Prolapse of the mitral valve (floppy valve) associated with Ebstein's anomaly of the tricuspid valve

CASE REPORTS

Prolapse of the Mitral Valve (Floppy Valve) Associated With Ebstein’s Anomaly of the Tricuspid WILLIAM C. ROBERTS, MD, FACC D. LUKE GLANCY, MD, FACC” RONALD P. SENINGEN, MD+ BARRY J. MARON, MD STEPHEN E. EPSTEIN, MD, FACC Bethesda,

Maryland

Valve

Prolapse of the mitral valve is described in two patients with the Ebstein’s anomaly of the tricuspid valve. This association has not been described previously. It is probable, however, that this association is not a rare one, but that clinical features of the prolapsing mitral valve are obscured by those resulting from the malformed tricuspid valve. Opportunity also was provided to study anatomically the mitral valve of a patient known to have a systolic click and a late systolic murmur (the Barlow syndrome). Although there have been several anatomic descriptions of floppy mitral valve at necropsy, they have been extremely rare in patients known to have the classic auscultatory features of the Barlow syndrome.

Ebstein’s anomaly of the tricuspid valve is usually either isolated or associated with a fossa ovalis type of atria1 septal defect. The Ebstein type of anomaly is also extremely common on the left side of the heart in patients with corrected transposition of the great vessels. Pulmonary stenosis, ventricular septal defect, hypoplastic pulmonary trunk, hypoplastic ascending aorta and pulmonary atresia with intact ventricular septum are other cardiac malformations that occasionally occur in patients with Ebstein’s anomaly. This report describes two patients with Ebstein’s anomaly who also had prolapsing posterior mitral leaflets, an association that, to our knowledge, has not been described previously. Report

of Patients

Case 1

From the Laboratory of Pathology and Cardiology Branch, National Heart and Lung Institute, and the Department of Diagnostic Radiology, Clinical Center, National Institutes of Health, Bethesda, Md. Manuscript received June 18, 1975; revised manuscript received July 31, 1975; accepted September 3, 1975. Present address: Department of Medicine, Hotel Dieu Hospital and Louisiana State University School of Medicine, New Orleans, La. 7016 1. f Present address: Northwestern Hospital, Chicago Ave. at 27th St., Minneapolis, Minn. 55407. Address for reprints: William C. Roberts, MD, Bldg. lOA, Rm. 3E30, NIH, Bethesda, Md. 20014. l

An 18 year old girl was found to have a precordial murmur at age 4 years. Although she led an active life she never had symptoms of cardiac dysfunction. Fourteen months before death she had a fracture of the right femur and was found to have Ewing’s sarcoma. Her condition progressively deteriorated thereafter and she had widespread metastases. During the last 14 months she was admitted on several occasions to the National Cancer Institute. The blood pressure was 100/60 mm Hg. The neck veins were flat. The heart was large (Fig. l), and a prominent impulse was palpated along the left sternal border. The heart sounds were normal and the second heart sound, heard at the base, was split normally. A systolic click was heard over the cardiac apex. A grade 3/6 late systolic murmur of the regurgitant type was heard over the precordium, left axilla and left side of the back, and it was loudest over the apex. No diastolic murmur was audible. The electrocardiogram (Fig. 2) revealed sinus tachycardia, nonspecific ST-T wave changes and an intraventricular conduction defect (QRS interval 0.09 second). At necropsy, she weighed 41 kg, and the bone tumor had metastasized widely. The heart weighed 300 g and the posterior wall of the right ventricle was thin and bulged prominently posteriorly (Fig. 3). The right atrium was huge. The entire septal and posterior tricuspid valve leaflets were displaced downward to the point where their basal attachment actually was to the endocardium of the ventricular septum (Fig. 3). Most of the anterior tricuspid leaflet arose normally from the true tricuspid valve anulus. The most caudal portion of the displaced tricuspid valve formed an accessory orifice about 2 by 2 cm. The outflow portion of the wall of the right ventricle was of normal thickness.

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FIGURE 1. Case 1. Chest roentgenograms demonstrating mild cardiomegaly with right ventricular prominence, normal pulmonary vascularity and normal-sized left atrium.

TABLE

I

Case 2: Intravascular Catheterization

Pressures (in mm Hg) at Cardiac

Age (vr)

21”

B-V.

6/26/70

FIGURE 2. Case 1. Electrocardiogram.

The left atrium was of normal size. A valve-competent patent foramen ovale was present (Fig. 3). The mitral leaflets were focally but extensively thickened and the posterior leaflet protruded abnormally backward toward the left atrium during simulated ventricular systole (Fig. 4). The left ventricular cavity appeared mildly dilated. Both semilunar valves were normal. Histologic study disclosed a marked increase in the amount of acid mucopolysaccharide material in the mitral valve leaflets (Fig. 4). Case

2

A 35 year old woman was found to have a precordial murmur when pregnant at age 21 years. After a full-term normal pregnancy and normal delivery she was admitted for evaluation of the murmur. She had always been entirely asymptomatic despite participation in strenuous activities. A brother had died of a cardiac condition at age 5 months, and a niece had had a cardiac operation for a congenital cardiac defect. On examination, an impulse and systolic thrill were palpated along the left sternal border. The second heart sound was widely split and the interval between its two components did not vary with respiration. A grade 2/6 systolic murmur was audible along the left sternal border. The chest roentgenogram (Fig. 5) disclosed pectus excavatum and slight cardiomegaly. The electrocardiogram revealed sinus rhythm and incomplete right bundle branch block (QRS interval 0.10 second). At cardiac catheterization (Table I), Cardiogreenn dye curves

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Pulmonary artery Right ventricle Right atrium Mean I/ wave Pulmonary arterial wedge Systemic artery Left ventricle *Preoperative age.

data before

18/4 1812

23

24114 2419

:

8 10

1

i i 6154

&I/55

closure

of atrial

33

1515 1513

septal defect

&=O 90/l 3 at this

revealed a left to right shunt at the atria1 level. The arterial oxygen saturation was 98 percent. At operation, the right atrium was very dilated and the tricuspid valve was displaced caudally. A defect, approximately 3 by 3 cm, was present in the midportion of the atria1 septum and was closed with a Teflon@ patch. The immediate postoperative period was uneventful. Postoperative course: When seen 20 months postoperatively (at age 23), she was asymptomatic and had given birth to another child without difficulty. Reexamination disclosed a left parasternal impulse and a grade l/6 early systolic murmur along the left sternal border. The second heart sound was normal. The electrocardiogram and chest roentgenogram were unchanged. Cardiac catheterization revealed normal intracardiac pressures (Table I) and no shunts. At age 31 (10 years postoperatively) the chest roentgenogram showed more cardiomegaly. She remained asymptomatic until age 33 when paroxysmal atria1 tachycardia with varying block suddenly developed. Reexamination disclosed elevated mean central venous pressure, normal cardiac sounds, a systolic click, and a grade 3/6 pansystolic murmur loudest over the cardiac apex with radiation into the left axilla. The murmur did not increase during inspiration. The chest roentgenogram (Fig. 5) now showed massive enlargement of the right atrium. The electrocardiogram revealed atria1 tachycardia and a right ventricular conduction defect.

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Cardiac catheterization (Table I) revealed no shunts; the cardiac index was 1.7 liters/min per m2. Right atria1 and right ventricular cineangiograms disclosed marked enlargement of the right atrium and caudal displacement of the tricuspid valve (Fig. 6); the levophase showed enlargement of the left atrium. The left ventriculogram showed mitral valve prolapse (Fig. 6). The presence of ventricular premature beats during the latter procedure prevented definitive determination of the presence or absence of mitral regurgitation. During the past 3 years she has received quinidine daily and has had no further arrhythmias. Echocardiographic studies have been obtained, and they are consistent with the diagnosis of mitral valve prolapse.

Comments Mitral valve prolapse in Ebstein’s anomaly: It is now well recognized that the mitral valve prolapse syndrome is a common condition, most often presenting as a mid-systolic click with or without a late systolic murmur. It occurs in all age groups, newborn to elderly, and it is probably more frequent in women. Although

PROLAPSE-ROBERTS

ET AL.

severe chest pain, serious ventricular arrhythmias and sudden death may occur, mitral valve prolapse is usually a benign condition. The “mid-systolic click and late systolic murmur syndrome” (the Barlow syndrome) probably occurs most frequently in persons without other evidence of cardiac disease, but mitral valve prolapse has been described in persons with underlying cardiac disease, including the Marfan syndrome, trauma, atria1 septal defect, hypertrophic cardiomyopathy and even ischemic and rheumatic heart disease. l-6 Its occurrence in patients with the Ebstein anomaly has not been described previously. The reasons may be several: (1) The association may be rare; (2) auscultatory findings, namely, the systolic click and mid-late systolic murmur, may be obscured by the murmur of tricuspid regurgitation and also by flow murmurs resulting from a right to left shunt at the atria1 level, a left to right shunt at the ventricular level, or both; (3) left ventricular angiographic studies are infrequently performed in patients with Ebstein’s anomaly; (4) there may be no

FIGURE 3. Case 1. The heart at autopsy. a, b and c, anterior, posterior and lateral views, respectively, of its external aspects demonstrating a thinned parchment-like (atrialized) right ventricular wall bulging posteriorly above the attachment of the tricuspid valve leaflets. d, opened right atrium (RA) and ventricle (RV) showing marked downward displacement of the posterior and septal tricuspid leaflets. The atrialized portion of the right ventricle behind the posterior leaflet is the part that bulges (b and c). Dashed line = true anulus; solid line = anulus in this patient. e, tricuspid valve (TV) from below displaced deep into the right ventricular cavity. Two valve orifices are present (TV, and TVs). 1, intact atrial septum from the left atrium with a valvular-competent foramen ovale. The patient was never cyanotic. LAA = left atrial appendage; LV = left ventricle: PT = pulmonary trunk; PV = pulmonary valve.

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evidence of mitral regurgitation; (5) typical electrocardiographic features of mitral valve prolapse, namely, T wave and S-T segment changes suggestive of posterior wall ischemia, may be overshadowed or obscured by the changes produced by Ebstein’s anomaly; and (6) because an association between Ebstein’s anomaly and mitral valve prolapse has not been recognized previously, the clinical features of this syndrome have not been carefully sought for.

Mitral valve prolapse was suspected in Patient 1 after auscultation, and in Patient 2 diagnosis was made with angiography. The levophase of the right ventricular cineangiogram suggested prolapsing mitral valve, and this diagnosis was confirmed by left ventricular cineangiogram. The major characteristic of Ebstein’s anomaly is a caudal displacement of the basal attachment of the tricuspid valve so that it inserts onto the right ventric-

FIGURE 4. Case 1. The mitral valve. a, prolapsed mitral valve leaflets as viewed from the left atrium. b, view of floppy leaflets from the left ventricle. c, opened valve showing elongated and focally thickened anterior (A) and posterior leaflets. d, longitudinal section through the left atrium (LA), posterior mitral leaflet and left ventricle (LV) showing the billowed posterior leaflet. e and f, photomicrographs of a portion of the posterior leaflet demonstrating focal thickening and increased acid-mucopolysaccharide deposits (dark staining). CT = chordae tendineae. (Acid-mucopolysaccharide [Reinhart] stains [e and f]: X 5 [e] and 36 [f], reduced by 22 percent.)

FIGURE 5. Case 2. Posteroanterior roentgenograms obtained on three occasions during a 12 year period. The left and center radiographs are similar, each showing mild cardiomegaly with prominent “main pulmonary segment,” normal pulmonary vascularity and a normal-sized left atrium. The radiograph taken at age 33 (12 years after operation) shows a significant increase in cardiac size with enlargement of the right atrium.

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ular free wall or, in some cases, onto the ventricular septum. The second major characteristic of Ebstein’s anomaly is a striking redundancy of the tricuspid leaflets. The displacement of these leaflets into the right ventricle and their close adherence to the underlying mural endocardium account for the absence of atria1 prolapsing of these leaflets during ventricular systole. Thus, if, as in Ebstein’s anomaly, the right atrioventricular valve is redundant, that is, floppy, it might be anticipated that the chance of finding redundant or floppy mitral valve leaflets would be increased. Patients with an atrial septal defect have an increased frequency of mitral valve prolapse.7-12 Obviously, pa-

ET AL.

tients with Ebstein’s anomaly often have defects in their atria1 septum. This association may account in part for the association of mitral valve prolapse with Ebstein’s anomaly. One of our patients had a valvular competent patent foramen ovale; the second had a large fossa ovalis defect that required operative closure. Anatomic findings in mitral valve prolapse: Although there is much clinical information, there is a striking paucity of anatomic information on patients with the “mid-late systolic click late systolic murmur syndrome.“2 The reason, as mentioned earlier, is simply that this clinical syndrome is usually (but not always13) benign. Thus, Case 1 provides an opportunity to study

FIGURE 6. Case 2. Right ventriculogram with line tracing (upper panels) in the posteroanterior projection demonstrates during diastole leftward displacement of the tricuspid valve (arrows). Dotted lines indicate the normal position of the tricuspid valve. The inferior border of the right ventricle (RV) is notched at the demarcation between the “atrialized right ventricle” (ARV) and the body of the right ventricle. The left ventriculogram with line tracing (lower panels) in the right anterior oblique view during systole demonstrates prolapsing posterior leaflet (PPL) of the mitral valve over its anulus (a) into the left atrium. The posterior leaflet is scalloped (horizontal arrows). LV = left ventricle.

THE SPECTRUM OF MITRAL

VALVE

PROLAPSE

I

No Click

I

FIGURE 7. Diagram showing likely auscultatory progression in the prolapsing mitral valve syndrome (see text). CHF = congestive heart failure.

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a floppy valve anatomically in a patient who had no symptoms of cardiac dysfunction as a result of the “floppiness.” This patient died of a malignant neoplasm, not of cardiac disease. Both mitral valve leaflets were thickened and their area was increased in a transverse dimension. Interestingly, the dimensions of the leaflets from their basal attachments to their distal margins were not increased and, furthermore, the chordae tendineae were not elongated; indeed, many appeared shorter than normal. Thus, elongation of the chordae tendineae is not necessary for a mitral valve leaflet to prolapse toward the left atrium during ventricular systole. Spectrum of mitral valve prolapse: In patients with severe mitral regurgitation due to prolapse of one or both leaflets, a systolic click is rarely present and the systolic murmur is pansystolic rather than occurring only in the late or mid-late phase of systole. It is likely, as has been suggested previously,4J4 that some or all of

these patients may have had lesser degrees of prolapse at an earlier time, and the process progressed as shown in Figure 7. A prolapsing but competent valve leads to an isolated click, a prolapsing valve that overshoots its coapting cusp only in the latter part of systole may result in the late systolic murmur with or without retention of the systolic click. As the prolapsing becomes even more severe, regurgitation occurs both in early and in late systole; the murmur thus becomes pansystolic and the click vanishes. Recent electrocardiographic studies15,16 have demonstrated that the click or the late systolic murmur, or both, may disappear entirely during some cardiac cycles; the changes are associated with a change in appearance of the type of posterior leaflet prolapse, that is, late systolic prolapse alternating with holosystolic prolapse. Once regurgitation occurs throughout systole, however, and is relatively persistent, it is unlikely that reversion to one of the early stages will occur (Fig. 7).

References 1. Barlow JB, Pocock WA, Marchand P, et al: The significance of late systolic murmurs. Am Heart J 66:443-452, 1963 2. Barlow JB, Bosman CK, Pocock WA, et al: Late systolic murmurs and non-ejection (“mid-late”) systolic clicks. An analysis of 90 patients. Br Heart J 30:203-216, 1966 3. Pocock WA, Barlow JB: Etiology and electrocardiographic features of the billowing posterior mitral leaflet syndrome. Analysis of a further 130 patients with a late systolic murmur or nonejection systolic click. Am J Med 51:731-739, 1971 4. Roberts WC, Dangel JC, Bulkley BH: Nonrheumatic valvular cardiac disease: a clinicopathologic survey of 27 different conditions causing valvular dysfunction. Cardiovasc Clin 5:333-446, 1973 5. Hancock EW, Cohn K: The syndrome associated with midsystolic click and late systolic murmur. Am J Med 41:163-196, 1966 6. Willems J, Roelandt J, De Geest H, et al: Late systolic murmurs and systolic non-ejection clicks. Acta Cardiol 24:456-481, 1969 7. Pocock WA, Barlow JB: An association between the billowing posterior mitral leaflet syndrome and congenital heart disease, particularly atrial septal defect. Am Heart J 81:720-721, 1971 8. McDonald A, Harris A, Jefferson K, et al: Association of prolapse of posterior cusp of mitral valve and atrial septal defect. Br Heart

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J 33:383-387, 1971 9. Danlels DH, D’Ambroso U, Bedynek J: Unusual abnormalities associated with the floppy mitral valve syndrome. Med Ann Dist Columbia 43:4-8, 1974 10. Victoria BE, Ellloll LP, Gessner IH: Ostium secundum atrial septal defect associated with balloon mitral valve in children. Am J Cardiol 33:668-673, 1974 11. Jeresaty RM: Atrial septal defect and myxomatous mitral-valve prolapse. N Engl J Med 290:1088, 1974 12. Jeresaty RM: Mitral valve prolapse-click syndrome in atrial septal defect. Chest 67:132-133, 1975 13. Marshall CE, Shappell SD: Sudden death and the ballooning posterior leaflet syndrome. Detailed anatomic and histochemical investigation. Arch Pathol 98:134-138, 1974 14. Jeresaty RM: Mitral valve prolapse-click syndrome. Prog Cardiovast Dis 15:623-652, 1973 15. Popp RL, Brown OR, Silverman JF, et al: Echocardiographic abnormalities in the mitral valve prolapse syndrome. Circulation 491428-433, 1974 16. De Maria AN, King JF, Bogren HG, et al: The variable spectrum of echocardiographic manifestations of the mitral valve prolapse syndrome. Circulation 50:33-41, 1974

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