Author + information
- Received August 31, 2013
- Revision received November 7, 2013
- Accepted November 12, 2013
- Published online April 29, 2014.
- William C. Roberts, MD∗,†,‡∗ (, )
- Travis J. Vowels, BBA∗,
- Jong M. Ko, BA∗ and
- Robert F. Hebeler Jr., MD§
- ∗Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas
- †Department of Internal Medicine (Division of Cardiology), Baylor University Medical Center, Dallas, Texas
- ‡Department of Pathology, Baylor University Medical Center, Dallas, Texas
- §Department of Cardiothoracic Surgery, Baylor University Medical Center, Dallas, Texas
- ↵∗Reprint requests and correspondence:
Dr. William C. Roberts, Baylor Heart and Vascular Institute, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, Texas 75246.
Objectives The aim of the study is to describe gross and histological features of operatively excised portions of mitral valves in patients with mitral valve prolapse (MVP).
Background Although numerous articles on MVP (myxomatous or myxoid degeneration, billowing or floppy mitral valve) have appeared, 2 virtually constant histological features have been underemphasized or overlooked: 1) the presence of superimposed fibrous tissue on both surfaces of the leaflets and surrounding many chordae tendineae; and 2) the absence of many chordae tendineae on the ventricular surfaces of the leaflets as the result of their being hidden (i.e., covered up) by the superimposed fibrous tissue.
Methods We examined operatively excised portions of prolapsed posterior mitral leaflets in 37 patients having operative repair.
Results Histological study of elastic-tissue stained sections disclosed that the leaflet thickening was primarily due to the superimposed fibrous tissue. All leaflets had variable increases in the spongiosa element within the leaflet itself with some disruption and/or loss of the fibrosa element and occasionally complete separation of it from the spongiosa element. Both the leaflet and chordae were separated from the superimposed fibrous tissue by their black-staining elastic membranes.
Conclusions These findings demonstrate that the posterior leaflet thickening in MVP is mainly due to the superimposed fibrous tissue rather than to an increased volume of the spongiosa element of the leaflet itself. The superimposed fibrous tissue on both leaflet and chordae is likely the result of subsequent abnormal contact of the leaflets and chordae with one another. Chordal rupture (i.e., missing chordae) occurred in all 37 patients, but finding individual ruptured chords was rare.
Although numerous publications have appeared describing auscultory, angiographic, echocardiographic, and morphological features of mitral valve prolapse (MVP) (myxomatous or myxoid degeneration), surprisingly, none have reproduced the various histological features of the operatively excised mitral valves or parts thereof in color after staining for elastic fibers, an absolute necessity for proper evaluation, because a black-staining elastic membrane separates the leaflet and chordae from the superimposed fibrous tissue, a constant feature of MVP. In this report, we focus on the contribution of the superimposed fibrous tissue to the leaflet and chordal thickening, and second, we introduce the concept that missing or hidden chords (those lying beneath the superimposed fibrous tissue) are equivalent to ruptured chords.
Since March 1993, all specimens excised at operation by cardiac surgeons at Baylor University Medical Center at Dallas have been submitted to the surgical pathology division of the pathology department, and all such specimens have been described by one of us (W.C.R.) who submitted the pathology report. Most gross specimens were photographed. After describing the submitted specimen, clinical, echocardiographic, and hemodynamic data were retrieved online via the Baylor University Medical Center at the Dallas Electronic Medical Records and the Apollo Cardiovascular Database. A total of 500 mitral valves or portions thereof were received from January 2005 through June 2013 (Fig. 1). Of this number, 140 patients underwent mitral valve repair or replacement for severe mitral regurgitation (MR) secondary to MVP. After excluding those patients where pre-operative echocardiograms (n = 71) were not available to us or histological sections of the excised valves were not prepared or retrievable (n = 14) or the patients had chronic renal failure (n = 4), 51 patients were available for study: 14 had mitral valve replacement and were then excluded from the present study; 37 had mitral valve repair, and in each, portions of the posterior leaflet were studied. Sections of the posterior leaflets were cut from the margin of attachment to the free margin and submitted for histological preparation. After processing in alcohol and xylene, 2 sections were cut from each paraffin block: one was stained by hematoxylin/eosin, and the other, by elastic van Geison.
Pertinent data from the 37 patients are summarized in Table 1. (Data on the 14 patients having mitral valve replacement for MVP are shown in the table simply for comparison.) The operative report in all 37 patients indicated “prolapse” of a portion of posterior mitral leaflet and that the prolapsed segment was the one almost always excised. None of the 37 had calcific deposits in the operatively excised specimens. All 37 patients also had an annular ring inserted.
Examination of the posterior mitral leaflet in the 37 patients disclosed several consistent features (Figs. 2 to 9, Table 2). All 37 operatively excised portions of posterior mitral leaflet had “missing” (i.e., ruptured) chordae tendineae on gross examination. Histologically, the leaflet itself and the chordae tendineae were clearly demarcated by an elastic membrane (elastic van Geison stain). Both atrial and ventricular aspects of the leaflet in all 37 patients contained superimposed fibrous tissue, thicker on the atrial side than on the ventricular side. Additionally, numerous elastic fibers were present in the superimposed fibrous tissue on the atrial aspect, whereas few if any were present in the superimposed fibrous tissue on the ventricular aspect. The fibrous tissue surrounding the chordae tendineae was similar to that on the ventricular aspect of the leaflet. Within the mitral leaflet itself—enclosed by the elastic membrane—the spongiosa element seemed increased in quantity in all patients, more so in the distal one-half than in the proximal one-half of the leaflet; and the fibrosa element was interrupted focally and/or decreased in quantity or both.
Examination of operatively excised portions of posterior mitral leaflet in each of the 37 patients having mitral repair for MVP produced 2 major findings: 1) the leaflet and chordal thickening in patients with MVP is due in large part to superimposed fibrous tissue on both the atrial and ventricular surfaces of the leaflets and surrounding the chordae tendineae; and 2) rupture of posterior leaflet chordae tendineae is a nearly universal finding in patients with MVP, and MR is severe enough to warrant operative repair but that seeing 1 or more ruptured chordae is infrequent, because they are covered (“hidden”) by the superimposed fibrous tissue on the ventricular surface of the leaflet. In essence, the absence of chordae (missing chordae) is synonymous with earlier rupture of chordae.
We surmise that the superimposed fibrous tissue on both leaflet and chordae is entirely due to abnormal contact of the leaflets with one another over many years or decades. That the underlying leaflet and chordae are essentially intact suggests that the basic process in MVP is a slow, gradual loss and/or interruption of collagen fibers (in the fibrosa element of the leaflet and in the chordae tendineae, which are devoid of a spongiosa element). The loss and/or interruption of collagen fibers within the leaflet and chordae seems to be responsible for the gradual elongation of the leaflets and chordae in MVP, which in turn leads to inappropriate leaflet contact and to the superimposed fibrous tissue (“callus” formation) (Fig. 10).
The superimposed fibrous tissue on the atrial and ventricular aspects of the posterior mitral leaflet is quite different histologically. On the atrial aspect, the surface is usually smooth, and the fibrous tissue is dense and contains numerous parallel-lying elastic fibers, simulating in a way the media of an elastic artery. By contrast, the superimposed fibrous tissue on the ventricular surface and surrounding the chordae tends to have an irregular surface, the collagen is less dense, and it contains few, if any, elastic fibers. The atrial surfaces, of course, are the ones making abnormal leaflet contact; the ventricular surfaces are receiving the impact of the left ventricular systolic pressure. The reason for the structural difference between the 2 surfaces is unclear.
That the identification of a ruptured chord is infrequent but that covered (by fibrous tissue) chordae are nearly universal in patients with MVP and MR severe enough to warrant operative repair strongly suggest that most chordal ruptures are clinically silent and occur possibly multiple times through the years. Also, the patients having acute heart failure might have ruptured a primary chord (i.e., one arising from a papillary muscle itself and not one actually attached to the mitral leaflet, as would be the case with a tertiary chord, which would unlikely lead to MR or to a sudden worsening of MR).
This article, of course, follows numerous ones discussing gross and histological features of prolapsed mitral valves examined at either necropsy or after operative excision (1–20). Few, however, mentioned the superimposed fibrous tissue on the leaflet and chordae, probably because elastic-tissue stains were not used, a requirement to see the outline of the underlying leaflet and chordae. Additionally, none mentioned hidden—previously ruptured—chordae by the overlying fibrous tissue. Thus, chordal rupture in MVP is far more common than previously appreciated (10,13,14,16,21–23).
Elastic-tissue stains were prepared on all histological sections of the operatively excised posterior mitral leaflets, a requirement to separate the superimposed fibrous tissue from the underlying leaflet itself. In all cases, the operative specimen and histological sections of it were studied and described by the same individual (namely, W.C.R.) and not by a variety of persons with varying knowledge of and interest in cardiovascular disease. All patients included had pre-operative echocardiograms described by the reader to be characteristic of MVP. The present report excluded all patients with angiographic evidence of significant coronary narrowing and any patient having coronary artery bypass grafting; all patients with a dysfunctioning aortic valve or aortic valve repair or replacement and all patients with associated mitral stenosis or prior infective endocarditis at any time were also excluded. All these exclusions were an attempt to make certain the patients included herein were a group with “pure” MVP.
We studied only patients with MVP who had MR severe enough to warrant mitral valve repair. Whether our observations hold true for younger patients (e.g., with mild MR from MVP) is unclear. Additionally, the amount of mitral leaflet tissue available to examine varied from patient to patient. Although all 37 patients had precordial systolic murmurs recorded in the medical record, whether the murmur was pansystolic or late systolic only or accompanied by 1 or more systolic clicks was not recorded. The echocardiograms were interpreted by a number of different echocardiographers. Details of the thickness of the mitral leaflets were not recorded in any echocardiographic report and not by any surgeon at operation.
This study of operatively-excised posterior mitral leaflets in patients with MR secondary to MVP indicates that the leaflet thickening is the result primarily of superimposed fibrous tissue on both surfaces of the leaflet and that previously ruptured chordae, nearly universal, are usually covered by the superimposed fibrous tissue on the ventricular surface by the time of operative intervention.
The study was funded by the Baylor Health Care System Foundation, Dallas, Texas. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- mitral regurgitation
- mitral valve prolapse
- Received August 31, 2013.
- Revision received November 7, 2013.
- Accepted November 12, 2013.
- American College of Cardiology Foundation
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