Purpose: Composition of pericardial adipose tissue (PAT) correlates with cardio-metabolic risk factors and coronary artery disease in humans while its removal exerts beneficial effects on post-myocardial infarction remodelling in mice. So far, the role of PAT in pressure-overload induced remodelling remains widely unknown. We assessed whether PAT removal influences the severity of heart failure (HF) with preserved (HFpEF) versus HF with reduced ejection fraction (HFrEF) by modulating pressure-overload induced hypertrophy of the underlying myocardium.

Methods and results: Progressive remodelling was assessed in male wild-type mice, randomly assigned to transaortic constriction (TAC) for 1 week (early pressure-overload), 8 weeks (HFpEF) or 12 weeks (HFrEF) with or without PAT removal during the surgical intervention. Sham-operated mice served as controls. Echocardiography confirmed TAC triggered induction (1 wk), progression (4 wks) and maintenance (8 wks and 12 wks) of left ventricular (LV) hypertrophy. At HFpEF stage, the pressure-overloaded hearts exhibited a pronounced increase in heart weight, LV wall thickness, cardiomyocyte size and interstitial fibrosis, accompanied by diastolic dysfunction, loss of contractile reserve and a reduced, yet preserved systolic function; all of which was widely unaffected by the absence of PAT (n≥8/group). However, at 12 wks, only TAC mice with intact PAT showed a further drastic LV dilatation and the simultaneous marked reduction in ejection fraction, thereby the transition from HFpEF to HFrEF. In contrast, PAT removal prevented an additional structural and functional deterioration beyond the HFpEF phenotype. This was associated with significantly lowered LV expression of heart failure markers Nppa and Nppb as well as reduced pro-fibrotic and pro-inflammatory gene transcription compared to 12 wks TAC mice with intact PAT (n≥8/group).

Conclusion: Our data suggest PAT to play divergent roles in HFpEF versus HFrEF: while widely not affecting the HFpEF phenotype, PAT removal prevents development of HFrEF in mice.