lr~terr~utronul Jw_mul of Cardiolofi)‘, rl’ 1997 Elsevier
37 (199.2) 79-89
Science Publishers B.V. All rights reserved
Surgical pathology of the mitral valve: gross and histological study of 1288 surgically excised valves Lucia Agozzino ‘, Antonio Falco “, Fabrizio de Vivo ‘, Carlo de Vincentiis Luigi de Luca T.S. ‘, Salvatore Esposito a and Maurizio Cotrufo h Itlstitutes of’ ‘I Pathology urtd h Medical and Strrgicul Curdiology,
1st Medical School, University of Nuples, Nuples, Italy
(Received 30 March 1992;accepted 25 April 1991)
L, Falco A, De Vivo F, De Vincentiis C, De Luca TS L, Esposito S, Cotrufo M. Surgical of the mitral valve: gross and histological study of 1288 surgically excised valves. Int J Cardiol
1992;37:79-89. A consecutive series of 1288 mitral valves surgically excised from 1981 through 1989 were studied macroscopically and histologically. The explanted valves were affected by: chronic rheumatic disease (1179, 91.5%0), floppy mitral valve (84, 6.5%), bacterial endocarditis (19, 1.5%), and post-ischemic mitral incompetence (6, 0.5%). Among 1179 post-rheumatic cases, mixed mitral stenosis and incompetence was the most frequent malfunction (747, 58%). Isolated mitral incompetence was diagnosed in 72 (6.11%) cases only, and isolated stenosis in 360 cases. In 52 valves, excised because of chronic rheumatic disease, the histology showed unexpected signs of acute rheumatism of the leaflets and the papillary muscles. In these patients clinical symptoms and blood tests were negative for rheumatic disease. Mitral incompetence, possibly due to papillary muscle dysfunction, was the prevalent lesion (61.5%). A total of 181 patients (14.05%) with pure mitral incompetence underwent surgery. In 84 patients (36.4%). the floppy mitral valve was the most frequent cause of valve dysfunction, 72 (39.8%) had rheumatic disease, 19 (10.5%) infective endocarditis, and 6 (3.4%) ischemic heart disease. In the group with floppy mitral valve, males were more prevalent than females (51 : 33). The mean age of the 4 patients with Marfan’s syndrome and non-Marfan patients was noticeably different (17 vs 49 yr). Moreover leaflet deformation, tendinous cord elongation and annulus dilatation were the most common causes of valve incompetence. Floppy mitral valve and infective endocarditis were the cause of cordal rupture in 43.5%~of the cases. This was a severe complication which always required emergency surgery. Key words: Floppy mitral valve; Rheumatic
heart disease; Endocarditis;
Cwr~spondence to: Prof. L. Agozzino M.D., lstituto di Anatomia
Via L. Armanni,
5, 80138 Napoli.
Introduction In the past years, the pathology of cardiac valves has been thoroughly studied at autopsy. Today the specimens obtained during cardiac surgery allow the study of a greater number of valves affected by different diseases. In addition to this selected material, much clinical and surgical information is also available to the pathologist [l]. The gross and histological examination of the surgically excised valves enhances the knowledge of native cardiac valve diseases [2,3]. Whole mitral valve pathology has rarely been described in literature 14-61. In fact, the majority of published papers focus on a single disease. Mitral valve prolapse with leaflet floppiness is the most investigated pathology [7-111. The goals of this study were: (1) to define the spectrum and incidence of the different valve pathologies in our surgical population, and (2) to identify the pathologic findings of the different mitral valve diseases (rheumatic, floppy valve, infective endocarditis).
Materials and Methods From January 1981 until December 1989, 1288 consecutive mitral valves were surgically excised at the Department of Medicaland Surgical Cardiology of the 1st Medical School, University of Naples, Naples, Italy. The valves were successively studied at the Institute of Pathology of the same University. Clinical and surgical data were included with each specimen sent from the Cardiovascular Department. Gross examination was performed in all cases and pictures of the specimens were subsequently taken. The 1288 explanted valves (Tables 1, 2) were affected by chronic rheumatic disease in 1179 cases (91.5%); of these 360 (30.5%) were stenotic, 72 (6.11%) were incompetent, and 747 (63.3%) had combined malfunction (Table 3). Floppy mitral valve (841, infective endocarditis (19) and ischemic heart disease (6) were other causes of pure mitral incompetence (Table 41. Chordal rupture and infective endocarditis were the most frequent complications in the group with floppy mitral valve (Table 51.
The histology was carried out on leaflet fragments obtained from the free margin and base of the leaflet, tendinous cords, and papillary muscles. The specimens were fixed in paraffin, sliced in 5-7 pm sections and stained with hematoxylin-eosin, Weigert Van Gieson, Alcian PAS, PAS and if needed, Von Kossa, Gram and Grocott. In order to identify fungal organisms, silver stain methods were also used. To allow a sufficient amount of tissue for the study, at least two-thirds of each papillary muscle was excised during surgery. The histoIogy was performed at the base of the papillary muscle in order to avoid the inflammation which sometimes diffuses from leaflets and tendinous cords to the papillary muscles. The degree of annulus dilatation in cases of isolated mitral valve incompetence, was obtained by subtracting the diameter of the used prosthesis minus the theoretical diameter of the normal mitral valve, based on the body surface area of the patient. A dilatation < to 3 mm was accepted as normal, between 3 and 6 mm the dilatation was considered mild, between 6 and 9 moderate, and > 9 mm severe. In order to perform a microscopic study, a fragment was taken from the annulus in 60% of the cases.
warts on the closure line of the mural leaflet (arrows).
Of the patients with chronic rheumatic mitral disease, 760 (64.5%) were females and 419 (35.5%) males. The mean age was 42 + 7 yr. Of these patients, 366 also had associated chronic rheumatic aortic disease. Table 3 gives the macroscopic changes observed on the specimens according to the type of pathology (Figs. 1, 2). Stenotic insufficiency was the most frequent dys-
Results Table 1 shows the incidence of the different mitral lesions. Rheumatic heart disease was the cause of valve malfunction in 91.5% of the patients. Table 2 gives the types of valve dysfunction in the overall population. Isolated incompetence was noted in 14% of the excised valves.
and fusion of tendinous feature (ventricular
combined cords with
function (747, 63.35%). Stenosis was seen in 360 (30.54%) of the valves while isolated incompetence was seen in 72 (6.11%). Of the 72 patients with isolated mitral incompetence, 32 showed microscopic findings of acute rheumatic disease (Table 3). The annulus was normal in 51 cases with post-rheumatic mitral incompetence, mildly dilated in 15, and moderately dilated in 6. The histology mainly showed fibrosis, hyalinosis and neovascularization (Fig. 3). Small fibrinous formations were sometimes found on the atria1 side of the leaflets. Acute rheumatic disease was microscopically diagnosed in 52 (4.41%) valves showing scattered lymphohistiocytic infiltrates of the leaflets with or without Aschoff cells and eventually fibrinoid necrosis (valvulitis). Thirty-two of 52 (61.54%) patients had pure mitral incompetence. All cases had papillary muscle myocarditis. This was nonspecific in the lymphohistiocytic interstitial infiltrates with or without Aschoff cells and myocytic necrosis in 49 cases, while the microscopic examination showed granulomatous myocarditis with Aschoff and aggressive muscle granulomas in 3 cases (Fig. 4). The Aschoff nodule was seen in its different evolutive stages, i.e. mucous edema and fibrinoid necrosis, granulomatous phase, and resolving phase. In all patients clinical symptoms and blood tests were negative for acute rheumatic disease. Mean age was 36 5 6 yr. Floppy mitral valve
Isolated mitral valve incompetence was treated in 181 patients (14%) (Table 2). The incidence of a floppy mitral valve was prevalent (46.4%) in this group while rheumatic disease was the cause of incompetence in 72 (39.5%) cases (Table 4). Myxomatous infiltration of the mitral valve (floppy mitral valve) was diagnosed in 84 (46.4%) patients (51 male and 33 female). The ages ranged between 7 and 63 yr, mean 49 yr. Marfan’s syndrome was diagnosed in 4 patients who were significantly younger (17 + 4 yr). Cardiac pathologies associated with non-rheumatic isolated mitral incompetence included: aortic incompetence due to myxomatous leaflet infil-
Fig. 3. Chronic
rheumatic mitral valve disease: (Van Gieson 100 X ).
tration (floppy aortic valve) in 13 patients, ostium secundum atria1 septal defect in 9 patients and tricuspid incompetence (floppy tricuspid valve) in 6. The valvular structures (annulus, leaflets, tendinous cords), all showed morphologic alterations. The annulus diameter was normal in 11 patients (13.1%), mildly dilated in 16 (19.5%), moderately dilated in 43 (51.19%) and severely dilated in 14 (16.67%). The pathologic findings were as follows: soft, redundant leaflets having a jelly-like aspect with dome-like prominences on the atria1 side of both the anterior (11.5%) and posterior (52.3%) leaflet. In 36.2% of the cases both leaflets were involved. The posterior leaflet frequently showed multiple scallops. One or more of these scallops were dome-shaped towards the left atrium and in some cases they were completely separated from each
other (Fig. 5). The commissures were never fused. Anomalous insertion of tendinous cords was reported in 10 cases (Figs. 5, 6).
Fig. 4. Aschoff
The histologic diagnosis of myxomatous mitral valve infiltration was made according to Guthrie and Edwards , and the criteria of Pomerance
cells in the subendocardium
(a. HE 25 X ;b, HE 100 x ).
Fig. 5. Floppy mitral valve: fully separated of the posterior leaflet. Tendinous cord muscles.
and domed scallops bridging 2 papillary
: (1) myxomatous infiltration and substitution (more than 50%) of the fibrous lamina, and (2) marked increase of the spongiosa (Fig. 7). The mitral valve annulus and tendinous cords showed myxomatous infiltration in 85% and 35% of the cases, respectively. Inflammatory reactions were never observed while neovascularization was only seen in association with endocarditis. The most frequent complication of floppy mitral valve was non-endocarditic rupture of the tendinous cords in 38 cases (43.5%) (Fig. 8).
Fig. 6. Floppy mitral valve: anterior leaflet. Two tendinous cords rising from a single stem, one inserted on the free edge of the leaflet and the other on the leaflet base producing an archlike shape.
Fig. 7. Floppy mitral valve: myxomatous degeneration of the leaflets’ fibrous layer. The whole tendinous cord structure was affected by the myxomatous degeneration, whereas the tendinous cord insertion was severely involved in the degenerative process.
Fig. 8. Floppy mitral valve: ruptured tendinous cords. Stumps of the ruptured cords for the mural leaflet are seen on the left.
There was associated infective endocarditis 91 in 11 (13.1%) cases (Table 5). Infective
Infective mitral endocarditis was diagnosed in 19 cases (1.5%, Table 1); 11 male and 8 female with a mean age of 36 + 5 yr. In all these cases the endocarditis caused mitral incompetence. There was one cerebral septic embolism. Ten patients also had an aortic endocarditis. Signs of chronic rheumatic disease were present in 4 mitral valves excised for infective endocarditis. In our population, endocarditis was the cause of isolated mitral incompetence in 10.5% (Table 4). Cases with infective endocarditis on the floppy mitral valve were not included in this group. The gross findings were mainly aneurysms, perforations and leaflet erosions. Polypoid vege-
Fig. 10. Infective endocarditis: large the anterior leaflet. Small vegetations
polypoid vegetations on on the tendinous cords.
tations were seen on the leaflets and tendinous cords. Post-endocarditic rupture of tendinous cords was reported in 6 cases (31.58%) (Figs. 9, 10, 111. The histologic findings were necrosis and lymphohistiocytic infiltrates. In 9 patients (42.11%) with negative blood cultures, the histology allowed the identification of the causative pathogens (bacteria, fungi).
Fig. 11. Mitral valve: infective endocarditis. Sharp central perforation of the anterior leaflet. Multiple erosions and vegetations of the posterior leaflet. Tendinous cord vegetations and rupture.
Fig. 12. Mitral valve: Infective
Post-ischemic mitral incompetence Post-ischemic mitral incompetence was seen in 6 patients. This pathoIogy accounts for 0.6% in the overall population and for 3.4% among the group of mitral incompetence. In all cases a papillary muscle dysfunction was identified as being causative of mitral incompetence. In 4 cases the anterior muscle was involved, and in 2 the posterior. Fracture of the posterior papillary muscle was observed in 1 patient with acute myocardial infarction. The histology showed ischemic myocell necrosis in 2 patients with recent acute myocardial infarction. Focal tissue fibrosis and muscle retraction was observed in 4 cases. Discussion In our study, rheumatic heart disease was the primary cause of mitral valve dysfunction. Postrheumatic valve stenosis and stenotic insufficiency represented 94% of the overall valvular pathologies (Table 3). Isolated incompetence was observed in 72 (6.1%) patients with chronic rheumatic disease. Almost half of these showed histologic signs of acute rheumatic disease.
seen from the atrial (a) and ventricular
Stenosis with normal subvalvular apparatus (diaphragmatic stenosis) was diagnosed in 30.5% of the cases. Females showed a higher incidence than males (760 : 419). In 52 specimens taken from patients with chronic rheumatic disease, the histology showed signs of acute rheumatic disease on the leaflets (valvulitis) and/or on the papillary muscles (myocarditis) of the excised valves. In 3 cases different evolutive stages of Aschoff nodules were found in the interstitium of papillary muscle. Valvulitis associated with myocarditis of the papillary muscles are pathognomonic for acute rheumatic disease [14,-161. The Aschoff nodules indicate a recent but not an ongoing rheumatic episode , and yet both clinical symptoms and blood tests were negative for acute rheu_matic disease in all patients. These findings confirm that chronic rheumatic mitral valve disease is an evolutive pathology. Subclinical episodes (recurrent rheumatism) may in fact, progressively worsen the valve malfunction requiring surgical replacement [14,16]. Furthermore, the fibrin deposits becoming fibrous tissue may cause a continuing deterioration of the valve function . In our experience fibrin deposits were frequently found on the atria1 side of the valves. These observations emphasize that
valve replacement is the treatment of choice in patients with chronic rheumatic disease. The group of patients with acute rheumatic disease was younger compared to the patients with chronic rheumatic disease (36 vs 42 yr). Pure mitral incompetence was diagnosed in more than half (61.5%). This could be due to a postmyocarditis papillary muscle dysfunction. In summary, the causes of mitral regurgitation in the group with mitral rheumatic incompetence were: t I) leaflet shortening, (2) annulus dilatation, and (3) papillary muscle dysfunction in patients with papillary muscle myocarditis. In our study and according to recent reports [4,18-221, the floppy mitral valve is the most frequently occurring non-rheumatic pathologic cause of mitral valve prolapse and pure mitral incompetence. In previously published papers, rheumatic disease is still considered to be the primary cause of pure mitral incompetence . However, an increase in degenerative versus post-inflammatory pathology has recently been noted [51. This could be due to the reduced incidence of rheumatic disease, to improved diagnostic techniques, and/or to the gross and histologic studies systematically performed on the surgically excised valves which allow a more frequent identification of this pathology. Contrary to the prevalence of females in the rheumatic disease group, males prevail in the group with floppy mitral valve (51: 33), as reported by Turri et al. [61. In the past, other authors [7,24,25] and we [261 have reported the prevalence of females in the group with floppy mitral valve. Macroscopic and histologic degenerations involve the whole valve structure, i.e. annulus, leaflets, and tendinous cords. In the non-endocarditic valves, the histology of the leaflets did not show inflammation. The floppy mitral valve specimens showing neovascularization were not included in this study, because the association of rheumatic disease and floppy mitral valve was not confirmed. A noticeable degree of annulus dilatation, caused by myxomatous degeneration, was seen in many of our specimens. On the other hand, mitral regurgitation itself played only a minor role in determining the annulus dilatation,
as demonstrated by post-rheumatic mitral incompetence where the annulus dilatation was less important and observed in only a few patients. In patients with or without cordal rupture the degree of dilatation was similar. As reported elsewere [7.26-291 and in our study, non-infective and non-traumatic spontaneous rupture of the tendinous cords was the most common complication of the floppy mitral valve. Most of the posterior leaflet cords were ruptured, whereas the posterior leaflet itself is more commonly affected by degenerative changes. In a small percentage (10.5%) both anterior and posterior leaflets were involved. The causes of cordal rupture were: (1) deformation and enlargement of the leaflets with progressive overtension and elongation of the cords, and (2) myxomatous infiltration frequently involving the tendinous cords [6,7,24,28,30]. Cordal rupture is a severe acute complication often requiring emergency surgery . In 9 patients an ostium secundum atrial septal defect was associated with the floppy mitral valve. This association is frequently reported [31-331 and might be due to hemodynamic 1341 or genetic causes (atria1 septal defect and valve malformation may be an expression of the same genetic disease) [351. On the other hand, some authors found only macroscopic but not histologic changes in patients with both atrial septal defect and floppy mitral valve associated with cordal rupture . The myxomatous infiltration of aortic and tricuspid valves represents a diffusion of the same degenerative disease. More than 30 yr have passed since the floppy mitral valve was first described in 1958 , and its pathogenesis is still controversial. Many theories have been proposed during these years. According to the myocardial theory. valve prolapse and degeneration might be caused by a segmental myocardial dysfunction [51, left ventricle asynergy [37,38] and papillary muscle dysfunction ; Roberts [351 includes the floppy mitral valve among the “congenital cardiovascular abnormalities usually silent until adulthood”; the floppy mitral valve has been considered a “forme fruste” of Marfan’s syndrome . Finally, some authors consider the disease to be a result of annulus
anomalies (dysjunction) [39,40] or tendinous cord insertion anomalies . Abnormal cord insertions were noted in our population, but it remains difficult to discern whether it is causative of the floppy mitral valve or an incidental finding. Conservative surgery is the treatment of choice for the floppy mitral valve. The intermediate follow-up of these patients shows good results [ 19,20,42]. However, morphologic studies demonstrate a slow but continuous progression of the disease, as expected in this degenerative pathology. There is always concern that cordal rupture could be an impending event in these patients who must be strictly controlled. Infective endocarditis represents 1.5% of the overall mitral pathology and 10.5% of the isolated mitral incompetence. In these cases, gross inspection showed polypoid, ulcerative and ulcerous-polypoid forms. In 9 patients with negative blood culture, the causative pathogen was identified at the microscopic study. It is significant that only 4 cases had associated chronic rheumatic disease. In our experience infective endocarditis does not affect rheumatic valves any more than normal valves. All patients with infective endocarditis underwent surgery for a pure mitral incompetence. Post-endocarditis cordal rupture was diagnosed in 31.5% of the cases. Cordal rupture is typical of floppy mitral valve and bacterial endocarditis. Spontaneous cordal rupture, unrelated to a traumatic event or to the above-mentioned diseases, is still being debated .
Conclusion It is important to study the pathology of the heart valves excised during cardiac surgery. This method allows better understanding of the structural changes and pathogenesis of the different diseases which affect cardiac valves. This paper focuses on the high incidence of mitral rheumatic disease and the growing incidence of degenerative mitral disease. Rheumatic heart disease is an evolutive disease, more frequently seen among females, which provokes stenosis, or incompetence, or combined malfunc-
tion with a low degree of annulus dilatation in cases of mitral incompetence. The floppy mitral valve is a degenerative disease more frequent in males, causing pure mitral incompetence due to annulus dilatation, cordal elongation and leaflet floppiness. Cordal rupture is an always impending complication.
Acknowledgement The authors thank Miss Janine Robinson R.N. for the revision of the English manuscript.
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