Characterization of the role of inflammation in the pathogenesis and prognosis of patients with peripartum cardiomyopathy (PPCM)

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Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy, in which previously healthy women present with heart failure due to left ventricular (LV) dysfunction during the last months of pregnancy or up to 5 months after delivery. Worldwide, the disease affects approximately 1 in 1000 pregnancies, however its prevalence differs significantly between different regions and ethnicities. Clinical presentation ranges from moderate heart failure symptoms to severe cardiogenic shock, which requires intensive care treatment.The aetiology and pathogenesis of PPCM remain poorly understood and require further research. Through largely unknown mechanisms, increased levels of oxidative stress cause a cleavage of the pregnancy hormone prolactin into a 16kDa fragment, which (through complex signaling pathways) causes endothelial dysfunction and ultimately results in cardiomyocyte death. These inflammatory, anti-angiogenic and pro-apoptotic processes seem to occur in patients with an underlying genetic susceptibility.Even though the majority of the women recover their cardiac function after 12 months, others remain with a persistently reduced LV function leading to chronic heart failure. As it remains difficult to predict which patients would recover their LV function, future research should aim at better characterisation of the factors that influence the outcome of patients with PPCM. This is crucial for the risk-stratification and optimal management of women with this condition.In my research project, I would like to to study the role of inflammation in the pathogenesis of PPCM and to characterise its impact on prognosis.As part of my research, I plan to perform a protein analysis (proteomics) on blood samples collected from patients with PPCM. By doing so, I would like to explore new inflammatory (bio-)markers that might play a role in the development of PPCM. Furthermore, by means of magnetic resonance imaging (MRI) and positron emission tomography / computed tomography (PET-CT), I would like to study the extent of inflammation in this condition (i.e. whether inflammation in PPCM is limited to the heart or whether the condition is associated with systemic inflammatory involvement). I also plan to study whether there is an association between the degree of inflammation and the increased susceptibility to arrhythmic events in PPCM. Finally, I intend to perform a genetic analysis, to see whether inflammation-related genes are up-regulated in women with PPCM and whether this could explain their possible genetic susceptibility of this condition.