In severe disease, valve orifices can be compromised by as much as 70% to 80% (from a normal area of approximately 4 cm2). Cardiac output is maintained only by virtue of concentric left ventricular hypertrophy; the chronic outflow obstruction can drive left ventricular pressures to 200 mm Hg or more. The hypertrophied myocardium is prone to ischemia, and angina may develop. Systolic and diastolic dysfunction collude to cause CHF, and cardiac decompensation eventually ensues. The development of angina, CHF, or syncope in aortic stenosis heralds the exhaustion of compensatory cardiac hyperfunction and carries a poor prognosis; without surgical intervention, 50% to 80% of patients die within 2 to 3 years.
In myxomatous degeneration of the mitral valve, one or both mitral leaflets are “floppy” and prolapse—they balloon back into the left atrium during systole. Primary mitral valve prolapse is a form of myxomatous mitral degeneration affecting some 0.5% to 2.4% of adults; thus, it is one of the most common forms of valvular heart disease, with women affected almost 7-fold more often than men. Conversely, secondary myxomatous mitral degeneration affects men and women equally, and can occur in any one of a number of settings in which mitral regurgitation is caused by some other underlying cause (e.g., IHD).
The basis for primary myxomatous degeneration of the mitral valve is unknown. Nevertheless, an underlying (possibly systemic) intrinsic defect of connective tissue synthesis or remodeling is likely. Thus, myxomatous degeneration of the mitral valve is a common feature of Marfan syndrome (due to fibrillin-1 mutations, Chapter 7) and occasionally occurs in other connective tissue disorders. In some patients with primary disease, additional hints of systemic structural abnormalities in connective tissue, including scoliosis and high-arched palate, may be found. Subtle defects in structural proteins (or the cells that make them) may cause hemodynamically stressed connective tissues rich in microfibrils and elastin (e.g., cardiac valves) to elaborate defective ECM. Secondary myxomatous change presumably results from injury to the valve myofibroblasts, imposed by chronically aberrant hemodynamic forces.
Fig.11.18 ).Theaffectedleafletsareenlarged,redundant,thick,andrubbery;thetendinouscordsalsotendtobeelongated,thinned,andoccasionallyrupture.Inthosewithprimarymitraldisease,concomitanttricuspidvalveinvolvementisfrequent(20%to40%ofcases);lesscommonly,aorticandpulmonicvalvesalsomaybeaffected.Onhistologicexamination,theessentialchangeisthinningofthevalvelayerknownasthefibrosa layerofthevalve,onwhichthestructuralintegrityoftheleafletdepends,accompaniedbyexpansionofthemiddlespongiosa layerowingtoincreaseddepositionofmyxomatous(mucoid)material.ThesamechangesoccurwhetherthemyxomatousdegenerationisduetoanintrinsicECMdefect(primary),oriscausedbyregurgitationsecondarytoanotheretiologicprocess(e.g.,ischemicdysfunction).
Fig. 11.18 Myxomatousdegenerationofthemitralvalve.Thereisprominenthoodingwithprolapseoftheposteriormitralleaflet(arrow) intotheleftatrium;theatriumalsoisdilated,reflectinglong-standingvalvularinsufficiencyandvolumeoverload.Theleftventricleisshownontheright inthisfour-chamberview.(Courtesy of William D. Edwards, MD, Mayo Clinic, Rochester, Minnesota.) http://ebooksmedicine.net