Myofilament remodeling and function is more impaired in peripartum cardiomyopathy compared to dilated cardiomyopathy and ischemic heart disease.

Peripartum cardiomyopathy (PPCM) and dilated cardiomyopathy (DCM) show similarities in clinical presentation. However, while DCM patients do not recover and slowly deteriorate further, PPCM patients show either a fast cardiac deterioration or complete recovery. The aim of this study was to assess if underlying cellular changes can explain the clinical similarities and differences in the two diseases. We therefore assessed sarcomeric protein expression, modification, titin isoform shift, and contractile behavior of cardiomyocytes in heart tissue of PPCM and DCM patients and compared these to non-failing controls. Heart samples from ischemic heart disease (ISHD) patients served as heart failure control samples. Passive force was only increased in PPCM samples compared to controls while PPCM, DCM and ISHD samples all showed increased myofilament Ca(2+)-sensitivity. Length-dependent activation was significantly impaired in PPCM compared to controls, while no impairment was observed in ISHD samples and DCM showed an intermediate response. Contractile impairments were caused by impaired PKA-mediated phosphorylation since exogenous PKA restored all parameters to control levels. While DCM samples showed re-expression of EH-myomesin, an isoform usually only expressed in the heart before birth, PPCM and ISHD did not. The lack of EH-myomesin, combined with low PKA-mediated phosphorylation of myofilament proteins and increased compliant titin isoform, may explain the increase in passive force and blunted length- dependent activation of myofilaments in PPCM samples.