Mitral heart
valve prolapse disease
in adults
with
congenital
James M. Rippe, B.A. Laurence J. Sloss, M.D. Gerald Angoff, M.D. Joseph S. Alpert, M.D. Boston,
Mass.
During the 15 years since Barlow and associates demonstrated that the click-murmur syndrome could be explained by mitral valve prolapse,’ the syndrome has continued to spark considerable interest. Barlow and colleagues’ initially suggested that the syndrome could arise from diverse etiologies. Recent angiographic and echocardiographic studies have confirmed this suggestion, greatly expanding the list of possible etiologies and conditions associated with mitral valve prolapse.:‘-” The association between atria1 septal defect and mitral valve prolapse (MVP) was noted in Barlow’s initial group of patients9 and was elaborated by subsequent investigators.‘0-17 Pocock and Barlow?’ also reported mitral valve prolapse associated with other congenital lesions including Eisenmenger’s syndrome (one case), and patent ductus arteriosus (one case) without noting an increased incidence of prolapse in these conditions. Recently, Ebstein’s anomaly has been added to the list of congenital lesions with associated mitral valve prolapse.‘* Questions remain concerning the spectrum of congenital diseases in which mitral valve prolapse occurs, the frequency of prolapse, possible etiologic links between the two entities, and the natural history of the combined lesions. During the past three years, echocardiograms have been performed at the Peter Bent Brigham From the Cardiovascular Boston, Mass.
Division,
Peter
Received
for publication
Sept.
6, 1978.
Accepted
for publication
Nov.
13, 1978.
Reprint requests: Joseph sion of Medicine, University Avenue North, Worcester.
0002~8703/79/050561
S. Alpert, M.D., of Massachusetts Mass. 01605.
+ 13$01.30/O
Bent
Brigham
Chief, Cardiovascular Medical Center,
0 1979 The
Hospital,
Diti55 Lake
C. V. Mosby
Co.
Hospital Heart Station on 120 adults with congenital heart disease, comprising virtually all patients with congenital heart lesions seen at the Peter Bent Brigham Hospital during this period. Mitral valve prolapse was present with surprising frequency in this group, with 40 documented cases (34 per cent of the entire group): ASD secundum, nine cases; VSD, 10 cases; PDA, five cases; tetralogy of Fallot, three cases; Ebstein’s anomaly, two cases; and miscellaneous congenital heart lesions, four cases. We report these 40 patients and discuss possible etiologic links and clinical relevance. Materials
and methods
Echocardiograms were examined from 120 adults with congenital heart disease studied in the Peter Bent Brigham Hospital Heart Station between December 1,1974, and December 1,1977. Since a large children’s hospital, Children’s Hospital Medical Center, is located in close proximity to the Peter Bent Brigham, children are rarely examined at our hospital, and no individual under the age of 17 is included in the present series. Forty patients (20 males and 20 females) ranging in age from 17 to 57 years, were found to have mitral valve prolapse. They had been referred for a variety of reasons. Many had been followed for congenital heart defects since childhood and had reached a point where definitive correction was felt to be necessary. Others had undergone repair of congenital defects as children, and were receiving routine periodic follow-up. Some patients were studied as part of regular care for lesions not considered significant enough to require surgical intervention. Finally, a small group of patients
American
Heart
Journal
561
Rippe
et al.
I. Prevalence of mitral valve prolapse with each type of congenital heart disease
Table
Type of CHD ASD II” ASD I” VSD PDA TOF PS Congenital LV outflow obstruction Ebstein’s anomaly Miscellaneous Totals
Total no. studied
No. with associated MVP
% with associated MVP
32 5 25 7 5 15 14
9 0 10 5 3 5 2
28% 0% 40% 71% 60% 33% 15%
3 14
2 4
67% 29%
120
40
33%
with abnormal cardiac examinations were studied and were found to have previously undiagnosed congenital lesions. None of the 40 patients was initially referred for evaluation of possible mitral valve prolapse. The diagnosis of congenital heart disease was confirmed by cardiac catheterization in the majority of patients with hemodynamically significant disease. In the remainder, the diagnosis was established by clinical evidence with supporting noninvasive examinations. The diagnosis of mitral valve prolapse was made by established echocardiographic criteria.lg All of the patients exhibited the characteristic pattern of posterior buckling or bulging of the mitral valve apparatus during systole, and displayed either late systolic “bowing” or holosystolic “hammocking.“2n Echocardiograms were obtained using standard techniques and were recorded on commercially available Irex or Smith-Kline recording devices interfaced with Irex strip chart recorders and 2.25 or 3.5 MHz transducers. The mitral valve was visualized in standard views” with particular care exercised to avoid “pseudo prolapse” or inferior angulation of the echo transducer which might alter the apparent location of the mitral valve.‘? Results a. ASD secundum. Of 32 patients with ASD secundum studied, nine (28 per cent) had associated mitral valve prolapse (Table I). One of the nine also had anomalous pulmonary venous
562
drainage, while the remaining eight patients had ASD secundum without associated anomalies. Eight of the nine patients had experienced at least mild shortness of breath or fatigue while only two were troubled by chest pain. Palpitations occurred in five of the nine patients (56 per cent). None had contracted SBE (Table II). Physical examination prior to surgical intervention revealed murmurs typical of ASD in eight of nine patients (89 per cent), the only exception being a patient whose ASD had been repaired. A murmur compatible with the click-murmur syndrome was heard in only one patient (11 per cent). In this patient, a mid-systolic click was noted on one physical examination and was confirmed by phonocardiography. Electrocardiograms were typical for ASD with either complete or incomplete right bundle branch block in all nine patients. In addition, RVH was present in four patients, and nonspecific ST and T wave abnormalities were present in three patients. On echocardiogram, both holosystolic and late systolic mitral valve prolapse were observed (Fig. 1). Surgical correction, undertaken in six of the nine cases(one patient had previously undergone surgery) was completed without complication or postoperative difficulties in any instance. No gross abnormalities of the mitral valve were noted at surgery, although its examination was limited. b. ASD primum. There were five patients with ASD primum examined during this period, and none had evidence of mitral valve prolapse. All showed typical features of ASD and endocardial cushion defects. c. VSD. Twenty-five patients with VSD were studied, and ten (40 per cent) were found to have associated mitral valve prolapse (Table I). Two of these ten had other congenital cardiac anomalies in addition to VSD (one pulmonic stenosis, one peripheral pulmonic stenosis), while the remaining eight had isolated VSD. In six individuals with larger defects, the diagnosis was confirmed by catheterization, while four patients had the diagnosis of a small VSD made clinically. Five of the ten patients (50 per cent) had symptoms of congestive failure, two had chest pain, and four had experienced palpitations. A question of SBE was raised in one instance (for a fever of unknown origin). This patient was treated with high dose
May,
1979, Vol. 97, No. 5
Mitral
valve prolapse
in CHD
Fig. 1. Patient with atria1 septal defect and mitral valve prolapse. A, Apex phonocardiogram and apexcardiogram (ACG). There is a loud mid-systolic click (MSC) as well as one or two clicks toward end systole which are unlabeled. Also recorded are typical auscultatory findings of a pre-systolic murmur (PSM), systolic ejection murmur (S&44), and tricuspid valve opening sound (OSTV), as well as a faintly recorded flow rumble (unlabeled) following OSTV. L = low frequency; M = mid frequency; H = high frequency; RFW = rapid filling wave. B, Echocardiogram of the mitral valve at the base of the left ventricle. There is late systolic prolapse (P) of the mitral valve (MV). Also seen is an enlarged right ventricle (RV) and abnormal anterior systolic motion (ASM) of the septum (S).
intravenous antibiotics, although no organism was isolated. Physical examination revealed the holosystolic murmur of VSD in eight of ten cases (the two exceptions had undergone surgical repair). A mitral regurgitant murmur was heard in only one instance, and no patient had a mid-systolic click (Table II). Electrocardiograms were normal in six of the ten patients, RVH or LVH was present in two, VPCs in one, and non-specific ST and T wave abnormalities were present in one. Chest x-rays were normal in the majority of these patients, On echocardiogram, in addition to MVP, LV volume overload was often noted. In one patient with a large, subaortic VSD, aortic overriding of the large defect was noted. The pattern of mitral valve prolapse was variable, and not different from the usual pattern (Fig. 2). Surgery was performed in two instances. In one patient a new aortic regurgitant murmur was heard three months postoperatively, subsequent-
American
Heart
Journal
ly found to be due to a perforation of the aortic valve. d. Patent ductus arteriosus. Seven cases of this entity were examined, and five were found to have associated mitral valve prolapse (71 per cent). Four of the five patients (80 per cent) had symptoms of CHF, none had chest pain, three had palpitations, and none had suffered SBE (Table II). On physical examination, four of the five patients had typical continuous “machinery” murmurs before surgical correction. In one case with associated pulmonary vascular obstruction a systolic murmur of tricuspid regurgitation was heard, while in two patients, murmurs of mitral regurgitation were heard. In one of these cases, a mid-systolic click was also present on physical examination, and was confirmed by phonocardiography (Fig. 3). Electrocardiograms were dominated by LVH, which was present in three of the five tracings,
563
Rippe
Table
et al.
II. Clinical data: Congenital heart disease and mitral valve prolapse Historical
Patient No.
Initials
Atria1 1
septal RM
Hospita1 No.
Sex Age
Twe of congenital heart disease
defect (secundum) 262143 M 38 ASD II” with anomalous pulm. venous drainage 222215 F 40 ASD II”
S.vmptoms of CHF
Chest pain
duta
Palpita tions
Physical
SBE
Clicks
Murmurs
exam. Marfans Habitus
Lnb. ECG
+
-
-
II/VI ASD
-
LAE; 1” AV block: RBBB LAAB
+
t
+
-
-
-
-
II/VI ASD II/VI ASD
-
+
+
+
-
+
t
+
t
3
GA
241109
F
45 ASD
II”
+
-
-
-
-
4
RK
186434
M
49 ASD
II”
+
-
+
-
-
II/VI ASD
-
5
RL
266609
F
45 ASD
II”
+
-
-
-
6
LL
274738
F
28 ASD
II”
+
-
+
-
-
-
inc. RBBB
7
PG
285203
F
30 ASD
II”
+
-
+
-
-
II/VI ASD I/VI dias. III/VI ASD I/VI dias. -
inc RBBB; RVA inc. RBBB; NSST lo AV block; inc. RBBB inc. RBBB
-
8
JH
205971
F
43 ASD
II”
+
-
+
-
-
III/VI ASD
-
9
NN
271608
F
30 ASD
II”
-
+
-
-
-
III/VI ASD
-
inc. RBBB NSST inc. RBBB; RVir inc. RBBB; RVH
22 VSD
-
-
-
II/VI VSD
-
sinus
+
prohable (no organism ) -
-
III/VI VSD III/VI VSD
-
Ventricular 10 AH
Surgeq
-
MP
defect
Cnth
+
2
Atria1 septal None
data
-
+
+(previous) +
+
+
-
-
WNL
+
-
NSST
-
-
(primum)
septal defect 244180 F
11
HG
158619
M
25 VSD
+
+
12
JF
282969
F
30 VSD
-
-
-
tachy
Abbreviations: AI = aortic regurgitation; AS = aortic stenosis: ASD = atria1 septal defect; COARCT = coarctation; DIAS = diastolic murmur: lo = first degree AV block; inc. RBBB = incomplete right bundle branch block: LAHB = left anterior hemiblock: LAE = left atria1 enlargement; LBBB = left bundle branch block; LVH = left ventricular hypertrophy: NSST = non-specific ST-T changes; PDA = patent ductus arteriosus; hypertrophy; sinus PR = pulmonic regurgitation; PS = pulmonic stenosis: RBBB = right bundle branch block; RVH = right ventricular tachy = sinus tachycardia; TOF = tetralogy of Fallot; TR = tricuspid regurgitation: VPCs = ventricular premature beats; VSD = ventricular septal defect: WNL = within normal limits.
564
Mitral
Table
NO.
in CHD
II. Cont’d Historical
Patient
valve prolapse
Initials
Ventricular
Hospital No.
TYPO of congenital heart Sex Age disease
septal defect
Symptoms of CHF
data
Physical exam. Marfans
Chest pain
-
Palpita tions
SBE
Clicks
Murmurs
Habitus
-
WNL
+
+
-
II/VI VSD; II/VI PS
-
+
+
-
IV/VI VSD III/VI VSD IV/IV VSD IV/VI VSD II/VI PR III/VI VSD
-
RVH; intraventricular conduct defect VPCS
-
-
WNL
-
-
-
WNL
+
-
-
LAE; LVH; RVH
+
+
-
WNL
+
inc. RBBB LVH; RVH; LVH w/ strain LAE
+
+
+
+
+
+
+
+
+
+
LAHB; RBBB LAHB; RBBB; LVH: RVH
+
+
+
+
LAHB; RBBB; LVH; RVH
+
+
246698
M
14
SM
490753
M
15
KG
213305
F
28 VSD, pulmonary stenosis 21 VSD, peripheral pulmonary stenosis 24 VSD
16
RR
267122
M
30 VSD
17
FM
280426 M
30 VSD
18
LS
242547
F
23 VSD
19
DL
237620 M
24 VSD
Patent ductus arteriosus 20 PC 264842 M
45 PDA
+
+
-
+
-
-
+
+
+
-
-
+
-
-
possible (no organism)
-
-
-
+
III/VI PDA
-
-
III/VI PDA III/VI PDA III/VI PDA
-
21
WS
222449
M
57 PDA
+
+
22
MW
268451
F
+
+
-
23
SA
226581
F
48 PDA aneurysm 31 PDA
+
+
-
24
JL
219518
M
22 PDA
-
-
-
III/VI PDA II/VI TR
-
Tetralogy of Fallot 25 JC 270342 M
30 TOF
+
-
+
-
III/VI PS II/VI PS; II/VI PR; II/VI VSD III/VI PR; VI/VI
-
26
FL
210431 M
32 TOF
+
-
-
-
27
RM
057009
32 TOF
+
-
-
-
Heart
Journal
SurCath gery
I/VI VSD
AE
American
ECG
-
13
M
Lab. data
-
-
-
counter clockwise rotation 1”AV block LVH
+
565
Rippe
Table
et al.
II. Cont’d
III
I
I
I
I
Type of Patient No.
Initials
Hospital No.
Congenital pulmonary 28 MK 282936
Sex Age
congenital c?i?~ heart disease
Historical
Symptoms
of CHF
stenosis F 27 PS
LM
282406
F
34 PS
30
EC
264805
M
21 PS
-
31
SM
285570
M
17 PS
-
32
FC
183483
F
24 PS
+
34
TR
left ventricular 286360
M
008753
M
EbsteinS anomaly 35 LF 215347
36
39
cc
278408
M
40
LM
222720
F
566
+
-
-
bi-
+
40 Peripheral pulmonary artery stenosis 24 Ruptured sinus of valsalva 22 Tricuspid atresia
-
-
-
-
F
F
Clicks
-
245239
281905
SBE
23 Ebstein’s Anomaly
M
DG
------I -.,I,
-
30 Ebstein’s Anomaly
38
Palpitations
-
F
RC
Miscellaneous 37 JW
outflow obstruction 27 Bicuspid Aortic Valve 24 Repaired coarct; cuspid aortic valve
Chest pain
Ph.%3ical Physical
+
29
Congenital 33 SA
data
25 Idiopathic dilatation of pulmonary artery
-
+ +
+
-
-
-
-
-
-
exam.
Murmurs
Marfans Habitus
Lab.
ECG
data
ICath Cath
Sur1 gery irh
III/VI PS III/VI PS V/VI PS III/VI PS I/VI PS
-
WNL
-
-
-
WNL
-
-
+
+
-
RVH w/ strain RBBB
-
-
-
WNL
+
-
I/VI AS; II/VI AI I/VI AS; II/VI AI
-
WNL
-
WNL
-
-
IV/VI AS; IV/VI AI II/VI AS II/VI AI
-
WNL
-
-
-
-
III/VI continuous M
-
RVH
+
-
III/VI continuous M V/VI TR
-
RVH
+
-
-
+
-
II/VI PS; II/VI PR
-
Intraventricular conduction defect WNL
-
-
-
May,
1979,
Vol.
97, No.
5
Mitral
valve prolapse
in CHD
-2 ‘~~-~~~ Q
Carotid -\. ’: \ ‘L..
ventricular septal defect and mitral valve prolapse. A, Echocardiogram of the mitral valve is late systolic sagging (unlabeled arrow). B, Left lower sternal border phonocardiogram and carotid pulse tracing. There is a crescendo mid and high frequency holosystolic murmur (HSM) with a normal carotid pulse. L = low frequency; M = mid frequency; H = high frequency; DN = dicrotic notch. C, Echocardiogram of the mitral valve during early Valsalva. There is more marked mitral valve prolapse (unlabeled) compared to the resting state. D, Echocardiogram of the mitral valve during late Valsalva. There is marked holosystolic prolapse of the mitral valve (unlabeled arrows). Fig.
2. Patient
with
(MV) at rest. There
while conduction defects were present in two (incomplete LBBB and first-degree AV block). Cardiac catheterization, performed in four instances, confirmed the presence of PDA. Echocardiograms showed dilated aortic roots and/or arches in three instances, left ventricular volume overload, and a spectrum of types of mitral valve prolapse. Corrective surgery was performed in all five cases. There was one postoperative death in a patient who underwent emergency surgery to repair a ruptured ductal aneurysm and who died of complications 72 hours after surgery. e. Tetralogy of Fallot. Five patients with this anomaly were examined, all of whom had previously undergone at least partial surgical correction. In three cases (60 per cent) associated mitral valve prolapse was found (Table I). All three patients with prolapse had undergone complete repair of their tetralogy. All three had
American
Heart
Journal
symptoms of congestive heart failure, none had experienced chest pain, one had experienced palpitations, and there was no patient with a history of SBE (Table II). Physical examination showed residual pulmanic stenotic murmurs in two instances. There was one murmur of mitral regurgitation although no systolic clicks were heard. Conduction defects predominated on the ECG with RBBB and LAHB present in all three cases. Biventricular hypertrophy was present in two instances. Preoperative cardiac catheterization had confirmed the diagnosis of Tetralogy of Fallot in all three cases. The echocardiograms performed as part of ongoing clinical follow-up showed a holosystolic pattern of mitral valve prolapse. f. Congenital pulmonic stenosis. Fifteen patients with this lesion were examined, and five had mitral valve prolapse (33 per cent) (Table I).
567
Rippe
et al.
lying
Sitting
Standing
Fig. 3. Patient with patent ductus arteriosus and mitral valve prolapse. A, Echocardiogram of the mitral valve sweeping from the left ventricle (at left) towards the base (right). Unlabeled arrows point to late systolic sagging of mitral valve (MV). B, Apex phonocardiogram and carotid pulse tracing at rest lying down. There are two prominent late systolic clicks (C). At this position, only the systolic portion of the continuous murmur is well recorded. DN = dicrotic notch. C, Apex phonocardiogram and carotid pulse (sitting). The systolic clicks (C) occur earlier in systole. D, Apex phonocardiogram and carotid pulse (standing). There is a loud multi-component systolic click in early systole.
Two of the five patients had experienced at least mild shortness of breath or fatigue, although none had experienced chest pain or palpitations. There were no casesof SBE (Table II). On physical examination all five patients had an ejection click and murmur typical of pulmonic stenosis, while none had either mid-systolic clicks or late systolic murmurs. Electrocardiograms were normal in three instances of mild pulmonic stenosis. RBBB was present in one individual, while RVH was found in another. Cardiac catheterization performed in two cases confirmed elevated RV pressures, and documented gradients of at least 20 mm. Hg across the pulmonic valve in both instances. Echocardiograms were consistent with pulmonic stenosis, and in addition, showed various patterns of mild mitral valve prolapse. g. Congenital left ventricular outflow obstruction. Fourteen patients were seenwith varieties of
568
congenital left ventricular outflow obstruction varying from membranous subaortic stenosis to coarctation of the aorta. Two of these patients had associated mitral valve prolapse (Table I). One had a bicuspid aortic valve while the other had a bicuspid aortic valve and repaired coarctation of the aorta. One patient had experienced symptoms of congestive failure, while the other had been troubled by chest pain. Neither had palpitations and neither had contracted SBE. On physical examination, both had murmurs of aortic stenosis and aortic insufficiency. Neither had a mitral murmur or a click. The electrocardiogram in one patient was within normal limits, while in the other patient LVH was present. Cardiac catheterization was not performed in either patient. Echocardiograms were consistent with aortic valve disease, with typical holosystolic mitral valve prolapse (Fig. 4).
May,1979,
Vol. 97, No. .5
Mitral
valve prolapse
in CHD
_._.-._----
Fig. 4. Patient with repaired coarctation of the aorta, bicuspid aortic valve, and mitral valve prolapse. A, Left mid-sternal border phonocardiogram and carotid pulse tracing. There is a crescendo-decrescendo systolic ejection murmur @EM) of flow across the aortic valve, an early decrescendo diastolic murmur (EDM) of aortic insufficiency, and a prominent systolic ejection click (EC). The carotid shows a somewhat delayed upstroke and a systolic thrill. DN = dicrotic notch. B, Echocardiogram of the aortic valve. The leaflets are thickened and closure is asymmetric. AV = aortic valve; Ao = aortic root; LA = left atrium, C, Echocardiogram of the mitral valve. Anterior leaflet excursion is large. There is holosystolic mitral valve prolapse (unlabeled arrows). Also seen is high frequency fluttering (fi.) of the mitral valve consistent with aortic insufficiency.
h. Ebstein’s anomaly. Three patients with this lesion were studied, and two had associated mitral valve prolapse (Table I). Both patients had experienced shortness of breath and fatigue, but neither had chest pain or palpitations. Neither had a history of SBE. On physical examination both had systolic and diastolic murmurs heard at the left sternal border. One had multiple systolic clicks. The electrocardiograms showed only first-degree AV block. Echocardiographic data was consistent with Ebstein’s anomaly with holosystolic mitral valve prolapse in both patients. g. Miscellaneous congenital defects. Fourteen patients with a variety of other congenital defects were examined, and four (29 per cent) were found to have associated mitral valve prolapse. The spectrum of defects included in this category ranged from peripheral pulmonary artery stenosis to parachute mitral valve. The primary diagnoses
American
Heart
Journa
I
of the four patients with echocardiographically demonstrated mitral valve prolapse were: peripheral pulmonary artery stenosis, ruptured sinus of Valsalva aneurysm with aorto-right heart communication, tricuspid atresia, and idiophatic dilatation of the pulmonary artery. The clinical presentation varied considerably according to the underlying lesion. Two patients had experienced symptoms of congestive heart failure (one chronically, and one acutely). Both of these patients had experienced chest pain, and one had also noted palpitations. Two of the patients were entirely asymptomatic. In the patient with ruptured sinus of Valsalva aneurysm, the question of SBE was raised but no organisms were isolated (Table II). Physical examination revealed murmurs compatible with each of the primary diagnoses, although no clicks or late systolic murmurs were heard. Electrocardiograms were normal in two
569
Rippe
et al.
instances, right ventricular hypertrophy was noted in one patient, and an intraventricular conduction defect was seen in the fourth. Cardiac catheterization performed in three instances confirmed the primary diagnosis. Echocardiographic data provided further confirmation. Several different patterns of prolapse were present. Discussion
The use of echocardiography to diagnose and monitor both congenital heart disease and mitral valve prolapse is well established.‘“. x 2:I-R0An association between these lesions has been suggested since the earliest work of Pocock and Barlow and others.“-‘8 Pocock and Barlow’s series,” which contained examples of four types of congenital lesion combined with mitral valve prolapse, suggested that mitral valve prolapse might be linked to a variety of congenital cardiac anomalies, and raised the possibility of a common etiology. Despite subsequent demonstration of a high incidence of mitral valve prolapse in ASD secundum, evidence linking prolapse to other congenital anomalies has been scanty. Recently, mitral valve prolapse has been demonstrated to occur with considerable frequency among several groups of presumably healthy adults.“‘, 32 The prevalence of mitral valve prolapse in patients with most types of congenital heart disease remains largely unexplored. a. The association with various forms
of mitral of congenital
valve heart
prolapse disease.
The association between ASD secundum and mitral valve prolapse has been well established. After Pocock and Barlow’s,” and Hancock and Cohn’s”’ initial suggestions of the association, numerous studies have confirmed the link.“-‘; By 1974 there were over 60 reported cases in the world literature.” In our current series, nine of 32 patients (40 per cent) with secundum ASD had associated mitral valve prolapse (Table I), an incidence similar to previously reported data.“’ However, in only one of these patients was the diagnosis of prolapse clinically suspected, a much higher incidence of “silent” mitral valve prolapse with ASD secundum than previously noted.” Although none of these patients suffered from palpitations, and there were no cases of SBE, it might be argued that a higher incidence of cardiac symptoms was found in these patients than
570
would be expected in ASD alone. The ECG changes which occurred can all be attributed to the atria1 septal defect. The absence of mitral valve prolapse associated with primum ASD is not surprising since this defect tends to limit motion of the mitral valve. Ventricular septal defect with associated mitral valve prolapse has received far lessattention than second degree ASD, a somewhat surprising fact in view of our finding that prolapse is at least as common in VSD (40 per cent) as in second degree ASD (28 per cent). Although Pocock and Barlow’i listed one case of mitral valve prolapse associated with Eisenmenger’s complex, we are unaware of further documentation other than the ten patients in our series. Just as in the patients with ASD and MVP, none of these patients was recognized as having prolapse on clinical grounds. Two of the ten patients did have histories suggestive of SBE. Since this is a recognized complication of VSD as well as the MVP, its significance is difficult to evaluate. Electrocardiograms in patients with significant shunts were once again compatible with VSD without mitral prolapse. Five of the seven patients with patent ductus arteriosus examined in our series had associated mitral valve prolapse, a strikingly high incidence. Although Pocock and Barlow” initially listed two examples of this combination, subsequent verification has been lacking and the association has received much less notice than prolapse associated with second degree ASD. One of these five patients was clinically suspected of having mitral prolapse in addition to a patent ductus. In the other four patients, the echocardiogram provided initial evidence of the prolapse. The high incidence of congestive failure (80 per cent) and palpitations (60 per cent) in these patients could be explained by the presence of a large patent ductus alone. Tetralogy of Fallot and congenital pulmonic stenosis are both congenital lesions without previously documented associated mitral valve prolapse. Five patients with repaired or palliated TOF were studied, and three (60 per cent) were found to have associated prolapse. Of the 15 patients with congenital pulmonic stenosis examined, five (33 per cent) had echocardiographic evidence of associated mitral valve prolapse. In neither of these conditions were physical findings typical of mitral valve prolapse found (possibly
May, 1979, Vol. 97, No. 5
Mitral
because the primary lesion obscured them) and in neither were complications attributable to prolapse documented. Two of our 14 patients with congenital left ventricular outflow obstruction had associated mitral valve prolapse. While to our knowledge this specific combination has not been previously noted, the association between LV outflow obstruction and other abnormalities of the mitral valve has been observed. Mitral regurgitation accompanying coarctation of the aorta is a recognized albeit uncommon association.“” In one series of 53 hearts with coarctation of the aorta studied at autopsy, 44 instances of associated mitral valve abnormalities were discovered.“” Neither of our two patients was thought to have prolapse before echocardiographic exam, and neither experienced complications or symptoms unexplainable by the outflow obstruction. The two cases of Ebstein’s anomaly with associated mitral valve prolapse (two of three casesof Ebstein’s anomaly examined) found in this series supports previously reported evidence of the association between these two entities.‘” The demonstration of mitral valve prolapse with four other miscellaneous congenital lesions (peripheral pulmonary artery stenosis, sinus of Valsalva aneurysm, tricuspid atresia, and idiopathic dilatation of the pulmonary artery) lends further credence to the widespread association between congenital heart diseaseand mitral valve prolapse. b. Accuracy nosis of mitral
of echocardiography in the diagvalve prolapse. Prior to the wide-
spread use of echocardiography, the diagnosis of mitral valve prolapse relied on clinical impression (when the click-murmur complex was present) combined with left ventricular angiography. As echocardiographic techniques have become more widespread and refined, echocardiography has become the primary means of diagnosing prolapse. By 1971, a good correlation between echocardiographic and angiographic evidence of mitral valve prolapse had been demonstrated’” and “typical” echocardiographic patterns of prolapse were beginning to be elucidated.“” Subsequent work by a variety of investigators refined echocardiographic techniques and criteria for diagnosing prolapse and established guidelines for minimizing false-positive diagnoses.‘“, “?.:K 3i All patients in our series fulfill established echocar-
American
Heart
Journal
valve prolapse
in CHD
diographic criteria for mitral valve prolapse, and exhibit previously described patterns of valve motion typical of the syndrome.20, :K :KG c. Etiology of mitral valve prolapse. Barlow and associates’ believed that the click-murmur syndrome was a non-specific response to underlying abnormalities. They listed rheumatic heart disease, Marfan’s syndrome, hereditary diathesis, and obstructive cardiomyopathy as underlying conditions capable of leading to mitral valve prolapse.? Subsequent investigators have added coronary artery disease and abnormal left ventricular contraction to the list of possible etiologies. The demonstration that mitral valve prolapse is a common concomitant suggests that congenital heart diseasemust be added to the list of possible etiologies for prolapse. The unusually high incidence of mitral valve prolapse in a wide variety of congenital heart diseasescompared to the lower incidence in presumably normal populationsZ1, X2suggests that congenital or constitutional abnormalities of the mitral valve, its supporting structure, or the left ventricle may be of major importance, rather than specific hemodynamic derangements, in the etiology of MVP. d. Clinical relevance of the association between congenital heart disease and mitral valve prolapse. Since the use of echocardiography is
well established for diagnosing and monitoring most forms of congenital heart disease, it is perhaps surprising that the prevalence of mitral valve prolapse has not attracted more attention. One possible explanation may involve the clinical masking of the physical findings of the mitral click and murmur by the abnormal ausculatory findings associated with each congenital lesion. In only three of our 40 cases was mitral valve prolapse considered clinically prior to echocardiography. Only two patients had the typical click-murmur on physical examination. Historical data also failed to predict the presence of mitral valve prolapse associated with congenital heart disease.Although seven of the 40 patients experienced chest pain and 14 had experienced palpitations, it was frequently difficult to pinpoint the origin of these complaints, and they did not appear to be associated specifically with prolapse, or to be unusually frequent in this subgroup. The present series is too small to judge the prevalence of known but infrequent complica-
571
Rippe et al.
tions of mitral valve prolapse such as SBE, arrhythmias, and sudden death when prolapse is associated with congenital heart disease.The case histories of the 40 patients point out several difficulties in the interpretation of data in the combined lesions. The possibility of SBE was actively considered in three cases.Although organisms were not isolated in any instance, all three cases occurred in congenital lesions which, by themselves, might be regarded as higher risks for SBE (two VSD, one ruptured sinus of Valsalva). Although ECG abnormalities were frequently recorded, in most instances they were readily explained by the congenital lesion alone.
7.
8.
9.
10.
11.
Conclusions
Our experience with 120 adults with congenital heart disease studied echocardiographically over the past three years suggests that associated mitral valve prolapse is much more common than previously recognized. Moreover, prolapsing mitral valve seems to be relatively common in a wide variety of congenital heart diseases rather than being confined to a few lesions, as the recent literature appears to indicate. Since the clinical diagnosis of mitral valve prolapse may be particularly difficult when it occurs with congenital heart disease, a careful echocardiographic examination of the mitral valve in patients with congenital heart disease is essential. The effect of associated prolapse on the prognosis of congenital heart diseaseis unknown, and awaits follow-up of patients in whom the syndrome has been recognized.
12. 13.
14.
15.
16.
17.
18.
19. REFERENCES 1.
2.
3.
4.
5.
6.
572
Barlow, J. B., Pocock, W. A., Marchand, P., and Denny, M.: The significance of late systolic murmurs, AM. HEART J. 66~443, 1963. Barlow. J. B.. Bosman. C. K.. Pocock. W. A.. and Marchand, P.:‘Late systolic murmurs and non-ejection (“mid-late”) systolic clicks: an analysis of 90 patients, Br. Heart J. 30:203, 1968. Nutter, D. O., Wickliffe, C., Gilbert, C. A., Moody, C., and King, S. B.: The pathophysiology of idiopathic mitral valve prolapse, Circulation 52:298, 1975. Scampardonis, G., Yang, S. S., Maranhao, V., Goldberg, H., and Gooch, A. S.: Left ventricular abnormalities in prolapsed mitral leaflet syndrome, Circulation 48:287, 1973. Leichtman, D., Nelson, R., Gobel, F. L., Alexander, C. S., and Cohn, J. N.: Bradycardia with mitral valve prolapse; a potential mechanism of sudden death, Ann. Intern. Med. 85:453, 1976. DeMaria, A. N., Amsterdam, E. A., Vismara, L. A., Neumann, A., and Mason, D. T.: Arrhythmias in the
20.
21. 22.
mitral valve prolapse syndrome; prevalence, nature and frequency, Ann. Intern. Med. 84:656, 1976. Roberts, W. C., Glancy, D. L., Seningen, R. P., Maron, B. J., and Epstein, S. E.: Prolapse of the mitral valve (floppy valve) associated with Epstein’s anomaly of the tricuspid valve, Am. J. Cardiol. 38:377, 1976. Gooch, A. S., Vicencio, F., Maranhao, V., and Goldberg, H.: Arrhythmias and left ventricular asynergy in the prolapsing mitral leaflet syndrome, Am. J. Cardiol. 29:611, 1972. Pocock, W. A., and Barlow, J. 8.: An association between the billowing posterior mitral leaflet syndrome and congenital heart disease, particularly atria1 septal defect, AM. HEART J. 81:720, 1971. Hancock, E. W., and Cohn, K.: The syndrome associated with mid-systolic click and late systolic murmur, Am. J. Med. 41:183, 1966. McDonald, A., Harris, A., Jefferson, K., Marshall, J., and McDonald, L.: Association of prolapse of the posterior cusp of the mitral valve and atria1 septal defect, Br. Heart J. 33:383, 1971. Jeresaty, R. M.: Atria1 septal defect and myxomatous mitral-valve prolapse, N. Engl. J. Med. 290:1088, 1974. Betriu, A., Wigh, E. D., Felderhof, C. H., and McLoughlin, M. J.: Prolapse of the posterior leaflet of the mitral valve associated with secundum atria1 septal defect, Am. J. Cardiol. 33:126, 1974. Victoria, B. E., Elliott, L. P., and Gessner, I. H.: Ostium secundum atria1 septal defect associated with balloon mitral valve in children, Am. J. Cardiol. 33:668, 1974. Hynes, K. M., Frye, R. L., Brandenburg, R. O., McGoon, D. C., Titus, J. L., and Giuliani, E. R.: Atria1 septal defect (secundum) associated with mitral regurgitation, Am. J. Cardiol. 34:333, 1974. Leachman, R. D., Cokkinos, D. V., and Cooley, D. A.: Association of ostium secundum atria1 septal defects with mitral valve prolapse, Am. J. Cardiol. 38:167, 1976. Lieppe, W., Scallion, R., Behar, V. S., and Kisslo, J. A.: Two-dimensional echocardiographic findings in atria1 septal defect, Circulation 56:447, 1977. Roberts, W. C., Glancy, D. L., Seningen, R. P., Maron, B. J., and Epstein, S. E.: Prolapse of the mitral valve (floppy valve) associated with Esbtein’s anomaly of the tricuspid valve, Am. J. Cardiol. 38:377, 1976. Dillon, J. C., Haine, C. L., Chang, S., and Feigenbaum, H.: Use of echocardiography in patients with prolapsed mitral valve, Circulation 43503, 1971. DeMaria, A. N., Neumann, A., Lee, G., and Mason, D. T.: Echocardiographic identification of the mitral valve prolapse syndrome, Am. J. Med. 62:819, 1977. Feigenbaum, H.: Echocardiography, second edition, Philadelphia, 1976, Lea & Febinger. Sahn, D. J., Wood, J., Allen, H. D., Peoples, W., and Goldberg. S. J.: Echocardioaranhic suectrum of mitral valve motion in children with and without mitral valve prolapse: the nature of false positive diagnosis, Am. J. Cardiol. 39:422, 1977. Goldberg, S. J., Allen, H. D., and Sahn, D. J.: Pediatric and Adolescent Echocardiography. A Handbook, Chicago, 1975, Year Book Medical Publishers. Meyer, R. A.: Pediatric Echocardiography, Philadelphia, 1977, Lea & Febinger. Meyer, R. A.: Echocardiography in congenital heart disease, Am. J. Med. 63:41, 1977. Williams, R. G., and Rudd, M.: Echocardiographic features of endocardiac cushion defects, Circulation 50:25, 1974. -,
23.
24. 25. 26.
I-
May,
-
1979, Vol. 97, No. 5
Mitral
27.
28.
29. 30.
31.
32.
Diamond, M. A., Dillon, J. C., Haine, C. L., Chang, S., and Feigenbaum, H.: Echocardiographic features of atria1 septal defect, Circulation 43:129, 1971. Lundstrom, N. R.: Echocardiography in the diagnosis of Ebstein’s anomaly of the tricuspid valve, Circulation 47597, 1973. Kotler, M. N.: Tricuspid valve in Ebstein’s anomaly, Circulation 49:194, 1974. Milner, S., Meyer, R. A., Venables, A. W., Korfhagen, J., and Kaplan, S.: Mitral and tricuspid valve closure in congenital heart disease, Circulation 53:513, 1976. Procacci, P. M., Savran, S. V., Schreiter, S. T., and Bryson, A. L.: Prevalence of clinical mitral-valve prolapse in 1169 young women, N. Engl. J. Med. 294: 1086, 1976. Markiewicz, W., Stoner, J., London, L., Hunt, S. A., and Popp, R. L.: Mitral valve prolapse in one hundred presumably healthy young females, Circulation 53:464, 1976.
I
Information
33.
34.
35.
36.
37.
valve prolapse
in CHD
Freed, M. D., Keane, J. F., van Praagh, R., Castaneda, A. R., Bernhard, W. F., and Nadas, A. S.: Coarctation of the aorta with congenital mitral regurgitation, Circulation 49:1175, 1974. Rosenquist, G. C.: Congenital mitral valve disease associated with coarctation of the aorta, Circulation 49:985, 1974. Kerber, R. E., Isaeff, D. M., and Hancock, W.: Echocardiographic patterns in patients with the syndrome of systolic click and late systolic murmur, N. Engl. J. Med. 284:691, 1971. Popp, R. L., Brown, 0. R., Silverman, J. F., and Harrison, D. C.: Echocardiographic abnormalities in the mitral valve prolapse syndrome, Circulation 49:428, 1974. Weiss, A. N., Mimbs, J. W., Ludbrook, P. A., and Sobel, B. E.: Echocardiographic detection of mitral valve prolapse: exclusion of false positive diagnosis and determination of inheritance, Circulation 52:1091, 1975.
for authors
Most of the provisions of the Copyright Act of 1976 became effective on January 1, 1978. Therefore, all manuscripts must be accompanied by the following written statement, signed by one author: “The undersigned author transfers all copyright ownership of the manuscript (title of article) to The C. V. Mosby Company in the event the work is published. The undersigned author warrants that the article is original, is not under consideration by another journal, and has not been previously published. I sign for and accept responsibility for releasing this material on behalf of any and all co-authors.” Authors will be consulted, when possible, regarding republication of their material.
American
Heart
Journal
573
valve prolapse disease
in adults
with
congenital
James M. Rippe, B.A. Laurence J. Sloss, M.D. Gerald Angoff, M.D. Joseph S. Alpert, M.D. Boston,
Mass.
During the 15 years since Barlow and associates demonstrated that the click-murmur syndrome could be explained by mitral valve prolapse,’ the syndrome has continued to spark considerable interest. Barlow and colleagues’ initially suggested that the syndrome could arise from diverse etiologies. Recent angiographic and echocardiographic studies have confirmed this suggestion, greatly expanding the list of possible etiologies and conditions associated with mitral valve prolapse.:‘-” The association between atria1 septal defect and mitral valve prolapse (MVP) was noted in Barlow’s initial group of patients9 and was elaborated by subsequent investigators.‘0-17 Pocock and Barlow?’ also reported mitral valve prolapse associated with other congenital lesions including Eisenmenger’s syndrome (one case), and patent ductus arteriosus (one case) without noting an increased incidence of prolapse in these conditions. Recently, Ebstein’s anomaly has been added to the list of congenital lesions with associated mitral valve prolapse.‘* Questions remain concerning the spectrum of congenital diseases in which mitral valve prolapse occurs, the frequency of prolapse, possible etiologic links between the two entities, and the natural history of the combined lesions. During the past three years, echocardiograms have been performed at the Peter Bent Brigham From the Cardiovascular Boston, Mass.
Division,
Peter
Received
for publication
Sept.
6, 1978.
Accepted
for publication
Nov.
13, 1978.
Reprint requests: Joseph sion of Medicine, University Avenue North, Worcester.
0002~8703/79/050561
S. Alpert, M.D., of Massachusetts Mass. 01605.
+ 13$01.30/O
Bent
Brigham
Chief, Cardiovascular Medical Center,
0 1979 The
Hospital,
Diti55 Lake
C. V. Mosby
Co.
Hospital Heart Station on 120 adults with congenital heart disease, comprising virtually all patients with congenital heart lesions seen at the Peter Bent Brigham Hospital during this period. Mitral valve prolapse was present with surprising frequency in this group, with 40 documented cases (34 per cent of the entire group): ASD secundum, nine cases; VSD, 10 cases; PDA, five cases; tetralogy of Fallot, three cases; Ebstein’s anomaly, two cases; and miscellaneous congenital heart lesions, four cases. We report these 40 patients and discuss possible etiologic links and clinical relevance. Materials
and methods
Echocardiograms were examined from 120 adults with congenital heart disease studied in the Peter Bent Brigham Hospital Heart Station between December 1,1974, and December 1,1977. Since a large children’s hospital, Children’s Hospital Medical Center, is located in close proximity to the Peter Bent Brigham, children are rarely examined at our hospital, and no individual under the age of 17 is included in the present series. Forty patients (20 males and 20 females) ranging in age from 17 to 57 years, were found to have mitral valve prolapse. They had been referred for a variety of reasons. Many had been followed for congenital heart defects since childhood and had reached a point where definitive correction was felt to be necessary. Others had undergone repair of congenital defects as children, and were receiving routine periodic follow-up. Some patients were studied as part of regular care for lesions not considered significant enough to require surgical intervention. Finally, a small group of patients
American
Heart
Journal
561
Rippe
et al.
I. Prevalence of mitral valve prolapse with each type of congenital heart disease
Table
Type of CHD ASD II” ASD I” VSD PDA TOF PS Congenital LV outflow obstruction Ebstein’s anomaly Miscellaneous Totals
Total no. studied
No. with associated MVP
% with associated MVP
32 5 25 7 5 15 14
9 0 10 5 3 5 2
28% 0% 40% 71% 60% 33% 15%
3 14
2 4
67% 29%
120
40
33%
with abnormal cardiac examinations were studied and were found to have previously undiagnosed congenital lesions. None of the 40 patients was initially referred for evaluation of possible mitral valve prolapse. The diagnosis of congenital heart disease was confirmed by cardiac catheterization in the majority of patients with hemodynamically significant disease. In the remainder, the diagnosis was established by clinical evidence with supporting noninvasive examinations. The diagnosis of mitral valve prolapse was made by established echocardiographic criteria.lg All of the patients exhibited the characteristic pattern of posterior buckling or bulging of the mitral valve apparatus during systole, and displayed either late systolic “bowing” or holosystolic “hammocking.“2n Echocardiograms were obtained using standard techniques and were recorded on commercially available Irex or Smith-Kline recording devices interfaced with Irex strip chart recorders and 2.25 or 3.5 MHz transducers. The mitral valve was visualized in standard views” with particular care exercised to avoid “pseudo prolapse” or inferior angulation of the echo transducer which might alter the apparent location of the mitral valve.‘? Results a. ASD secundum. Of 32 patients with ASD secundum studied, nine (28 per cent) had associated mitral valve prolapse (Table I). One of the nine also had anomalous pulmonary venous
562
drainage, while the remaining eight patients had ASD secundum without associated anomalies. Eight of the nine patients had experienced at least mild shortness of breath or fatigue while only two were troubled by chest pain. Palpitations occurred in five of the nine patients (56 per cent). None had contracted SBE (Table II). Physical examination prior to surgical intervention revealed murmurs typical of ASD in eight of nine patients (89 per cent), the only exception being a patient whose ASD had been repaired. A murmur compatible with the click-murmur syndrome was heard in only one patient (11 per cent). In this patient, a mid-systolic click was noted on one physical examination and was confirmed by phonocardiography. Electrocardiograms were typical for ASD with either complete or incomplete right bundle branch block in all nine patients. In addition, RVH was present in four patients, and nonspecific ST and T wave abnormalities were present in three patients. On echocardiogram, both holosystolic and late systolic mitral valve prolapse were observed (Fig. 1). Surgical correction, undertaken in six of the nine cases(one patient had previously undergone surgery) was completed without complication or postoperative difficulties in any instance. No gross abnormalities of the mitral valve were noted at surgery, although its examination was limited. b. ASD primum. There were five patients with ASD primum examined during this period, and none had evidence of mitral valve prolapse. All showed typical features of ASD and endocardial cushion defects. c. VSD. Twenty-five patients with VSD were studied, and ten (40 per cent) were found to have associated mitral valve prolapse (Table I). Two of these ten had other congenital cardiac anomalies in addition to VSD (one pulmonic stenosis, one peripheral pulmonic stenosis), while the remaining eight had isolated VSD. In six individuals with larger defects, the diagnosis was confirmed by catheterization, while four patients had the diagnosis of a small VSD made clinically. Five of the ten patients (50 per cent) had symptoms of congestive failure, two had chest pain, and four had experienced palpitations. A question of SBE was raised in one instance (for a fever of unknown origin). This patient was treated with high dose
May,
1979, Vol. 97, No. 5
Mitral
valve prolapse
in CHD
Fig. 1. Patient with atria1 septal defect and mitral valve prolapse. A, Apex phonocardiogram and apexcardiogram (ACG). There is a loud mid-systolic click (MSC) as well as one or two clicks toward end systole which are unlabeled. Also recorded are typical auscultatory findings of a pre-systolic murmur (PSM), systolic ejection murmur (S&44), and tricuspid valve opening sound (OSTV), as well as a faintly recorded flow rumble (unlabeled) following OSTV. L = low frequency; M = mid frequency; H = high frequency; RFW = rapid filling wave. B, Echocardiogram of the mitral valve at the base of the left ventricle. There is late systolic prolapse (P) of the mitral valve (MV). Also seen is an enlarged right ventricle (RV) and abnormal anterior systolic motion (ASM) of the septum (S).
intravenous antibiotics, although no organism was isolated. Physical examination revealed the holosystolic murmur of VSD in eight of ten cases (the two exceptions had undergone surgical repair). A mitral regurgitant murmur was heard in only one instance, and no patient had a mid-systolic click (Table II). Electrocardiograms were normal in six of the ten patients, RVH or LVH was present in two, VPCs in one, and non-specific ST and T wave abnormalities were present in one. Chest x-rays were normal in the majority of these patients, On echocardiogram, in addition to MVP, LV volume overload was often noted. In one patient with a large, subaortic VSD, aortic overriding of the large defect was noted. The pattern of mitral valve prolapse was variable, and not different from the usual pattern (Fig. 2). Surgery was performed in two instances. In one patient a new aortic regurgitant murmur was heard three months postoperatively, subsequent-
American
Heart
Journal
ly found to be due to a perforation of the aortic valve. d. Patent ductus arteriosus. Seven cases of this entity were examined, and five were found to have associated mitral valve prolapse (71 per cent). Four of the five patients (80 per cent) had symptoms of CHF, none had chest pain, three had palpitations, and none had suffered SBE (Table II). On physical examination, four of the five patients had typical continuous “machinery” murmurs before surgical correction. In one case with associated pulmonary vascular obstruction a systolic murmur of tricuspid regurgitation was heard, while in two patients, murmurs of mitral regurgitation were heard. In one of these cases, a mid-systolic click was also present on physical examination, and was confirmed by phonocardiography (Fig. 3). Electrocardiograms were dominated by LVH, which was present in three of the five tracings,
563
Rippe
Table
et al.
II. Clinical data: Congenital heart disease and mitral valve prolapse Historical
Patient No.
Initials
Atria1 1
septal RM
Hospita1 No.
Sex Age
Twe of congenital heart disease
defect (secundum) 262143 M 38 ASD II” with anomalous pulm. venous drainage 222215 F 40 ASD II”
S.vmptoms of CHF
Chest pain
duta
Palpita tions
Physical
SBE
Clicks
Murmurs
exam. Marfans Habitus
Lnb. ECG
+
-
-
II/VI ASD
-
LAE; 1” AV block: RBBB LAAB
+
t
+
-
-
-
-
II/VI ASD II/VI ASD
-
+
+
+
-
+
t
+
t
3
GA
241109
F
45 ASD
II”
+
-
-
-
-
4
RK
186434
M
49 ASD
II”
+
-
+
-
-
II/VI ASD
-
5
RL
266609
F
45 ASD
II”
+
-
-
-
6
LL
274738
F
28 ASD
II”
+
-
+
-
-
-
inc. RBBB
7
PG
285203
F
30 ASD
II”
+
-
+
-
-
II/VI ASD I/VI dias. III/VI ASD I/VI dias. -
inc RBBB; RVA inc. RBBB; NSST lo AV block; inc. RBBB inc. RBBB
-
8
JH
205971
F
43 ASD
II”
+
-
+
-
-
III/VI ASD
-
9
NN
271608
F
30 ASD
II”
-
+
-
-
-
III/VI ASD
-
inc. RBBB NSST inc. RBBB; RVir inc. RBBB; RVH
22 VSD
-
-
-
II/VI VSD
-
sinus
+
prohable (no organism ) -
-
III/VI VSD III/VI VSD
-
Ventricular 10 AH
Surgeq
-
MP
defect
Cnth
+
2
Atria1 septal None
data
-
+
+(previous) +
+
+
-
-
WNL
+
-
NSST
-
-
(primum)
septal defect 244180 F
11
HG
158619
M
25 VSD
+
+
12
JF
282969
F
30 VSD
-
-
-
tachy
Abbreviations: AI = aortic regurgitation; AS = aortic stenosis: ASD = atria1 septal defect; COARCT = coarctation; DIAS = diastolic murmur: lo = first degree AV block; inc. RBBB = incomplete right bundle branch block: LAHB = left anterior hemiblock: LAE = left atria1 enlargement; LBBB = left bundle branch block; LVH = left ventricular hypertrophy: NSST = non-specific ST-T changes; PDA = patent ductus arteriosus; hypertrophy; sinus PR = pulmonic regurgitation; PS = pulmonic stenosis: RBBB = right bundle branch block; RVH = right ventricular tachy = sinus tachycardia; TOF = tetralogy of Fallot; TR = tricuspid regurgitation: VPCs = ventricular premature beats; VSD = ventricular septal defect: WNL = within normal limits.
564
Mitral
Table
NO.
in CHD
II. Cont’d Historical
Patient
valve prolapse
Initials
Ventricular
Hospital No.
TYPO of congenital heart Sex Age disease
septal defect
Symptoms of CHF
data
Physical exam. Marfans
Chest pain
-
Palpita tions
SBE
Clicks
Murmurs
Habitus
-
WNL
+
+
-
II/VI VSD; II/VI PS
-
+
+
-
IV/VI VSD III/VI VSD IV/IV VSD IV/VI VSD II/VI PR III/VI VSD
-
RVH; intraventricular conduct defect VPCS
-
-
WNL
-
-
-
WNL
+
-
-
LAE; LVH; RVH
+
+
-
WNL
+
inc. RBBB LVH; RVH; LVH w/ strain LAE
+
+
+
+
+
+
+
+
+
+
LAHB; RBBB LAHB; RBBB; LVH: RVH
+
+
+
+
LAHB; RBBB; LVH; RVH
+
+
246698
M
14
SM
490753
M
15
KG
213305
F
28 VSD, pulmonary stenosis 21 VSD, peripheral pulmonary stenosis 24 VSD
16
RR
267122
M
30 VSD
17
FM
280426 M
30 VSD
18
LS
242547
F
23 VSD
19
DL
237620 M
24 VSD
Patent ductus arteriosus 20 PC 264842 M
45 PDA
+
+
-
+
-
-
+
+
+
-
-
+
-
-
possible (no organism)
-
-
-
+
III/VI PDA
-
-
III/VI PDA III/VI PDA III/VI PDA
-
21
WS
222449
M
57 PDA
+
+
22
MW
268451
F
+
+
-
23
SA
226581
F
48 PDA aneurysm 31 PDA
+
+
-
24
JL
219518
M
22 PDA
-
-
-
III/VI PDA II/VI TR
-
Tetralogy of Fallot 25 JC 270342 M
30 TOF
+
-
+
-
III/VI PS II/VI PS; II/VI PR; II/VI VSD III/VI PR; VI/VI
-
26
FL
210431 M
32 TOF
+
-
-
-
27
RM
057009
32 TOF
+
-
-
-
Heart
Journal
SurCath gery
I/VI VSD
AE
American
ECG
-
13
M
Lab. data
-
-
-
counter clockwise rotation 1”AV block LVH
+
565
Rippe
Table
et al.
II. Cont’d
III
I
I
I
I
Type of Patient No.
Initials
Hospital No.
Congenital pulmonary 28 MK 282936
Sex Age
congenital c?i?~ heart disease
Historical
Symptoms
of CHF
stenosis F 27 PS
LM
282406
F
34 PS
30
EC
264805
M
21 PS
-
31
SM
285570
M
17 PS
-
32
FC
183483
F
24 PS
+
34
TR
left ventricular 286360
M
008753
M
EbsteinS anomaly 35 LF 215347
36
39
cc
278408
M
40
LM
222720
F
566
+
-
-
bi-
+
40 Peripheral pulmonary artery stenosis 24 Ruptured sinus of valsalva 22 Tricuspid atresia
-
-
-
-
F
F
Clicks
-
245239
281905
SBE
23 Ebstein’s Anomaly
M
DG
------I -.,I,
-
30 Ebstein’s Anomaly
38
Palpitations
-
F
RC
Miscellaneous 37 JW
outflow obstruction 27 Bicuspid Aortic Valve 24 Repaired coarct; cuspid aortic valve
Chest pain
Ph.%3ical Physical
+
29
Congenital 33 SA
data
25 Idiopathic dilatation of pulmonary artery
-
+ +
+
-
-
-
-
-
-
exam.
Murmurs
Marfans Habitus
Lab.
ECG
data
ICath Cath
Sur1 gery irh
III/VI PS III/VI PS V/VI PS III/VI PS I/VI PS
-
WNL
-
-
-
WNL
-
-
+
+
-
RVH w/ strain RBBB
-
-
-
WNL
+
-
I/VI AS; II/VI AI I/VI AS; II/VI AI
-
WNL
-
WNL
-
-
IV/VI AS; IV/VI AI II/VI AS II/VI AI
-
WNL
-
-
-
-
III/VI continuous M
-
RVH
+
-
III/VI continuous M V/VI TR
-
RVH
+
-
-
+
-
II/VI PS; II/VI PR
-
Intraventricular conduction defect WNL
-
-
-
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1979,
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97, No.
5
Mitral
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in CHD
-2 ‘~~-~~~ Q
Carotid -\. ’: \ ‘L..
ventricular septal defect and mitral valve prolapse. A, Echocardiogram of the mitral valve is late systolic sagging (unlabeled arrow). B, Left lower sternal border phonocardiogram and carotid pulse tracing. There is a crescendo mid and high frequency holosystolic murmur (HSM) with a normal carotid pulse. L = low frequency; M = mid frequency; H = high frequency; DN = dicrotic notch. C, Echocardiogram of the mitral valve during early Valsalva. There is more marked mitral valve prolapse (unlabeled) compared to the resting state. D, Echocardiogram of the mitral valve during late Valsalva. There is marked holosystolic prolapse of the mitral valve (unlabeled arrows). Fig.
2. Patient
with
(MV) at rest. There
while conduction defects were present in two (incomplete LBBB and first-degree AV block). Cardiac catheterization, performed in four instances, confirmed the presence of PDA. Echocardiograms showed dilated aortic roots and/or arches in three instances, left ventricular volume overload, and a spectrum of types of mitral valve prolapse. Corrective surgery was performed in all five cases. There was one postoperative death in a patient who underwent emergency surgery to repair a ruptured ductal aneurysm and who died of complications 72 hours after surgery. e. Tetralogy of Fallot. Five patients with this anomaly were examined, all of whom had previously undergone at least partial surgical correction. In three cases (60 per cent) associated mitral valve prolapse was found (Table I). All three patients with prolapse had undergone complete repair of their tetralogy. All three had
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symptoms of congestive heart failure, none had experienced chest pain, one had experienced palpitations, and there was no patient with a history of SBE (Table II). Physical examination showed residual pulmanic stenotic murmurs in two instances. There was one murmur of mitral regurgitation although no systolic clicks were heard. Conduction defects predominated on the ECG with RBBB and LAHB present in all three cases. Biventricular hypertrophy was present in two instances. Preoperative cardiac catheterization had confirmed the diagnosis of Tetralogy of Fallot in all three cases. The echocardiograms performed as part of ongoing clinical follow-up showed a holosystolic pattern of mitral valve prolapse. f. Congenital pulmonic stenosis. Fifteen patients with this lesion were examined, and five had mitral valve prolapse (33 per cent) (Table I).
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lying
Sitting
Standing
Fig. 3. Patient with patent ductus arteriosus and mitral valve prolapse. A, Echocardiogram of the mitral valve sweeping from the left ventricle (at left) towards the base (right). Unlabeled arrows point to late systolic sagging of mitral valve (MV). B, Apex phonocardiogram and carotid pulse tracing at rest lying down. There are two prominent late systolic clicks (C). At this position, only the systolic portion of the continuous murmur is well recorded. DN = dicrotic notch. C, Apex phonocardiogram and carotid pulse (sitting). The systolic clicks (C) occur earlier in systole. D, Apex phonocardiogram and carotid pulse (standing). There is a loud multi-component systolic click in early systole.
Two of the five patients had experienced at least mild shortness of breath or fatigue, although none had experienced chest pain or palpitations. There were no casesof SBE (Table II). On physical examination all five patients had an ejection click and murmur typical of pulmonic stenosis, while none had either mid-systolic clicks or late systolic murmurs. Electrocardiograms were normal in three instances of mild pulmonic stenosis. RBBB was present in one individual, while RVH was found in another. Cardiac catheterization performed in two cases confirmed elevated RV pressures, and documented gradients of at least 20 mm. Hg across the pulmonic valve in both instances. Echocardiograms were consistent with pulmonic stenosis, and in addition, showed various patterns of mild mitral valve prolapse. g. Congenital left ventricular outflow obstruction. Fourteen patients were seenwith varieties of
568
congenital left ventricular outflow obstruction varying from membranous subaortic stenosis to coarctation of the aorta. Two of these patients had associated mitral valve prolapse (Table I). One had a bicuspid aortic valve while the other had a bicuspid aortic valve and repaired coarctation of the aorta. One patient had experienced symptoms of congestive failure, while the other had been troubled by chest pain. Neither had palpitations and neither had contracted SBE. On physical examination, both had murmurs of aortic stenosis and aortic insufficiency. Neither had a mitral murmur or a click. The electrocardiogram in one patient was within normal limits, while in the other patient LVH was present. Cardiac catheterization was not performed in either patient. Echocardiograms were consistent with aortic valve disease, with typical holosystolic mitral valve prolapse (Fig. 4).
May,1979,
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_._.-._----
Fig. 4. Patient with repaired coarctation of the aorta, bicuspid aortic valve, and mitral valve prolapse. A, Left mid-sternal border phonocardiogram and carotid pulse tracing. There is a crescendo-decrescendo systolic ejection murmur @EM) of flow across the aortic valve, an early decrescendo diastolic murmur (EDM) of aortic insufficiency, and a prominent systolic ejection click (EC). The carotid shows a somewhat delayed upstroke and a systolic thrill. DN = dicrotic notch. B, Echocardiogram of the aortic valve. The leaflets are thickened and closure is asymmetric. AV = aortic valve; Ao = aortic root; LA = left atrium, C, Echocardiogram of the mitral valve. Anterior leaflet excursion is large. There is holosystolic mitral valve prolapse (unlabeled arrows). Also seen is high frequency fluttering (fi.) of the mitral valve consistent with aortic insufficiency.
h. Ebstein’s anomaly. Three patients with this lesion were studied, and two had associated mitral valve prolapse (Table I). Both patients had experienced shortness of breath and fatigue, but neither had chest pain or palpitations. Neither had a history of SBE. On physical examination both had systolic and diastolic murmurs heard at the left sternal border. One had multiple systolic clicks. The electrocardiograms showed only first-degree AV block. Echocardiographic data was consistent with Ebstein’s anomaly with holosystolic mitral valve prolapse in both patients. g. Miscellaneous congenital defects. Fourteen patients with a variety of other congenital defects were examined, and four (29 per cent) were found to have associated mitral valve prolapse. The spectrum of defects included in this category ranged from peripheral pulmonary artery stenosis to parachute mitral valve. The primary diagnoses
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of the four patients with echocardiographically demonstrated mitral valve prolapse were: peripheral pulmonary artery stenosis, ruptured sinus of Valsalva aneurysm with aorto-right heart communication, tricuspid atresia, and idiophatic dilatation of the pulmonary artery. The clinical presentation varied considerably according to the underlying lesion. Two patients had experienced symptoms of congestive heart failure (one chronically, and one acutely). Both of these patients had experienced chest pain, and one had also noted palpitations. Two of the patients were entirely asymptomatic. In the patient with ruptured sinus of Valsalva aneurysm, the question of SBE was raised but no organisms were isolated (Table II). Physical examination revealed murmurs compatible with each of the primary diagnoses, although no clicks or late systolic murmurs were heard. Electrocardiograms were normal in two
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instances, right ventricular hypertrophy was noted in one patient, and an intraventricular conduction defect was seen in the fourth. Cardiac catheterization performed in three instances confirmed the primary diagnosis. Echocardiographic data provided further confirmation. Several different patterns of prolapse were present. Discussion
The use of echocardiography to diagnose and monitor both congenital heart disease and mitral valve prolapse is well established.‘“. x 2:I-R0An association between these lesions has been suggested since the earliest work of Pocock and Barlow and others.“-‘8 Pocock and Barlow’s series,” which contained examples of four types of congenital lesion combined with mitral valve prolapse, suggested that mitral valve prolapse might be linked to a variety of congenital cardiac anomalies, and raised the possibility of a common etiology. Despite subsequent demonstration of a high incidence of mitral valve prolapse in ASD secundum, evidence linking prolapse to other congenital anomalies has been scanty. Recently, mitral valve prolapse has been demonstrated to occur with considerable frequency among several groups of presumably healthy adults.“‘, 32 The prevalence of mitral valve prolapse in patients with most types of congenital heart disease remains largely unexplored. a. The association with various forms
of mitral of congenital
valve heart
prolapse disease.
The association between ASD secundum and mitral valve prolapse has been well established. After Pocock and Barlow’s,” and Hancock and Cohn’s”’ initial suggestions of the association, numerous studies have confirmed the link.“-‘; By 1974 there were over 60 reported cases in the world literature.” In our current series, nine of 32 patients (40 per cent) with secundum ASD had associated mitral valve prolapse (Table I), an incidence similar to previously reported data.“’ However, in only one of these patients was the diagnosis of prolapse clinically suspected, a much higher incidence of “silent” mitral valve prolapse with ASD secundum than previously noted.” Although none of these patients suffered from palpitations, and there were no cases of SBE, it might be argued that a higher incidence of cardiac symptoms was found in these patients than
570
would be expected in ASD alone. The ECG changes which occurred can all be attributed to the atria1 septal defect. The absence of mitral valve prolapse associated with primum ASD is not surprising since this defect tends to limit motion of the mitral valve. Ventricular septal defect with associated mitral valve prolapse has received far lessattention than second degree ASD, a somewhat surprising fact in view of our finding that prolapse is at least as common in VSD (40 per cent) as in second degree ASD (28 per cent). Although Pocock and Barlow’i listed one case of mitral valve prolapse associated with Eisenmenger’s complex, we are unaware of further documentation other than the ten patients in our series. Just as in the patients with ASD and MVP, none of these patients was recognized as having prolapse on clinical grounds. Two of the ten patients did have histories suggestive of SBE. Since this is a recognized complication of VSD as well as the MVP, its significance is difficult to evaluate. Electrocardiograms in patients with significant shunts were once again compatible with VSD without mitral prolapse. Five of the seven patients with patent ductus arteriosus examined in our series had associated mitral valve prolapse, a strikingly high incidence. Although Pocock and Barlow” initially listed two examples of this combination, subsequent verification has been lacking and the association has received much less notice than prolapse associated with second degree ASD. One of these five patients was clinically suspected of having mitral prolapse in addition to a patent ductus. In the other four patients, the echocardiogram provided initial evidence of the prolapse. The high incidence of congestive failure (80 per cent) and palpitations (60 per cent) in these patients could be explained by the presence of a large patent ductus alone. Tetralogy of Fallot and congenital pulmonic stenosis are both congenital lesions without previously documented associated mitral valve prolapse. Five patients with repaired or palliated TOF were studied, and three (60 per cent) were found to have associated prolapse. Of the 15 patients with congenital pulmonic stenosis examined, five (33 per cent) had echocardiographic evidence of associated mitral valve prolapse. In neither of these conditions were physical findings typical of mitral valve prolapse found (possibly
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Mitral
because the primary lesion obscured them) and in neither were complications attributable to prolapse documented. Two of our 14 patients with congenital left ventricular outflow obstruction had associated mitral valve prolapse. While to our knowledge this specific combination has not been previously noted, the association between LV outflow obstruction and other abnormalities of the mitral valve has been observed. Mitral regurgitation accompanying coarctation of the aorta is a recognized albeit uncommon association.“” In one series of 53 hearts with coarctation of the aorta studied at autopsy, 44 instances of associated mitral valve abnormalities were discovered.“” Neither of our two patients was thought to have prolapse before echocardiographic exam, and neither experienced complications or symptoms unexplainable by the outflow obstruction. The two cases of Ebstein’s anomaly with associated mitral valve prolapse (two of three casesof Ebstein’s anomaly examined) found in this series supports previously reported evidence of the association between these two entities.‘” The demonstration of mitral valve prolapse with four other miscellaneous congenital lesions (peripheral pulmonary artery stenosis, sinus of Valsalva aneurysm, tricuspid atresia, and idiopathic dilatation of the pulmonary artery) lends further credence to the widespread association between congenital heart diseaseand mitral valve prolapse. b. Accuracy nosis of mitral
of echocardiography in the diagvalve prolapse. Prior to the wide-
spread use of echocardiography, the diagnosis of mitral valve prolapse relied on clinical impression (when the click-murmur complex was present) combined with left ventricular angiography. As echocardiographic techniques have become more widespread and refined, echocardiography has become the primary means of diagnosing prolapse. By 1971, a good correlation between echocardiographic and angiographic evidence of mitral valve prolapse had been demonstrated’” and “typical” echocardiographic patterns of prolapse were beginning to be elucidated.“” Subsequent work by a variety of investigators refined echocardiographic techniques and criteria for diagnosing prolapse and established guidelines for minimizing false-positive diagnoses.‘“, “?.:K 3i All patients in our series fulfill established echocar-
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valve prolapse
in CHD
diographic criteria for mitral valve prolapse, and exhibit previously described patterns of valve motion typical of the syndrome.20, :K :KG c. Etiology of mitral valve prolapse. Barlow and associates’ believed that the click-murmur syndrome was a non-specific response to underlying abnormalities. They listed rheumatic heart disease, Marfan’s syndrome, hereditary diathesis, and obstructive cardiomyopathy as underlying conditions capable of leading to mitral valve prolapse.? Subsequent investigators have added coronary artery disease and abnormal left ventricular contraction to the list of possible etiologies. The demonstration that mitral valve prolapse is a common concomitant suggests that congenital heart diseasemust be added to the list of possible etiologies for prolapse. The unusually high incidence of mitral valve prolapse in a wide variety of congenital heart diseasescompared to the lower incidence in presumably normal populationsZ1, X2suggests that congenital or constitutional abnormalities of the mitral valve, its supporting structure, or the left ventricle may be of major importance, rather than specific hemodynamic derangements, in the etiology of MVP. d. Clinical relevance of the association between congenital heart disease and mitral valve prolapse. Since the use of echocardiography is
well established for diagnosing and monitoring most forms of congenital heart disease, it is perhaps surprising that the prevalence of mitral valve prolapse has not attracted more attention. One possible explanation may involve the clinical masking of the physical findings of the mitral click and murmur by the abnormal ausculatory findings associated with each congenital lesion. In only three of our 40 cases was mitral valve prolapse considered clinically prior to echocardiography. Only two patients had the typical click-murmur on physical examination. Historical data also failed to predict the presence of mitral valve prolapse associated with congenital heart disease.Although seven of the 40 patients experienced chest pain and 14 had experienced palpitations, it was frequently difficult to pinpoint the origin of these complaints, and they did not appear to be associated specifically with prolapse, or to be unusually frequent in this subgroup. The present series is too small to judge the prevalence of known but infrequent complica-
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tions of mitral valve prolapse such as SBE, arrhythmias, and sudden death when prolapse is associated with congenital heart disease.The case histories of the 40 patients point out several difficulties in the interpretation of data in the combined lesions. The possibility of SBE was actively considered in three cases.Although organisms were not isolated in any instance, all three cases occurred in congenital lesions which, by themselves, might be regarded as higher risks for SBE (two VSD, one ruptured sinus of Valsalva). Although ECG abnormalities were frequently recorded, in most instances they were readily explained by the congenital lesion alone.
7.
8.
9.
10.
11.
Conclusions
Our experience with 120 adults with congenital heart disease studied echocardiographically over the past three years suggests that associated mitral valve prolapse is much more common than previously recognized. Moreover, prolapsing mitral valve seems to be relatively common in a wide variety of congenital heart diseases rather than being confined to a few lesions, as the recent literature appears to indicate. Since the clinical diagnosis of mitral valve prolapse may be particularly difficult when it occurs with congenital heart disease, a careful echocardiographic examination of the mitral valve in patients with congenital heart disease is essential. The effect of associated prolapse on the prognosis of congenital heart diseaseis unknown, and awaits follow-up of patients in whom the syndrome has been recognized.
12. 13.
14.
15.
16.
17.
18.
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Barlow, J. B., Pocock, W. A., Marchand, P., and Denny, M.: The significance of late systolic murmurs, AM. HEART J. 66~443, 1963. Barlow. J. B.. Bosman. C. K.. Pocock. W. A.. and Marchand, P.:‘Late systolic murmurs and non-ejection (“mid-late”) systolic clicks: an analysis of 90 patients, Br. Heart J. 30:203, 1968. Nutter, D. O., Wickliffe, C., Gilbert, C. A., Moody, C., and King, S. B.: The pathophysiology of idiopathic mitral valve prolapse, Circulation 52:298, 1975. Scampardonis, G., Yang, S. S., Maranhao, V., Goldberg, H., and Gooch, A. S.: Left ventricular abnormalities in prolapsed mitral leaflet syndrome, Circulation 48:287, 1973. Leichtman, D., Nelson, R., Gobel, F. L., Alexander, C. S., and Cohn, J. N.: Bradycardia with mitral valve prolapse; a potential mechanism of sudden death, Ann. Intern. Med. 85:453, 1976. DeMaria, A. N., Amsterdam, E. A., Vismara, L. A., Neumann, A., and Mason, D. T.: Arrhythmias in the
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mitral valve prolapse syndrome; prevalence, nature and frequency, Ann. Intern. Med. 84:656, 1976. Roberts, W. C., Glancy, D. L., Seningen, R. P., Maron, B. J., and Epstein, S. E.: Prolapse of the mitral valve (floppy valve) associated with Epstein’s anomaly of the tricuspid valve, Am. J. Cardiol. 38:377, 1976. Gooch, A. S., Vicencio, F., Maranhao, V., and Goldberg, H.: Arrhythmias and left ventricular asynergy in the prolapsing mitral leaflet syndrome, Am. J. Cardiol. 29:611, 1972. Pocock, W. A., and Barlow, J. 8.: An association between the billowing posterior mitral leaflet syndrome and congenital heart disease, particularly atria1 septal defect, AM. HEART J. 81:720, 1971. Hancock, E. W., and Cohn, K.: The syndrome associated with mid-systolic click and late systolic murmur, Am. J. Med. 41:183, 1966. McDonald, A., Harris, A., Jefferson, K., Marshall, J., and McDonald, L.: Association of prolapse of the posterior cusp of the mitral valve and atria1 septal defect, Br. Heart J. 33:383, 1971. Jeresaty, R. M.: Atria1 septal defect and myxomatous mitral-valve prolapse, N. Engl. J. Med. 290:1088, 1974. Betriu, A., Wigh, E. D., Felderhof, C. H., and McLoughlin, M. J.: Prolapse of the posterior leaflet of the mitral valve associated with secundum atria1 septal defect, Am. J. Cardiol. 33:126, 1974. Victoria, B. E., Elliott, L. P., and Gessner, I. H.: Ostium secundum atria1 septal defect associated with balloon mitral valve in children, Am. J. Cardiol. 33:668, 1974. Hynes, K. M., Frye, R. L., Brandenburg, R. O., McGoon, D. C., Titus, J. L., and Giuliani, E. R.: Atria1 septal defect (secundum) associated with mitral regurgitation, Am. J. Cardiol. 34:333, 1974. Leachman, R. D., Cokkinos, D. V., and Cooley, D. A.: Association of ostium secundum atria1 septal defects with mitral valve prolapse, Am. J. Cardiol. 38:167, 1976. Lieppe, W., Scallion, R., Behar, V. S., and Kisslo, J. A.: Two-dimensional echocardiographic findings in atria1 septal defect, Circulation 56:447, 1977. Roberts, W. C., Glancy, D. L., Seningen, R. P., Maron, B. J., and Epstein, S. E.: Prolapse of the mitral valve (floppy valve) associated with Esbtein’s anomaly of the tricuspid valve, Am. J. Cardiol. 38:377, 1976. Dillon, J. C., Haine, C. L., Chang, S., and Feigenbaum, H.: Use of echocardiography in patients with prolapsed mitral valve, Circulation 43503, 1971. DeMaria, A. N., Neumann, A., Lee, G., and Mason, D. T.: Echocardiographic identification of the mitral valve prolapse syndrome, Am. J. Med. 62:819, 1977. Feigenbaum, H.: Echocardiography, second edition, Philadelphia, 1976, Lea & Febinger. Sahn, D. J., Wood, J., Allen, H. D., Peoples, W., and Goldberg. S. J.: Echocardioaranhic suectrum of mitral valve motion in children with and without mitral valve prolapse: the nature of false positive diagnosis, Am. J. Cardiol. 39:422, 1977. Goldberg, S. J., Allen, H. D., and Sahn, D. J.: Pediatric and Adolescent Echocardiography. A Handbook, Chicago, 1975, Year Book Medical Publishers. Meyer, R. A.: Pediatric Echocardiography, Philadelphia, 1977, Lea & Febinger. Meyer, R. A.: Echocardiography in congenital heart disease, Am. J. Med. 63:41, 1977. Williams, R. G., and Rudd, M.: Echocardiographic features of endocardiac cushion defects, Circulation 50:25, 1974. -,
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I
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Freed, M. D., Keane, J. F., van Praagh, R., Castaneda, A. R., Bernhard, W. F., and Nadas, A. S.: Coarctation of the aorta with congenital mitral regurgitation, Circulation 49:1175, 1974. Rosenquist, G. C.: Congenital mitral valve disease associated with coarctation of the aorta, Circulation 49:985, 1974. Kerber, R. E., Isaeff, D. M., and Hancock, W.: Echocardiographic patterns in patients with the syndrome of systolic click and late systolic murmur, N. Engl. J. Med. 284:691, 1971. Popp, R. L., Brown, 0. R., Silverman, J. F., and Harrison, D. C.: Echocardiographic abnormalities in the mitral valve prolapse syndrome, Circulation 49:428, 1974. Weiss, A. N., Mimbs, J. W., Ludbrook, P. A., and Sobel, B. E.: Echocardiographic detection of mitral valve prolapse: exclusion of false positive diagnosis and determination of inheritance, Circulation 52:1091, 1975.
for authors
Most of the provisions of the Copyright Act of 1976 became effective on January 1, 1978. Therefore, all manuscripts must be accompanied by the following written statement, signed by one author: “The undersigned author transfers all copyright ownership of the manuscript (title of article) to The C. V. Mosby Company in the event the work is published. The undersigned author warrants that the article is original, is not under consideration by another journal, and has not been previously published. I sign for and accept responsibility for releasing this material on behalf of any and all co-authors.” Authors will be consulted, when possible, regarding republication of their material.
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