First of all, I have a strong pererence for large watches, none to large for me, including my 47mm Panerai ones.
I don't think that either of these wear particularly large on the wrist or feel uncomfortable or heavy or clumbsy.
In fact, the 4500v at 41mm seems to wear smaller than the Historique American 1921 at 40mm.
It's probably more because of the square vs. round shape. FYI the American 1921 comes in a 36mm case,
which I tried on and it did nothing on my wrist. You might be referring to another 1921.
Anyway, I love both of these and how they look on my wrist. But I guess you need to try them on to see how they fit on your wrist.