia. JACC Cardiovasc Imaging 11(11):1557–1565
Olsen FJ, Christensen LM, Krieger DW, Højberg S, Høst N, Karlsen FM, Svendsen JH, Christensen H, Biering-Sørensen T (2020) Relationship between left atrial strain, diastolic dysfunction and subclinical atrial fibrillation in patients with cryptogenic stroke: the SURPRISE echo substudy. Int J Cardiovasc Imaging 36(1):79–89
Pagola 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, González-Alujas T, Alvarez-Sabin J, Molina CA, Crypto-AF study group (2021) Predicting atrial fibrillation with high risk of embolization with atrial strain and NT-proBNP. Transl Stroke Res 12(5):735–741
Kawakami H, Ramkumar S, Pathan F, Wright L, Marwick TH (2020) Use of echocardiography to stratify the risk of atrial fibrillation: comparison of left atrial and ventricular strain. Eur Heart J Cardiovasc Imaging 21(4):399–407
Sieweke JT, Biber S, Weissenborn K, Heuschmann PU, Akin M, Zauner F, Gabriel MM, Schuppner R, Berliner D, Bauersachs J, Grosse GM, Bavendiek U (2020) Septal total atrial conduction time for prediction of atrial fibrillation in embolic stroke of unknown source: a pilot study. Clin Res Cardiol 109(2):205–214
Deferm S, Bertrand PB, Churchill TW, Sharma R, Vandervoort PM, Schwamm LH, Yoerger Sanborn DM (2021) Left atrial mechanics assessed early during hospitalization for cryptogenic stroke are associated with occult atrial fibrillation: a speckle-tracking strain echocardiography study. J Am Soc Echocardiogr 34(2):156–165
Kusunose K, Takahashi H, Nishio S, Hirata Y, Zheng R, Ise T, Yamaguchi K, Yagi S, Fukuda D, Yamada H, Soeki T, Wakatsuki T, Shimada K, Kanematsu Y, Takagi Y, Sata M (2021) Predictive value of left atrial function for latent paroxysmal atrial fibrillation as the cause of embolic stroke of undetermined source. J Cardiol 78(5):355–361
Ble M, Benito B, Cuadrado-Godia E, Pérez-Fernández S, Gómez M, Mas-Stachurska A, Tizón-Marcos H, Molina L, Martí-Almor J, Cladellas M (2021) Left atrium assessment by speckle tracking echocardiography in cryptogenic stroke: seeking silent atrial fibrillation. J Clin Med 10(16):3501
Sade LE, Keskin S, Can U, Çolak A, Yüce D, Çiftçi O, Özin B, Müderrisoğlu H (2022) Left atrial mechanics for secondary prevention from embolic stroke of undetermined source. Eur Heart J Cardiovasc Imaging 23(3):381–391
Bufano G, Radico F, D’Angelo C, Pierfelice F, De Angelis MV, Faustino M, Pierdomenico SD, Gallina S, Renda G (2022) Predictive value of left atrial and ventricular strain for the detection of atrial fibrillation in patients with cryptogenic stroke. Front Cardiovasc Med 25(9):869076
Vera A, Cecconi A, Ximénez-Carrillo Á, Ramos C, Martínez-Vives P, Lopez-Melgar B, Sanz-García A, Ortega G, Aguirre C, Vivancos J, Jiménez-Borreguero LJ, Alfonso F, DECRYTORING Study Investigators (2022) Advanced echocardiography with left atrial strain and indexed left atrial three-dimensional volume for predicting underlying atrial fibrillation after cryptogenic stroke. Am J Cardiol 185:87–93
Alhakak AS, Biering-Sørensen SR, Møgelvang R, Modin D, Jensen GB, Schnohr P, Iversen AZ, Svendsen JH, Jespersen T, Gislason G, Biering-Sørensen T (2022) Usefulness of left atrial strain for predicting incident atrial fibrillation and ischaemic stroke in the general population. Eur Heart J Cardiovasc Imaging 23(3):363–371
Gladstone DJ, Spring M, Dorian P et al (2014) Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 370:2467–2477
Sanna T, Diener HC, Passman RS et al (2014) Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 370:2478–2486
Rubiera M, Aires A, Antonenko K, Lémeret S, Nolte CH, Putaala J, Schnabel RB, Tuladhar AM, Werring DJ, Zeraatkar D, Paciaroni M (2022) European Stroke Organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin. Eur Stroke J 7(3):CVII–CXXXIX
Chew DS, Rennert-May E, Quinn FR, Buck B, Hill MD, Spackman E, Manns BJ, Exner DV (2021) Economic evaluation of extended electrocardiogram monitoring for atrial fibrillation in patients with cryptogenic stroke. Int J Stroke 16(7):809–817
Thijs VN, Brachmann J, Morillo CA, Passman RS, Sanna T, Bernstein RA, Diener HC, Di Lazzaro V, Rymer MM, Hogge L, Rogers TB, Ziegler PD, Assar MD (2016) Predictors for atrial fibrillation detection after cryptogenic stroke: results from CRYSTAL AF. Neurology 86(3):261–269
Riordan M, Opaskar A, Yoruk A, Younis A, Ali A, McNitt S, Sahin B, Rosero S, Goldenberg I, Aktas MK (2020) Predictors of atrial fibrillation during long-term implantable cardiac monitoring following cryptogenic stroke. J Am Heart Assoc 9(15):e016040
Xu J, Sethi P, Biby S, Allred J, Seiler A, Sabir R (2020) Predictors of atrial fibrillation detection and features of recurrent strokes in patients after cryptogenic stroke. J Stroke Cerebrovasc Dis 29(9):104934
Rodríguez-Yáñez M, Arias-Rivas S, Santamaría-Cadavid M, Sobrino T, Castillo J, Blanco M (2013) High pro-BNP levels predict the occurrence of atrial fibrillation after cryptogenic stroke. Neurology 81(5):444–447
Palà E, Pagola J, Juega J, Francisco-Pascual J, Bustamante A, Penalba A, Comas I, Rodriguez M, De Lera AM, Arenillas JF, de Torres R, Pérez-Sánchez S, Cabezas JA, Moniche F, González-Alujas T, Molina CA, Montaner J (2021) B-type natriuretic peptide over N-terminal pro-brain natriuretic peptide to predict incident atrial fibrillation after cryptogenic stroke. Eur J Neurol 28(2):540–547
Wasser K, Weber-Krüger M, Gröschel S, Uphaus T, Liman J, Hamann GF, Kermer P, Seegers J, Binder L, Gelbrich G, Gröschel K, Wachter R (2020) Brain natriuretic peptide and discovery of atrial fibrillation after stroke: a subanalysis of the find-AFRANDOMISED trial. Stroke 51(2):395–401
Perlepe K, Sirimarco G, Strambo D, Eskandari A, Karagkiozi E, Vemmou A, Koroboki E, Manios E, Makaritsis K, Vemmos K, Michel P, Ntaios G (2020) Left atrial diameter thresholds and new incident atrial fibrillation in embolic stroke of undetermined source. Eur J Intern Med 75:30–34
Baturova MA, Sheldon SH, Carlson J, Brady PA, Lin G, Rabinstein AA, Friedman PA, Platonov PG (2016) Electrocardiographic and Echocardiographic predictors of paroxysmal atrial fibrillation detected after ischemic stroke. BMC Cardiovasc Disord 16(1):209
Boyd AC, Richards DA, Marwick T, Thomas L (2011) Atrial strain rate is a sensitive measure of alterations in atrial phasic function in healthy ageing. Heart 97(18):1513–1519
Morris DA, Takeuchi M, Krisper M, Köhncke C, Bekfani T, Carstensen T, Hassfeld S, Dorenkamp M, Otani K, Takigiku K, Izumi C, Yuda S, Sakata K, Ohte N, Tanabe K, Osmanoglou E, Kühnle Y, Düngen HD, Nakatani S, Otsuji Y, Haverkamp W, Boldt LH (2015) Normal values and clinical relevance of left atrial myocardial function analysed by speckle-tracking echocardiography: multicentre study. Eur Heart J Cardiovasc Imaging 16(4):364–372
Thomas L, Marwick TH, Popescu BA, Donal E, Badano LP (2019) Left atrial structure and function, and left ventricular diastolic dysfunction: JACC state-of-the-art review. J Am Coll Cardiol 73(15):1961–1977
Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G, Galderisi M, Marwick T, Nagueh SF, Sengupta PP, Sicari R, Smiseth OA, Smulevitz B, Takeuchi M, Thomas JD, Vannan M, Voigt JU, Zamorano JL (2011) Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. Eur J Echocardiogr 12(3):167–205
Badano LP, Kolias TJ, Muraru D et al (2018) Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging [published correction appears in Eur Heart J Cardiovasc Imaging. 2018 Jul 1;19(7):830-833]. Eur Heart J Cardiovasc Imaging 19(6):591–600
Barbier P, Solomon SB, Schiller NB, Glantz SA (1999) Left atrial relaxation and left ventricular systolic function determine left atrial reservoir function. Circulation 100(4):427–436
Hoit BD (2022) Left atrial reservoir strain: its time has come. JACC Cardiovasc Imaging 15(3):392–394
Habibi M, Lima JA, Khurram IM, Zimmerman SL, Zipunnikov V, Fukumoto K, Spragg D, Ashikaga H, Rickard J, Marine JE, Calkins H, Nazarian S (2015) Association of left atrial function and left atrial enhancement in patients with atrial fibrillation: cardiac magnetic resonance study. Circ Cardiovasc Imaging 8(2):e002769
Peters DC, Duncan JS, Grunseich K, Marieb MA, Cornfeld D, Sinusas AJ, Chelikani S (2017) CMR-verified lower LA strain in the presence of regional atrial fibrosis in atrial fibrillation. JACC Cardiovasc Imaging 10(2):207–208
Kuppahally SS, Akoum N, Burgon NS, Badger TJ, Kholmovski EG, Vijayakumar S, Rao SN, Blauer J, Fish EN, Dibella EV, Macleod RS, McGann C, Litwin SE, Marrouche NF (2010) Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI. Circ Cardiovasc Imaging 3(3):231–239
Nattel S (2017) Molecular and cellular mechanisms of atrial fibrosis in atrial fibrillation. JACC Clin Electrophysiol 3(5):425–435
Yue L, Xie J, Nattel S (2011) Molecular determinants of cardiac fibroblast electrical function and therapeutic implications for atrial fibrillation. Cardiovasc Res 89(4):744–753
Miragoli M, Gaudesius G, Rohr S (2006) Electrotonic modulation of cardiac impulse conduction by myofibroblasts. Circ Res 98(6):801–810
Zlochiver S, Muñoz V, Vikstrom KL, Taffet SM, Berenfeld O, Jalife J (2008) Electrotonic myofibroblast-to-myocyte coupling increases propensity to reentrant arrhythmias in two-dimensional cardiac monolayers. Biophys J 95(9):4469–4480
Yue L, Feng J, Gaspo R, Li GR, Wang Z, Nattel S (1997) Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ Res 81(4):512–525
Schotten U, Duytschaever M, Ausma J, Eijsbouts S, Neuberger HR, Allessie M (2003) Electrical and contractile remodeling during the first days of atrial fibrillation go hand in hand. Circulation 107(10):1433–1439
Acknowledgements
IA, CK, and GG were involved in study conception and design. MK and EL were involved in searching databases and extracting data of interest. IA, NTP, and GG were involved in data analysis and interpretation. IA, MK, NTP, and NS drafted the manuscript. CK, SD, and GG critically revised the drafted version of the manuscript.
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Anagnostopoulos, I., Kousta, M., Kossyvakis, C. et al. Atrial strain and occult atrial fibrillation in cryptogenic stroke patients: a systematic review and meta-analysis. Clin Res Cardiol 112, 1600–1609 (2023). https://doi.org/10.1007/s00392-023-02218-z
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DOI: https://doi.org/10.1007/s00392-023-02218-z