Etiologic Classification of Degenerative Mitral Valve Disease: Barlow’s Disease and Fibroelastic Deficiency Ani C. Anyanwu, MD, and David H. Adams, MD Barlow’s disease and fibroelastic deficiency are the two dominant forms of degenera- tive mitral valve disease and have unique differentiating characteristics on clinical and echocardiographic assessment. Preoperative differentiation of patients by both cardi- ologists and surgeons is important because the techniques, surgical skill, and expertise required to achieve a repair vary among these etiological subsets. Barlow’s patients often have multiple complex lesions, thus high rates of repair are only likely to be achieved by a reference mitral valve repair surgeon. In contrast, many forms of fibroelastic disease should be repaired at a high rate by experienced general cardiac surgeons. In this article, we highlight the differentiation of Barlow’s disease and fibroelastic deficiency. Semin Thorac Cardiovasc Surg 19:90-96 © 2007 Elsevier Inc. All rights reserved. KEYWORDS mitral valve repair, Barlow’s disease, fibroelastic deficiency egenerative mitral valve disease refers to a spectrum Historical Perspective Dof conditions in which morphologic changes in the connective tissue of the mitral valve cause structural le- Although the syndrome of a midsystolic click and systolic sions that prevent normal function of the mitral apparatus. murmur, now known as Barlow’s disease, was first described 2 Degenerative lesions, such as chordal elongation, chordal in 1887 by Cuffer and Barbillon, it was not until the 1960s rupture, leaflet tissue expansion, and annular dilation typ- that these findings were recognized to be due to mitral valve ically result in mitral regurgitation due to leaflet prolapse. prolapse. Although some early workers, such as Griffith in 3 4 Degenerative mitral valve disease is recognized as an im- 1892 and Hall in 1903, had suggested they were caused by portant cause of cardiovascular morbidity and mortality.1 mitral regurgitation, the pervading opinion until the early 1960s was that these murmurs were “innocent” and caused Although mitral valve prolapse with severe mitral valve by pleuro-pericardial adhesions or extracardiac disease.5 The regurgitation is a common indication for surgical referral, theory of pericardial or extracardiac origin was challenged by differentiation into the specific degenerative process that Reid in 1961, who, again, suggested that mitral regurgitation results in the mitral regurgitation has generally been less was the cause of midsystolic murmurs and that the click emphasized. Differentiating degenerative mitral valve dis- probably arose from sudden tautening of previously lax chor- ease, specifically Barlow’s disease from fibroelastic defi- dae.6 Barlow and colleagues validated Reid’s theory in 1963; ciency, is, however, important because key aspects of sur- using cine ventriculography, they were able to demonstrate gery may depend on this distinction. This review focuses conclusively the presence of mitral regurgitation in seven on the classification of degenerative mitral valve disease, patients with midsystolic murmurs.7 Barlow and colleagues with a specific emphasis on the differentiation of Barlow’s were therefore the first to provide direct evidence that the disease from fibroelastic deficiency (Table 1). murmur and click were due to mitral regurgitation. However, they wrongly ascribed the findings to fibrosed chordae due to rheumatic valve disease and recommended that patients be Department of Cardiothoracic Surgery, Mount Sinai Medical Center, New placed on antibiotic therapy against rheumatic fever.7 Barlow York, New York. Address reprint requests to David H. Adams, MD, Professor and Chairman, later presented his findings at Johns Hopkins Hospital, where 8 Department of Cardiothoracic Surgery, Mount Sinai Hospital, 1190 Fifth Criley correctly interpreted the mechanism of regurgitation Avenue, New York, NY 10029. E-mail: [email protected] as excessive posterior leaflet motion into the atrium during 90 1043-0679/07/$-see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2007.04.002 Etiologic classification of degenerative mitral valve disease 91 Table 1 Key Differences Between Barlow’s Disease and Fibroelastic Deficiency at Time of Surgical Presentation Barlow’s Disease Fibroelastic Deficiency Pathology Myxoid infiltration Impaired production of connective tissue (Typical age Young (<60 years) Older (60؉ years Duration of known Several years to decades Months mitral disease Long history of murmur Usually No Familial history Sometimes No Marfanoid features Sometimes No Auscultation Midsystolic click and late systolic murmur Holosystolic murmur Echocardiography Bulky, billowing leaflets, multi-segmental Thin leaflets, prolapse of single prolapse segment, ruptured chord(s) Surgical lesions Excess tissue, thickened and tall leaflets, Thin leaflets, thickening and excess chordal thickening or thinning, chordal tissue (if present) limited to prolapsing elongation or rupture, atrialization of segment, ruptured chordae leaflets, fusion, fibrosis or calcification of chords, papillary muscle calcification, annular calcification Mitral valve repair More complex Less complex systole, a phenomenon he termed mitral valve prolapse.Bythe familial component,15,16 the majority of cases are sporadic. mid 1960s, the syndrome was recognized to be of a degen- The pathological hallmarks are myxoid infiltration, which erative rather than rheumatic etiology because myxoid de- destroys the 3-layer leaflet architecture, and also collagen generation was found on histolgical examination of ex- alterations seen on histological examination.17 This myxoid planted valves. The macroscopic features of the Barlow valve infiltration is responsible for the thick, redundant leaflets were described and included voluminous thickening of the seen in Barlow’s disease. Because the infiltration affects the leaflets, and elongation, thickening, or thinning of the entire valve, billowing and/or prolapse of multiple segments chords.9,10 It was also appreciated that left ventricular dys- of the valve are common findings. function coexisted in up to 80% of patients with the syn- drome, leading some workers to suggest that the valve de- Clinical Assessment generation was secondary to a cardiomyopathy.11 With the Ͻ introduction of 2-dimensional echocardiography, the echo- Patients with Barlow’s disease are typically young (age 40 cardiographic features of mitral valve prolapse were defined, years), more often women, and asymptomatic at first presen- and, in the early 1980s, this modality superseded cineangiog- tation, having been found to have a murmur on physical raphy as the tool of choice for diagnosing mitral valve pro- examination. Many patients are then followed up by an in- lapse. Barlow and Pocock later coined the term billowing mi- ternist or primary care doctor for an interval of several years tral leaflet syndrome to describe the billowing of mitral leaflets before being referred for cardiologic assessment. On first pre- as seen on echocardiography.12 It is not clear when the ep- sentation to the cardiac surgeon, most patients will therefore onym was first used to describe the disease, but references to have a long history of a cardiac murmur. Some patients may Barlow’s syndrome appeared in the medical literature as early have a family history of mitral valve prolapse. Surgical refer- as 1974.13 Carpentier and colleagues characterized the surgi- ral is often triggered by declining ventricular function, onset cal lesions seen in Barlow’s disease14 and were the first to of atrial fibrillation, or the development of symptoms includ- differentiate it from another category of mitral valve prolapse ing palpitations, fatigue, dyspnea, and presyncope. Ventric- where there was no billowing or excess tissue.14 Carpentier ular arrhythmias, syncope, angina, endocarditis, and cere- used the term fibroelastic deficiency to describe this other de- brovascular accidents are less common presentations. generative process, which was generally associated with Patients with longstanding disease and left ventricular dys- thinned and ruptured chordae, and typically involved a sin- function may present with symptoms of heart failure. The gle segment of the posterior leaflet (P2). recognition that clinical events and reduced life expectancy can occur in asymptomatic or minimally symptomatic pa- tients with severe mitral regurgitation has lead some workers Barlow’s Disease to recommend surgical intervention before the onset of Barlow’s disease is a degenerative mitral valve disease in symptoms, arrhythmias, or ventricular dysfunction.18 Pa- which myxoid infiltration of the valve results in a myxoma- tients are typically around 50 years of age at the time of tous-appearing valve that is remarkable for excess thickened surgical intervention,19 although they can be of any age. leaflet tissue. Chordae are sometimes thin but more com- General physical examination is often unremarkable, but monly are thickened, fused, or even calcified. Chordal elon- some patients have extracardiac signs, such as skeletal abnor- gation is more frequent than rupture. The etiology is un- malities, suggestive of a forme fruste of Marfan’s syndrome.20 known; although some cases have a significant genetic or The auscultatory findings in Barlow’s disease were well char- 92 A.C. Anyanwu and D.H. Adams Figure 1 Echocardiographic differentiation of degenerative disease. (A) Barlow’s disease with posterior leaflet prolapse (transgastric, 4-chamber