logo

Home  ||   Editorial Board  ||  Related Links ||  News & Events ||   Rights & Permissions   ||  Contact us  
November 19, 2017
Degenerative Disease Clinical Presentation & Pathology

Clinical Presentation & Pathology

Introduction

Degenerative mitral valve disease has become the predominant cause of mitral regurgitation in developed countries during the last three decades mainly because of the eradication of rheumatic fever and the aging population. The two most common etiologies are Barlow's disease and fibroelastic deficiency. Marfan disease, the third etiology, is encountered in a minority of patients. In about 10-20 % of patients, although the valve displays some characteristics compatible with either Barlow's disease or fibroelastic deficiency, it is difficult to determine the exact etiology leading Carpentier to suggest the concept of "spectrum of degenerative mitral valve disease".

The original and historic contributions of John Barlow and Alain Carpentier who described for the first time the characteristic features of these two clinical entities were extensively discussed in the Historic Review section. Here, we will focus on the state-of-the-art knowledge in the diagnosis and surgical treatment of patients with degenerative valve disease.

 

Clinical presentation & Pathology

Barlow's disease

Barlow's disease is encountered in about 5 % of the general population. As mentioned in the historic review, familial forms have been reported as early as 1960's. Genetic studies during the last two decades have shown a strong association between this disease and alteration sites of chromosomes 11, 13 and 16 with an autosomal dominant transmission mode.

Barlow's disease is often diagnosed in the first three decades of life during a routine medical examination. The prevalence of the disease is greater in women; however, most patients that require surgical intervention for severe valvular regurgitation are male. In the majority of cases, the disease is benign and patients remain asymptomatic throughout their life with none or minimal valve regurgitation. Occasionally, patients may complain of a variety of clinical symptoms including dyspnea, fatigue, chest pain, and palpitation. These symptoms may occur in the absence of mitral regurgitation. At physical examination, the main characteristics are a midsystolic click and an apical late systolic murmur.

In about 5% of patients, valvular degeneration may progressively evolve leading to significant mitral regurgitation. Patients with severe valvular regurgitation may remain asymptomatic for certain period of time or develop symptoms such as fatigue, dyspnea, syncope or palpitation. They often seek medical advice for the first time at this occasion. Patients who require surgical intervention to correct valvular regurgitation are often in the fourth or fifth decades of their life.

From pathologic point of view, Barlow's valve is characterized by myxomatous proliferation. The three-layer leaflet tissue structure is disrupted by myxoid degeneration. These structural changes lead to specific morphologic features: excess mitral leaflet tissue with billowing of the bellies of the leaflets into the left atrium.

In Barlow's disease, leaflet tissue is excessively redundant and thick, predominantly at the coaptation zone. Chordae are often thick and elongated. Occasionally, they are thin and may be shortened. The interconnection between marginal and secondary chordae displays a typical mesh-like configuration. Papillary muscles are sometimes elongated. The mitral annulus is severely dilated and may be calcified. The excess leaflet tissue may cause an outward displacement of the posterior leaflet attachment to the crest of the ventricle, creating cul-de-sacs that can become calcified over time.

The mechanism of mitral regurgitation is almost always Carpentier's type II dysfunction with leaflet prolapse, which affects invariably multiple segments of the valve. Leaflet prolapse results from chordae elongation or rupture with the former being more frequent than the latter. Severe annular dilatation plays also an important role in the genesis of regurgitation. In some instances, extensive calcification of the antero-lateral papillary muscle with restricted leaflet motion of the P1 segment and anterior commissure can be at the origin of mitral regurgitation.



Stephen Hales
Stephen Hales
Stephen Hales

 Fibroelastic deficiency

During the last three decades, the incidence of fibroelastic deficiency has been steadily increasing in the developed countries because of the aging population. It is currently the second most frequent cause of degenerative mitral valve disease. In contrast to Barlow's disease, Fibroelastic deficiency is most common in elderly patients (>65 years). They often present with a relatively short history of systolic murmur of mitral regurgitation. They do not have any family history of mitral valve disease as fibroelastic deficiency is not linked to any genetic abnormalities. At the time of presentation, they are usually symptomatic with fatigue, dyspnea on exertion, or palpitation due to atrial fibrillation. Occasionally sudden development of mitral regurgitation due to chordae rupture can cause pulmonary edema and congestive heart failure.

From pathologic point of view, Fibroelastic deficiency is characterized by a rarefaction of connective tissue, with paucity of collagen, elastin and proteoglycanes. Despite these histologic changes, it is important to stress that the three-layer structure of the valve is preserved. Mitral valve leaflets are very thin and transparent without excess tissue. Similarly, chordae are very fragile and thin. The mitral annulus is mildly and symmetrically dilated with occasional calcification at its posterior segment.

The mechanism of mitral regurgitation is Carpentier's type II dysfunction with leaflet prolapse, which usually affects one segment of the valve, mostly the P2 segment. Chordae rupture is the most common lesion leading to leaflet prolapse. Although type II-P2 is the most common dysfunction and segmental localization, fibroelastic deficiency can also present with anterior or bileaflet prolapse due to chordae elongation and/or rupture.

An important feature of fibroelastic deficiency is the development of secondary lesions at the level of prolapsing segment with myxoid degeneration, excess tissue, and leaflet thickening which may entertain the confusion with the diagnosis of Barlow's disease on echocardiography or histologic analysis.



Stephen Hales
From Carpentier A, Adams DH, Filsoufi F. Carpentier's Reconstructive Valve Surgery. Saunders (Elsevier), 2010
Stephen Hales
Stephen Hales



REFERENCES

Barlow JB, Pocock WA, Marchand P, Denny M. The significance of late systolic murmurs. Am Heart J 1963;66:443

Barlow J, Bosman CK. Aneurysmal protrusion of the posterior leaflet of the mitral valve; An auscultatory-electrocardiographic syndrome. Am Heart J 1966;71:166-78

Barlow JB, Bosman CK, Pocock WA, Marchand P. Late systolic murmurs and non-ejection ("mid-late") systolic clicks. An analysis of 90 patients. Br Heart J 1968;30:203-18

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 non ejection systolic click. AM J Med 1971;51:731-39

Carpentier A, Chauvaud S, Fabiani JN, et al. Reconstructive surgery of mitral valve incompetence: ten-year appraisal. J Thorac Cardiovasc Surg, 1980 Mar;79(3):338-48

Fornes P, Heudes D, Fuzellier JF, et al. Correlation between clinical and histologic patterns of degenerative mitral valve insufficiency: a histomorphometric study of 130 excised segments. Cardiovasc Pathol 1999;8(2):81-92

Disse S, Abergel E, Berrebi A, et al. Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1. Am J Hum Genet 1999;65(5):1242-1251

Freed LA, Acierno JS Jr, Dai D, et al. A locus for autosomal dominant mitral valve prolapse on chromosome 11p15.4. Am J Hum Genet 2003;72:1551-1559

Nesta F, Leyne M, Yosefy C, et al. New Locus for autosomal dominant mitral valve prolapse on chromosome 13: clinical insights from genetic studies. Circulation 2005;27(13):2022-2030


Top

Echocardiography


Announcements