Myocardial remodeling (REM) is a deleterious processcharacterized by gradual cardiac enlargement, cardiacdysfunction and typical molecular changes. It is a universalphenomenon, being caused by many pathological condi-tions [1, 2].Of these, myocardial infarction is the more common. Ithas been estimated that even with the timely use of primaryangioplasty, and with the subsequent use of all the cur-rently recommended drug therapies, which will be dis-cussed later, the emergence of REM is around 30%,eventually leading to heart failure and death [3, 4]. It hasbeen stressed that if 20% of the ‘‘myocardium at risk’’ issalvaged, the course toward heart failure can be avoided[5].Moreover, uncontrolled hypertension is still a majorcause of heart failure, evolving to REM. It must not beforgotten that valvular heart disease, even with the progressof cardiac surgery, can still lead to cardiac dilatation,effectively REM.Only very recently it was stated that in mitral regurgi-tation, operation before the left ventricular end-systolicdiameter exceeds 40 mm, survival is higher [6]. REM isalso an end result of cardiomyopathy, either post-myocar-ditis or genetically produced, and cancer chemotherapy [7].The term was first introduced by Janice Pfeffer’s group in1985 [8].A comprehensive review was given 4 years ago by Opieet al. [9]. One part of the 1990 definition which theyre-iterate is very important, i.e. it represents an importanttherapeutic target. REM must be viewed as a process that isinitially ‘‘adaptive’’; aiming at offsetting an unfavorablesituation. Thus, in aortic stenosis and hypertension, theensuing left ventricular concentric hypertrophy results inreduced myocardial wall stress; conversely, in the course,in mitral and aortic regurgitation, left ventricular eccentrichypertrophy concerns stroke volume conservation. Thus,hypertrophy finally leads to ventricular dilatation andbecomes ‘‘maladaptive’’ and detrimental [10].However, it is not only the myocardium that undergoespathological changes. It is currently widely recognized thattwo more elements contribute to REM and cardiacmalfunction:– The development of myocardial fibrosis, resultingfrom increased abnormal collagen production. Fibrosisresults in systolic but also diastolic dysfunction throughincreased cardiac stiffness [11].– The inadequate increase in capillary density of thehypertrophying and remodeling myocardium thatresults in inadequate oxygenation [12]. Indeed, evenafter an acute myocardial infarction, capillary density isdecreased as REM ensues [13]As already mentioned, a main characteristic of theremodeling myocardium is the return to the ‘‘fetal’’ phe-notype, which is characterized by decreased contractilitybut also lower energy consumption [14]. Also, the ratioHMC a/b is decreased, ANP and BNP and a-actin over-expressed, and the SERCA/phospholamban activitydecreased.
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Oct 1, 2011
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