Atrial Cardiopathy and Likely Pathogenic Patent Foramen Ovale in Embolic Stroke of Undetermined SourceFunding This analysis was performed in the data set of the AF-ESUS (Prediction of AF in ESUS) study (ClinicalTrials.gov Identifier: NCT02766205), which is an investigator-initiated study supported by Pfizer through the BMS/Pfizer European Thrombosis Investigator Initiated Research Program (ERISTA). The Swiss Cardiology Foundation supported data collection in the ASTRAL registry.
Background Atrial cardiopathy and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear.
Methods Atrial cardiopathy was defined as increased left atrial diameter index (> 23 mm/m2) or left atrial volume index (> 34 mL/m2), or PR prolongation (≥ 200 ms), or presence of supraventricular extrasystoles in the electrocardiograms performed during hospitalization for the index stoke. The presence of PFO was assessed by transthoracic echocardiography with microbubble test or by transesophageal echocardiography. The presence of PFO was considered as likely pathogenic if the Risk of Paradoxical Embolism score was 7 to 10.
Results Among 367 ESUS patients with available information about the presence of PFO and the presence of atrial cardiopathy (median age: 61 years, 40.6% women), likely pathogenic PFO was diagnosed in 62 (16.9%) and atrial cardiopathy in 122 (33.2%). Only 4 patients (1.1%) had both likely pathogenic PFO and atrial cardiopathy. The prevalence of atrial cardiopathy was lower in patients with likely pathogenic PFO (6.5%) compared with patients with likely incidental PFO (31.2%) or without PFO (40.6%) (Pearson's chi-square test: 26.08, p < 0.001; adjusted odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.09–0.86). The prevalence of likely pathogenic PFO was lower in patients with atrial cardiopathy compared with patients without atrial cardiopathy (3.3% vs. 23.7%, respectively [Pearson's chi-square test: 24.13, p < 0.001; adjusted OR: 0.2, 95% CI: 0.02–0.6]).
Conclusion The presence of atrial cardiopathy is inversely related to the presence of likely pathogenic PFO in patients with ESUS.
Keywordsembolic stroke of undetermined source - patent foramen ovale - RoPE score - atrial cardiopathy
Received: 08 June 2020
Accepted: 17 July 2020
02 September 2020 (online)
Georg Thieme Verlag KG
Stuttgart · New York
- 1 Hart RG, Diener HC, Coutts SB. , et al; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 2014; 13 (04) 429-438
- 2 Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source: a systematic review and clinical update. Stroke 2017; 48 (04) 867-872
- 3 Ntaios G, Papavasileiou V, Milionis H. , et al. Embolic strokes of undetermined source in the Athens stroke registry: a descriptive analysis. Stroke 2015; 46 (01) 176-181
- 4 Ntaios G, Papavasileiou V, Milionis H. , et al. Embolic strokes of undetermined source in the Athens stroke registry: an outcome analysis. Stroke 2015; 46 (08) 2087-2093
- 5 Ntaios G. Embolic stroke of undetermined source: JACC review topic of the week. J Am Coll Cardiol 2020; 75 (03) 333-340
- 6 Kent DM, Ruthazer R, Weimar C. , et al. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology 2013; 81 (07) 619-625
- 7 Thaler DE, Ruthazer R, Weimar C. , et al. Recurrent stroke predictors differ in medically treated patients with pathogenic vs. other PFOs. Neurology 2014; 83 (03) 221-226
- 8 Pristipino C, Sievert H, D'Ascenzo F. , et al; European Association of Percutaneous Cardiovascular Interventions (EAPCI); European Stroke Organisation (ESO); European Heart Rhythm Association (EHRA); European Association for Cardiovascular Imaging (EACVI); Association for European Paediatric and Congenital Cardiology (AEPC); ESC Working group on GUCH; ESC Working group on Thrombosis; European Haematological Society (EHA). European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism. EuroIntervention 2019; 14 (13) 1389-1402
- 9 Ntaios G, Tzikas A, Vavouranakis E. , et al. Expert consensus statement for the management of patients with embolic stroke of undetermined source and patent foramen ovale: a clinical guide by the working group for stroke of the Hellenic Society of Cardiology and the Hellenic Stroke Organization. Hellenic J Cardiol 2020; S1109-9666(20)30032-4
- 10 Ntaios G, Perlepe K, Sirimarco G. , et al. Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source. Neurology 2019; 92 (23) e2644-e2652
- 11 Leventis I, Perlepe K, Sagris D. , et al. Characteristics and outcomes of embolic stroke of undetermined source according to stroke severity. Intl J Stroke 2020; 1747493020909546
- 12 Lang RM, Badano LP, Mor-Avi V. , et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28 (01) 1-39 e14
- 13 Galderisi M, Cosyns B, Edvardsen T. , et al; 2016–2018 EACVI Scientific Documents Committee; 2016–2018 EACVI Scientific Documents Committee. Standardization of adult transthoracic echocardiography reporting in agreement with recent chamber quantification, diastolic function, and heart valve disease recommendations: an expert consensus document of the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2017; 18 (12) 1301-1310
- 14 Thijs VN, Brachmann J, Morillo CA. , et al. Predictors for atrial fibrillation detection after cryptogenic stroke: results from CRYSTAL AF. Neurology 2016; 86 (03) 261-269
- 15 Ntaios G, Perlepe K, Lambrou D. , et al. Prevalence and overlap of potential embolic sources in patients with embolic stroke of undetermined source. J Am Heart Assoc 2019; 8 (15) e012858
- 16 Murakoshi N, Xu D, Sairenchi T. , et al. Prognostic impact of supraventricular premature complexes in community-based health checkups: the Ibaraki Prefectural Health Study. Eur Heart J 2015; 36 (03) 170-178
- 17 O'Neal WT, Kamel H, Kleindorfer D. , et al. Premature atrial contractions on the screening electrocardiogram and risk of ischemic stroke: the reasons for geographic and racial differences in stroke study. Neuroepidemiology 2016; 47 (01) 53-58
- 18 Ntaios G, Hart RG. Embolic stroke. Circulation 2017; 136 (25) 2403-2405
- 19 Ntaios G, Pearce LA, Veltkamp R. , et al. Potential embolic sources and outcomes in embolic stroke of undetermined source in the NAVIGATE-ESUS trial. Stroke 2020; STROKEAHA119028669
- 20 Kamel H, Pearce LA, Ntaios G. , et al. Atrial cardiopathy and nonstenosing large artery plaque in patients with embolic stroke of undetermined source. Stroke 2020; STROKEAHA119028154
- 21 Ntaios G, Wintermark M, Michel P. Supracardiac atherosclerosis in embolic stroke of undetermined source: the underestimated source. Eur Heart J 2020; ehaa218
- 22 Elkind MSV. Atrial cardiopathy and stroke prevention. Curr Cardiol Rep 2018; 20 (11) 103
- 23 Kamel H, Longstreth Jr WT, Tirschwell DL. , et al. The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: rationale and methods. Int J Stroke 2019; 14 (02) 207-214
- 24 Geisler T, Poli S, Meisner C. , et al. Apixaban for treatment of embolic stroke of undetermined source (ATTICUS randomized trial): rationale and study design. Int J Stroke 2017; 12 (09) 985-990
- 25 Schnabel RB, Haeusler KG, Healey JS. , et al. Searching for atrial fibrillation poststroke: a white paper of the AF-SCREEN international collaboration. Circulation 2019; 140 (22) 1834-1850
- 26 Healey JS, Gladstone DJ, Swaminathan B. , et al. Recurrent stroke with rivaroxaban compared with aspirin according to predictors of atrial fibrillation: secondary analysis of the NAVIGATE ESUS randomized clinical trial. JAMA Neurol 2019; 76 (07) 764-773
- 27 Sagris D, Georgiopoulos G, Perlepe K. , et al. Antithrombotic treatment in cryptogenic stroke patients with patent foramen ovale: systematic review and meta-analysis. Stroke 2019; STROKEAHA119026512
- 28 Ntaios G, Papavasileiou V, Sagris D. , et al. Closure of patent foramen ovale versus medical therapy in patients with cryptogenic stroke or transient ischemic attack: updated systematic review and meta-analysis. Stroke 2018; 49 (02) 412-418
- 29 Kasner SE, Swaminathan B, Lavados P. , et al; NAVIGATE ESUS Investigators. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial. Lancet Neurol 2018; 17 (12) 1053-1060