Immune dysregulation as a key driver of peripartum cardiomyopathy – an exploratory advanced imaging and biomarker study

Abstract

Aims: Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy occurring in women in the late stages of pregnancy or in the postpartum period and is associated with significant morbidity, mortality, and persistent left ventricular dysfunction. PPCM pathogenesis involves multiple putative mechanisms including inflammation. We aimed to explore the acute inflammatory processes in PPCM using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT), cardiovascular magnetic resonance (CMR), and inflammasome profiling. Methods and results: Women with a new diagnosis of PPCM (n = 10, all within 3 months postpartum), five healthy postpartum controls (HPC), and five healthy non-postpartum controls (HNPC), underwent 18FDG-PET-CT, CMR, and serum inflammatory proteomic profiling. PPCM patients had a median age of 34 years (interquartile range [IQR] 30.3–38.5, similar in control groups), and a median parity of 3 (IQR 1–4). PPCM patients presented with severe, symptomatic heart failure (all New York Heart Association functional class III/IV), reduced median left ventricular ejection fraction of 35.5% (IQR 18.1–37.9). PPCM and HPC groups showed higher myocardial and splenic 18FDG uptake compared to HNPC. On CMR, myocardial interstitial fibrosis (elevated T1 time, extracellular volume, and late gadolinium enhancement mass) was solely present in PPCM. Inflammatory profiling showed pro-inflammatory cytokine dysregulation in PPCM (elevated neutrophil-to-lymphocyte ratio, C-reactive protein, interleukin-6, tumour necrosis factor-α, chemokine (C-C motif) ligand 3, hepatocyte growth factor, chemokine (C-X-C motif) ligand 10 and colony-stimulating factor-1) compared to controls. Conclusions: Patients with PPCM exhibited a dysregulated immune response, associated with early myocardial interstitial fibrosis and adverse cardiac remodelling. This highlights the importance of rapid initiation of guideline-directed medical therapy especially with drugs documented to have anti-fibrotic effects.