Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress

A long-standing hypothesis has been that hypertrophy is compensatory and by normalizing wall stress acts to maintain normal cardiac function. Epidemiological data, however, have shown that cardiac hypertrophy is associated with increased mortality, thus casting doubt on the validity of this hypothesis. To determine whether cardiac hypertrophy is necessary to preserve cardiac function, we used 2 genetically altered mouse models that have an attenuated hypertrophic response to 8 weeks of pressure overload. End-systolic wall stress (sigma(es)) obtained by sonomicrometry after 1 week of pressure overload showed complete normalization of sigma(es) in pressure-overloaded wild-type mice (287+/-39 versus sham, 254+/-34 g/cm2), whereas the blunted hypertrophic response in the transgenic mice was inadequate to normalize sigma(es) (415+/-81 g/cm2, P