Infection. The nucleic acid “footprints” of coxsackievirus B and other enteroviruses can occasionally be detected in the myocardium from late-stage DCM patients. Moreover, sequential endomyocardial biopsies have documented instances in which infectious myocarditis progressed to DCM. Simply finding viral transcripts or demonstrating elevated anti-viral antibody titers may be sufficient to invoke a myocarditis that was “missed” in its early stages. Consequently, many cases of DCM are attributed to viral infections, even though inflammation is absent from the end-stage heart.
Alcohol or other toxic exposure. Alcohol abuse is strongly associated with the development of DCM. Alcohol and http://ebooksmedicine.net
Toxic (e.g., alcohol) 20-50% genetic causes Various proteins (cell membrane, cytoskeleton, sarcomere, nuclear envelope, or mitochondrial)
Defect in force generation, force transmission, and/or myocyte signaling
Defect in energy transfer from mitochondria to sarcomere and/or direct sarcomeric dysfunction
Hypertrophy, marked
Fibrosis, interstitial and replacement • Hypertrophy • Dilation • Fibrosis, interstitial • Intracardiac thrombi Dilated cardiomyopathy phenotype • Heart failure • Sudden death • Atrial fibrillation • Stroke Clinical
Fig. 11.24 Causesandconsequencesofdilatedandhypertrophiccardiomyopathy.Asignificantfractionofdilatedcardiomyopathies—andvirtuallyallhyper-trophiccardiomyopathies—haveageneticorigin.Dilatedcardiomyopathiescanbecausedbymutationsincytoskeletal,sarcomeric,nuclearenvelope,ormitochondrialproteins;hypertrophiccardiomyopathiestypicallyarecausedbysarcomericproteinmutations.Althoughthetwoformsofcardiomyopathydifferincauseandmorphology,theyhavecommonclinicalendpoints.LV, Leftventricle.
its metabolites (especially acetaldehyde) have a direct toxic effect on the myocardium. Moreover, chronic alcoholism can be associated with thiamine deficiency, introducing an element of beriberi heart disease (Chapter 8). DCM also can develop after exposure to other toxic agents, such as cobalt, and particularly doxorubicin (Adriamycin), a chemotherapeutic drug.
Peripartum cardiomyopathy occurs late in gestation or several weeks to months postpartum. The etiology is multifactorial, including pregnancy-associated hypertension, volume overload, nutritional deficiency, metabolic derangements (e.g., gestational diabetes), and/or immunologic responses. Recent work suggests that the primary defect is impaired angiogenesis within the myocardium leading to ischemic injury. Antiangiogenic cleavage products of the hormone prolactin (which rises late in pregnancy) and placental-derived antagonists to the VEGF have been implicated. Fortunately, approximately one half of these patients spontaneously recover normal function.
Iron overload in the heart can result either from hereditary hemochromatosis (Chapter 16) or from multiple transfusions. Iron overload also can cause restrictive cardiomyopathy due to interstitial fibrosis, but DCM is the most common manifestation; it has been attributed to interference with metal-dependent enzyme systems or to injury caused by iron-mediated production of reactive oxygen species.
MORPHOLOGYTheheartinDCMcharacteristicallyisenlarged(uptotwotothreetimesthenormalweight)andflabby, withdilationofallchambers(