Charakterisierung der Rolle von Inflammation für die Pathogenese und Prognose von Patientinnen mit einer peripartalen Kardiomyopathie (PPCM)
Zusammenfassung der Projektergebnisse
Peripartum cardiomyopathy (PPCM) is an idiopathic form of dilated cardiomyopathy, presenting with heart failure secondary to left ventricular (LV) systolic dysfunction towards the end of pregnancy or up to five months postpartum. PPCM is a global disease, affecting approximately 1:1000 women worldwide. The aetiology of PPCM remains incompletely understood and appears to be multi-factorial. Recent literature suggests a ‘multiple-hit’ model consisting of a genetic susceptibility, hemodynamic changes of pregnancy, vascular, and hormonal factors as well as inflammatory/immune responses. The outcomes of the disease are variable. PPCM is a leading cause of maternal morbidity and mortality worldwide. LV recovery in PPCM remains markedly heterogenous and differs significantly between countries and ethnicities. It is poorly understood why the outcomes differ. For this project, I intended to evaluate the role of inflammation in the pathogenesis of PPCM and its impact on prognosis. I first conducted a systematic review and meta-analysis to summarise the existing evidence on outcomes in PPCM globally. More than half of patients with PPCM had LV recovery (LVEF ≥50%) after one year, however, global mortality rates were still high. We identified important regional differences in both all-cause mortality and LV recovery in PPCM. These differences may be explained by variable prescription of guideline-directed medical therapy and access to health care services in different parts of the world. Studies that reported high prescription rates of beta-blockers, ACE-inhibitors/ARBs, and bromocriptine were associated with better rates of LV recovery and lower all-cause mortality. Our results highlight that timely initiation and up-titration of heart failure therapy should therefore be strongly encouraged to improve outcome in PPCM. We used cardiac magnetic resonance (CMR), a non-invasive imaging modality free of ionizing radiation, to study the extent of cardiac inflammation and fibrosis present in patients with a new diagnosis of PPCM. We found a high prevalence of myocardial fibrosis in well-phenotyped patients with newly diagnosed PPCM. Cardiac fibrosis was associated with more severe impairments in LV strain, LVEF and RVEF. CMR therefore had an incremental value to echocardiography in the risk stratification of women with PPCM. Positron emission tomography (PET) imaging with F-18-labelled 2-fluoro 2-deoxy-D glucose (F-18 FDG) is a well-utilized functional imaging modality to visualize inflammation within the human body. Due to an increased glucose metabolism 18F–FDG accumulates in inflammatory cells causing an increased accumulation at the site of inflammation/infection, which can be visualised by PET-CT. We are currently conducting a study using 18F–FDG-PET-CT to study the extent of inflammatory processes in PPCM. This may further our understanding of the pathogenesis and may help to identify new diseasespecific therapeutic targets, which could improve outcomes in PPCM.
Projektbezogene Publikationen (Auswahl)
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Outcomes and complications of peripartum cardiomyopathy: protocol for a systematic review and meta-analysis. BMJ Open, 11(10), e054994.
Hoevelmann, Julian; Muller, Elani; Hohlfeld, Ameer; Böhm, Michael; Sliwa, Karen; Engel, Mark E. & Viljoen, Charle André
