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March 23, 2021; 96 (12) Article

Stroke, Timing of Atrial Fibrillation Diagnosis, and Risk of Death

Anjali Bhatla, Yuliya Borovskiy, Ronit Katz, View ORCID ProfileMatthew C. Hyman, Parin J. Patel, Jeffrey Arkles, David J. Callans, Neel Chokshi, Sanjay Dixit, Andrew E. Epstein, David S. Frankel, Fermin C. Garcia, Ramanan Kumareswaran, Jackson J. Liang, David Lin, Steven R. Messé, Saman Nazarian, Michael P. Riley, Pasquale Santangeli, Robert D. Schaller, Gregory E. Supple, Scott E. Kasner, Francis Marchlinski, Rajat Deo
First published February 3, 2021, DOI: https://doi.org/10.1212/WNL.0000000000011633
Anjali Bhatla
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Yuliya Borovskiy
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Ronit Katz
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Matthew C. Hyman
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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  • ORCID record for Matthew C. Hyman
Parin J. Patel
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Jeffrey Arkles
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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David J. Callans
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Neel Chokshi
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Sanjay Dixit
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Andrew E. Epstein
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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David S. Frankel
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Fermin C. Garcia
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Ramanan Kumareswaran
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Jackson J. Liang
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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David Lin
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Steven R. Messé
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Saman Nazarian
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Michael P. Riley
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Pasquale Santangeli
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Robert D. Schaller
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Gregory E. Supple
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Scott E. Kasner
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Francis Marchlinski
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Rajat Deo
From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.
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Stroke, Timing of Atrial Fibrillation Diagnosis, and Risk of Death
Anjali Bhatla, Yuliya Borovskiy, Ronit Katz, Matthew C. Hyman, Parin J. Patel, Jeffrey Arkles, David J. Callans, Neel Chokshi, Sanjay Dixit, Andrew E. Epstein, David S. Frankel, Fermin C. Garcia, Ramanan Kumareswaran, Jackson J. Liang, David Lin, Steven R. Messé, Saman Nazarian, Michael P. Riley, Pasquale Santangeli, Robert D. Schaller, Gregory E. Supple, Scott E. Kasner, Francis Marchlinski, Rajat Deo
Neurology Mar 2021, 96 (12) e1655-e1662; DOI: 10.1212/WNL.0000000000011633

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Abstract

Objective To evaluate the prognosis of patients with ischemic stroke according to the timing of an atrial fibrillation (AF) diagnosis, we created an inception cohort of incident stroke events and compared the risk of death between patients with stroke with (1) sinus rhythm, (2) known AF (KAF), and (3) AF diagnosed after stroke (AFDAS).

Methods We used the Penn AF Free study to create an inception cohort of patients with incident stroke. Mortality events were identified after linkage with the National Death Index through June 30, 2017. We also evaluated initiation of anticoagulants and antiplatelets across the study duration. Cox proportional hazards models evaluated associations between stroke subtypes and death.

Results We identified 1,489 individuals who developed an incident ischemic stroke event: 985 did not develop AF at any point during the study period, 215 had KAF before stroke, 160 had AF detected ≤6 months after stroke, and 129 had AF detected >6 months after stroke. After a median follow-up of 4.9 years (interquartile range 1.9–6.8), 686 deaths occurred. The annualized mortality rate was 8.8% in the stroke, no AF group; 12.2% in the KAF group; 15.8% in the AFDAS ≤6 months group; and 12.7% in the AFDAS >6 months group. Patients in the AFDAS ≤6 months group had the highest independent risk of all-cause mortality even after multivariable adjustment for demographics, clinical risk factors, and the use of antithrombotic therapies (hazard ratio 1.62 [1.22–2.14]). Compared to the stroke, no AF group, those with KAF had a higher mortality risk that was rendered nonsignificant after adjustment.

Conclusions The AFDAS group had the highest risk of death, which was not explained by comorbidities or use of antithrombotic therapies.

Glossary

AF=
atrial fibrillation;
AFDAS=
atrial fibrillation detected after stroke;
ECG=
electrocardiogram;
EHR=
electronic health record;
ICD-9=
International Classification of Diseases–9;
IQR=
interquartile range;
KAF=
known atrial fibrillation;
PAFF=
Penn Atrial Fibrillation Free

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 557

  • Received July 14, 2020.
  • Accepted in final form December 18, 2020.
  • © 2021 American Academy of Neurology
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