The pericardial fluid (PF) is an ultrafiltrate of plasma contained within the double-walled pericardial sac (also known as pericardium) that surrounds the heart and the roots of the great vessels (ascending aorta, superior and inferior vena cavae, pulmonary arteries and pulmonary veins) bringing blood to and from the heart cells (see Figure S1).1 The pericardium is composed of two layers: (1) the superficial fibrous pericardium, composed of connective tissue, is continuous with the tunica adventitia of the great blood vessels and anchors the heart to the surrounding walls, and (2) the serous pericardium, composed of mesothelial cells. The serous pericardium is in turn formed by a parietal layer that fuses with the fibrous pericardium at the great vessels roots and the epicardium, which sits on and signals to the myocardium.2 Proteins introduced at the cavity surface of the endocardium can cross this layer, move between the myocardial cells, and accumulate under the epicardial mesothelium.3 Moreover, myocardial interstitial fluid can be drained from the subendocardium to the subepicardium via a network of intramyocardial lymphatic capillaries.4 Subsequently, molecules can be transported from the pericardial cavity to the peripheral circulation by the thoracic duct via the parietal pericardium, by the right lymphatic duct via the right pleural cavity,5 or through the capillary network and the venous system.6, 7 Cardiac enzymes and troponins are present at higher levels in the PF than the peripheral blood, and increased levels of these molecules are used to aid the diagnosis of fatal myocardial infarct post-mortem.8, 9 Additionally, the PF contains biologically active factors and components, of possible myocardial origin, including atrial and brain natriuretic peptides and endothelin-1.10 From the above, the myocardial contribution to PF content is apparent, and we reasoned that the PF composition might reflect, at least in part, the myocardium expression profile in health and disease.