Cardiac manifestations after subarachnoid hemorrhage: A systematic review of the literature

Cardiac Manifestations After SubarachnoidHemorrhage: A Systematic Review of theLiterature

Yasser L. Sakr, Issam Ghosn, and Jean Louis Vincent

Cardiac alterations associated with subarachnoidhemorrhage (SAH) have been recognized and fre-quently reported. We systematically reviewed the lit-erature on MEDLINE using the key words: SAH �(heart, cardiac, electrocardiogram, cardiac enzymes,troponin, myoglobin, echocardiography, scintigra-phy, Holter, and regional wall motion abnormalities)and included all articles describing cardiac abnormal-ities in the course of SAH whether spontaneous orsecondary. The diagnosis of SAH was established bycomputed tomography scan, lumbar puncture, orbrain autopsy. Cardiac abnormalities were identifiedby electrocardiogram, enzymatic elevation, Holtermonitoring, echocardiography, cardiac scintigraphy,coronary angiography, or autopsy. Despite the con-siderable literature describing cardiac alterations dur-ing the course of SAH, epidemiological, pathophysi-ological, and prognostic aspects are yet to be clari-fied. Further studies are needed to evaluate the mag-nitude of this problem.Copyright 2002, Elsevier Science (USA). All rightsreserved.

The interconnection between the central ner-vous system (CNS) and the heart was first

described by Cushing at the turn of the previouscentury.1 Cardiac abnormalities were describedthereafter, associated with various CNS diseases.In 1947, Byer et al2 reported electrocardiographic(ECG) alterations during subarachnnoid hemor-rhage (SAH), and these changes have subse-quently been fairly extensively studied. Othersigns of cardiac dysfunction have been reportedalso, but the epidemiology, pathophysiology, pat-terns, and prognostic implications of CNS-medi-ated cardiac alterations with SAH remain incom-pletely defined.One of the reasons for the general lack of consen-

sus on cardiac abnormalities in SAH is that reporting

the incidence of ECG abnormalities, as well as othercardiac abnormalities, could be biased. First, manystudies, especially early reports, included only pa-tients with the considered cardiac abnormalities, sothat the incidence of these cannot be determined.Second, the presence of dropout cases with prehos-pital mortality prevents accurate determination ofthe incidence of cardiac abnormalities. Third, manyprospective studies excluded patients with underly-ing heart disease, resulting in an underestimation ofthe overall incidence. Fourth, procedures may bemore commonly performed in patients with sus-pected cardiac abnormality; thus, retrospectivestudies may overestimate the incidence of cardiacabnormalities. Fifth, the utilization of different tech-niques, with different degrees of accuracy, to mea-sure the samevariable in different studieswill lead tofaulty estimation, as for reporting arrhythmias byHolter monitoring rather than 12-lead ECG, or re-porting left ventricular ejection fraction angio-graphically rather than by echocardiography.

Methods

We systematically reviewed the literature onMEDLINE using the key words: SAH � (heart,cardiac, ECG, cardiac enzymes, troponin, myo-globin, echocardiography, scintigraphy, Holter,and regional wall motion abnormalities). Weincluded all articles describing cardiac abnor-

From the Department of Intensive Care, Erasme Hos-pital, Free University of Brussels.Address reprint requests to Prof. J. L. Vincent, Depart-

ment of Intensive Care, Erasme University Hospital, Routede lennik 808, 1070 Bruxelles, Belgium.Copyright 2002, Elsevier Science (USA). All rights reserved.0033-0620/02/4501-0001$35.00/22/1/124633doi:10.1053/pcad.2002.124633

67Progress in Cardiovascular Diseases, Vol. 45, No. 1, (July/August) 2002: pp 67-80

malities in the course of SAH whether sponta-neous or secondary. The diagnosis of SAH wasestablished by computed tomography (CT)scan, lumbar puncture, or brain autopsy. Aneu-rysmal SAH was identified by cerebral angiogra-phy. Cardiac abnormalities were identified byECG, enzymatic elevation, Holter monitoring,echocardiography, cardiac scintigraphy, coro-nary angiography, or autopsy. The epidemiol-ogy, pathophysiology, patterns, interrelations,and prognostication of various abnormalitieswere identified.

Epidemiology of CardiacAbnormalities With SAH

ECG Alterations

The incidence of ECG abnormalities ranged from49% to 100% (Table 1). Rudehill et al3 prospectivelystudied 406patientswith SAHand foundECGalter-ations in 82% of the patients regardless of underly-ing heart disease, electrolyte disturbances, and treat-ment that might affect the ECG. As expected,patients with other conditions that might affect the

Table 1. Morphological Electrocardiographic Changes in Subarachnoid Hemorrhage

InvestigatorsNo. ofPatients

Incidence ofECG Changes(%)

T-WaveChanges

QT-Prolongation

ST-SegmentChanges

Presence ofU Wave

PathologicalQ Wave

Tall PWave LVH

Lan-Sheng et al128 7 100 2 6 — 4 — — —Cropp and Manning78 29 86 16 14 13 8 4 3 4Shuster68 19† ? 15 — 7 10 — — —Hersh129�¶ 20 ? 4 9 10 8 — 8 —Ananthachari & Anto130 20§ 100 15 15 11 5 — — 1Hunt et al131� 20 60 10 5 2 — — — —Kreus et al69� 35 71 14 8 6 11 — — —Umali et al70 11 ? 6 1 6 1 — — —Eisalo et al54 20 100 9 11 15 13 — 7 1Cruickshank et al55� 40 80 29 22 16 10 2 16 —Page et al132� 95 ? 5 21 16 — 3 2 —Dimant and Grob133 10 80 2 2 5 1 — — 3Doshi and Neil-Dwyer52¶ 12 ? 3 1 2 1 — — —Goldstein75 28 71 7 20 11 9 — — —Stober and Kunze134‡ 89 81 30 16 66 13 — — 20Rudehill et al64 22 91 15 15 10 9 — — —Page et al135� 100 80 36 21 16 28 3 2 —Melin and Fogelhom136‡ 76 ? 16 8 15 3 — 2 —Di Pasqualle et al137 120# 67 15 — 44 19 1 — 4Rudehill et al3¶ 406 82 129 94 62 190 — — —Brouwers et al77� 61 100 36 24 31 27 8 7 22Ramani et al138� 19 84 13 6 2 2 — — 2Grad et al58 40 75 20 26 16 26 — — —Davis et al13� 45 49 8 — — — 1 1 —Rinkel et al139 32 56 7 7 7 — 6Szabo et al11 19 100 10 5 — 2 — — —Kono et al12 12 100 — — 7 — — — —Brouwers et al59¶ 37 81 13 — 18 — 6 — —Mayer et al8‡ 57 100 34 23 2 18 1 2 6Manninen et al140‡ 70 100 12 — 9 — 1 — —Svigelj et al60¶ 22 ? 8 14 5 14 — — —Zaroff et al141‡� 59 100 48 — 22 — 8 — —Parekh et al10‡ 39 100 18 — 18 — — — —Total 1,691 605 387 470 410 45 50 69(%) (36%) (23%) (28%) (24%) (3%) (3%) (4%)

†12 spontaneous and 7 secondary.‡Retrospective study.§12 spontaneous and 8 secondary.#99 aneurysmal, 5 AV malformation, 16 no vascular lesion.¶case control study.�Patients with underlying heart disease were excluded.Abbreviations: LVH: Left ventricular hypertrophy; ?, undefined; ECG, electrocardiogram; SAH, subarachnoid hemorrhage; AV, atrioven-

tricular.

68 SAKR, GHOSN, AND VINCENT

ECG had a greater overall incidence of ECG alter-ations, ST-segmentdepression, andQT-interval pro-longation (P � .001). This study outlined the possi-bility that including patients with extra-CNSconditions that may affect cardiac electrophysiolog-ical and morphological parameters may result in anincorrect estimation of the incidence of SAH-in-duced cardiac alterations.Reviewing the data from a large randomized,

controlled trial of the calcium antagonist, nicardi-pine, after SAH, Solenski et al4 reported that 50%of 457 patients in the placebo limb had an abnor-mal admission ECG, with nearly one fourth ofpatients having either ST-segment or T-wavechanges.

Cardiac Dysfunction

Several studies have reported clinical or electro-cardiographic cardiac dysfunction with SAH. Theincidence of impaired left ventricular function inthe form of either regional wall motion abnormal-ities (RWMAs) or globally impaired contractilityby echocardiography ranged from 8% to 100%.5-12

This wide range can be explained by the samefactors that bias the incidence of ECG alterations.Pollick et al,5 reported that 4 of 13 patients

(31%) had echocardiographic evidence ofRWMA; only 2 patients (15%) had clinical pulmo-nary edema. Kuroiwa et al,7 reported that all 23patients with SAH and an elevated ST-segmenthad reversible RWMA; 8 patients underwent cor-onary angiography that showed normal coronaryarteries and corresponding RWMA. Mayer et al8

studied 57 patients with SAH and without historyof cardiac diseases; 5 patients (9%) had RWMA. Ina recent retrospective study of 589 patients withSAH, 147 of whom had echocardiograms per-formed during their acute hospitalization, globalwall motion abnormalities or RWMA were foundin 28% of cases, including 8% with a history ofcoronary artery disease (CAD) or cardiomyopa-thy; the incidence of clinical cardiac dysfunctionwas not evaluated in this study.9 Parekh et al10

reported that 9 (15%) of 39 patients with SAH hadRWMA, of whom 5 (13%) had clinical or radio-logical evidence of myocardial dysfunction.Cardiac scintigraphy has been used to assess

myocardial perfusion abnormalities. Szabo et al11

prospectively studied 19 patients with SAH whohad ECG abnormalities. Thallium scintigraphy

was performed 3 � 2 days after admission; 6 pa-tients (32%) had abnormal thallium scans at rest,but there was no link between the type of ECGabnormality and the presence or absence of amyo-cardial perfusion abnormality.Kono et al12 studied left ventriculography in 12

patients with SAH, of whom 7 had elevated STsegment with corresponding RWMA; echocardio-graphic evidence of improvement in wall motionwas noted in all patients except 1 who died earlyin the clinical course.

Pathophysiology of CardiacAbnormalities With SAH

Proposed Mechanisms

A complex network of cortical and subcorticalneural systems in the telenceplalon, diencepha-lon, pons, and medulla provides autonomic ner-vous system control.13 Several hypothalamic re-gions are particularly involved in the pathogenesisof cardiac dysfunction, especially in the ECG al-terations, observed in the course of SAH.TheCNS is believed to affect cardiac function in

2 ways. First, an indirect effect can be mediatedthrough release of humoral substances such asepinephrine and norepinephrine. Second, directcontrol occurs through efferent and afferent con-nections with the 2 main divisions of the auto-nomic, the parasympathetic, and the sympathaticnervous systems.

Animal Models of Hypothalamic Stimulation

The effect of hypothalamic stimulation. Severalexperimental animal studies have demonstratedthe influence of the CNS on cardiac function. ECGalterations and myocardial damage on autopsyhavemost commonly been studied, and as early as1913, Levy14 reported that premature ventricularbeats caused by chloroform anesthesia could beabolished by cardiac sympathetic denervation. Af-ter the induction of ventricular arrhythmias bystimulation of the hypothalamus in cats, Brow etal15 demonstrated that cutting fibers originatingfrom the hypothalamus prevented these arrhyth-mias, suggesting a direct neural effect. This find-ing prompted several investigators to attempt tolocalize areas within the hypothalamus capable ofaffecting cardiac function and to define the pres-

69SUBARACHNOID HEMORRHAGE

ence or absence of direct neural connections to theheart.Several studies have demonstrated the effect of

hypothalamic stimulation at different points oncardiac rhythm as well as on ECG morphology.Stimulation of the lateral hypothalamus has beenshown to cause frequent ventricular arrhyth-mias.,16 and stimulation of the lateral and poste-rior hypothalamus led tomarked alterations in theQRS-T morphology, changes in rhythm such asbigeminy and trigeminy, A-V dissociation, extra-systoles, paroxysmal nodal and ventricular tachy-cardias, and Wolff-Parkinson-White configura-tion.17 Porter et al18 stimulated the ventralhippocampus and the medial nuclei of the amyg-dala to induce ECG alterations, of which repolar-ization phase abnormalities were the most com-mon. The changes were transient during the firstperiod of stimulation but became persistent aftersubsequent stimulation.Other areas also have been claimed to be in-

volved in the pathogenesis of ECG alterations.Stimulation of the reticular formation producedtachycardia, widening of the QRS complex, tran-sient A-V dissociation with nodal escape, ventric-ular ectopics, and fusion beats, the ECG changesresembling those that occurred with stimulationof the posterolateral hypothalamus, raising thepossibility of the involvement of the reticular for-mation in the genesis of various cardiac arrhyth-mias.19 Yanwowitz et al20 demonstrated changesin ventricular repolarization by unilateral satellateganglionectomy or stimulation of the ganglion ofthe opposite side, a finding that suggests that localdifferences in sympathatic tone of the heart mus-cle may cause this particular pattern.

Mechanism of signal transformation. Directneural connections as well as humoral factors,have been implicated in transforming signals forcardiac affection. Beattie et al21 and Magouin22

confirmed the existence of nerve tracts connectinghypothalamic centers to the spinal sympathaticcenter, thus demonstrating a neurological roadmap potentially accounting for the CNS-cardiacinterconnection. Several studies18,23,24 have re-ported that transsection of the cervical spinal cordcaused the ECG abnormalities produced by hypo-thalamic stimulation to disappear, favoring thepresence of a direct neural connection to theheart. Other studies16,25 showed that ECGchanges after hypothalamic stimulation were

abolished by vagotomy combined with section ofthe spinal cord, demonstrating an interplay ofsympathetic and parasympathetic factors.Direct intracoronary injections of epineph-

rine18,26 and acetylcholine27 have been shown toinduce ECG alterations, favoring the presence ofhumoral mechanisms. Jacobson and Danufsky28

were able to abolish most of the ECG changes byparenteral administration of atropine, while�-blockers abolished arrhythmias produced byhypothalamic stimulation.29 The ability of vago-lytic and adrenergic blockade to abolish centrallyinitiated ECG abnormalities favors a humoralmechanism, and it was, thus, proposed that theadrenal glands may be involved. However, Benserand Weinstein30 showed that bilateral adrenalec-tomy could blunt or inhibit the vasopressor re-sponse but not the ECG alterations of hypotha-lamic stimulation, suggesting a more complexinterplay between direct and humoral factors.

Animal Models of SAH

Cardiac alterations. Several animal models ofSAH have been used to study cardiac alterationsand to study the pathophysiological aspects ofCNS-mediated cardiac damage. The incidence ofECG changes in these models ranged from 33% to100%, and the spectrum of ECG alterations in-volved almost all possible morphological andrhythmic alterations.31-45

Elrifai et al31 demonstrated RWMAs of variablelocation and severity in 9 dogs with SAH. Re-cently, Zaroff et al32 demonstrated that RWMAswere more prevalent in dogs with SAH than incontrol subjects (89% v 20%; P � .002), withoutevidence of coronary artery disease or spasm bycoronary angiography, without alterations in re-gional myocardial blood flow as assessed by radio-labeled microspheres, and without any perfusiondefects using myocardial contrast echocardiogra-phy.The effect of repeated hemorrhage on ECG al-

terations has been studied also, with the fre-quency of ECG disturbances and the degree ofhemodynamic and ECG alterations increasingwith repeated hemorrhagic episodes.33,34

Mechanism of CNS stimulation. Two mecha-nisms of CNS stimulation have been proposed,including direct mechanical irritation by theblood or one of its components on CNS centers


and increased intracranial tension (ICT) second-ary to SAH.In mice, Hawkins et al35 demonstrated that in-

jection of saline into the subarachnoid spacecaused a lower incidence of myocardial damageon autopsy than injection of blood, suggestingthat the irritant nature of blood is responsible forCNS stimulation. However, Lacy and Earle36

showed that ECG abnormalities did not appearwhen the cannula used for introducing the bloodinto the subarachnoid space had pierced andrested within the brain tissue or had been misdi-rected towards the spinal cord; injection of 0.9%saline or different colloids did not reproduce theECG changes, suggesting that the ability of bloodto maintain an elevated ICT was responsible forthe ECG alterations. In cats, similar increases insympathatic activity were noted whether blood orcerebrospinal fluid (CSF) was injected into thesubarachnoid space,37 and in rabbits intracisternalinjection of prostaglandin F2 in rabbits producedsevere ECG changes similar to those observedwith SAH, but not observed with saline injec-tion.38 Lorenzo et al39 studied the effect of variousblood products as well as 0.9% saline and dextranwhen injected into the subarachnoid space in rats.Packed red blood cells had the most potent ar-rhythmogenic effect, associated with significantQT-interval prolongation and cardiac histopatho-logical changes, indicating that packed red bloodcells may play a role in the etiology of post-SAHarrhythmias.In contrast, Estanol et al40 reproduced the same

ECG changes seen in SAH by rapid saline injec-tion in dogs, proposing that increasing ICT is thestimulating factor for ECG alterations, and Ver-looy et al34 demonstrated that 0.9% saline repro-duced the same hemodynamic and ECG alter-ations observed in SAH in mice. Similarly,increased ECG alterations with increased ICThave been reported in a baboon model of SAH,supporting the role of increased ICT in the genesisof ECG alterations.41

Mechanisms of signal transformation. Direct aswell as humoral mechanisms of signal transforma-tion have been studied. Offerhaus and van Gool42

reported an increased myocardial catecholamineconcentration in rabbits with SAH compared withcontrol subjects. Moreover, administration of pro-pranolol was successful in abolishing arrhyth-mias. In rats with intracranial hemorrhage, a

lower incidence of myocardial damage was dem-onstrated with administration of sympatholyticagents.,35 and Smith and Ray43 prevented or abol-ished arrhythmias induced by a sudden increasein ICT by administration of atropine and vagot-omy. Boddin et al44 showed that induction of SAHin dogs resulted in an increase in the plasma epi-nephrine concentration; the relation of plasmacatecholamines to tissue catecholamines was in-consistent. Estanol et al40 studied the effect ofvagotomy (or atropine), sympathetic denervation(or�-blockers), and spinal cord resection on abol-ishing arrhythmias due to SAH in dogs; a combi-nation of the 3 methods was the sole meansof abolishing arrhythmia effectively. Lacy andEarle45 also demonstrated that different neuralmechanisms underly the bradycardia generatedfrom the ventral brain and cisterna magna, as ev-ident from a variable response to administrationof atropine, isoproterenol, and vagotomy.The notion that hypothalamic centers are re-

sponsible for the ECG changes has also beenraised, based on previously mentioned studies.However, Lacy and Earle46 demonstrated that pre-mature ventricular contractions (PVCs) are medi-ated by forebrain areas and require the integrity ofthe neuroanatomical connections with structuresthat are caudal to the midbrain; thus, they couldbe abolished by midcolicular lesions. However,sinus tachycardia and other ECG abnormalitiesare mediated by brain stem only.

CNS-Mediated Myocardial Damage inAutopsy of Animal Models

Although some early studies18,42 failed to demon-strate myocardial alterations after either hypotha-lamic stimulation or experimental SAH, otherstudies demonstrated various degrees of myocar-dial damage. Hawkins et al35 showed that focalnecrosis or myocardial hemorrhage was consis-tent in all mice with SAH. Areas of necrosis weresmall with individual necrotic fibers. The necroticmuscle fibers appeared swollen and hyalinized,with a loss of their striations and nuclei. The ne-crotic areas were often located over both ventri-cles, and leukocytes were present in many of theseareas. Cardiac hemorrhage appeared to be relatedto the areas of extensive necrosis. An unexpect-edly high incidence of myocardial damage oc-curred in the saline-injected group and the nee-


dle-controlled group that was explained by theauthors as being caused by blood release in thesubarachnoid space during the procedure. Lorenzoet al39 demonstrated contraction band necrosismost frequently in the midmural region of theventricular septum at the midcavity levels in miceinjected with packed red blood cells or wholeblood. All lesions were distributed as isolated cellsor in small clusters.Themyocardial lesions observed in SAH are not

pathognomonic to the disease.47 Several stud-ies48-50 have reported the same lesions with vari-ous anxiety stimuli. These lesions differ histolog-ically from those of the coagulation necrosisseen with ischemic infarction and from otherordinarily recognized cytoplasmic degenerativechanges, such as cloudy swelling, hyalinosis, andfatty changes.47 This difference is reflected bysuch terms as infarct-like, accelerated necrosis,necrobiosis, and myocytolysis, which have beenused to describe the myocardial damage observedin these cases.

Mechanisms of CNS-Mediated Cardiac Effectsin Clinical Studies

Mechanisms of CNS stimulation. The mecha-nism of CNS stimulation in patients with SAH isnot well defined but may indeed originate in thehypothalamus as proposed by animal studies.Hammermeister and Reichenbach51 reported a pa-tient with transmural MI after SAH who also hadpyknosis and chromolysis of cells of the hypothal-amus. In postmortem examinations of the hypo-thalamus of 12 patients who died from SAH and 6who died from other intracranial pathology,Doshi and Neil-Dwyer52 noted that 6 of the pa-tients with SAH showed small perivascular hem-orrhage and edema in the periventricular region, 2had distension of perforating vessels, and another2 had marked edema of vascular endothelial cellswith perivascular cuffing by polymorphonuclearleucocytes in the periventricular nucleus. One pa-tient had severe ECG changes associated withcomplete hypothalamic infarction. The sectionsobtained from the hypothalamus were completelynormal in patients with other intracranial pro-cesses.

Mechanisms of signal transformation. Both di-rect and humoral factors are likely to be impli-cated in signal transformation. Electron micros-

copy studies have demonstrated an abundance ofnerve fibers adjacent to myocardial cells, indicat-ing the potential for a direct autonomic effect.53

Catecholamines have also been implicated inthe cardiac alterations observed in SAH. Similarmyocardial lesions were observed in patients inthe so-called “catecholamine” heart as in patientswith pheochromocytoma,47 prompting several in-vestigators to study the hormonal profile of pa-tients with SAH.Eisalo et al54 studied urinary excretion of cat-

echolamines and metanephrines, and plasma cor-tisol levels, in 20 patients with SAH. Urinary epi-nephrine excretion was determined at least oncein 18 patients, of whom 11 patients (61%) hadelevated titers. Higher titers were associated withpoor prognosis. Urinary metanephrines were ele-vated in only 1 of 9 patients, and 9 (53%) of 17patients had elevated plasma corticosteroids.None of the measured parameters were correlatedto the ECG alterations. Cruickshank et al55

showed that urinary catecholamines and serumcorticosteroid levels were increased in SAH pa-tients with abnormal ECGs. Elevated plasma cor-ticosteroid levels were associated with hypokale-mia; both were believed to potentiate the toxiceffects of catecholamines on the heart. The inter-pretation of the significance of 24-hour urinarycatecholamine levels should be cautious. Whileurinary levels represent, to some extent, an overallestimate of sympathetic activity, they are unlikelyto reflect the influence of transitory changes. Theyare also dependent on renal blood flow and func-tion.56

Serum catecholamines have also been evaluatedin patients with SAH. Benedict and Loach57 foundthat plasma epinephrine and norepinephrine lev-els were significantly raised in patients recoveringfrom SAH, and higher levels on admission wereassociated with a poor outcome. Grad et al58 re-ported elevated plasma norepinephrine levels onadmission in 20 (50%) of 40 patients with SAH.The elevated levels were correlated only with si-nus tachycardia and T-wave inversion, so that thecause-effect relationship was not obvious. Brou-wers et al59 studied serial ECGs and serial plasmanorepinephrine concentrations in 37 consecutivepatients with aneurysmal SAH and 18 operatedcontrol subjects. ECG abnormalities were signifi-cantly higher in the SAH group. By contrast,plasma norepinephrine concentrations were higher


in control subjects than in patients and higherin patients with poor prognosis but showed co-variance with established predictors of outcomesuch as the Glasgow coma score (GCS) on ad-mission, the amount of extravasated blood onthe initial CT, and patient age. Plasma cortisolwas found to be more elevated in SAH patientsthan in control subjects. This study demon-strated that high plasma norepinephrine con-centrations did not explain the occurrence ofECG abnormalities and were not useful as inde-pendent predictors of poor outcome. Othershave also reported that ECG abnormalities inpatients with SAH are not correlated withplasma norepinephrine levels.60 Indeed, thevariability of plama catecholamine levels ques-tions the value of their measurement.

CNS-Mediated Myocardial Damage inClinical Studies

CNS-mediated myocardial damage can be as-sessed indirectly by measurement of markers ofmyocardial damage and directly by visualizationof myocardial sections at autopsy.Several markers have been used to demonstrate

myocardial damage with various degrees of accu-racy, including, most commonly, cardiac en-zymes, especially creatine phosphokinase MBfraction (CK-MB), serum myoglobin, and tropo-nin I. Determination of CK-MB in patients withSAH has yielded conflicting results. Althoughsome studies demonstrated increased serum lev-els,5,61-63 others did not.10,64 The potential braincontribution to serum CK-MB levels limits itsspecificity as a marker of myocardial damage.Also, the frequency and timing of determinationsvary among different studies.Several studies10,64 failed to demonstrate a sig-

nificant increase in serum myoglobin in patientswith SAH. Recently, however, cardiac troponin I(cTnI) levels were found to be elevated in patientswith SAH.10,65 cTnI has the advantage of beingable to identify, with high sensitivity and specific-ity, myocardial cell damage that is undetectable byconventional enzyme methods.66 Parekh et al10

studied the incidence of myocardial injury in 32patients with aneurysmal SAH using cTnI assay,correlated with CK-MB, myoglobin, and catechol-amine metabolites. Eight patients (25%) demon-strated elevated cTnI levels, and 5 patients (11%)

had abnormal CK-MB levels. Patients with moresevere grades of SAH were most likely to haveelevated cTnI and to clinically manifest myocar-dial dysfunction. The predictive value of cTnI formyocardial dysfunction was better than that ofCK-MB. Myoglobin levels were not significantlyelevated. Further studies are needed to confirmthese findings.Several studies5,52,54,67-77 have described the

myocardial alterations in patients with SAH at au-topsy. While some studies failed to demonstrateany myocardial alterations,54,67-71,78 others re-ported various degrees of myocardial dam-age.5,52,72-77 Greenhoot and Reichenbach73 re-ported acute multifocal myocardial damage intissue sections of all 20 patients with SAH whenspecial stains were applied. Three pathologicalchanges were found; increased eosinophilic stain-ing, myocyte swelling and indistinct cross-stria-tions, and myofibril degeneration similar to thatobserved in experimental models. The relation ofthese findings to the clinical condition beforedeath was not clear. In 11 patients (92%), out of12 who died from SAH, Doshi and Neil-Dwyer52

demonstrated focal necrosis, interstitial infiltra-tion, or myocytolysis. The abnormalities were notevident in another 6 patients who died due toother intracranial pathology. In another study, thesame authors76 reported the same changes in twothirds of patients who died of SAH; 1 patient alsohad a congested myocardium, and 6 patients hadpatchy myocardial hemorrhages. Neil-Dwyer etal74 studied the effects of administration of pro-pranolol and phentolamine to patients with SAH.Of the 12 patients who died, 6 patients were re-ceiving propranolol and phentolamine, and 6were receiving placebo. Necrotic myocardial le-sions were present in all 6 patients who had re-ceived placebo. No necrotic lesions were observedin patients who were receiving propranolol andphentolamine, suggesting a cardioprotective ef-fect of sympatholytic agents in the course of SAH.Although there is strong evidence of myocardialdamage with SAH, the potential reversibility ofthis damage, as described with different variablessuch as ECG and RWMAs, renders the detectionof this damage time-sensitive. In other words, pa-tients could develop reversible myocardial dam-age, which will not be observed at autopsy.


Patterns of CNS-Mediated CardiacAffection

Case Reports

We identified case reports51,73,78-127 describingcardiac alterations defined as any clinical, ECG,echocardiographic, or zymologic alteration in pa-tients with SAH, in a total of 80 patients (33 men,47 women), with a mean age of 50 years (10 to 77years).2,51,67,73,79-127 Based on these reports, 26 pa-tients (33%) had systemic hypertension, 15 (19%)were diabetic, and 3 had a history of previous headtrauma. Previous ECGs were available in only 6patients (8%). The main presentation of SAH wasby severe, agonizing headache in 37 patients(46%) followed by coma in 29 patients (36%).Syncope was reported in 12 patients (15%), and 7patients (9%) described ischemic chest pain. Thediagnosis of SAHwas established by CT scan in 36patients (45%), lumbar puncture in 39 patients(49%), and at autopsy in 5 patients (6%). SAHwasspontaneous in 74 patients, and in others second-ary to head trauma (4 patients), cocaine use (1patient), and AV malformation (1 patient). Hypo-kalemia was reported in only 3 patients.The most common morphological changes

were T-wave alterations (61%); T wave was in-verted in 43%, flat in 9%, and peaked in 9%. ST-segment abnormalities were present in 42% of pa-tients; elevated in 27%, and depressed in 15%. QTprolongation was present in 40%. A U wave waspresent in 9%. Pathological Q wave was present in9%. The most common arrhythmia was sinustachycardia (18%), followed by PVC (14%), tor-sade de pointes (10%), ventricular tachycardia(9%), and ventricular fibrillation (5%). Sinus bra-dycardia was reported once. Conduction abnor-malities occurred in 20% of cases, with completeheart block (7.5%), sinus arrest (4%), and type Isecond degree AV block (4%).Cardiac enzymes were measured in 46 patients.

CKwas elevated in 11 patients (24%), and CK-MBwas elevated in seven patients (15%). Cardiac en-zymes were normalized in all patients with ele-vated titers within a maximum of 48 hours. cTnIwas increased in 1 patient with proved MI. Echo-cardiography performed in 15 patients showedRWMAs in 12 patients (80%) and impaired leftventricular systolic function in 8 patients (53%).The alterations were reversible in 5 patients

within 2 weeks. Myocardial scintigraphy, per-formed in 4 patients, was unremarkable. Coro-nary angiography, performed in 10 patients,showed coronary artery disease in 1 patient. Nec-ropsy was performed on 16 (20%) of the 43 pa-tients who died and showed myocytolysis in 5patients (31%).

Clinical Studies

Severalprospectiveandretrospectivestudieshavebeenconducted to evaluate themyocardial alterations asso-ciated with SAH.3,4,8,10-13,52,54,55,58-60,64,68-70,77,78,128-144

ECG alterations were the most commonly studiedmyocardial feature. Several morphological andrhythm alterations were described (Tables 1 and 2).The most common morphological alterations wereT-wave abnormalities (36%) andST-segment abnor-malities (28%). U waves were reported in 24% ofcases QT intervals were prolonged in 23% of cases.Pathological Q wave and tall P waves were eachreported in 3% of cases.The most commonly reported arrhythmias

were sinus bradycardia (15%) followed by sinustachycardia (13%) and premature ventricularbeats (13%). Atrial fibrillation and ventriculartachycardia were reported in 2% of cases, AVblock in 1.5%, and asystole in 1% of cases.Zaroff et al9 retrospectively studied RWMAs in

30 patients with SAH and evidence of coronaryartery disease. Both regional and global wall mo-tion patterns were observed. Preservation of api-cal function relative to the base was observed in57% of cases. Many of the wall motion patternswere atypical of coronary artery disease but corre-lated with the distribution of myocardial sympa-thetic nerve terminals. This previously unre-ported apex-sparing pattern of left ventriculardysfunction provides indirect evidence for a neu-rally mediated mechanism of cardiac injury. Fur-ther studies are needed to confirm this observa-tion.

Prognostic Implications of CardiacAlterations Associated With SAH

The relation of CNS-mediated cardiac alterationsto morbidity and mortality has been a matter ofdebate. Hersh129 noted in 7 patients in whom se-rial ECGs were performed that the incidence ofdepressed ST segments was increased in those


who died. This observation supports the work ofCruickshank et al145 who prospectively showedabnormal ECGs in patients with SAH who died.The presence of Q waves or raised ST segmentsindicated a poor prognosis. The 2 patients withpathological Q waves both died, and 3 patientswith raised ST segments developed arterial spasm,1 of whom died. A high incidence of peaked Pwave, short PR interval, a long QTc, and tall Uwaves occurred in the ECGs of the 6 patients whodied. Various combinations of these 4 ECGchanges, in addition to peaking of T waves, indi-cated a bad prognosis irrespective of the type oftreatment. Others have also shown that ECGchanges have a prognostic significance.132 In thisstudy, conscious patients mainly had bradycardia,but patients in a coma had pronounced T-wave

inversion, suggesting greater sympathatic stimu-lation in patients with more severe neurologicalalterations.In contrast, other studies have failed to demon-

strate significant prognostic implications of ECGalterations with SAH. Shuster68 found that ECGchanges were not related to brain damage as as-sessed clinically, and Ananthachari and Anto130

reported that the occurrence or persistence ofECG alterations did not affect the course of illnessadversely. These findings agree with others indi-cating no correlation between ECG alterationsand the development of vasospasm.7,146

Other studies demonstrated a relationship be-tween the severity of CNS lesions and ECGchanges but failed to demonstrate a direct relationto cardiac-related morbidity and mortality. Brow-

Table 2. Rhythm Disturbances in Subarachnoid Hemorrhage

InvestigatorsNo. ofPatients AF

SinusTachycardia

SinusBradycardia Asystole SVT AV Block PVC VT

Lan-Sheng et al128 7 — 1 — — — — — —Cropp & Manning78 29 — 2 4 1 — 1 — —Shuster68 19* 1 — 8 — — — 19 —Hersh129 20 ? ? — — 1 1 3 —Ananthachari & Anto130 20 1 5 7 — — — 1 —Hunt et al131 20 — — 6 1 — — — —Umali et al70 11 — 2 — — 1 — 2 —Eisalo et al54 20 2 5 7 — — — 2 —Cruickshank et al55 40 — 13 9 — — — 5 —Page et al132 95 — 10 — — — 1 5 —Dimant and Grob133 10 — — — — — 1 — —Goldstein75 28 3 10 — — — 3 2 —Stober and Kunze, 1982134 89 — 10 22 — — — 6 —Rudehill et al64 22 1 — — — — — 3 1Page et al135 100 — 10 32 — — 3 5 —Melin and Fogelholm136‡ 76 7 7 21 — — 2 8 —Di Pasquale et al137 107§ 2 32 42 5 7 6 49 5Rudehill et al3 406 — 9 20 — — 7 12 —Andreoli et al142 70 — 5 7 — — — 3 7Stober et al143 52§ 2 43 12 13 — 4 44 14Brouwers et al77 61 4# 12 31 — — ? 9† 9†Ramani et al138 19 — 2 2 — — — — —Davis et al13 45 — 4 5 — — — 1 —Grad et al58 40 3 16 — — — — 13 2Manninen et al140‡ 70 — 1 5 — — — 1 —Solenski et al4 455 13 49 51 — 7 3 41 2Mayer et al8 57 — 7 7 — — — — —Randell et al144 26§ 1 — — — 11 — 12 —Total 2,014 39 255 298 20 27 32 246 40(%) (2%) (13%) (15%) (1%) (1.5%) (1.5%) (13%) (2%)

*12 spontaneous, 7 secondary SAH.†Combined PVCs, ventricular tachycardia, ventricular fibrillation, ventricular flutter.‡Retrospective study.§Holter monitoring.#atrial flutter fibrillation and SVT.Abbreviations: AF, atrial fibrillation; SVT, supraventricular tachycardia; PVC, premature ventricular contractions; VT,

ventricular tachycardia.


ers et al77 found that ECG changes were related tothe initial level of consciousness, to subsequentevents, and to outcome after 3 months. In addi-tion, they reported that cardiac disease did notcontribute directly to morbidity or mortality. Fastrhythm disturbances, ischemic changes, or bothwere significantly correlated with poor outcomebut not with specific outcome events, like rebleed-ing and cerebral ischemia, concluding that ECGabnormalities do not herald impending cardiacdisease but indirectly reflect adverse intracranialfactors. Manninen et al140 reported that the inci-dence of ECG abnormalities was statisticallygreater for patients with increased amounts of in-tracranial blood orwith intracerebral clots seen onthe CT scan. Neither the amount of blood nor theincidence of ECG alterations was useful in pre-dicting patient outcome. Recently, in a retrospec-tive study of 58 patients with SAH and ECG alter-ations, Zaroff et al141 reported that all the 20fatalities were due to noncardiac causes. In a mul-tivariate analysis, age over 65 years and Hunt andHess grade of at least 3 were predictive of all-causemortality. The ECG abnormalities were associatedwith more severe neurological injury but were notindependently predictive of all-cause mortality.Neil-Dwyer et al147 studied the effect of admin-

istration of sympatholytic agents on morbidityandmortality after SAH. Significantly greater neu-rological improvement was observed in patientswho received the �-blocker, phentolamine, withthe �-blocker, propranolol, than those who re-ceived phentolamine and placebo. They proposedthat the protective effects of propranolol might becaused by reduction in plasma renin activity, re-duction in pulmonary edema, prevention of myo-cardial infarcts, and reduction in cerebral oxygenconsumption.The evaluation of the prognostic value of CNS-

mediated cardiac alterations is limited because ofthe small sample sizes in some studies and theretrospective nature of other studies with a highincidence of dropped-out cases. Further studiesare needed to clarify this issue.

Conclusion

Cardiac alterations associatedwith SAHhave beenrecognized and frequently reported. Experimentalanimal studies provide strong evidence of theCNS-cardiac interrelation. ECG repolarization ab-

normalities are the most commonly reported ab-normality. Myocardial dysfunction has also beenreported and evaluated using various approaches.The magnitude of the cardiac alterations shouldbe viewed globally in terms of morphological aswell as electrophysiological alterations. Despitethe considerable literature describing cardiac al-terations during the course of SAH, epidemiolog-ical, pathophysiological and prognostic aspectsare yet to be clarified. Further studies are neededto evaluate the magnitude of this problem.

References1. Cushing H: The blood pressure reaction of acutecerebral compression illustrated by cases of intra-cranial hemorrhage. Am J Med Sc 125:1017-1044,1903

2. Byer E, Ashman R, Toth LA: Electrocardiograms withlarge, upright T waves and QT intervals. Am Heart J33:796-806, 1947

3. Rudehill A, Olsson GL, Sundqvist K, et al: ECGabnormalities in patients with subarachnoid haem-orrhage and intracranial tumours. J Neurol Neuro-surg Psychiatry 50:1375-1381, 1987

4. Solenski NJ, Haley EC Jr, Kassell NF, et al: Medicalcomplications of aneurysmal subarachnoid hemor-rhage: A report of the multicenter, cooperativeaneurysm study. Participants of the Multicenter Co-operative Aneurysm Study. Crit Care Med 23:1007-1017, 1995

5. Pollick C, Cujec B, Parker S, et al: Left ventricularwall motion abnormalities in subarachnoid hemor-rhage: An echocardiographic study. J Am Coll Car-diol 12:600-605, 1988

6. Davies KR, Gelb AW, Manninen PH, et al: Cardiacfunction in aneurysmal subarachnoid haemorrhage:A study of electrocardiographic and echocardio-graphic abnormalities. Br J Anaesth 67:58-63, 1991

7. Kuroiwa T, Morita H, Tanabe H, et al: Significance ofST segment elevation in electrocardiograms in pa-tients with ruptured cerebral aneurysms. Acta Neu-rochir (Wien) 133:141-146, 1995

8. Mayer SA, LiMandri G, Sherman D, et al: Electrocar-diographic markers of abnormal left ventricular wallmotion in acute subarachnoid hemorrhage. J Neu-rosurg 83:889-896, 1995

9. Zaroff JG, Rordorf GA, Ogilvy CS, et al: Regionalpatterns of left ventricular systolic dysfunction aftersubarachnoid hemorrhage: Evidence for neurallymediated cardiac injury. J Am Soc Echocardiogr13:774-779, 2000

10. Parekh N, Venkatesh B, Cross D, et al: Cardiactroponin I predicts myocardial dysfunction in aneu-rysmal subarachnoid hemorrhage. J Am Coll Cardiol36:1328-1335, 2000

11. Szabo MD, Crosby G, Hurford WE, et al: Myocardialperfusion following acute subarachnoid hemorrhage


in patients with an abnormal electrocardiogram.Anesth Analg 76:253-258, 1993

12. Kono T, Morita H, Kuroiwa T, et al: Left ventricularwall motion abnormalities in patients with subarach-noid hemorrhage: Neurogenic stunned myocardium.J Am Coll Cardiol 24:636-640, 1994

13. Davis TP, Alexander J, Lesch M: Electrocardio-graphic changes associated with acute cerebrovas-cular disease: A clinical review. Prog Cardiovasc Dis36:245-260, 1993

14. Levy AG: The exciting causes of ventricular fibrilla-tion in animals under chloroform anesthesia. Heart4:319-378, 1913

15. Brow GR, Long CN, Beattie J: Irregularities of heartunder chloroform; their dependence on sympatheticnervous system. JAMA 95:715-717, 1930

16. Manning JW, De Vacotter M: Mechanisms of cardiacarrhythmias induced by diencephalic stimulation.Am J Physiol 203:1120-1124, 1962

17. Weinberg SJ, Fuster JM: Electrocardiographicchanges produced by hypothalamic stimulation.Ann Intern Med 53:332-338, 1960

18. Porter RW, Kamikana K, Greenhoot JH: Persistentelectrocardiographic abnormalities experimentallyinduced by stimulation of the brain. Am Heart J64:815-819, 1962

19. Attar HJ, Gutierrez MT, Bellet S, et al: Effects ofstimulation of hypothalamic and reticular activatingsystems on production of cardiac arrhythmias. CircRes 12:14-21, 1963

20. Yanwowitz F, Preston JB, Abildskov JA: Functionaldistribution of right and left stellate innervation to theventricles: Production of neurogenic electrocardio-graphic changes by unilateral alteration in sympa-thetic tone. Circ Res 18:416-428, 1966

21. Beattie J, Brow GR, Long CN: Physiological andanatomical evidence for the existence of nervesconnecting the hypothalamus with spinal sympa-thetic centers. Proc R Soc Lond (Biol) 106:253-275,1930

22. Magouin HW: Descending connection from the hy-pothalami and central levels of autonomic function.Procedures associated for research in nervous andmental disease. Baltimore, Williams &Willkins, 1941:pp 270-285

23. Kortwieg GC, Boeles JT, Cafe JT: Influence of stim-ulation of subcordal areas on electrocardiogram.J Neurophysiol 20:100-107, 1957

24. Mauck HB, Hockman CH, Hoff EC: ECG changesafter cerebral stimulation; Anomalous atrioventricu-lar excitation elicited by electrical stimulation of themesencephalic reticular formation. Am Heart J 68:98-101, 1964

25. Meville KI, Blum B, Shister HE, et al: Cardiac isch-emic changes and arrhythmias induced by hypotha-lamic stimulation. Am J Cardiol 12:781-791, 1963

26. Barger AC, Herd JA, Liebowitz MR: Chronic cathe-terization of coronary artery: Induction of ECG pat-tern of myocardial ischemia by intracoronary epi-nephrine. Proc Soc Exp Biol Med 107:471-477,1961

27. Hoffman F, Hoffman EJ, Middleton S, et al: Stimu-lating effect of acetylcholine on mammalian heartand liberation of epinephrine-like substance by iso-lated heart. Am J Physiol 144:189-198, 1945

28. Jacobson SA, Danufsky P: Marked electrocardio-graphic changes produced by experimental headtruma. J Neuropathol Exp Neurol 13:462-466, 1954

29. Hockman CH, Mauck HP Jr, Hoff EC: ECG changesresulting from cerebral stimulation. II. A spectrum ofventricular arrhythmias of sympathetic origin. AmHeart J 71:695-700, 1966

30. Benser MB, Weinstein EA: Hypothalamic stimulationyielding adrenal reversal effects. Am J Physiol 136:576-580, 1942

31. Elrifai AM, Bailes JE, Shih SR, et al: Characterizationof the cardiac effects of acute subarachnoid hem-orrhage in dogs. Stroke 27:737-741, 1996

32. Zaroff JG, Rordorf GA, Titus JS, et al: Regionalmyocardial perfusion after experimental subarach-noid hemorrhage. Stroke 31:1136-1143, 2000

33. Steiner L, Lofgren J, Zwetnow NN: Characteristicsand limits of tolerance in repeated subarachnoidhemorrhage in dogs. Acta Neurol Scand 52:241-267, 1975

34. Verlooy J, Van Reempts J, Haseldonckx M, et al:Haemodynamic, intracranial pressure and electro-cardiographic changes following subarachnoidhaemorrhage in rats. Acta Neurochir (Wien) 115:118-122, 1992

35. Hawkins WE, Clower BR: Myocardial damage afterhead trauma and simulated intracranial haemor-rhage in mice: The role of the autonomic nervoussystem. Cardiovasc Res 5:524-529, 1971

36. Lacy PS, Earle AM: A small animal model for elec-trocardiographic abnormalities observed after anexperimental subarachnoid hemorrhage. Stroke 14:371-377, 1983

37. Pasztor E, Fedina L, Kocsis B, et al: Activity ofperipheral sympathetic efferent nerves in experi-mental subarachnoid haemorrhage. Part I: Observa-tions at the time of intracranial hypertension. ActaNeurochir (Wien) 79:125-131, 1986

38. Uchida M, Saito K, Niitsu T, et al: Model of electro-cardiographic changes seen with subarachnoidhemorrhage in rabbits. Stroke 20:112-118, 1989

39. Lorenzo NY, Earle AM, Peterson LL, et al: The rela-tionship of the subarachnoid injection of blood andblood fractions with cardiac rate change and ar-rhythmias. J Neurol Sci 127:134-142, 1994

40. Estanol BV, Loyo MV, Mateos JH: Cardiac arrhyth-mias in experimental subarachnoid hemorrhage.Stroke 8:440-449, 1977

41. Jakubowski J, Bell BA, Symon L, et al: A primatemodel of subarachnoid hemorrhage: Change in re-gional cerebral blood flow, autoregulation carbondioxide reactivity, and central conduction time.Stroke 13:601-611, 1982

42. Offerhaus L, van Gool J: Electrocardiographicchanges and tissue catecholamines in experimentalsubarachnoid haemorrhage. Cardiovasc Res 3:433-440, 1969


43. Smith M, Ray CT: Cardiac arrhythmias, increasedintracranial pressure, and the autonomic nervoussystem. Chest 61:125-133, 1972

44. Boddin M, Van Bogaert A, Dierick W: Cat-echolamines in blood and myocardial tissue in ex-perimental subarachnoidal hemorrhage. Cardiology58:229-237, 1973

45. Lacy PS, Earle AM: A correlation between multipleunit activity in the hypothalamus and electrocardio-graphic changes during a subarachnoid hemor-rhage. Brain Res 373:146-152, 1986

46. Lacy PS, Earle AM: Central neural control of bloodpressure and cardiac arrhythmias during subarach-noid hemorrhage in rats. Stroke 16:998-102, 1985

47. Reichenbach DD, Benditt EP: Myofibrillar degener-ation. A response of the myocardial cell to injury.Arch Pathol 85:189-199, 1968

48. Sulkin NM, Sulkin DF: An electron microscopicstudy of the effects of chronic hypoxia on cardiacmuscle, hepatic, and autonomic ganglion cells. LabInvest 14:1523-1546, 1965

49. Anderson HN, Reichenbach DD, Steinmetz GP, etal: An evaluation and comparison of effects of alter-ating and direct current electrical discharges oncanine hearts. Ann Surg 160:251-257, 1964

50. Taylor CB, Davis CB, Vawter GF, et al: Controlledmyocardial injury by a hypothermal injury. Circula-tion 3:239-245, 1951

51. Hammermeister KE, Reichenbach DD: QRS changes,pulmonary edema, and myocardial necrosis associ-ated with subarachnoid hemorrhage. Am Heart J78:94-100, 1969

52. Doshi R, Neil-Dwyer G: Hypothalamic and myocar-dial lesions after subarachnoid haemorrhage. J Neu-rol Neurosurg Psychiatry 40:821-826, 1977

53. Norberg KA: Transmitter histochemistry of the sym-pathetic adrenergic nervous system. Brain Res5:125-170, 1967

54. Eisalo A, Perasalo J, Halonen PI: Electrocardio-graphic abnormalities and some laboratory findingsin patients with subarachnoid haemorrhage. BrHeart J 34:217-226, 1972

55. Cruickshank JM, Neil-Dwyer G, Stott AW: Possiblerole of catecholamines, corticosteroids, and potas-sium in production of electrocardiographic abnor-malities associated with subarachnoid haemor-rhage. Br Heart J 36:697-706, 1974

56. Fluck DC: Catecholamines. Br Heart J 34:869-873,1972

57. Benedict CR, Loach AB: Clinical significance ofplasma adrenaline and noradrenaline concentra-tions in patients with subarachnoid haemorrhage.J Neurol Neurosurg Psychiatry 41:113-117, 1978

58. Grad A, Kiauta T, Osredkar J: Effect of elevatedplasma norepinephrine on electrocardiographicchanges in subarachnoid hemorrhage. Stroke 22:746-749, 1991

59. Brouwers PJ, Westenberg HG, Van Gijn J: Nor-adrenaline concentrations and electrocardiographicabnormalities after aneurysmal subarachnoid haem-

orrhage. J Neurol Neurosurg Psychiatry 58:614-617,1995

60. Svigelj V, Grad A, Kiauta T: Heart rate variability,norepinephrine and ECG changes in subarachnoidhemorrhage patients. Acta Neurol Scand 94:120-126, 1996

61. Fabinyi G, Hunt D, McKinley L: Myocardial creatinekinase isoenzyme in serum after subarachnoidhaemorrhage. J Neurol Neurosurg Psychiatry 40:818-820, 1977

62. Kaste M, Somer H, Konttinen A: Heart type creatinekinase isoenzyme (CK MB) in acute cerebral disor-ders. Br Heart J 40:802-805, 1978

63. Kettunen P: Subarachnoid haemorrhage and acuteheart injury. Clin Chim Acta 134:123-127, 1983

64. Rudehill A, Gordon E, Sundqvist K, Sylven C, et al: Astudy of ECG abnormalities and myocardial specificenzymes in patients with subarachnoid haemor-rhage. Acta Anaesthesiol Scand 26:344-350, 1982

65. Horowitz MB, Willet D, Keffer J: The use of cardiactroponin-I (cTnI) to determine the incidence of myo-cardial ischemia and injury in patients with aneurys-mal and presumed aneurysmal subarachnoid hem-orrhage. Acta Neurochir (Wien) 140:87-93, 1998

66. Adams JE III, Bodor GS, Davila-Roman VG, et al:Cardiac troponin I. A marker with high specificity forcardiac injury. Circulation 88:101-106, 1993

67. Koskelo P, Pinsar S, Spilia W: Subarachnoid hem-orrhage and ECG changes in intracranial bleeding.Br Med J 1:1479-1480, 1964

68. Shuster S: The electrocardiogram in subrachnoidhemorrhage. Br Heart J 22:316-320, 1960

69. Kreus KE, Kemila SJ, Takala JK: Electrocardio-graphic changes in cerebrovascular accidents. ActaMed Scand 185:327-334, 1969

70. Umali F, Gould L, Gomprecht RF: Electrocardio-graphic changes in intracranial lesions. Angiology22:616-621, 1971

71. Galloon S, Rees GA, Briscoe CE, et al: Prospectivestudy of electrocardiographic changes associatedwith subarachnoid haemorrhage. Br J Anaesth 44:511-516, 1972

72. Conner RC: Heart damage associated with intracra-nial lesions. Br Med J 3:29-31, 1968

73. Greenhoot JH, Reichenbach DD: Cardiac injury andsubarachnoid hemorrhage. A clinical, pathological,and physiological correlation. J Neurosurg 30:521-531, 1969

74. Neil-Dwyer G, Walter P, Cruickshank JM, et al: Ef-fect of propranolol and phentolamine on myocardialnecrosis after subarachnoid haemorrhage. Br Med J2:990-992, 1978

75. Goldstein DS: The electrocardiogram in stroke: Re-lationship to pathophysiological type and compari-son with prior tracings. Stroke 10:253-259, 1979

76. Doshi R, Neil-Dwyer G: A clinicopathological studyof patients following a subarachnoid hemorrhage.J Neurosurg 52:295-301, 1980

77. Brouwers PJ, Wijdicks EF, Hasan D, et al: Serialelectrocardiographic recording in aneurysmal sub-arachnoid hemorrhage. Stroke 20:1162-1167, 1989


78. Cropp GL, Manning GW: Electrocardiographicchanges simulating myocardial ischemia and infarc-tion associated with spontaneous intracranial hem-orrhage. Circulation 22:25-38, 1960

79. Wasserman F, Choquette G, Cassinelli R, et al:Electrocardiographic observations in patients withcerebrovascular accidents; report of 12 cases. Am JMed Sc 231:502-510, 1956

80. Beard EF, Robertson JW, Robertson RC: Spontane-ous subarachnoid hemorrhage simulating acutemyocardial infarction. Am Heart J 58:755-759, 1951

81. Mehta AC, Aziz A: Electrocardiographic abnormali-ties associated with subarachnoid hemorrhage.Lancet 1:822, 1965

82. De Swiet J: Abnormal U waves in the electrocardio-gram in subarachnoid haemorrhage. Br Heart J 31:526-528, 1969

83. Parizel G: Life-threatening arrhythmias in subarach-noid hemorrhage. Angiology 24:17-21, 1973

84. Smith M: Ventricular bigeminy and quadrigeminyoccurring in a case of subarachnoid hemorrhage. JElectrocardiol 5:78-85, 1972

85. De Sweit J: Changes simulating hypothermia in theelectrocardiogram in subarachnoid hemorrhage. JElectrocardiol 5:93-95, 1972

86. Ciongoli AK, Poser CM: Pulmonary edema secondaryto subarachnoid hemorrhage. Neurology 22:867-870,1972

87. Yarnell PR, Godfrey C: EKG changes after spinalsubarachnoid hemorrhage. Stroke 4:156-159, 1973

88. Anderson GJ, Woodburn R, Fisch C: Cerebrovascu-lar accident with unusual electrocardiographicchanges. Am Heart J 86:395-398, 1973

89. Hammer WJ, Luessenhop AJ, Weintraub AM: Ob-servations on the electrocardiographic changesassociated with subarachnoid hemorrhage withspecial reference to their genesis. Am J Med 59:427-433, 1975

90. Estanol BV, Marin OS: Cardiac arrhythmias and sud-den death in subarachnoid hemorrhage. Stroke6:382-386, 1975

91. Goldman MR, Rogers EL, Rogers MC: Subarach-noid hemorrhage. Association with unusual electro-cardiographic changes. JAMA 234:957-958, 1975

92. Grossman MA: Cardiac arrhythmias in acute centralnervous system disease. Successful managementwith stellate ganglion block. Arch Intern Med 136:203-207, 1976

93. Toyama Y, Tanaka H, Nuruki K, et al: Prinzmetal’svariant angina associated with subarachnoid hem-orrhage: A case report. Angiology 30:211-218, 1979

94. Guintran JL, Allard P, Capdevielle P, et al: [Electro-cardiographic disturbances in subarachnoid hemor-rhage]. Nouv Presse Med 7:3154-3155, 1978

95. Lowensohn RI, Weiss M, Hon EH: Heart-rate vari-ability in brain-damaged adults. Lancet 1:626-628,1977

96. Carruth JE, Silverman ME: Torsade de pointe atyp-ical ventricular tachycardia complicating subarach-noid hemorrhage. Chest 78:886-888, 1980

97. Pinciroli D, Moretti M, Landi G, et al: Recurrent

ventricular fibrillation after subarachnoid haemor-rhage. Dose-related effect of lidocaine infusion.J Neurol 227:43-47, 1982

98. Gascon P, Ley TJ, Toltzis RJ, et al: Spontaneoussubarachnoid hemorrhage simulating acute trans-mural myocardial infarction. Am Heart J 105:511-513, 1983

99. Hust MH, Nitsche K, Hohnloser S, et al: Q-T prolon-gation and torsades de pointes in a patient withsubarachnoid hemorrhage. Clin Cardiol 7:44-48,1984

100. Boreux JL, Ducobu J, Boulanger M, et al: [Electro-cardiographic abnormalities and cerebromeningealdisorders]. Acta Clin Belg 39:154-158, 1984

101. Choo MH, Chia BL, Tan L: Stroke masking electrocar-diographic abnormalities. J Electrocardiol 18:405-407,1985

102. Marik PE, Angel ME, Eidelman J, et al: Subarach-noid haemorrhage. A report of 2 cases. S Afr Med J71:389-390, 1987

103. Wojak JC, Flamm ES: Intracranial hemorrhage andcocaine use. Stroke 18:712-715, 1987

104. Di Pasquale G, Pinelli G, Andreoli A, et al: Torsadede pointes and ventricular flutter-fibrillation follow-ing spontaneous cerebral subarachnoid hemor-rhage. Int J Cardiol 18:163-172, 1988

105. Nakamura Y, Kaseno K, Kubo T: Transient ST-seg-ment elevation in subarachnoid hemorrhage. J Elec-trocardiol 22:133-137, 1989

106. Yuki K, Kodama Y, Onda J, et al: Coronary vaso-spasm following subarachnoid hemorrhage as acause of stunned myocardium. Case report. J Neu-rosurg 75:308-311, 1991

107. Handlin LR, Kindred LH, Beauchamp GD, et al:Reversible left ventricular dysfunction after sub-arachnoid hemorrhage. Am Heart J 126:235-240,1993

108. Dubrey S, Huehns TY, Brooks AP: Subarachnoidhaemorrhage: A cause of left bundle branch block?Postgrad Med J 70:578-580, 1994

109. Yasu T, Owa M, Omura N, et al: Transient ST ele-vation and left ventricular asynergy associated withnormal coronary artery in aneurysmal subarachnoidhemorrhage. Chest 103:1274-1275, 1993

110. Asplin BR, White RD: Subarachnoid hemorrhage:Atypical presentation associated with rapidlychanging cardiac arrhythmias. Am J Emerg Med12:370-373, 1994

111. Svigelj V, Grad A, Tekavcic I, et al: Cardiac arrhyth-mia associated with reversible damage to insula in apatients with subarachnoid hemorrhage. Stroke 25:1053-1055, 1994

112. Nash SD, Patt MV: Sinus arrest after nimodipinetreatment for a head injury. Tex Heart Inst J 21:177-178, 1994

113. Pinto RJ, Goyal V, Sharma S, et al: Transient myo-cardial dysfunction in a patient with subarachnoidhaemorrhage. Int J Cardiol 46:289-291, 1994

114. de Marchena E, Pittaluga JM, Ferreira AC, et al:Subarachnoid hemorrhage simulating myocardial


infarction. Cathet Cardiovasc Diagn 37:170-173,1996

115. Pine DS, Tierney L Jr: Clinical problem-solving. Astressful interaction. N Engl J Med 334:1530-1534,1996

116. Raymer K, Choi P: Concurrent subarachnoid haem-orrhage and myocardial injury. Can J Anaesth 44:515-519, 1997

117. Soman P, Senior R: Severe ventricular dysfunctionsecondary to subarachnoid hemorrhage. Clin Car-diol 20:402-403, 1997

118. Delgado C, Rubert C, Barturen F: [Myocardial stun-ning in the context of a subarachnoid hemorrhage].Rev Esp Cardiol 51:840-843, 1998

119. Dominguez H, Torp-Pedersen C: Subarachnoidhaemorrhage with transient myocardial injury andnormal coronary arteries. Scand Cardiovasc J 33:245-247, 1999

120. Chang PC, Lee SH, Hung HF, et al: Transient STelevation and left ventricular asynergy associatedwith normal coronary artery and Tc-99m PYP myo-cardial infarct scan in subarachnoid hemorrhage. IntJ Cardiol 63:189-192, 1998

121. Yoshikawa D, Hara T, Takahashi K, et al: An asso-ciation between QTc prolongation and left ventricu-lar hypokinesis during sequential episodes of sub-arachnoid hemorrhage. Anesth Analg 89:962-964,1999

122. Perron AD, Brady WJ: Electrocardiographic mani-festations of CNS events. Am J Emerg Med 18:715-720, 2000

123. Rogers ER, Phan TG, Wijdicks EF: Myocardial injuryafter hemorrhage into the lateral medulla oblongata.Neurology 56:567-568, 2001

124. Wong TL, Cooper ES: Atrial fibrillation with ventric-ular slowing in patients with spontaneouse sub-arachnoid hemorrhage. Am J Cardiol 23:473-477,1969

125. Estanol B, Aguilar F, Badui E, et al: Stellate ganglionblockade and atropine do not affect the electrocar-diographic changes of subarachnoid hemorrhage.Arch Invest Med (Mex) 15:339-348, 1984

126. Swartz PJ, Malliani A: Electrical alteration of theT-waves: Clinical and expermental evidence of itsrelationship with sympathetic nervous system andwith the long Q-T syndrome. Am Heart J 89:45-50,1975

127. Sakka SG, Huettemann E, Reinhart K: Acute leftventricular dysfunction and subarachnoid hemor-rhage. J Neurosurg Anesthesiol 11:209-213, 1999

128. Lan-Sheng K, Ting-Kun H, Hung HF, et al: Theelectrocardiogram in cerebrovascular accidents.Chin Med J 76:445-454, 1958

129. Hersh C: Electrocardiographic changes in sub-arachnoid hemorrhage, meningitis and intracranialspace occupying lesions. Br Heart J 26:785-792,1964

130. Ananthachari MD, Anto CD: A study of ECGchanges in 20 cases of subarachnoid haemorrhage.Indian Heart J 19:105-113, 1967

131. Hunt D, McRae C, Zapf P: Electrocardiographic and

serum enzyme change in subarachnoid hemor-rhage. Am Heart J 77:479-488, 1969

132. Page A, Boulard G, Guerin J, et al: [Electrocardio-graphic abnormalities during meningeal hemor-rhage]. Nouv Presse Med 5:1405-1408, 1976

133. Dimant J, Grob D: Electrocardiographic changesand myocardial damage in patients with acute ce-rebrovascular accidents. Stroke 8:448-455, 1977

134. Stober T, Kunze K: Electrocardiographic alterationsin subarachnoid haemorrhage. Correlation betweenspasm of the arteries of the left side on the brain andT inversion and QT prolongation. J Neurol 227:99-113, 1982

135. Page A, Boulard G, Guerin J: [Electrocardiographicanomalies in subarachnoid hemorrhage]. Arch MalCoeur Vaiss 76:1031-1038, 1983

136. Melin J, Fogelholm R: Electrocardiographic findingsin subarachnoid hemorrhage. A population study.Acta Med Scand 213:5-8, 1983

137. Di Pasquale G, Pinelli G, Andreoli A, et al: Holterdetection of cardiac arrhythmias in intracranial sub-arachnoid hemorrhage. Am J Cardiol 59:596-600,1987

138. Ramani A, Shetty U, Kundaje GN: Electrocardio-graphic abnormalities in cerebrovascular accidents.Angiology 41:681-686, 1990

139. Rinkel GJ, Wijdicks EF, Vermeulen M, et al: Theclinical course of perimesencephalic nonaneurys-mal subarachnoid hemorrhage. Ann Neurol 29:463-468, 1991

140. Manninen PH, Ayra B, Gelb AW, et al: Associationbetween electrocardiographic abnormalities and in-tracranial blood in patients following acute sub-arachnoid hemorrhage. J Neurosurg Anesthesiol7:12-16, 1995

141. Zaroff JG, Rordorf GA, Newell JB, et al: Cardiacoutcome in patients with subarachnoid hemorrhageand electrocardiographic abnormalities. Neurosur-gery 44:34-39, 1999

142. Andreoli A, Di Pasquale G, Pinelli G, et al: Subarach-noid hemorrhage: Frequency and severity of cardiacarrhythmias. A survey of 70 cases studied in theacute phase. Stroke 18:558-564, 1987

143. Stober T, Anstatt T, Sen S, et al: Cardiac arrhyth-mias in subarachnoid haemorrhage. Acta Neurochir(Wien) 93:37-44, 1988

144. Randell T, Tanskanen P, Scheinin M, et al: QT dis-persion after subarachnoid hemorrhage. J Neuro-surg Anesthesiol 11:163-166, 1999

145. Cruickshank JM, Neil-Dwyer G, Brice J: Electrocar-diographic changes and their prognostic signifi-cance in subarachnoid hemorrhage. J Neurol Neu-rosur Psych 37:755-759, 1974

146. Wilkins RH, Alexander JA, Odom GL: Intracranialarterial spasm: A clinical analysis. J Neurosurg 29:121-134, 1968

147. Neil-Dwyer G, Walter P, Cruickshank JM: Beta-blockade benefits patients following a subarachnoidhaemorrhage. Eur J Clin Pharmacol 28(suppl):25-29, 1985


Documents

Cardiac manifestations after subarachnoid hemorrhage: A systematic review of the literature