stretch during repeated respiratory efforts equivalent to Muellermaneuvers causes the release of atrial natriuretic peptide (ANP). ANPincreases sodium and water excretion, leading to reductions in bloodvolume and a reduction of BP [11].

Treatment of SRBD by nocturnal CPAP may thus improve sympatho-vagal balance. This has been demonstrated for the night period [13–15].The effectiveneness of this treatment for improving daytime vasovagalepisodes in our patients argues in favor of the persistence of its efficacyduring the day. Our hypothesis is currently based on the observation of afew patients without long-term follow-up. However, in the absence ofeffective therapy for recurrent vasovagal syncope, the treatment of SRBDmay be of value and treatment by CPAP merits investigation in patientswith signs of fragmented sleep. A randomized controlled trial comparingeffective to sham CPAP is required to validate this hypothesis.

References

[1] Serletis A, Rose S, Sheldon AG, Sheldon RS. Vasovagal syncope in medical students andtheir first-degree relatives. Eur Heart J 2006;27:1965–70.

[2] Pepin JL, Guillot M, Tamisier R, Levy P. The upper airway resistance syndrome.Respiration 2012;83:559–66.

[3] Alboni P, AlboniM, Bertorelle G. The origin of vasovagal syncope: to protect the heart orto escape predation? Clin Auton Res 2008;18:170–8.

[4] Bracha HS, Bracha AS, Williams AE, Ralston TC, Matsukawa JM. The human fear-circuitry and fear-induced fainting in healthy individuals–the paleolithic-threathypothesis. Clin Auton Res 2005;15:238–41.

[5] Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms inobstructive sleep apnea. J Clin Invest 1995;96:1897–904.

[6] Shepard Jr JW. Gas exchange and hemodynamics during sleep. Med Clin North Am1985;69:1243–64.

[7] Lazarus A, Py A, Guerin F, Valty J, Le Heuzey JY. Arrhythmia and syndrome of obstructivesleep apnea in adults. Arch Mal Coeur Vaiss 1993;86:1753–9.

[8] Hanly PJ, George CF, Millar TW, Kryger MH. Heart rate response to breath-hold,Valsalva and Mueller maneuvers in obstructive sleep apnea. Chest 1989;95:735–9.

[9] Andreas S, Hajak G, von Breska B, Ruther E, Kreuzer H. Changes in heart rate duringobstructive sleep apnoea. Eur Respir J 1992;5:853–7.

[10] Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros P. A cause of excessive daytimesleepiness. The upper airway resistance syndrome. Chest 1993;104:781–7.

[11] Guilleminault C, Faul JL, Stoohs R. Sleep-disordered breathing and hypotension. Am JRespir Crit Care Med 2001;164:1242–7.

[12] Guilleminault C, Poyares D, Rosa A, Huang YS. Heart rate variability, sympathetic andvagal balance and EEG arousals in upper airway resistance and mild obstructive sleepapnea syndromes. Sleep Med 2005;6:451–7.

[13] Chrysostomakis SI, Simantirakis EN, Schiza SE, et al. Continuous positive airwaypressuretherapy lowers vagal tone in patients with obstructive sleep apnoea–hypopnoeasyndrome. Hellenic J Cardiol 2006;47:13–20.

[14] Maser RE, Lenhard MJ, Rizzo AA, Vasile AA. Continuous positive airway pressuretherapy improves cardiovascular autonomic function for persons with sleep-disordered breathing. Chest 2008;133:86–91.

[15] Kuramoto E, Kinami S, Ishida Y, Shiotani H, Nishimura Y. Continuous positive nasalairway pressure decreases levels of serum amyloid A and improves autonomicfunction in obstructive sleep apnea syndrome. Int J Cardiol 2009;135:338–45.

0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved.http://dx.doi.org/10.1016/j.ijcard.2013.03.061

Cardiac wall motion abnormality associated with spontaneousintracerebral hemorrhage

Joji Inamasu a,⁎,1, Keisuke Ito a,1, Keiko Sugimoto b,1, Eiichi Watanabe c,1, Yoko Kato a,1, Yuichi Hirose a,1

a Department of Neurosurgery, Fujita Health University School of Medicine, Toyoake, Japanb Department of Medical Technology, Fujita Health University School of Health Sciences, Toyoake, Japanc Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan

a r t i c l e i n f o

Article history:Received 11 March 2013Accepted 23 March 2013Available online 17 April 2013

Keywords:CatecholamineEchocardiographyOutcomeSpontaneous intracerebral hemorrhageWall motion abnormality

Spontaneous intracerebral hemorrhage (SICH) is a subtype of strokewith high morbidity/mortality rate. Release of massive catecholaminesinto the systemic circulation has been reported in SICH patients [1,2],which may explain high frequency of reversible ECG changes in thatpopulation [3]. However, cardiac wall motion abnormality (WMA),another subtype of reversible cardiac injury associated with “catecho-lamine storm”, in SICH patients has rarely been investigated [4]. This

retrospective study was conducted to evaluate the incidence of WMA,association between WMA and plasma catecholamine levels, and toidentify variables correlated with WMA in SICH patients. Demographicvariables, plasma catecholamine levels, and outcomes were comparedbetween WMA+ and WMA− groups. Multivariate logistic regressionanalysis was used to identify variables correlated with WMA. Linearregression analysis was used to evaluate the relationship betweenplasma catecholamine levels and left ventricular ejection fraction(LVEF). Data are indicated by mean ± SD, and p b 0.05 was consideredstatistically significant.

Data on 126 SICH patients (77 men/49 women, mean: 67.8 ±12.4 years) admitted between April 2011 and March 2012 and under-went transthoracic echography (TTE) and plasma catecholaminemeasurement within 24 h of onset were analyzed. Experienced ultra-sound technicians performed the TTE procedures, and the followingimages were routinely obtained: parasternal long axis; parasternal shortaxis at the level of themitral valve, papillarymuscles, and apex; apical 2-,3-, and 4-chamber; subcostal 4-chamber; and subcostal short axis. TheAmerican Society of Echocardiography's 16 segment model and regionalwall motion score index (RWMSI) were used for evaluation of WMA [5].All TTE and ECG studies were interpreted by a blinded board-certifiedcardiologist.

Eighteen patients (14%) sustained WMA, with a frequency of 17% inmen and 10% in women. Twenty-five patients (20%) had history ofischemic heart disease (IHD), and WMA was observed in 9 of them.By contrast, WMA was observed in 9 of the 101 patients without IHD.The difference was statistically significant (36% vs. 9%, p=0.002).

⁎ Corresponding author at: Department of Neurosurgery, FujitaHealthUniversity Schoolof Medicine,1-98 Kutsukake, Toyoake 470-1192, Japan. Tel.: +81562 93 9153; fax:+8156293 3118.

E-mail address: inamasu@fujita-hu.ac.jp (J. Inamasu).1 Takes responsibility for all aspects of the reliability and freedom from bias of the

data presented and their discussed interpretation.

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Demographic variables were compared betweenWMA+ (n= 18) andWMA− (n = 108) groups, with such variables as age, gender, history ofIHD, history of hypertension, frequency of anticoagulants/antiplateletuse, frequency of patients with admission Glasgow Coma Scale (GCS)≤8, frequency of patients with hematoma volume N10 mL, frequency ofECG abnormality, admission systolic blood pressure (SBP), and LVEF(Table 1). History of IHD was significantly more frequent in WMA+group (50%vs.15%,p= 0.002). Admission SBP (171.8 ± 36.9 vs.193.2 ±32.7 mmHg, p= 0.01) and LVEF (47 ± 14% vs. 67 ± 8%, p b 0.001)were significantly lower in WMA+ group. RWMSI in WMA+ groupranged from 1.05 to 2.50 (mean: 1.59 ± 0.44). Plasma epinephrine

Table 1Comparison of demographic variables between WMA+ and WMA− group.

WMA− (n = 108) WMA+ (n = 18) p

Age (y) 67.3 ± 12.3 70.5 ± 12.7 0.31Male vs. female 64:44 13:5 0.43History of IHD 16 (15%) 9 (50%) 0.002*History of hypertension 90 (83%) 16 (89%) 0.80Use of AC/AP 24 (22%) 8 (44%) 0.09Admission GCS score ≤ 8 19 (18%) 4 (22%) 0.89Hematoma volumeN10 mL

40 (37%) 8 (44%) 0.74

ECG abnormality 85 (79%) 15 (83%) 0.89Systolic blood pressure(mm Hg)

193.2 ± 32.7 171.8 ± 36.9 0.01**

Regional wall motionscore index

1a 1.05–2.50(mean: 1.59 ± 0.44)

N/A

Left ventricular ejectionfraction (%)

67 ± 8 47 ± 14 b0.001***

AC/AP anticoagulant/antiplatelet; ECG electrocardiogram; GCS Glasgow Coma Scale;IHD ischemic heart disease; N/A not applicable; WMA wall motion abnormality.*, **, *** Statistically significant.

a By definition.

Fig. 1. Comparison of plasma epinephrine (A) and norepinephrine (B) levels. Theepinephrine levels in patients with wall motion abnormality (WMA) were significantlyhigher than those without WMA (p= 0.01) (A). By contrast, There was no significantdifference in the plasma levels of norepinephrine between the two groups (B).

Fig. 2. Linear regression analysis showing mild inverse correlation between plasmaepinephrine levels and left ventricular ejection fraction (LVEF) (R =−0.22, p=0.02)(A). By contrast, there was no correlation between plasma norepinephrine levels andLVEF (R = 0.014, p= 0.88) (B).

Table 2Multivariate logistic regression analysis to identify variables correlated with WMA in126 patients with spontaneous intracerebral hemorrhage.

Clinical variables OR 95% CI p

Age 1.026 0.963–1.094 0.419Male sex 4.009 0.704–22.839 0.118History of IHD 5.615 1.291–24.427 0.021*Admission GCS score ≤8 1.549 0.159–15.075 0.706Hematoma volume N10 mL 2.967 0.616–14.291 0.175Epinephrine (pg/mL) 1.010 1.001–1.019 0.035**Norepinephrine (pg/mL) 1.002 0.096–1.009 0.102

CI confidence interval; GCS Glasgow Coma Scale; IHD ischemic heart disease; OR oddsratio; WMA wall motion abnormality.*, ** Statistically significant.

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levels were significantly higher in WMA+ group (177.4 ± 283.5 vs.88.3 ± 84.3 pg/mL, p= 0.01) (Fig. 1A). By contrast, there was nosignificant intergroup difference in plasma norepinephrine levels(1005.9 ± 1206.1 vs. 887.0 ± 600.1 pg/mL, p= 0.53) (Fig. 1B). Linearregression analysis revealed mild inverse correlation between plasmaepinephrine levels and LVEF (R=−0.22, p= 0.02) (Fig. 2A). Bycontrast, there was no correlation between plasma norepinephrinelevels and LVEF (R= 0.014, p= 0.88) (Fig. 2B).

Multivariate logistic regression analysis demonstrated that history ofIHD (OR, 5.615; 95% CI, 1.291–24.417; p= 0.02) and increased plasmaepinephrine levels (OR, 1.010; 95% CI, 1.001–1.019; p= 0.04) werecorrelated with WMA (Table 2). In WMA+ group, 3 died duringadmission with the inpatient mortality rate of 17%. In WMA− group, 7died during admission with the inpatient mortality rate of 7%. Thedifference in the mortality rates was not statistically significant(p=0.40).

Cardiac WMA occurs relatively frequently after subarachnoidhemorrhage (SAH), with a reported incidence of 8%–27% [6–8]. Bycontrast, little has been known about WMA associated with SICH. Theoverall incidence of WMA in our cohort was 14%. However, 20% of ourpatients had underlying IHD, and as expected, those with IHD exhibitedsignificantly higher incidence of WMA than those without IHD (36% vs.9%, p= 0.002), whichmeans that obtaining history of IHD is importantin predicting the presence ofWMA inpatientswith SICH. This is thefirstclinical study that systemically documents those incidences, suggestingthat WMA associated with SICH may not be as rare as has previouslybeen thought: mild to moderate WMAmay be present in SICH patientswithout being noticed, althoughWMA in thosewithout history of IHD isuncommon.

In SAH patients, advanced age, female sex, and poor clinical gradewere the predictive factors for WMA [6–9]. By contrast, neitheradvanced age nor female sex was correlated with WMA in this study.In addition, variables suggestive of severe brain damage, i.e., admissionGCS score ≤8 and hematoma volume N10 mL were not correlated withWMA. Those results suggest that SICH severity may not be correlatedwithWMA. Furthermore, substantial pathophysiological differencemayexist between WMA by SAH and that by SICH: while increased plasmanorepinephrine plays an important role in the former [6–8], increasedplasma epinephrine rather than norepinephrinemay be correlatedwithWMA in SICH patients. Only plasma epinephrine levels were inverselycorrelated with LVEF (Fig. 2). The reason for the lack of correlation

between increased plasma norepinephrine levels and WMA in thisstudy is unclear. However, it may be speculated that SICH patients maybecome relatively insensitive to the increase in plasma norepinephrine:most SICH patients have underlying hypertension, and they may havebeen exposed to chronic elevation in plasma norepinephrine levelswhich are partially responsible for their hypertension [10].

The degree of cardiac injury was more severe in WMA+ group(Table 1). However, there was no significant difference in the inhospitalmortality rate regardless of the presence of WMA, indicating thatWMAmay not be predictive of poor outcomes of SICH patients. The clinicalefficacy of TTE in SICH patients was reported previously [3]. Theexamination has no adverse effects, and it may reliably detectundiagnosed WMA in SICH patients. However, WMA is mostlysubclinical in severity, and routine acquisition of TTE may not changethe course of treatment and hence may not be essential.

The authors of this article certify that they comply with the principlesof Ethical Publishing in the International Journal of Cardiology.

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[6] Sugimoto K, Inamasu J, Hirose Y, et al. The role of norepinephrine and estradiol in thepathogenesis of cardiac wall motion abnormality associated with subarachnoidhemorrhage. Stroke 2012;43:1897–903.

[7] Sugimoto K, Inamasu J, Kato Y, et al. Association between elevated plasmanorepinephrine levels and cardiacwallmotion abnormality inpoor-grade subarachnoidhemorrhage patients. Neurosurg Rev 2013;36:259–66.

[8] Inamasu J, Nakatsukasa M,Mayanagi K, et al. Subarachnoid hemorrhage complicatedwith neurogenic pulmonary edema and takotsubo-like cardiomyopathy. Neurol MedChir (Tokyo) 2012;52:49–55.

[9] Lee VH, Connolly HM, Fulgham JR, et al. Tako-tsubo cardiomyopathy in aneurysmalsubarachnoid hemorrhage: an underappreciated ventricular dysfunction. J Neurosurg2006;105:264–70.

[10] Goldstein DS. Plasma catecholamines and essential hypertension. An analytical review.Hypertension 1983;5:86–99.

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