ltal. J. Neurol. Sci. 13.'409-413, 1992
Electrocardiographic changes in subarachnoid hemorrhage secondary to cerebral aneurysm. Report of 70 cases Salvati M.*, Cosentino F.**, Artico M.*, Ferrari M.*, Franchi D.*, Domenicucci M.*, Ramundo Orlando E.*, Tacconi L.*, Cosentino F. jr.*** * Dipartimento di Scienze Neurologiche, Neurochirurgia, Universit?~ "La Sapienza", Roma ** Servizio di Cardiologia, Universitg~ "La Sapienza", Roma *** Dipartimento di Medicina lnterna, H Universitgt "Tor Vergata", Roma
Electrocardiographic (ECG) alterations in the course of sub-arachnoid hemorrhage (SAH) have frequently been reported. The most frequent anomalies reported were lengthening of the QT interval, very negative or positive deep T waves, elevation or depression of the ST segment and the presence of U waves. We report 70 cases of SAH secondary to rupture of intracranial aneurysm (part of a larger group of 150) with ECG changes. We review the literature with particular regard to discussion of the possible pathogenesis of ECG changes and to the way they may affect the general clinical course.
Key Words: Subarachnoid hemorrhage (SAH) - - ECG - - cerebral aneurysm - - autonomic nervous system.
The correlation between acute cerebrovascular diseases and the appearance of ECG changes has been the subject of numerous studies [1,5,6,11,21,22]. This association has been found in many intracranial pathologies such as subarachnoid hemorrhage (SAH), intra-parenchymal hemorrhage, head trauma, cerebral tumors, meningo-encephalitis and ischemic lesions [22,26]. The first pertinent study was that of Harvey Cushing in 1903, who described the onset of arterial hypertension and bradycardia in many patients with intracranial hypertension [11]. It was followed in 1929 by Beattie et al.'s experimental study [4], which defined the role of the periventricular hypothalamic nuclei in the onset of cardiac arrhythmias in cats, that of Aschenbrenner
and Bodechtel in 1938 [2] showing the relationship between intracranial alterations and ECG anomalies and then those of Byer et al. (1947 [7]) and Burch et al. (1954 [6]), which pointed out the association between subarachnoid hemorrhage and ECG changes. Since then many studies have been undertaken in an attempt to shed light on the various aspects of this correlation, how ECG modifications influence long-term prognosis and the possibility of establishing a protocol for their prevention and treatment. In this study we analyze, on the basis of the published data and the present series, the various pathogenetic hypotheses proposed, with the aim of pinpointing the frequency and nature of the ECG changes occurring during SAH and speculating on how they may influence general clinical progress.
Received 20 March 1991 - Accepted 30 November 1991
409
Introduction
The Italian Journal of Neurological Sciences
TABLE I. Type and frequency of ECG changes. ECG Changes T w a v e inversion QT prolongation Prominent U w a v e s ST depression Sinus b r a d y c a r d i a Atrial fibrillation Supraventricular premature beats ST elevation Sinus t a c h y c a r d i a Phasic sinus arrhythmia Right bundle branch block Left bundle branch b l o c k
N. of cases
Percentage Rate
20 15 10 5 5 4 4
28.6 21.4 14.3 7.2 7.2 5.7 5.7
3 1 1 1
4.3 1.4 1.4 1.4
1
1.4
Patients and method
This study comprised 70 patients (30 males, 40 females with ages ranging from 25 to 72 years, mean 53.9) presenting transient or stable ECG changes during SAH. This group was part of a larger series of 150 patients with SAH treated in our Department between 1980 and 1985. SAH was diagnosed by neurological examination with or without puncture and brain CT scan as well as subsequent cerebral midstream angiography. Only patients with intracranial aneurysm were admitted to this study. All the patients studied underwent surgery to exclude the aneurysm. Besides electrolyte and enzyme tests and repeat CT scans, serial ECG examinations were performed in all cases. The last 70 patients also un-
derwent continuous monitoring of ECG parameters for the first 72 hours at least. On the basis of their neurological status on admission, patients were assigned to 3 groups according to the Hunt and Hess scale currently used, namely: group A: patients with headache, vomiting and rigor nuchalis; group B: patients with neurological deficits but no significant loss of consciousness; group C: patients with the disturbances of the above 2 groups plus loss of consciousness. 70 patients were group A (46.7%), 30 group B (20%) and 50 group C (33.3%). Results
In 70 patients out of 150 (46.6%) ECG anomalies were present. This relatively low percentage is explained by the fact that continuous ECG monitoring, which is capable of picking up practically all transient modifications of rhythm, was not performed in all patients. In fact, its use in the last 70 cases brought the frequency of arrhythmias up to 70% (49 out of 70). Of the patients with ECG changes 30 had the aneurysm in the anterior communicating artery, 27 in the posterior communicating artery, 10 in the middle cerebral artery and 1 case each in the basilar artery, the internal carotid artery and the posterior inferior cerebellar artery. The most frequent ECG changes encountered were inversion of the T wave in 20 of the 70 cases (28.6%) followed by an increased QT interval in 15 cases (21.4%) and prominent U waves in 4 cases (14.3%). A comprehensive summary of these data is presented in Table I.
TABLE II. ECG changes in relation to neurological Status. Group B
Group C
Total Number
T w a v e inversion
ECG Changes
6
2
12
20
QT prolongation
7
2
6
15
10
--
--
ST depression
2
3
--
Sinus b r a d y c a r d i a
2
--
Atrial fibrillation
4
--
--
4
Supraventricular premature beats
2
2
--
4
2
--
U waves
ST elevation
Group A
3
1
5 5
3
Sinus t a c h y c a r d i a
--
1
Phasic sinus arrhythmia
--
--
1
1
Right bundle branch b l o c k
--
--
1
1
Left bundle branch b l o c k
--
--
Total N u m b e r
35
10
410
--
10
1
1
1
25
70
Salvati M,: E,C.G. changes in subarachnoid hemorrhage secondary to aneurysm.
Cardiovascular and/or metabolic risk factors were present in 80% of patients, namely, in order of frequency, arterial hypertension (35 cases, 50%), dyslipidemias and diabetes mellitus (7 cases each, 10%), broncopulmonary and liver diseases (5 cases, 7.1% and 2 cases, 2.9% respectively). No significant blood enzyme or electrolytic movements were observed, and values were around normal despite the ECG modifications that occurred. Table I! summarizes the ECG modifications in relation to the patients' neurological status. The foregoing data offer no significant evidence for a relation between a worse clinical status and an increase in the frequency of cardiac rhythm anomalies: indeed, these were more frequent in group A. Finally, 3 deaths (4.3%) were directly attributable to cardiovascular conditions; the first on day 3 in a group B patient with a significant depression of the ST segment, the second and third on day 1 in two group A patients affected by atrial fibrillation, one at a high ventricular rate. Discussion
The presence of ECG changes during SAH is well documented although the percentages reported vary considerably, partly as a result of the type of ECG recording used. In fact, their frequency ranges from about 41% to 98% [1,5,8,12,19, 31,32]. The most frequently reported anomalies include an increase in the QT interval, significantly negative or positive deep T waves, elevation or depression of the QT segment and the appearance of U waves [10,14]. Q waves are an uncommon finding during SAH and it would seem that their appearance negatively influences prognosis [10]. The ECG modifications found in our series (inversion of the U wave in 20 cases, lengthened QT interval in 15, prominent U waves in 10, see Table I) were similar. However, these anomalies more often occur in patients already suffering from heart disease and/or with risk factors [8,31]. In our study as many as 54 out of 70 patients (80%) presented general risk factors or metabolic disease, chiefly arterial hypertension (35 cases, 50%). Systematic use of continuous dynamic ECG was clearly useful for studying cardiac changes during acute cerebrovascular disease, particularly for prompt diagnosis and control of the evolution. In our series too, the percentage of ECG changes in the group of patients subjected to continuous ECG monitoring clearly differed from that in the pat}ents controlled serially (70% versus 26.2%). The early onset of ECG anomalies also found confirmation. In fact, it appears that these mainly
occur within the first 24-48 hours after hemorrhage (1), especially life-threatening arrhythmia (LTA), the frequency of which ranges from 3% to 50% according to series [1,12,15,24]. It seems that LTAs have their onset strictly within 24 hours of SAH and are very often associated with increased length of the QT interval and hypopotassemia (1): on this point too, our results conform to the current data. In line with the literature [1] no significant relationship emerged between the severity of the arrhythmias, when present, and neurological status. Indeed, in our series, the highest frequency of arrhythmias was found in group A patients, namely those in better neurological shape than those of the other 2 groups considered separately. Although the association between cardiac disturbances and acute cerebrovascular diseases has been acknowledged for many years, only during the past 20 years have theories been proposed to explain it [22,31]. These theories have varied widely and have focused, from time to time, on factors such as electrolytic imbalance, hyperactivity of the neurovegetative system and hypertension. No doubt exists however, that the key role is played by the hypothalamus, particularly its posterior and lateral zones, and, to a lesser extent, by the amygdala, pons and medulla oblongata on the autonomic cardiac regulation by means of multisynaptic projections at spinal level [3,4,9,13,17,18,20,22,23,31]. Besides this, the posterior and lateral zones of the hypothalamus are also responsible for control of the sympathetic system [22]. Furthermore, the experimental finding that both resection of the cervical spinal cord at C2 level and bilateral adrenalectomy block rhythm anomalies demonstrates the importance of the hypothalamic-spinal pathways directed towards the suprarenal gland [4,16,22]. Correlations have been reported between the frequency of arrhythmia and the site of aneurysm, which in the majority of cases affected the anterior cerebral circulation [8,24,34]. Andreoli et al. [1] do not share this view: they found no significant correlation between the site of the aneurysm responsible for the bleed and consequent SAH and the frequency and severity of any arrhythmia. Our data accord with their findings. The physiopathological substratum may be attributable to hypothalamic damage. Bleeding into the subarachnoid space following rupture of an aneurysm of the circle of Willis may be followed by vasoconstriction of the hypothalamic arterial vessels and liberation of catecholamines due to direct action on the sympathetic nervous system [25,33} and of cortisol due to indirect action on the hypothalamo-hypophyseal axis [18,251. 411
The Italian Journal of Neurological Sciences
Cortisol may increase the sensitivity of the cardiac muscle to the action of catecholamines and intracellular hypokaliemia [27,30]. Catecholamines may also produce transient cardiac effects such as modifications of electrical activity and/or permanent effects such as myofibrillary degeneration and subendocardial focal lesions [29]. The effects described above may come about as a result of either the hypertensive action or the direct toxic action of these molecules [5,22]. In particular, changes in the ST segment and T wave are typically attributable to the effects of catecholamine. The use of catecholamine-blockers would only cancel out evidence of these anomalies. However, some ECG anomalies, such as bradycardia, respiratory sinus arrhythmia and atrialventricular block, may be attributed to parasympathetic hyperactivity [22]. Intermittent hypokaliemia, a frequent cause of neurogenous arrhyth-
mia, correlates with activation of the renin-angiotensin-aldosterone system. Stober et al. [31] have in fact evaluated the plasma renin activity in patients with SAH presenting complications and found much higher values than normal in 6 out of 7 patients. It has not yet been established however, whether the level of plasma renin is determined by the direct hypothalamic lesion or by increased sympathetic activity. This still leaves the problem of medical treatment: the use of beta-blockers for this purpose has been proposed in order to prevent catecholaminedependent arrhythmia and vagolytics for those due to parasympathetic hypertonus. Parasympatholytics may be of real benefit but they require careful monitoring because of the risk of hypoperfusion and the possibility of bradyarrhythmia [ 10,28,31 ]. Indeed, no therapeutic protocol validated by longterm controlled clinical studies exists as yet.
Sommario Alterazioni elenrocardiografiche in corso di emorragia subaracnoidea sono state frequentemente descritte in letteratura. Le anomalie pia frequentemente segnalate sono state: allungamento dell'intervallo QT, presenza di onde T profonde e ampiamente positive o negative, sopraslivellamento o sottoslivellamento del trano ST e presenza di onde U. Gli autori riportano 70 casi di emorragia subaracnoidea secondaria a rottura di aneurisma intracranico (facenti parte di una pi~ ampia casistica di 150 individui) associata ad anomalie elettrocardiografiche. La letteratura sull'argomento viene accuratamente analizzata con particolare riguardo per la discussione della possibile patogenesi delle anomalie elettrocardiografiche e per l'influenza che tali ano: malie hanno sul decorso clinico dei pazienti.
Address reprint requests to: Prof. Fausto Cosentino Dipartimento di Scienze Neurologiche Neurochirurgia - - Universith "La Sapienza" Servizio di Cardiologia Viale dell'Universith 30/A - - 00185 Roma
References [1] ANDREOLI A., DE PASQUALE G., PINELLI G., GRAZl P., TOGNE'VFI F., TESTA C.: Subarachnoid hemorrhage: frequen O' and severity of cardiac ar-
rhythmias. A survey of 70 cases studied in the acute phase. Stroke, 18:558-564, 1987. [2] ASCHENBRENNER R., BODECHTEL G.: Uber EKGVeranderungen bei Hirntumorkranken. Klin. Wochenschr., 17:298-302, 1938. [3] ATTAR H.J., GUTIERREZM.T., BELLET S., RAV-
412
ENS J.R.: Effects of stimulation of hypothalamus and reticular activating system on production of cardiac arrhythmias. Circ. Res., 12:14-21, 1963. [4] BEATTIEJ., BROW G.R., LONG C.N.H.: Physiological and anatomical evidence of the existence of nerves connecting the hypothalamus with spinal sympathetic centers. Proc. R. Soc. Lond (Biol.), 106:253-275, 1930. [5] BROUWERSP.I.A.M., WUDICKSE.F.M., HASAND., VERMEULEN M., WEVER E.F.D., FRERICKS H., VAN GUN J.: Serial electrocardiographic recording in
Sah'ati M.: E.C.G. changes in subarachnoid hemorrhage secondary" to atteu(ysm.
aneurvsmal subarachnoid hemorrhage. Stroke, 20:1162-1167, 1989. [6] BURCH G.E., MEYERS, AB1LDSKOV J.A.: A new electrocardiographic pattern observed in cerebravascular accidents. Circulation, 9:719-723, 1954. [7] BYER E., ASHMAN R., TOTH L.A.: Electrocardiograms with large, upright T waves and long QT intervals. Am. Heart J., 33:796-806, 1947. [8] COSENTINO F., DOMENICUCCI M., FERRARI M., FRANCHI D., DI GIUGNO G., GAGLIARD1 F.M., GUGLmLM1 G.: Considerazioni cliniche generali in eorso di emorragia subaracnoidea da ronura di a,eurisma: studio retrospettivo in 71 casi. Giom. It. Angiol., 8:78-82, 1988. [9] CROMPTON M.R.: Hypothalamic lesions fi)llowing the rupture q[" cerebral ber O' aneurysms. Brain, 86:301-314, 1963. [10] CRUICKSHANK J.M., NEIL-DWYER G., BR1CE J.: Electrocardiographic changes and their prognostic significance in subarachnoid hemorrhage. J. Neurol. Neurosurg. Psychiatry, 37:755-759, 1974. [11] CUSHING H.: The blood-pressure reaction of acute cerebrcd compression illustrated by cases of intracranial hemorrhage: a sequel to the Mutter lecture for 1901. Am. J. Med. Sci., 125:1017-1044, 1903. [12] DI PASQUALE G., PINELI,I G., ANDREOLI A., MANINI G., GRAZI P., TOGNETTI F.: Holter detection of cardiac arrhvthmias in intracranial subarachnoid hemorrhage. Am. J. Cardiol., 59:596-600, 1987. [13] DOSHI R., NEm-DWYER G.: Hypothalamic and myocardial lesions after subarachnoid hemorrhage. J. Neurol. Neurosurg. Psychiatry, 40:821826, 1977. [14] EISALO A., PERASALO J., HALONEN P.I.: Electrocardiographic abnormalities and some laborutor)" findings in patients with subarachnoid hemorrhage. Br. Heart J., 34:217-226, 1972. [15] ESTANOL B.V., MARIN O.S.M.: Cardiac arrhythmias and sudden death in subarachnoid hemorrhage. Stroke, 6:382-385, 1975. [16] HAWKINS W.E., Ct,OWER B.R.: Myocardial damage c~'ter head trauma and simulated intrucranial hemorrhage in mice: the role of the autonomic nen,ous system. Cardiovasc. Res., 5:524-529, 1971. [17] HOUSSAY B.A., MOLINELH E.A.: Centre adrenalino-secreteur hypothalamique. C.R. Soc. Biol. (Pails), 93:1454-1455, 1925. [18] JENKINS J.S., BUCKELL M., CARTER A.B.: Hypothalamic-pituitarv-adrenal function after subarachnoid hemorrhage. Br. Med. J., 4:707-709, 1969. [19] KAYE M.P., McDONALD R.G., RANDALL W.C.:
Systolic hypertension and subendocardial hemorrhages produced by electrical stimulation of the stellate ganglion. Circ. Res., 9:1164, 1961. [20] KORTEWEG G.C.J., BOELES J.T.F., TENCATE J.: blfluence of stimulation of some subcortical areas on electrocardiogram. J. Neurophysiol., 20:100107, 1957. [21] KREUS K.E., KEMILA S.J., TAKALA J.K.: Electrocardiographic changes in cerebrovascular accidents. Acta Med. Scand., 185:327-334, 1969. [22] MAroON D.W., SEGAL R., THOMPSON M.E.: Subarachnoid hemorrhage and the heart. Neurosurgery, 18:101-106, 1986. [23] MELVILLE K.I., BLUM B., SHISTER H.E., SILVER M.D.: Cardiac ischemic changes and arrhvthmias induced by hypathahunic stimulation. Am. J. Cardiol., 12:781-791, 1963. [24] MIKOLICH J.R., JACOBS W.C., FLETCHER G.F.: Cardiac arrhythmias in patient with acute cerebrovascular accidents. JAMA, 246:1314-1317, 1981. [25] NEm-DwYEr G., WALTER P., CRUICKSHANK J.M., DOSHI B., O'GORMAN P.: Effect of propranolol and phentolamine on myocardial necrosis after subarachnoid hemorrhage. Br. Med. J., 2:990-992, 1978. [26] OPPENHEIMER S.M., CECHETTO D.F., HACmNSKI V.C.: Cerebrogenic cardiac arrhythmias. Cerebral electrocardiographic influences and their role in sudden death. Arch. Neurol., 47:513-519, 1990. [27] RAAB W.: Emotional and senso o, stress factors in myocardial pathology. Am. Heart J., 72:538, 1966. [28] RANT D., GATE 1.: Myocardial lesions following experimental intracranial hemorrhage. Prevention with propranolol. Am. Heart J., 83:232, 1972. [29] REICHENBACH D.D., BENDITT E.P.: Catecholamines and cardiomyopathy: the pathogenesis and potential importance of myofibrillar degeneration. Hum. Pathol., 1: 125-150, 1970. [30] SELYE H.: The evolution of the stress concept. Am. J. Cardiol., 26:289, 1970. [31] STOBER T., ANSTATT T.H., SEN S., SCHIMRtGK, JAGER H.: Cardiac arrhvthmias in subarachnoid hemorrhage. Acta Neurochir., 93:37-44, 1988. [32] SURAVLCZ B.: Electrocardiographic patterns of cerebrovascular accident. JAMA, 197:913, 1966. [33] TOMOMATSU T., UEBA Y., MATSUMOTO T.: Electrocardiographic observations and urinary excretion of catecholamines in cardiovascular disorders. Jap. Circ. J., 28:905-912, 1964. [34] YAMOUR B.J., SRIDHARAN M.R., RICE J.R., FLOWERS N.C.: Electrocardiographic changes in cerebro-vascular hemorrhage. Am. Heart J., 99:294-300, 1980.
413
Electrocardiographic changes in subarachnoid hemorrhage secondary to cerebral aneurysm. Report of 70 cases Salvati M.*, Cosentino F.**, Artico M.*, Ferrari M.*, Franchi D.*, Domenicucci M.*, Ramundo Orlando E.*, Tacconi L.*, Cosentino F. jr.*** * Dipartimento di Scienze Neurologiche, Neurochirurgia, Universit?~ "La Sapienza", Roma ** Servizio di Cardiologia, Universitg~ "La Sapienza", Roma *** Dipartimento di Medicina lnterna, H Universitgt "Tor Vergata", Roma
Electrocardiographic (ECG) alterations in the course of sub-arachnoid hemorrhage (SAH) have frequently been reported. The most frequent anomalies reported were lengthening of the QT interval, very negative or positive deep T waves, elevation or depression of the ST segment and the presence of U waves. We report 70 cases of SAH secondary to rupture of intracranial aneurysm (part of a larger group of 150) with ECG changes. We review the literature with particular regard to discussion of the possible pathogenesis of ECG changes and to the way they may affect the general clinical course.
Key Words: Subarachnoid hemorrhage (SAH) - - ECG - - cerebral aneurysm - - autonomic nervous system.
The correlation between acute cerebrovascular diseases and the appearance of ECG changes has been the subject of numerous studies [1,5,6,11,21,22]. This association has been found in many intracranial pathologies such as subarachnoid hemorrhage (SAH), intra-parenchymal hemorrhage, head trauma, cerebral tumors, meningo-encephalitis and ischemic lesions [22,26]. The first pertinent study was that of Harvey Cushing in 1903, who described the onset of arterial hypertension and bradycardia in many patients with intracranial hypertension [11]. It was followed in 1929 by Beattie et al.'s experimental study [4], which defined the role of the periventricular hypothalamic nuclei in the onset of cardiac arrhythmias in cats, that of Aschenbrenner
and Bodechtel in 1938 [2] showing the relationship between intracranial alterations and ECG anomalies and then those of Byer et al. (1947 [7]) and Burch et al. (1954 [6]), which pointed out the association between subarachnoid hemorrhage and ECG changes. Since then many studies have been undertaken in an attempt to shed light on the various aspects of this correlation, how ECG modifications influence long-term prognosis and the possibility of establishing a protocol for their prevention and treatment. In this study we analyze, on the basis of the published data and the present series, the various pathogenetic hypotheses proposed, with the aim of pinpointing the frequency and nature of the ECG changes occurring during SAH and speculating on how they may influence general clinical progress.
Received 20 March 1991 - Accepted 30 November 1991
409
Introduction
The Italian Journal of Neurological Sciences
TABLE I. Type and frequency of ECG changes. ECG Changes T w a v e inversion QT prolongation Prominent U w a v e s ST depression Sinus b r a d y c a r d i a Atrial fibrillation Supraventricular premature beats ST elevation Sinus t a c h y c a r d i a Phasic sinus arrhythmia Right bundle branch block Left bundle branch b l o c k
N. of cases
Percentage Rate
20 15 10 5 5 4 4
28.6 21.4 14.3 7.2 7.2 5.7 5.7
3 1 1 1
4.3 1.4 1.4 1.4
1
1.4
Patients and method
This study comprised 70 patients (30 males, 40 females with ages ranging from 25 to 72 years, mean 53.9) presenting transient or stable ECG changes during SAH. This group was part of a larger series of 150 patients with SAH treated in our Department between 1980 and 1985. SAH was diagnosed by neurological examination with or without puncture and brain CT scan as well as subsequent cerebral midstream angiography. Only patients with intracranial aneurysm were admitted to this study. All the patients studied underwent surgery to exclude the aneurysm. Besides electrolyte and enzyme tests and repeat CT scans, serial ECG examinations were performed in all cases. The last 70 patients also un-
derwent continuous monitoring of ECG parameters for the first 72 hours at least. On the basis of their neurological status on admission, patients were assigned to 3 groups according to the Hunt and Hess scale currently used, namely: group A: patients with headache, vomiting and rigor nuchalis; group B: patients with neurological deficits but no significant loss of consciousness; group C: patients with the disturbances of the above 2 groups plus loss of consciousness. 70 patients were group A (46.7%), 30 group B (20%) and 50 group C (33.3%). Results
In 70 patients out of 150 (46.6%) ECG anomalies were present. This relatively low percentage is explained by the fact that continuous ECG monitoring, which is capable of picking up practically all transient modifications of rhythm, was not performed in all patients. In fact, its use in the last 70 cases brought the frequency of arrhythmias up to 70% (49 out of 70). Of the patients with ECG changes 30 had the aneurysm in the anterior communicating artery, 27 in the posterior communicating artery, 10 in the middle cerebral artery and 1 case each in the basilar artery, the internal carotid artery and the posterior inferior cerebellar artery. The most frequent ECG changes encountered were inversion of the T wave in 20 of the 70 cases (28.6%) followed by an increased QT interval in 15 cases (21.4%) and prominent U waves in 4 cases (14.3%). A comprehensive summary of these data is presented in Table I.
TABLE II. ECG changes in relation to neurological Status. Group B
Group C
Total Number
T w a v e inversion
ECG Changes
6
2
12
20
QT prolongation
7
2
6
15
10
--
--
ST depression
2
3
--
Sinus b r a d y c a r d i a
2
--
Atrial fibrillation
4
--
--
4
Supraventricular premature beats
2
2
--
4
2
--
U waves
ST elevation
Group A
3
1
5 5
3
Sinus t a c h y c a r d i a
--
1
Phasic sinus arrhythmia
--
--
1
1
Right bundle branch b l o c k
--
--
1
1
Left bundle branch b l o c k
--
--
Total N u m b e r
35
10
410
--
10
1
1
1
25
70
Salvati M,: E,C.G. changes in subarachnoid hemorrhage secondary to aneurysm.
Cardiovascular and/or metabolic risk factors were present in 80% of patients, namely, in order of frequency, arterial hypertension (35 cases, 50%), dyslipidemias and diabetes mellitus (7 cases each, 10%), broncopulmonary and liver diseases (5 cases, 7.1% and 2 cases, 2.9% respectively). No significant blood enzyme or electrolytic movements were observed, and values were around normal despite the ECG modifications that occurred. Table I! summarizes the ECG modifications in relation to the patients' neurological status. The foregoing data offer no significant evidence for a relation between a worse clinical status and an increase in the frequency of cardiac rhythm anomalies: indeed, these were more frequent in group A. Finally, 3 deaths (4.3%) were directly attributable to cardiovascular conditions; the first on day 3 in a group B patient with a significant depression of the ST segment, the second and third on day 1 in two group A patients affected by atrial fibrillation, one at a high ventricular rate. Discussion
The presence of ECG changes during SAH is well documented although the percentages reported vary considerably, partly as a result of the type of ECG recording used. In fact, their frequency ranges from about 41% to 98% [1,5,8,12,19, 31,32]. The most frequently reported anomalies include an increase in the QT interval, significantly negative or positive deep T waves, elevation or depression of the QT segment and the appearance of U waves [10,14]. Q waves are an uncommon finding during SAH and it would seem that their appearance negatively influences prognosis [10]. The ECG modifications found in our series (inversion of the U wave in 20 cases, lengthened QT interval in 15, prominent U waves in 10, see Table I) were similar. However, these anomalies more often occur in patients already suffering from heart disease and/or with risk factors [8,31]. In our study as many as 54 out of 70 patients (80%) presented general risk factors or metabolic disease, chiefly arterial hypertension (35 cases, 50%). Systematic use of continuous dynamic ECG was clearly useful for studying cardiac changes during acute cerebrovascular disease, particularly for prompt diagnosis and control of the evolution. In our series too, the percentage of ECG changes in the group of patients subjected to continuous ECG monitoring clearly differed from that in the pat}ents controlled serially (70% versus 26.2%). The early onset of ECG anomalies also found confirmation. In fact, it appears that these mainly
occur within the first 24-48 hours after hemorrhage (1), especially life-threatening arrhythmia (LTA), the frequency of which ranges from 3% to 50% according to series [1,12,15,24]. It seems that LTAs have their onset strictly within 24 hours of SAH and are very often associated with increased length of the QT interval and hypopotassemia (1): on this point too, our results conform to the current data. In line with the literature [1] no significant relationship emerged between the severity of the arrhythmias, when present, and neurological status. Indeed, in our series, the highest frequency of arrhythmias was found in group A patients, namely those in better neurological shape than those of the other 2 groups considered separately. Although the association between cardiac disturbances and acute cerebrovascular diseases has been acknowledged for many years, only during the past 20 years have theories been proposed to explain it [22,31]. These theories have varied widely and have focused, from time to time, on factors such as electrolytic imbalance, hyperactivity of the neurovegetative system and hypertension. No doubt exists however, that the key role is played by the hypothalamus, particularly its posterior and lateral zones, and, to a lesser extent, by the amygdala, pons and medulla oblongata on the autonomic cardiac regulation by means of multisynaptic projections at spinal level [3,4,9,13,17,18,20,22,23,31]. Besides this, the posterior and lateral zones of the hypothalamus are also responsible for control of the sympathetic system [22]. Furthermore, the experimental finding that both resection of the cervical spinal cord at C2 level and bilateral adrenalectomy block rhythm anomalies demonstrates the importance of the hypothalamic-spinal pathways directed towards the suprarenal gland [4,16,22]. Correlations have been reported between the frequency of arrhythmia and the site of aneurysm, which in the majority of cases affected the anterior cerebral circulation [8,24,34]. Andreoli et al. [1] do not share this view: they found no significant correlation between the site of the aneurysm responsible for the bleed and consequent SAH and the frequency and severity of any arrhythmia. Our data accord with their findings. The physiopathological substratum may be attributable to hypothalamic damage. Bleeding into the subarachnoid space following rupture of an aneurysm of the circle of Willis may be followed by vasoconstriction of the hypothalamic arterial vessels and liberation of catecholamines due to direct action on the sympathetic nervous system [25,33} and of cortisol due to indirect action on the hypothalamo-hypophyseal axis [18,251. 411
The Italian Journal of Neurological Sciences
Cortisol may increase the sensitivity of the cardiac muscle to the action of catecholamines and intracellular hypokaliemia [27,30]. Catecholamines may also produce transient cardiac effects such as modifications of electrical activity and/or permanent effects such as myofibrillary degeneration and subendocardial focal lesions [29]. The effects described above may come about as a result of either the hypertensive action or the direct toxic action of these molecules [5,22]. In particular, changes in the ST segment and T wave are typically attributable to the effects of catecholamine. The use of catecholamine-blockers would only cancel out evidence of these anomalies. However, some ECG anomalies, such as bradycardia, respiratory sinus arrhythmia and atrialventricular block, may be attributed to parasympathetic hyperactivity [22]. Intermittent hypokaliemia, a frequent cause of neurogenous arrhyth-
mia, correlates with activation of the renin-angiotensin-aldosterone system. Stober et al. [31] have in fact evaluated the plasma renin activity in patients with SAH presenting complications and found much higher values than normal in 6 out of 7 patients. It has not yet been established however, whether the level of plasma renin is determined by the direct hypothalamic lesion or by increased sympathetic activity. This still leaves the problem of medical treatment: the use of beta-blockers for this purpose has been proposed in order to prevent catecholaminedependent arrhythmia and vagolytics for those due to parasympathetic hypertonus. Parasympatholytics may be of real benefit but they require careful monitoring because of the risk of hypoperfusion and the possibility of bradyarrhythmia [ 10,28,31 ]. Indeed, no therapeutic protocol validated by longterm controlled clinical studies exists as yet.
Sommario Alterazioni elenrocardiografiche in corso di emorragia subaracnoidea sono state frequentemente descritte in letteratura. Le anomalie pia frequentemente segnalate sono state: allungamento dell'intervallo QT, presenza di onde T profonde e ampiamente positive o negative, sopraslivellamento o sottoslivellamento del trano ST e presenza di onde U. Gli autori riportano 70 casi di emorragia subaracnoidea secondaria a rottura di aneurisma intracranico (facenti parte di una pi~ ampia casistica di 150 individui) associata ad anomalie elettrocardiografiche. La letteratura sull'argomento viene accuratamente analizzata con particolare riguardo per la discussione della possibile patogenesi delle anomalie elettrocardiografiche e per l'influenza che tali ano: malie hanno sul decorso clinico dei pazienti.
Address reprint requests to: Prof. Fausto Cosentino Dipartimento di Scienze Neurologiche Neurochirurgia - - Universith "La Sapienza" Servizio di Cardiologia Viale dell'Universith 30/A - - 00185 Roma
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