16 Coumel P. Supraventricular tachycardias. In: Krikler DM, Godwin JF, eds. Cardiac arrhythmias.

London: WB Saunders,
1975:116-143
17 Marquez-Montes J, Rufilanchas JJ, Esteve-Alderete JJ, Mendez
J, Ugarte J, Rodriguez E, et al. Tratamiento quirurgico en 24
pacientes con sindrome de Wolff-Parkinson-White y taquicardias: diagnostic0 topografico de 10s haces de Kent y evaluation de
resultados. Rev Esp Cardiol 1981; 34:271-281
18 Josephson ME, Horowitz LN, Farshidi A, Spear JF, Kastor JA,
Moore EN. Recurrent sustained ventricular tachycardia: 2.
Endocardia mapping. Circulation 1978; 57:440447
19 Janse MJ, Van Capelle FJL, Anderson RH, Touboul P, Billette J.
Electrophysiology and structure of the atrioventricular node of
the isolated rabbit heart. In: Wellens HJJ, Lie KI, et al, eds. The
conduction system ofthe heart. Leiden: Stenfert & Kroese, 1976:
296-315

Reversed Rivero-Carvallo's Sign in

Right-Sided Hypertrophic
Obstructive Cardiomyopathy*
Kyozo Ishikawa, M. D . , E C . C . P ; Fukiyo Hirata, M . D . ;
Shunkichi Hirata, M . D . ; and Masarnichi lshikawa, M.D

An 18-year-old patient had right-sided hypertrophic

obstructive cardiomyopathy. His case was quite unique in
that the intensity of the systolic murmur was apparently
decreased during the inspiratory phase and increased during the expiratory phase (reversed Rivera-Carvalloi sign).

ypertrophic cardiomyopathy is classically associated

with predominant left-sided obstruction, but cases of
isolated and dominant right ventricular outflow obstruction
(RVO) have been described.14 I t is usually expected that the
*From the Kyorin University School of Medicine, Second Department of Internal Medicine, Tokyo, Japan.
Reprint requests: D1: Ishikawa, Kyorin University, 6-20 Shinkawa,
Mitaka City, Tokyo, lapan

Expiration

systolic m u r m u r resulting from subpulmonic stenosis in RVO

may b e increased in intensity during t h e inspiratory phase
and decreased during t h e expiratory phase (Rivero-Carvallo's
sign). T h e present patient with RVO in hypertrophic cardiornyopathy was quite unique in that the intensity of the
systolic m u r m u r was apparently decreased during t h e inspiratory phase and increased during the expiratory phase
(reversed Rivero-Carvallo's sign).

The patient, an 18-year-old man, was referred to us for cardiac

evaluation because of cardiac murmur. He had been in good health
and asymptomatic. He had never experienced chest pain or any kind
of unconsciousness. Examination revealed a grade 316 systolic
murmur with late systolic accentuation. This systolic murmur
became louder on expiration and quieter on inspiration (Fig 1).
Intracardiac phonocardiogram recorded in the right ventricular
outflow portion apparently demonstrated that the systolic murmur
became louder on expiration than on inspiration (Fig 2). Cardiac
catheterization revealed no intracardiac shunts, and a systolic
gradient of 7 mm Hg was recorded between the right ventricular
inflow and outflow tracts (Fig3). The pulmonary artery pressure was
1718 mm Hg. No pressure gradient was recorded in the left
ventricular cavity. Electrocardiograms showed right axis deviation
and right ventricular hypertrophy (Fig 4).
A selective angiogram with right ventricular injection revealed
protrusion of the interventricular septum into the right ventricular
outflow tract. Left ventricular obstruction was not demonstrated by
the left ventricular angiogram. Echocardiography demonstrated a
thick interventricular septum (27 mm) but did not reveal systolic
fluttering of the pulmonary valve, which was considered to be
characteristic of RV0.3.4

The data from t h e cardiac catherization and angiography

demonstrated t h e presence of isolated RVO. T h e systolic
pressure gradient within the right ventricle was slight in
degree (7 m m Hg) b u t apparently nonartifactual. D u r i n g t h e
cardiac catheterization, t h e pressure recordings within t h e
right ventricle were carefully repeated several times, reveal-

Inspiration

FIGURE
1. Respiratory change in the intensity of systolic murmur. During expiration the intensity of the
systolic murmur was increased whereas its intensity was markedly decreased during inspiration.
Reversed Riveco-Carvallo's Sign (lshikawa eta/)

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matim

Expiration

FIGURE
2. Intracardiac phonocardiography recorded in the outflow tract ofthe right ventricle. ?he systolic
murmur became louder on expiration than on inspiration.

ing the constant existence of a systolic pressure gradient

within the right ventricle. It seems most likely that the
systolic murmur in the present case originated from subpulmonic stenosis due to RVO. The question then arises as to
why the systolic murmur became louder in expiration and
not in inspiration. In cases where the systolic murmur is from
a right-sided origin, its intensity would tend to be increased
in inspiration, which is commonly understood as RiveroCarvallo's sign. However, the systolic murmur in the present
case apparently increased in expiration, which is
diametrically opposite to Ftivero-Cwallo's sign. The precise
mechanism responsible for such a "reversed Rivero-Carvallo's sign" remains unclear. However, it is tempting to
speculate that an increase in the venous return into the right
ventricle in inspiration may dilate the dimensions of the right
ventricle as well as the obstructed portion of the right

PA

ventricular o u a o w tract. As a result, the systolic murmur

originating from the RVO may b e decreased. Such a reversed
Rivero-Cwallo's sign has never been described previously
in ~ u b l i s h e dcases with RV0.14
The degree of the right intraventricular systolic pressure
daerences in a number of RVO collected from published
reports was found to vary from 7 to 118 mm Hg.' It would
appear that the distensibility of the obstructed portion may
b e ereater in mild cases than in more severe cases. Consequently, in mild cases such as the present case, an increase in
the venous return in inspiration might dilate the obstructed
portion with a resultant decrease in the intensity of the
systolic murmur. On the other hand, in severe cases, the
hstensibility and dilatation of the obstructed portion could
not be expected to decrease the systolic murmur to such an
extent.

RV

RA

FIGURE
3. Right heart catheterization. The pressure was continuously recorded while the catheter tip was
being slowly drawn from the pulmonary artery to the right atrium. n e r e was a slight but clearly apparent
pressure gradient between the right ventricular outflow portion and inflow portion.
CHEST 1 83 I 4 1 Aprfl, 1983

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6QS

VI

v
2

v
3

v
4

1/2

112

112

v
5

I t is possible b u t not certain that, with advancing severity

of this disease, the intensity of t h e systolic m u r m u r might

vary from inspiratory decrease to inspiratory increase. However, long-term follow-up observations will b e required to
confirm t h e validity of such a hypothesis.

1 Lockhart A. Charpentier S, Bourdarias JP, Ismail MB, Ourbak P,

Scebat L. Right ventricular involvement in obstructive cardiomyopathies; haemodynamic studies in 13 cases. Br Heart J
1966; 28:122
2 Momw AG, Fisher RD, Fogarty TJ. Isolated hypertrophic
obstruction to right ventricular outflow: clinical, hemodynamic,
and angiographic findings before and after operative treatment.
Am Heart J 1969; 77:814
3 Cardiel EA, Alonso M, Delcan JL, Menarguez L: Echocardiographic sign of right-sided hypertrophic obstructive cardiomyopathy. Br Heart J 1978; 40:1321
4 Kishimoto C, Kaburagi T, Takayam S, Kanyu I, Yokoyama S,
Ekatsu Y: A case of hypertrophic obstructive cardiomyopathy
with isolated obstruction to the right ventricular outflow: the
echocardiographic findings. J Cardiography 1980; 10:881

Azathioprine-Associated
Pulmonary Dysfunction*
Michael J. Krowka, M.D.t; Richard I . Breuer, M.D.S;and
Thomas]. Kehoe, M.D.5

We present a case of azathioprine-associated alveolitis

diagnosed by gallium-67 scanning and transbronchial biopsy. I h e patient denied respiratory symptoms, exhibited
spiking fevers, and had normal chest roentgenograms.
Allopurinol inhibition of a z a t h i o p ~ emetabolism may have
been a contributing factor.

ulmonary toxicity of immunosuppressive and cytotoxic

agents has been recently reviewed.'.' Respiratory dysfunction is usually characterized by dyspnea, cough, abnormal pulmonary function tests, and chest roentgenographic
-

*From the Department of Medicine, Evanston Hospital, Northwestern University Medical School, Evanston, Illinois.
tResident in Internal Medicine.
$Associate Professor, Division of Gastroenterology.
%AssociateAttending. Division of Pulmonary Medicine.

696

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v6

F I G U R E4. Electrocardiogram showing right

axis deviation and right ventricular hypertrophy.

changes in a febrile patient. Early detection of such toxicity,

prior to chest roentgenographic abnormalities, has been
described and may have a significant impact o n morbidity
and ~ n o r t a l i t y .We
~ describe a patient with azathioprinerelated pulmonary dysfunction characterized by normal
findings o n c h e s t r o e n t g e n o g r a m a n d a b n o r m a l galli~m-67(~~G
lung
a ) scan.

A 35-year-old man was admitted for evaluation of intermittent

fever (39.4OC). Crohn's disease had been diagnosed when he was
aged 17. Four bowel operations performed because of obstruction or
fistulas resulted in an ileostomy in 1970. Subsequent medical
therapy included a two-month trial of azulfidine because of radiologic demonstration ofileal recurrence two years prior to admission.
Kidney stones were passed in 1971, 1972, and 1979. Stone analysis
indicated 90 percent urate in each instance. Allopurinol therapy was
begun two years prior to admission and continued at doses ranging
from 100 to 200 mglday. Eight months prior to admission, ileal
obstruction resolved with tube decompression and initiation of
prednisone therapy, 60 mg/day. The prednisone was decreased to 20
mg/day, but four months later bleeding from the ileum recurred.
Azathioprine, 50 mgtday, along with prednisone, 40 mg/day, successfully controlled the bleeding. By one month prior to admission,
prednisone had been reduced to 40 mg every other day and
azathioprine had been increased to 125 mg/day. At no time did the
patient complain of respiratory difficulties.
Physical examination indicated blood pressure of 120180 mm Hg
without orthostatic changes. Temperature was 39.1C orally, respirations 18 per minute, with a regular pulse rate of SO per minute. The
chest was clear to auscultation and percussion. Cardiac examination
was within normal limits. Abdominal examination was significant for
mild, &se tenderness without rebound or hepatosplenomegaly.
There was no adenopathy, and the neurologic examination was
normal.
Fever workup included cultures of induced sputum, urine, blood,
spinal fluid, and bone marrow. All were negative. Chest roentgenograms were normal. The WBC was elevated to 15,50O/cu mm, with
65 percent polymorphonuclear leukocytes and no eosinophils.
Atypical lymphocytes were not seen on the peripheral smear.
Antinuclear antibody and rheumatoid factor titers were less than
1:20. Lymphocyte stimulation, immune complex, and complement
studies were not done. Hepatorenal function was normal, and the
urinalysis was unremarkable. Forty-eight hours after admission,
azathioprine and allopurinol therapy was stopped, and prednisone
administration continued at 40 mg/day. AGCascan obtained to locate
a possible abdominal abscess was unremarkable. However, both
lungs demonstrated spectacular uptake at 6, 24, and 48 hours after
A z a t h i i n e - W a t e d Pulmonary Dysfunction (Krowke et al)