Journal of the American College of Cardiology 2000 by the American College of Cardiology Published by Elsevier Science Inc.

Vol. 35, No. 3, 2000 ISSN 0735-1097/00/$20.00 PII S0735-1097(99)00588-4

Pediatric Cardiology

Clinical Features and Management of Isolated Cleft Mitral Valve in Childhood

Masamichi Tamura, MD,* Samuel Menahem, MD, FRACP, FACC,* Christian Brizard, MD Melbourne, Australia
OBJECTIVES We reviewed an institutional experience of isolated cleft mitral valve (ICMV), its clinical features, and management in a pediatric population.

BACKGROUND As ICMV is relatively uncommon, earlier reports highlighted its anatomical and echocardiographic features. Few studies have collated their clinical features with their outcome. METHODS RESULTS All patients with ICMV were retrospectively reviewed. Patients who were considered to have an atrioventricular septal defect or variant were excluded. Twenty patients (9 male, 11 female) were diagnosed with ICMV. Seven patients had associated cardiac lesions. The median age of diagnosis was 5.2 years (range 0.4 to 13.6 years). Echocardiography aided by color Doppler demonstrated the ICMV in all patients. However, an incomplete diagnosis was made in 4 of 20 patients before surgery. The severity of the mitral regurgitation (MR) at presentation was mild in 11, moderate in 8, and severe in 1 patient. In the 13 patients without associated cardiac lesions, 5 underwent mitral valve (MV) repair at median age of 5.2 years (range 1.2 to 7.7 years) for moderate to severe MR, 4 being symptomatic. The severity of the MR in seven of the eight unoperated patients has remained unchanged over the follow-up period (median 8.3 years, range 0.7 to 14.4 years). In total, 10 patients underwent MV repair (median 6.4, range 0.4 to 13.8 years). No patient required MV replacement. None of the 10 patients had more than mild MR over the follow-up period (median 0.6, range 0.2 to 11.0 years).

CONCLUSIONS Now readily diagnosable by echocardiography, ICMV is a correctable cause of MR with a good outcome. Surgery is indicated in those patients with moderate to severe MR and probably should be done early following diagnosis. (J Am Coll Cardiol 2000;35:764 770) 2000 by the American College of Cardiology

Isolated cleft mitral valve (ICMV) is a rare cause of congenital mitral regurgitation (MR). Its importance lies in its potential for surgical correction with generally good to excellent results. Before the introduction of high-resolution, crosssectional echocardiography, the diagnosis of ICMV was usually not made until surgery or at autopsy (1). With the advent of cross-sectional echocardiography, ICMV may be readily diagnosed (2,3). At the same time it has been possible to differentiate between ICMV with its separate left atrioventricular junctions and an atrioventricular septal defect (AVSD) with its common atrioventricular junction (2,4,5). Although ICMV is relatively uncommon (4,6), earlier reports highlighted its anatomical and echocardiographic features (1 6) as well as its surgical repair (79). However, few studies have collated its clinical features with its outcome (1,5,7). In addition, some earlier reported cases

may have had a common atrioventricular junction, suggesting an AVSD or a variant (6). We wish to review our experience of a pediatric population with ICMV to highlight its clinical features and its medical and surgical outcome.

SUBJECTS AND METHODS

All patients with ICMV diagnosed by echocardiography and/or surgery at the Royal Childrens Hospital, Melbourne, since 1976 were studied. Their medical records, investigations and surgical reports were reviewed, and wherever possible the patients were examined by one of the study investigators. Care was taken to clarify the normal offsetting of the atrioventricular valves to exclude any patients with an AVSD or a variant. The severity of the MR was assessed semiquantitatively as being trivial, mild, moderate or severe by echocardiography aided by pulsed (10,11) and color Doppler (12,13). Additional help was obtained from systolic pulmonary venous ow reversal (14,15). In those patients who presented prior to the availability of cross-sectional echocardiography, the severity of the MR was determined on clinical, chest X-ray,

From the *Department of Cardiology and Victorian Cardiac Surgical Unit, Royal Childrens Hospital, Melbourne, Australia. Supported by Royal Childrens Hospital Research Institute Part-time Career Grant. Manuscript received December 31, 1998; revised manuscript received September 23, 1999, accepted November 10, 1999.

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Abbreviations AVSD ICMV LA MR MV TOE VSD

and Acronyms atrioventricular septal defect isolated cleft mitral valve left atrium mitral regurgitation mitral valve transesophageal echocardiography ventricular septal defect

electrocardiography and cardiac catheter ndings. Transesophageal echocardiography (TOE) has more recently been used.

RESULTS
Table 1 summarizes the clinical features of the patients seen. The nding of ICMV was diagnosed in 20 patients. In the four patients seen prior to the advent of echocardiography, three were considered to have a ventricular septal defect (VSD) or MR while the fourth appeared to have MR following repair of a coarctation of the aorta. The ICMV was only conrmed subsequently when cross-sectional echocardiography became available.

The median age at presentation was 3.8 years (15 days to 12.7 years). The median age at diagnosis was 5.2 years (0.4 to 13.6 years). The median follow-up period was 7.2 years (0.7 to 17.4 years). Associated cardiac lesions were present in 7 of 20 patients (Table 1). Three patients had an additional mitral valve (MV) anomaly (Patients 14, 15, 16), two with a double orice MV but only a single cleft, whereas four had additional (nonvalvular) cardiac anomalies (patients 17 through 20). The later included three patients with a perimembranous or outlet VSD. Each had accessory chordal attachments to the ventricular septum without evidence of straddling. Eleven of the 13 patients without associated cardiac lesions and the three with an additional MV anomaly presented with an asymptomatic murmur, typically an apical systolic murmur of MV regurgitation. A mid systolic click was audible in 3 of the 16 patients. Four patients with additional cardiac anomalies were symptomatic. The chest X-ray at presentation, available in all but one patient, showed cardiomegaly in ve and left atrial (LA) enlargement in seven patients. Two patients in addition showed features of pulmonary congestion. The ECGs available in 19 patients were essentially normal. None had left axis

Table 1. Age and Mode of Presentation, Duration of Follow-up and Associated Features
Age at First Presentation (yr) 5.1 2.6 5.1 5.6 5.4 4.4 3.7 12.7 3.9 3.1 1.1 1.9 2.3 8.9 7.4 7.3 0.1 0.4 0.0 0.4 Age at Diagnosis of ICMV (yr) 5.1 3.8 6.5 13.6 5.6 4.4 3.7 12.7 3.9 3.1 1.1 1.9 7.6 8.9 7.4 11.3 3.0 0.4 7.3 5.3

Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Gender M M M F M F F M M F M M F F F F F F F M

Follow-up Period (yr) 7.4 9.6 14.4 10.6 8.3 5.0 0.7 5.0 4.0 7.5 0.8 0.7 16.3 0.7 1.7 7.0 14.2 5.1 11.8 17.4

Presentation Heart murmur Heart murmur Heart murmur Heart murmur Heart murmur Heart murmur Heart murmur Heart murmur Heart murmur Heart murmur Heart murmur, failure to thrive Heart murmur, frequent RTI Heart murmur Heart murmur Heart murmur Heart murmur Failure to thrive, heart murmur Tachypnoea, heart murmur Heart murmur Failure to thrive

Associated Cardiac Anomaly

Associated Features

Down syndrome

Double orice mitral valve Double orice mitral valve Mitral valve prolapse VSD(peri), ASD(II) VSD(peri), PDA, RVOTO VSD(peri), PDA CoA

Marfan syndrome

Dysmorphic with normal chromosome Down syndrome

ASD atrial septal defect; CoA coarctation of the aorta; ICMV isolated cleft mitral valve; PDA patent ductus arteriosus; RVOTO right ventricular outow tract obstruction; RTI respiratory tract infection; VSD(peri) perimembranous ventricular septal defect.

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Table 2. Echocardiographic and Electrocardiographic Features

Chodal Attachment to the Ventricular Septum YES YES YES YES YES NIL YES YES YES NIL YES NIL YES YES YES YES YES YES YES YES Electrocardiographic Data TOE Findings Severity of MR at Presentation Mild Moderate #Mild #Mild Mild Mild Mild Mild Moderate Moderate Severe Moderate #Moderate Moderate Moderate Mild Mild Mild Mild #Moderate Changes in MR Severity Mild Moderate Mild Mild Mild Moderate Mild Mild Moderate Severe Severe Moderate Severe Moderate Severe Severe Mild Mild Trivial Moderate PR Interval (s) 0.18 0.17 0.15 0.14 0.12 0.13 0.16 0.12 0.18 0.12 0.14 0.18 0.13 0.14 0.17 0.12 0.12 0.16 0.12 QRS Axis (degree) 60 65 50 35 80 100 45 70 30 80 10 20 70 50 20 90 145 60 25

Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Origin of the MR Jet Cleft Cleft Cleft Uncertain Uncertain Cleft Cleft Uncertain Cleft Cleft Cleft Cleft Uncertain Cleft Cleft Coaptation Cleft Cleft Cleft Cleft

Direction of the MR Jet Postero-superior Posterior Posterior Uncertain Uncertain Posterior Posteri-superior Uncertain Posterior Posterior Posterior Posterior Uncertain Posterior Posterior Postero-lateral Posterior Posterior Posterior Posterior

Conrmed Uncertain Conrmed Conrmed Uncertain Uncertain

Conrmed

MR mitral regurgitation; TOE transoesophageal echocardiography; # evaluated before echocardiography; IRBBB incomplete right bundle branch block; s seconds.

deviation, whereas two had an incomplete right bundle branch block pattern (Table 2). Cross-sectional echocardiography aided by pulsed and color Doppler interrogation demonstrated a cleft dividing the aortic (anterior) leaet of MV into two and best seen in diastole, the regurgitant jet coming through the cleft in systole (Fig. 1). The cleft was correctly identied in all of the 13 patients without associated cardiac lesions. In contrast, in two patients with a double orice MV, echocardiography, although highly suggestive in one, failed to show the MV anomaly in the other, which was only conrmed at surgery. The second orice is usually competent and therefore not highlighted by color Doppler. In two of the four patients with additional cardiac anomalies, the ICMV was not recognized prior to surgery. Accessory chordal attachments to the ventricular septum were found in 17 cases, though only observed in three patients on the initial studies. No left ventricular outow tract obstruction was noted in this series. A TOE was performed in seven patients, ve being done at the time of surgery to assess the degree of incompetence prior to and following repair. However, this failed to demonstrate clearly the ICMV in three of the seven patients. The outcome of the MR is summarized in Figure 2. In the 13 patients without associated cardiac lesions, six of the seven patients with mild MR at presentation remained unaltered over the median follow-up period of 7.9 years (0.7 to 14.4 years) (Table 1). One patient developed moderate

MR but remained asymptomatic. Three of the ve patients with moderate MR at presentation remained unaltered, although two proceeded to surgery. The other two developed severe MR and required surgery, as did another patient who had severe MR at presentation. These ve patients with moderate to severe MR (Patients 9 through 13), four being symptomatic, had repair of their cleft at a median age of 5.2 years (1.2 to 7.7 years) with a median follow-up period of 2.1 years (0.1 to 5.3 years). The three patients with additional MV anomalies proceeded to surgery, the severity of the MR having worsened in two of three patients. In the four patients with additional cardiac anomalies, two of them did not have repair of their unrecognized ICMV at the time of the initial surgery. The severity of the MR had not shown any deterioration in either of them. The other two patients had their ICMV repaired at the time of initial surgery for the associated cardiac anomalies, the MR being mild in both of them. A total of 10 patients underwent MV repair at the median age of 6.4 years (0.4 to 13.8 years) (Table 3). The mean cardiopulmonary bypass and aortic cross-clamp times were 59.5 19.4 min and 38.5 17.8 min, respectively. The surgical techniques used in each patient are delineated in Table 3. In the two patients with a double orice MV, closure of the minor orice, which was a defect in the belly of the septal leaet with a separate well-dened suspension apparatus, did not lead to subsequent mitral stenosis. No patient required MV replacement. None of the 10 patients who underwent MV repair had more than mild MR over

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normal mitral valve. In addition, the former is eminently suitable for surgical correction where indicated (8,9), in contrast to the more problematic repair of the atrioventricular valve incompetence arising from an AVSD (4,6,9). Diagnosis. In our series, cross-sectional echocardiography aided by color Doppler echocardiography was able to demonstrate the ICMV in all patients when it became available. The echocardiographic features noted were consistent with previous studies (2,3), the cleft being directed toward the left ventricular outow tract in all cases, with normal offsetting of the atrioventricular valves. However, 4 of the 20 patients (20%) had an incomplete diagnosis on echocardiography. Subsequent review of the echocardiograms conrmed the ndings noted at surgery. In addition, chordal attachments between the cleft and the ventricular septum were only reported in three of our patients (15%) on the initial echocardiogram, which was strikingly less when compared with previous echocardiographic and autopsy reports (3 6), in which they were observed in all patients. Further review of the echocardiograms conrmed chordal attachments in an additional 14 cases. As Kohl et al. (4) concluded, the divided aortic leaet of the MV would be ail without such attachments. Our results suggest that echocardiography aided by Doppler interrogation is essential in diagnosing an ICMV, especially if isolated. The diagnosis might be overlooked if there are associated cardiac lesions; therefore, repeated and careful reviews may be necessary to clarify the mechanism of any MR observed in a pediatric population. Although we have found that TOE has been helpful in assessing the success of the valve repair for MR (20), little additional information was obtained about the site and size of the cleft. Further study is necessary to clarify the role of TOE in ICMV. Left axis deviation as well as a prolonged PR interval are common ndings in patients with an AVSD, which have a specic anomaly of the conduction system (21,22). According to Di Segni et al. (1), left axis deviation was found in 33% of reported cases of ICMV. By contrast, in our series the ECG was especially normal, though one patient had an axis of 10. All patients had a normal PR interval. Our series did not include patients with an inlet VSD or a univentricular heart in contrast with the previously reported cases, making it less likely for a conduction anomaly to be present. Although left axis deviation with a counterclockwise rotation of the initial vector on the frontal plane (23) has been previously observed, our results would suggest that patients with an ICMV had a normal frontal plane QRS axis if an AVSD or variant was excluded. Other researchers (7) seem to support our ndings, although their patient population was small. Clinical and surgical outcome. The age at presentation varied in our series; it ranged from 15 days to 12.7 years of age, a nding noted previously with ages ranging from 1 day to 52 years (1,3,7,23). However, when we compared the

Figure 1. A, Parasternal short-axis view at the level of the mitral valve. A cleft divides the aortic mitral leaet into two segments in diastole. (MV, mitral valve). B, Parasternal short-axis view at the level of the mitral valve. Color Doppler shows the regurgitant jet coming through the cleft. C, Parasternal long-axis view shows a break in the aortic mitral leaet. (LA, left atrium; LV, left ventricle; LVOT, left ventricular outow tract). D, Parasternal long-axis view with color Doppler. The regurgitant jet passes through the cleft being directed posteriorly.

the median follow-up period of 0.6 years (0.2 to 11.0 years). No surgical mortality occurred.

DISCUSSION
Although an uncommon congenital cardiac abnormality (4,6), ICMV is a well-recognized cause of congenital MR. Most commonly, the cleft involves the aortic leaet of the MV (6), although an isolated cleft on the mural (posterior) leaet has been described (16,17). Following the advent of high-resolution cross-sectional echocardiography, ICMV has been more readily diagnosed and appears to be more common than previously thought (4,18). It is important to distinguish ICMV from the cleft seen with an AVSD (5,19). Sigfusson et al. (5) emphasized the fundamental difference in morphology between ICMV and the cleft in AVSD. In the former, the cleft leaet is supported by a discrete left atrioventricular junction, there being a mural leaet comparable in size to the dimensions seen in the

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Figure 2. The outcome and management of the MR seen in patients with ICMV. # Mitral valve repair was performed at the time of initial surgery for the associated cardiac lesion.

patients with and without associated cardiac lesions, all four patients with additional cardiac anomalies presented before 0.4 years of age with signicant cardiac symptoms related more to the associated cardiac lesions than to the ICMV. In fact, two patients whose ICMV was not recognized before the initial surgery failed to have their MV repaired, one of whom showed improvement of her severity of her MR from mild to trivial (Patient 19), whereas the other remained unchanged (Patient 20) with moderate severity of his MR. In contrast, patients without associated cardiac lesions presented later, at a median age of 3.9 years (range 1.1 to 12.7 years), although two patients (15%) presented before two years of age with signicant cardiac symptoms of failure to thrive and/or recurrent respiratory infections arising from their moderate to severe MR. They required semi-urgent surgical intervention. In addition, a further child presented with an incidental heart murmur arising from moderate MR. She went on to develop over the next ve years severe myocardial dysfunction and severe MR. Fortunately, her cardiac function recovered after MV repair. Our study demonstrated that six of the seven patients (86%) who presented with mild MR remained unchanged (Fig. 2). The remaining patient showed signicant deterioration of the MR without development of symptoms after 5.0 years of follow-up. In contrast, all the patients except one (83%) who presented with moderate to severe MR required surgical intervention over the follow-up period. Our results suggest that those with mild MR remained

stable and required only long-term clinical and echocardiographic review. Conversely, in the patients who presented with more than moderate MR, surgical intervention may need to be considered semi-electively or at presentation so as to avoid the development of possible cardiac dysfunction as seen in one patient, and/or possible thickening of the cleft edges (6). It has been well accepted that conservative MV repair is feasible in most cases with congenital MR (9). In our series, MV repair was carried out in 10 patients and led to a satisfactory result at a median follow-up of 3.2 years, with no surgical mortality or signicant morbidity. Di Segni et al. (6) reported that a positive relationship existed between the age of the subjects and the thickness of the cleft edges, which may increase the difculty of the MV repair. Another team (7) reported that a direct suture repair was possible only in their youngest patient, aged 13 years, while others ranging from 25 to 41 years required augmentation of the leaet. We therefore suggest that patients with increasing or hemodynamically signicant MR should have early surgical intervention regardless of their symptomatology. In our two patients with a double orice MV, closure of the second orice was probably unnecessary as the usual intraoperative testing of the valve with saline may well have conrmed its competence. Conclusions. We conclude that cross-sectional echocardiography, aided by color Doppler interrogation, is especially

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JACC Vol. 35, No. 3, 2000 March 1, 2000:764770 Table 3. Patients Subjected to Mitral Valve Repair
Follow-up Period Clinical Findings and Before Indication of the MVRE (y) Mitral Valve Repair 3.8 Progressive exercise intolerance Initial Severity of MR Moderate

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Patient No. 9

Age for MVRE (y) 7.7

Surgical Summary Suture of cleft in the posterior leaet, autologous pericardial patch repair of the cleft in the anterior leaet Suture of cleft Suture of cleft, MAP Suture of cleft, MAP Suture of cleft, MAP Suture of cleft, pericardial patch closure of the minor orice Suture of cleft, pericardial patch closure of the minor orice Suture of cleft, MAP, shortening of paramedian chordae to correct localized MV prolapse Suture of cleft Suture of cleft

Severity of MR at the Operation Moderate

Postoperative Outcome Trivial

Follow-up Period After MVRE (y) 0.2

10 11 12 13 14 15 16

5.2 1.2 2.1 7.7 9.3 8.5 13.8

2.1 0.1 0.2 5.3 0.5 1.2 6.5

Asymptomatic, due to increase in MR Cardiac failure Frequent respiratory tract infections with signicant MR Progressive cardiac failure with LV dysfunction Asymptomatic Increase in MR with progressive exercise intolerance Increase in MR with progressive exercise intolerance Cardiac failure due to associated cardiac lesions Cardiac failure due to associated cardiac lesions

Moderate Severe Moderate #Moderate Moderate Moderate Mild

Severe Severe Moderate Severe Moderate Severe Severe

Mild Mild Trivial Trivial Trivial Trivial Mild

5.4 0.7 0.5 11.0 0.2 0.5 0.5

17 18

3.3 0.4

3.2 0.0

Mild Mild

Mild Mild

Trivial Mild

11.0 5.1

MAP mitral annuloplasty; MR mitral regurgitation; MVRE mitral valve repair; # evaluated prior to echocardiography; y years.

helpful in demonstrating an ICMV. However, the presence of associated cardiac anomalies may cause an ICMV to be overlooked. Therefore, the presence of MR requires careful and at times repeated study to clarify its mechanisms. The possibility of an ICMV should be considered even if not immediately recognized during an echocardiographic study. In addition, ICMV is a correctable cause of congenital MR with good surgical results. Such surgery is indicated for patients with moderate to severe MR even if asymptomatic. It probably should be done relatively early as the results of such repair are good and may avoid the risk of valve replacement or cardiac dysfunction. Acknowledgments Dr. Tom Karl kindly reviewed the manuscript, which was prepared by Ms. Margaret Meyers.
Reprint requests and correspondence: Prof. Samuel Menahem, Department of Cardiology, Royal Childrens Hospital, Flemington Road, Parkville, Victoria, 3051, Australia. E-mail: menahems@cryptic.rch.unimelb.edu.au.

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

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