Various lines of evidence point to time-dependent changes in the up- and downregulation of remodelling pathways in chronic primary MR.26 This process is initiated by diastolic mechanical stretch due to an increase in end-diastolic wall stress, leading to an early increase in reactive oxygen species (ROS) generation, inflammatory cytokine expression and neurohormonal activation, with increases in angiotensin II and catecholamine levels. This evidence concerns the gene AGT and miotic rate.