In human HHD, the peripheral ratio of MMPs/TIMP1 indicates progression to HF, suggesting that tissue remodeling could be a dynamic process in the continuum of transition from asymptomatic diastolic dysfunction to symptomatic diastolic and then systolic dysfunction as it can be observed in the inversion of the ratio in stage IV of HDD [71,72,73]. Here, TIMP1 is linked to hydrops fetalis.