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Shiroto H, Hagii J. Biomarkers for the detection of covert atrial fibrillation after ischemic stroke: NT-proBNP or BNP? J Stroke Cerebrovasc Dis 2025; 34:108239. [PMID: 39900314 DOI: 10.1016/j.jstrokecerebrovasdis.2025.108239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 01/10/2025] [Accepted: 01/11/2025] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND Atrial fibrillation often leads to ischemic stroke. For secondary prevention, clinicians typically switch from antiplatelet to anticoagulant therapy for patients with confirmed atrial fibrillation. This study examined the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) for detecting covert paroxysmal atrial fibrillation (PAF) in patients with ischemic stroke (PWIS). METHODS We enrolled 438 patients with acute stroke in sinus rhythm on admission from July 2021 to March 2023 and measured their NT-proBNP and BNP levels to evaluate their association with PAF detection. Data analysis included logistic regression, receiver operating characteristic curves, and integrated discrimination improvement (IDI). RESULTS Among our 438 enrolled participants, 43 (9.8%) were in the PAF group and the remaining were in the non-PAF group. PAF group patients were older than those in the non-PAF group (PAF group vs. non-PAF group; 84 [78-89] vs. 79 [71-85] years) and had higher levels of both NT-proBNP (581.0 [264.5-1,234.5] vs. 168.0 [76.0-412.5] pg/mL) and BNP (186.0 [100.4-313.0] vs. 56.4 [26.9-118.0] pg/mL). The PAF group also had a higher prevalence of chronic heart failure (30% vs. 10%). Both biomarkers were independent predictors of PAF detection, and there was no significant difference in their predictive accuracy for PAF. However, BNP had a slight advantage in the IDI score over NT-proBNP (-0.03 [-0.05 to -0.01]). CONCLUSION NT-proBNP and BNP can both effectively predict covert PAF in PWIS in sinus rhythm. Thus, either biomarker should be incorporated into treatment planning strategies for these patients.
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Affiliation(s)
- Hiroshi Shiroto
- Department of Internal Medicine, Hirosaki Stroke and Rehabilitation Center, Hirosaki, 036-8104 Japan; Aomori University of Health and Welfare Graduate School of Health Sciences, Aomori, 030-0947 Japan.
| | - Joji Hagii
- Department of Internal Medicine, Hirosaki Stroke and Rehabilitation Center, Hirosaki, 036-8104 Japan
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Moriyama T, Todo K, Yamagami H, Kimura Y, Yamamoto S, Nagano K, Doijiri R, Yamazaki H, Sonoda K, Koge J, Nakayama T, Iwata T, Ueno Y, Gon Y, Okazaki S, Sasaki T, Mochizuki H. Relationship between initial B-type natriuretic peptide levels and detection of atrial fibrillation with an insertable cardiac monitor in cryptogenic stroke: CRYPTON-ICM registry. Front Neurol 2024; 15:1436062. [PMID: 39359870 PMCID: PMC11445933 DOI: 10.3389/fneur.2024.1436062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 09/06/2024] [Indexed: 10/04/2024] Open
Abstract
High B-type natriuretic peptide (BNP) levels are associated with new atrial fibrillation (AF). This study investigated the distribution of AF detection rates according to BNP levels in patients with cryptogenic stroke (CS) using an insertable cardiac monitor (ICM). We enrolled consecutive patients with CS who underwent ICM implantation between October 2016 and September 2020 at eight stroke centers in Japan. Those with BNP levels were divided into three groups by tertiles. We evaluated the association of BNP levels with AF detection. Youden's index was calculated to identify the optimal cutoff for BNP. Of 417 patients, we analyzed 266 patients with BNP data. The tertile range of BNP level was 19.0 to 48.5 pg/mL. AF detection rate was 13.3%/year, 12.8%/year, and 53.7%/year in the low-BNP (≤19.0), mid-BNP (19.1-48.4), and high-BNP (≥48.5) groups, respectively (log-rank trend p < 0.01). Compared with low-BNP group, the adjusted hazard ratios for AF detection in mid-and high-BNP groups were 0.91 [95% confidence interval (CI) 0.46-1.78] and 2.17 (95% CI 1.14-4.13), respectively. Receiver operating characteristic curve analysis showed the optimal cutoff value was 43.4 pg/mL. The area under curve using BNP to predict AF detection was 0.69. The BNP level was associated with AF detection in patients with CS. This relationship changed around the BNP levels of 40-50 pg/mL.
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Affiliation(s)
- Takuya Moriyama
- Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan
- Department of Neurology, NHO Osaka National Hospital, Osaka, Japan
| | - Kenichi Todo
- Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroshi Yamagami
- Department of Neurology, NHO Osaka National Hospital, Osaka, Japan
- Division of Stroke Prevention and Treatment, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Yoko Kimura
- Department of Neurology, NHO Osaka National Hospital, Osaka, Japan
| | - Shiro Yamamoto
- Department of Neurology, NHO Osaka National Hospital, Osaka, Japan
| | - Keiko Nagano
- Department of Neurology, NHO Osaka National Hospital, Osaka, Japan
| | - Ryosuke Doijiri
- Department of Neurology, Iwate Prefectural Central Hospital, Morioka, Japan
| | - Hidekazu Yamazaki
- Department of Neurology, Yokohama Shintoshi Neurosurgical Hospital, Yokohama, Japan
| | - Kazutaka Sonoda
- Department of Neurology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan
| | - Junpei Koge
- Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Taira Nakayama
- Department of Neurology, Tokai University, Isehara, Japan
| | - Tomonori Iwata
- Department of Neurology, Tokai University, Isehara, Japan
| | - Yuji Ueno
- Department of Neurology, Juntendo University Faculty of Medicine, Bunkyo, Japan
| | - Yasufumi Gon
- Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Shuhei Okazaki
- Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan
- Department of Neurology, NHO Osaka National Hospital, Osaka, Japan
| | - Tsutomu Sasaki
- Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hideki Mochizuki
- Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan
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Johansen MC, von Rennenberg R, Nolte CH, Jensen M, Bustamante A, Katan M. Role of Cardiac Biomarkers in Stroke and Cognitive Impairment. Stroke 2024; 55:2376-2384. [PMID: 39016019 PMCID: PMC11347090 DOI: 10.1161/strokeaha.123.044143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2024]
Abstract
This topical review assesses the growing role of cardiac biomarkers beyond cardiovascular health and focuses on their importance in stroke and dementia. The first part describes blood-based cardiac biomarkers in patients with stroke and highlights applications in the setting of early diagnosis, poststroke complications, outcome prediction as well as secondary prevention. Among other applications, natriuretic peptides can be helpful in differentiating stroke subtypes. They are also currently being investigated to guide prolonged ECG monitoring and secondary prevention in patients with stroke. Elevated cardiac troponin after ischemic stroke can provide information about various poststroke complications recently termed the stroke-heart syndrome. The second part focuses on the role of cardiac biomarkers in vascular cognitive impairment and dementia, emphasizing their association with structural brain lesions. These lesions such as silent brain infarcts and white matter hyperintensities often co-occur with cardiac disease and may be important mediators between cardiovascular disease and subsequent cognitive decline. ECG and echocardiogram measurements, in addition to blood-based biomarkers, show consistent associations with vascular brain changes and incident dementia, suggesting a role in indicating risk for cognitive decline. Together, the current evidence suggests that cardiac blood-based, electrophysiological, and imaging biomarkers can be used to better understand the heart and brain connection in the setting of not only stroke but also dementia.
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Affiliation(s)
- Michelle C. Johansen
- Department of Neurology, Cerebrovascular Division, John Hopkins University School of Medicine, Baltimore, USA
| | - Regina von Rennenberg
- Department of Neurology with experimental Neurology and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Christian H. Nolte
- Department of Neurology with experimental Neurology and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Märit Jensen
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Alejandro Bustamante
- Stroke Unit, Department of Neurology, Hospital Universitari Germans Trias i Pujol, Germans Trias i Pujol Research Institute (IGTP) Barcelona, Spain
| | - Mira Katan
- Department of Neurology, Stroke Center, University and University Hospital of Basel, Basel, Switzerland
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Patel J, Bhaskar SMM. Diagnostic Utility of N-Terminal Pro-B-Type Natriuretic Peptide in Identifying Atrial Fibrillation Post-Cryptogenic Stroke: A Systematic Review and Meta-Analysis. PATHOPHYSIOLOGY 2024; 31:331-349. [PMID: 39051222 PMCID: PMC11270372 DOI: 10.3390/pathophysiology31030024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 06/12/2024] [Accepted: 06/29/2024] [Indexed: 07/27/2024] Open
Abstract
BACKGROUND Atrial fibrillation (AF) significantly contributes to acute ischemic stroke, with undetected AF being a common culprit in cryptogenic strokes. N-terminal pro-B-type natriuretic peptide (NT-proBNP), indicative of myocardial stress, has been proposed as a biomarker for AF detection, aiding in the selection of patients for extended cardiac monitoring. However, the diagnostic accuracy of NT-proBNP remains uncertain. METHODS We conducted a meta-analysis to evaluate the diagnostic accuracy of NT-proBNP in detecting AF among cryptogenic stroke patients. A comprehensive literature search was conducted across PubMed, Embase, and Cochrane databases to identify relevant studies. Studies reporting NT-proBNP levels in stroke patients and data on the proportion of patients with AF above a specified cut-off were included. Meta-analyses were performed using the midas command in STATA. RESULTS Seven studies encompassing 2171 patients were included in the analysis, of which five studies contained cohorts with cryptogenic strokes. Among patients with cryptogenic stroke, NT-proBNP demonstrated a diagnostic accuracy of 80% (Area Under the Receiver Operating Curve 0.80 [95% CI 0.76-0.83]), with a sensitivity of 81% (95% CI 0.68-0.89) and a specificity of 68% (95% CI 0.60-0.75). CONCLUSION Our meta-analysis indicates that NT-proBNP exhibits a good-to-very-good diagnostic accuracy for detecting AF in patients with cryptogenic stroke. These findings suggest potential implications for utilizing NT-proBNP in guiding the selection of patients for prolonged cardiac monitoring, thereby aiding in the management of cryptogenic stroke cases.
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Affiliation(s)
- Jay Patel
- Global Health Neurology Laboratory, Sydney, NSW 2150, Australia;
- UNSW Medicine and Health, University of New South Wales (UNSW), South West Sydney Clinical Campuses, Sydney, NSW 2170, Australia
| | - Sonu M. M. Bhaskar
- Global Health Neurology Laboratory, Sydney, NSW 2150, Australia;
- Department of Neurology & Neurophysiology, Liverpool Hospital, South West Sydney Local Health District, Liverpool, NSW 2170, Australia
- NSW Brain Clot Bank, NSW Health Pathology, Sydney, NSW 2170, Australia
- National Cerebral and Cardiovascular Center (NCVC), Department of Neurology, Division of Cerebrovascular Medicine and Neurology, Suita 564-8565, Osaka, Japan
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Justo ASDS, Nóbrega SMA, Silva ALA. Cardiac Blood-Based Biomarkers of Myocardial Stress as Predictors of Atrial Fibrillation Development in Patients With Embolic Stroke of Undetermined Source/Cryptogenic Stroke: A Systematic Review and Meta-Analysis. J Clin Neurol 2024; 20:256-264. [PMID: 38171502 PMCID: PMC11076184 DOI: 10.3988/jcn.2023.0068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 05/29/2023] [Accepted: 06/27/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND AND PURPOSE Undiagnosed atrial fibrillation (AF) is a major risk factor for stroke that can go unnoticed in individuals with embolic stroke of undetermined source (ESUS) or cryptogenic stroke (CS). Early detection is critical for stroke prognosis and secondary prevention. This study aimed to determine if blood biomarkers of myocardial stress can accurately predict AF in patients with ESUS/CS, which would allow the identification of those who would benefit from closer monitoring. METHODS In February 2023 we performed a systematic date-unrestricted search of three databases for studies on patients with ESUS/CS who were subsequently diagnosed with AF. We examined the relationships between AF and serum myocardial stress markers such as brain natriuretic peptide (BNP), N-terminal-pro-BNP (NT-proBNP), midregional proatrial natriuretic peptide, and troponin. RESULTS Among the 1,527 studies reviewed, 23 eligible studies involving 6,212 participants, including 864 with AF, were analyzed. A meta-analysis of 9 studies indicated that they demonstrated a clear association between higher NT-proBNP levels and an increased risk of AF, with adjusted and raw data indicating 3.06- and 9.03-fold higher AF risks, respectively. Lower NT-proBNP levels had a pooled negative predictive value of 91.7%, indicating the potential to rule out AF with an 8% false-negative rate. CONCLUSIONS Further research is required to fully determine the potential of biomarkers for AF detection after stroke, as results from previous studies lack homogeneity. However, lower NT-proBNP levels have potential in ruling out AF in patients with ESUS/CS. Combining them with other relevant biomarkers may enhance the precision of identifying patients who will not benefit from extended monitoring, which would optimize resource allocation and patient care.
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Affiliation(s)
| | | | - Ana Luísa Aires Silva
- Department of Neurology, Faculty of Medicine, Centro Hospitalar Universitário São João, Porto, Portugal
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Anagnostopoulos I, Kousta M, Kossyvakis C, Paraskevaidis NT, Schizas N, Vrachatis D, Deftereos S, Giannopoulos G. Atrial strain and occult atrial fibrillation in cryptogenic stroke patients: a systematic review and meta-analysis. Clin Res Cardiol 2023; 112:1600-1609. [PMID: 37154833 DOI: 10.1007/s00392-023-02218-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 04/27/2023] [Indexed: 05/10/2023]
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.
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Affiliation(s)
- Ioannis Anagnostopoulos
- Cardiology Department, Athens General Hospital "G. Gennimatas", 154 Mesogion Avenue, 11527, Athens, Greece.
| | - Maria Kousta
- Cardiology Department, Athens General Hospital "G. Gennimatas", 154 Mesogion Avenue, 11527, Athens, Greece
| | - Charalampos Kossyvakis
- Cardiology Department, Athens General Hospital "G. Gennimatas", 154 Mesogion Avenue, 11527, Athens, Greece
| | | | - Nikolaos Schizas
- Department of Cardiothoracic Surgery, Hygeia Hospital, Athens, Greece
| | - Dimitrios Vrachatis
- 2nd Department of Cardiology, National and Kapodistrian University of Athens, Athens, Greece
| | - Spyridon Deftereos
- 2nd Department of Cardiology, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Giannopoulos
- 3rd Department of Cardiology, Aristotle University of Thessaloniki, Thessaloniki, Greece
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7
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Francisco Pascual J, Jordan Marchite P, Rodríguez Silva J, Rivas Gándara N. Arrhythmic syncope: From diagnosis to management. World J Cardiol 2023; 15:119-141. [PMID: 37124975 PMCID: PMC10130893 DOI: 10.4330/wjc.v15.i4.119] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/02/2023] [Accepted: 04/10/2023] [Indexed: 04/20/2023] Open
Abstract
Syncope is a concerning symptom that affects a large proportion of patients. It can be related to a heterogeneous group of pathologies ranging from trivial causes to diseases with a high risk of sudden death. However, benign causes are the most frequent, and identifying high-risk patients with potentially severe etiologies is crucial to establish an accurate diagnosis, initiate effective therapy, and alter the prognosis. The term cardiac syncope refers to those episodes where the cause of the cerebral hypoperfusion is directly related to a cardiac disorder, while arrhythmic syncope is cardiac syncope specifically due to rhythm disorders. Indeed, arrhythmias are the most common cause of cardiac syncope. Both bradyarrhythmia and tachyarrhythmia can cause a sudden decrease in cardiac output and produce syncope. In this review, we summarized the main guidelines in the management of patients with syncope of presumed arrhythmic origin. Therefore, we presented a thorough approach to syncope work-up through different tests depending on the clinical characteristics of the patients, risk stratification, and the management of syncope in different scenarios such as structural heart disease and channelopathies.
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Affiliation(s)
- Jaume Francisco Pascual
- Unitat d'Arritmies Servei de Cardiologia VHIR, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
- Grup de Recerca Cardiovascular, Vall d'Hebron Institut de Recerca, Barcelona 08035, Spain
- CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid 28029, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain.
| | - Pablo Jordan Marchite
- Unitat d'Arritmies Servei de Cardiologia VHIR, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Jesús Rodríguez Silva
- Unitat d'Arritmies Servei de Cardiologia VHIR, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
| | - Nuria Rivas Gándara
- Unitat d'Arritmies Servei de Cardiologia VHIR, Hospital Universitari Vall d'Hebron, Barcelona 08035, Spain
- CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid 28029, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain
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Diener HC, Wachter R, Wong A, Thijs V, Schnabel RB, Ntaios G, Kasner S, Rothwell PM, Passman R, Saver JL, Albers BA, Bernstein RA. Monitoring for atrial fibrillation prior to patent foramen ovale closure after cryptogenic stroke. Int J Stroke 2023; 18:400-407. [PMID: 36050817 PMCID: PMC10037544 DOI: 10.1177/17474930221124412] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Patients who had a cryptogenic stroke (CS) suspected to be causally related to a patent foramen ovale (PFO) are candidates for percutaneous PFO closure. In such patients, it is important to screen for atrial fibrillation (AF). Limited guidance is available regarding AF monitoring strategies in CS patients with PFO addressing optimal monitoring technology and duration. AIM To provide a narrative review of cardiac rhythm monitoring in CS patients considered for PFO closure, including current practices, stroke recurrences after CS, findings from monitoring studies in CS patients, and predictors for AF detection published in the literature. To propose a personalized strategy for cardiac monitoring in CS patients, accounting for aspects predicting AF detection. SUMMARY OF REVIEW AF detection in CS patients is predicted by age, left atrial enlargement, prolonged PR interval, frequent premature atrial contractions, interatrial conduction block, diabetes, prior brain infarctions, leukoaraiosis, elevated B-type natriuretic peptide (BNP)/N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and a family history of AF, as well as composed scores (e.g. CHA2DS2-VASc, atrial fibrillation in embolic stroke of undetermined source (AF-ESUS)). The causal role of the PFO may be accounted for by the risk of paradoxical embolism (RoPE) score and/or the PFO-Associated Stroke Causal Likelihood (PASCAL) classification. CONCLUSION A personalized approach to AF detection in CS patients is proposed, accounting for the likelihood of AF detection and aimed at obtaining sufficient confidence regarding the absence of AF in patients considered for PFO closure. In addition, the impact of high-risk PFO features on the monitoring strategy is discussed.
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Affiliation(s)
- Hans-Christoph Diener
- Department of Neuroepidemiology, Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), Medical Faculty of the University of Duisburg-Essen, Essen, Germany
| | - Rolf Wachter
- Department of Cardiology, University Hospital Leipzig, Leipzig, Germany
| | - Andrew Wong
- Neurology Department, Royal Brisbane and Women's Hospital and the University of Queensland, Brisbane, QLD, Australia
| | - Vincent Thijs
- Stroke Theme, The Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC, Australia
- Department of Neurology, Austin Health, Heidelberg, VIC, Australia
| | - Renate B Schnabel
- Department of Cardiology, University Heart & Vascular Center Hamburg, Hamburg, Germany
- German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
| | - George Ntaios
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Scott Kasner
- Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Peter M Rothwell
- Wolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
| | - Rod Passman
- Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jeffrey L Saver
- Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Bert A Albers
- Albers Clinical Evidence Consultancy, Winterswijk Woold, The Netherlands
| | - Richard A Bernstein
- Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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Muscari A, Evangelisti E, Faccioli L, Forti P, Ghinelli M, Puddu GM, Spinardi L, Barbara G. Probability of Cardioembolic vs. Atherothrombotic Pathogenesis of Cryptogenic Strokes in Older Patients. Am J Cardiol 2023; 192:51-59. [PMID: 36736013 DOI: 10.1016/j.amjcard.2022.12.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 11/12/2022] [Accepted: 12/26/2022] [Indexed: 02/04/2023]
Abstract
Some clinical, laboratory, ECG, and echocardiographic parameters could provide useful indications to assess the probability of cardioembolism or atherothrombosis in cryptogenic strokes. We retrospectively examined 290 patients with ischemic stroke aged ≥60 years, divided into 3 groups: strokes originating from large artery atherothrombosis (n = 92), cardioembolic strokes caused by paroxysmal atrial fibrillation (n = 88) and cryptogenic strokes (n = 110). In addition to echocardiographic and routine clinical-laboratory variables, neutrophil:lymphocyte ratio, red blood cell distribution width, mean platelet volume, P wave and PR interval duration and biphasic inferior P waves, both on admission and after 7 to 10 days, were also considered. By multiple logistic regression, cardioembolic strokes were compared with large artery atherothrombosis strokes, and beta coefficients were rounded to produce a scoring system. Late PR interval ≥188 ms, left atrium ≥4 cm, left ventricular end-diastolic volume <65 ml, and posterior circulation syndrome were associated with paroxysmal atrial fibrillation (positive scores). In contrast, male gender, hypercholesterolemia, and initial platelet count ≥290 × 109/L were associated with atherothrombosis of large arteries (negative scores). The algebraic sum of these scores produced values indicative of cardioembolism if >0 (positive predictive value 89.1%), or of atherothrombosis, if ≤0 (positive predictive value 72.5%). The area under the receiver operating characteristic curve was 0.85. Among cryptogenic strokes, 41.5% had a score >0 (probable atrial fibrillation) and 58.5% had a score ≤0 (possible atherothrombosis). In conclusion, a scoring system based on electrocardiogram, laboratory, clinical and echocardiographic parameters can provide useful guidance for further investigations and secondary prevention in older patients with cryptogenic stroke.
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Affiliation(s)
- Antonio Muscari
- Stroke Unit; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
| | - Eleonora Evangelisti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Paola Forti
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Marco Ghinelli
- Department of Cardiothoracic and Vascular Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | | | - Giovanni Barbara
- Stroke Unit; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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10
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Kerr B, Brandon L. Atrial Fibrillation, thromboembolic risk, and the potential role of the natriuretic peptides, a focus on BNP and NT-proBNP - A narrative review. IJC HEART & VASCULATURE 2022; 43:101132. [PMID: 36246770 PMCID: PMC9562601 DOI: 10.1016/j.ijcha.2022.101132] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/30/2022] [Accepted: 10/05/2022] [Indexed: 10/25/2022]
Abstract
Atrial fibrillation (AF) is one of the most commonly encountered arrythmia in clinical practice. AF itself can be driven by genetic predisposition, ectopic electrical activity, and abnormal atrial tissue substrates. Often there is no single etiological mechanism, but rather a combination of factors that feed back to remodel and worsen tissue substrate, "AF begets AF". The clinical consequences of AF can often include emboli, heart failure, and early mortality. The classical AF cardioembolic (CE) concept requires thrombus formation in the left atrial appendage, with subsequent embolization. The temporal dissociation between AF occurrence and CE events has thrown doubt on AF as the driver of this mechanism. Instead, there has been a resurgence of the "atrial cardiomyopathy" (ACM) concept. An ACM is proposed as a potential mechanism of embolic disease through promotion of prothrombotic mechanisms, with AF instead reflecting atrial disease severity. Regardless, AF has been implicated in 25% to 30% of cryptogenic strokes. Natriuretic peptide(NP)s have been shown to be elevated in AF, with higher levels of both NT-proBNP and BNP being predictive of incidental AF. NPs potentially reflect the atrial environment and could be used to identify an underlying ACM. Therefore, this narrative review examines this evidence and mechanisms that may underpin the role of NPs in identifying atrial dysfunction, with focus on both, BNP and NTproBNP. We explore their potential role in the prediction and screening for both, ACM and AF. Moreover, we compare both NPs directly to ascertain a superior biomarker.
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Key Words
- ACM, Atrial cardiomyopathy
- AF, Atrial fibrillation
- ARISTOTLE trial, Apixaban For Reduction In Stroke And Other Thromboembolic Events In Atrial Fibrillation Trial
- ASSERT trial, Atrial Fibrillation Evaluation In Pacemaker Patient’s Trial
- ASSERT-II trial, Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial
- AUC, Area Under The Curve
- Atrial cardiomyopathy
- Atrial fibrillation
- BNP
- BNP, Brain natriuretic peptide
- CE, Cardioembolic
- CHA2DS2-Vasc, Congestive Heart Failure, Hypertension, Age ≥ 75, Diabetes, Stroke/TIA/Thromboembolism, Vascular Disease, Age 65–74
- CHARGE, Cohorts For Heart And Aging Research In Genomic Epidemiology
- CI, Confidence Intervals
- CNP, C-type natriuretic peptide
- EHRAS, EHRA/ HRS/APHRS/SOLAECE
- ESUS, Embolic Stroke of Unknown Source
- IMPACT Trial, Implementation of An RCT To Improve Treatment With Oral Anticoagulants In Patients With Atrial Fibrillation
- MR-proANP, Mid Regional Pro-Atrial Natriuretic Peptide
- NP, Natriuretic peptide
- NT-proBNP
- NT-proBNP, N-Terminal Pro Brain Natriuretic Peptide
- Natriuretic peptides
- RE-LY study, The Randomized Evaluation of Long-Term Anticoagulation Therapy study
- SE, Standard Error
- TE, Thromboembolic event
- TIA, Transient ischemic attack
- TRENDS trial, A Prospective Study of the Clinical Significance of Atrial Arrhythmias Detected by Implanted Device Diagnostics
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Affiliation(s)
- Brian Kerr
- Department of Cardiology, St James Hospital, James Street, Dublin 8, Ireland
| | - Lisa Brandon
- Department of Cardiology, St James Hospital, James Street, Dublin 8, Ireland
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11
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Benito B, García-Elías A, Ois Á, Tajes M, Vallès E, Ble M, Yáñez Bisbe L, Giralt-Steinhauer E, Rodríguez-Campello A, Cladellas Capdevila M, Martí-Almor J, Roquer J, Cuadrado-Godia E. Plasma levels of miRNA-1-3p are associated with subclinical atrial fibrillation in patients with cryptogenic stroke. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2022; 75:717-726. [PMID: 35067470 DOI: 10.1016/j.rec.2021.12.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 11/30/2021] [Indexed: 06/14/2023]
Abstract
INTRODUCTION AND OBJECTIVES Identifying biomarkers of subclinical atrial fibrillation (AF) is of most interest in patients with cryptogenic stroke (CrS). We sought to evaluate the circulating microRNA (miRNA) profile of patients with CrS and AF compared with those in persistent sinus rhythm. METHODS Among 64 consecutive patients with CrS under continuous monitoring by a predischarge insertable monitor, 18 patients (9 with AF and 9 in persistent sinus rhythm) were selected for high-throughput determination of 754 miRNAs. Nine patients with concomitant stroke and AF were also screened to improve the yield of miRNA selection. Differentially expressed miRNAs were replicated in an independent cohort (n=46). Biological markers were stratified by the median and included in logistic regression analyses to evaluate their association with AF at 6 and 12 months. RESULTS Eight miRNAs were differentially expressed between patients with and without AF. In the replication cohort, miR-1-3p, a gene regulator involved in cardiac arrhythmogenesis, was the only miRNA to remain significantly higher in patients with CrS and AF vs those in sinus rhythm and showed a modest association with AF burden. High (= above the median) miR-1-3p plasma values, together with a low left atrial ejection fraction, were independently associated with the presence of AF at 6 and 12 months. CONCLUSIONS In this cohort, plasma levels of miR-1-3p were elevated in CrS patients with subsequent AF. Our results preliminarily suggest that miR-1-3p could be a novel biomarker that, together with clinical parameters, could help identify patients with CrS and a high risk of occult AF.
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Affiliation(s)
- Begoña Benito
- Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Spain.
| | - Anna García-Elías
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Research Center, Montreal Heart Institute, Montreal, Canada
| | - Ángel Ois
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Servicio de Neurología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Marta Tajes
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain
| | - Ermengol Vallès
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Servicio de Cardiología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Mireia Ble
- Servicio de Cardiología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | | | - Eva Giralt-Steinhauer
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Servicio de Cardiología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Ana Rodríguez-Campello
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Servicio de Cardiología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Mercè Cladellas Capdevila
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Servicio de Cardiología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Julio Martí-Almor
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Servicio de Cardiología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Jaume Roquer
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Servicio de Cardiología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Elisa Cuadrado-Godia
- Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Parc de Salut Mar, Barcelona, Spain; Servicio de Cardiología, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
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12
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Palà E, Bustamante A, Pagola J, Juega J, Francisco-Pascual J, Penalba A, Rodriguez M, De Lera Alfonso M, Arenillas JF, Cabezas JA, Pérez-Sánchez S, Moniche F, de Torres R, González-Alujas T, Clúa-Espuny JL, Ballesta-Ors J, Ribas D, Acosta J, Pedrote A, Gonzalez-Loyola F, Gentile Lorente D, Ángel Muñoz M, Molina CA, Montaner J. Blood-Based Biomarkers to Search for Atrial Fibrillation in High-Risk Asymptomatic Individuals and Cryptogenic Stroke Patients. Front Cardiovasc Med 2022; 9:908053. [PMID: 35859587 PMCID: PMC9289129 DOI: 10.3389/fcvm.2022.908053] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 06/15/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Atrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations. METHODS Two hundred seventy-four subjects aged 65-75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately. RESULTS Atrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665-0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654-0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively. CONCLUSION Blood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.
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Affiliation(s)
- Elena Palà
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research, Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Alejandro Bustamante
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research, Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
- Stroke Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Jorge Pagola
- Stroke Unit, Medicine Department, Vall d’Hebrón Hospital and Autonomous University of Barcelona, Barcelona, Spain
| | - Jesus Juega
- Stroke Unit, Medicine Department, Vall d’Hebrón Hospital and Autonomous University of Barcelona, Barcelona, Spain
| | - Jaume Francisco-Pascual
- Arrhythmia Unit-Cardiology Department, Vall d’Hebrón Hospital, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain
| | - Anna Penalba
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research, Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maite Rodriguez
- Stroke Unit, Medicine Department, Vall d’Hebrón Hospital and Autonomous University of Barcelona, Barcelona, Spain
| | | | | | | | | | | | - Reyes de Torres
- Stroke Unit, University Hospital Virgen Macarena, Seville, Spain
| | - Teresa González-Alujas
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain
- Echocardiography Lab Cardiology Department, Vall d’Hebrón Hospital, Barcelona, Spain
| | - Josep Lluís Clúa-Espuny
- Equip d’Atenció Primària Tortosa Est, SAP Terres de l’Ebre, Institut Català de la Salut, Tortosa, Spain
- Institut d’Investigació en Atenció Primària IDIAP Jordi Gol, Ebrictus Group, Barcelona, Spain
| | - Juan Ballesta-Ors
- Institut d’Investigació en Atenció Primària IDIAP Jordi Gol, Ebrictus Group, Barcelona, Spain
| | - Domingo Ribas
- EAP Sant Pere i Sant Pau, DAP Camp de Tarragona, Institut Català de la Salut, Tarragona, Spain
| | - Juan Acosta
- Department of Cardiology, Hospital Universitario Virgen del Rocio, Seville, Spain
| | - Alonso Pedrote
- Department of Cardiology, Hospital Universitario Virgen del Rocio, Seville, Spain
| | - Felipe Gonzalez-Loyola
- Gerència Atenció Primària de Barcelona, Institut Català de la Salut, Barcelona, Spain
- Institut d’Investigació en Atenció Primària IDIAP Jordi Gol, Unitat Suport Recerca Barcelona, Barcelona, Spain
| | - Delicia Gentile Lorente
- Institut d’Investigació en Atenció Primària IDIAP Jordi Gol, Ebrictus Group, Barcelona, Spain
- Cardiology Department, Hospital Verge de la Cinta, Institut Català de la Salut, Tortosa, Spain
| | - Miguel Ángel Muñoz
- Gerència Atenció Primària de Barcelona, Institut Català de la Salut, Barcelona, Spain
- Institut d’Investigació en Atenció Primària IDIAP Jordi Gol, Unitat Suport Recerca Barcelona, Barcelona, Spain
| | - Carlos A. Molina
- Stroke Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Joan Montaner
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research, Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
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Diener HC, Easton JD, Hart RG, Kasner S, Kamel H, Ntaios G. Review and update of the concept of embolic stroke of undetermined source. Nat Rev Neurol 2022; 18:455-465. [PMID: 35538232 DOI: 10.1038/s41582-022-00663-4] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2022] [Indexed: 12/28/2022]
Abstract
Ischaemic strokes have traditionally been classified according to the TOAST criteria, in which strokes with unclear aetiology are classified as cryptogenic strokes. However, the definition of cryptogenic stroke did not meet the operational criteria necessary to define patient populations for randomized treatment trials. To address this problem, the concept of embolic stroke of undetermined source (ESUS) was developed and published in 2014. A hypothesis that underpinned this concept was that most strokes in patients with ESUS are caused by embolic events, perhaps many cardioembolic, and that anticoagulation would prevent secondary ischaemic events. On this basis, two large randomized trials were conducted to compare the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran and rivaroxaban with aspirin. Neither NOAC was superior to aspirin in these trials, although subgroups of patients with ESUS seemed to benefit specifically from anticoagulation or antiplatelet therapy. The neutral results of the trials of anticoagulation and insights into ESUS from research conducted since the concept was introduced warrant reassessment of the ESUS construct as a research concept and a treatment target. In this Review, we discuss the evidence produced since the concept of ESUS was introduced, and propose updates to the criteria and diagnostic algorithm in light of the latest knowledge.
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Affiliation(s)
- Hans-Christoph Diener
- Department of Neuroepidemiology, Institute for Medical Informatics, Biometry and Epidemiology (IMIBE) Medical Faculty of the University Duisburg-Essen, Essen, Germany.
| | - J Donald Easton
- Department of Neurology, University of California, San Francisco, San Francisco, CA, USA
| | - Robert G Hart
- Population Health Research Institute/McMaster University, David Braley Cardiac, Vascular and Stroke Research Institute (DBCVSRI), Hamilton, Ontario, Canada
| | - Scott Kasner
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Hooman Kamel
- Clinical and Translational Neuroscience Unit, Department of Neurology and Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
| | - George Ntaios
- Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
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14
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Palà E, Pagola J, Juega J, Francisco-Pascual J, Penalba A, Rodriguez M, De Lera Alfonso M, Arenillas JF, Cabezas JA, Moniche F, de Torres R, Perez-Sanchez S, González-Alujas T, Molina CA, Bustamante A, Montaner J. Proteins and pathways in atrial fibrillation and atrial cardiomyopathy underlying cryptogenic stroke. IJC HEART & VASCULATURE 2022; 39:100977. [PMID: 35281755 PMCID: PMC8913305 DOI: 10.1016/j.ijcha.2022.100977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 11/21/2022]
Abstract
BACKGROUND Atrial fibrillation (AF) is one of the most prevalent causes of cryptogenic stroke. Also, apart from AF itself, structural and remodelling changes in the atria might be an underlying cause of cryptogenic stroke. We aimed to discover circulating proteins and reveal pathways altered in AF and atrial cardiomyopathy, measured by left atrial volume index (LAVI) and peak atrial longitudinal strain (PALS), in patients with cryptogenic stroke. METHODS An aptamer array (including 1310 proteins) was measured in the blood of 20 cryptogenic stroke patients monitored during 28 days with a Holter device as a case-control study of the Crypto-AF cohort. Protein levels were compared between patients with (n = 10) and without AF (n = 10) after stroke, and the best candidates were tested in 111 patients from the same cohort (44 patients with AF and 67 without AF). In addition, in the first 20 patients, proteins were explored according to PALS and LAVI values. RESULTS Forty-six proteins were differentially expressed in AF cases. Of those, four proteins were tested in a larger sample size. Only DPP7, presenting lower levels in AF patients, was further validated. Fifty-seven proteins correlated with LAVI, and 270 correlated with PALS. NT-proBNP was common in all the discovery analyses performed. Interestingly, many proteins and pathways were altered in patients with low PALS. CONCLUSIONS Multiple proteins and pathways related to AF and atrial cardiomyopathy have been revealed. The role of DPP7 as a biomarker for stroke aetiology should be further explored. Moreover, the present study may be considered hypothesis-generating.
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Affiliation(s)
- Elena Palà
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Spain
| | - Jorge Pagola
- Stroke Unit, Vall d’Hebrón Hospital and Autonomous University of Barcelona, Medicine Department, Barcelona, Spain
| | - Jesus Juega
- Stroke Unit, Vall d’Hebrón Hospital and Autonomous University of Barcelona, Medicine Department, Barcelona, Spain
| | - Jaume Francisco-Pascual
- Arrhythmia Unit-Cardiology Department, Vall d’Hebrón Hospital, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, CIBERCV, Spain
| | - Anna Penalba
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Spain
| | - Maite Rodriguez
- Stroke Unit, Vall d’Hebrón Hospital and Autonomous University of Barcelona, Medicine Department, Barcelona, Spain
| | | | | | | | | | - Reyes de Torres
- Stroke Unit, University Hospital Virgen Macarena, Seville, Spain
| | | | - Teresa González-Alujas
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, CIBERCV, Spain
- Echocardiography Lab Cardiology Department, Vall d’Hebrón Hospital, Barcelona, Spain
| | - Carlos A. Molina
- Stroke Unit, Vall d’Hebrón Hospital and Autonomous University of Barcelona, Medicine Department, Barcelona, Spain
| | - Alejandro Bustamante
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Spain
| | - Joan Montaner
- Neurovascular Research Laboratory, Vall d’Hebron Institute of Research (VHIR), Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Spain
- Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville & Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain
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15
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Benito B, García-Elías A, Ois Á, Tajes M, Vallès E, Ble M, Yáñez Bisbe L, Giralt-Steinhauer E, Rodríguez-Campello A, Cladellas Capdevila M, Martí-Almor J, Roquer J, Cuadrado-Godia E. La concentración plasmática de microARN-1-3p se asocia con fibrilación auricular subclínica en los pacientes con ictus criptogénico. Rev Esp Cardiol 2022. [DOI: 10.1016/j.recesp.2021.11.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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16
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Werhahn SM, Becker C, Mende M, Haarmann H, Nolte K, Laufs U, Zeynalova S, Löffler M, Dagres N, Husser D, Dörr M, Gross S, Felix SB, Petersmann A, Herrmann‐Lingen C, Binder L, Scherer M, Hasenfuß G, Pieske B, Edelmann F, Wachter R. NT-proBNP as a marker for atrial fibrillation and heart failure in four observational outpatient trials. ESC Heart Fail 2022; 9:100-109. [PMID: 34850596 PMCID: PMC8788004 DOI: 10.1002/ehf2.13703] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 10/10/2021] [Accepted: 10/29/2021] [Indexed: 01/04/2023] Open
Abstract
AIMS Heart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). It is known that AF impairs the diagnostic accuracy of NT-proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT-proBNP for HF and AF in stable outpatients with cardiovascular risk factors. METHODS AND RESULTS Data were obtained from the DIAST-CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population-based cohorts using the same inclusion/exclusion criteria: LIFE-Adult (n = 2869), SHIP (n = 2013), and SHIP-TREND (n = 2408). Serum levels of NT-proBNP were taken once at baseline. The DIAST-CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF (n = 1375) had a median NT-proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF (n = 93), NT-proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group (P < 0.001) and compared with those with only HF [n = 201; 158 (66;363) pg/mL; P < 0.001]. The highest levels of NT-proBNP [868 (213;1397) pg/mL] were measured in patients with concomitant HF and AF (n = 58; P < 0.001 vs. control and vs. HF, P = 1.0 vs. AF). In patients with AF, NT-proBNP levels did not differ between those with HF and preserved ejection fraction (EF) > 50% [n = 38; 603 (175;1070) pg/mL] and those without HF (P = 1.0). Receiver-operating characteristic curves of NT-proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79-0.88]) and for HF with EF < 50% (0.78 [0.72-0.85]; P = 0.18). The AUC for HF with EF > 50% was significantly lower (0.61 [0.56-0.65]) than for AF (P = 0.001). During follow-up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT-proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75-0.83]) than of newly diagnosed HF (0.59 [0.55-0.63]; P < 0.001). Data were validated in three independent population-based cohorts (LIFE-Adult, n = 2869; SHIP, n = 2013; and SHIP-TREND, n = 2408). CONCLUSIONS In stable outpatients, NT-proBNP is a better marker for prevalent and incident AF than for HF. In AF patients, the diagnostic value of NT-proBNP for HF with EF > 50% is very limited.
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Affiliation(s)
- Stefanie M. Werhahn
- Clinic for Cardiology and PneumologyUniversity Medical Center GöttingenGöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Christian Becker
- Clinic for Cardiology and PneumologyUniversity Medical Center GöttingenGöttingenGermany
| | - Meinhard Mende
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE)University Hospital LeipzigLeipzigGermany
| | - Helge Haarmann
- Clinic for Cardiology and PneumologyUniversity Medical Center GöttingenGöttingenGermany
| | - Kathleen Nolte
- Clinic for Cardiology and PneumologyUniversity Medical Center GöttingenGöttingenGermany
| | - Ulrich Laufs
- Department of CardiologyUniversity Hospital, Leipzig UniversityLeipzigGermany
| | - Samira Zeynalova
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE)University Hospital LeipzigLeipzigGermany
- LIFE Research Center for Civilization DiseasesLeipzigGermany
| | - Markus Löffler
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE)University Hospital LeipzigLeipzigGermany
- LIFE Research Center for Civilization DiseasesLeipzigGermany
| | | | - Daniela Husser
- Department of ElectrophysiologyHeart CenterLeipzigGermany
| | - Marcus Dörr
- Department of Internal Medicine BUniversity Medicine GreifswaldGreifswaldGermany
- German Centre for Cardiovascular Research (DZHK), partner site GreifswaldGreifswaldGermany
| | - Stefan Gross
- Department of Internal Medicine BUniversity Medicine GreifswaldGreifswaldGermany
- German Centre for Cardiovascular Research (DZHK), partner site GreifswaldGreifswaldGermany
| | - Stephan B. Felix
- Department of Internal Medicine BUniversity Medicine GreifswaldGreifswaldGermany
- German Centre for Cardiovascular Research (DZHK), partner site GreifswaldGreifswaldGermany
| | - Astrid Petersmann
- Institute of Clinical Chemistry and Laboratory MedicineUniversity Medicine GreifswaldGreifswaldGermany
| | - Christoph Herrmann‐Lingen
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
- Department of Psychosomatic Medicine and PsychotherapyUniversity of Oldenburg Medical CentreOldenburgGermany
| | - Lutz Binder
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
- Institute for Clinical Chemistry/UMG‐LaboratoriesUniversity Medical Center GöttingenGöttingenGermany
| | - Martin Scherer
- Department of Primary Medical CareUniversity Medical Centre Hamburg‐EppendorfHamburgGermany
| | - Gerd Hasenfuß
- Clinic for Cardiology and PneumologyUniversity Medical Center GöttingenGöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
| | - Burkert Pieske
- Department of CardiologyCharité University Medicine, Campus Virchow KlinikumBerlinGermany
- German Centre for Cardiovascular Research (DZHK), partner site BerlinBerlinGermany
- German Heart CenterBerlinGermany
| | - Frank Edelmann
- Clinic for Cardiology and PneumologyUniversity Medical Center GöttingenGöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
- Department of CardiologyCharité University Medicine, Campus Virchow KlinikumBerlinGermany
- German Centre for Cardiovascular Research (DZHK), partner site BerlinBerlinGermany
| | - Rolf Wachter
- Clinic for Cardiology and PneumologyUniversity Medical Center GöttingenGöttingenGermany
- German Centre for Cardiovascular Research (DZHK), partner site GöttingenGöttingenGermany
- Department of CardiologyUniversity Hospital, Leipzig UniversityLeipzigGermany
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Lip GYH, Lane DA, Lenarczyk R, Boriani G, Doehner W, Benjamin LA, Fisher M, Lowe D, Sacco RL, Schnabel R, Watkins C, Ntaios G, Potpara T. OUP accepted manuscript. Eur Heart J 2022; 43:2442-2460. [PMID: 35552401 PMCID: PMC9259378 DOI: 10.1093/eurheartj/ehac245] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 03/11/2022] [Accepted: 04/27/2022] [Indexed: 11/12/2022] Open
Abstract
The management of patients with stroke is often multidisciplinary, involving various specialties and healthcare professionals. Given the common shared risk factors for stroke and cardiovascular disease, input may also be required from the cardiovascular teams, as well as patient caregivers and next-of-kin. Ultimately, the patient is central to all this, requiring a coordinated and uniform approach to the priorities of post-stroke management, which can be consistently implemented by different multidisciplinary healthcare professionals, as part of the patient ‘journey’ or ‘patient pathway,’ supported by appropriate education and tele-medicine approaches. All these aspects would ultimately aid delivery of care and improve patient (and caregiver) engagement and empowerment. Given the need to address the multidisciplinary approach to holistic or integrated care of patients with heart disease and stroke, the European Society of Cardiology Council on Stroke convened a Task Force, with the remit to propose a consensus on Integrated care management for optimizing the management of stroke and associated heart disease. The present position paper summarizes the available evidence and proposes consensus statements that may help to define evidence gaps and simple practical approaches to assist in everyday clinical practice. A post-stroke ABC pathway is proposed, as a more holistic approach to integrated stroke care, would include three pillars of management:
A: Appropriate Antithrombotic therapy. B: Better functional and psychological status. C: Cardiovascular risk factors and Comorbidity optimization (including lifestyle changes).
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Affiliation(s)
| | - Deirdre A Lane
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Radosław Lenarczyk
- Division of Medical Sciences in Zabrze, Department of Cardiology, Congenital Heart Diseases and Electrotherapy, The Medical University of Silesia, Silesian Center of Heart Diseases, Curie-Sklodowska Str 9, 41-800 Zabrze, Poland
| | - Giuseppe Boriani
- Cardiology Division, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Policlinico di Modena, Modena, Italy
| | - Wolfram Doehner
- BIH Center for Regenerative Therapies (BCRT) and Department of Internal Medicine and Cardiology (Virchow Klinikum), German Centre for Cardiovascular Research (DZHK) partner site Berlin and Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Laura A Benjamin
- Laboratory of Molecular and Cell Biology, University College London National Hospital for Neurology and Neurosurgery, Queen Square, London
| | - Marc Fisher
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Deborah Lowe
- Wirral University Teaching Hospital NHS Foundation Trust, Wirral CH49 5PE, UK
| | - Ralph L Sacco
- UM Clinical & Translational Science Institute, University of Miami, Miller School of Medicine, Miami, FL, USA
| | - Renate Schnabel
- University Heart & Vascular Center Hamburg Eppendorf, German Center for Cardiovascular Research (DZHK) partner site Hamburg/Kiel/Lübeck, Hamburg, Germany
| | - Caroline Watkins
- Faculty of Health and Care, University of Central Lancashire, Preston PR1 2HE, UK
| | - George Ntaios
- Department of Internal Medicine, School of Health Sciences, Faculty of Medicine, University of Thessaly, Larissa, Greece
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18
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Francisco-Pascual J, Cantalapiedra-Romero J, Pérez-Rodon J, Benito B, Santos-Ortega A, Maldonado J, Ferreira-Gonzalez I, Rivas-Gándara N. Cardiac monitoring for patients with palpitations. World J Cardiol 2021; 13:608-627. [PMID: 34909127 PMCID: PMC8641003 DOI: 10.4330/wjc.v13.i11.608] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 06/27/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023] Open
Abstract
Palpitations are one of the most common reasons for medical consultation. They tend to worry patients and can affect their quality of life. They are often a symptom associated with cardiac rhythm disorders, although there are other etiologies. For diagnosis, it is essential to be able to reliably correlate the symptoms with an electrocardiographic record allowing the identification or ruling out of a possible rhythm disorder. However, reaching a diagnosis is not always simple, given that they tend to be transitory symptoms and the patient is frequently asymptomatic at the time of assessment. In recent years, electrocardiographic monitoring systems have incorporated many technical improvements that solve several of the 24-h Holter monitor limitations. The objective of this review is to provide an update on the different monitoring methods currently available, remarking their indications and limitations, to help healthcare professionals to appropriately select and use them in the work-up of patients with palpitations.
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Affiliation(s)
- Jaume Francisco-Pascual
- Unitat d'Arritmies, Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid 28029, Spain.
| | - Javier Cantalapiedra-Romero
- Unitat d'Arritmies, Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
| | - Jordi Pérez-Rodon
- Unitat d'Arritmies, Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Begoña Benito
- Unitat d'Arritmies, Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Alba Santos-Ortega
- Unitat d'Arritmies, Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Jenson Maldonado
- Unitat d'Arritmies, Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
| | - Ignacio Ferreira-Gonzalez
- Unitat d'Arritmies, Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Nuria Rivas-Gándara
- Unitat d'Arritmies, Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona 08035, Spain
- Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid 28029, Spain
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19
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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. Predictive value of left atrial function for latent paroxysmal atrial fibrillation as the cause of embolic stroke of undetermined source. J Cardiol 2021; 78:355-361. [PMID: 34119401 DOI: 10.1016/j.jjcc.2021.05.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/28/2021] [Accepted: 05/05/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND In patients with embolic stroke of undetermined source (ESUS), paroxysmal atrial fibrillation (AF) is often diagnosed, however, the risk of paroxysmal AF in ESUS has not been well described. Several studies have suggested a linkage between left atrial (LA) functional parameters and risk of AF in stroke patients. The aim of this study was to assess the role of LA functional parameters as predictors of latent paroxysmal AF in ESUS on admission. METHODS Between January 2015 and December 2019, consecutive stroke patients with suspected ESUS at admission were prospectively included in this study. They were under hospital electrocardiographic monitoring for detection of new-onset AF. Various echocardiographic parameters including left atrial strain were assessed for association with new-onset AF. RESULTS We gathered 1082 consecutive patients with ischemic stroke. After exclusions, 121 patients with suspected ESUS at admission formed the study cohort. New-onset AF was detected in 46 (38%) patients during hospital electrocardiographic monitoring (median follow-up: 18 days). LA pump and reservoir strains were significantly and independently associated with new-onset AF. Receiver operating characteristic analysis for the association with new-onset AF showed that the areas under the curve (AUCs) of clinical parameters plus one of each strain (LA pump strain: AUC: 0.86±0.04 and LA reservoir strain: AUC: 0.76±0.05) models were significantly better than plus LA volume index (AUC: 0.68±0.04, compared p-values <0.05). CONCLUSIONS LA strain was significantly associated with new development of AF. Patients with impaired LA function at admission should be carefully monitored to find AF.
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Affiliation(s)
- Kenya Kusunose
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan.
| | - Hironori Takahashi
- Ultrasound Examination Center, Tokushima University Hospital, Tokushima, Japan
| | - Susumu Nishio
- Ultrasound Examination Center, Tokushima University Hospital, Tokushima, Japan
| | - Yukina Hirata
- Ultrasound Examination Center, Tokushima University Hospital, Tokushima, Japan
| | - Robert Zheng
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
| | - Takayuki Ise
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
| | - Koji Yamaguchi
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
| | - Shusuke Yagi
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
| | - Daiju Fukuda
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
| | - Hirotsugu Yamada
- Department of Community Medicine for Cardiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Takeshi Soeki
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
| | - Tetsuzo Wakatsuki
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
| | - Kenji Shimada
- Department of Neurosurgery, Tokushima University Hospital, Tokushima, Japan
| | - Yasuhisa Kanematsu
- Department of Neurosurgery, Tokushima University Hospital, Tokushima, Japan
| | - Yasushi Takagi
- Department of Neurosurgery, Tokushima University Hospital, Tokushima, Japan
| | - Masataka Sata
- Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan
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20
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Markus A, Valerie S, Mira K. Promising Biomarker Candidates for Cardioembolic Stroke Etiology. A Brief Narrative Review and Current Opinion. Front Neurol 2021; 12:624930. [PMID: 33716927 PMCID: PMC7947187 DOI: 10.3389/fneur.2021.624930] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 01/11/2021] [Indexed: 01/09/2023] Open
Abstract
Determining the cause of stroke is considered one of the main objectives in evaluating a stroke patient in clinical practice. However, ischemic stroke is a heterogeneous disorder and numerous underlying disorders are implicated in its pathogenesis. Although progress has been made in identifying individual stroke etiology, in many cases underlying mechanisms still remain elusive. Since secondary prevention strategies are tailored toward individual stroke mechanisms, patients whose stroke etiology is unknown may not receive optimal preventive treatment. Cardioembolic stroke is commonly defined as cerebral vessel occlusion by distant embolization arising from thrombus formation in the heart. It accounts for the main proportion of ischemic strokes, and its share to stroke etiology is likely to rise even further in future decades. However, it can be challenging to distinguish cardioembolism from other possible etiologies. As personalized medicine advances, stroke researchers' focus is increasingly drawn to etiology-associated biomarkers. They can provide deeper insight regarding specific stroke mechanisms and can help to unravel previously undetected pathologies. Furthermore, etiology-associated biomarkers could play an important role in guiding future stroke prevention strategies. To achieve this, broad validation of promising candidate biomarkers as well as their implementation in well-designed randomized clinical trials is necessary. This review focuses on the most-promising candidates for diagnosis of cardioembolic stroke. It discusses existing evidence for possible clinical applications of these biomarkers, addresses current challenges, and outlines future perspectives.
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Affiliation(s)
- Arnold Markus
- Department of Neurology, University Hospital of Zurich, Zurich, Switzerland
| | - Schütz Valerie
- Department of Neurology, University Hospital of Zurich, Zurich, Switzerland
| | - Katan Mira
- Department of Neurology, University Hospital of Zurich, Zurich, Switzerland
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21
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Yan L, Huangfu C, Yang N, Li R, Yang X, Feng Y, Xuan L, Wang Q, Meng Y, Hou X, Li X. Sex- related differences in the factors associated with outcomes among patients with strokes of undetermined source: a hospital-based follow-up study. Postgrad Med 2021; 133:428-435. [PMID: 33554703 DOI: 10.1080/00325481.2021.1886770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Objective: Sex-related differences are well established among stroke patients, including the incidence and prevalence of stroke being higher among men than among women. However, the sex-related factors for differences in the outcomes of strokes of undetermined source (SUSs) have not been well described, especially in the Chinese population. We assessed the sex-related differences in the factors associated with outcomes among patients with SUSs in China.Method: Between January 2011 and December 2018, we recruited 205 patients diagnosed with SUSs from Kailuan General Hospital (China). The clinical features, risk factors, and outcome data were collected for the patients at 3 and 12 months after their strokes.Results: There were higher frequencies of hyperlipidemia (27.8% vs. 26.4%), smoking (41.4% vs. 5.6%), and alcohol consumption (21.8% vs. 0%) for male patients than for female patients. However, women were more likely than men to have hypertension (63.9% vs. 46.6%), diabetes (27.8% vs. 20.3%), and atrial fibrillation (9.7% vs. 5.3%); they were also more likely to be obese (16.7% vs. 12.0%). There were no significant differences in outcome between the sexes. Among men, severe strokes were associated with higher case fatality and disability risks at 12 months after stroke onset; hyperlipidemia was a risk factor for recurrence within 3 months of the initial stroke. Among women, severe strokes also increased the risk of disability; in women, high total cholesterol (TC) and age were associated with poor outcomes.Conclusion: The factors associated with outcomes in SUS differed by sex. For male patients, more severe stroke and hyperlipidemia were associated with poor outcomes in SUS. Risk factors for poor outcomes in female patients were stroke severity, age, and TC level. These findings suggest that taking measures to manage blood lipid levels and severe stroke among patients with SUS is important for both male and female patients and is crucial for reducing the burden of stroke in China.
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Affiliation(s)
- Lili Yan
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Chunmei Huangfu
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Na Yang
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Renzi Li
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Xiuping Yang
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Yujing Feng
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Lihui Xuan
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Qian Wang
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Yanhong Meng
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Xiaoqiang Hou
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
| | - Xuemei Li
- Department of Neurology, Kailuan General Hospital. Tangshan, Hebei Province, China
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