Per- and Polyfluoroalkyl Substances (PFAS) Within the Exposome: Cellular and Molecular Mechanisms Underlying a...

Background: Per- and polyfluoroalkyl substances (PFAS) represent a large class of synthetic fluorinated compounds characterized by highly stable carbon-fluorine bonds that confer exceptional environmental persistence and bioaccumulative properties. Although regulatory measures have restricted the production of several PFAS, including perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), their environmental persistence continues to maintain widespread human exposure, while newly introduced replacement compounds raise additional toxicological concerns. Notably, the recent evidence demonstrating PFAS-induced alterations in key cardiac ion channel activity and electrocardiographic parameters suggest potential electrophysiological mechanisms that may contribute to arrhythmogenesis and cardiac arrhythmias including the most frequent one, atrial fibrillation (AF). Methods: We conducted a narrative literature review of experimental, epidemiological, and mechanistic studies investigating and reporting the cardiovascular, electrophysiological, and potential arrhythmogenic effects of PFAS. Results: Available evidence indicates that PFAS exposure is associated with alterations in cardiac electrophysiology, including modulation of ion channel activity (notably sodium, calcium, and potassium channels), disruption of calcium handling, and changes in electrocardiographic parameters such as QT interval prolongation, which are key contributors to arrhythmogenesis and AF. Conclusions: This review highlights the need for improved understanding of PFAS-induced electrophysiological alterations, to clarify the role of PFAS in cardiac arrhythmias including AF.