The long-term prognosis after MI depends on many factors, the most important of which are the quality of left ventricular function and the severity of atherosclerotic narrowing of vessels perfusing the remaining viable myocardium. The overall mortality rate within the first year is about 30%, including deaths occurring before the patient reaches the hospital. Thereafter, the annual mortality rate for patients who have suffered an MI is 3% to 4%.
Chronic IHD, also called ischemic cardiomyopathy, is progressive heart failure secondary to ischemic myocardial damage. In most instances, there is a known clinical history of previous MI. After prior infarction(s), chronic IHD appears when the compensatory mechanisms (e.g., hypertrophy) of residual myocardium begin to fail. In other cases, severe CAD can cause diffuse myocardial dysfunction, and even micro-infarction and replacement fibrosis, without any clinically evident episode of frank infarction.
The heart failure of chronic IHD is typically severe and is occasionally punctuated by new episodes of angina or infarction. Arrhythmias, CHF, and intercurrent MI account for most of the associated morbidity and mortality.
MORPHOLOGYPatientswithchronicIHDtypicallyexhibitleftventriculardilationandhypertrophy,oftenwithdiscreteareasofgray-whitescarringfromprevioushealedinfarcts.Invariably,thereismoderatetosevereatherosclerosisofthecoronaryarteries,sometimeswithtotalocclusion.Theendocardiumgenerallyshowspatchy,fibrousthickening,andmuralthrombimaybepresent.Microscopicfindingsincludemyocardialhypertrophy,diffusesubendocardialmyocytevacuolization,andfibrosisfrompreviousinfarction.
Because of the serious morbidity associated with IHD, there is much interest in exploring the possibility of using cardiac stem cells to replace damaged myocardium. Although cardiac regeneration in metazoans (such as newts and zebrafish) is well described, cardiac myocytes of higher-order animals are classically considered a post-mitotic cell population without replicative potential. Increasing evidence, however, points to the presence of bone marrow–derived precursors—as well as a small resident stem cell population within the myocardium—capable of repopulating the mammalian heart. These cells express a cluster of cell surface markers that allow their isolation and purification, and like all other tissue stem cells, they occur in very low frequency.
Besides self-renewal, these cardiac stem cells can generate all cell lineages seen within the myocardium. They have a slow intrinsic rate of proliferation, which is greatest in neonates and decreases with age. Of interest, stem cell numbers and progeny also increase after myocardial injury or hypertrophy, albeit to a limited extent, since hearts that suffer an MI clearly do not recover any significant function in the necrotic zone. Nevertheless, the potential for stimulating the proliferation of these cells in vivo is tantalizing because it could facilitate recovery of myocardial function after acute MI or chronic IHD. Ex vivo expansion and subsequent administration of such cells after an MI is another area of vigorous investigation. Unfortunately, results thus far have been less than exciting.
Inthevastmajorityofcases,cardiacischemiaisduetocoronaryarteryatherosclerosis;vasospasm,vasculitis,andembolismarelesscommoncauses.
Cardiacischemiaresultsfromamismatchbetweencoronarysupplyandmyocardialdemandandmanifestsasdifferent,albeitoverlappingsyndromes:
Angina pectoris isexertionalchestpainduetoinadequateperfusion,andistypicallyduetoatheroscleroticdiseasecausinggreaterthan70%fixedstenosis(so-called“criticalstenosis”).