Hypertrophic cardiomyopathy (HCM) is characterized by myocardial hypertrophy, defective diastolic filling, and— in one third of cases—ventricular outflow obstruction. The heart is thick-walled, heavy, and hypercontractile, in striking contrast to the flabby, poorly contractile heart in DCM. Systolic function usually is preserved in HCM, but the myocardium does not relax and therefore exhibits primary diastolic dysfunction. HCM needs to be distinguished clinically from disorders causing ventricular stiffness (e.g., amyloid deposition) and ventricular hypertrophy (e.g., aortic stenosis and hypertension).
Most cases of HCM are caused by missense mutations in one of several genes encoding proteins that form the contractile apparatus. The usual pattern of transmission is autosomal dominant, with variable expression. Although more than 400 causative mutations in nine different genes have been identified, all have one unifying feature: they all affect sarcomeric proteins and increase myofilament function. This results in myocyte hypercontractility, increased energy use, and a net negative energy balance. Of the various sarcomeric proteins, β-myosin heavy chain is most frequently involved, followed by myosin-binding protein C and troponin T. Mutations in these three genes account for 70% to 80% of all cases of HCM.
Some of the genes mutated in HCM also are mutated in DCM (e.g., beta-myosin), but in DCM the mutations depress motor function as opposed to the gain of function seen in HCM.
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Fig. 11.26 Arrhythmogenicrightventricularcardiomyopathy.(A)Therightventricleismarkedlydilatedwithfocal,almosttransmuralreplacementofthefreewallbyadiposetissueandfibrosis.Theleftventriclehasagrosslynormalappearanceinthisheart;itcanbeinvolved(albeittoalesserextent)insomeinstances.(B)Therightventricularmyocardium(red) isfocallyreplacedbyfibrousconnectivetissue(blue, arrow) andfat(Massontrichromestain).
Fig.11.27A).Classically, thereisdisproportionatethickeningoftheventricularseptumrelativetotheleftventriclefreewall(so-calledasymmetric septal hypertrophy);nevertheless,inabout10%ofcasesofHCM,concentrichypertrophyisseen.Onlongitudinalsectioning,theventricularcavitylosesitsusualround-to-ovoidshapeandiscompressedintoa“banana-like”configuration.Theanteriormitralleafletcontactstheseptumduringventricularsystole,producingaplaqueintheleftventricularoutflowtractandthickeningofthemitralleaflet;thesechangescorrelatewithfunctionalleftventricularoutflowtractobstructionduetosystolicanteriormotionofthemitralvalve.
ThecharacteristichistologicfeaturesinHCMaremarkedmyocytehypertrophy,haphazardmyocyte (andmyofiber)disarray, andinterstitialfibrosis(
Fig.11.27B