The heart in scleroderma

Reviews The Heart MARVIN

A.

SACKNER,

in Scleroderma*

M.D.,? E. R.~LFH

HEINZ,

Philadelphia,

S

CLERODERMA terized

tive

is a systelnic

by excessive

tissue, atrophy

turbances. organs

of muscle,

Conspicuous

has given

“scleroderma lung,”

rise

to

heart

regard

to

impairment

patients

tions,

constituting

ha\re been

with

arterial

congestive

failure

frequently

tients

scleroderma.’

dial

fibrosis

were

for

heart

failure,

filling

might

strictive from

other

causes.

has not been Rather, nary

hypertension

is the

of cardiac

stances.2

In other

sufficiency

associated

scleroderlna

from failure. derrna

kidney”

show

systelnic

malignant

with

factor

factors

may

scleroderma. that

puhnofor

in many

to

inin-

distinguish

lungs

and

Pllllno-

kidneys.

in 38 of these

studies

in 18 have

patients

been

and

previotlsly

failure

associated

of 25

of

right

with

both

cardiac

of the 65 patients period

of

perforllled obtained

in

in the study died

observation. 25

cases.

in an additional

Cardiac

Heart:

“sclerobecause

the

FEATURES Xccropsies biopsies

Lrmg

5 cases.

RESULTS

heart

have

Thus, alter

attention cramina-

.Methods: In the myocardium. the presence of fibrosis, edema, or inHammation was ascribed to scleroderma only if these change? WCL‘C present in multiple sections and were unassociated with coronary artery diseace. In lung sections. vascular alterations and interstitial fibrosis were graded according to the following scheme : normal, mild, moderate, and marked abnormality. ‘I’he grading was made without knowledge of the clinical or physiologic findings, and close agreement of histologic grading kvas obtained on two occasions separated by a )-ear’s interval. The kidneys were examined for the presence of malignant nephrosclerosis.

pulmonary fibrosis

who

nephrosclerosis.3

indirect

were

fibrosis

of congestive

hypertension

were

finding

responsible

difficult

left heart

Forty-three during

of con-

the respiratory

signs

patients

pa-

ventricular

function

be and

Finally,

severe and

nlay

in

of

indicate

with the

the synlptonx

the

responsible

hernodynamic

instances,

for

factor

myocardial

studies

in

if Inyocar-

as in cases

seen in patients

physiologic

abnormalities

in

This

directed

studies

PATHOLOGIC

disease,”

observed

and

function

We

and laboratory

reported.’

altera-

to account

restriction

pericarditis

supply

However,

be expected,

of the heart,

nary

\VC

hospitalized

1950 to 1963 at the Philadel-

Hospital.

tions

of these factors,

of 65 patients

pathologic

with

Such heart

the primary

the period General

hernodynalnic

pathologic

blood

“scleroderma by some

M.D.

of Inyocardial

scleroderma.

thought

with

In

is not associated

of coronary

some

the records

to clinical,

“esophageal

areas

distribution

during

“scleroderrna

abnormalities,

.J. STEINBERG,

assess the significance

phia

as

scleroderma.”

has revealed

whose

dis-

terminology

disease,”

To

reviewed

of specific

kidney,”

cardiac

examination fibrosis

such

and “intestinal

charac-

and vascular

ALLEN

Pennsylvania

of connec-

involvement

“scleroderma

scleroderma”

disorder

proliferation

M.D. and

patients ventricular

hypertrophy

direct

trophy.

function

lesions,

in sclerodernla.

By

cnlargeuxnt

(Fig.

1).

was fooluld in 18

Seven

hearts

hypertrophy,

6 left

and

5 combined

ventricular

our

criteria

“scleroderlna

heart

of diffuse disease”

showed

ventricular hyper-

nlyocardial was

found

* From the Dcpartnwnts of Medicine, Pathology and Kadiology and thr Division of Cardiology, Philadelphia General Hospital and the Department of Physiology, Graduate School of Medicine, University of Pennsylvania, Philadelphia, Pa. This work was supported in part by a grant front the Smith, Kline and French Foundation, a contract from thr U. S. Public Nom 2744-00 from the Office of Naval Research, Department of the Navy. and Grant H-4797 Health Service, Bethesda, Md. t Present addrrss: Cardio-Pulmonary Laboratory, Mount Sinai Hospital, Miami Beach, Fla.

542

THE AMERICAN JOURNAL OF CARDIOLOGY

Heart

in Scleroderma

543

700

TABLE I Pericardial

Disease

in Scleroderrna Cases

600

No. Acute fibrinous pericarditis Uremia Chronic pericarditis Chronic adhesive pericarditis Pericardial effusion No pericardial disease Total

cases

(%)

5

(20%)

9 4 7

(36%) (16’7,)

4 1

25

(28%) (100%)

X

300I-

@I “d)x

200,-NORMAL

RVH

LVH

FIG. 1. Heart weights UPISUSchamber enlmgement in 25 cme~ of sclwodrma. 0 indicates nomml pulmonary vasculature, 0 mild abnormality of pulmonary vessels, X moderate abnormality of pulmonary vessels and + marked abnormality of pulmonary vessels. [ ] indicates cases of sclerodernm heart, ( ) casesof scleroderrna kidney and ( ) case of cardiac amyloidosis. The figure indicates that cardiac enlargement in sclrroderma is generally not extreme and that enlargement can usually be attributed to puln~onnrp \-ascular disease or “scleroderma kidney.” Further, in the 3 cases of scleroderrna heart disease, the heart weights indicate moderate enlargement only.

in only 3 of the 25 hearts in the series. The coronary arteries in these hearts were normal, and coronary artery disease of a severe nature was conspicuously absent for the entire group. Tfle cases of “scleroderma heart disease” included the following. Thefirst (Case 1) occurred in a 56 year old Negro man who died of anaphylactic shock after a penicillin injection. Sections of the myocardium revealed edema and vacuolization of the interstitial ground substance associated with compression, distortion, atrophy and degeneration of myocardial fibers (Fig. 2A). Interstitial edema was also present among nervous structures, the conduction system and blood Inflammatory infiltration was virvessels. tually absent. Tfre second patient (Case 2), a 39 year old Negro woman, died in intractable ccngestive heart failure. Myocardial fibers showed marked degeneration and atrophy, associated with a moderate number of round cells, mesenchymal cells, capillaries as well as fibrosis in areas where myocardial fibers were abnormal (Fig. 2B). The third patient (Case 3) was a 41 VOLUME17. APRIL 1966

year old Negro man who died in left heart failure and uremia due to “scleroderma kidney.” Sections of the heart showed severe acute and moderate fibrosis and chronic inflammation, myocardial degeneration. The inflammatory pattern suggested a granulomatous myocarditis (Fig. 2C). In addition to the preceding myocardial abnormalities, the first 2 patients exhibited right ventricular hypertrophy; the third, left ventricular hypertrophy. Hearts with rig/It ventricular fzypertrophy were associated with moderate to marked pulmonary vascular sclerosis while hearts with left ventricular hypertrophy were frequently associated with “scleroderma kidney” (Fig. 1). One heart with combined ventricular hypertrophy had amyloidosis. In 2 hearts with mild left ventricular hypertrophy and 3 with combined ventricular hypertrophy, the etiology of the left ventricular hypertrophy could not be established. Pericardial disease was found in 78 of the 25 necropsy patients with scleroderma (Table I). Acute fibrinous pericarditis occurred in 5, but 4 had uremia due to “scleroderma kidney.” The exception showed both acute and chronic pericardial inflammation. Nine patients (36%) had a chronic, nonspecific, adhesive pericarditis Pericarwhich was not constrictive in nature. dial effusions, ranging from 150 to 340 ml., were observed in 4 cases in whom the pericardium was normal or slightly fibrotic. Healed mitral valvulitis which produced rninor valvular deformity was found in 4 hearts, and in 1 the tricuspid valve was also involved. There was no pathologic evidence for a rheumatic origin. Lungs: The lower lobes were the most frequent site of pulmonary fibrosis when this lesion Eleven of the 30 cases showed severe occurred. pulmonary fibrosis, 19 had no evidence of

Sackner,

544

Heinz

and

Steinberg:

FIG. 2. Histolqic vc/ions o/ nyocardium ire .i CUSY.Io/ .xlproderma heart d&me. A, Case 1, 56 ycnr old man. The myocardiuln shows edema and vacuolization of the interstitial ground substance associated with compression-distortion atrophy and degeneration of myocardial fibers (magnification X 140 reduced by I‘he myo18yG). B, Case 2, 39 year old WOIIIXII. cardial fibers show marked degeneration and atrophy, and there are large areas of Inyocnrdium replaced by fibrous tissue (Inagnification X 45 reduced by 18y”). C, Case 3, 41 year old man. A granulomatous myocarditis is present (magnification X 140 reduced by 18:‘;).

fibrosis and the retnainder, fibrosis (Fig. 3). Ahnormalitirs

of

th

pulmonnry

in the large elastic small muscular puhnonary seen

mild

to moderate

vascular

tree were

pulmonary arteries, arteries and pulmo-

The large pulrnouar)- arteries nary arterioles. often were dilated, contained intimal plaques, and showed intinlal connective tissue proliferation. The small, muscular pulmonary arteries frequently showed medial hypertrophy and THE AMERICAN

JOURNAL

OF

CARDIOLOGY

Heart

in Schleroderma

545 TABLE II Symptoms

of Sclerodern~a Initial Symptonls

a.

0

0

a.

00

1

MILD

KDERATE MARKED

PULMONARY i4lscuLAR SCLEROSIS FIG. 3.

Uegree of pulmonary zmcular sclerosis versus pulmonary jibrosis assessed from lungs of patients with sclero-

derma.

intilnal fibrosis. The pulmonary arterioles, which normally contain little visible muscular media, often had fibromuscular hypertrophy of The this tunic with narrowing of the lumen. arterioles were the site of the most consistent changes, and analysis of these vessels revealed abnormalities in 26 of the 30 lung specimens (Fig. In 8 cases, these changes were marked. 3). The pulmonary vascular abnormalities did not appear to correlate with the degree of pulmonary In neither the bronchial nor pulmofibrosis. nary circulation was it possible to demonstrate an inflammatory arteritis or fibrinoid degeneration of the medial coat. Five of 25 necropsy cases showed Kidneys: histologic findings consistent with malignant nephrosclerosis and were considered to represent “scleroderma kidney.”

Articular Vasospastic Dermal Dyspnea At rest On exertion Dysphagia Total cases

28 18 13 4

(43%) (28%) (20%) (6%)

2 (3%) 65 (100%)

VOLUME

17,

APRIL

1966

53 (82:%,) 54 (83’);) 65 (1007;) 52 (8Oci) 34 ’ 18 33 (51:;)

resistances were 963, 1,745 and 993 dyne sec. cm-b. However, dyspnea \vas a common symptom during the course of the disease (Table II). It occurred at rest in 34 patients and only during exertion in 18 others. Dyspnea was associated with pulmonary hypertension or pulmonary fibrosis, or both, in the majority of cases (Table III). Other possible causes of breathlessness included pulmonar)congestion associated with “scleroderma kidney,” coronary artery disease, acute pericarditis, rheumatic heart disease and pulmonary tuberculosis. In 4 cases there was no apparent reason for the dyspnea even by necropsy exalnination. In 2 patients in whom necropsy was not performed, dyspnea was associated with cardiac enlargement of uncertain etiology. Chest pain was recorded in 9 of the 65 patients. In 4 it was related to coronary artery disease and in 4 was a pleuropericardial type of pain. Persistent cough was an uncommon symptom in the entire group. It often occurred, however, in

vascular

TABLE

Associations

III

of Dyspnea

in Sclerodernxx Cases

CLINICAL FEATURES Symjtoms: Complaints referable to the cardiorespiratory system as an initial manifestation of scleroderma were uncommon. Only 4 of the 65 patients presented with exertional dyspnea as the first symptom (Table II). Subsequent examinations of these 4 patients revealed that 3 had severe puhnonary hypertension with minimal pulmonary fibrosis while 1 had marked pulmonary fibrosis. Cardiac catheterization in the 3 with severe pulmonary hypertension revealed pulmonary arterial pressures of 80/36 (50), 78/33 (50) and 69/32 (47). The pulmonary

Frequency of Syn~ptoms

Pulmonary fibrosis &/or puhnonary hypertension Scleroderma kidney Scleroderma heart with pulmonary hypertension or scleroderlna kidney Coronary artery disease Acute pericarditis Mitral valvular disease Pulmonary tuberculosis Cause undetermined (necropsy in 4 cases) Cardiac enlargement, cause undetermined

No.

(:a)

27 7

(52%) (13%)

3 3 2 2 1

I::; (4& (4%) (2%)

5

(10%)

2

(4%)

Sackner,

546

Heinz

0

0

0

00

mxxx+

m

l xx

00x+

aoxx

0-t

++

and

Steinberg

rumble with presystolic accentuation was heard in a patient with coexistent mitral stenosis. Pericardial friction rubs were noted in 3 with acute pericarditis believed to be directly due to scleroderma since common causes could be excluded. Two patients with urelnia due to “scleroderma kidney,” 2 with pulmonary hypertension, 1 with pulmonary fibrosis and 1 with amyloidosis manifested transient pleuropericardial rubs. Response

to

Therapy:

Patients

with

congestive

secondary to pulmonary hypertension responded moderately well to digitalis and diuretic agents except when concomitant advanced pulmonary insufficiency from pulmonary fibrosis was present. When the latter coexisted, the patients generally died within a few weeks to few months. In patients with left-sided failure secondary to “scleroderma kidney,” digitalis, diuretic agents and antihypertensive drugs had little effect on modifying the course of this condition, which always terminated in death. In 3 cases of acute pericarditis the following was observed. In 1 patient, the pericarditis resolved spontaneously after one week of bed rest. In another patient, there was a dramatic resolution of a pericardial effusion after 36 hr. oi steroid therapy. In the third patient, despite steroid therapy, the pericarditis continued unabated for two weeks until death. Clinical and physiologic observations indicated that treatment with paraminobenzoic acid, steroids or sodium Versenate@ was not beneficial in ilnproving the pulmonary status. heart failure

0

~ NORMAL

MILD IINCREASE

MARKED 1

IINCREASE

HEART SIZE K~vnfymo,pq?hic ,brominence of pulmonary artery seclor C‘PISU> hart .sm rrlated to the analysis of interstitial markings. The intm-stitial markings are graded: 0 indicates norn~l, 0 mild increase, X moderate increase and + xlnrked increase. FE.

4.

patients with cystic bronchiectasis and was generally nonproductive. Physical Findings: The blood pressure was elevated in all 9 patients diagnosed as having “scleroderma kidney.” In 4 other patients a moderate hypertension was present. Clubbing of the fingers was observed in 3 patients, all of whom had marked pulmonary fibrosis. In 40 of the 65 patients, scattered, fine inspiratory rales were detected at the lung bases. Hepatolneglly was observed in 18 of 65 patients, but in only half of them could the hepatic enlargement be attributed with certainty to right-sided failure. Fourteen patients showed mild to rnoderate pitting edema of the lower limbs and 1 also had ascites. This edema was believed to be of cardiac origin in 12 cases; the cause could not be determined in 2. Auscultation of the heart revealed the following findings. The pulmonary second sound was A gallop rhythm accentuated in 33 patients. was heard in 28 of 65 patients; in 22 the gallop was presystolic in time; in the remaining 6, protodiastolic. Systolic murmurs interpreted as functional in type were heard at the apex in 13 patients and at the base in 5. Holosystolic murmurs at the apex were observed in 1 patient with rheumatic mitral insufficiency and in another with dilatation of the mitral valve associated with amyloidosis. A mitral diastolic

ROENTGENOGRAPHIC

FEATURES

Chest roentgenograrns were available the 65 patients in the series.

in 60 of

Methods: Except for the age and sex of the patients, the chest roentgenograms were interpreted without knowledge of the clinical or pathophysiologic findings. The transverse diameter of the heart, the pulmonary artery sector and pulmonary interstitial markings (the soft tissue linear shadows radiating from the hila to the periphery) were graded as normal, mildly increased, moderately increased and markedly increased. ‘The roentgenograms were graded on two occasions, six months apart, and the agreement between interpretations was satisfactory. RESULTS

Heart: Forty-five of the 60 cases showed roentgenographic evidence of cardiac enlargeThe cardiac size was generally mildly to ment. cardiac enmoderately increased ; massive

THE AMERICAN

JOURNAL

OF CARDIOLOGY

Heart

in Scleroderma

547

Fro. 5. E~~olutionof @nonaryhy‘mension. A, March 1960. ‘The patient was asymptomatic with mild prollCnrnce of Pulmonary arterial pressure was 55/22 (35); puln~onary vascular pulmonary sector and mild cardiac enlargement. 1961. The patient was in congestive heart failure for the lint time. resistance, 418 dyne sec. cm--5. 13, Scptenlbrr Bilateral pleural effusions are also Triangular configuration of the heart is probably due to prricardial effusion. C, April 1962. 7 he patient has fax compensation of heart failure. Marked prominence of pulrrronxry artery present. sector

and moderate

right ventricular

cardiac

enlargement

are present.

largement was unusual. Frequently, with the cardiac enlargement, there was a corresponding increase in the prominence of the pulmonary The configuration artery sector (Fig. 4 and 5). of the cardiac silhouette was not distinctive when the pulmonary artery sector was normal or slightly prominent. However, the cases with moderate to marked prominence of the pulmonary artery sector often showed elevation and rounding of the apex probably representing right ventricular hypertrophy. Elongation of the left ventricular border downward occurred in 3 cases of “ scleroderma kidney” with severe systemic hypertension. In 8 cases, the heart This was exhibited a triangular configuration. due to pericardial effusion in 3 cases, right ventricular hypertrophy in 2 and to uncertain cause in 3 cases. LungJ: In 23 chest roentgenograms the interin 7 there was a stitial markings were normal; marked increase. The increase of these markings and the prominence of the pulmonary artery sector appeared to be independent phenomena The cases with a marked increase in (Fig. 4). markings showed fairly consistent correlations with physiologic findings of pulmonary fibrosis, i.e., decrease of lung volumes and lung comHowever, in cases with normal to pliance. moderately increased markings, there was a wide degree of scatter for the correlation between VOLUME

17,

APRIL

Rounding

and upward

displacement

of the ape\; suggests

hypertrophy.

1966

the roentgenographic ologic data.

findings

and these physi-

ELECTROCARDIOGRAPHIC FE.4TURES Multiple electrocardiograms were obtained in 60 of 65 patients, and the tracing nearest to the end of the study period or closest to death was selected for analysis. Methods: Frontal plane vectors were calculated for the P wave, QRS complex and ventricular graNormal values for the latter t\vo components dient. were taken from the data of Ashman.” Criteria for left umtricuLar hypertrophy included at least two of the following signs: (1) the S-T segment depressed more than 1 mm. or T wave less than 1 mm in lead I; (2) the sum of the S wave in lead VI and R wave in Vg (3) “strain” pattern in or V, greater than 35 mm.; lateral precordial leads; and (4) intrinsicoid deflection greater than 0.045 sec. in V;, or Vg. Criteria for right ventricular hypertrophJ included at least two of the (1) R wave in Vr greater than 7 following sign@: (2) sum of R wave mm. or S wave less than 2 mm.; in Vr and S wave in Vj greater than 10.5 mm. ; (3) qR, R, Rs, or QRS complex in Vr or VsR; and (4) rS in Vs. The criteria for low voltage was a QRS complex less than 5 mm. in the standard leads and 8 in the precordial leads.” Results:

were normal mal (85%).

In 9 patients the electrocardiograms (15ye), and in 51 patients, abnorThe majority had a displacement

548

Sackner,

Heinz and Steinberg

FE. 8. Ventrmdargradient in &roderma plotted on the triaxial reference system of Bayley. The bold line encloses norlnal values according to Ashman.? The symbols are same as in Figure 7.

FIG. 6. .-TP in scleroderma plotted system of Rayley for 57 cases.

on the triaxial

reference

of AP to greater than 60’ (Fig. 6). In about half the patients A(QlXS was normal; 111ost of the patients with right ventricular hypertrophy showed a tendency to right axis deviation and low amplitude (Fig. 7). The ventricular gradient generally showed a low amplitude (Fig. About half had abnormal ventricular gra8). dients and these usually had concomitant right or left ventricular hypertrophy. The commonest rlectrocardiograpfric abnormality in the present series was right ventricular hypertrophy, which occurred in 27 per cent of cases (Table IV). P pulmonale occurred in 15 per The P wave appeared notched in the cent. Signs of standard leads in 12 per cent cases. left ventricular hypertrophy were observed in 15 per cent. Only 5 per cent of cases showed low voltage. Signs of acute myocardial infarction occurred in 2 patients and of old myocardial infarction in 2. First degree heart block was present in 15 per cent of cases. Tfre 3 cases with pathologically

FIG. 7. AQRS in scleroderma plotted on the triaxial reference system of Bayley. The bold line encloses normal values according to Ashmam4 The symbols are as follows: 0 no ventricular hypertrophy, 0 right ventricular hypertrophy, X left ventricular hypertrophy and f combined ventricular hypertrophy.

proved

scleroderma

fleart

disease

showed

right ventricular hypertrophy because of pulmonary hypertension (pulmonary arterial pressure 55/22 (35), pulmonary vascular resistance 418 dyne sec. cmp5.), left ventricular hypertrophy because of systemic hypertension, and (3) pattern of apical infarction (Fig. 9). the following

patterns:

(1)

BALLISTOCARDIOGRAPHIC

Ballistocardiograms tients. THE

FEATURES

were obtained

AMERICANJOURNALOF

from 26 pa-

CARDIOLOGY

Heart

in Scleroderma

549 TABLE IV

Electrocardiographic

Findings in 60 Cases of Sclerodrrma Cases

RVH LVH RVH & LVH P pulrnonale Notched P, standard leads Low voltage Right bundle branch block Left bundle branch block Pericarditis Myocardial infarction 1’ heart block 2” heart block Atria1 fibrillation Paroxysmal atria1 tachycardia Atria1 extrasystoles Ventricular extrasystoles

Ballistocardiographic

FIG. 9. I%c~mcardio,~rams of patimt with “sclerodmna heart d&arc” and pulmonary hyjwtmsion (Case 2, Fig. 2B). A, January 1956. Raynaud’s phenomenon; normal chest B, SepNormal electrocardiogram. roentgrnogram. tembcr 1958. Pulmonary arterial pressure was 39117 vascular resistance, 428 dyne sec. (24) ; pulmonary cnv-5. Cardiac enlargement and pulmonary hypertension are indicated. First degree heart block and right bundle branch block and right ventricular hypertrophy C, October 1958 and D, December 1958. arc present. Roth have the pattern of apical infarction.

Merhods; A Starr high-frequency ballistocardiographic table was used to obtain ballistocardiograms. The tracings were analyzed according to the criteria of Scarborough et a1.r They were further classified according to the method of Brown and co-worker@: grade 1 shows Grade 0 indicates a normal tracing; preservation of regularity and definitiveness, normal grade 2 inspiratory I J but decreased expiratory IJ; shows half or more abnormal complexes mainly durin reging expiration ; grade 3 shows abnormality ularity and definitiveness as well as low amplitude; grade 4 shows totally abnormal complexes of low amplitude which are unidentifiable and irregular. \rhen multiple tracings were obtained, the final tracing only was reported.

Results: A review of multiple tracings in 26 that only 1 patient had a concases revealed sistently

normal

ballistocardiogram.

common

abnorrnality

cotnples,

a finding

cent \‘OL”ME

of cases

(Table

17. .4PRIL

1966

was which v).

a decrease

The

most

of the

IJ

occurred in 69 per Marked slurring of the

TABLE v Findings Scleroderma

No.

(‘;i

16 9 3 9 7 3 3 1 2 4 9 1 5 5 5 4

(27%) (15%) (5%)) (15%) (12%)

)

(5%) (5%) (2%) (3::a) (7%) (15%) (2%) (8%) (8%) (8%) (7%)

in 26 Cases

of

Cases Decrease of I J complex Marked slurring of IJ or JK complexes LM wave greater in amplitude than IJ wave Decrease of ratio IJE,,,iration to IJIWirat,“” Increase of ratio Increase of ratio

JEu*l,r,lti<,n

JK to IJ HErairnti,,,, to

18

(69%)

10

(38%)

10

(38%)

8 4

(3195)

2

(15%) (SC%)

IJ or JK complexes and large diastolic waves Such (LM greater than IJ) were common. changes and analysis of the Brown classification were not too helpful in distinguishing quantitative severity of the rnyocardial involvement (Fig. 10). PHONOCARDIOGRAPHIC FEATURES Phonocardiograrns were obtained routinely in 33 patients hospitalized from 1958 to 1963. Methods: The patients were placed in the recumbent position and auscultation performed during normal breathing and held end-expiration. A logarithmic phonocardiogram and simultaneous electrocardiogram were recorded with a Sanborn TwinBeam apparatus. Intracardiac phonocardiograms were recorded in 5 cases with a barium titanate phonocatheter connected to a Cambridge acoustic amplifier.

Sackner,

Heinz

and Steinberg ‘I‘ABLE

Phonocardiographic

2

Il\pertrc,phy No RV RV

Cases Accentuation of pulmonic component of second heart sound

I_

7-k BROWN

Presystolic gallop* Protodiastolic gallop* Apical systolic murmur Basilar systolic murmur Pericardkl friction rub

.

*

3 CLASSIFICATION

4

FIG. 10. Ballistocardiographic abnormalities in sclwodernm. [ ] indicates cases of “scleroderma heart disease,” ( }

“scleroderma kidney,” ( ) cardiac amyloidosis, > rheumatic heart disease and /I coronary artery disease. Chamber enlargement was obtained from clinical and pathologic data. The Brown classification 0 is normal and through 4 indicates progressive degrees of abnormality.

The pulmonic component of the second heart sound was identified with the aid of simultaneous carotid pulse tracings or by noting that the pulmonic followed the aortic component during the physiologic splitting of the second sound caused by respiration. The pulmonic component was considered abnormal if it was of greater intensity than the aortic component The splitting of or if it was transmitted to the apex. the second heart sound was measured to the nearest 0.005 sec. from records obtained at the pulmonic or Erbs area of auscultation. The widest degree of splitting during normal inspiration and the narroxvest degree of splitting during normal expiration was The preaveraged during five respiratory cycles. systolic gallop (fourth heart sound, atria1 gallop) was identified as a low frequency sound which followed the P wave of the electrocardiogram, preceded the first heart sound, and was synchronous with the presystolic wave of the apex cardiogram.

The phonocardiographic findings Results: were correlated with the cardiac status according to the assessment of the clinical condition, chest roentgenogram and electrocardiogram, This permitted division into three necropsy. main groups based upon an estimation of right ventricular insufficiency and several lessergroups with “scleroderma kidney” and cardiac lesions due to diseases other than scleroderma. There

was

accentuation

of the pulmonic

component

in 1 of 13 cases with no evidence of right ventricular hypertrophy, 8 of 9 with right ventricular hypertrophy and 8 of 8 of the second

heart

sound

VI

Findings in Scleroderma

Numbers in parentheses tqxm clinical auacultation. RV = right vrntricular.

RiShtSided Failure

13

9

8

ScleroClPmM Kidney

5

1

R

8

0

7 (3) l(l) 2 1 1

5 (4)

n (81

4 (4)

2 0 0

2 0 2

I 2 0

represent

cases in which

10)

0 (0)

g.dlop

l(1)

was heard

The with right heart failure (Table VI, Fig. 11). only patient with accentuation of the pulrnonic component of the second sound and no clinical signs of right ventricular hypertrophy had thoracic scoliosis and marked rotation of the With an increasing degree of right venheart. tricular insufficiency, the second sound tended to show wider splitting but still remained within the normal ranges (Fig. 12). The splitting of the second sound during quiet inspiration appeared to be greater when the lung compliance was reduced, but this correlation v\-asnot statistically significant (Fig. 13). A jresystolic gallop was recorded in 7 of 13 cases with no clinical evidence of right ventricular hypertrophy, 5 of 9 with right ventricular hypertrophy, 8 of 8 with an episode of right-sided heart failure, and 4 of 5 with “scleroderma kidney” (Table VI). The gallop was heard with the clinical stethoscope prior to taking the phonocardiogram in 19 of the 24 patients in There were no whom the gallop was recorded. consistent variations in the timing or intensity of The mean the gallop during quiet respiration. duration from the onset of the P wave to the onset of the gallop (P-aG) was 0.13 sec. (range 0.11 to 0.18 sec.) in cases classified according to right ventricular insufficiency and 0.13 sec. (range 0.10 to 0.18 sec.) in cases of “scleroderma The apex cardiogram showed a prekidney.” systolic wav-e in all cases in which a presystolic gallop was recorded, but in 2 cases a presystolic wave was unaccompanied by- a presystolic The ratio of the height of pregallop (Fig. 14). systolic to systolic waves of the apex cardiogram was greater than 0.11, the upper limit of normal,‘” in all but 1 of the cases in which a presystolic gallop was heard. Intracardiac ptconocardiycrums obtained from the THE

AMERICAN

JOUR”AL

OF

CARDIOLOGY

Heart

551

in Scleroderma

c

._.y_ _._

D

. A, case of mild pulmonary FIG. 11. Representative phonocardiograms in scleroderma. hypertension. Pulmonary arterial pressure was 34115 (21); pulmonary x-ascular resistance 187 dyne sec. cn--S. This shows a protodiastolic gallop (labeled 3) and a presystolic B, case of moderate pulmonary gallop (labeled 4). An early systolic murmur is present. hypertension diagnosed clinically. A, presystolic gallop is present. C, Case of marked Pulmonary arterial pressure was pulmonary hypertension with right heart failure. 80/36 (50); pulmonary vascular resistance, 963 dyne sec. cm-s. In addition to the presystolic gallop, the pulmonic component of the second heart sound (P) is transmitted to the apex. D, Case 1, moderate pulmonary hypertension and “scleroderma heart disease.” Pulmonary arterial pressure was 55/22 (35); pulmonary vascular resistance, 318 dyne sec. cm--5. There is a presystolic gallop and split second sound at the apex.

right side of the heart in 3 cases with presystolic gallops revealed that the gallop had its greatest In cases intensity within the right ventricle. with “scleroderma kidney” and severe systemic hypertension, the presystolic gallop presumably originated in the left ventricle, although intracardiac phonocardiograms were not done under such circumstances. The murmur> in patients with scleroderma not complicated by heart disease of other etiologies These were soft, blowing and systolic in time. VOLUME

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were heard best at the apex in 7 instances and at With coexisting rheuthe base in 2 (Table VI). matic heart disease, the murmurs of mitral and aortic stenosis were heard in 1 case and mitral A patient with coinsufficiency in the other. existing cardiac amyloidosis had a mitral regurgitant murmur and protodiastolic gallop secondary to functional dilatation of the mitral Pericardial friction rubs were recorded in ring. 3 cases and were loudest during the presystolic period.

Sackner,

552

NORVH

-_._.!

07

I

I

-1

a.

m

I .~_##@# -.-. 00 l g iT5 3__ . a-.’ .a 0.0 id 4 .02-

0

Ia a-al

I0

I: -

I@ a. I

E

l

q . -._

--

.Ol-

SK _.-._I I

I .06.05-

T _._

Heinz

I I

E

FIG. 12. Splittingof second sound in .rcltroderma. Key: no RVH includes cases without right ventricular hypertrophy; RVH, cases with right ventricular hypertrophy; RVH-CHF, cases with right-sided heart failure; SK cases of “scleroderma kidney;” I, inspiration; and E, expiration. The horizontal lines indicate the mtan and range of normal values.9

DISCUSSION Histopathologic Changes in the Heart: The resemblance of the skin and cardiac lesions in scleroderma was first noted in the latter part of the nineteenth century.1~~‘2 It served to point out the systemic nature of the disease and to Howsuggest a specific cardiac involvement. heart disever, the concept of a “scleroderma In that ease” was not popularized until 1943. year, Weiss et al.1 reported that overgrowth of fibrous tissue in the heart might embarrass cardiac function in patients with scleroderma. A few years later, Goetz1?j14 meticulously described the histopathologic changes in such These changes consisted of areas exhearts. hibiting replacement of muscle with dense collagenous tissue amidst which were occasionally The dense colwell preserved muscle fibers. lagenous fibers ran paral!el to one another and bore no relation to diminished vascular supply. The connective tissue did not contain hemosiderin usually seen in lesions of muscle origin. In other areas of the heart, hyperemia or separation of muscle fibers by a young, highly vascular

and

Steinberg

connective tissue \vas observed. Interstitial edema of the myocardium with no cellular infiltrate has been reported.‘“l16 The mutinous character of the edema was accentuated by a toluidine blue stain.‘” This lesion was found in our Case 1 and might be the earliest cardiac lesion of “scleroderma heart disease.” Under these circumstances, the heart is grossly enlarged because of edema rather than muscular hypertrophy ; the muscle fibers show slight compression. There is a paucity of cellular infiltration in this stage. The fibrous lesions may be an evolutionary pattern of the prccedillg as illustrated in Case 2. In this stage. the niuscle fibers appear atrophied, fractured and disintegrated and resemble the changes seen in constrictive pericarditis to which the term “atrophy of disease” has been applied.17 Although it has been reported that fibrosis in\,olves the left ventricle most frequently,‘* quantitatively similai changes were seen in the right ventricle and the atria of our cases. Occasionally, certain muscle fibers appear dark red and homogeneous when stained with trichrome. This is due to extrelne muscular contraction and should not be confused with fibrinoid degeneration.‘” The latter does not occur in “scleroderma heart disease.” Granulornatous myocarditi?” as in our Case 3 is an uncomInon cardiac lesion in scleroderma. Extrenne cardiac enlargement is also unusual. Pulmonary or systemic hypertension is often the primary or contributary cause of cardiac enlargement in the majority of cases. The true C‘/FRC ooe-

.

.

---_---_ 096

owl

-

-:_

-_

-**

. 002-

0-

-

.

.

001 002 SPLIT OF S-Z

003 DURING NOR%%

.' : .

.

I 006

SEC.

INSP%,ON

13. Lung complmnce and splittz’n~ of the second .mund. Values of lung compliance per unit of functional residual capacity (CL/FRC)2 are plotted against the duration The of the split second sound during inspiration. hatched horizontal lines indicate the normal range for CJFRC and values below 0.04 indicate low lung corn-pliance or increase of stiffness of the lungs. The reduced lung compliance appeared to be associated with a wider split of the second sound, but this trend was not statistically signilicant. FIG.

TIIE AMERICAN

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incidence of direct myocardial involvement in Focal scleroderma is difficult to ascertain. fibrosis of the myocardium is commonly observed in patients dying of other diseases, and such a finding in scleroderma should be interWe diagnosed “scleropreted with great care. derma heart disease” in our patients only when the lesions were distributed diffusely throughout the ventricles and atria and were unassociated Only 3 of our 25 with coronary artery disease. necropsied cases showed “scleroderma heart disease.” This should be contrasted to the incidence of myocardial fibrosis in necropsy cases of scleroderma reported in the literature from In 159 of 275 cases, fibrosis or 1950 to 1963. “scleroderma heart disease” was mentioned. Many of these cases had pulmonary or systemic hypertension, or both; in other cases, the fibrosis may have been related to coronary arterial insufficiency or had a focal distribution. The

importawe

tflat

pulmonary

vasoconstrirtion

f~yprrtro~f~y in scleroderma was appreciated by MatsuP as early as 1924. At least 31 per cent of necropsy cases reported during 1950 through 1963 showed pulmonary vascular changes which were frequently associated with right ventricular hypertrophy. Another equally important cause of cardiac enlargement in scleroderma is “scleroThis entity which is characderma kidney.” terized by the explosive onset of malignant hypertension, oliguria and uremia leads rapidly to left ventricular hypertrophy and dilatation” (Fig. 1). Approximately 41 per cent of necropsy cases reported during 1950 through 1963 had left ventricular hypertrophy as a result of this condition. The major coronar_v arteries are usually normal in scleroderma. Fibrinoid degeneration in these vessels is a rare occurrence.2n A nonspecific intimal thickening of the intramyocardial ramifications of the coronary vessels has been described,18 but does not seem severe enough to account for the fibrosis in scleroderrna heart disease. Myocardial infarctions have been reported in 9 of the 275 necropsy cases over the period 1950 to 1963. Pericarditis or pericardial @usion in which a uremic etiology could be excluded was present in at least 49 of the 275 necropsy cases (147,) reported from 1950 to 1963. The pericarditis generally was of a chronic adhesive type which The effusion was did not limit cardiac motion. characterized by a high protein content and low cell count,22 and the pericardium was normal or Flays

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Nomli

FIG. 14. Apex cardiqram in scleroderma.This is a semischematic diagram in which the apex cardiograms have been redrawn to the same time scale. Key: 1 and 2 indicate the first and second heart sounds; 3, the third heart sound or protodiastolic gallop; 4, the fourth heart sound or presystolic gallop; and 0, gallop sound. No RVH, cases without right ventricular hypertrophy; RVH, cases with right ventricular hypertrophy; and RVH & CHF, cases with right-sided heart failure. 0 above the presystolic wave of the apex cardiogram, a rccorded presystolic gallop.

slightly thickened in these cases. The thinness of the pericardium might be the reason for the absence of cardiac tamponade with such effusions. Acute fibrinous pericarditis was frequently produced by the uremic state associated with “scleroderma kidney.” An acute fibrinous pericarditis directly due to scleroderma was unusual but did occur in 1 of our cases. Mild mitral and tricuspid valuular thickening or healed verrucous endocarditis of nonspecific origin was noted occasionally in our series and Aortic valve involvement was rare. by others. Such lesions did not appear to be hemodynamically significant.*” Two of our patients had rheumatic mitral and aortic involvement clinically but did not come to necropsy. None of our necropsy cases showed typical rheumatic lesions but necropsy cases of rheumatic mitra! stenosis and insufficiency have been described by others.‘8J4 Histopathologic Changes in tfle Lungs: Two thirds of our 30 cases showed evidence of pulmonary fibrosis. In only half of our cases with The fibrosis was this process considered severe. dichotomy between the severity of the lnedial hypertrophy and intimal proliferation of the pulmonary vessels and the pulmonary fibrosis was apparent in the present series and that reported by Naeye.‘” The physiologic expression of the pathologic abnormalities such as pulmo-

554

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Heinz

nary hyperte!lsion and restrictive disease of the lung lnay also be dissociated in severity.” \t:ith regard to the pathologic changes in the pulmonary vessels, these findings are nonspecific and ha\-e been described in other prllmonary hypertensive states. There is an absence of inflaminatory cells and necrosis in the vessels; pulmonary arteritis with fibrinoid necrosis and inflammation is extremely rare.2fi In both the present study and that of iVaeye,*s lesions of the bronchial arteries and pulmonary veins were rare. Pulnlonary atherosclerosis of major pulmonary arteries \vas found when there were marked abnormalities in the smaller vessels. ,411~ persistent functional increase in pultnonary vascrllar tone tnay lead to intilnal proliferation and medial hypertrophy.27 Our physiologic studies,2 the absence of pulmonary vasctllar inflammation, and the dissociation of the severity of the parenchynlal lesions to the vascular alterations lead us to conclltde that the structural vasclllar changes are secondary to an increase of vasomotor tone in this disease. The e\.entual outcome is right ventricular hypertrophy due to increased resistance to blood flow through the plllnlonary arterial bed. Clinical Findings: Ilysf’nea, particularly upon is the conunonest cardioresiirator) exertion, Iii inost cases, symptom found in sclerodertna. it occurs prior to overt congestive heart failure and is not a grave prognostic sign as suggested by some allthors.2” In our experience the dyspnea can generally be ascribed to pulmonary fibrosis of pulmonary hypertension. T/Wmechanism for

the dysf,nea

in pulmonary

jibrosis

may he (1)

an increase of the work of breathing secondary to a lowered lung compliance and (2) hyperventilation brought abollt by (a) increase of reflex ilnpulses stimulated by fibrotic changes in and about the bronchial walls and vascular channels and (b) increase of widening of the airways and inequalities of ventilation-perfusion ratios.2 Not only do patients with sclerodertna have pultnonary fibrosis as a basis for dyspnea, but pulrnonary hypertension alone is often associated with extreme hyperventilation, particularly on exercise.29 Thus, about half the sclerodertna patients in one reported series given a standardized exercise test showed a higher ventilation than controls3” Althollgh tightness of the skin o\.er the chest wall in scleroderma has long been incriminated as a cause for the dyspnea, physiologic studies indicate that neither tightness of the skin nor weakness of the chest muscles alters p1llinonary function.2

and Steinberg The occurrence of r&ht heart failure does not appear to aggravate the pre-existing dyspnea in patients with ~nini~nal restrictive pulmonar) disease. This heart failure usually responds ~~11 clinically to digitalis. As in other diseases with severe pulmonary fibrosis, the development of congestive heart failure in patients with fibrosis secondary to scleroderma is often irreversible and a terminal event. Tfle

left

fleart failure

of

“scleroderma

kidney”

is

intractable and uniformly fatal. In our series, “scleroderlna heart disease” was an uncolnttion cause of dyspnea or congestive heart failure. However, in our cases of “scleroderma heart disease” diagnosed pathologically, intractable congestive heart failure was present terminally. In 2 of these cases, puhnonary hypertension was a Inajor clinical lesion, and thlls the poor rcsponse to medical therap), in such casts offers a clue to clinical diagnosis. Congestive heart failrlre due to “scleroderrua heart disease” has been diagnosed in a higher incidence in other series, but criteria for pathologic diagnosis ma); differ from ours. For example, in 31 nccrops) cases of sclcrodcrlila reported by Piper and Helwig,31 12 had congestive heart failure which the authors thought could be explained only on the basis of “scleroderlna heart disease.” i/%e

commonest

auscultatory

abnormality

of

tt’ce

//cart reported

previously in scleroderrna was an Illlirillllr.l”)aI:~~ Both clinically apical systolic and phonocardiographically, the chief findings of the present study Mcrc the high incidence of the accentuated pnlmonic second sound and presystolic gallop. Accentuation

of tire ,t)ulmonic

component

of the second

was folmd in cases of scleroderrna with moderate and severe pulmonary hypertension but not in those with mild pulmonary hypertension. There have been argutnents as to whether the dliration of splitting of the second heart sound in pulmonary hypertension was eithet In scleroshorter9”J4 or longer than nornlaL3~ derma, another factor which lnust be considered in interpreting the duration of the split is the redliced lung compliance which cornrnonlyoccurs in this disease.” It was suggested that reduced lung compliance with its attendant abnormal increase of intrathoracic pressure should promote wider during inspiration splitting of the second sound because of increased systemic venous return.3fi This presupposed a normal or greater than normal tidal volume since intrathoracic pressure might be nortnal in cases with low lling compliance if the inspired volume sound

THE AMERICAN

JOURNAL

OF CARDIOLOGY

Heart

in Scleroderma

In the present study, there was a was small. trend to widening of the split related to both pulmonary hypertension and diminished lung this sign had little compliance ; however, diagnostic significance because of the wide scatter of values. The high incidence of a firesystolic gzllo;b in the present study is significant because this sound is It is most often not heard in normal subjects. associated with those conditions in which there is systolic overloading of the ventricles, for example, systemic or pulmonary hypertension and Although it has aortic or pulmonic stenosis. been reported that the intensity of the presystolic gallop increases during inspiration in cases with car pulmonale, 37 this could not be confirmed in our cases of pulmonary hypertension secondary In addition to the patients with to scleroderma. the presystolic gallop emanating from the right side of the heart, those with “scleroderma kidney” show a presystolic gallop presumably arising from the left side of the heart because of sysFinally, although peritemic hypertension. cardial disease is common in scleroderma, the apical impulse as reflected by the apex cardiogram did not show signs of a pericardial scar, “the diastolic heart beat.“38 Pericardial friction rubs associated with ancillary signs of pericarditis were occasionally heard in The incidence of pericardial disscleroderma. ease at necropsy is much higher than that found clinically. Acute pericarditis associated with it scleroderma was noted in 3 of our 65 cases; was diagnosed in 2 of 21 cases in another series.32 Weiss et al.’ were struck by the triangular appearance of the heart in the chest roentgenographs of 6 of their 9 cases of “scleroderma heart They believed that this appearance disease.” These may was related to pericardial effusions. persist for months and occasionally embarrass cardiac function, although acute cardiac tamThe mechanism ponade has not been reported. for the chronic pericardial effusion is unknown. We observed 2 patients in other institutions in whom pericardial aspirations were performed several times during a few months period until death occurred from other causes. The alterations of the skin in scleroderma may obscure signs frequently associated with abnorPeriphmalities of cardiopulmonary function. eral edema due to right heart failure may be erroneously attributed to early skin lesions of scleroderma. Later, when the skin becomes tightened, there may be accumulation of nonpitting edema. Although clubbing of the VOLUME

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fingers occurs in one third of patients with idiopathic pulmonary fibrosis,39 it is much less common in scleroderma patients with severe pulmonary fibrosis. This probably is due in part to restriction of the skin covering the fingers and in part due to coexisting Raynaud’s phenomenon which limits peripheral blood flow. Roentgenography of the Chest: In the past, the emphasis on the interpretation of roentgenographic features of the chest has been placed on the nature of the pulmonary fibrosis in scleroder1na.Q In early stages, the lung markings appear accentuated and a fine reticulation can In advanced stages, be observed at the bases. the parenchymal infiltration becomes more dense with stranding or areas of honeycombing The apices are often free of this change form. or show hyperillumination. A normal appearance of the lung parenchyma is far more common than the picture of advanced pulmonary Patients in whom advanced pulmofibrosis. nary fibrosis is diagnosed by x-ray invariably show marked physiologic abnormalities of the restrictive type. However, patients with a relatively normal appearance of the parenchyma demonstrate all gradations of physiologic abnorThe incidence of increased promimalities. nence of the pulmonary artery sector in scleroderma has received little attention as a diagnostic sign. It reflects the pulmonary hypertension so common in the disease and is not dependent upon the severity of the interstitial pulmonary fibrosis. Initial reports indicated a high incidence of a triangular-shaped cardiac silhouette in the chest roentgenograms of patients with scleroderlna. This configuration was attributed mainly to pericardial effusion,’ but both right ventricular hypertrophy41 and pleuropericardial fibrosis42 were also cited. Subsequent investigators failed to confirm the high frequency of the abA normality mentioned in the original report. triangular cardiac silhouette was found in 8 of 60 cases in the present study, but in only 3 could pericardial effusion be diagnosed with certainty. In other series, the incidence of this finding ranged from 0 to 14 per cent.32@v43 Seventy-five per cent of our cases showed cardiac enlargement roentgenographically, which was generally of a mild to moderate degree ; in other series the incidence ranged from 9 to 45 per cent.40*44-48 Electrocardiogram: The incidence of electrocardiographic abnormalities ranges from 9 per cent reported by Windesheim and Parkin

556

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Heinz

to 28 per-cent reported by Stava,@ 50 by Escudero and McDevitt,“” 66 by Rodnanj’ and 75 per cent by us. The abnormalities were generally disturbances in iliorphologic character of the complexes rather than arrhythmias. Electrocardiogra/Aic criteria that myht detect mpocardial jihrosis due to scEeroderma inctude (1) abnorrnalities in the ventricular gradient, (2) left axis deviation with peri-infarction block or parietal block, (3) low voltage, and (4) the pattern of myocardial infarction. An abnormal ventricular gradient is indicative of primary T wave changes due to Both left and right myocardial distru-bances. ventricular hypertrophy due to other diseases are usually associated with an abnormal ventricular gradient. Comparison of the ventricular gradient of our scleroderlna cases with hypertrophies of other callses3* failed to reveal any This differences between the two groups. suggests that either the diagnosis of rnyocardial fibrosis is obscllred by ventricular hypertrophy or that a significant degree of fibrosis was not present in our cases. Left axis deviation with peri-infarction block or parietal block is an uncommon finding. Moreover, there is evidence that peri-infarction block carries no inore significance than left axis deviation itself.“Y Interstitial myocardial edema or fibrosis lnay cause low voltage because of short circuiting of potentials of individual myocardial fibers.z4 Low voltage is diagnosed only when present in both the lit& and chest leads. In 01~ series, this finding is rare and not found in our pathologically proved cases of “scleroderltia heart disease.” Although in other clinical series of patients with scleroderma, low voltage is reported in up to 20 per cent of cases,“” personal scrutiny of Inany electrocardiograms pllblished as exarnplcs of “low voltage” show it in the limb but not the Fibrosis of the heart in scleroderma chest leads. may simulate the pattern of myocardial infarc1 of our patients tion.?” In this connection, heart disease” showed an with “scleroderlna electrocardiogram consistent with an extensive apical infarction. However, the electrocardiographic pattern of myocardial infarction in patients with scleroderma is generally due to coronary artery disease rather than sclerodcrInatom involvement. Escude1.o and McDevitt”” found that the most freqllent electrocardiographic alteration in their patients with scleroderrna (31 of 60 patients) was notching of the P waves in the standard leads. These authors attributed the high incidence of this finding to atria1 fibrosis

and

Steinberg

which occurred in all their necr-opsy cases. They state it “creates the suspicion of rnyocardial dalnage by scleroderma.” However, this sign occurred in only 7 of ollr 60 patients and we cannot attach the saine significance to it. The P wave axis was greater than 60” in the Inajority of our cases of scleroderlna. This was also a frequent finding in other patients with car puliiionale.Sz Tt~e electrocardiographic pattern of right ventricular lypertrophv occurred in 27 per cent of our cases. The minimal resting pulmonary vascular resistance at which this was seen was 418 dynes cm. set-“. and the minimal mean resting pulutonary arterial pressure was 27 mm. Hg. In patients with chronic car pultnonale of other causes, all cases with pulmonary vascular resistance greater than 750 dynes ~111. set-j. showed right ventricular hypertrophy, and occasionally it was seen with lower values.SG Four of our 7 patients with difflise pulmonary fibrosis had right ventricular hypertrophy. This contrasts with the 16 per cent incidence of right ventricular hypertrophy in cases of diffuse pulmonary fibrosis of other causes.57 The pattern of left ventricular hypertrophy occurs uiost frequently in cases of systemic hypertension associated with “scleroderrna kidney.” Atria1 arrhythmias such as atria1 fibrillation and paroxysmal atria1 tachycardia are usually easily controlled with drug therapy in patients The more frequent ocwith sclerodcrma. currence of right rather than left atria1 enlargeittentS probably accounts for the low incidence of atria1 arrhythmia. Heart blocks occasionally are found in scleroderrna, the commonest variety being prolongation of the P-R interval. Complete heart block is a rare occurrence and may be due to fibrosis of the conducting systeril.z8 Limited investigations Ballistocardiogram: have been ruldertaken of ballistocardiographic If myocardial features in scleroderrna.“g~6” fibrosis were comtno~l in cases of scleroderrna, one Illight expect a high incidence of markedly 2X hallistocardiogralns in severe abnotmal However, other faccoronary artery disease. tors that co~~unonly occur in scleroderma, such as pulttlonary fibrosis, ventricular hypertrophics? congestive heart failure and pericardial disease, also prodllcc hallistocardiographic aimorrnalitics. Thus, Bcrreta et al.c’j found severe abnorlt\alities (Brown classification 3 artd 4) in all 7 cases they studied, while we found that 61 per cent of our 26 cases showed such changes. In o11r pathologically proved 3 cases of scleroTlIlS AMERICAN

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CARDIOLOGY

Heart

in Scleroderma

dernla heart disease, 1 was classified as grade 2 DinCnution and 2 as grade 3 abnormalities. of the systolic con~plexes and prolninence of the diastolic waves were the commonest findings in our series. PronCnence of the diastolic waves has been described in other states of congestive heart failure, pericardial disease and pulmonary hypertension.“g~fil The ballistocardiogratn appeared to bc of little diagnostic or prognostic significance but did indicate the almost universal impairment of cardiac function in the disease. SUMMARY “Scleroderma heart disease” is a pathologic This condirather than a clinical diagnosis. tion, in its advanced stage, is characterized by widespread proliferation of connective tissue and degeneration of rnyocardial fibers, but by itself rarely produces significant clinical lnaniIndeed, when criteria for diagnosis festations. require changes throughollt nniltiple histologic sections, the incidence of “sclerodernia heart Only 3 of disease” is low even at necropsy. our 25 necropsy cases of sclerodernla met these vascular Pulnionary and systemic criteria. abnornialities played a nlore inlportant role in disturbing cardiac function. Thus, right ventricular hypertrophy was caused by puhnonary hypertension found alone or in association with puhnonary fibrosis. Left ventricular hypertrophy was caused by lnalignant systemic hypertenkidney.” The sion produced by “scleroderrna preceding extracardiac factors occurred in all 3 of our cases of “sclerodertna heart disease” and caused the major clinical sylnptoniatology. The lilost frequent site of cardiac involvement in cases of scleroderrna is the pericardiuni. Pathologically, the conunonest lesion is a chronic adhesive pericarditis (36u/0 of our cases) which Acute pericardidoes not restrict cardiac filling. tis during the clinial course of the disease is far less frequent than the pathologic lesions would Large pericardial effusions associated indicate. with a relatively normal pericardiuni histologiMinor deformities cally lnay be seen clinically. of the mitral and tricuspid valves occur uncon~nonly in scleroderrna; valvular lesions of hernodynanGc significance are due to coexistent rheuniatic lesions. Dyspnea, particularly upon exertion, occurred during the course of the disease in 80 per cent It can be generally ascribed to of our cases. pulmonary hypertension, puhnonary fibrosis, or left heart failure associated with “scleroderma VOLUME

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kidney.” It therefore is rarely necessar). to heart disease” as a cause invoke “scleroderma for dyspnea. Right ventricular hypertrophy associated with pulmonary hypertension can be suspected clinically by the loud intensity of the puhnonic coniponent of the second heart sound at Erb’s point or by its transmission to the apex and by the presence of a presystolic gallop. There is also a good correlation between the hernodynaniic severity of the pulnlonary hypertension and the incidence of the electrocardiographic pattern of right ventricular hypertrophy and the roentgenographic analysis of the prominence of the prtlnlonary artery sector. Front a physiologic and pathologic standpoint, the puhnonary hypertension and puhnonary fibrosis appear to be two independent phenoniena. It is postulated that pulnlonary hypertension in sclerodernia is another expression of the heightened vasornotor tone in the disease, naniely, Raynaud’s phenonlenon and “scleroderlna kidney.” Although electrocardiograms and ballistocardiogranis are often abnorlnal in sclerodernia, the findings are generally of a nonspecific nature. In only 1 of our 3 cases of “scleroderrna heart disease” did the electrocardiogranl show an unusual patterrlpthat of apical infarction. In the 2 remaining cases the pattern of right ventricular hypertrophy donlinated in 1 as a result of coexisting puhnonary hypertension, and left ventricular hypertrophy as a result of coexisting systentic hypertension in the other. In conclusion, “sclerodernia heart disease” is an unconnnon clinicopathologic entity. Nevertheless, abnornialities of cardiac function in sclerodernla often are of niajor clinical significance because nlyocardial function is affected secondarily by (1) pulmonary hypertension, (2) systelnic hypertension associated with “scleroderrna kidney,” (3) pericarditis and pericardial effusion and (4) hypoxia associated with restrictive puhnonary disease. REFERENCES 1. \Vhss, s., S.I.EAD,E. A.,

JR., \vARREN, J. V. and BAILEY, 0. T. Scleroderrna heart diseask; with a consideration of certain other visceral manifestations of scleroderma. Arch. Int. Mrd., 71 : 749, 1943. 2. SACKNER, M. A., AKGUN, N., KIMBEL., P. and LE\VIS, D. H. The pathophysiology of scleroderma involving the heart and respiratory system. :Inn. Znf. Med., 60: 611, 1964. 3. RODNAN, G. P., SCHREINER, G. E. and BLACK, R. L. Renal involvement in progressive systemic sclerosis

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11. 12.

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Heinz and Steinberg

(genrralized sclcrodermn). _4m. J. 1M&., 23: 445, 1957. ASHMAN, R. A statistical study of the ventricular gradient and the QRS complex of the electrocardiogram. .4rch. Imt. cardiol. MGco, 15: 266. 1945. ALLENSTEIN, B. J. and Mow, H. Evaluation 01 electrocardiographic diagnosis of ventricular hypertrophy based on autopsy comparison. C~rc&/ion, 21 : 40, 1960. BARKER, J. M. The Unipolar Electrocardiogralll; A Clinical Interpretation, p. 575. New York. 1952. Appleton-Century-Crofts, Inc. SC.ARBOROUGH, W. R. et al. 4 ballistocardiographic study of 369 apparently normal persons; an and “bordwline” ballistoanalysis of “normal” cardiograms. llm. Heart J., 45: 161, 1953. BROWN, H. R., .JR., DELALLA, V., JR., EPSTEIN, M. A. and HOFFMAN, M. J. Clinical Ballistocardiography, p. 133. New York, 1952. The Macmillan Co. AYGEN, M. M. and BRAUNWALD, E. The splitting of the second heart sound in normal sub.jects and in patients with congenital heart disease. Circulalmn, 25: 328. 1962. ‘The aprx BENCHIMOL, A. and DIMOND, E. G. cardiogram in ischemic heart diseasr. &I/. Hrnrt J., 24: 581, 1962. Beitrag zur Kenntniss der ScleroWorrERs, M. dermie. Arch. Dumaf. u. Syph., 24: 695, 1892. VON NcrrrHAFFT, A. F. Neuere Arbeiten und Ansichten uber Sklerodermie (Zusammenf. Ref. mit Beschreibung eines nruen Falles dieser Krankheit) Als Anhang: Die Zellgewebsverhartung der Ncugeborenen. Zoztralbl. allg. Path., 9 : 870, 1898. GOEIZ, R. H. The pathology of progressive systemic sclerosis (generalised scleroderma); with special reference to changes in the viscera. C/in. Proc., 4: 337, 1945. GOETZ, R. H. The heart in generalised scleroderma: progressive systemic sclerosis. An,$olqv, 2 : 555, 1951. I~IRAYAMA, .J. Ein Fall van diffuser Sklerodermic Tr. Sot. mit hochgradigen Organveranderungen. Path. J@an, 28: 409, 1928. WEGELIUS, 0. and WAIILBERG, P. Early cardiac connective tissue changes in scleroderrna; report of a case. Acta med. scandinac., 156: 487, 1957. ROBERTS, .I. T. The heart in connective tissue diseases. In: Progress in Arthritis, p. 406. Edited by TALBOTT, J. H. and LOCKIE, I,. M. New York, 1958. Grune K: Stratton. ROTTENBERG, E. N. The heart in progressive systemic sclerosis: A clinical pathologic study. Thesis, Mayo Clinic, 1957. GREENFIELD, J. G., SHY, G. M., ALVORD, E. C., JR. and BERG, L. An Atlas of Muscle Pathology in Neuromuscular Diseases, p. 6. Edinberg, 1957. E. S. Livingston Ltd. MASUGI, M. and YA, S. Die diffuse Sklerodermie und ihre Gefassveranderung. Vwchoux Arch. path. Anat., 302: 39, 1938.

21.

MATSUI, S. Uber die Pathologic van Sclerodermia universalis. Tokyo, 31: 55, 1924.

22.

MELTZER, J. I. Pericardial effusion in generalized scleroderma. Am. J. Med.. 20: 638, 1956.

23.

24.

25. 26.

27.

28.

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30. 31.

32. 33.

34.

35.

36.

37.

38.

39.

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