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Atrial septal defect associated with mitral stenosis
Atrial Septal Defect Associated with Mitral Stenosis* The Lutembacher
WALTER STEINBRUNN, KEITH
E. COHN,
ARTHUR
Revisited
Five patients are described with large, congenital secundum atrial septal defects combined with acquired rheumatic mitral stenosis. In one additional patient mitral stenosis was associated with a small patency of the foramen ovale, perhaps secondary to atrial wall stretching. Clinically, these cases of Lutembacher’s syndrome may resemble pure mitral stenosis in some instances and pure atrial septal defect in others. The dangers of incomplete diagnosis and surgery are emphasized: Increased pressure developing in the left atrium after closure of the atrial defect resulted in pulmonary edema and death in one case and in reopening of the atrial septal defect in two others. Although not a particularly distinctive syndrome, distinguishing features of both conditions are usually present and may permit establishment of the correct diagnosis.
M.D.+
M.D.
SELZER,
San Francisco,
Syndrome
M.D.
California
The association of atrial septal defect and rheumatic mitral stenosis, customarily referred to as Lutembacher’s syndrome [l], is a recognized pathologic entity; yet its clinical features have not been precisely defined. The older literature stressed the frequency of this syndrome, largely because early workers failed to recognize the fact that the diastolic murmurs of atrial septal defect were due to increased tricuspid flow and did not represent evidence of mitral stenosis [2]. More recently, Lutembacher’s syndrome has been considered to be quite rare. Our purpose here is to review six cases, to attempt to identify the clinical and hemodynamic features which would permit establishment of the diagnosis and to describe the hazards of misdiagnosis. MATERIAL
AND
METHODS
This report includes six patients with a defect in the atrial septum associated with mitral stenosis. Five of these cases were found among 128 consecutive patients
(over the age of eighteen)
with atrial septal defect who were the sub-
ject of an earlier report [3]. The sixth case was a patient seen by one of us (A.S.) at the Veterans Administration Hospital. All patients underwent a complete diagnostic evaluation, which included history, physical examination and electrocardiographic and roentgenographic studies; phonocardiograms were available in three cases. In all patients cardiac catheterization studies were performed, and three had more than one study. Most hemodynamic studies were made when left-sided cardiac catheterizations were not routinely performed, hence a direct gradient across the mitral valve is available only in one patient. All patients underwent cardiac surgery, some more than once. The diagnosis of mitral stenosis was based on the surgical assessment of the mitral valve and was accepted only if the surgeon reported significant obstruction at the mitral valve. In one case (V.A.) mitral stenosis was not recognized during life, but it was found at necropsy * From
the
Hospital, tute
of
fornia.
Cardiopulmonary
Pacific Medical These
Grants
HE
Center,
Sciences,
San
06311,
HE
ship
1.F3-HE-36,084.01 of Health, grant
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for Seizer,
the
Volume
San
Medical Francisco,
Insti-
and
in
Special
the
Calipart
Fellow-
National and
Heart
by
Instia fellow-
Association.
be addressed Center, California
to
Clay
Dr. and
94115.
Cardiopulmonary
Unit,
Birmensdorferstrasse
497,
Switzerland.
48, March
Area
the
Francisco,
Maryland,
should
address:
Stadtspital-striemli Zurich,
Bay
Pacific
Streets,
t Present
from
reprints
Presbyterian and
supported
5497
Bethesda,
from
Requests
were
studies
tutes ship
Unit,
Medical
1970
CASE
REPORTS
Case 1. This thirty-nine
year old woman (M.B.) had had a cardiac murmur since childhood. There was a history of rheumatic fever, the details of which were not available. In 1958, at the age of thirty-six, while virtually asymptomatic, she underwent a diagnostic study that included cardiac catheterization, and the diagnosis of atrial septal defect was established. In March 1958 closed repair of the atrial septum was performed. Shortly after the operation shortness of breath and easy fatigability developed. The patient was admitted to the hospital for study in April 1960. Physical examination revealed prominent jugular venous pulsation with the patient in the sitting position. The lungs were 295
TtiE
LUTEMBACHER
SYNDROME
-
STEINBRUNN
ET AL.
AVL
AVR
AVF
Comment:
This case demonstrates that mitral stenosis may be masked when associated with a secundum atrial septal defect. Both the right and left atrial pressures were initially normal in this case, since the defect a:. lowed decompression into the systemic veins. Closure of the defect, however, evoked an increase in pressure within the left atrium, thus precipitating the onset of symptoms and reopening of the atrial septal defect.
Case 2.
This fifty-seven year old woman (V.A.) had had an attack of rheumatic fever at the age of nine. She was known to have had a heart murmur since then but had remained Fig. 1. left
and
and
right
Case 1. Electrocardiogram possibly
right
ventrxular
atrial
of patient
showing sinus rhythm, right QRS axis deviation
enlargement.
hypertrophy.
clear. Increased precordial motion was noted. The first heart sound was accentuated and the second sound showed wide splitting that did not vary with respiration. An ejection type systolic murmur was heard along the upper left sternal border: auscultation in the apical region revealed a pansystolic murmur of medium intensity and a long diastolic rumbling murmur. An electrocardiogram showed biatrial hypertrophy, right axis deviation of the QRS axis, incomplete rjght bundle branch block and right ventricular hypertrophy (Fig. 1). Chest roentgenogram showed a vigorously pulsating, enlarged hilar vasculature; right atrial and right ventricular enlargement were also noteworthy. Repeat cardiac catheterization (Table I) showed a large left to right shunt at the atrial level, increased right and left atrial pressures and moderate pulmonary arterial hypertension. The physical and catheterization findings at that time were thought to indicate the diagnosis of Lutembacher’s syndrome. An operation, performed in February 1961, confirmed the coexistence of severe mitral stenosis with some valvular incompetence and a large atrial septal defect. Both lesions were corrected: the patient made an uneventful recovery and has remained asymptomatic.
TABLE
I
Cardiac
Catheterization
asymptomatic until 1956. At that time, at the age of fortyseven, she experienced dyspnea and palpitations, and atrial fibrillation was found. Her clinical condition remained satisfactory, controlled by digitalis, until 1960 when symptoms became more severe and fluid retention developed: this was only partly relieved by the administration of diuretics. When seen in 1966 she appeared chronically ill, and her exercise tolerance was limited. Physical examination revealed jugular venous pulsation, with a prominent V wave, extending to the lobes of the ear. The lungs were clear. A marked parasternal lift was present. The first sound was loud the second sound widely split and fixed. In addition,
opening snap was heard, followed by a diastolic rumbling murmur. A diffuse pansystolic murmur was present, which increased in intensity with inspiration. The patient had a large, pulsating liver and marked ankle edema. An electrocardiogram showed atrial fibrillation, right axis deviation and incomplete right bundle branch block with evidence of right ventricular hypertrophy (Fig. 2). A chest roentgenogram showed marked cardiomegaly with enlargement of both atria and the right ventricle. The central hilar vessels appeared as large “cannon balls” and then tapered peripherally; there was a hilar dance and calcification of the left pulmonary artery (Fig. 3). A clinical diagnosis of pulmonary hypertension and tricuspid insufficiency, presumably due to mitral stenosis, was made. At catheterization, however, an atrial septal defect was discovered, and on the basis of a left atrial pressure of only 11 mm Hg the diagnosis of mitral stenosis was discarded.
Findings
Case4
Case1 Z/7/58
Data Arterial oxygen saturation Pulmonary cardiac
(%)
94
4/4/69 92
Case 2 Z/17/66 88
Case3 3/8/57
~ 5/22/57
94
94
4/22/58 97
Case 6 Case 5 Z/4/65 93
3/17/60 ...
6/10/66 95
index (L/min/M*) Systemic cardiac
9.4
20.0
3.9
7.3
4.8
5.3
7.0
...
2.8
index (L/min/Mt) Pulmonary: systemic
2.6
3.0
1.4
2.1
2.2
2.0
2.9
...
1.6
3.5:1 2.2:1 4:l 2.8:l 3.6:1 flow ratio 13 9 v = 25, 15 v = 14, 10 6 Right atrium (mm Hg) 68/15 59/8 63/O-20 60/O-9 27/O-2 Right ventricle (mm Hg) 65/22, 35 57/29, 39 60/25, 37 26/10, 15 65/26, 44 Pulmonary artery (mm Hg) 17 9+ 20 v = 15,11+ . ,. Pulmonary artery wedge (mm Hg) ’’’ ... ... ... Left ventricle (mm Hg) 174/75, 108 ::: 110/64, 80 82/50, 62 ... Systemic artery (mm Hg) Total pulmonary resistance Pulmonary vascular resistance Total systemic resistance (dynes
set
cm-&/l.7 Mz)
70
... ...
NOTE: Underscore figures equal mean * = right-to-left shunt of 0.5 L/min. + = left atrial pressure. 296
left and an
90 50
1,200
500 350
2,300
220 110
2,300
380 290
...
2.6:1 14 73/14 76/28, 43 *.*
*” 103/75, 85 380
... 2,000
.., 1.75:1 2.4:l 5 v = 20, 19 v = 19, 13 40/O-8 100/27 46/5-g 35/16, 28 115/60, 72 46/21, 30 18 35 v = 40,23 9. . 117/O-17 ... 142/86, 146/90, 107 150/80, lJ3 100 ... 1,020 240 ... 530 50
2,000
...
2,450
pressure.
The American
Journal of Medicine
THE
LUTEMBACHER
SYNDROME
STEINBRUNN
-
Case 3.
This forty-three year old man (R.D.) had had no definite history of rheumatic fever in childhood but had suffered from repeated sore throats. He had no knowledge of cardiac disease until the age of twenty-seven when he
Fig. of
3.
Case
patient
and
Volume
the
2.
Chest
show right
48,
marked ventricle.
March
1970
roentgenograms cardiomegaly There
is
(posteroanterior with marked
and
lateral)
AL.
AVF
AVL
At surgery a large secundum atrial defect and severe tricuspid regurgitation with rupture of two chordae tendineae arising from the anterior leaflet of the tricuspid valve were found. The atrial septal defect was sutured closed and the tricuspid valve was repaired by valvuloplasty and anuloplasty. The mitral valve was described as normal on palpatory exploration. The postoperative course was complicated by respiratory insufficiency, and mechanical respiratory assistance was required for several weeks. The patient died two months later; postmortem examination revealed the associated rheumatic mitral stenosis.
Comment: This case exemplifies the potential hazards of failing to recognize mitral stenosis in a case of Lutembacher’s syndrome, with consequent mortality from the intractable pulmonary congestion following closure of the atrial septal defect. It also demonstrated an unusual and apparently rare cause of tricuspid insufficiency; the mitral stenosis and atrial septal defect evidently led to massive dilation of the right heart chambers, perhaps producing stretch and increased tension on some of the tricuspid chordae and eventual rupture. At postmortem the tricuspid valve was thought not to be involved in the rheumatic process, and there was no evidence of bacterial endocarditis.
ET
,
Fig.
2.
tion,
Case
right
bundle
2.
axis
branch
Electrocardiogram deviation
block
of
which
the may
of
patient
showing
QRS
segment
and
signify
right
ventricular
atrial
fibrilla-
incomplete
right
hypertrophy.
began to have attacks of rapid heart action. The diagnosis of mitral stenosis was made, and the arrhythmia was recognized as paroxysmal atrial flutter. Two years later atrial flutter became chronic despite quinidine therapy, and the ventricular rate was controlled by digitalis. Within the next five years the patient experienced two episodes diagnosed as embolism to the kidneys. In 1956, at the age of fortytwo, right ventricular failure developed with fluid retention; this was initially controlled by diuretics but subsequently became more and more resistant to therapy. The patient was admitted to the hospital in May 1957 in intractable
branches
enlargement
of
both
atria
of
dilatation
of
the
hilar
aneurysm
the
of
both
vessels of the
pulmonary
arteries
beyond
the
hilar
left
pulmonary
regions
with
rapid and
decrease
calcification
in of
caliber a
large
artery.
297
THE
LUTEMBACHER
cardiac
failure.
marked
left
sound,
widely
SYNDROME
-
Pertinent
STEINBRUNN
physical
parasternal
lift,
split
sound,
second
an
ET
findings
included
accentuated followed
AL.
a
was
found.
first
heart
stenosis
by a mitral
open-
suggesting
In
addition,
of the mitral that
some
a
clinically
unsuspected
valve was found
with
a valve
insufficiency
of the
valve
severe deformity was
aIs,)
ing snap. There was an apical diastolic rumbling murmur as well as a moderately loud apical pansystolic murmur, which
present. Ivalonv
increased with inspiration. A systolic ejection type murmur was present at the base of the heart on both sides of the sternal border. An early diastolic blowing murmur was heard at the lower left sternal border. The patient appeared cyanotic with a malar flush. A jugular venous pulse was visible
were performed. ‘The initial postoperative course was satisfactory, but on the third postoperative day cardiac arrest occurred and the patient could not be resuscitated. Autopsy revealed a completely closed lnteratrial defect and a successfully repaired rheumatic mitral stenosis (Table II).
with the patient in the sitting position, ears. The lungs were clear. The liver
up to the lobe of the was greatly enlarged
and showed considerable pulsation. Moderate anasarca was present. The patient’s electrocardiogram showed complete right bundle branch block and atrial fibrillation. A chest roentgenogram revealed a markedly enlarged right atrium and dilated right ventricle, a slightly enlarged left atrium and a normal left ventricle with bulging pulmonary arteries and signs of pulmonary hypervascularity. On the basis of the clinical findings a diagnosis of mitral stenosis with secondary tricuspid incompetence was made. Cardiac catheterization was performed on March 8, 1957. The findings, presented in Table I, established the additional diagnosis of atrial septal defect. Because of the desperate clinical situation surgical treatment was attempted, combining mitral commissurotomy with repair of the atrial septum, using a modified Sondergaard technic. At operation a tight mitral stenosis and a large atrial septal defect were found. The patient did not survive the procedure. Permission to perform
an autopsy
electrocardiogram
partial
right
pertrophy. megaly signs
bundle A chest
with of
pulmonary
was performed, 298
large
showed branch
atrial
block
fibrillation,
and
right
roentgenogram
revealed
dilated
pulmonary
central
hypetvascularity.
and at operation
Open
a large atrial
right
arteries heart septal
and
with the aid of ail and valvuloplast~{
of the v,alve commissures effected. The patient’s condition improved but within five years her symptoms recurred, and in November 1960 she underwent repeat operation. At that time closed transventricular mitral valvulotomy was performed. The patient showed clinical improvement again until 1964, when clinical symptoms recurred. She entered this hospital in February 1965 for diagnostic evaluation. Physical examination showed jugular venous pulsation with the patient in the sitting position. The lungs were clear. cardiac findings included accentuation wide and fixed splitting of the second
of the sound
and an opening snap, initiating an apical diastolic rumbling murmur. In addition, an apical pansystolic murmur radiating to the axilla was described (Fig. 4). Severe hepatomegaly and edema were present. Electrocardiogram showed atrial fibrillation, right axis deviation of the QRS, incomplete right bundle branch block and right ventricular hypertrophy (Fig.
TABLE II Case No.
Patient
Summary
of Pathologic
Atrial Septal
and
Defect
Surgical
Mitral
Findings
Valve
M.B.
Ostium secundum 4by3cm
Stenotic and somewhat incompetent
V.A.
Ostium secundum 4by5cm
Marked degree of thickening of the leaflets and more pronounced thickening and shortening of the chordae tendineae-two chordae of the anterior leaflet ruptured
R.D.
Ostium secundum 4by5cm
Very tight, calcified
R.C.
Ostium secundum 5 by3cm
Tight stenosis with thickening and fusion of the cusps and chordaeleakin the anterior commissure
C.W.
Ostium secundum with calcified rim 4 by3cm
Moderately stenotic with fusion of the chordae
J.R.
Patent foramen ovale 1 by 1 cm
Completely destroyed calcified-obliteration of the commissures subvalvular fusions
hy-
cardio-
was closed valvulotomy
heart disease was obtained, as both her mother and sister had mitral stenosis. She was known to have a cardiac murmur but remained asymptomatic until the age of thirtyfour when, in 1953, palpitations and dyspnea developed, and atrial fibrillation was noted. Later that year closed mitral valvulotomy was performed. At operation a tight mi. tral stenosis was found and a satisfactory finger fracture
axis,
ventricular marked
defect mitral
This forty-six year old woman (R.W.) had had Case 5. chorea at the age of twelve. A family history of rheumatic
Auscultatoty first sound,
was refused.
Case 4. This forty-six year old woman (R.C.) was known to have a cardiac murmur since the age of eleven. At the age of thirty-two she had an illness diagnosed as acute rheumatic fever, the details of which were not available. In 1952, at the age of forty, she experienced dyspnea on effort in association with palpitations. The condition remained stationary until 1956, when she was striken with a left-sided hemiparesis. Following recovery from this episode in May 1957, she underwent cardiac catheterization. The diagnosis of atrial septal defect was made, and surgical repair was undertaken elsewhere in September 1957, using the hypothermia technic. The patient’s symptoms were not relieved by the operation, and gradually her condition worsened. In April 1958 a repeat cardiac catheterization study was performed (Table II) which showed persistence of an interarterial shunt comparable with that prior to the operation. Pulmonary arterial pressures were higher than in the previous study. The patient entered this hospital in August 1958 showing evidence of severe cardiac failure. Upon physical examination a cyanotic tinge was noted. A large jugular venous wave pulse was visible with the patient in the sitting position suggesting the presence of tricuspid insufficiency; the lungs were clear. Examination of the heart revealed exaggerated precordial motion; the first sound was loud, the second sound was widely split, followed by an opening snap. A mid-systolic ejection type murmur was present at the left upper sternal border; at the apical region a loud pansystolic murmur was heard, followed by the mid-diastolic rumbling murmur. In addition, an early diastolic blowing murmur was heard at the lower left sternal border. Moderate hepatomegaly was present and ankle edema was noted. The patient still exhibited residual changes from her hemiplegia. The
The septal patch, and
surgery defect The
American
scarred
Journal
and
and and
of Medicine
THE
5). An electrocardiogram right atrial enlargement.
taken Chest
LUTEMBACHER
SYNDROME
-
STEINBRUNN
ET
AL.
in 1953 had shown left and roentgenogram revealed en-
largement of both atria and of the right ventricle with engorgement of the central pulmonary vessels and the presence of Kerley’s B lines (Fig. 6). Cardiac catheterization was performed in February 1965 for the first time (Table I). It revealed a clinically unsuspected left to right atrial shunt of moderate proportions. The diagnosis of mitral stenosis and atrial septal defect was thus established. At operation, open mitral valvulotomy and valvuloplasty and closure of a moderately large secundum type atrial septal defect were accomplished. Her recovery was uneventful and she has remained well.
AORTA *Y-
Case 6.
This forty-one year old man (J.R.) was found to have a heart murmur at the age of twenty-one. There was no history of rheumatic fever, but he had suffered from repeated bouts of “growing pains” in childhood. He remained asymptomatic until the age of thirty-five, in 1960, when
dyspnea on effort and easy fatigability developed. Cardiac catheterization was performed in 1960 (Table I) and the findings confirmed the clinical diagnosis of mitral stenosis
followed
and insufficiency.
components
candidate
pulse
for
The patient was not considered a suitable cardiac surgery and was maintained on a
medical regimen for the next six years. Gradually he became more symptomatic and in June 1966 was readmitted for reinvestigation. At that time he appeared to be in right and left ventricular failure. Physical examination revealed prominent jugular venous pulse with the patient in the sitting position. Auscultatory findings included accentuation of the first heart sound and fixed splitting of the second sound. No opening snap was heard. A moderately loud pansystolic apical murmur was heard as well as a long apical diastolic rumbling murmur. An early diastolic blowing murmur was also audible at the left sternal border. Moderate hepatomegaly was present, as was mild peripheral edema. The electrocardiogram showed sinus rhythm, left atrial enlargement and incomplete right bundle branch block. A chest roentgenogram indicated moderate cardiomegaly with evidence of pulmonary venous congestion. Cardiac catheterization was performed in June 1966 (Table II). The presence of mitral stenosis with pulmonary hypertension and a 1.7:1 atrial left to right shunt were found. There was also a large pressure differential between the right atrium (19 mm Hg) and left atrium (pulmonary artery wedge pressure = 35 mm Hg). On June 21 another procedure was performed, which included transseptal left heart catheterization and angiocardiographic study with injection into the left atrium, demonstrating the interatrial shunt directly. In August 1966 open heart surgery was performed with replacement of the mitral valve with a ball-valve prosthesis and closure of a patent foramen ovale.
Fig.
4.
heart
Case sound
5.
Phonocardiogram
(8)
by an
and
wide
opening
of the
snap
second
of
splitting (0,s.).
heart
of
Volume
48,
March
1970
the
AZ and
sound.
showing
second R
CP =
=
a
sound
aortic
indirect
loud
first
(0.06
set)
and
pulmonic
carotid
arterial
tracing.
spection of the atrial septum and of the mitral valve during open heart surgery. In one patient (Case 2) the mitral valve was examined during surgery by palpatory exploration only. In two patients autopsy findings also were available. A summary of the anatomic findings is presented in Table II. In five patients a large, secundum-type congenital atrial septal defect was present. In one patient (Case 6) a small patency of the foramen ovale was found. All patients showed typical rheumatic scarring of the mitral valve leading to gross deformity of that valve and producing either pure mitral valve stenosis or insufficiency with predominant stenosis. It is clear from these findings that in five of the six cases congenital atrial septal defect coexisted with acquired, rheumatic mitral valve disease. The possibility exists that in the sixth case patency of the foramen ovale may have developed secondarily to stresses upon the atrial wall from the valvular disease [4]. Clinical Features. A history of rheumatic fever was obtained in four patients; in two the presence of rheumatic fever in childhood was considered possible but not definite. The patients remained asymptomatic until the
COMMENTS In reviewing the combined
presence of mitral stenosis and atrial septal defect, three fundamental questions should be considered: (1) Does this combination constitute a true syndrome, that is, a distinctive clinical pattern, rather than the coexistence of two unrelated diseases? (2) Can the diagnosis of the combined lesions be made clinically? (3) Does either of the diseases alter the course and prognosis of the other? In order to answer these questions, the salient features of the six patients described will be analyzed and discussed in the light of previously expressed views concerning the Lutembacher syndrome. Anatomic Features. Description of the anatomic findings in five cases of this series is based on surgical in-
patient
AVR
Fig.
5.
Case
l&ion,
right
bundle
branch
5. axis
Electrocardiogram deviation
block
which
of the may
in QRS signify
patient segment right
AVL
showing and ventricular
AVF
atrial incomplete
fibrillaright
hypertrophy.
THE
Fig. of
LUTEMBACHER
6. patient
ventricle
Case
5.
reveal with
SYNDROME
Chest
roentgenograms
moderate
engorgement
-
enlargement of the
central
STEINBRUNN
ET
(posteroanterior of
both
pulmonary
atria
AL.
and and vessels
lateral) the
right
in the
more origlnal
distally.
Kerley
B lines
It
Ihe
right
base
were
e ,i-
roentgenogram
tapering
ages of twenty-seven to forty-seven years (average time of onset of symptoms, thirty-seven years). The duration of symptoms until the diagnostic evaluation varied from three to sixteen years (average nine years). Palpitation was the initial symptom in four patients; dyspnea on efort was present in five and easy fatigability in all cases. One patient underwent closure of the atrial septal defect while asymptomatic (Case l), but dyspnea developed after the first operation. Only one patient (Case 6) had a history of orthopnea and paroxysmal nocturnal dyspnea. Hemoptysis, marked cyanosis or clubbing was not found in our series. Evidence of congestive heart failure with edema, anasarca and pulsatile neck veins was observed at some point in the course of all cases. Large V waves, which were assumed initially to represent tricuspid insufficiency, were noted in five patients. Bedside examination at first suggested the diagnosis of isolated mitral stenosis in four instances, and atrial septal defect in two, although in retrospect these patients actually did present with physical findings characteristic of both lesions. A parasternal heave-presumably right ventricular in origin-a loud or snapping first sound and wide splitting of the second sound were uniformly either heard or noted on the phonocardiogram. An opening snap was present in four cases. A pansystolic murmur, heard at the left sternal border and apex, was noted in all cases; in two this murmur seemed to increase in intensity with inspiration. Hence the diagnosis of mitral stenosis with associated mitral or tri300
moderately dent
cuspid regurgitation was frequently considered. An ejection-type systolic murmur was mentioned specifically in three cases. In addition to the characteristic apical diastolic murmur, heard in six patients, a higher pitched parasternal diastolic murmur, probably due to increased tricuspid flow, was described in two cases. Electrocardiographic examination of the patients revealed atrial fibrillation or flutter in four patients. Five patients had a rightward QRS-axis deviation and incomplete right bundle branch block with evidence of right ventricular hypertrophy. One patient had a complete right bundle branch block and the patient with patent foramen ovale (Case 6) had a normal QRSaxis. Roentgenographic examination disclosed varying degrees of cardiac enlargement. The right atrium was markedly dilated in all patients, whereas the left atrium was normal or only slightly enlarged in four. Two patients had marked left atrial enlargement (Cases 5 and 6). In these two patients the pressures in the left atrium were significantly higher than in the right atrium (Table I). The left ventricle was normal or slightly enlarged in five patients, whereas in one (Case 6) moderate prominence of the left ventricle was noted. Dilated, vigorously pulsating pulmonary arteries and their branches combined with roentgenologic evidence of pulmonary hypervascularity was noted in five patients (Cases 1 through 5). In two patients there was evidence of pulmonary venous congestion (Kerley’s B-lines), and in one The
American
Journal
of Medicine
THE LUTEMBACHER
(Case 2) these developed after closure of the atrial septal defect. From the diagnostic standpoint, then, it is clear that some of our patients were considered clinically to have simple atrial septal defects and others to have simple mitral stenosis, depending upon the predominant clinical features; one lesion tended to mask the other. Yet this review of the clinical features, particularly the findings on physical examination and phonocardiography, suggests that with an especially high index of suspicion the correct diagnosis can be established. Among noteworthy signs are the joint presence of a widely split second sound showing little respiratory variation, an opening snap and accentuation of the first heart sound. The presence of a diastolic rumbling murmur in the apical region need not indicate mitral stenosis, for such transmission of a tricuspid flow murmur occurs in patients with pure atrial septal defect and very large right ventricles extending to the apex of the heart: however, audibility of the diastolic rumble over an unusually long area might be suspicious of mitral stenosis in a case otherwise suggesting atrial septal defect. The electrocardiogram is helpful in patients with clearcut clinical signs of mitral stenosis since incomplete or complete right bundle branch block would then suggest the possibility of an atrial septal defect. The chest roentgenogram and fluoroscopic examination may be valuable when large pulmonary arterial branches with excessive pulsation and suggestion of increased blood flow to the lungs are associated with a large right atrium. Hemodynamic Findings (Table I). In all patients the oxygen content of blood obtained from the right atrium, and downstream from it, was higher than that in the superior vena caval blood. Calculation of flow ratios was made on the basis of superior vena caval blood as representing systemic venous return, which has been shown to have an oxygen content reasonably close to that of pulmonary arterial blood in patients without shunts [5]. On this basis, all patients but one (Case 6) had pul-. monary flows greater than two and one half times the systemic flow. The systemic cardiac index was smaller than 2.5 L per minute per M2 in four patients and normal in two. Another consistent finding in this series was the elevation of right atrial pressure with prominence of V waves. Systemic venous congestion and elevated right atrial pressures are usually seen only in the older patients with isolated atrial septal defect and often appear after the onset of chronic atrial fibrillation [3]. Systemic venous congestion in cases of pure atrial defect is considered by Dexter [6] and Tikoff et al. [7] to reflect left rather than right ventricular failure, although more recently Flamm et al. [8] have shown that this may be caused by failure of either ventricle. The cases described herein emphasize the importance of considering other possible factors in the genesis of systemic congestion in atrial septal defect. In most of our cases the mitral stenosis elevated the left and, by continuity, the right atrial pressures. By causing pulmonary hypertension and right ventricular failure, the increase in systemic venous pressure was probably potentiated. We have also seen three patients with rheumatic mitral insufficiency and secundum atrial septal defects. Clinically these patients Volume 48, March
1970
SYNDROME
-
STEINBRUNN
ET AL.
seemed to have mitral regurgitation with tricuspid insufficiency with widely radiating pansystolic murmurs and markedly pulsatile neck veins with large V waves. At surgery the absence of tricuspid regurgitation was demonstrated in all instances. The V waves in the neck, therefore, were merely reflections of the mitral reflux. The ruptured chordae tendineae producing severe tricuspid insufficiency in one of our patients (Case 2) provides yet another source of increased venous pressure in cases such as these. Pressures in the pulmonary artery were elevated in all patients, but pulmonary vascular resistance was not appreciably increased in any except the one with the patent foramen ovale. A hyperkinetic type of hypertension, therefore, appears most common. Incidence, Significance and Definition of Lutembacher’s Syndrome. Since 1813 the association of atrial septal defect with mitral stenosis has been described many times. Lutembacher [l] drew special attention to the condition in 1916 and described it as an anatomic and pathophysiologic entity. Because of the misunderstanding of the mid-diastolic murmur found in atrial septal defect, Lutembacher’s syndrome was previously diag nosed with great frequency. Nadas and Alimurung [2] were the first to point out the rarity of this syndrome and to emphasize the proper, tricuspid origin of the diastolic flow murmur in the atrial septal defect. In an autopsy series of 25,000 cases from five Boston hospitals, five cases of Lutembacher’s syndrome and eighty-seven cases of atrial septal defect were found. Angelino et al. [9] found six cases of this syndrome among 120 cases of atrial septal defect and 2,000 cases of mitral stenosis. Fontana and Edwards [lo] reported thirty-one examples of isolated atrial septal defect and two instances of Lutembacher’s syndrome. Our results show a similar incidence: Five cases of Lutembacher’s syndrome were found among 128 cases of adult atrial septal defect and 700 to 800 cases of mitral stenosis. The prevalence in our series is therefore 4 per cent of cases of atrial septal defect and 0.6 to 0.7 per cent of cases of mitral stenosis. The incidence of mitral stenosis in patients with atrial septal defect thus appears to be considerably higher than a chance coexistence of two diseases. This notion is supported by the figures cited and by the fact that not a single instance of mitral stenosis was found in association with other common congenital lesions (ventricular septal defect, pulmonary stenosis) in our series. The cause for preferential acquisition of rheumatic mitral stenosis by patients with congenital atrial septal defect is not known. Lutembacher believed that the defect within the atrial septum was congenital, rather than an acquired, stretched foramen ovale. The findings of large secundum atrial septal defects in Cases 1 through 5 tend to substantiate the congenital nature of this anomaly. One patient (Case 6) in this series merely had a patent foramen ovale, considerably smaller than the other defects, perhaps secondary to atrial stretching in the course of mitral stenosis [4], and therefore should not be considered as an example of Lutembacher’s syndrome [ll]. He is included nonetheless, for purposes of contrast. In Lutembacher’s original case there was no history of rheumatic fever and he, and several other 301
THE
LUTEMEACHER
SYNDROME
-
STEINBRUNN
ET AL.
early workers, assumed that the mitral lesion was of congenital origin. More recent pathologic and surgical observations. however, as well as the findings in this series, support the contention that the mitral stenosis is of rheumatic etiology in the majority of the cases of Lutembacher’s syndrome. All of Espino-Vela’s [12] cases were pathologically proved examples of rheuma. tic mitral stenosis. Ferencz et al. [13] and Van der Horst and Hastreiter congenital
an associated Having atrial
in their
secundum defect
concerning
that
this
and acquired
when
the
the two lesions
mitral
of congenital stenosis
rare, it is necessary
of the two lesions previously
point
were
purely
clarified.
[9,11,15]
and our
series
imposition
of mitral
stenosis
considerations
speculative,
concepts However,
have shown
is unto con-
to each other.
published
hemodynamic
were
with
who had
atrial septal defect.
but not exquisitely
It is obvious
of 122 children
that the coexistence
sider the relationship
written
review
stenosis found only one patient
established
septal
common,
[14]
mitral
recent that
upon an atrial
mostly
of neither the
of
studies super-
septal defect
the usually benign may, in some cases, complicate course of the atrial septal defect [3]. The same is true for an atrial septal defect associated with mitral insufficiency [16].
On the other hand, it is likely that the atrial septal defect exerts a protective influence upon mitral stenosis by decompressing the left atrium and the pulmon ary venous system. This thesis is based upon the obse-vations that our patients experienced no paroxysmal attacks of dyspnea or pulmonary edema; moreover, closure of the atrial septal defect in two cases exacerbated the signs and symptoms of pulmonary congestion. This belief is also supported by observations on four patients with ostium secundum atrial septal defect and mitral insufficiency who showed a significant rise in pulmonary artery and pulrnonary artery wedge pressures with de velopment of pulmonary congestion after isolated clo sure of the interatrial communication [16]. In conclusion, we believe that the concurrence of atrial septal defect and mitral stenosis simply reflects the coexistence of two unrelated diseases which occur together more frequently than by chance alone. Although identifying features of both conditions are generally present, we consider that these features are not so distinctive as to justify application of the term “syndrome” to this combination.
ACKNOWLEDGMENT We are indebted to Dr. Harold W. March, ministration Hospital, for supplying details
Veterans Adof Case 6.
REFERENCES in1. Lutembacher R: De la stenose mitrale avec communication terauriculaire. Arch Mal Coeur 9: 237, 1916. 2. Nadas AS, Alimurung MM: Apical diastolic murmurs in congenital heart disease. The rarity of the Lutembacher’s syndrome. Amer Heart J 43: 691, 1952. 3. Craig RJ, Seizer A: Natural history and prognosis of atrial septal defect. Circulation 37: 805, 1968. by 4. Marshall RJ, Warden HE: Mitral valve disease complicated left-to-right shunt at atrial level. Circulation 29: 432, 1964. 5. Seizer A. Popper RW, Mints F: Evaluation of left-to-right cardiac shunts. J Cardiovasc Surg 5: 285, 1964. 6. Dexter L: Atrial septal defect. Brit Heart J 18: 209. 1956. 7. Tikoff G. Schmidt AM, Kuida H, Hecht HH: Heart failure in atrial septal defect. Amer J Med 39: 533, 1965. 8. Flamm MD, Cohn KE. Hancock RN: Ventricular function in atrial septal defect. Circulation 37, 38: (Supp. VI) 77, 1968. 9. Angelino PF, Garbagni R. Tatara D: Le sydrome de Lutembacher. Observations cliniques et hemodynamiques avant et apres intervention. Arch Mal Coeur 54: 511. 1961.
302
10. Fontana RS. Edwards JE: Congenital cardiac disease: a review of 357 cases studied pathologically. Philadelphia and London, W.B. Saunders. 1962. D 70. 11. Sambhi MP. Zimmermann HA: Pathologic physiology bather’s syndrome. Amer J Cardiol 2: 681. 1958.
of Lutem-
12. Espino-Vela J: Rheumatic heart disease associated with atrial septal defect. Clinical and pathologic study of 12 cases of Lutembacher’s syndrome. Amer Heart J 57: 185, 1959. 13. Ferencz C, Johnson AL, Wiglesworth FW: Congenital mitral stenosis. Circulation 9: 161. 1954. 14. Van der Horst RL, Hastreiter AR: Congenital mitral stenosis. Amer J Cardiol 20: 773, 1967. 15. Soulie P. Acar J, Plainfosse MC: Le syndrome de Lutembacher, a propos de 15 cas. Arch Mal Coeur 57: 158, 1964. 16. Himbert J. Cachin JC, Lenegre J: Une cardiopathie meconnue: La communication interauriculaire (ostium secundum) avec insuffisance mitrale. Presse Med 75: 2507, 1967.
The American
Journal of Medicine
WALTER STEINBRUNN, KEITH
E. COHN,
ARTHUR
Revisited
Five patients are described with large, congenital secundum atrial septal defects combined with acquired rheumatic mitral stenosis. In one additional patient mitral stenosis was associated with a small patency of the foramen ovale, perhaps secondary to atrial wall stretching. Clinically, these cases of Lutembacher’s syndrome may resemble pure mitral stenosis in some instances and pure atrial septal defect in others. The dangers of incomplete diagnosis and surgery are emphasized: Increased pressure developing in the left atrium after closure of the atrial defect resulted in pulmonary edema and death in one case and in reopening of the atrial septal defect in two others. Although not a particularly distinctive syndrome, distinguishing features of both conditions are usually present and may permit establishment of the correct diagnosis.
M.D.+
M.D.
SELZER,
San Francisco,
Syndrome
M.D.
California
The association of atrial septal defect and rheumatic mitral stenosis, customarily referred to as Lutembacher’s syndrome [l], is a recognized pathologic entity; yet its clinical features have not been precisely defined. The older literature stressed the frequency of this syndrome, largely because early workers failed to recognize the fact that the diastolic murmurs of atrial septal defect were due to increased tricuspid flow and did not represent evidence of mitral stenosis [2]. More recently, Lutembacher’s syndrome has been considered to be quite rare. Our purpose here is to review six cases, to attempt to identify the clinical and hemodynamic features which would permit establishment of the diagnosis and to describe the hazards of misdiagnosis. MATERIAL
AND
METHODS
This report includes six patients with a defect in the atrial septum associated with mitral stenosis. Five of these cases were found among 128 consecutive patients
(over the age of eighteen)
with atrial septal defect who were the sub-
ject of an earlier report [3]. The sixth case was a patient seen by one of us (A.S.) at the Veterans Administration Hospital. All patients underwent a complete diagnostic evaluation, which included history, physical examination and electrocardiographic and roentgenographic studies; phonocardiograms were available in three cases. In all patients cardiac catheterization studies were performed, and three had more than one study. Most hemodynamic studies were made when left-sided cardiac catheterizations were not routinely performed, hence a direct gradient across the mitral valve is available only in one patient. All patients underwent cardiac surgery, some more than once. The diagnosis of mitral stenosis was based on the surgical assessment of the mitral valve and was accepted only if the surgeon reported significant obstruction at the mitral valve. In one case (V.A.) mitral stenosis was not recognized during life, but it was found at necropsy * From
the
Hospital, tute
of
fornia.
Cardiopulmonary
Pacific Medical These
Grants
HE
Center,
Sciences,
San
06311,
HE
ship
1.F3-HE-36,084.01 of Health, grant
Arthur Webster
for Seizer,
the
Volume
San
Medical Francisco,
Insti-
and
in
Special
the
Calipart
Fellow-
National and
Heart
by
Instia fellow-
Association.
be addressed Center, California
to
Clay
Dr. and
94115.
Cardiopulmonary
Unit,
Birmensdorferstrasse
497,
Switzerland.
48, March
Area
the
Francisco,
Maryland,
should
address:
Stadtspital-striemli Zurich,
Bay
Pacific
Streets,
t Present
from
reprints
Presbyterian and
supported
5497
Bethesda,
from
Requests
were
studies
tutes ship
Unit,
Medical
1970
CASE
REPORTS
Case 1. This thirty-nine
year old woman (M.B.) had had a cardiac murmur since childhood. There was a history of rheumatic fever, the details of which were not available. In 1958, at the age of thirty-six, while virtually asymptomatic, she underwent a diagnostic study that included cardiac catheterization, and the diagnosis of atrial septal defect was established. In March 1958 closed repair of the atrial septum was performed. Shortly after the operation shortness of breath and easy fatigability developed. The patient was admitted to the hospital for study in April 1960. Physical examination revealed prominent jugular venous pulsation with the patient in the sitting position. The lungs were 295
TtiE
LUTEMBACHER
SYNDROME
-
STEINBRUNN
ET AL.
AVL
AVR
AVF
Comment:
This case demonstrates that mitral stenosis may be masked when associated with a secundum atrial septal defect. Both the right and left atrial pressures were initially normal in this case, since the defect a:. lowed decompression into the systemic veins. Closure of the defect, however, evoked an increase in pressure within the left atrium, thus precipitating the onset of symptoms and reopening of the atrial septal defect.
Case 2.
This fifty-seven year old woman (V.A.) had had an attack of rheumatic fever at the age of nine. She was known to have had a heart murmur since then but had remained Fig. 1. left
and
and
right
Case 1. Electrocardiogram possibly
right
ventrxular
atrial
of patient
showing sinus rhythm, right QRS axis deviation
enlargement.
hypertrophy.
clear. Increased precordial motion was noted. The first heart sound was accentuated and the second sound showed wide splitting that did not vary with respiration. An ejection type systolic murmur was heard along the upper left sternal border: auscultation in the apical region revealed a pansystolic murmur of medium intensity and a long diastolic rumbling murmur. An electrocardiogram showed biatrial hypertrophy, right axis deviation of the QRS axis, incomplete rjght bundle branch block and right ventricular hypertrophy (Fig. 1). Chest roentgenogram showed a vigorously pulsating, enlarged hilar vasculature; right atrial and right ventricular enlargement were also noteworthy. Repeat cardiac catheterization (Table I) showed a large left to right shunt at the atrial level, increased right and left atrial pressures and moderate pulmonary arterial hypertension. The physical and catheterization findings at that time were thought to indicate the diagnosis of Lutembacher’s syndrome. An operation, performed in February 1961, confirmed the coexistence of severe mitral stenosis with some valvular incompetence and a large atrial septal defect. Both lesions were corrected: the patient made an uneventful recovery and has remained asymptomatic.
TABLE
I
Cardiac
Catheterization
asymptomatic until 1956. At that time, at the age of fortyseven, she experienced dyspnea and palpitations, and atrial fibrillation was found. Her clinical condition remained satisfactory, controlled by digitalis, until 1960 when symptoms became more severe and fluid retention developed: this was only partly relieved by the administration of diuretics. When seen in 1966 she appeared chronically ill, and her exercise tolerance was limited. Physical examination revealed jugular venous pulsation, with a prominent V wave, extending to the lobes of the ear. The lungs were clear. A marked parasternal lift was present. The first sound was loud the second sound widely split and fixed. In addition,
opening snap was heard, followed by a diastolic rumbling murmur. A diffuse pansystolic murmur was present, which increased in intensity with inspiration. The patient had a large, pulsating liver and marked ankle edema. An electrocardiogram showed atrial fibrillation, right axis deviation and incomplete right bundle branch block with evidence of right ventricular hypertrophy (Fig. 2). A chest roentgenogram showed marked cardiomegaly with enlargement of both atria and the right ventricle. The central hilar vessels appeared as large “cannon balls” and then tapered peripherally; there was a hilar dance and calcification of the left pulmonary artery (Fig. 3). A clinical diagnosis of pulmonary hypertension and tricuspid insufficiency, presumably due to mitral stenosis, was made. At catheterization, however, an atrial septal defect was discovered, and on the basis of a left atrial pressure of only 11 mm Hg the diagnosis of mitral stenosis was discarded.
Findings
Case4
Case1 Z/7/58
Data Arterial oxygen saturation Pulmonary cardiac
(%)
94
4/4/69 92
Case 2 Z/17/66 88
Case3 3/8/57
~ 5/22/57
94
94
4/22/58 97
Case 6 Case 5 Z/4/65 93
3/17/60 ...
6/10/66 95
index (L/min/M*) Systemic cardiac
9.4
20.0
3.9
7.3
4.8
5.3
7.0
...
2.8
index (L/min/Mt) Pulmonary: systemic
2.6
3.0
1.4
2.1
2.2
2.0
2.9
...
1.6
3.5:1 2.2:1 4:l 2.8:l 3.6:1 flow ratio 13 9 v = 25, 15 v = 14, 10 6 Right atrium (mm Hg) 68/15 59/8 63/O-20 60/O-9 27/O-2 Right ventricle (mm Hg) 65/22, 35 57/29, 39 60/25, 37 26/10, 15 65/26, 44 Pulmonary artery (mm Hg) 17 9+ 20 v = 15,11+ . ,. Pulmonary artery wedge (mm Hg) ’’’ ... ... ... Left ventricle (mm Hg) 174/75, 108 ::: 110/64, 80 82/50, 62 ... Systemic artery (mm Hg) Total pulmonary resistance Pulmonary vascular resistance Total systemic resistance (dynes
set
cm-&/l.7 Mz)
70
... ...
NOTE: Underscore figures equal mean * = right-to-left shunt of 0.5 L/min. + = left atrial pressure. 296
left and an
90 50
1,200
500 350
2,300
220 110
2,300
380 290
...
2.6:1 14 73/14 76/28, 43 *.*
*” 103/75, 85 380
... 2,000
.., 1.75:1 2.4:l 5 v = 20, 19 v = 19, 13 40/O-8 100/27 46/5-g 35/16, 28 115/60, 72 46/21, 30 18 35 v = 40,23 9. . 117/O-17 ... 142/86, 146/90, 107 150/80, lJ3 100 ... 1,020 240 ... 530 50
2,000
...
2,450
pressure.
The American
Journal of Medicine
THE
LUTEMBACHER
SYNDROME
STEINBRUNN
-
Case 3.
This forty-three year old man (R.D.) had had no definite history of rheumatic fever in childhood but had suffered from repeated sore throats. He had no knowledge of cardiac disease until the age of twenty-seven when he
Fig. of
3.
Case
patient
and
Volume
the
2.
Chest
show right
48,
marked ventricle.
March
1970
roentgenograms cardiomegaly There
is
(posteroanterior with marked
and
lateral)
AL.
AVF
AVL
At surgery a large secundum atrial defect and severe tricuspid regurgitation with rupture of two chordae tendineae arising from the anterior leaflet of the tricuspid valve were found. The atrial septal defect was sutured closed and the tricuspid valve was repaired by valvuloplasty and anuloplasty. The mitral valve was described as normal on palpatory exploration. The postoperative course was complicated by respiratory insufficiency, and mechanical respiratory assistance was required for several weeks. The patient died two months later; postmortem examination revealed the associated rheumatic mitral stenosis.
Comment: This case exemplifies the potential hazards of failing to recognize mitral stenosis in a case of Lutembacher’s syndrome, with consequent mortality from the intractable pulmonary congestion following closure of the atrial septal defect. It also demonstrated an unusual and apparently rare cause of tricuspid insufficiency; the mitral stenosis and atrial septal defect evidently led to massive dilation of the right heart chambers, perhaps producing stretch and increased tension on some of the tricuspid chordae and eventual rupture. At postmortem the tricuspid valve was thought not to be involved in the rheumatic process, and there was no evidence of bacterial endocarditis.
ET
,
Fig.
2.
tion,
Case
right
bundle
2.
axis
branch
Electrocardiogram deviation
block
of
which
the may
of
patient
showing
QRS
segment
and
signify
right
ventricular
atrial
fibrilla-
incomplete
right
hypertrophy.
began to have attacks of rapid heart action. The diagnosis of mitral stenosis was made, and the arrhythmia was recognized as paroxysmal atrial flutter. Two years later atrial flutter became chronic despite quinidine therapy, and the ventricular rate was controlled by digitalis. Within the next five years the patient experienced two episodes diagnosed as embolism to the kidneys. In 1956, at the age of fortytwo, right ventricular failure developed with fluid retention; this was initially controlled by diuretics but subsequently became more and more resistant to therapy. The patient was admitted to the hospital in May 1957 in intractable
branches
enlargement
of
both
atria
of
dilatation
of
the
hilar
aneurysm
the
of
both
vessels of the
pulmonary
arteries
beyond
the
hilar
left
pulmonary
regions
with
rapid and
decrease
calcification
in of
caliber a
large
artery.
297
THE
LUTEMBACHER
cardiac
failure.
marked
left
sound,
widely
SYNDROME
-
Pertinent
STEINBRUNN
physical
parasternal
lift,
split
sound,
second
an
ET
findings
included
accentuated followed
AL.
a
was
found.
first
heart
stenosis
by a mitral
open-
suggesting
In
addition,
of the mitral that
some
a
clinically
unsuspected
valve was found
with
a valve
insufficiency
of the
valve
severe deformity was
aIs,)
ing snap. There was an apical diastolic rumbling murmur as well as a moderately loud apical pansystolic murmur, which
present. Ivalonv
increased with inspiration. A systolic ejection type murmur was present at the base of the heart on both sides of the sternal border. An early diastolic blowing murmur was heard at the lower left sternal border. The patient appeared cyanotic with a malar flush. A jugular venous pulse was visible
were performed. ‘The initial postoperative course was satisfactory, but on the third postoperative day cardiac arrest occurred and the patient could not be resuscitated. Autopsy revealed a completely closed lnteratrial defect and a successfully repaired rheumatic mitral stenosis (Table II).
with the patient in the sitting position, ears. The lungs were clear. The liver
up to the lobe of the was greatly enlarged
and showed considerable pulsation. Moderate anasarca was present. The patient’s electrocardiogram showed complete right bundle branch block and atrial fibrillation. A chest roentgenogram revealed a markedly enlarged right atrium and dilated right ventricle, a slightly enlarged left atrium and a normal left ventricle with bulging pulmonary arteries and signs of pulmonary hypervascularity. On the basis of the clinical findings a diagnosis of mitral stenosis with secondary tricuspid incompetence was made. Cardiac catheterization was performed on March 8, 1957. The findings, presented in Table I, established the additional diagnosis of atrial septal defect. Because of the desperate clinical situation surgical treatment was attempted, combining mitral commissurotomy with repair of the atrial septum, using a modified Sondergaard technic. At operation a tight mitral stenosis and a large atrial septal defect were found. The patient did not survive the procedure. Permission to perform
an autopsy
electrocardiogram
partial
right
pertrophy. megaly signs
bundle A chest
with of
pulmonary
was performed, 298
large
showed branch
atrial
block
fibrillation,
and
right
roentgenogram
revealed
dilated
pulmonary
central
hypetvascularity.
and at operation
Open
a large atrial
right
arteries heart septal
and
with the aid of ail and valvuloplast~{
of the v,alve commissures effected. The patient’s condition improved but within five years her symptoms recurred, and in November 1960 she underwent repeat operation. At that time closed transventricular mitral valvulotomy was performed. The patient showed clinical improvement again until 1964, when clinical symptoms recurred. She entered this hospital in February 1965 for diagnostic evaluation. Physical examination showed jugular venous pulsation with the patient in the sitting position. The lungs were clear. cardiac findings included accentuation wide and fixed splitting of the second
of the sound
and an opening snap, initiating an apical diastolic rumbling murmur. In addition, an apical pansystolic murmur radiating to the axilla was described (Fig. 4). Severe hepatomegaly and edema were present. Electrocardiogram showed atrial fibrillation, right axis deviation of the QRS, incomplete right bundle branch block and right ventricular hypertrophy (Fig.
TABLE II Case No.
Patient
Summary
of Pathologic
Atrial Septal
and
Defect
Surgical
Mitral
Findings
Valve
M.B.
Ostium secundum 4by3cm
Stenotic and somewhat incompetent
V.A.
Ostium secundum 4by5cm
Marked degree of thickening of the leaflets and more pronounced thickening and shortening of the chordae tendineae-two chordae of the anterior leaflet ruptured
R.D.
Ostium secundum 4by5cm
Very tight, calcified
R.C.
Ostium secundum 5 by3cm
Tight stenosis with thickening and fusion of the cusps and chordaeleakin the anterior commissure
C.W.
Ostium secundum with calcified rim 4 by3cm
Moderately stenotic with fusion of the chordae
J.R.
Patent foramen ovale 1 by 1 cm
Completely destroyed calcified-obliteration of the commissures subvalvular fusions
hy-
cardio-
was closed valvulotomy
heart disease was obtained, as both her mother and sister had mitral stenosis. She was known to have a cardiac murmur but remained asymptomatic until the age of thirtyfour when, in 1953, palpitations and dyspnea developed, and atrial fibrillation was noted. Later that year closed mitral valvulotomy was performed. At operation a tight mi. tral stenosis was found and a satisfactory finger fracture
axis,
ventricular marked
defect mitral
This forty-six year old woman (R.W.) had had Case 5. chorea at the age of twelve. A family history of rheumatic
Auscultatoty first sound,
was refused.
Case 4. This forty-six year old woman (R.C.) was known to have a cardiac murmur since the age of eleven. At the age of thirty-two she had an illness diagnosed as acute rheumatic fever, the details of which were not available. In 1952, at the age of forty, she experienced dyspnea on effort in association with palpitations. The condition remained stationary until 1956, when she was striken with a left-sided hemiparesis. Following recovery from this episode in May 1957, she underwent cardiac catheterization. The diagnosis of atrial septal defect was made, and surgical repair was undertaken elsewhere in September 1957, using the hypothermia technic. The patient’s symptoms were not relieved by the operation, and gradually her condition worsened. In April 1958 a repeat cardiac catheterization study was performed (Table II) which showed persistence of an interarterial shunt comparable with that prior to the operation. Pulmonary arterial pressures were higher than in the previous study. The patient entered this hospital in August 1958 showing evidence of severe cardiac failure. Upon physical examination a cyanotic tinge was noted. A large jugular venous wave pulse was visible with the patient in the sitting position suggesting the presence of tricuspid insufficiency; the lungs were clear. Examination of the heart revealed exaggerated precordial motion; the first sound was loud, the second sound was widely split, followed by an opening snap. A mid-systolic ejection type murmur was present at the left upper sternal border; at the apical region a loud pansystolic murmur was heard, followed by the mid-diastolic rumbling murmur. In addition, an early diastolic blowing murmur was heard at the lower left sternal border. Moderate hepatomegaly was present and ankle edema was noted. The patient still exhibited residual changes from her hemiplegia. The
The septal patch, and
surgery defect The
American
scarred
Journal
and
and and
of Medicine
THE
5). An electrocardiogram right atrial enlargement.
taken Chest
LUTEMBACHER
SYNDROME
-
STEINBRUNN
ET
AL.
in 1953 had shown left and roentgenogram revealed en-
largement of both atria and of the right ventricle with engorgement of the central pulmonary vessels and the presence of Kerley’s B lines (Fig. 6). Cardiac catheterization was performed in February 1965 for the first time (Table I). It revealed a clinically unsuspected left to right atrial shunt of moderate proportions. The diagnosis of mitral stenosis and atrial septal defect was thus established. At operation, open mitral valvulotomy and valvuloplasty and closure of a moderately large secundum type atrial septal defect were accomplished. Her recovery was uneventful and she has remained well.
AORTA *Y-
Case 6.
This forty-one year old man (J.R.) was found to have a heart murmur at the age of twenty-one. There was no history of rheumatic fever, but he had suffered from repeated bouts of “growing pains” in childhood. He remained asymptomatic until the age of thirty-five, in 1960, when
dyspnea on effort and easy fatigability developed. Cardiac catheterization was performed in 1960 (Table I) and the findings confirmed the clinical diagnosis of mitral stenosis
followed
and insufficiency.
components
candidate
pulse
for
The patient was not considered a suitable cardiac surgery and was maintained on a
medical regimen for the next six years. Gradually he became more symptomatic and in June 1966 was readmitted for reinvestigation. At that time he appeared to be in right and left ventricular failure. Physical examination revealed prominent jugular venous pulse with the patient in the sitting position. Auscultatory findings included accentuation of the first heart sound and fixed splitting of the second sound. No opening snap was heard. A moderately loud pansystolic apical murmur was heard as well as a long apical diastolic rumbling murmur. An early diastolic blowing murmur was also audible at the left sternal border. Moderate hepatomegaly was present, as was mild peripheral edema. The electrocardiogram showed sinus rhythm, left atrial enlargement and incomplete right bundle branch block. A chest roentgenogram indicated moderate cardiomegaly with evidence of pulmonary venous congestion. Cardiac catheterization was performed in June 1966 (Table II). The presence of mitral stenosis with pulmonary hypertension and a 1.7:1 atrial left to right shunt were found. There was also a large pressure differential between the right atrium (19 mm Hg) and left atrium (pulmonary artery wedge pressure = 35 mm Hg). On June 21 another procedure was performed, which included transseptal left heart catheterization and angiocardiographic study with injection into the left atrium, demonstrating the interatrial shunt directly. In August 1966 open heart surgery was performed with replacement of the mitral valve with a ball-valve prosthesis and closure of a patent foramen ovale.
Fig.
4.
heart
Case sound
5.
Phonocardiogram
(8)
by an
and
wide
opening
of the
snap
second
of
splitting (0,s.).
heart
of
Volume
48,
March
1970
the
AZ and
sound.
showing
second R
CP =
=
a
sound
aortic
indirect
loud
first
(0.06
set)
and
pulmonic
carotid
arterial
tracing.
spection of the atrial septum and of the mitral valve during open heart surgery. In one patient (Case 2) the mitral valve was examined during surgery by palpatory exploration only. In two patients autopsy findings also were available. A summary of the anatomic findings is presented in Table II. In five patients a large, secundum-type congenital atrial septal defect was present. In one patient (Case 6) a small patency of the foramen ovale was found. All patients showed typical rheumatic scarring of the mitral valve leading to gross deformity of that valve and producing either pure mitral valve stenosis or insufficiency with predominant stenosis. It is clear from these findings that in five of the six cases congenital atrial septal defect coexisted with acquired, rheumatic mitral valve disease. The possibility exists that in the sixth case patency of the foramen ovale may have developed secondarily to stresses upon the atrial wall from the valvular disease [4]. Clinical Features. A history of rheumatic fever was obtained in four patients; in two the presence of rheumatic fever in childhood was considered possible but not definite. The patients remained asymptomatic until the
COMMENTS In reviewing the combined
presence of mitral stenosis and atrial septal defect, three fundamental questions should be considered: (1) Does this combination constitute a true syndrome, that is, a distinctive clinical pattern, rather than the coexistence of two unrelated diseases? (2) Can the diagnosis of the combined lesions be made clinically? (3) Does either of the diseases alter the course and prognosis of the other? In order to answer these questions, the salient features of the six patients described will be analyzed and discussed in the light of previously expressed views concerning the Lutembacher syndrome. Anatomic Features. Description of the anatomic findings in five cases of this series is based on surgical in-
patient
AVR
Fig.
5.
Case
l&ion,
right
bundle
branch
5. axis
Electrocardiogram deviation
block
which
of the may
in QRS signify
patient segment right
AVL
showing and ventricular
AVF
atrial incomplete
fibrillaright
hypertrophy.
THE
Fig. of
LUTEMBACHER
6. patient
ventricle
Case
5.
reveal with
SYNDROME
Chest
roentgenograms
moderate
engorgement
-
enlargement of the
central
STEINBRUNN
ET
(posteroanterior of
both
pulmonary
atria
AL.
and and vessels
lateral) the
right
in the
more origlnal
distally.
Kerley
B lines
It
Ihe
right
base
were
e ,i-
roentgenogram
tapering
ages of twenty-seven to forty-seven years (average time of onset of symptoms, thirty-seven years). The duration of symptoms until the diagnostic evaluation varied from three to sixteen years (average nine years). Palpitation was the initial symptom in four patients; dyspnea on efort was present in five and easy fatigability in all cases. One patient underwent closure of the atrial septal defect while asymptomatic (Case l), but dyspnea developed after the first operation. Only one patient (Case 6) had a history of orthopnea and paroxysmal nocturnal dyspnea. Hemoptysis, marked cyanosis or clubbing was not found in our series. Evidence of congestive heart failure with edema, anasarca and pulsatile neck veins was observed at some point in the course of all cases. Large V waves, which were assumed initially to represent tricuspid insufficiency, were noted in five patients. Bedside examination at first suggested the diagnosis of isolated mitral stenosis in four instances, and atrial septal defect in two, although in retrospect these patients actually did present with physical findings characteristic of both lesions. A parasternal heave-presumably right ventricular in origin-a loud or snapping first sound and wide splitting of the second sound were uniformly either heard or noted on the phonocardiogram. An opening snap was present in four cases. A pansystolic murmur, heard at the left sternal border and apex, was noted in all cases; in two this murmur seemed to increase in intensity with inspiration. Hence the diagnosis of mitral stenosis with associated mitral or tri300
moderately dent
cuspid regurgitation was frequently considered. An ejection-type systolic murmur was mentioned specifically in three cases. In addition to the characteristic apical diastolic murmur, heard in six patients, a higher pitched parasternal diastolic murmur, probably due to increased tricuspid flow, was described in two cases. Electrocardiographic examination of the patients revealed atrial fibrillation or flutter in four patients. Five patients had a rightward QRS-axis deviation and incomplete right bundle branch block with evidence of right ventricular hypertrophy. One patient had a complete right bundle branch block and the patient with patent foramen ovale (Case 6) had a normal QRSaxis. Roentgenographic examination disclosed varying degrees of cardiac enlargement. The right atrium was markedly dilated in all patients, whereas the left atrium was normal or only slightly enlarged in four. Two patients had marked left atrial enlargement (Cases 5 and 6). In these two patients the pressures in the left atrium were significantly higher than in the right atrium (Table I). The left ventricle was normal or slightly enlarged in five patients, whereas in one (Case 6) moderate prominence of the left ventricle was noted. Dilated, vigorously pulsating pulmonary arteries and their branches combined with roentgenologic evidence of pulmonary hypervascularity was noted in five patients (Cases 1 through 5). In two patients there was evidence of pulmonary venous congestion (Kerley’s B-lines), and in one The
American
Journal
of Medicine
THE LUTEMBACHER
(Case 2) these developed after closure of the atrial septal defect. From the diagnostic standpoint, then, it is clear that some of our patients were considered clinically to have simple atrial septal defects and others to have simple mitral stenosis, depending upon the predominant clinical features; one lesion tended to mask the other. Yet this review of the clinical features, particularly the findings on physical examination and phonocardiography, suggests that with an especially high index of suspicion the correct diagnosis can be established. Among noteworthy signs are the joint presence of a widely split second sound showing little respiratory variation, an opening snap and accentuation of the first heart sound. The presence of a diastolic rumbling murmur in the apical region need not indicate mitral stenosis, for such transmission of a tricuspid flow murmur occurs in patients with pure atrial septal defect and very large right ventricles extending to the apex of the heart: however, audibility of the diastolic rumble over an unusually long area might be suspicious of mitral stenosis in a case otherwise suggesting atrial septal defect. The electrocardiogram is helpful in patients with clearcut clinical signs of mitral stenosis since incomplete or complete right bundle branch block would then suggest the possibility of an atrial septal defect. The chest roentgenogram and fluoroscopic examination may be valuable when large pulmonary arterial branches with excessive pulsation and suggestion of increased blood flow to the lungs are associated with a large right atrium. Hemodynamic Findings (Table I). In all patients the oxygen content of blood obtained from the right atrium, and downstream from it, was higher than that in the superior vena caval blood. Calculation of flow ratios was made on the basis of superior vena caval blood as representing systemic venous return, which has been shown to have an oxygen content reasonably close to that of pulmonary arterial blood in patients without shunts [5]. On this basis, all patients but one (Case 6) had pul-. monary flows greater than two and one half times the systemic flow. The systemic cardiac index was smaller than 2.5 L per minute per M2 in four patients and normal in two. Another consistent finding in this series was the elevation of right atrial pressure with prominence of V waves. Systemic venous congestion and elevated right atrial pressures are usually seen only in the older patients with isolated atrial septal defect and often appear after the onset of chronic atrial fibrillation [3]. Systemic venous congestion in cases of pure atrial defect is considered by Dexter [6] and Tikoff et al. [7] to reflect left rather than right ventricular failure, although more recently Flamm et al. [8] have shown that this may be caused by failure of either ventricle. The cases described herein emphasize the importance of considering other possible factors in the genesis of systemic congestion in atrial septal defect. In most of our cases the mitral stenosis elevated the left and, by continuity, the right atrial pressures. By causing pulmonary hypertension and right ventricular failure, the increase in systemic venous pressure was probably potentiated. We have also seen three patients with rheumatic mitral insufficiency and secundum atrial septal defects. Clinically these patients Volume 48, March
1970
SYNDROME
-
STEINBRUNN
ET AL.
seemed to have mitral regurgitation with tricuspid insufficiency with widely radiating pansystolic murmurs and markedly pulsatile neck veins with large V waves. At surgery the absence of tricuspid regurgitation was demonstrated in all instances. The V waves in the neck, therefore, were merely reflections of the mitral reflux. The ruptured chordae tendineae producing severe tricuspid insufficiency in one of our patients (Case 2) provides yet another source of increased venous pressure in cases such as these. Pressures in the pulmonary artery were elevated in all patients, but pulmonary vascular resistance was not appreciably increased in any except the one with the patent foramen ovale. A hyperkinetic type of hypertension, therefore, appears most common. Incidence, Significance and Definition of Lutembacher’s Syndrome. Since 1813 the association of atrial septal defect with mitral stenosis has been described many times. Lutembacher [l] drew special attention to the condition in 1916 and described it as an anatomic and pathophysiologic entity. Because of the misunderstanding of the mid-diastolic murmur found in atrial septal defect, Lutembacher’s syndrome was previously diag nosed with great frequency. Nadas and Alimurung [2] were the first to point out the rarity of this syndrome and to emphasize the proper, tricuspid origin of the diastolic flow murmur in the atrial septal defect. In an autopsy series of 25,000 cases from five Boston hospitals, five cases of Lutembacher’s syndrome and eighty-seven cases of atrial septal defect were found. Angelino et al. [9] found six cases of this syndrome among 120 cases of atrial septal defect and 2,000 cases of mitral stenosis. Fontana and Edwards [lo] reported thirty-one examples of isolated atrial septal defect and two instances of Lutembacher’s syndrome. Our results show a similar incidence: Five cases of Lutembacher’s syndrome were found among 128 cases of adult atrial septal defect and 700 to 800 cases of mitral stenosis. The prevalence in our series is therefore 4 per cent of cases of atrial septal defect and 0.6 to 0.7 per cent of cases of mitral stenosis. The incidence of mitral stenosis in patients with atrial septal defect thus appears to be considerably higher than a chance coexistence of two diseases. This notion is supported by the figures cited and by the fact that not a single instance of mitral stenosis was found in association with other common congenital lesions (ventricular septal defect, pulmonary stenosis) in our series. The cause for preferential acquisition of rheumatic mitral stenosis by patients with congenital atrial septal defect is not known. Lutembacher believed that the defect within the atrial septum was congenital, rather than an acquired, stretched foramen ovale. The findings of large secundum atrial septal defects in Cases 1 through 5 tend to substantiate the congenital nature of this anomaly. One patient (Case 6) in this series merely had a patent foramen ovale, considerably smaller than the other defects, perhaps secondary to atrial stretching in the course of mitral stenosis [4], and therefore should not be considered as an example of Lutembacher’s syndrome [ll]. He is included nonetheless, for purposes of contrast. In Lutembacher’s original case there was no history of rheumatic fever and he, and several other 301
THE
LUTEMEACHER
SYNDROME
-
STEINBRUNN
ET AL.
early workers, assumed that the mitral lesion was of congenital origin. More recent pathologic and surgical observations. however, as well as the findings in this series, support the contention that the mitral stenosis is of rheumatic etiology in the majority of the cases of Lutembacher’s syndrome. All of Espino-Vela’s [12] cases were pathologically proved examples of rheuma. tic mitral stenosis. Ferencz et al. [13] and Van der Horst and Hastreiter congenital
an associated Having atrial
in their
secundum defect
concerning
that
this
and acquired
when
the
the two lesions
mitral
of congenital stenosis
rare, it is necessary
of the two lesions previously
point
were
purely
clarified.
[9,11,15]
and our
series
imposition
of mitral
stenosis
considerations
speculative,
concepts However,
have shown
is unto con-
to each other.
published
hemodynamic
were
with
who had
atrial septal defect.
but not exquisitely
It is obvious
of 122 children
that the coexistence
sider the relationship
written
review
stenosis found only one patient
established
septal
common,
[14]
mitral
recent that
upon an atrial
mostly
of neither the
of
studies super-
septal defect
the usually benign may, in some cases, complicate course of the atrial septal defect [3]. The same is true for an atrial septal defect associated with mitral insufficiency [16].
On the other hand, it is likely that the atrial septal defect exerts a protective influence upon mitral stenosis by decompressing the left atrium and the pulmon ary venous system. This thesis is based upon the obse-vations that our patients experienced no paroxysmal attacks of dyspnea or pulmonary edema; moreover, closure of the atrial septal defect in two cases exacerbated the signs and symptoms of pulmonary congestion. This belief is also supported by observations on four patients with ostium secundum atrial septal defect and mitral insufficiency who showed a significant rise in pulmonary artery and pulrnonary artery wedge pressures with de velopment of pulmonary congestion after isolated clo sure of the interatrial communication [16]. In conclusion, we believe that the concurrence of atrial septal defect and mitral stenosis simply reflects the coexistence of two unrelated diseases which occur together more frequently than by chance alone. Although identifying features of both conditions are generally present, we consider that these features are not so distinctive as to justify application of the term “syndrome” to this combination.
ACKNOWLEDGMENT We are indebted to Dr. Harold W. March, ministration Hospital, for supplying details
Veterans Adof Case 6.
REFERENCES in1. Lutembacher R: De la stenose mitrale avec communication terauriculaire. Arch Mal Coeur 9: 237, 1916. 2. Nadas AS, Alimurung MM: Apical diastolic murmurs in congenital heart disease. The rarity of the Lutembacher’s syndrome. Amer Heart J 43: 691, 1952. 3. Craig RJ, Seizer A: Natural history and prognosis of atrial septal defect. Circulation 37: 805, 1968. by 4. Marshall RJ, Warden HE: Mitral valve disease complicated left-to-right shunt at atrial level. Circulation 29: 432, 1964. 5. Seizer A. Popper RW, Mints F: Evaluation of left-to-right cardiac shunts. J Cardiovasc Surg 5: 285, 1964. 6. Dexter L: Atrial septal defect. Brit Heart J 18: 209. 1956. 7. Tikoff G. Schmidt AM, Kuida H, Hecht HH: Heart failure in atrial septal defect. Amer J Med 39: 533, 1965. 8. Flamm MD, Cohn KE. Hancock RN: Ventricular function in atrial septal defect. Circulation 37, 38: (Supp. VI) 77, 1968. 9. Angelino PF, Garbagni R. Tatara D: Le sydrome de Lutembacher. Observations cliniques et hemodynamiques avant et apres intervention. Arch Mal Coeur 54: 511. 1961.
302
10. Fontana RS. Edwards JE: Congenital cardiac disease: a review of 357 cases studied pathologically. Philadelphia and London, W.B. Saunders. 1962. D 70. 11. Sambhi MP. Zimmermann HA: Pathologic physiology bather’s syndrome. Amer J Cardiol 2: 681. 1958.
of Lutem-
12. Espino-Vela J: Rheumatic heart disease associated with atrial septal defect. Clinical and pathologic study of 12 cases of Lutembacher’s syndrome. Amer Heart J 57: 185, 1959. 13. Ferencz C, Johnson AL, Wiglesworth FW: Congenital mitral stenosis. Circulation 9: 161. 1954. 14. Van der Horst RL, Hastreiter AR: Congenital mitral stenosis. Amer J Cardiol 20: 773, 1967. 15. Soulie P. Acar J, Plainfosse MC: Le syndrome de Lutembacher, a propos de 15 cas. Arch Mal Coeur 57: 158, 1964. 16. Himbert J. Cachin JC, Lenegre J: Une cardiopathie meconnue: La communication interauriculaire (ostium secundum) avec insuffisance mitrale. Presse Med 75: 2507, 1967.
The American
Journal of Medicine