Skip to main content
NCBI home page
Medicine logoLink to Medicine
. 2019 Jan 25;98(4):e14086. doi: 10.1097/MD.0000000000014086

Impact of atrial fibrillation on in-hospital mortality of ischemic stroke patients and identification of promoting factors of atrial thrombi – Results from the German nationwide inpatient sample and a single-center retrospective cohort

Karsten Keller b,a,∗, Martin Geyer a, Thomas Münzel a,b,c, Mir Abolfazl Ostad a, Tommaso Gori a,b,c
Editor: Ovidiu Constantin Baltatu
PMCID: PMC6358348  PMID: 30681566

Abstract

Ischemic stroke is one of the leading causes of death and disability. Atrial fibrillation (AF) is a well-recognized risk factor for ischemic stroke.

We aimed to investigate the impact of AF on in-hospital mortality of ischemic stroke patients and to identify parameters associated with intra-cardiac thrombogenic material.

Patients were selected by screening the nationwide sample for ischemic stroke by ICD-Code (I63), stratified for AF. In this cohort, the association between in-hospital deaths and AF was investigated.

In a second study, we performed a retrospective analysis of patients who underwent transesophageal echocardiography (TEE) for various reasons, assigned these to 2 groups based on the heart-rhythm (sinus-rhythm [SR] vs AF) and examined associations between clinical and echocardiographic parameters and intra-cardiac thrombogenic material.

The Nationwide sample comprised 292,401 inpatients (48.5% females) with ischemic stroke. Incidence was 360 per 100,000 citizens, with an age-dependent increase. In-hospital mortality rate was 8.2%; AF patients had 1.85-fold higher mortality rate (12.1% vs 6.5%).

In the retrospective study, 219 patients (median age 67 [59.1–77.3] years, 39.3% females) were included: 115 patients with AF (median age 71 [59.0–78.0] years, 41.7% females) and 104 patients (median age 68 [56.3–76.8] years, 36.5% females) with SR. Solid thrombus or spontaneous-echo-contrast) was detected in 16 TEEs. Atrial dimensions were significantly enlarged in AF patients. Age, blood-flow velocity in LAA, LAA diameters, atrial areas, AF, and CHA2DS2-VASc-score were associated with thrombogenic material.

Incidence of ischemic stroke increased with age. AF was connected with higher stroke mortality. Presence of intra-cardiac thrombogenic material was associated with AF and most CHA2DS2-VASc-score factors. AF was associated with larger atrial dimensions and larger cavities favored thrombogenic material.

Keywords: atrial fibrillation, echocardiography, intracardiac thrombogenic material, left atrial appendage, mortality, stroke

1. Introduction

With an overall prevalence of 1% to 2%, an age-dependent increase and a trend to double in the next 50years,[3,12,13] atrial fibrillation (AF) is a well-recognized cause of ischemic stroke and one of the leading causes of death and disability.[3,6,9,17,19,27] Patients with AF have a 3- to 5-fold elevated relative risk for the occurrence of stroke in comparison to individuals without.[17,19] The hypothesis that AF produces stasis of blood resulting in thrombogenic material formation and thromboembolism to the brain has been proposed more than 100 years ago, but is still the most frequently suggested pathomechanism.[17,19] Thromboembolic strokes due to AF are common and frequently devastating, leading to severe impairment or death in 3/4 of the patients.[10,28] If rhythm control with an early cardioversion of AF patients in sinus rhythm (SR) is the strategy of choice, transesophageal echocardiography (TEE) has been shown to be suitable to exclude the majority of left atrial thrombi.[4,20] The left atrial appendage (LAA) is a blind pouch of the left atrium (LA), accounting for approximately 90% of intra-cardiac thrombi in AF.[8]

The objectives of our study were to investigate the impact of AF on the in-hospital mortality of ischemic stroke in a nationwide inpatient sample and to identify parameters associated with intra-cardiac thrombogenic material formation in patients examined with TEE in a retrospective cohort at the University Medical Center Mainz.

2. Methods and patients

Two separate patient cohorts were analyzed:

  • 1.

    Analysis of incidence and in-hospital death in ischemic stroke patients: The German nationwide inpatient statistics (Diagnosis related groups [DRG statistics]) of the year 2015 was consulted for this analysis. Information includes treatment data from all inpatients processed according to the DRG system. In Germany, diagnoses of inpatients are coded according to ICD-10-GM (International Classification of Diseases, 10th Revision with German Modification). The DRG-coded diagnoses data of all hospital patients are gathered at the Federal Statistical Office in Germany (Statistisches Bundesamt, DEStatis). For our analysis, mortality data of in-patients diagnosed for ischemic stroke (ICD code I63) with and without additionally coded AF (ICD code I48) were obtained from the Federal Statistical Office of Germany (Statistisches Bundesamt, DEStatis, source: DRG-Statistik, Sonderauswertung des Statistischen Bundesamtes). Since this study did not involve direct access by the investigators to data on individual patients but only to summary results provided by the Research Data Center, approval by an ethics committee and informed consent were not required according to German law.

  • 2.

    Correlation between echocardiographic parameters, clinical features, and stroke: Patients who underwent TEE in the Center of Cardiology at the University Medical Center Mainz (Mainz, Germany) were included in this retrospective analysis. This cohort included consecutive patients, aged ≥18 years, who were examined in the echocardiography department Center of Cardiology, University Medical Center Mainz by TEE (01/2013–03/2013). Patients were stratified by heart rhythm into 2 groups either SR or AF (all different clinical patterns of AF were assigned to the AF group). Patients which could not clearly be assigned to one group were excluded from analysis. We assessed patients’ characteristics, comorbidities, and echocardiographic parameters and calculated the CHA2DS2-VASc-score.[25] Echocardiographic measurements were obtained by evaluation of 2- and 3-dimensional TEE loops stored on the clinic's server in DICOM-standard and assessment via Philips Xcelera and Qlab software (trademark by Philips healthcare). All echocardiographic analysis was performed and confirmed by at least 2 experienced echocardiographers. The echocardiographic measurements comprised evaluation of solid thrombogenic material or spontaneous echo contrast (SEC) in the LAA, blood flow velocity in LAA detected by Pulsed-waved (PW-) Doppler as well as the spatial dimensions of the LAA in kind of width (septal-lateral diameter obtained in short axis view/ 45° angulation) and length (aperture-apex) of the LAA in TEE (Fig. 1). Confirmation or exclusion of thrombogenic material (solid thrombi as well as the assessment of SEC) was performed in all recorded angulations and 3-dimensional reconstructions, if available. Left ventricle ejection fraction (LVEF), left and right septal-lateral and longitudinal diameters, as well as atrial areas and systolic pulmonary artery pressure, were measured, if a TTE was available from the same hospital visit. Ventricular dimensions, ejection fraction and atrial areas were determined in apical 4 chamber view using Simpson's method according to the EACVI- and ASE-recommendations on cardiac chamber quantification.[22] Proposed systolic artery pressure was estimated from Doppler regurgitation velocity on tricuspid regurgitation (Fig. 1). Since the study involved an anonymous, retrospective analysis of diagnostic standard data, ethics approval was not required according to German laws.

Figure 1.

Figure 1

Open in a new tab

Assessment of LAA diameters and LAA velocity. LAA expansions were measured by determining orifice width and LAA depth. LAA orifice width (marked as red arrow) was estimated by measuring septo-lateral diameter in short axis view (SAX) as an approximated plane from the left coronary height (septal) to 1 to 2 cm below the highest point of the LUPV (left upper pulmonary vein)-limbus ("rim” / lateral); LAA depth (marked as blue arrow) was determined as distance from orifice plane to the deepest point of the LAA. If available, measurements were performed by multi-planar reconstruction of three-dimensional echo loops (Panels A, B, D: Panel A shows a reconstructed plane resembling SAX-view in left upper quadrant, Panel B another reconstructed longitudinal plane orthogonal on Panel A, Panel D the reconstructed "orifice” of the LAA). Panel C demonstrates measurements in "conventional” 2-dimensional TEE at about 45° resembling SAX-view. Panel E shows spatial relations in the LA in a 3-dimensional overview in "non-surgical” orientation. Panel F shows the determination of blood velocity in the LAA via PW-doppler in a patient with present atrial fibrillation (obviously shown by PW-curve demonstrating rapid and irregular LAA contractions). Ao = indicates aortic valve, l = lateral orientation, LAA = left atrial appendage, LUPV = left upper pulmonary vein, M = mitral valve, s = septal orientation.

3. Statistics

First, we calculated the incidence of ischemic stroke in Germany (2015) in the nationwide sample. Total numbers of inpatients with ischemic stroke with and without AF as well as the relative mortality of AF related to no AF was computed.

In the second retrospective study cohort, we compared patients with thrombogenic material, defined as detected solid thrombus or SEC in the left atrium and especially in the LAA with those without these findings to identify factors associated with thrombogenic material.

Descriptive statistics for the relevant baseline comparison of both groups are provided with mean ± standard deviation, median and interquartile range (IQR), depending on Gaussian or skewed distribution, or absolute numbers and corresponding percentages. Continuous variables found not to follow a normal distribution, when tested with the modified Kolmogorov–Smirnov test, were compared using the Wilcoxon-Whitney U test. Normal distributed continuous variables were compared using the Students t test and categorical variables with Fisher exact or Chi2 test, as appropriate.

We calculated univariate logistic regression models to examine different parameters as predictors for thrombogenic material. Additionally, multivariate logistic regression analyses adjusted for age an AF were performed for predictors. For the association of the comorbidity AF with thrombogenic material, multivariate logistic regression adjusted for age and congestive heart failure was used.

Parameters associated with thrombogenic material were entered in a receiver operating characteristics (ROC) analysis.

The software SPSS (version 22.0; SPSS Inc., Chicago, Illinois) was used for the majority of computerized analysis. For the calculation of the Youden cut-off values, specificity, sensitivity, and rate of misclassification in ROC analyses, BIAS (version 10.04; epsilon press, Frankfurt, Germany) was used. Only P values of < .05 (two-sided) were considered to be statistically significant.

4. Results

4.1. Analysis of the predictors of death in ischemic stroke patients

The nationwide sample comprised 292,401 inpatients (48.5% females) with ischemic stroke in Germany 2015. Calculated incidence for ischemic stroke was 360.1/100,000 citizens with an age dependent increase (Fig. 2A). Similarly, total numbers of ischemic stroke events increased up to the age-group ≥75years <80years (Fig. 2C).

Figure 2.

Figure 2

Open in a new tab

Incidence of ischemic stroke per 100,000 citizens (A), mortality rate (B), total numbers of ischemic stroke events (C) and relative mortality rate (D) stratified by different age groups in Germany in the year 2015. In Figure C the solid black line represents all ischemic stroke patients, the grey line those without AF and the dashed black line these with AF. In Figure D, the relative mortality rate in ischemic stroke patients with additional AF compared to those without AF is shown stratified for different age-groups (ischemic stroke patients without AF are the reference group and equated with 1). AF = atrial fibrillation.

In total, 24,054 patients with ischemic stroke died in-hospital (8.2%). The stroke-attributable mortality was 29.6/100 000 inhabitants, whereas the mortality-to-incidence ratio was 0.082. Ischemic stroke patients’ mortality rate stratified for age groups increased distinctly in age groups >60years (Fig. 2B). Stroke patients with AF had a higher in-hospital mortality rate compared to those without (12.1% vs 6.5%). Highest relative mortality rates in ischemic stroke patients with additional AF compared to those without AF, could be detected in the age group ≥20 years up to <50years, with exception of stroke patients between ≥30 to <35years (Fig. 2D).

4.2. Correlation between echocardiographic parameters, clinical features, and stroke

Overall, 225 consecutive patients who underwent TEE for various reasons were enrolled. Among these, 6 patients were excluded due to heart rhythm which could not be clearly assigned to one of the study groups. Therefore, 219 patients (median age 67years [59.1–77.3], 39.3% females) remained for analysis. The medical indication for TEE comprised evaluation regarding intra-cardiac thrombogenic material before planned cardioversion in 54.8%, further evaluation of valve disorders (including suspected endocarditis) in 26.0%, as well as other reasons in 19.2%. CHA2DS2-VASc-score of the whole study population regardless of underlying heart rhythm was 3points in median.

In total, 115 (52.5%) patients presented with AF and 104 (47.5%) patients with SR. Patients’ characteristics did not differ significantly in age, most comorbidities and CHA2DS2-VASc-score (Table 1), but patients without AF were more likely to suffer from coronary artery disease.

Table 1.

Clinical characteristics and echocardiographic parameters in patients with sinus rhythm and patients with atrial fibrillation.

4.2.

Open in a new tab

Solid thrombus could be proven by TEE in only 4 (1.8%) patients, whereas relevant SEC was observed in 12 (5.5%) patients. The study groups differed significantly in identified thrombogenic material defined as solid thrombus and/or SEC (AF: 13.7% vs SR: 2.5%, P = .007)

Echocardiographic diameters were significantly larger in patients with AF compared to those with SR and PW-Doppler revealed lower blood flow velocity in AF patients (Table 1). Univariate logistic binary regression models demonstrated associations of the parameters age, blood flow velocity in the LAA detected by PW- Doppler, LAA longitudinal and septal-lateral diameter, right and left atrial areas, presence of AF, diabetes mellitus, heart failure, peripheral artery disease, and CHA2DS2-VASc-score with thrombogenic material. The presence of AF and heart failure were associated with 6.2- and 4.2-fold risk of intra-cardiac thrombogenic material, respectively (Table 2). Each additional point in the CHA2DS2-VASc-score was accompanied by 66% increase in the risk of developing thrombogenic material.

Table 2.

Univariate regression analyses for the associations between several parameters and intra-cardiac thrombus formation in kind of solid thrombi and spontaneous echo contrast.

4.2.

Open in a new tab

After adjustment for age and AF, blood flow velocity in the LAA detected by PW-Doppler (OR 0.948 (95% CI 0.910–0.988, P = .011)), LAA longitudinal (OR 4.708 (95% CI 1.757–12.616, P = .002) and septal-lateral (OR 3.670 (95% CI 1.402–9.604), P = .008) diameter, right (OR 1.125 (95% CI 1.003–1.262), P = .045) atrial area, presence of heart failure (OR 4.845 (95% CI 1.546–15.184), P = .007), diabetes mellitus (OR 3.121 (95% CI 1.024–9.515), P = .045), and peripheral artery disease (OR 3.537 (95% CI 1.013–12.347), P = .048) remained significantly associated with thrombogenic material in multivariate regression analysis. In addition, AF was also still associated with thrombogenic material in multivariate logistic regression model after adjustment for age and heart failure (OR 7.557 (95% CI 1.542–37.021), P = .013).

The ROC curves identifying the thresholds as best cut-off for the prediction of the presence of thrombogenic material are shown in Figures 3 and 4. These cut-offs were associated with a sensitivity >65% and a specificity >61% in the prediction of SEC. The highest accuracy was observed for blood flow velocity determination in LAA by PW-Doppler with an area under the curve of 0.799 (Table 3).

Figure 3.

Figure 3

Open in a new tab

ROC curves for age (A), Pulsed-waved Doppler (B), Left atrial appendage longitudinal diameter (C), Left atrial appendage septal-lateral diameter (D), Right atrial area (E), and Left atrial area (F) as predictors of intra-cardiac thrombogenic material (solid thrombus and spontaneous echo contrast).

Figure 4.

Figure 4

Open in a new tab

ROC curve for CHA2DS2-VASc-score as predictors of intra-cardiac thrombogenic material (solid thrombus and spontaneous echo contrast).

Table 3.

Prognostic performance for prediction of thrombogenic material (solid thrombus and spontaneous echo contrast). Risk of misclassification is defined as sum of false positive and false negative values.

4.2.

Open in a new tab

5. Discussion

Ischemic stroke, one of the leading causes of death and disability worldwide,[1,15,19,27] shows large differences in incidence, prevalence, and mortality between different regions, especially between Eastern and Western Europe.[1,21,30] The calculated incidence of ischemic stroke in Germany was 360/100,000 citizens and therefore lower than in Eastern Europe but distinctly higher than in other parts of the world.[21] Importantly, the incidence of stroke appears thus to be increasing as compared to earlier years.[21,30]

The stroke-attributable mortality was 29.6/100,000 persons (2015) in Germany, lower than in Russia,[21] but similar to the USA and France.[30] Hence, the higher incidence in comparison to former years and other countries detected by national coding system might be driven by coding differences.

The mortality-to-incidence ratio was very low, similar to the high-income regions of North America and east Asia.[21] The mortality rate increased from <4% in patients aged younger than 50years to >13% in those ≥85years old, presumably attributable to the growing number of comorbidities.

In accordance with previous studies, the results of the German nationwide sample demonstrated an increase of the stroke incidence with growing age[8,29,30] and a 1.85-fold higher case fatality rate during in-hospital stay in those stroke patients with a comorbidity of AF in comparison to those without.[16,23,29] This fatal correlation proved to be most pronounced in the relatively young group of ischemic stroke patients younger than 45years of age.

It is well known that patients with AF are at increased risk for stroke.[3,5,11,24,25,27,29] Overall, 15% to 30% of all strokes are due to AF - presumably this rate is even underestimated due to unidentified “silent” or paroxysmal AF.[7,9,19,26,27]

The LAA is the primary localization for intra-cardiac thromboembolic material in non-valvular AF and the primary cause of cardioembolic strokes with approximately 90% of intra-cardiac thrombi.[7,8,24] TEE is the standard procedure for the diagnosis or exclusion of intra-cardiac thrombi in AF patients.[2,7,14] In accordance with the literature we found larger atrial diameters and areas including larger LAA diameters in AF patients in comparison to those with SR.[8,18] In this context, the blood flow velocity in the LAA measured by PW-Doppler was also lower in AF patients.

Our study demonstrated that besides AF, a larger size of the atria and the LAA and lower blood flow velocity were associated with thrombogenic material defined as solid thrombi and SEC, which may reflect microthrombi development.[8] Of note, the present data do not allow a definite conclusion whether larger dimensions are direct causes of the thrombogenic material formation or if they are the consequence of AF and therefore only cofactors of AF in thrombogenic material formation. Additionally, diabetes, heart failure, peripheral artery disease, and advanced age were also associated with thrombogenic material occurrence. As expected, a CHA2DS2-VASc-score >2.5 was predictive for thrombogenic material.

6. Limitations

Of course, our study has some limitations. The data of the nationwide sample from Federal Statistical Office of Germany (Statistisches Bundesamt, DEStatis) for this analysis are pooled/aggregated data. Therefore, we can only present a descriptive data analysis, without statistical testing for difference with P-values and without adjustment for age and other cofactors such as comorbidities (e.g., cardiovascular disease). Furthermore, only patients treated in-hospital were included.

The central limitations of the second study-part are the single-center design and the retrospective data assessment of a medium sized patient cohort. Follow-up examinations are missing. In addition, only a small number of solid thrombi could be detected in the patient cohort, not allowing for statistically significant evidence. Thus, we decided to analyze solid thrombi and SEC as equivalent for thrombogenic material, respectively intra-cardiac thrombus formation. The occurrence of SEC was assessed by at least 2 experienced echocardiographers. Despite these limitations, we were able to identify important factors of intra-cardiac formation of thrombogenic material.

7. Conclusions

The incidence of ischemic stroke in the German nationwide sample of inpatients in 2015 was 360/100,000 citizens and increased with age. AF was connected to higher in-hospital mortality in ischemic stroke. AF was associated with 6-fold higher risk of thrombogenic material compared to SR.

Acknowledgments

We thank the Federal Statistical Office of Germany (Statistisches Bundesamt, DEStatis) for providing the pooled data for the study cohort of ischemic stroke patients in Germany 2015 and the kind permission to publish these data/results.

Author contributions

Conceptualization: Karsten Keller, Martin Geyer.

Data curation: Karsten Keller, Martin Geyer.

Formal analysis: Karsten Keller.

Investigation: Karsten Keller.

Methodology: Karsten Keller, Martin Geyer, Tommaso Gori.

Project administration: Karsten Keller.

Resources: Karsten Keller.

Software: Karsten Keller.

Statistical analysis: Karsten Keller, Martin Geyer

Supervision: Karsten Keller, Thomas Münzel, Mir Abolfazl Ostad, Tommaso Gori.

Validation: Karsten Keller, Martin Geyer.

Visualization: Karsten Keller, Martin Geyer.

Writing - original draft: Martin Geyer, Karsten Keller

Writing – review & editing: Karsten Keller, Martin Geyer, Thomas Münzel, Mir Abolfazl Ostad, Tommaso Gori

Karsten Keller orcid: 0000-0002-0820-9584.

Footnotes

Abbreviations: AF = atrial fibrillation, BMI = body mass index, CI = confidence intervall, DRG = diagnosis related groups, ICD-10-GM = International Classification of Diseases, 10th Revision with German Modification, IQR = interquartile range, LA = left atrium, LAA = left atrial appendage, LVEF = left ventricle ejection fraction, OR = odds ratio, SEC = spontaneous echo contrast, SR = sinus rhythm, TIA = transient ischemic attack, TTE = transesophageal echocardiography, VTE = venous thromboembolism.

KK and MG contributed equally and should both be considered as first authors.

This study was supported by the German Federal Ministry of Education and Research (BMBF 01EO1003 and BMBF 01EO1503). The authors are responsible for the contents of this publication.

The authors declare that there is no conflict of interest to disclose.

References

  • [1].European Stroke Organisation (ESO) Executive Committee, ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25:457–507. [DOI] [PubMed] [Google Scholar]
  • [2].Anter E, Silverstein J, Tschabrunn CM, et al. Comparison of intracardiac echocardiography and transesophageal echocardiography for imaging of the right and left atrial appendages. Heart Rhythm 2014;11:1890–7. [DOI] [PubMed] [Google Scholar]
  • [3].Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010;31:2369–429. [DOI] [PubMed] [Google Scholar]
  • [4].Cappato R, Ezekowitz MD, Klein AL, et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014;35:3346–55. [DOI] [PubMed] [Google Scholar]
  • [5].Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139–51. [DOI] [PubMed] [Google Scholar]
  • [6].Dobkin BH. Clinical practice. Rehabilitation after stroke. N Engl J Med 2005;352:1677–84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Donal E, Yamada H, Leclercq C, et al. The left atrial appendage, a small, blind-ended structure: a review of its echocardiographic evaluation and its clinical role. Chest 2005;128:1853–62. [DOI] [PubMed] [Google Scholar]
  • [8].Fuller CJ, Reisman M. Stroke prevention in atrial fibrillation: atrial appendage closure. Curr Cardiol Rep 2011;13:159–66. [DOI] [PubMed] [Google Scholar]
  • [9].Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke 2011;42:227–76. [DOI] [PubMed] [Google Scholar]
  • [10].Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 2014;370:2467–77. [DOI] [PubMed] [Google Scholar]
  • [11].Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981–92. [DOI] [PubMed] [Google Scholar]
  • [12].Guo Y, Tian Y, Wang H, et al. Prevalence, incidence, and lifetime risk of atrial fibrillation in China: new insights into the global burden of atrial fibrillation. Chest 2015;147:109–19. [DOI] [PubMed] [Google Scholar]
  • [13].Heeringa J, van der Kuip DA, Hofman A, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J 2006;27:949–53. [DOI] [PubMed] [Google Scholar]
  • [14].January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014;130:2071–104. [DOI] [PubMed] [Google Scholar]
  • [15].Jauch EC, Saver JL, Adams HP, Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870–947. [DOI] [PubMed] [Google Scholar]
  • [16].Kaarisalo MM, Immonen-Raiha P, Marttila RJ, et al. Atrial fibrillation and stroke. Mortality and causes of death after the first acute ischemic stroke. Stroke 1997;28:311–5. [DOI] [PubMed] [Google Scholar]
  • [17].Kamel H, Okin PM, Elkind MS, et al. Atrial fibrillation and mechanisms of stroke: time for a new model. Stroke 2016;47:895–900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Kerut EK. Anatomy of the left atrial appendage. Echocardiography 2008;25:669–73. [DOI] [PubMed] [Google Scholar]
  • [19].Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: the Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC Endorsed by the European Stroke Organisation (ESO). Eur Heart J 2016;37:2893–962. [DOI] [PubMed] [Google Scholar]
  • [20].Klein AL, Grimm RA, Murray RD, et al. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411–20. [DOI] [PubMed] [Google Scholar]
  • [21].Krishnamurthi RV, Feigin VL, Forouzanfar MH, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health 2013;1:e259–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].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. Eur Heart J Cardiovasc Imaging 2015;16:233–70. [DOI] [PubMed] [Google Scholar]
  • [23].Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996;27:1760–4. [DOI] [PubMed] [Google Scholar]
  • [24].Lockwood SM, Alison JF, Obeyesekere MN, et al. Imaging the left atrial appendage prior to, during, and after occlusion. JACC Cardiovasc Imaging 2011;4:303–6. [DOI] [PubMed] [Google Scholar]
  • [25].Olesen JB, Lip GY, Hansen ML, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011;342:d124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Pepi M, Evangelista A, Nihoyannopoulos P, et al. Recommendations for echocardiography use in the diagnosis and management of cardiac sources of embolism: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Echocardiogr 2010;11:461–76. [DOI] [PubMed] [Google Scholar]
  • [27].Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014;370:2478–86. [DOI] [PubMed] [Google Scholar]
  • [28].Steger C, Pratter A, Martinek-Bregel M, et al. Stroke patients with atrial fibrillation have a worse prognosis than patients without: data from the Austrian Stroke registry. Eur Heart J 2004;25:1734–40. [DOI] [PubMed] [Google Scholar]
  • [29].Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991;22:983–8. [DOI] [PubMed] [Google Scholar]
  • [30].Zhang Y, Chapman AM, Plested M, et al. The incidence, prevalence, and mortality of stroke in France, Germany, Italy, Spain, the UK, and the US: a literature review. Stroke Res Treat 2012;2012:436125. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Medicine are provided here courtesy of Wolters Kluwer Health

RESOURCES