Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults

Rasmus Bach Sindre; Eva Gerdts; Jukka Putaala; Lisa M D Grymyr; Helga Midtbø; Ana G Almeida; Odd Bech-Hanssen; Raila Busch; Rune K Eilertsen; Ana Catarina Fonseca; Marja Hedman; Juha Huhtakangas; Pekka Jäkälä; Riikka Lautamäki; Mika Lehto; Nicolas Martinez-Majander; Petra Redfors; Tomi Sarkanen; Bettina von Sarnowski; Juha Sinisalo; Marko Virtanen; Ulrike Waje-Andreassen; Nilufer Yesilot; Pauli Ylikotila; Dana Cramariuc

doi:10.1016/j.jacadv.2024.100903

Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults

JACC Adv. 2024 Mar 14;3(4):100903. doi: 10.1016/j.jacadv.2024.100903. eCollection 2024 Apr.

Authors

Rasmus Bach Sindre¹, Eva Gerdts², Jukka Putaala³, Lisa M D Grymyr^{1

4}, Helga Midtbø^{2

4}, Ana G Almeida⁵, Odd Bech-Hanssen⁶, Raila Busch⁷, Rune K Eilertsen¹, Ana Catarina Fonseca⁸, Marja Hedman⁹, Juha Huhtakangas^{10

11}, Pekka Jäkälä¹², Riikka Lautamäki¹³, Mika Lehto¹⁴, Nicolas Martinez-Majander¹⁵, Petra Redfors^{16

17}, Tomi Sarkanen¹⁸, Bettina von Sarnowski¹⁹, Juha Sinisalo²⁰, Marko Virtanen²¹, Ulrike Waje-Andreassen²², Nilufer Yesilot²³, Pauli Ylikotila²⁴, Dana Cramariuc^{1

4}

Affiliations

¹ Department of Clinical Science, University of Bergen, Bergen, Norway.
² Department of Clinical Science, Center for Research on Cardiac Disease in Women, University of Bergen, Bergen, Norway.
³ Department of Neurology, Helsinki University Hospital and University of Helsinki, Finland.
⁴ Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
⁵ Cardiology, Heart and Vessels Department, Faculty of Medicine of Lisbon University, University Hospital Santa Maria, Lisbon, Portugal.
⁶ Department of Clinical Physiology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁷ Department of Internal Medicine B (Cardiology), University Medicine Greifswald, Greifswald, Germany.
⁸ Department of Neurosciences (Neurology), Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal.
⁹ Heart Center and Clinical Imaging Center, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
¹⁰ Department of Neurology, Oulu University Hospital, Oulu, Finland.
¹¹ Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland.
¹² Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
¹³ Heart Centre, Turku University Hospital and University of Turku, Turku, Finland.
¹⁴ Department of Internal Medicine, Jorvi Hospital, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹⁵ Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹⁶ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁷ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁸ Department of Neurology, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹⁹ Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
²⁰ Department of Cardiology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
²¹ Heart Hospital, Tampere University Hospital, Tampere, Finland.
²² Department of Neurology, Haukeland University Hospital, Bergen, Norway.
²³ Istanbul Faculty of Medicine, Department of Neurology, Istanbul University, Istanbul, Turkiye.
²⁴ Neurocenter, Turku University Hospital and Clinical Neurosciences, University of Turku, Turku, Finland.

Abstract

Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored.

Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults.

Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e' velocity (E/e')/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness.

Results: Increased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05).

Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725).

Keywords: cryptogenic ischemic stroke; left atrial mechanics; left atrial stiffness; obesity; stroke in young adults.

Associated data

ClinicalTrials.gov/NCT01934725