Neurogenic cardiac outcome in patients after acute ischemic stroke: The brain and heart connection



      Neurogenic cardiac impairment can occur after acute ischemic stroke (AIS), but the mapping of the neuroanatomic correlation of stroke-related myocardial injury remains uncertain. This study aims to identify the association between cardiac outcomes and middle cerebral artery (MCA) ischemic stroke, with or without insular cortex involvement, as well as the impact of new-onset atrial fibrillation (AF) after AIS on recurrent stroke.


      Serial measurements of high sensitivity troponin T (TnT), brain natriuretic peptide (BNP), electrocardiography (ECG), echocardiogram, and cardiac monitoring were performed on 415 patients with imaging confirmed MCA stroke, with or without insular involvement. Patients with renal failure, recent cardiovascular events, or congestive heart failure were excluded.


      One hundred fifteen patients (28%) had left MCA infarcts with insular involvement, 122 (29%) had right MCA infarcts involving insular cortex, and 178 (43%) had no insular involvement. Patients with left MCA stroke with insular involvement tended to exhibit higher BNP and TnI, and transient cardiac dysfunction, which mimicked Takotsubo cardiomyopathy in 10 patients with left ventricular ejection fraction (LVEF) of 20-40%. Incidence of new-onset AF was higher in right MCA stroke involving insula (39%) than left MCA involving insula (4%). Nine out of fifty-three patients with new-onset AF were not on anticoagulant therapy due to various reasons; none of them experienced recurrent AF or stroke during up to a 3-year follow-up period. Statistically significant correlations between BNP or TnT elevation and left insular infarcts, as well as the incidence of AF and right insular infarcts, were revealed using linear regression analysis.


      The present study demonstrated that acute left MCA stroke with insular involvement could cause transient cardiac dysfunction and elevated cardiac enzymes without persistent negative outcomes in the setting of health baseline cardiac condition. The incidence of new-onset AF was significantly higher in patients with right MCA stroke involving the insula. There was no increased risk of recurrent ischemic stroke in nine patients with newly developed AF who were not on anticoagulant therapy, which indicated a need for further research on presumed neurogenic AF and its management.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • GBD 2019 Stroke Collaborators
        Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the global burden of disease study 2019.
        Lancet Neurol. 2021; 20 (995-820)
        • McLeod A.A.
        • Nei-Dwyer G.
        • Meyer C.H.A.
        • Richardson P.L.
        • Cruickshank J.
        • Bartlett J.
        Cardiac sequelae of acute head injury.
        Br Heart J. 1982; 47: 221-226
        • Levy A.G.
        The exciting causes of ventricular fibrillation in animals under chloroform anesthesia.
        Heart. 1913; 4: 319-326
        • Levy AG.
        Further remarks on ventricular extrasystoles and fibrillation under chloroform.
        Heart. 1919; 7: 105-112
        • Beattie J.
        • Brow G.R.
        • Long CNH.
        Physiological and anatomical evidence for the existence of nerve tracts connecting the hypothalamus with spinal sympathetic centers.
        Proc R Sco Lond (Biol). 1930; 106: 253-275
        • Aschenbrenner R.
        • Bodechtel G.
        Ueber EKG veranderungern bie hirntumorkranken.
        Klin Wochen. 1938; 17: 298-302
        • McLeod A.A.
        • Neil-Dwyer G.
        • Meyer C.H.A.
        • Richardson P.L.
        • Cruickshank J.
        • Bartlett J.
        Cardiac sequelae of acute head injury.
        Br Hear J. 1982; 47: 221-226
        • Teves D.
        • Videen T.O.
        • Cryer P.E.
        • Powers WJ.
        Activation of human medial prefrontal cortex during autonomic responses to hypoglycemia.
        Proc Nat Acad Sci USA. 2004; 101: 6217-6221
        • Min J.
        • Farooq U.M.
        • Greenberg E.
        • et al.
        Cardiac dysfunction after left permanent cerebral focal ischemia. The brain and heart connection.
        Stroke. 2009; 40: 2560-2563
        • Oppenheimer S.M.
        • Gelb A.
        • Girvin J.P.
        • Hachinski V.C.
        Cardiovascular effects of human insular cortex stimulation.
        Neurology. 1992; 42: 1727-1732
        • Hachinski V.
        • Cechetto DF.
        Cardiovascular consequence of experimental stroke.
        Baillieres Clin Neurol. 1997; 6: 297-308
        • Min J.
        • Meissner A.
        • Geldmacher H.
        • Alexander H.
        • El-Mokhtari N.E.
        • Simon R.
        Heterogeneity of noninvasive arrhythmic risk indications in patients with ischemic cardiomyopathy.
        J Electrocardiology. 1998; 31: 221-226
        • Laowattana S.
        • Zeger S.L.
        • Lima J.A.C.
        • Goodman S.N.
        • Wittstein I.S.
        • Oppenheimer S.M.
        Left insular stroke is associated with adverse cardiac outcome.
        Neurology. 2006; 66: 477-483
        • Colivicchi F.
        • Bassi A.
        • Santini M.
        • Caltagione C.
        cardiac autonomic derangement and arrhythmias in right-sided stroke with insular involvement.
        Stroke. 2004; 35: 2094-2098
        • Powers W.J.
        • Rabinstein A.A.
        • Ackerson T.
        • et al.
        Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American heart association/American stroke association.
        Stroke. 2019; 50: e344-e418
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • et al.
        2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2013; 62: e147-e239
        • Foulkes M.A.
        • Wolf P.A.
        • Price T.R.
        • Mohr J.P.
        • Hier D.B.
        The stroke data bank: design, methods, and baseline characteristics.
        Stroke. 1988; 19: 547-554
        • Adams Jr, H.P.
        • Bendixen B.H.
        • Kappelle L.J.
        • et al.
        Classification of subtype of acute ischemic stroke definitions for use in a multicenter clinical trial. Trial of Org 10172 in acute stroke treatment.
        Stroke. 1993; 24: 35-41
        • Ay H.
        • Korshetz W.J.
        • Benner T.
        • et al.
        Neuroanatomic correlates of stroke-related myocardial injury.
        Neurology. 2006; 66: 1325-1329
        • Brott T.
        • Adams Jr, H.P.
        • Olinger C.P.
        • et al.
        Measurements of acute cerebral infarction: a clinical examination scale.
        Stroke. 1989; 20: 864-870
        • Elrifai A.M.
        • Brillman J.
        Characterization of the cardiac effects of acute subarachnoid hemorrhage in dogs.
        Stroke. 1996; 27: 737-741
        • van der Bilt I.A.C.
        • Hasan D.
        • Vandertop W.P.
        • Wilde A.A.M.
        • Visser F.C.
        • Rinkel G.J.E.
        Impact of cardiac complications on outcome after aneurysmal subarachnoid hemorrhage: a meta-analysis.
        Neurology. 2009; 72: 635-642
        • Opie L.H.
        • Walpoth B.
        • Barsacchi R.
        Calcium and catecholamines: relevance to cardiomyopathy and significance in therapeutic strategies.
        JMCC. 1985; 17: 21-34
        • Fang C.X.
        • Wu S.
        • Ren J.
        Intracerebral hemorrhage elicits aberration in cardiomyocyte contractile function and intracellular Ca2+ transients.
        Stroke. 2006; 37: 1875-1882
        • Min J.
        • Hampton T.G.
        • Wang J.F.
        • DeAngelis J.
        • Morgan J.P.
        Depressed tolerance of fluorocarbon-simulated ischemia in failing rat myocardium due to impaired intracellular Ca2+ modulation.
        Am J Physiol. 2000; 278: H1446-H1456
        • Min J.
        • Sullivan M.F.
        • Yan X.
        • et al.
        Attenuation of postinfarcted myocardial dysfunction in transgenic mice with overexpression of Na+/Ca2+ exchanger.
        Am J Physiol. 2002; 283: H2466-H2471
        • Brand F.N.
        • Abbott R.D.
        • Kannel W.B.
        • Wolf P.A.
        Characteristics and prognosis of lone atrial fibrillation: 30-year follow-up in the Framingham study.
        JAMA. 1985; 254: 3449-3453
        • Sposato L.A.
        • Cerasuolo J.O.
        • Cipriano L.E.
        • et al.
        on behalf of the PARADISE Study Group. Atrial fibrillation detected after stroke is related to a low risk of ischemic stroke recurrence.
        Neurology. 2018; 90: e924-e931
        • Ruthirago D.
        • Julayanont P.
        • Tantrachoti P.
        • Kim J.
        • Nugent K.
        Cardiac arrhythmias and abnormal electrocardiograms after acute stroke.
        Am J Med Sci. 2016 Jan; 351: 112-118
        • Wang Y.
        • Qian Y.
        • Smerin D.
        • Zahgn S.
        • Zhao Q.
        • Xiong X.
        Newly detected atrial fibrillation after acute stroke: a narrative review of causes and implications.
        Cardiology. 2019; 144: 112-121
        • Agarwal S.K.
        • Norby F.L.
        • Whitsel E.A.
        Cardiac autonomic dysfunction and incidence of atrial fibrillation: results from 20 years follow-up.
        J Am Coll Cardiol. 2017; 69: 291-299
        • van der Bilt I.A.
        • Vendeville J.P.
        • van de Hoef T.P.
        • et al.
        Myocarditis in patients with subarachnoid hemorrhage: A histopathologic study.
        J Crit Care. 2016; 32: 196-200
        • Shichita T.
        • Hasegawa E.
        • Kimura A.
        • et al.
        Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain.
        Nat Med. 2012; 18: 911-917
        • Liesz A.
        • Dalpke A.
        • Mracsko E.
        • et al.
        DAMP signaling is a key pathway inducing immune modulation after brain injury.
        J Neurosci. 2015; 35: 583-598
        • Hu Y.F.
        • Chen Y.J.
        • Lin Y.J.
        • Chen SA.
        Inflammation and the pathogenesis of atrial fibrillation.
        Nat Rev Cardiol. 2015; 12: 230-243
        • Walkey A.J.
        • Quinn E.K.
        • Winter M.R.
        • McManus D.D.
        • Benjamin E.J.
        Practice patterns and outcomes associated with use of anticoagulation among patients with arial fibrillation during sepsis.
        JAMA Cardiol. 2016; 1: 682-690
        • Yang X.
        • Rao Z.
        • Gu H.
        • et al.
        Atrial fibrillation known before or detected after stroke share similar risk of ischemic stroke recurrence and death.
        Stroke. 2019; 50: 1124-1129