The Heart-Brain Syndrome in clinical practice: A comprehensive approach from cardiac imaging for differential diagnosis
DOI:
https://doi.org/10.37615/retic.v9n1a2Keywords:
stroke heart syndrome, takotsubo, stroke, neurocardiology, echocardiography, cardiac magnetic resonanceAbstract
Introduction: Stroke heart syndrome (SHS) is a frequent and clinically relevant condition characterized by myocardial injury, arrhythmias, or acute ventricular dysfunction secondary to severe neurological damage. Troponin elevation, present in a high percentage of patients, poses the dilemma of distinguishing between neurogenic stress cardiomyopathy and a true acute coronary syndrome (ACS) that may either cause or result from the cerebral event. Objective: To provide clinical cardiologists and cardiac imaging specialists with a practical, evidence based framework in which noninvasive imaging techniques play a central role for the differential diagnosis and management of SHS. Development: An integrative pathophysiological update is presented, ranging from classical neurohumoral mechanisms to recent findings on inflammation and genetic susceptibility. Based on this foundation, the different clinical phenotypes of SHS are delineated and a sequential diagnostic approach is detailed. Bedside-applicable algorithms are provided to guide the selection and interpretation of each imaging modality: transthoracic and transesophageal echocardiography, cardiac magnetic resonance, and computed tomography. Conclusion: The structured application of these algorithms allows optimization of diagnostic accuracy, refinement of risk stratification, and support for personalized therapeutic management in this particularly challenging patient population.
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References
Zhao B, Li T, Fan Z, et al. Heart-brain connections: Phenotypic and genetic insights from magnetic resonance images. Science. 2023;380(6648):eabn6598. doi: 10.1126/science.abn6598.
Scheitz JF, Nolte CH, Doehner W, Hachinski V, Endres M. Stroke-heart syndrome: clinical presentation and underlying mechanisms. Lancet Neurol. 2018;17(12):1109-1120. doi: 10.1016/S1474-4422(18)30336-3.
Scheitz JF, Sposato LA, Schulz-Menger J, Nolte CH, Backs J, Endres M. Stroke-Heart Syndrome: Recent Advances and Challenges. J Am Heart Assoc. 2022;11(17):e026528. doi: 10.1161/JAHA.122.026528.
Wang M, Peng Y. Advances in brain-heart syndrome: Attention to cardiac complications after ischemic stroke. Front Mol Neurosci. 2022;15:1053478. doi: 10.3389/fnmol.2022.1053478.
Rosso M, Ramaswamy S, Kvantaliani N, et al. Stroke-Heart Syndrome: Does Sex Matter? J Am Heart Assoc. 2023;12(21):e029799. doi: 10.1161/JAHA.123.029799.
Tang H, Xing X, Han Y, et al. A Retrospective Study of Brain-Heart Syndrome in Patients with Acute Cerebrovascular Diseases. Risk Manag Healthc Policy. 2024;17:2161-2168. doi: 10.2147/RMHP.S467205.
Fan X, Cao J, Li M, et al. Stroke Related Brain-Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms. Adv Sci. 2024;11(14):2307698. doi: 10.1002/advs.202307698.
Zou L, Han R. Inflammatory Response and Immune Regulation in Brain-Heart Interaction after Stroke. Cardiovasc Ther. 2022;2022:2406122. doi: 10.1155/2022/2406122.
Vornholz L, Nienhaus F, Gliem M, et al. Acute Heart Failure After Reperfused Ischemic Stroke: Association With Systemic and Cardiac Inflammatory Responses. Front Physiol. 2021;12:782760. doi: 10.3389/fphys.2021.782760.
Hu JR, Abdullah A, Nanna MG, Soufer R. The Brain-Heart Axis: Neuroinflammatory Interactions in Cardiovascular Disease. Curr Cardiol Rep. 2023;25(12):1745-1758. doi: 10.1007/s11886-023-01990-8.
Brazdil V, Kala P, Hudec M, et al. The role of central autonomic nervous system dysfunction in Takotsubo syndrome: a systematic review. Clin Auton Res. 2022;32(1):9-17. doi: 10.1007/s10286-021-00844-z.
Suzuki H, Yasuda S, Shimokawa H. Brain-heart connection in Takotsubo syndrome before onset. Eur Heart J. 2021;42(19):1909-1911. doi: 10.1093/eurheartj/ehab026.
Markousis-Mavrogenis G, Pepe A, Bacopoulou F, et al. Combined Brain-Heart Imaging in Takotsubo Syndrome: Towards a Holistic Patient Assessment. J Clin Med. 2024;13(10):2991. doi: 10.3390/jcm13102991.
Lesch H, Kruska M, Marx A, et al. The phenomenon of dynamic change of cardiac troponin levels in patients with spontaneous intracerebral hemorrhage increases in-hospital mortality independent of macrovascular coronary artery disease. J Neurol Sci. 2025;476:123633. doi: 10.1016/j.jns.2025.123633.
Suzuki H, Yasuda S, Shimokawa H. Brain-heart connection in Takotsubo syndrome. Eur Heart J. 2021;42(19):1909-1911. doi: 10.1093/eurheartj/ehab026.
Zheng J, Ma Y, Guo X, Wu J. Immunological characterization of stroke-heart syndrome and identification of inflammatory therapeutic targets. Front Immunol. 2023;14:1227104. doi: 10.3389/fimmu.2023.1227104.
Sethi Y, Murli H, Kaiwan O, et al. Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management. J Clin Med. 2022;12(1):125. doi: 10.3390/jcm12010125.
Liang Y, Wang G, Fan S, et al. Brain-to-heart cholinergic synapse-calcium signaling mediates ischemic stroke-induced atrial fibrillation. Theranostics. 2024;14(17):6625-6649. doi: 10.7150/thno.99065.
Myrmel GMS, Waje-Andreassen U, Pirinen J, et al. Multimodality Cardiac Imaging in Ischemic Stroke: Insights into the Heart-Brain Interaction. Cardiology. 2025;150(5):525-539. doi: 10.1159/000543170.
Cau R, Porcu M, Suri JS, et al. Heart-Brain axis: is microvascular dysfunction the link between stroke and Takotsubo syndrome? Int J Cardiovasc Imaging. 2025;41(10):1895-1906. doi: 10.1007/s10554-025-03477-9.
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(3):233-270. doi: 10.1093/ehjci/jev014.
Voigt JU, Pedrizzetti G, Lysyansky P, et al. Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur Heart J Cardiovasc Imaging. 2015;16(1):1-11. doi: 10.1093/ehjci/jeu184.
Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29(4):277-314. doi: 10.1016/j.echo.2016.01.011.
Kerro A, Woods T, Chang JJ. Neurogenic stunned myocardium in subarachnoid hemorrhage. J Crit Care. 2017;38:27-34. doi: 10.1016/j.jcrc.2016.10.010.
Ghadri JR, Wittstein IS, Prasad A, et al. International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology. Eur Heart J. 2018;39(22):2032-2046. doi: 10.1093/eurheartj/ehy076.
Templin C, Ghadri JR, Diekmann J, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med. 2015;373(10):929-938. doi: 10.1056/NEJMoa1406761.
Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, et al. Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA. 2011;306(3):277-286. doi: 10.1001/jama.2011.992.
Saric M, Armour AC, Arnaout MS, et al. Guidelines for the Use of Echocardiography in the Evaluation of a Cardiac Source of Embolism. J Am Soc Echocardiogr. 2016;29(1):1-42. doi: 10.1016/j.echo.2015.09.011.
Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364-e467. doi: 10.1161/STR.0000000000000375.
Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: a JACC White Paper. J Am Coll Cardiol. 2009;53(17):1475-1487. doi: 10.1016/j.jacc.2009.02.007.
Ferreira VM, Schulz-Menger J, Holmvang G, et al. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072.
Ferreira VM, Schulz-Menger J, Holmvang G, et al. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol. 2018;72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072.
Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021;42(5):373-498. doi: 10.1093/eurheartj/ehaa612.
Rubiera M, Aires A, Antonenko K, et al. European Stroke Organisation (ESO) guideline on screening for subclinical atrial fibrillation after stroke or transient ischaemic attack of undetermined origin. Eur Stroke J. 2022;7(3):VI. doi: 10.1177/23969873221099478.
Mas JL, Derumeaux G, Guillon B, et al. Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke. N Engl J Med. 2017;377(11):1011-1021. doi: 10.1056/NEJMoa1705915.
Søndergaard L, Kasner SE, Rhodes JF, et al. Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke. N Engl J Med. 2017;377(11):1033-1042. doi: 10.1056/NEJMoa1707404.
Habib G, Lancellotti P, Antunes MJ, et al. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023;44(39):3948-4042. doi: 10.1093/eurheartj/ehad193.
Tamis-Holland JE, Jneid H, Reynolds HR, et al. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019;139(18):e891-e908. doi: 10.1161/CIR.0000000000000670.
Juncà G, Teis A, Kasa G, et al. Timing of cardiac magnetic resonance and diagnostic yield in patients with myocardial infarction with nonobstructive coronary arteries. Rev Esp Cardiol (Engl Ed). 2024;77(7):515-523. doi: 10.1016/j.rec.2023.11.013.
Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407-477. doi: 10.1093/eurheartj/ehz425.
Romero J, Husain SA, Kelesidis I, et al. Detection of left atrial appendage thrombus by cardiac computed tomography in patients with atrial fibrillation: a meta-analysis. Circ Cardiovasc Imaging. 2013;6(2):185-194. doi: 10.1161/CIRCIMAGING.112.000153.
Yu S, He W, Wang R, et al. Cardiac Computed Tomography Versus Transesophageal Echocardiography for the Detection of Left Atrial Appendage Thrombus: A Systemic Review and Meta-Analysis. J Am Heart Assoc. 2021;10(23):e022505. doi: 10.1161/JAHA.121.022505.
Spagnolo P, Giglio M, Di Marco D, et al. Diagnosis of left atrial appendage thrombus in patients with atrial fibrillation: delayed contrast-enhanced cardiac CT. Eur Radiol. 2021;31(3):1236-1244. doi: 10.1007/s00330-020-07172-2.
Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain. Circulation. 2021;144(22):e368-e454. doi: 10.1161/CIR.0000000000001029.
Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407-477. doi: 10.1093/eurheartj/ehz425.
Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370(26):2467-2477. doi: 10.1056/NEJMoa1311376.
Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370(26):2478-2486. doi: 10.1056/NEJMoa1313600.
Saver JL, Carroll JD, Thaler DE, et al. Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke. N Engl J Med. 2017;377(11):1022-1032. doi: 10.1056/NEJMoa1610057.
Mas JL, Derumeaux G, Guillon B, et al. Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke. N Engl J Med. 2017;377(11):1011-1021. doi: 10.1056/NEJMoa1705915.
Søndergaard L, Kasner SE, Rhodes JF, et al. Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke. N Engl J Med. 2017;377(11):1033-1042. doi: 10.1056/NEJMoa1707404.
Markousis-Mavrogenis G, Sfikakis PP, Mavrogeni SI, Tektonidou MG. Combined brain/heart magnetic resonance imaging in antiphospholipid syndrome-two sides of the same coin. Clin Rheumatol. 2021;40(7):2559-2568. doi: 10.1007/s10067-020-05498-2.
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Copyright (c) 2026 José Alberto Sánchez-Guerra, Pedro María Azcárate Agüero, Miguel Ángel García Fernández
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