507

Isolated Noncompaction ofLeft Ventricular Myocardium

A Study of Eight Cases

Thomas K. Chin, MD, Joseph K. Perloff, MD, Roberta G. Williams, MD,

Kenneth Jue, MD, and Renee Mohrmann, MD

Isolated noncompaction of left ventricular myocardium is a rare disorder of endomyocardialmorphogenesis characterized by numerous, excessively prominent ventricular trabeculationsand deep intertrabecular recesses. This study comprised eight cases, including three atnecropsy. Ages ranged from 11 months to 22.5 years, with follow-up as long as 5 years. Grossmorphological severity ranged from moderately abnormal ventricular trabeculations to pro-foundly abnormal, loosely compacted trabeculations. Echocardiographic images were diagnos-tic and corresponded to the morphological appearances at necropsy. The depths of theintertrabecular recesses were assessed by a quantitative echocardiographic X-to-Y ratio andwere significantly greater than in normal control subjects (p<0.001). Clinical manifestationsof the disorder included depressed left ventricular systolic function in five patients, ventriculararrhythmias in five, systemic embolization in three, distinctive facial dysmorphism in three,and familial recurrence in four patients. We conclude that isolated noncompaction of leftventricular myocardium is a rare if not unique disorder with characteristic morphologicalfeatures that can be identified by two-dimensional echocardiography. The incidence ofcardiovascular complications is high. The disorder may be associated with facial dysmorphismand familial recurrence. (Circulation 1990;82:507-513)

In the early embryo, the heart is a loose interwo-ven mesh of muscle fibers.1-3 The developingmyocardium gradually condenses, and the large

spaces within the trabecular meshwork flatten ordisappear. Trabecular compaction is normally morecomplete in left ventricular than in right ventricularmyocardium. Noncompaction of ventricular myocar-dium (sometimes referred to as "spongy myocar-dium") is believed to represent an arrest in endomyo-cardial morphogenesis.4,5 The gross anatomicalappearance is characterized by numerous, excessivelyprominent trabeculations and deep intertrabecularrecesses. Rare in any case, noncompaction is almostinvariably associated with other congenital cardiacmalformations.45 Isolated noncompaction of left ven-tricular myocardium (INVM) (i.e., without associ-ated anomalies) is rarer still.5-7 This report repre-sents the largest study population to date.

From the Division of Pediatric Cardiology, Departments ofPediatrics and Pathology, UCLA Center for the Health Sciences,Los Angeles, Calif.

Presented in part at the 61st Scientific Sessions, American HeartAssociation, Washington, D.C., November 1988.

Address for correspondence: Joseph K. Perloff, MD, Division ofCardiology, Room 47-123, UCLA Medical Center, Los Angeles,CA 90024-1736.

Received September 27, 1989; revision accepted April 3, 1990.

MethodsThe study comprised eight patients referred to the

UCLA Medical Center during a 5-year period endingin December 1988. The sex ratio was 1.7:1 (fivemales and three females). The mean age at presen-tation was 8.9 years (range, 11 months to 22.5 years).The data included a personal and family history,physical examination, 12-lead scalar electrocardio-gram, chest roentgenogram, two-dimensional echocar-diogram with Doppler interrogation, and necropsystudies in three patients (patients 1, 5, and 6; Table 1).Patients 4, 7, and 8 had 24-hour Holter monitoring,and patients 7 and 8 had intracardiac electrophysio-logical studies.

Two-dimensional echocardiograms were recordedin all patients with the ATL Ultramark 6 or 8Advanced Technology Laboratories, Bothwell, Wash.Diagnoses of INVM were based on the presence ofnumerous, excessively prominent trabeculationsassociated with deep intertrabecular recesses (Fig-ures 1 and 2). Coexisting cardiac anomalies weremeticulously excluded. Standard measurements ofleft ventricular end-diastolic dimensions (LVEDD),left ventricular free wall thickness at end diastole(LVWTd), and fractional shortening (FS) were nor-malized to body surface area. LVWTd was measured

by guest on October 5, 2017

http://circ.ahajournals.org/D

ownloaded from

508 Circulation Vol 82, No 2, August /990

TABLE 1. Clinical Information

Age ClinicalPatient (yr) Sex presentation

1 2.3 M SVD

23

94

mF

4 1.5 F

5 5.5 M

ComplicationsSVD, VA, SE

Asymptomatic Developmental impairmentVA SVD, VA

VA SVD, VA

Seizures SVD, VA, SE

6 22.5 F SVD SVD, SE7 14.5 M Asymptomatic VA, sinus bradycardia,

exercise-induced PVCs8 13 M Heart murmur Sinus bradycardia

Associatedfindings Outcome

FD, FR Died after cerebralembolus

FD, FR ...

FD Free from VA onamiodarone

. Free from VA afterpacemaker, digitalis,and quinidine

. . Died in ventricularfibrillation

. . Died with SVDFR ...

FR ...

SVD, systolic ventricuilar dysfunction; VA, ventricular arrhythmia; SE, systematic embolization; FD, facialdysmorphism; FR, familial recuirrence; PVC, premature ventricular contraction.

at the level of the mitral valve and at the level of thepapillary muscles with the parasternal long-axis view.Measurements at the apex used the suibxiphoid orapical four-chamber views.To quantify the depth of penetration of the inter-

trabecular recesses with two-dimensional echocardi-ography, an X-to-Y ratio was developed (Figure 3).This ratio is the quotient of the distance between theepicardial surface and trough of a trabecular recess

(represented by X) and the distance between theepicardial surface and peak of the trabeculation(represented by Y). The X-to-Y ratios at the levels ofthe mitral valve, papillary muscles, and apex inpatients with INVM were compared with values froma control group of eight subjects with normal two-dimensional echocardiograms (sex ratio, 1.7: 1; meanage, 5 years; range, 1.3-10.8 years). Two observersindependently interpreted the echocardiograms in

FIGURE 1. Echocardiogram ofpatient 1. Subxiphoid long-axisview shows numerous prominentleft ventricular trabeculations,increased depth of intertrabecularrecesses (arrows), and apicalthickening. LA, left atrium; LV,left ventricle; s, superior; i, inferior;r, right; 1, left.

by guest on October 5, 2017

http://circ.ahajournals.org/D

ownloaded from

Chin et al Isolated Noncompaction of LV Myocardium 509

oF l~ -, GE

o*% 2 i

3p

o or ER.

E

~

s0 C

= Z AzX

t

cl,~

by guest on October 5, 2017

http://circ.ahajournals.org/D

ownloaded from

510 Circulation Vol 82, No 2, August 1990

INTERTRABECULARRECESSES

PEAK OF/-x TRABECULATION

y

EPICARDIAL SURFACE THOUGH OF

TRABECULATIONFIGURE 3. Method for determining X-to-Y ratio. Depth ofintertrabecular recesses relative to posterior wall thickness isquantified by comparing distance between epicardial surfaceand trough of recess (X) with distance between epicardialsurface and peak of trabeculation (Y). SmallerX-to-Yratio inisolated noncompaction of left ventricular myocardium com-pared with normal reflects increased depth of intertrabecularrecesses in this disease.

the patients and the controls. Results were evaluatedfor the degree of interobserver variation with thepaired Student's t test. Significant differences inX-to-Y ratios between patients and controls weredetermined with the nonpaired Student's t test.Necropsy studies were performed on the three

patients who died. After formalin fixation, histologi-cal sections of ventricular myocardium and septumwere stained with hematoxylin and eosin, Massontrichrome, and Van Gieson elastic stains.

ResultsClinical InformationTwo patients were asymptomatic but were identi-

fied because of a sibling who had INVM (Table 1).Depressed left ventricular systolic function was clin-ically overt in five patients (63%). FS ranged from10% to 33%. LVEDD (five patients) and LVWTd(six patients), adjusted for body surface area, weregreater than the 95th percentile.

Five patients (63%) had ventricular arrhythmiasranging from isolated, unifocal premature ventricularbeats not clearly outside normal range (patients 1and 7) to ventricular tachycardia and fibrillation(patients 3-5). Patient 3 had supraventricular tachy-cardia with Wolff-Parkinson-White bypass tracts(documented at 2 months of age) and experiencedfour episodes of cardiac arrest ascribed to ventricularfibrillation (when 6-15 months old). Patient 4 exhib-ited runs of ventricular tachycardia; subsequentdevelopment of complete heart block requiredresuscitation and a right ventricular pacemaker.Patients 7 and 8 had resting heart rates of less than40 beats/min. Patient 7's heart rate decreased to 20beats/min during sleep. Premature ventricular beatsoccurred during subsequent exercise testing in thispatient, but ventricular tachycardia was not induc-ible during intracardiac electrophysiological study.Patient 5 had no history of ventricular arrhythmiasbut died in ventricular fibrillation after hospitaliza-

FIGURE 4. Photograph of patient 3 showing dysmorphicfacial appearance represented byprominent forehead, bilateralstrabismus, low-set ears, and micrognathia. Contracture of leftelbow can be seen. (Not sho-wt.n is high-arched palate.)

tion for a cerebral embolus and depressed leftventricular function.

Systemic emboli were clinically overt in threepatients (38%). In patients 1 and 5, the emboli werecerebral. Patient 6 had a saddle embolus to thebifurcation of the abdominal aorta. Left ventricularmural thrombi were identified on echocardiographyin patient 5 and at necropsy in patient 6 (Figure 2b).Noncardiac malformations included a distinctive

dysmorphic facial appearance characterized by prom-inent forehead, strabismus, low-set ears, high-archedpalate, and micrognathia (patients 1-3; Figure 4). Thethree patients with facial dysmorphism exhibitedmotor and speech defects; these defects had beenpresent since birth in patients 1 and 2. In patient 3,these defects were attributed (perhaps incorrectly) tocerebral hypoxia after cardiac arrest.

Familial recurrence of INVM was present in twobrothers (patients 7 and 8). There was also familialrecurrence in two half-brothers (patients 1 and 2)born to the same mother.

Scalar electrocardiograms showed left- or right-axis deviation in two patients (patients 2 and 8),broad or peaked P waves in three (patients 2, 4, and5), first-degree heart block in two (patients 1 and 2),and left ventricular conduction defects (intraventric-ular) in two (patients 4 and 5).

Chest roentgenograms were normal in the asymp-tomatic patients. There was cardiomegaly in patients1 and 4-6, who had clinically overt depressed left

by guest on October 5, 2017

http://circ.ahajournals.org/D

ownloaded from

Chin et al Isolated Noncompaction of LV Myocardium 511

X0.7-

Normal* 0.6 ....-...

INVM A 0. XT

0~

.3 --M--

.2--------

.1 -------

0 MV Pap. m. ApexMEASUREMENT SITE

(mm)25

20

LZNormals

XINVM 0;10

0

MV Pap. m. Apex

MEASUREMENT SITE

FIGURE 5. Top panel: Bar graph ofX-to-Y ratio and (bot-tom panel) of left ventricular wall thickness at end diastole(LVWTd) in patients with isolated noncompaction of leftventricular myocardium (INVM) compared with normal con-

trol subjects. In patients with INVM, X-to-Yratio decreased andLVWTd increased as measurements were obtained from levelsof mitral valve to papillary muscles to apex. Bars equal ±1

SEM. W, mitral valve; Pap.m., papillaty muscle.

ventricular function. Pulmonary edema was evidentin the roentgenograms of patients 5 and 6.

Two-dimensional echocardiograms disclosed numer-ous prominent trabeculations and deep intertrabecularrecesses (Figure 1) in all eight patients. The trabecula-tions were least prominent and less numerous near thelevel of the mitral valve where the X-to-Y ratio was0.92+0.07 (mean±SEM). The X-to-Y ratio decreasedto 0.59+0.05 at the papillary muscle level anddecreased further to 0.20±0.04 at the apex of the leftventricle (Figure 5a) where the depth of the intertra-becular recesses and the increased wall thickness weremost prominent. The mean LVWTd was 8.6±+1.6 mmat the level of the mitral valve, 13.3+1.2 mm at thepapillary muscle level, and 22.9+1.2 mm at the apex(Figure Sb). The control echocardiograms did notdisclose the progressive decrease in the X-to-Y ratioand the accompanying increase in LVWTd from mitralvalve level to apex (Figure 5). There was a markedincrease in apical wall thickness (Y) when normalcontrol subjects were compared with patients (5.6 ver-sus 22.9 mm, respectively), but epicardial surface totrough of trabeculation (X) was virtually the same (4.8versus 4.7 mm, respectively). These observationsencouraged our belief that the calculated abnormalitiesin X-to-Y ratios reflected the disease process-

noncompaction -rather than a technical error in mea-surement because of proximity of the transducer to theheart in the apical view or a tangential beam in thesubcostal view. The difference in X-to-Y ratio betweenpatients and controls at the mitral valve level was notsignificant. At the levels of the papillary muscles andapex, the X-to-Y ratio was significantly smaller in thepatients (p<0.001). Interobserver variation in mea-surements of the X-to-Y ratio were insignificant at thelevels of the mitral valve and papillary muscles but weresignificant at the apex (p<0.001). Echocardiographicabnormalities of right ventricular myocardium were notdetected.At necropsy (three patients), the gross left ventric-

ular endomyocardial morphology (Figure 2) corre-sponded to the two-dimensional echocardiographicpatterns. Patient 6 had clot within the intertrabecularrecesses of the left ventricular apex (Figure 2b). Thedeep intertrabecular recesses were successfully exam-ined histologically in two patients. The recesses,including their troughs, were lined with endotheliumthat was continuous with ventricular endocardialendothelium (Figure 6), indicating that the recesseswere not sinusoids. Zones of fibrous and elastic tissuewere scattered on the endocardial surfaces, withextension into the intertrabecular recesses (Figure 2).Because areas of normal endomyocardium might beinterspersed with noncompaction (patient 5), sectionswere taken with meticulous care to avoid missing thetypical histology of noncompaction. In patient 1, theright ventricular trabeculations and intertrabecularrecesses were relatively prominent, but no quantitativeconclusions could be drawn.

Discussion"Discrete muscle bundles, more than 2 mm in

diameter, that stood out against the background of theleft ventricular endocardium" have been reported in68% of normal hearts but are virtually always three orless in number.8 In contrast, noncompaction of ven-tricular myocardium, exemplified by our cases, ischaracterized by numerous, prominent trabeculationsand conspicuous intertrabecular recesses that pene-trate deep into the left ventricular myocardium (Fig-ures 1, 2, and 6). Left ventricular noncompaction-arare if not unique disorder of endomyocardial mor-phogenesis -consists of trabeculations that are bothincreased in prominence and excessive in number.The echocardiographic pattern is diagnostic (Figure1) and can be quantified with relative confidence by anX-to-Y ratio that decreases from the level of thepapillary muscles to the apex (Figure 5a). Discrimina-tion of the epicardial surface was difficult at the leftventricular apex due to proximity of the echocardio-graphic transducer to the heart. Accordingly, therewas significant interobserver variation in the X-to-Yratio at the apex in contrast to insignificant interob-server variation at the levels of the mitral valve andpapillary muscles. However, variation in measurementat the apex in any given case was small (mean±+SEM,1.4+0.5 mm; range, 0-5 mm) compared with the

by guest on October 5, 2017

http://circ.ahajournals.org/D

ownloaded from

512 Circulation Vol 82, No 2, August 1990

ITR

-- --tEis. -

B>E - ,9 .NXR'iXtEu .

.. .E t.Sif4z .X.Ew$e SLE

:* ::rE g; .te 6t)! ffii-+wzE'oN ,5(w <tE ,#i:-S

_- wo S-^Fse i X ; v e: - x S 1.m_6 r :9 uY R- vE Ci@ t k t esteWE; N u7-- ll Wo2 t Fiaag i: *, B. 8is $-: e i t s §_. >: : -eF *S_ * , ':a_ wi

s-.-;owiS,X t$kn.: SBm>>:,,''X<'>z>t }. v G 2 S. ,Ya BE>st izer9x.9r r .' . v S *N- X --s* E / ffi ti . i .Gi-EL ^ H 8 n- E 2 si_Ms

FIGURE 6. Photomicrograph of histological findings (low power; hematoxylin and eosin stain) in patient 1. Cross section of leftventricular myocardium shows endothelium (arrows) in continuity with intertrabecular recesses (ITR).

differences between patient and control groups(mean + SEM, 4.8± 0.2 versus 4.7 + 1.0 mm for X and5.6±0.2 versus 22.9+1.2 mm for Y).

Histological examination disclosed that the deepintertrabecular recesses were lined with endotheliumthat was continuous with the endocardial endothe-lium (Figure 6), indicating that the "spongy" appear-ance of noncompaction was due to the deep intertra-becular recesses per se and not to intramyocardialsinusoids. Accordingly, the term "persistent sinu-soids" is not appropriate. The descriptive term"spongy myocardium" has the virtue of precedence,but we prefer "ventricular noncompaction" for tworeasons. First, it underscores the hypothesis that thebasic morphogenetic abnormality may be an arrest ofthe normal process of compaction of the loose inter-woven mesh of myocardial fibers in the embryo.Second, some hearts with "spongy myocardium"have heavy trabeculations in the affected ventricle,but it does not follow that every heavily trabeculatedventricle has a "spongy myocardium."

Relatively rare in any case, ventricular noncompac-tion has almost invariably been associated with othercongenital cardiac malformations, including anoma-lous origin of the left coronary artery from the pulmo-nary trunk9 and obstruction to right or left ventricularoutflow.9-11 Isolated left ventricular noncompaction iseven more rare5-7; its natural history and clinicalmanifestations have therefore been ill defined. Oureight patients represent the largest study populationto date and shed new light on the clinical and mor-phological spectrum of this disorder. Based on these

observations, three major cardiac risks emerged: 1)depressed systolic function of the noncompacted leftventricle, 2) endocardial clot with systemic emboliza-tion, and 3) ventricular arrhythmias, sometimes fatal.

Depressed left ventricular function may be absent atthe time of presentation (patients 2, 7, and 8) or may beclinically overt since infancy or childhood (patients 1and 3-5) or since young adulthood (patient 6). Thecause of depressed left ventricular function is notclear. The coronary arterial circulation is normal inhearts with isolated ventricular noncompaction (non-compacted left ventricle perfused by a morphologicalleft coronary artery), so extramural myocardial bloodsupply is not likely to be at fault. However, intramu-ral perfusion, particularly subendocardial, may beadversely affected by the prominent trabeculationsand deep intertrabecular recesses. The increasedfibrous and elastic tissue on the endocardium andwithin the intertrabecular recesses (Figure 2) may bedue to subendocardial ischemia, perhaps in responseto isometric contraction among the trabeculae andwithin the recesses. The prominent trabeculations ofleft ventricular noncompaction resemble right ven-tricular endomyocardial morphology. It may there-fore be relevant that patients with univentricularhearts of the morphological right ventricular typehave poorer ventricular function than those of theleft ventricular type,12 despite similar extramuralcoronary circulations.The endomyocardial morphology of left ventricular

noncompaction lends itself to the development ofmural thrombi within the deep intertrabecular recesses

by guest on October 5, 2017

http://circ.ahajournals.org/D

ownloaded from

Chin et al Isolated Noncompaction of LV Myocardium 513

(Figure 2b). Three of our patients (1, 5, and 6) hadovert systemic emboli from this source. In two patients(1 and 5), the emboli were cerebral. Accordingly, it isprudent to repeat the echocardiogram at periodic inter-vals, regardless of whether clot is initially identified.Anticoagulants are warranted when thrombi are seenon echocardiography.

Ventricular arrhythmias were documented in fiveof the eight patients and were the presenting com-plications in two. It is unclear why isolated leftventricular noncompaction is arrhythmogenic. Zonesof thin ventricular wall in the troughs of the intertra-becular recesses are reminiscent of the morphologyof the right ventricle in arrhythmogenic right ventric-ular dysplasia. An analogy to arrhythmogenic rightventricular dysplasia is attractive but conjectural.13-15

Patients 1 and 2 and patients 7 and 8 are the firstknown examples of familial recurrence of isolatednoncompaction of left ventricular myocardium.Because of potential familial recurrence, identificationof an index case warrants echocardiographic assess-ment of first-degree relatives, particularly siblings;patients 2 and 7 were identified in this fashion. Patients1-3 represent the first reported association betweenfacial dysmorphism and INVM (Figure 4). These threedysmorphic patients also had developmental and men-tal defects. Patient 3's motor and cognitive abnormali-ties were attributed (perhaps incorrectly) to cerebralhypoxia induced by cardiac arrest.

ConclusionsIsolated noncompaction of left ventricular myocar-

dium is a rare if not unique disorder that may manifestitself from infancy through young adulthood. Bothsexes are affected. Distinct morphological features canbe diagnosed on two-dimensional echocardiography;these features correspond to the gross endomyocar-dial morphology at necropsy. Isolated noncompactionof left ventricular myocardium is accompanied bythree major cardiac risks: 1) depressed ventricularfunction, 2) endocardial clot with systemic emboliza-tion, and 3) ventricular arrhythmias, sometimes fatal.The disorder may be familial and may be associatedwith distinctive facial dysmorphism.

AcknowledgmentsWe wish to thank Drs. Henry Heins, Thomas

Santulli, Rick Wittner, and Mirka Zednikova forpermission to include cases referred by them.

References

1. Patten BM: Development of the heart, in Gould SE (ed):Pathology of the Heart. Springfield, Ill, Charles C. Thomas,1968

2. Volodaver Z, Neufeld HN, Edwards JE: Coronary ArterialVariations in the Normal Heart and in Congenital Heart Disease.New York, Academic Press, 1975

3. Grant RT: Development of the cardiac coronary vessels in therabbit. Heart 1926;13:261-271

4. Chenard J, Samson M, Beaulieu M: Embryonal sinusoids inthe myocardium: Report of a case successfully treated surgi-cally. Can Med Assoc J 1965;92:1356-1357

5. Jenni R, Goebel N, Tartini R, Schneider J, Arbenz U, Oswald 0:

Persisting myocardial sinusoids of both ventricles as an isolatedanomaly: Echocardiographic, angiographic, and pathologic ana-

tomical findings. Cardiovasc Intervent Radiol 1986;9:127-1316. Engberding R, Bender F: Echokardiographischer Nachweis

persistierender myokardialer sinusoide. Z Kardiol 1984;73:786-788

7. Goebel N, Jenni R, Gruntzig A: Persistierende myokardialesinusoide: Echokardiographie und angiokardiographie. FortschrRoentgenstr 1985;142:692-693

8. Boyd MT, Seward JB, Tajik AJ, Edwards WD: Frequency andlocation of prominent left ventricular trabeculations at autopsy in474 normal human hearts: Implications for evaluation of muralthrombi by two-dimensional echocardiography.JAm Coll Cardiol1987;9:323-326

9. Dusek J, Bohuslav O, Duskova M: Postnatal persistence ofspongy myocardium with embryonic blood supply. Arch Pathol1975;99:312-317

10. Freedom RM, Patel RG, Bloom KR, Duckworth JWA, SilverMM, Dische R, Rowe RD: Congenital absence of the pulmo-nary valve associated with imperforate membrane type oftricuspid atresia, right ventricular tensor apparatus and intactventricular septum: A curious developmental complex. Eur JCardiol 1979;10:171-196

11. Feldt RH, Rahimtoola SH, Davis GD, Swan HJC, Titus JL:Anomalous ventricular myocardial pattern in a child withcomplex congenital heart disease. Am J Cardiol 1969;23:732-734

12. Sano T, Ogawa M, Yabuuchi H, Matsuda H, Nakano S,Shimazaki Y, Taniguchi K, Arisawa J, Hirose H, Kawahima Y:Quantitative cineangiographic analysis of ventricular volumeand mass in patients with single ventricle: Relation to ventric-ular morphologies. Circulation 1988;77:62-69

13. Blomstrom-Lundqvist C, Sabel KG, Olsson SB: A long termfollow up of 15 patients with arrhythmogenic right ventriculardysplasia. Br Heart J 1987;58:477-488

14. Matsuoka Y, Kawaguchi K, Okishima T, Hayakawa K: Aninfant with suspected right ventricular dysplasia presentingunique ventriculograms. Clin Cardiol 1988;11:55-58

15. Nava A, Gaetano T, Canciani B, Scognamiglio R, Daliento L,Buja G, Martini B, Stritoni P, Fasoli G: Familial occurrence ofright ventricular dysplasia: A study involving nine families. JAm Coll Cardiol 1988;12:1222-1228

KEYWORDS * endomyocardial morphogenesis * arrhythmias Ecardiomyopathies * ventricular dysfunction

by guest on October 5, 2017

http://circ.ahajournals.org/D

ownloaded from

T K Chin, J K Perloff, R G Williams, K Jue and R MohrmannIsolated noncompaction of left ventricular myocardium. A study of eight cases.

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1990 American Heart Association, Inc. All rights reserved.

is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation doi: 10.1161/01.CIR.82.2.507

1990;82:507-513Circulation. 

http://circ.ahajournals.org/content/82/2/507the World Wide Web at:

The online version of this article, along with updated information and services, is located on

  http://circ.ahajournals.org//subscriptions/

is online at: Circulation Information about subscribing to Subscriptions: 

http://www.lww.com/reprints Information about reprints can be found online at: Reprints:

  document. Permissions and Rights Question and Answer information about this process is available in the

located, click Request Permissions in the middle column of the Web page under Services. FurtherEditorial Office. Once the online version of the published article for which permission is being requested is

can be obtained via RightsLink, a service of the Copyright Clearance Center, not theCirculationpublished in Requests for permissions to reproduce figures, tables, or portions of articles originallyPermissions:

by guest on October 5, 2017

http://circ.ahajournals.org/D

ownloaded from