Serial Cardiac Catheterizations Exercise Hemodynamics...

Serial Cardiac Catheterizations and ExerciseHemodynamics after Correction of

Tetralogy of Fallot

Average Follow-Up 13 Months and 7 Years after Operation

By J. DAvm BmSTOW, M.D., FRANK E. KLOSTER, M.D., MARTIN H. LEEs, M.D.,

VICTOR D. MENASHE, M.D., HERBERT E. GRISWOLD, M.D., AND ALBERT STARR, M.D.

SUMMARYEleven patients had right heart catheterization an average of 13 mo after total

correction of tetralogy of Fallot, and the procedures were then repeated an averageof 7 years postoperatively. In the intervening time there was generally no im-portant change in the pressure gradient between the right ventricle and pulmonaryartery or in right ventricular systolic pressure. Mean right atrial pressure tended tofall with time. Arteriovenous oxygen difference at rest was lower at the secondstudy, and the resting cardiac output was generally normal. One patient with a

persistent ventricular septal defect had progressive hemodynamic deteriorationbetween the two studies. Exercise performance up to 10 years postoperatively was

also assessed. The relationship between oxygen consumption and cardiac outputwas usually normal, but exercise magnified the right heart's filling pressure abnor-malities. In the absence of an easily demonstrable ventricular septal defect, rightheart hemodynamics were either stable or improved up to 10 years postoperatively.The exercise response of cardiac output was usually normal at moderate work loads.

Additional IndexingPulmonic regurgitationOpen heart surgery

Words:Ventricular

Cardiacseptal defectoutput

Infundibular stenosisExercise capabilities

T OTAL surgical correction is well estab-lished as successful treatment for tetralo-

gy of Fallot, many reports having de-scribed the highly satisfactory results usuallyachieved. 1-7 Postoperative cardiac catheteriza-tions have demonstrated residual hemodynam-ic abnormalities, however, and these are asource of uncertainty in the long-rangeoutlook for these children.2 8-14 One concern

From the Division of Cardiology, Department ofMedicine, Department of Pediatrics, and Division ofCardiopulmonary Surgery, University of OregonMedical School, Portland, Oregon.

-This investigation was supported in part byProgram Project Grant HE 06336 from the NationalHeart and Lung Institute.

Received December 19, 1969; accepted for publica-tion February 9, 1970.

Circulation, Volume XLI, June 1970

is pulmonic valve regurgitation, especiallylikely to be of significant degree when aprosthetic or pericardial patch is employed toenlarge the right ventricular outflow tract orhypoplastic pulmonary artery. Because of thiscomplication and its unknown long-termeffects, the trend in recent years has been toavoid the use of an outflow patch wheneverpossible and to avoid cutting the pulmonicvalve annulus.15, 16 A second problem isresidual obstruction of the right ventricularoutflow tract which is usually mild in the earlyyears after correction but is the cause of amodest systolic pressure gradient between theventricle and pulmonary artery. A thirdconcern is the permanence of repair of thelarge ventricular septal defect seen in tetralo-gy. Finally, there is little information about

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BRISTOW ET AL.

Table 1Ages and Time Intervals for All Patients

Time from operationAge at To To

operation 1st cath. 2nd cath.(yr) (yr-mo) (yr-mo)

Average, repeatcaths. group

Average, exercisegroup

188

117341074201637669

10

1-52-00-60-90-9

0-101-50-100-52-40-81-109-65-105-9

1-1

12 6-10

Abbreviations: PA = patch entended across pulmonic annulus into the artery; cath. = rightheart catheterization.

the hemodynamic response to exercise inpatients who have had these residual abnor-malities for several years.

It is essential to detennine whether thepostoperative hemodynamic findings remainstable or become progressively more abnormalas time passes and children grow. It is equallyimportant to understand their capability torespond to the demands of exercise. Thispaper reports cardiac catheterization in thefirst few years after surgical correction whichwas then repeated up to 10 years postopera-tively in the same patients, most of whom hadoutflow tract prostheses. Attention was espe-cially directed to the levels of the right heartpressures, the pressure gradient between theright ventricle and pulmonary artery, and thepresence of residual left-to-right ventricularshunts. Exercise capability was also appraisedby cardiac catheterization up to 10 years

postoperatively.

MethodsFifteen patients were selected because of their

availability and willingness to have the postopera-tive procedures done (table 1). The surgicalfindings had confirmed the diagnosis of tetralogyaccording to criteria published previously.3 Cor-rection had been performed by closure of theventricular septal defect with a polyvinyl patch.Outflow tract resection or pulmonic valvotomy, orboth, were done, and 11 of the 15 patients had aTeflon outflow tract prosthesis placed to widenthe outflow tract and proximal pulmonaryartery.Eleven had two cardiac catheterizations after

surgery; their average age at the time of operationwas 10 years, with a range from 3 to 20 years.The first catheterization was performed anaverage of 13 mo postoperatively and the secondan average of 7 years and 3 mo after operation.The average age at the time of the second studywas 17 years.

Six of the foregoing patients and four othershad exercise studies perforned an average of 6years and 8 mo postoperatively. Nine of the 10had operation more than 5 years previously, and

CiGcation, Volume XLI, June 1970

0

CtsN._

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4i0

123456789101112131415

Age atlastcath.(yr)

25

16

18

15

9142013 X10 x26 '-

1)22 .*38 a16 X1215

7-47-67-27-116-09-7

10-0

5-86-65-66-5

7- 3

Outflowtract

prosthesis

Yes, to PAYes, to PAYes, to PA

NoYes, to PA

Yes, to PAYes

Yes, to PAYes, to PA

NoYes, to PA

NoYes, to PA

NoYes

17

19

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CATHETERIZATION AND EXERCISE HEMODYNAMICS

Table 2Serial Catheterizations in 10 Patients Without Significant Left-to-Right Shunting

Upper Catherization Probabilitynormal oflimit No. 1 (range) No. 2 (range) difference*

Mean right atrial 5 6.6 3.7 NSpressure (mm Hg) (2-12) (1-6)

Right ventricular 5 5.7 5.9 NSend-diastolic (0-10) (2-8)pressure (mm Hg)

Right ventricular 30 44 44 NSsystolic (30-67) (29-65)pressure (mm Hg)

Pulmonary arterial 30 31 27 NSsystolic (2545) (1640)pressure (mm Hg)

RV-PA pressure 0 14 16 NSgradient (mm Hg) (0-34) (5-34)

Pulmonary arterial 20 17 15 NSmean pressure (mm Hg) (10-21) (7-20)

Systemic arterial - 93.9 95.2 NSoxygen saturation (%0) (88.0-95.9) (89.3-98.5)

Arteriovenous - 5.1 3.7 < 0.01oxygen difference (vol %) (4.2-6.9) (2.6-4.7)

Cardiac index - 3.10t 4.36 NS(L/min/M2) (2.80-3.41) (2.25-7.00)

Oxygen consumption - 152t 153 NS(ml/min/m2) (128-195) (106-182)

*Student's t-test for difference between means.tSix patients only.Abbreviations: NS = not significant at 0.05 level; RV =

arterial.

three were more than 9 years from surgery. Theirmean age was 183; years when studied.

Right heart catheterization was usually per-formed from an antecubital vein cutdown and abrachial artery was cannulated. Cardiac outputwas measured by the Fick principle using analysisof expired air by the Scholander technic, andmeasurement of oxygen content of blood sampleswith the Van Slyke apparatus. At the time of thesecond studies dye-dilution curves were performedby pulmonary arterial injection of indocyaninegreen, and systemic arterial sampling, through acuvette densitometer. Appearance times of in-haled hydrogen were used to detect left-to-rightshunts, using a platinum-tipped catheter in theright heart chambers.17 18 Exercise was per-formed in the supine position by pedalling anelectrically braked bicycle ergometer. Threepatients performed during a single work loadwhereas the other seven had measurements madeat two different loads.Circulation, Volume XLI, June 1970

right ventricular; PA = pulmonary

ResultsSerial CatheterizationOne patient had a large left-to-right shunt

and is considered separately from the other 10who had repeat catheterization.Ten Patients Without Significant Residual ShuntThe right heart pressures are summarized in

table 2 and figure 1. Peak right ventricularpressures were remarkably consistent. Thegreatest difference between the two proce-dures was a fall of 16 mm Hg, and theaverages were identical at the two times at 44mm Hg. The peak pressure gradient betweenthe body of the right ventricle and thepulmonary artery was also nearly constantover the years, averaging 14 and 16 mm Hg.Mean pulmonary arterial pressure averaged 17

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10

cZ~

0l

2 2A B

Figure 1

Results from cardiac catheterizations an average of

13 mo (no. 1) and 7 years (no. 2) after operation.(A) Mean right atrial pressures decreased from ab-normal levels to the normal range in six subjectsand rose to an abnormal level in one other. (B) Ar-teriovenous oxygen difference was lower in all sub-jects at the time of the second catheterization.

mm Hg at the first procedure and 15 mm Hglater.Hemodynamic evidence of pulmonic regur-

gitation was judged by equality or near

equality of end-diastolic pressures in the rightventricle and pulmonary artery. At the secondcatheterization the pressures in these twochambers were equal to or within 2 mm Hgof those at the first catheterization in eight ofthese 10 patients. Right ventricular end-diastolic pressure was abnormal in five pa-

tients at both times; the highest value in themore recent study was 8 mm Hg.At the time of the first catheterization, mean

right atrial pressure was greater than normalin six patients; when the second procedurewas perforned, only one patient had a slightlyabnormal level. The average mean right atrialpressure fell from 6.6 to 3.7 mm Hg and some

decreases were as great as from 12 to 2 mmHg (fig. 1). Despite the individual changes,the difference of the means for the group was

not statistically significant.

The arteriovenous oxygen difference de-creased with time in all patients (fig. 1). Theaverage value was 5.1 vol% initially, the upperlimit of normal, and fell to 3.7 vol% at thesecond study. No one then had an abnormalvalue. At the first postoperative procedure sixof the 10 patients had determinations ofcardiac output. The average value was higherat the second catheterization in the six, but nodefinite trend of increase or decrease occurred.At the second catheterization, the cardiacindex was normal (greater than 2.5 L/min/m2)in nine of the 10 patients.Measurements of pulmonary vascular resis-

tance were within normal limits.Three patients had systemic arterial satura-

tion below 94% initially. In one it was belowthis value at the second catheterization.Although unexplained, it is assumed to beventilatory in origin.At the second study, the presence of left-to-

right shunting was evaluated by three meth-ods: oximetry of right heart blood samples,use of systemic arterial indocyanine green-dilution curves, and the detecting of singlebreaths of inhaled hydrogen by a platinum-tipped catheter in the right heart chambersand pulmonary artery. Hydrogen curves wererecorded for nine of the 10 subjects. For thetenth, dye-dilution curves were normal. Fourpatients had early appearance of inhaledhydrogen in the right heart or pulmonaryartery. In all four, sampling of blood foroxygen saturation during a single pass throughthe right heart failed to detect a significantstep-up. A definite diagnosis of a smallventricular shunt was made in two of thesepatients. In the other two, hydrogen appearedearly in the right atrium (appearance time 4and 2 sec). The presence of an undiscoveredatrial defect is an unlikely explanation, andtwo other possibilities remain. A small ventric-ular septal defect with tricuspid insufficiencycould produce this finding but seems improb-able on clinical grounds and in the presence ofnormal right atrial pressure. Early return ofcoronary circulation, however, could explainthe short appearance time in these twosubjects. In summary, two patients have


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shunting was present. The resulting systemicarterial saturation was 84%. He was reoperatedupon and only a small remnant of Ivalon waspresent around the margin of the ventricularseptal defect.

This is the one patient of the 11 whose serialcatheterizations documented a marked in-crease in right heart pressures over the yearsand the one of 11 whose values were in aseriously abnormal range.Effects of Exercise Late After Correction

*/ The magnitude of the work load was judged* in terms of total body oxygen consumption.

./ The average resting value was tripled at thehighest work level, changing from 150 to 453ml/min/m2; the cardiac index rose about 50%.The heart rate increased 10 to 50 beats/min,with an average increase of 29. The relation-

I ship between oxygen consumption and cardiac200 400 600 index in these patients is shown in figure 2.V02 /M2 The slope of the lines is an expression of the

Figure 2 exercise factor, namely milliliter increase inrelationship between oxygen conusmption, cor- cardiac output per 100-ml increase in oxygen

>d for body surface area, and cardiac index at consumption. Estimates of the lower limit ofrest and during one or more levels of exercise.

persistent small ventricular septal defects, andthis possibility is unlikely but not completelyexcluded in two others. None of the four hashad a significant change in right heartpressures between the two catheterizations.

Patient with a Large Left-to-Right Shunt

This patient, an 18-year-old man, had evi-dence of an open ventricular septal defect atcatheterization 18 mo postoperatively. Thepulmonary-to-systemic flow ratio was 1.5,right ventricular pressure was 48/9 mm Hg,and mean pulmonary arterial pressure was 22.No operation was advised. Restudy 6 years

later, 71 years postoperatively, showed severe

right heart failure with a right ventricularpressure of 95/24 and mean right atrialpressure of 17. Right ventricular blood had a

20% increase in oxygen saturation compared tothat in the right atrium. The pulmonary-to-systemic flow ratio was 1.7. Both systemic andpulmonary flows, however, were lower than atthe previous catheterization, and right-to-leftCirculation, Volume XLI, June 1970

B

8,

4 2

Normals

r- 0.88Exercise factor 620

200 400

°2V02/

600 800 1000

Figure 3

The relationship between oxygen consumption andcardiac index for normal subjects at rest and exer-

cise is shown by the solid dots. These values were

taken from other publications.23-30 Seventeen pointsshown by the stars are values during exercise from our

10 patients studied after correction of tetralogy. Theline is the calculated regression for the normal data,with a slope equivalent to an exercise factor of 620.

8

6

4"- 4

b

.t

2

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10

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5

R E

50 e

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R E R E

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Pressures, in mm Hg,by horizontal bars.

30

'% 20

g 10

E R

Figure 4at rest and with exercise for

30 V

20 r

10 K

E R E

individual patients. Averages are shown

normal for exercise factor vary between 550and 800 mi.19-22 The average exercise factordetermined from a large number of publishedresults by others is about 620, as shown by thecalculated line in figure 3,23-30 Harvey and hercolleagues,21 however, have suggested that ahigher value (800) is closer to the true lowerlimit of normal if one is completely assured of

a basal resting state (in other words, judgedby a cardiac index less than 3.5). The higherthe cardiac output at rest, the less the increasein output expected with exercise, at least atmoderate levels of oxygen consumption. Inour young group in this paper, half of thepatients had an index at rest above 3.5, andwe chose to use 550 as the lower normal limit


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for exercise factor. Comparing the oxygenconsumption and cardiac output at rest withthat of maximum exercise, the average in ourpatients was 715, although five had valuesbelow 550.The cardiac output response can also be

appraised by judging individual values ofcardiac index during exercise in relation to theactual oxygen consumption, rather than thechange from rest to a level of exercise. This isshown in figure 3 in which are plotted normalresults from several reports in the literature.Seventeen points obtained during exercise inthe present study are also shown (sevenpatients with two levels of exercise and threewith one level). Two points appear abnormal-ly low.

Stroke volume rose with exercise in six ofthe 10 patients, was unchanged in one, andfell in three. Averages were 50.7 ml/beat/iM2at rest and 53.6 with exercise, a statisticallyinsignificant change. There was no correlationbetween the change in stroke volume and theexercise factor.

Pressures are shown in figure 4. Rightventricular systolic pressure was measured inboth states in nine of the patients andincreased an average of 11 mm Hg withexercise, reaching 47. The peak pressuregradient between the right ventricle andpulmonary artery did not change in aconsistent way with exercise, however, and theincrease in right ventricular pressure wasusually translated into increased pulmonarvarterial pressure. Decreases in the gradient intwo subjects are of interest but are notexplained. Mean pulmonary arterial pressurerose an average of 6 mm Hg but remained inthe normal range in all but one patient. Innine patients right ventricular end-diastolicpressure was measured at rest and exerciseand was found to rise in six. Values above 5mm Hg were found in five of these, and thehighest was 11 mm Hg. Eight subjects hadright atrial pressure measured at rest and withexercise, and slight increases occurred in four.One rose to an abnormal level.

Systemic arterial oxygen saturation was


normal in both states in all but one patient,who had a value of 93.4% with exercise.

DiscussionThe results of the repeat catheterizations

allow an optimistic outlook as to the assess-ment of the long-term course of the 10patients without marked left-to-right shunting.In general, over the average span of 6 yearsbetween procedures, the right ventricularsystolic pressure remained the same and thesystolic pressure gradient between the ventri-cle and the pulmonary artery did not changeappreciably. Similar results were reportedrecently in seven patients who were restudied5 years after an earlier postoperative catheter-ization, showing stability of the hemodynamicfindings.3' It appears that as patients grow,inadequacy of outflow tract dimensions willnot be a problem. Most of our patients wereof adult or near adult size at the time of thesecond procedure.

Evidence of pulmonic regurgitation re-mained obvious in many, however. It was notpossible to measure the amount of regurgitantflow in our studies, but the influence of thisvalvular defect is reflected by the resultingright heart filling pressures and the cardiacoutput. The average right ventricular end-diastolic pressure was slightly above normallimits on both occasions and presumably isassociated with an elevated ventricularend-diastolic volume due to valve in-competence.32' 33 A decrease in mean rightatrial pressure over the years was associated,however, due to falls from distinctly abnormallevels in several patients. Since right ventricu-lar end-diastolic pressure did not change forthe group and right atrial pressure tended tofall, it may be that improved atrial or tricuspidvalve function occurred. In any event, rightatrial pressure is now normal in most of thesubjects, and ventricular diastolic pressure,although persistently abnormal in several, hasnot changed in a consistent way.Concern about postoperative pulmonic

valve function has been expressed in severalpapers that recommend avoidance of prosthet-ic or pericardial widening of the outflow tractwhenever possible, to prevent pulmonic regur-

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gitation. This attitude is maintained, even tothe point of acceptance of a substantialpressure gradient by some surgeons. Othershave employed aortic valve homograft re-placement of the pulmonic valve as part ofcorrection of tetralogy.34 The extent to whichthis new approach with its own problems isexplored surely should be influenced bycatheterization findings over the years in thoseoperated upon by established technics. Thepresent work is not intended to makerecommendations about surgical technics. Wehave shown, however, that pulmonic regurgi-tation has been tolerated well up to 10 yearspostoperatively, and this permits some confi-dence in managing those patients who requirewidening of the outflow tract with a patch.The cardiac output at rest was normal up to

10 years after surgery and comparison of thearteriovenous oxygen differences over theyears shows a consistently improved state ofoxygen delivery to the body.35 Although left-to-right shunting would raise the pulmonaryarterial oxygen content, this is not believed tobe a significant factor in the diminution ofarteriovenous oxygen difference with time.With one exception, residual shunts were notdetectable by step-ups in oxygen levels in theright heart chambers and most of the patientshad no evidence of shunting at all.The exercise results demonstrate cardiac

output increments which were slightly sub-normal in some patients, as evaluated by theexercise factor. This may be accounted for bythe relatively high values at rest in this youngpopulation. When judged with the largenumber of such measurements taken from theliterature, the actual cardiac output levels at agiven oxygen consumption were usually com-parable with normals. Our conclusion that thecardiac output response is usually normal issimilar to that reached by Gotsman33 in aprevious study of six patients after opera-tion.The pressure changes with exercise, how-

ever, magnified the abnormalities found atrest. Abnormalities of right ventricular func-tion were shown by increases in rightventricular end-diastolic pressure with exercise

to abnormal levels in several patients2" andmay be largely the result of pulmonicregurgitation. The lack of appreciable increasein pressure gradient between the right ventri-cle and pulmonary artery with exercise isencouraging.The fate of repair of ventricular septal

defect is another consideration of importance.Two of our patients who had repeat catheteri-zations had definite evidence of small left-to-right shunts. The more delicate means fordetecting them were not employed at the timeof the first catheterization and thus it is notcertain whether they are of long-standing orrecent development. Since they were notdetectable by oximetry on either occasion,there is no sign of progressive enlargement.Similarly, there were no important changes inright heart pressures in these patients. Thepresence of a larger residual ventricular septaldefect was evident early in one other patient'scourse, however, and culminated in severeheart failure. Although broad generalizationscannot be made from experience with thisindividual, it is clear that patients with anobvious left-to-right shunt after operationshould be followed more closely than others.

ConclusionsOur study, which was intended to help

define the hemodynamic course after totalcorrection of tetralogy of Fallot, shows that thecourse of the original lesion is grossly alteredby operation, with a very favorable clinicaloutcome. During the first 10 years aftercorrection of the lesion the residual abnonnal-ities of pulmonic valve function and rightheart filling pressure were tolerated well and,if anything, right heart filling pressures de-crease with time. Further evidence of accom-modation to the new dynamics is shown byimprovement in oxygen delivery to the body,as judged by the arteriovenous oxygen differ-ence. The ultimate results of this procedurestill remain to be defined, but the presentstudy does demonstrate stability of hemody-namics during the first 10 years after correc-tion and an acceptable response to thedemands of moderate exercise. Exceptions tothis evolution may be found in those with


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significant left-to-right shunt postoperative-ly.

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Direct vision intracardiac surgical correction ofthe tetralogy of Fallot, pentalogy of Fallot, andpulmonary atresia defects. Ann Surg 142: 401,1955

2. KIRKLIN JW, ELLIS FH, MCGoON DC, Er AL:Surgical treatment for the tetralogy of Fallotby open intracardiac repair. J Thorac Surg 37:22, 1959

3. BRiSTOW JD, MENASHE VD, GRIsWoLD HE, ETAL: Total correction of tetralogy of Fallot:Complications and results. Amer J Cardiol 8:358, 1961

4. KIRKLIN JW, WALLACE RB, MCGOON DC, ETAL: Early and late results after intracardiacrepair of tetralogy of Fallot. Ann Surg 162:578, 1965

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6. GERBODE F, JOHNSTON JB, SADER AA, ET AL:Complete correction of tetralogy of Fallot.Arch Surg 82: 793, 1961

7. MALM JR, BLUMENTHAL S, BOWMAN FO JR, ETAL: Factors that modify hemodynamic resultsin total correction of tetralogy of Fallot. JThorac Cardiovasc Surg 52: 502, 1966

8. BRIsTow JD, ADROUNY ZA, PORTER GA, ET AL:Hemodynamic studies after total correction oftetralogy of Fallot. Amer J Cardiol 9: 924,1962

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14. HALLIDIE-SMITH KA, DULAKE M, WONG M, ETAL: Ventricular structure and function after


radical correction of the tetralogy of Fallot.Brit Heart J 29: 533, 1967

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16. GOLDMAN BS, MUSTARD WT, TRUSLER GS: Totalcorrection of tetralogy of Fallot: Review of tenyears experience. Brit Heart J 30: 563, 1968

17. CLARK LC JR, BARGERON LM JR: Detection anddirect recording of left to right shunts with thehydrogen electrode catheter. Surgery 46: 797,1959

18. HUGENHOLTZ PG, SCHWARK T, MONROE RG, ETAL: The clinical usefulness of hydrogen gas asan indicator of left to right shunts. Circulation28: 542, 1963

19. FERRER MI, HARVEY RM, CATHCART RT, ET AL:Hemodynamic studies in rheumatic heartdisease. Circulation 6: 688, 1952

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Mechanical and myocardial factors in rheu-matic heart disease with mitral stenosis.Circulation 11: 531, 1955

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Eulogy to Physicians

For these friends of ours who have gone before, there is now no more toil; theystart from their slumbers no more at the cry of pain; they sally forth no more into thestorms; they ride no longer over the lonely roads that knew them so well; their wheelsare rusting on their axles or rolling with other burdens; their watchful eyes are closedto all the sorrows they lived to soothe. Not one of these was famous in the great world;some were almost unknown beyond their own immediate circle. But they have leftbehind them that loving remembrance which is better than fame, and if their epitaphsare chiselled briefly in stone, they are written at full length on living tablets in athousand homes to which they carried their ever-welcome aid and sympathy -OLIVERWENDELL HOLMES: Currents and Counter-Currents in Medical Science. Boston, Ticknowand Fields, 1861, p. 3.


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MENASHE, HERBERT E. GRISWOLD and ALBERT STARRJ. DAVID BRISTOW, FRANK E. KLOSTER, MARTIN H. LEES, VICTOR D.

Tetralogy of Fallot: Average Follow-Up 13 Months and 7 Years after OperationSerial Cardiac Catheterizations and Exercise Hemodynamics after Correction of

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1970 American Heart Association, Inc. All rights reserved.

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Serial Cardiac Catheterizations Exercise Hemodynamics...

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