Heart Rate Variability and Recurrent Stroke and Myocardial Infarction in Patients With Acute Mild to Moderate Stroke

What research will your doctors and hospital initiate to prevent recurrent vascular events? If nothing, then you don't have a functioning stroke hospital.

Heart Rate Variability and Recurrent Stroke and Myocardial Infarction in Patients With Acute Mild to Moderate Stroke

Regina von Rennenberg^1,2,3*, Thomas Krause⁴, Juliane Herm^1,2, Simon Hellwig^1,2, Jan F. Scheitz^1,2,5, Matthias Endres^1,2,3,5, Karl Georg Haeusler^6† and Christian H. Nolte^1,2,3,5†

• ¹Klinik und Hochschulambulanz für Neurologie, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany
• ²Center for Stroke Research Berlin (CSB), Charité – Universitätsmedizin Berlin, Berlin, Germany
• ³German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen), Berlin, Germany
• ⁴Department of Neurology, Jüdisches Krankenhaus Berlin, Berlin, Germany
• ⁵German Center for Cardiovascular Research (Deutsches Zentrum für Herz-Kreislaufforschung), Berlin, Germany
• ⁶Department of Neurology, Universitätsklinikum Würzburg, Würzburg, Germany

Objectives: In patients with acute ischemic stroke, reduced heart rate variability (HRV) may indicate poor outcome. We tested whether HRV in the acute phase of stroke is associated with higher rates of mortality, recurrent stroke, myocardial infarction (MI) or functional outcome.

Materials and Methods: Patients with acute mild to moderate ischemic stroke without known atrial fibrillation were prospectively enrolled to the investigator-initiated Heart and Brain interfaces in Acute Ischemic Stroke (HEBRAS) study (NCT 02142413). HRV parameters were assessed during the in-hospital stay using a 10-min section of each patient's ECG recording at day- and nighttime, calculating time and frequency domain HRV parameters. Frequency of a combined endpoint of recurrent stroke, MI or death of any cause and the respective individual events were assessed 12 months after the index stroke. Patients' functional outcome was measured by the modified Rankin Scale (mRS) at 12 months.

Results: We included 308 patients (37% female, median NIHSS = 2 on admission, median age 69 years). Complete follow-up was achieved in 286/308 (93%) patients. At 12 months, 32 (9.5%), 5 (1.7%) and 13 (3.7%) patients had suffered a recurrent stroke, MI or death, respectively. After adjustment for age, sex, stroke severity and vascular risk factors, there was no significant association between HRV and recurrent stroke, MI, death or the combined endpoint. We did not find a significant impact of HRV on a mRS ≥ 2 12 months after the index stroke.

Conclusion: HRV did not predict recurrent vascular events in patients with acute mild to moderate ischemic stroke.

Introduction

The state of the autonomic nervous system can be assessed by heart rate variability (HRV) using long term (i.e. 24 h) or short term (i.e. 5–10 min) Holter ECG (1). To date, there is no universal recommendation which HRV parameters are best to examine the autonomic nervous system. One can calculate time domain (differences in beat-to-beat intervals) and frequency domain (spectral components of the tachogram) parameters (1).

Large prospective studies conducted in the general population have shown an association between HRV and incident stroke (2, 3). In hypertensive patients, reduced HRV was associated with an increased risk of stroke as well as acute coronary syndrome (ACS) (4). Moreover, previous studies have reported that HRV is reduced in acute ischemic stroke patients compared to healthy controls (5–7). Compared to stroke patients with normal HRV, those with reduced HRV showed increased mortality and poor functional outcome in several retrospective and prospective studies (5, 8–10). However, these studies were based on <100 stroke patients and data on the association between HRV and adverse vascular events such as recurrent stroke or myocardial infarction (MI) are lacking in stroke patients. Furthermore, the exact mechanism by which reduced HRV leads to poor outcome in stroke patients is unknown (6, 8, 9). There is evidence that ischemic brain injury itself may induce dysregulation of the central autonomic network, which may subsequently lead to myocardial injury and even myocardial infarction (11, 12). On the other hand, reduced HRV may also be present before stroke, indicating a pre-existing stroke risk factor. Whatever the exact mechanism, dysregulation of the autonomic nervous system may contribute to risk of recurrent stroke and MI.

In this cross-sectional study, we examined the impact of HRV parameters as predictors of recurrent stroke, MI, mortality as well as on functional outcome in patients with acute ischemic stroke.

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