Hi Garth,
I was looking at a best practice document by MS from what i saw the CAS has a local sql and the Americas are using remote sql.. my now thinking is to go this route with primaries on the cluster using mulitple instance ...i really have not seen anything via technet other than MI's are supported ....btw client is on sccm 2012 r2 160k the focus right now is U.S.A. then address global sites later... correction there is one CAS/2 primaries 44k in one site and 32 in the other.
I also saw active/active cluster not sure if this will work for a Hierarchy. I wished they kept local sql on all primaries believe me the discussion in regards to the advantage of this was beaten but the org wants HA of the site database...