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Association between elevated plasma norepinephrine levels and cardiac wall motion abnormality in poor-grade subarachnoid hemorrhage patients

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Abstract

Patients with aneurysmal subarachnoid hemorrhage (SAH) are frequently complicated by acute cardiac dysfunctions, including cardiac wall motion abnormality (WMA). Massive release of catecholamine into the systemic circulation after aneurysmal rupture is believed to result in WMA, and poor-grade SAH seems to be the most important risk factor. However, plasma catecholamine levels have rarely been measured in SAH patients with WMA, and previous studies indicated that the elevated levels might not necessarily predict WMA. The objective of this study is (1) to evaluate relationship between WMA and plasma catecholamine levels in poor-grade SAH patients in the acute phase and (2) to clarify clinical characteristics of SAH patients with WMA. Among 142 poor-grade (World Federation of Neurosurgical Societies grades IV and V) SAH patients, 48 underwent both transthoracic ultrasound and measurement of plasma catecholamine levels within 24 h of SAH onset. They were divided into WMA+ (n = 23) and WMA− (n = 25) groups, and intergroup comparison was made on demographics, plasma catecholamine levels, and outcomes. Plasma norepinephrine levels were significantly higher in WMA+ group than in WMA− group (2,098.4 ± 1,773.4 vs. 962.9 ± 838.9 pg/mL, p = 0.02), and the former showed significantly worse outcomes 90 days after admission. There were no intergroup differences in the plasma levels of epinephrine. Plasma norepinephrine levels were inversely correlated with left ventricular ejection fraction. Multivariate logistic regression analysis revealed that increased plasma norepinephrine levels were predictive of WMA, although age, female sex, and grade V SAH were not. This retrospective study highlights the role of norepinephrine in pathogenesis of SAH-induced WMA.

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Acknowledgments

None of the authors have financial disclosure or conflict of interest regarding the content of this manuscript.

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Authors and Affiliations

  1. Department of Medical Technology, Fujita Health University School of Health Sciences, Toyoake, Japan

    Keiko Sugimoto

  2. Department of Neurosurgery, Fujita Health University School of Medicine, 1-98 Kutsukake, Toyoake, 470-1192, Japan

    Joji Inamasu, Yoko Kato, Yasuhiro Yamada, Tsukasa Ganaha, Motoki Oheda, Natsuki Hattori & Yuichi Hirose

  3. Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan

    Eiichi Watanabe & Yukio Ozaki

Authors
  1. Keiko Sugimoto
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  2. Joji Inamasu
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  3. Yoko Kato
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  4. Yasuhiro Yamada
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  5. Tsukasa Ganaha
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  6. Motoki Oheda
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  7. Natsuki Hattori
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  8. Eiichi Watanabe
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  9. Yukio Ozaki
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  10. Yuichi Hirose
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Corresponding author

Correspondence to Joji Inamasu.

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Comments

Ernst Delwel, Rotterdam, The Netherlands

Sugimoto and co-authors have greatly contributed to the understanding of cardiac complications of a subarachnoid hemorrhage (SAH). Where previous publications have shown contradicting results regarding the relationship between catecholamine release and cardiac complications, the authors have convincingly shown that in poor-grade SAH, due to high initial plasma levels of norepinephrine, cardiac wall motion abnormality (WMA) occurs significantly more in lower grade SAH, and that there is a reverse relationship between plasma norepinephrine levels and left ventricular ejection fraction. By multivariate regression analysis, it is shown that high levels of norepinephrine are the primary predictive parameter. Age, gender, and high-grade SAH score are not predictive of WMA.

In contrast to previous related studies, the authors were able to perform plasma catecholamine measurement and transthoracic ultrasound evaluation of the cardiac wall soon after onset of the SAH in 48 low-grade SAH patients.

Although the difference in levels of norepinephrine in the group with WMA and the group without WMA is statistically significant (P = 0.02), the spreading/standard deviation of the values is large in both groups (Table 2).

Since catecholamines are rapidly metabolized, the high rate of catecholamine release after a SAH should be considered a long-term sustained process. It would be interesting to perform further studies with more consecutive samples examining the decay curve of norepinephrine levels from the onset of the SAH in low-grade SAH patients in relationship to cardiac wall motion abnormalities and clinical outcome.

Tetsuya Goto, Matsumoto, Japan

The authors examined serum catecholamine level and echocardiogram in severe SAH patients within 24 h after ictus. They concluded that plasma norepinephrine levels were significantly higher in WMA (wall motion abnormality)+ group, and that norepinephrine plays an important role in pathogenesis of SAH-induced WMA.

An interpretation of the authors' definition of WMA+, RWMS (regional wall motion score) greater than 1.0, is most important to understand this report. The detail is described in reference [8]: “Each of the 16 wall-motion segments was assigned a wall-motion score: normal = 1; hypokinetic = 2; and akinetic or dyskinetic = 3.” and “The average wall-motion index (WMI) was calculated by adding the scores for each segment and dividing the sum by the number of segments analyzed. A normal ventricle would have an index of 1 and the maximal WMI would be 3 if all segments were akinetic or dyskinetic.” If their calculation of RWMS is the same method as the average WMI in reference [8], WMA + group can include the patient with hypokinetic or dyskinetic movement detected only in one part of the 16 wall segments in the left ventricle. Further analysis of their results on the degree of WMA will be expected.

Takeshi Mikami, Sapporo, Japan

In this report, the authors analyzed serum catecholamine levels in patients with poor-grade subarachnoid hemorrhage (SAH). Their report provides valuable data from the viewpoint of resuscitation. Primary irreversible brain damage due to intracranial pressure elevation and SAH-induced cardiac dysfunction are thought to constitute the mechanisms of poor-grade SAH. As the authors mentioned, the latter is referred to as the catecholamine hypothesis, suggesting involvement of abnormally enhanced catecholamines. Hypothalamic damage due to SAH gives rise to sympathetic hypertonia, which leads to the development of hypokalemia, cardiomyopathy, severe left-sided heart failure, pulmonary edema, lethal arrhythmias, and myocardial stunning. Therefore, it is important to manage cardiopulmonary complications by controlling the catecholamine level using intensive care in cases of poor-grade SAH.

In this study, the authors paid attention to norepinephrine, and discussed its clinical relevance to cardiac wall motion abnormality and prognosis. Although the small amount of data is a statistically weak point, the data is meaningful for the recognition of pathophysiology in this type of SAH. In future, selective control of norepinephrine will become a target of medical treatment for poor-grade SAH.

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Sugimoto, K., Inamasu, J., Kato, Y. et al. Association between elevated plasma norepinephrine levels and cardiac wall motion abnormality in poor-grade subarachnoid hemorrhage patients. Neurosurg Rev 36, 259–266 (2013). https://doi.org/10.1007/s10143-012-0424-z

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