Many other agents, such as lithium, phenothiazines, and chloroquine, have been implicated in myocardial injury and sometimes sudden death. Common findings in hearts injured by many of these chemicals and drugs (including diphtheria exotoxin and doxorubicin) are myofiber swelling, cytoplasmic vacuolization, and fatty change. Discontinuing such agents can lead to complete resolution, with no apparent sequelae. Sometimes, however, more extensive damage produces myocyte necrosis and leads to a dilated cardiomyopathy.
Foci of myocardial necrosis with contraction bands, often associated with a sparse mononuclear inflammatory infiltrate (mostly macrophages), can occur in individuals with pheochromocytoma, a tumor that elaborates catecholamines (Chapter 20). Similar changes can occur with a variety of agents—endogenous or exogenous—under the rubric of “catecholamine effect.” These include cocaine, high doses of ephedrine (an adrenergic agent in many cold and allergy formulations), intense autonomic stimulation secondary to intracranial lesions, or vasopressor agents such as dopamine. The mechanism of catecholamine cardiotoxicity is uncertain, but seems to relate either to a direct toxicity of catecholamines on cardiac myocytes via calcium overload or to vasoconstriction in the face of an increased heart rate. The mononuclear cell infiltrate is probably a reaction to microscopic foci of myocyte cell death.
Cardiomyopathy referstointrinsiccardiacmuscledisease;theremaybespecificcauses,oritmaybeidiopathic.
Thethreegeneralpathophysiologiccategoriesofcardiomyopathyaredilated (accountingfor90%ofthecases),hypertrophic, andrestrictive (leastcommon).
DCMresultsinsystolic(contractile)dysfunction.Causesincludemyocarditis,toxicexposures(e.g.,alcohol),andpregnancy.In20%to50%ofcases,mutationsaffectingcytoskeletalproteinsareresponsible.
HCMresultsindiastolic(relaxation)dysfunction.Virtuallyallcasesareduetoautosomaldominantmutationsintheproteinsthatmakeupthecontractileapparatus,inparticularβ-myosinheavychain.
Restrictivecardiomyopathyresultsinastiff,noncompliantmyocardiumandcanbeduetodepositions(e.g.,amyloid),increasedinterstitialfibrosis(e.g.,duetoradiation),orendomyocardialscarring.
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Fig. 11.28 Myocarditis.(A)Lymphocyticmyocarditis,withedemaandassociatedmyocyteinjury.(B)Hypersensitivitymyocarditis,characterizedbyperivasculareosinophil-richinflammatoryinfiltrates.(C)Giantcellmyocarditis,withlymphocyteandmacrophageinfiltrates,extensivemyocytedamage,andmultinucleategiantcells.(D)Chagasmyocarditis.Amyofiberdistendedwithtrypanosomes(arrow) ispresent,alongwithmononuclearinflammationandmyofibernecrosis.
Arrhythmogenicrightventricularcardiomyopathyisanautosomaldominantdisorderofcardiacmusclethatmanifestswithright-sidedheartfailureandrhythmdisturbancesthatcancausesuddencardiacdeathinathletes.
Myocarditisisaninflammatorydisordercausedbyinfectionsorimmunereactions.CoxsackievirusesAandBarethemostcommonpathogensintheUnitedStates.Clinically,myocarditismaybeasymptomatic,giverisetoacuteheartfailure,orevolvetoDCM.