CHRONIC CONSTRICTIVE PERICARDITS COMBINEDWITH HYPOPROTEINAEMIA

BY

F. KUIPERSFrom the Paediatric Clinic of the University of Amsterdan, the Netherlands

(RECEIVED FOR PUBLICATION DECEMBER 24, 1954)

Constrictive pericarditis usually affects males inthe third and fourth decades of life (PauL Castlemanand White, 1948; Chambliss, Jaruszewski, Brofman,Martin and Feil, 1951), but is rare under the ageof 10. Rothstein (1934) collected 34 cases from theliterature in children up to 15 years old, who hadbeen operated on, but only 12 were younger than 10.More reports have appeared since, but the childrenare now usually included in large series of patientswho have undergone an operation. It is oftenimpossible to select the children from those seriesand thus to establish any special features that mightoccur in childhood, for instance hypoproteinaemia,as has been suggested by McKusick (1952). Therarity of the disease in children, together with thedifficulties we originally had in making the diagnosis,have prompted the following case report.

Case ReportOn March 3, 1954, a 7-year-old boy was referred to

the Children's Clinic for investigation of hypopro-teinaemic oedema and ascites. He was the eighth of11 children. The family history contributed nothing butthe boy had been treated badly during the first six monthsof life and a state of malnutrition had developed. Hewas then brought up by step-parents on a farm and hehad not been ill since.An inguinal hernia was operated upon in February,

1953. Much fluidihad appeared from the abdominal

TABLE I

LEVEL OF BLOOD PROTEINS (METHOD OF HOWE)ON VARIOUSADATES

Date 918 9/17 9/29 10119 1/28 223 313 4/14 7181953 1954

Albumin .. 3-54 3 3 3-17 3-08 2-58 2-63 2-53 2-45 4 64Globulin . 0-96 1-93 1-62 1-42 1-72 1-37 0-92 1-4

Total 4-5 5-2 5-1 4-7 4-0 4-35 3-9 3-37 6-04

Electrophoretic fraionation according to the Tiselius method:albumin 19 -32, a-globulin 5-91, -globulin 6-54, --globulin 3 22 g1I.Total serum proteins= 34 g. per 1.

cavity. The boy had made an uneventful recovery.During the summer he had measles and chickenpox, andafterwards oedema of the face and feet was noted. Hisappetite decreased and periodically he had loose stools.During clinical observation elsewhere (August, 1953) anenlarged liver and ascites were found. The blood proteinlevels were low (Table 1), the cholesterol content of theblood was normal (Table 2) as were the temperature andpulse rate. No protein could be demonstrated in theurine. A series of liver function tests did not show anyabnormalities. No tubercle bacilli could be culturedfrom the ascites. A needle biopsy of the liver did notshow histological abnormalities. The tuberculin test ofthe skin was negative. The boy now had a ravenousappetite. His condition improved although the bloodprotein levels did not change much, and even showed a

TABLE 2BIOCHEMICAL DATA AND LIVER FUNCTION TESTS ON

VARIOUS DATES

Sept., Feb., April,1953 1954 1954

E.S.R. (mm. in I hour Wester-gen)

Alkaline phosphatase level(Bodansky units) .. ..

Cholesterol (mg, 100 ml.serum)Esters (%) - -van den Bergh test: direct . .

indirectUrea (mg./L. blood) .. ..Thymol turbidity (units) ..Bromsulphalein test (40mg.

intravenously) .. ..(value after 3'= 100.) .

4

10-1170

NegatiseTrace333

2 3 to 6

6-7185

NegativeNegative

250

Urobilimuria Negative Trace

Galactose tolerance (excretionaftcr ingestion of 24 g. bymouth) . 0-04 g

Basal metabolic rate ..Ncutral fat in faecs %wetFatty acids in faeces Sweight

90-14174

3863

Neg. after 30'45 */. after 6'Neg. after 30'

0- 16 g.-1%0 31 -3

Blood suwar levels (mg.j 100 ml.) fasting and at various timnes afterthe ingestion by mouth of glucose and fructose

After0 30' 60' 90' 150'

30-0 g. glucose .- 119 179 189 165 9336-5 g. fructose . . 105 126 133 121 122

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ARCHIVES OF DISEASE IN CHILDHOOD

I ...FK;. 1.-Radiograph of the heart before operation.

tendency to decrease (Table 1). He was treated with adiet poor in salt, but rich in proteins plus methionine andvitamin B complex and liver injections. Shortly after apurulent otitis the ascites again increased considerablyand he was readmitted at the end of January, 1954.Biochemical results were as before, and he was trans-ferred to the Children's Clinic for further investigation.We found a short, stubby boy (somatic development

about 5 years old) with a considerably enlaged chestcircumference similar to that of a child of 11 years. Hisweight was 21 kg. He was in no apparent distress buton exertion easily became dyspnoeic. No cyanosis waspresent, the respiration rate being about 20 per minute.His face was puffy and slight oedema was present aroundthe eyelids. The heart sounds were normal. The liveredge was felt 5 cm. below the costal margin and thepresence of free fluid in the abdominal cavity could easilybe demonstrated. Compared with slight oedema in thelegs the amount of ascites was considerable. Bloodpressure measured 95/60 mm. of mercury, and engorge-ment of the neck veins with pulsations of a level about4 cm. above the angle of the stemum indicated anincreased venous pressure. No protein or otherabnormality could be demonstrated in_ the urine.Urobilinuria was sometimes increased.Chronic constrictive pericarditis was suspected. The

heart seemed to be somewhat enlarged to the left (Fig. 1)but pulsations were thought to be normalI duringfluoroscopy and no deposits of calcium could be seen.The radiokymograph demonstrated fair pulsations of theleft border of the heart (Fig. 2). Although the rightborder did not pulsate this was not accepted asevidenceof constrictive pericarditis, because the auricles generallydo not show evident pulsations on a kymograph. Anelectrocardiogram demonstrated right axis deviation in

the standard limb leads and severe right axis strain inthe V leads. The height of the excursions was thoughtto be normal, although in several leads the P and theT waves could barely be distinguished (Fig. 3).The diuresis measured between 200 and 400 ml. per

day, while the fluid intake was free (about 700 to 1,000 ml.per day). The specific gravity of the urine was 1,020 ormore. The daily output of chlorides was less than5 mEq., but the salt in the diet was restricted.During the first fortnight of observation the level of

the pulsations in the veins of the neck decreased graduallyuntil it corresponded with the level of the angle of Louisnmsured by the method of Borst and Molhuysen (1952).The body weight remained fairly constant and no changeoccurred in the size of the liver nor in the amount of theascites. In the meantime a series of liver functiontests gave normal results, including two bromsul-phthalein tests (Table 2). Also the tuberculin test withI mg. of old tuberculin was negative, as were serologicaltests for syphilis.So far we had not obtained a satisfactory explanation

for the syndrome of oedema, enlargement of the liver,ascites, inreased venous pressure and hypoproteinaemia.Malnutrition, the nephrotic syndrome or cirrhosis of theliver could be ruled out. In spite of the changes in theelectrocardiogram and the increased venous pressureheart failure seemed unlikely, because two bromsul-phalein tests and the circulation time were normal.No evidence of chronic constrictive pericarditis had beenfound on the x-ray pictures.

FiG. 2.-Radiokymograph before operation.

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CONSTRICTIVE PERICARDITIS AND HYPOPROTEINAEMIA

b c

FIG. 3a-c.-Eklctrocardiogram showing right ventricular strain.

We first decided to investigate the effect of digitalis onthe diuresis and on the increased venous pressure. Thediuresis increased to 550 and 700 ml. during the first twodays of digitalization with the equivalent of 100 mg.digitalis per day. However, the backward failure ofthe right heart got worse. The venous pressure rose tomore than 5 cm. above the sternal angle (Lewis, 1930;Borst, 1943; Borst and Molhuysen, 1952) orthopnoea andmoist riles indicated acute congestion of the lungs. Aninconstant triple rhythm was heard and a paradoxicalfilling of the pulse was noted. The temperature thensuddenly rose to 39 6- C. but with the aid of penicillinand the withdrawal of digitalis the boy managed toweather this period of severe congestive heart failurewith respiratory infection. The increased venouspressure dropped gradually. Ten days later the im-provement was such that catheterization of the heartwas possible to obtain further information about thecirculatory relations in the heart (Dr. M. L. M. Houben).The catheter could easily be brought into the branches

of the pulmonary artery. No abnormalities were foundin the vessels or in the septum of the heart. The pressurecurves of the right chambers, however, showed certainpeculiarities characteristic of constrictive pericarditis.

FiG. 4.-ElerocardiogrAm showing the pressure curve as t

These changes were indicated for the first time byBloomfield, Lauson, Cournand, Breed and Richards(1946), and have been elaborated extensively by Hansen,Eskildsen and Gotzsche (1951), Yu, Lovejoy, Joos, Nyeand Mahoney (1953) and Tourniaire, Blum, Deyrieux,and Tartulier (1953). They have been aptly sununarizedby Yu et al. as follows:

'The auricular pressure curve shows a M-or-W-shaped pattem, with two upward and two down-ward deflections, both failing to reach the base line.The mean pressure in the auricle is moderatelyelevated. The right ventricular pressure curveshows a slightly elevated systolic pressure and arapid diastolic dip followed by a high diastolicplateau and high diastolic end-pressure. The ratioof the diastolic end-pressure to systolic pressure ismore than one-third. The diastolic plateau is theexpression of the diastolic filling defect being theessential haemodynamic change in- constictivepericarditis. The plateau has disappeared inpatients successfully operated.'

When failure of the right ventricle is present in con-ditions such as stenosis of the pulmonary artery, mitralstenosis or severe emphysema, diastolic end-pressure canbe elevated also. Yu et al. investigated 132 patients, but

always found theratio between dia-stolic end-pressure

--- -:-and systolic pressureto be less than one-

-*_-___._. ..t _ _+,third in conditionsother than constric-tive pericarditis. Inour case this ratio

I :1 5f Ag > w Mvaried between one-half and two-thirds.

- The pressure curvehe cathet was wthdrw, during Lwithdrawal

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ARCHIVES OF DISEASE IN CHILDHOODof the catheter from the right ventricle is shown in Fig. 4.The pressures in the caval vein and in the right auricle wereconsiderably elevated (maximum 20, minimum 10 mm. ofmercury), while the diastoLic pressure in the right ventriclewas especially increased (20 to 24 mm.). The fluctuationof the pressure curve in the ventricle increased abnormallyduring deep respirations (f.i. 40/30 and 18/12 mm.respectively), a demonstration of paradoxical filling ofthe pulse. The oxygen saturation varied between 65and 700o in the right heart chambers and in the pul-monary artery. In the 'capillaries' of the lung artery asaturation of 93% was found. The mean pressure therewas rather high (about 20 mm.) and the fluctuations werelarge. This indicates serious involvement of the leftventricle (Sawyer, Burwell, Dexter, Eppinger, Goodale,Gorlin, Harken and Haynes, 1952), indicating that thesurgeon should liberate the left side first (Isaacs, Carter,Noland and Haller, 1952).

In this case cardiac catheterization led us back to theright track again, but we might have made the correctdiagnosis earlier had we taken to heart the advice ofBarroy and van Heerswynghels (1946), who demonstratedlayers of calcium in the pericardium by means of extrahard x rays. By this technique calcium could bedemonstrated (Figs. 5 and 6) over the left ventricle in ourpatient also. The radiokymogram had been thought toshow normal pulsations, but perhaps electrokymographicanalysis (McKusick, 1952) would have prevented thisassumption. Unfortunately no facilities to apply thismethod were available in this hospital.

In the next two weeks the condition of our patientimproved further, the level of the pulsations in the neck

veins dropping to below the sternal angle. The amountof ascites was plainly diminishing. However, the spon-taneous improvement did not continue and the oedemaand ascites were again progressing. The effect of amercurial diuretic was only of very short duration. Theonly effective treatment was clearly resection of thepericardium. This was performed by Professor I.Boerema on June 14.

After a median incision the sternum was split and afew adhesions between the pericardium and the chestwall were removed. The heart was enveloped by apergameneous pericardium, that also adhered to theepicardium. The adhesions were easily loosened. Firstthe left ventricle was liberated, then the right ventricleand finally the mouths of the large veins also. Nextthe myocardium turned out to be covered by a thicknew layer of fibrous epicardium. This was also removedfor the most part. A small haemorrhage at the level ofthe auricles was stopped in a few moments. The wholemyocardium had become bare, with the exception of afibrinous cover in the region of the tip of the heart. Thepulsations of the heart were visibly improved and thechest wall was closed. The first day after operation theboy was orthopnoeic and he was put into an oxygen tent.Soon his condition improved, the heart action becameregular, and he lost the oedema. Also the ascites andthe enlargement of the liver disappeared in a few weeks.The QRS waves increased somewhat in height. Thevolume of the heart increased also, as could be shownby radiographs and fluoroscopy (Fig. 7). Three weeksafter the resection of the peri- and epi-cardium the bloodproteins had become normal (Table 1). The patient was

F - an 6i

FiGs. 5 and 6.-Arrowbs point towards calcium deposits in epicardium.

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CONSTRICTIVE PERICARDITIS AND HYPOPROTEINAEMIAdischarged in a very much improved condition, thevenous pressure being normal (level of the pulsations3 cm. below the sternal angle).

FK;. 7.-Radiograph of the heart after operation. Augmentation in

volume (compare with Fig. 1).

DiscussiThe syndrome of constrictive pericarditis is rare,

especially in children, although dense, scar-likeadhesions of the pericardium are found in 2 to 4%of all necropsies (Moschcowitz, 1953). Largesurveys on diagnosis and treatment have beenpublished during recent years by Holman and Willett(1949), Paul et al. (1948), White, Alexander,Churchill and Sweet (1948) and Chambliss et al.(1951). No special attention has been paid todiffererces in the syndrome at various ages, butMcKusick (1952) mentions the possibility that theassociation of constrictive pericarditis with hypo-proteinaemia might be a special feature in children.In the large series no separate reports are givenabout children but a few observations (McQuarrie,1942; Stadler and Stinger, 1941) support thisassumption. Moreover the first patient of Barroyand van Heerswynghels (1946) was reported to havea total level of blood proteins of 3-74% (albumin1-675%); this girl was 7 years old. Another girl ofII had a level of 6-55% of blood proteins. InMcKusick's (1952) series of 20 patients six had a

serum albumin level of 3 -5 g. per 100 ml. or less.All these patients had had the disease from at leastthe early'teens. With one exception they were more

than 20 years old when they were inwestigated. Thesefigures do not differ very much from those given byChambliss et al. (1951), who found an average of3 46 g. albumin per 100 ml. of serum in 39 patients,most of them adults. In 44 of their patients totalblood proteins averaged 6-0%, the patients withoedema having an average of 0- 5-g. blood proteinsless than those without oedema. The degree of hypo-albuniunaemia in young children is evidently lowerthan in adults, even when only the method of Howeis used for fractionation.A decrease of the level of albumin in the blood

has also been shown to occur in heart failure fromcauses other than constrictive pericarditis (Herr-mann, 1946), although this does not always implythat the production of albumin is impaired, becausethe total volume of plasma is usually considerablyincreased (Gerbrandy, 1952). The changes in bloodvolume and in the content of blood proteins inconstrictive pericarditis are different from those inother causes of backward failure: the blood volumewas only at the upper normal limit in Chambliss'spatients and no increase of the level of globulinwas present. The circulation time varied between13 and 45 seconds; in 40% of the cases it was lessthan 24 seconds, so it can be normal as it was in ourpatient (8 seconds). This unexpected finding couldperhaps be explained by assuming that at least apart of the magnesium sulphate is being pumpedthrough the lungs without delay, the emptying ofboth ventricles not being materially impaired. Thecardiac index in our patient, as calulated from dataobtained during catheterization, measured

2 42-4-=3 310.7333per minute per square metre of body surface.No satisfactory explanation can be given of the

hypoproteinaemia in constrictive pericarditis. Appar-ently the production of albumin in the liver isimpaired, but why are no other functions alsoimpaired and why does constrictive pericarditisespecially cause hypoproteinaemia, in contrast toother causes of chronic heart failure? The conditionis quickly reversible as has been demonstrated in ourpatient, so it can hardly be due to fibrosis. Niggli(1950) has found a relation between the severity andlength of congestive heart failure, the decrease ofalbumin in the blood and the presence of fibrosisin the liver, but all these patients were adults.

Finally we should like to stress -that in our patientthe aetiology of the constrictive pericarditis couldnot be tuberculous, which is at variance with severalrecent publications (e.g. Andrews, Pickering andSellors (1948). The tuberculin test with I mg. ofold tuberculin was repeatedly negative, which rules

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290 ARCHIVES OF DISEASE IN CHILDHOOD

out active tuberculosis with certainty. The histo-logical examination of the pericardium gave nofurther clue as to the aetiology (J. F. Hampe).

Although the triad of Beck (1935)-high venouspressure, ascites and a quiet heart-diagnostic ofchronic cardiac compression, was present in ourpatient, the ordinary investigations, namely, electro-cardiography, fluoroscopy, radiokymography andmeasurement of circulation time did not confirm atentative diagnosis of constrictive pericarditis. Theunfavourable effect of digitalization and the typicalchanges found during catheterization led ourthoughts back to the right diagnosis. Less timewould have been lost had we taken the 'hard' x-raypictures earlier. Therefore we wish to stress theimportance of this technique, together withcatheterization of the heart, in children havinghypoproteinaemic oedema, ascites and increasedvenous pressure, which can be so easily demonstratedin the engorged veins of the neck.

SummaryA case is presented with constrictive pericarditis

in a 7-year-old boy, demonstrating some atypicalsigns. Hypoproteinaemia and ascites were dominat-ing. No complaints or signs of heart failure werepresent, with the exception of increased venouspressure, as could be demonstrated in the neck.The radiokymograph showed fair pulsations of theventricles but the data of the pressure curves fromthe right auricle, right ventricle and pulmonaryartery gave definite evidence of constrictive peri-carditis. The presence of calcium in the pericardiumcould be demonstrated only on pictures taken with'hard' x rays.

A successful peri- and epicardectomy (nearlytotal) was done, which was followed by restorationof the blood proteins in three weeks.The association of hypoproteinaemia and con-

strictive pericarditis in childhood was commentedupon.

I wish to thank Prof. I. Boerema, Prof. S. van Creveldand Dr. H. A. Ph. Hartog for helpful criticism, andG. G. A. Mastenbroek, Ph.D., for advice on the electro-phoretic fractionation.

I am further much indebted to Dr. H. L. J. M. Bartelsfor his cooperation and his permission to use his data.

R EFE

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