Supravalvular Aortic StenosisClinical, Hemodynamic and Pathologic Observations

By ANDREW G. MORROW, M.D., JOHN A. WALDHAUSEN, M.D.,

ROBERT L. PETERS, M.D., ROBERT D. BLOODWELL, M.D., AND

EUGENE BRAUNWALD, M.D.

In 3 patients obstruction to left ventricular outflow was shown to be due to a localizednarrowing of the aortic root at the point of insertion of the aortic leaflets. The site ofobstruction was localized by left heart catheterization and selective angiography. Thepathologic findings in 2 patients are described and the problem of the surgical manage-

ment of this unusual form of aortic stenosis is discussed.

P REVIOUS reports1'2have dealt in detailwith the clinical and hemodynamie

findings ill patients with obstruction to leftventricular outflow caused by congenital val-vular or subvalvular aortic stenosis. Morerecently it has been shown that a systolicpressure gradient between the left ventricleand aorta may also result from functionalobstruction in the outflow tract of the ven-tricle secondary to massive left ventricularhypertrophy.3-- Among the group of patientsWith (congoeniital aortic stenosis who have beeiistifdlied at the National Heart Institute, 3have lbeeni showni to have obstruction to out-flow cauised by a constriction in the aortaItself immediately distal to the valve. Ini the1)resent report the results of diagnostic studiesin these 3 patients are described and thepathologic findings in 2 of them are presented.

CLINICAL SUMMARIES1. J. R., an 8-year-old girl was, first admitted

to the National Heart Institute in November 1956,known to. have a heart murmur since birth. Her,growth and development have been markedly re-tarded (her weight was below the third percentileon a standard grid) and she had been subject tofrequent respiratory infections. The heart wasenlarged and the point of maximal impulse wasthe sixth intercostal space in the mnidelavie-ular line. A systolic thrill was palpable at thebase of the heart and over the carotid arteries.The second heart sound in the pulmonary area

From the Clinic of Surgery, National Heart Insti-tute, and the Department of Pathological Anatomy,the National Institutes of Health, Bethesda, Md.

1003

was accentuated and split. A grade-IV/VI sys-tolic ejection murmur was heard best along theright sternal border and was transmitted to theneck. The rhythm was regular. The blood pies-sure in the right arin was 106/16 and in the leftarm 112/0 m1n. Hg. The electrocardiogram re-vealed sinus tachycardia, left ventricular hyper-trophy, right axis deviation, and P waves sugges-tive of right atrial enlargement. Fluoroscopicand radiographic examinations demonstrated en-largemient of both ventricles. The aorta was notdilated. At right heart catheterization the pulmo-nary artery pressure was 70/24 nim. Hg, and thecatheter was passed through a patent ductus intothe descending aorta. A retrograde thoracie aor-togram was carried out (fig. 1). The sinuses ofValsalva appeared normal, and there was an ap-parent constriction of the aortic root imminiediatelyabove them. Some left ventricular opacificationtindicated mild coexisting aortic regurgiitation. Theaorta itself was smaller than normal. The patentductus was again demonstrated.

In February 1957 the patent ductus was closedthrough a posterolateral thoracotomy. Althoughthe aortic root could not be inspected, a pressuregradient between the left ventricle and aorta fol-lowing closure of the ductus was confirmed bysimultaneous pressure measurements. The leftventricular pressure at this time was 194/10 mm11.Hg and the peak systolic gradient was 81 mm1111.Hg.

In the 2 years following this operation, thechild experienced no further serious respiratoryinfections but still failed to grow and gain weight.She began to complain of fatigability and becamedizzy with strenuous exercise on several occasions.She was readmitted to the Institute in July 19.5Sfor re-evaluation and aortic valvulotomy.The physical findings on this occasion revealed a

blood pressure of 96/80. The classic thrill andmurmur of aortic stenosis were present, and the

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MORROW, WALDHAUSEN, PETERS, BLOODWELL, BRAUNWALD

Flo. 1. Lateral view of the thoracic aortogramn

(top) amId its schematic initerpretation (bottom) oh-

taimed in Ipatient J.R. Time supravalvumlar area of com-

striction is indicated.

Lcoronavy_

FIG. 2. 1)r.a~~inig of the heart andorta of patientJ .R. The constriction at the upper inargins of the.sinuses, of Valsalva and the valve deformity are

showni. The enclosed area is sovii liicroseol)ica.lly iifigure 3.

secoid heart sound in the aortie area was dimin-ished in intensity.. Another righ.lt heart ca.thieter~i-zation was performed; the pulmlonarly- 'artery pres-sure had fallen to 45/8 mmn. Hg-, and absence ofa left-to-rig~ht shunt was shown by ai pulmiona.ry~artery. nitrous oxide test of 11 per ,enit.") Pereln-taneous puncture of the left ventricle7 wascarried out under general anesthesia. The pasystolic gradient lbetwecn the left v-entriele andi~femoral artery was 52 mm. Jg. Operation foirrelief of the supra,.va.lvular obstruction was recomi-mended but on the mnorning of the scheduled pro-cedure the child had cardinearrs on the w-ard a mI.attempts at resuscitation were unsuccessful.

Patholoqic Description. The heart weighed 200Gmn. and both ventricles were hvpertrophied. Theaorta and pulmonary artery were in normal posi-tion and there were no abnormalities of the (hiamibers or septa. The deformities of the aortie valveand ascending. aorta which produced stenosis areillustrated in figure 2. There were 3 normal-sizedbut thickened valve leaflets. A fibrous band orig-mnated at the center of the free edge of each leaf-let and inserted into the thickened aortic intfinmalplica at the upper margin of the sinuses of Val-salva. The resulting shelf-like thickening' nar-rowed the aortic orifice to a diami~eteri of 5 mm.

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SUPRAVALVULAR AORTIC STENOSIS

Above the stenosis the aorta was 10 mm. in diani-(eter.

The uiiicroscopic appearanee of a vertical sectionthrough the left coronary leaflet is shown in figure3. There was considerable fibrous thickening ofthe upper portion of the leaflet. The nodule ofArantii was absent and the sinus of Valsalva wasbridged by a band of dense connective tissue thatinserted into the intinia of the thickened aorta atthe upper margin of the sinus. An area of sub-endothelial fibrosis in the base of the sinus re-semibled a "jet" lesion. There was moderate coro-mary arteriosclerosis.

2. E. B., was an 18-year-old boy in whom a inur-mur had first been noted immediately after birth.At the age of 7 years he developed subacute bac-terial endoearditis and pneumococcus type I Vwas cultured from his blood. The infection wascured by the administration of penicillin and hehad no symptoms until age 17, when he experi-enced sudden severe precordial pain and was hos-pitalized for 3 days. A chest x-ray is said tohave shown a calcified aneurysm of the aseendingaorta. The patient had no further chest pain orlimitation of activity and was asymptomatic atthe time of his first admission to the NationalIleart Institute a year later.

Physical examination at this tinie revealed nor-inal development and was unremarkable exceptfor the cardiovascular system. The heart was en-hirged and the point of maximal impulse was inthe sixth left intercostal space outside the mid-claviciular line. A left ventricular lift was pal-pable at the apex and a systolic thrill was felt tothe right of the sternum and over the carotid ves-sels. The aortic second sound was decreased anda grade-V/VI harsh systolic ejection murmur wasaudible over the entire precordium; it was of max-irnal intensity in the second and third right inter-costal spaces. Blood pressure in the right ariwas 110/70 mm. Hg and in the left arm 90/60.The peripheral pulses were palpable and thelhvthm was regular.The electrocardiogram revealed left bundle-

branch block and there were occasional prematureventricular contractions. Fluoroscopic and radio-g-raphic examinations of the chest demonstratedappreciable enlargement of the left ventricle, anda calcified mass was seen to the right of the aorticareh. Right heart catheterization revealed a pul-monary artery pressure of 20/8 mmnn. Hg and thepulmonary artery nitrous oxide test was negative(15 per cent). The cardiac output at rest was2.26 L. per minute per M.2 and on exercise roseto 4.26 L. per minute per M.2 Left heart catheteri-zation was carried out by the transbronchial meth-od.8 The mean left atrial pressure was 12 mm.Hg and its contour was normal. The left ven-

LV

FIG. 3. Photomnicrograph. of section through the leftcoronary leaflet of the aortic valve in patient J .R.Orientation as illustrated in flgure 2. PA, pulmonaryartery; PV, pulmonary valve; LV, left ventricularcavity; AA, ascending aorta; RA, root of aorta;AC, left coronary aortic leaflet; 8V, sinus of Val-salva; FB, fibrous band attaching leaflet to aorticwall.; J, jet lesion in base of sinus; LCA, left antc-rior descending coronary artery. Orecin-hematoxylin,X 6.5.

FIG. 4. Pressure recording made in patient E.B. asa catheter weas withdrawn from the left ventricle(LV) into the aortic arch. The intraaortic pressuregradient is shoopn. The feitioral artery pressure (FA)is also indicated.

tricular pressure was 300/15 inin. Hg and theright radial artery pressure, measured simultan-eously, was 155/86 mm. Hg, resulting in a peaksystolic gradient of 145 mmn. Hg. The cardiac

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MORROW, WALI)IIAUSEN, PETERS, BLOODWELI, BRAUNWALD

FIG. 5. Antero-posterior view of the left ventricularselective angiocardiogramii (top)) amid its schematic

interpretation (bottom) in jpatienii E.B. The left

ventricle is emlarged anld its wa.ll is greatly thickened.

Both coronary arteries are grossly dilated. The aortic

constriction iiniiiedliately .al)ove the imorimial sinuses of

Valsalva is iiidicate(1. The sacculara.tiieuirysnii at the

oliigat of the illloitlilnate :i -tely is aliso opacified.

output at this time was 6.50 L. p)er minute (iindi-(cator-dilutioil method) and the calculated area

of the stenotic orifice was 0.48 em.2/ M.2 body

surface area.

Because of the difference in blood pressure be-tween the right and left arias the left ventricleand aorta, were catheterized fromn the right radialartery. On this o(ccafsion, under general .nesthesia,the left ventricular pressure was 1S0/12 niiiii. Hga id, as the catheter was withdrawn, progressivelylower aortic pressures were recorded (fig. 4).Iiiiiiiediately distal to the valve it was 180/75 11Mm.:rg, alnd ill the aortic arch the pressure was 1 20/7,5 nionii. Hg. The femnoral artery pressure was110 75. The pressure tracings were considereddiagnostic of supravalvular aortic stenosis, andto characterize the lesion further the catheter wasreplaced in the left ventricle and a selective angio-cardiot-rain carried out: 50 nil. of 70 per cent Uro-kon were injected with a Gidlund syringe andanteroposterior and lateral films were simultan-eously exposed at the rate of 6 per second (figs.5 and 6). These demnonstrated the left ventricleto be large and thick-walled. The aortic leafletswere normal in position and mobility. Immedi-aitely above the valve there was an apparentlydiscrete narrowing of the aortic root. The sinusesof Valsalva were somewhat enlarged and allbranches of both coronary arteries were enormous-1 dilated and tortuous. The ascending aorta it-self was sniall and a saccular aneurysm was seento fill froni the aorta near the origin of the in-nominate artery. The lateral views (fig. 6) alsodemonstrated sonie reduction in the lumen of thetransverse portion of the aortic arch.

Operation for relief of the supraventricular ob-struction was recommended but deferred for 1 yearaIt the patient's re(quest. He was rea.dimiitted illJuly 1958 at which timie physical and laboratoryfilndings were unchanged. At operation (July 17,19.58) the aorta was found to be snmall and therewas tan intense systolic thrill palpable within it. Thehuge coronary arteries were again noted. Theaortic root was dissected and, after the institutionof cardiopulmionary bypass and elective cardiacarrest, the aorta was widely opened. The site ofstenosis was a thick fibrous ridge and local resec-tion was deemed impossible. The lumen of theaorta at the site of constriction was enlarged bythe insertion of a diamond-shaped prosthesis ofcompressed polyvinyl sponge. After 67 minutescoronary perfusion was restored but ain effectiveheart beat never resulted.

Pathologic Description. The heart was greatlyenlarged, weighIingi, 8,50 Gill., and there was a 2.5-(111i. Calcified saccular aneurysmn arising from the.ascelding aorta inear the origin of the innomi-nate artery. The entire aorta was hypoplasticaind was only 12 inan. in outside dianmeter. Thecoronary arteries were enormously dilated andtortuous; the right was 10 mil. in diameter andthe left 7 mm.

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SIJPRAVALVULAR AORTIC STENOSIS

In figure 7 the aorta has been opened to showthe stenotie segment, 18 mnm. long, immediatelyabove the upper niargin of the aortie valve. Thepolyvinyl prosthesis lay in the position shownand the diameter of this stenotic seg-ment, includ-ing the prosthesis, was only 9 11mm. The aorticvalve leaflets were thin and saccular and theirfree mnar-ins at the conminissures were elongatedso that the margins of the leaflets lay 4 mm1111. be-low the orifices of the coronary arteries.

Just above the orifice of the saceularl aneu-rysmn was a healed dissecting aneurysni that re-entered the aorta just beyond the orig.in of theleft subelavian artery.

Histologie sections of the aorta revealed degen-eration and fibrosis of the nmedia. These changeswere particularly pronounced in the thickenedstenotic segment of the ascending aorta (fig. 8).

3. J. J., a 7-year-old boy was admitted to theNational lleart Institute in August 1958. A MllI'-mur had been first noted shortly after his birth.lie had been asymptomatic except for slight fa-tigability. The child exhibited normal develop-ment and the significant physical findings werelimited to the cardiovascular system. The bloodpressure was 94/70, the peripheral pulses werenormal. The heart was not enlarged but a ven-tricular lift was palpable at the apex. There wasa coarse systolic thrill over the base of the heartwhich was also felt in the suprasternal notch andover the carotid arteries. A grade-V //VI ejection-type immurmaur was maximal in the second and thirdright intercostal spaces and was referred to thieneck. The second heart sound was inaudible atthe aortic area.

The electrocardiogram demonstrated left veii-tricular hypertrophy, and this finding was con-firmed by the fluoroscopic and radiographic ap-pearance of the heart. Poststenotic dilatation ofthe aorta was not apparent. At right heart cath-eterization the pulmonary artery pressure was20/6 min. Hg. and the pulmonary artery nitrousoxide index was 3 per cent. Percutaneous punc-ture of the left ventricle was performed and theleft ventricular pressure was 170/5 main. H-g. Thefemmioral arterial pressure was 110/65 mmiiii. Hgaind the peak systolic gradient was 60 nan. Hg(g-eneral anesthesia).These findings were confirmatory of congenital

aortie steniosis and operation was carried out inOctober 19,58. At thoracotoimv the entire ascend-ing aorta was smnall and an intense systolic thrillwas palpable within it. All the visible coronaryarteries were greatly enlarged and tortuous. Whenthe aRortie root was dissected, a constrictioni imme-ditatelv distal to the sinuses of Valsalva was ap-parelnt (fig. 9). No thrill was felt ini the sinusestImemmmselve, which wvere (f mioimal ssize. A. athle-

FIG. 6. Lateral view of the left ventriclar selectiveanigiocardiograma (top) anid its initer)reta.tioni (bot-tors) in patient E.B. The supravalvular stenosis,dilatedl coronary arteries, anid the aortic aneurysiaa me seell. The siall1 size of the aorta ite'f i.; a s(omell demonstratedt(l.

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MORROW, WALDHAIUSEN, PETERS, BLOODWELL, BRAUNWALD

BFIG. 7. Postmortem appearance of the heart and

aorta of patient E.B. The stenotic segment of aortaand the prosthesis employed to enlarge the area areshown. The saccular aneurysm of the aorta and thedissection associated with it are also indicated.

ter was passed from the apex of the left ventricleinto the aorta and the withdrawal tracing provedthe presence of obstruction immediately distal tothe valve (fig. 10). An attempt at surgical cor-tection of the lesion was deemed inadvisable. The(hild remains essentially asymptomatic.

DISCUSSIONSupravalvular aortie stenosis has been

described only rarely but in the recent reportby Denie and Verheugt9 a review of casespreviously described is included. The mostcommon anatomic lesion is apparently ashelf-like thickening and hypertrophy of theplica at the upper margin of the sinuses ofValsalva. This type of stenosis may be asso-ciated with a valvular deformity as in pa-tient J.R. The fibrous bands that extendedfrom the free margin of each aortic leaflet tothe thickened plica were in this instance ap-parently responsible for associated aortic re-gurgitation. The morphology of the valve de-formity in patient J.R. suggests that thehollowing of the endocardial cushions was de-fectively performed and that the hypertro-I)hied plica may have beein similarly derived.Iii the patient reported by Denieg the free

FIG. 8. Photomicrograph of the stenotic segment ofaorta of patient E.B. There is separation and fray-ing of elastic fibers and vascularization and fibrosisin the media. Orecin-hematoxylini, X 260.

margin of the left coronary leaflet was fusedto the aortic wall. The operative appearanceof the lesion of patient J.J. suggested that itwas of a similar type.The anatomic lesion of patient E.B. is

probably not embryologically similar to thestenosis described above. The stenotie seg-ment was relatively long and was associatedwith hypoplasia of the aorta as well as de-generation and fibrosis of the aortic media.The history of endocarditis suggests this asan etiologic agent although the infectioncould have and probably did originate on a

previously existing congenital stenosis. Thefact that the entire aorta was hypoplastic inthis, as well as the other patients, would sub-stantiate congenital narrowing as the basiclesion.A third type of lesion that mnay produce

supravalvular stenosis was described by

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SUPRAVALVULAR AORTIC STENOSIS

000^,$/ y 2;:#Lcoroncary

FIG. 9. Operative appearance of the heart and aorta

of patient J.J. The cha~racteristic hypoplasia of the

aorta, and dilated coronairy arteries are well demon-

strated. The site of supra~valvular obstruction is in-

dicated.

(>heu, Fiese,7 and Hatayama.10 This patient

had a crescent-shaped fibrous membrane that

encircled three fourths of the circumference

of the lumen of the aorta and projected 1.2

cm. into the lumen. Two normal aortic valve

cusps were attached to the membrane. Anom-

alous supravalvular aortic bands have been

described and are included in the tabulation

of Denie and Verheugt.' 1n spite of their

speculative interest or possible embryologic

relationship to anomalous valve development,

clinical disease has not been evident in re-

ported patients and the lesion has generally

bcen an incidental autopsy finding.

On clinical examination the only finding

that may serve to suggest the diagnosis of

supravalvular aortic stenosis is the absence

of poststenotic dilatation of the aorta. Since

the aorta may not be dilated when subvalvu-

lar or functional stenosis exists,2' 3 the pres-

ence of supravalvular obstruction can be

proved only by left heart catheterization or

c'ontrast radiography. The demonstration of a

systolic pressure gradient within the aortic

root clearly localizes the site of obstruction

to a point distal to the valve (figs. 4 and 10).

Left ventricular selective angiography and

aortography proved the presence of the le-

sion in the 2 patients in whom contrast

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FIG. 10. Pressure recording obtained at operation inpatient J.J. The intraaortic pressure gradient isclearly shown.

studies were carried out. The mere demon-stration of a systolic pressure difference be-tween the left ventricle and aorta does notlocalize the obstruction. Complete left heartcatheterization is therefore necessary in theprecise preoperative evaluation of any patientwith congenital aortic stenosis.

Supravalvular aortic stenosis would seemto carry with it the relatively grave prog-nosis associated with the more common formsof obstruction to left ventricular outflow.Although the coronary arteries originate be-low the stenosis and are subjected to an ab-normally high perfusion pressure, the addi-tional coronary flow provided apparentlydoes not compensate for the increased burdenimposed upon the left ventricle. When theleaflets are fused to the aorta, the entrancesto the sinuses of Valsalva may be obstructedand compromise coronary filling.The method of surgical treatment employed

in patient E.B. and contemplated in patientJ.R. was suggested by Dr. John W. Kirklin.1'He emphasized that excision of the obstruc-ting ridge would necessitate severance of theattachments of the aortic leaflets and wouldcertainly result in gross aortic regurgitation.The accuracy of this observation is shownby the relationships of the leaflets to theobstruction in figures 2 and 7. Kirklin suc-cessfully enlarged the diameter of the aorticroot by the insertion of a diamond-shapedpolyvinyl patch in a patient in whom theanatomic lesion was similar to those described.A significant reduction in the intraaorticpressure gradient was achieved and it wouldseeni that this method of operative repairwill find increasing application.

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M() ;ROW, WALDHAITSEN, PETERS, BLOODWELL, BRAUNWALD

SUMMARYThe cliiiical and hemodynamie findings in

3 patients with supravalvular aortic stenosisare described. The diagnosis was establishedby left heart catheterization and selectiveangiography. Two patients died, one fol-lowing an unsuccessful attempt at surgicalcorrection of the lesion. Pathologic findingsin these patients indicate that the stenosis,which occurs at the site of insertion of theaortic leaflets, is of congenital origin. Thedifferentiation of this lesion from the morecommon forms of aortic stenosis and theproblem of its surgical management aredescribed.

SUMMARIO IN INTERLINGUAEs describite le constatationes clinic e

hemodynamic in 3 patientes con stenosisaortic supravalvular. Le diagnose essevaestablite per catheterismo sinistro-cardiac eangiographia selective. Duo del patientesmoriva, le un post le van essayo de corrigerle lesion per medios chirurgic. Le constata-tiones pathologic in iste patientes indica quele stenosis, que occurre al sito del insertiondel cuspides aortic, es de origine congenite.Le differentiation de iste lesion ab le formasplus commun de stenosis aortic e le problemade su tractamento chirurgic es describite.

REFERENCES1. MORROW, A. G., BRAUNWALD, E., AND SHARP,

E. H.: The clinical features and surgicaltreatment of congenital aortic stenosisProgress in Cardiovascular Diseases 1: 80,1958.

9. , SHARP, E. H., AND BRAUNWALD, E.: Con-genital aortic stenosis: Clinical and hemo-dynamic findings, surgical technic, and re-sults of operation. Circulation 18: 1091,1958.

3. -, AND BRAUNWALD, E.: Functional aorticstenosis. A malformation characterized byresistance to left ventricular outflow withoutanatomic obstruction. Circulation 20: 181,1959.

4. BERCU, B. A., DIETTERT, G. A., DANFORTH,W. H., PUND, E. E., JR., AHLVIN, R. C.,AND BELLIVEAU, R. R.: Pseudoaortic steno-sis produced by ventricular hyperthrophy.Am. J. Med. 25: 814, 1958.

5. BROCK, R. C.: Functional obstruction of theleft ventricle: acquired aortic subvalvularstenosis. Guy's Hospital Rep. 106: 221,1957.

6. SANDERS, R. J., AND MORROW, A. G.: Thediagnosis of circulatory shunts by the nitrousoxide test. Improvements in technic andmethods for quantification of the shunt. Cir-culation 18: 856, 1958.

7. BROOK, R., MILSTEIN, B. B., AND ROSS, D. N.:Percutaneous left ventricular puncture inthe assessment of aortic stenosis. Thorax11: 163, 1956.

S. MORROW, A. G., BRAUNWALD, E., HALLER,J. A., AND SHARP, E. H.: Left heart cathe-terization by the transbronchial route. Tech-nic and applications in physiologic anddiagnostic investigations. Circulation 16:1033, 1957.

9. DENIE, J. J., AND VERHEUGT, A. P.: Supra-valvular aortic stenosis. Circulation 18: 902,1958.

10. CHEU, S., FIESE, M. J., AND HATAYAMA, E.:Supra-aortic stenosis. Am. J. Clin. Path.28: 293, 1957.

11. KIRKLIN, J. W.: Personal communication.

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ROBERT D. BLOODWELL and EUGENE BRAUNWALDANDREW G. MORROW, JOHN A. WALDHAUSEN, ROBERT L. PETERS,

ObservationsSupravalvular Aortic Stenosis: Clinical, Hemodynamic and Pathologic

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1959 American Heart Association, Inc. All rights reserved.

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