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Hi

I have the 2X4HD, dual SVS SB2000 Pro subs, Denon X4500H AVR, NAD M33 Integrated AMP. 

There are two separate subwoofer outputs on the Denon and NAD, but both can be configured to use a single sub.

I want to feed sub1 out from Denon to input 1 on 2X4HD, and feed sub1 out from NAD to input 2 on 2X4HD.

Then connect output 1 to subwoofer 1 and output 2 to subwoofer 2.

Then, run REW calibration twice, one for Denon (single sub, but actually dual), and one for NAD (single sub but dual).

How do I setup the 2X4HD after I did a full factory reset? I need the 2X4HD to take input 1 and split it to outputs 1 and 2 and apply all necessary DSP crossover. Then do the same for input 2 separately. Dual sub signals will arrive from both Denon and NAN, mixed and split into two subwoofers.

Is this possible and how to setup correctly (the I/O matrix)?

Thanks
 

I think you want to create two configurations.
configuration 1 takes input 1 for all 4 outputs. 
config 2 takes input 2 for all outputs. 
connect Denon to input 1 and connect the NAD to input two. 
the two subs can use any of the outputs.

Now switch to configuration 1, do the whole setup for the Denon. Then switch to configuration 2 and do the whole setup for the NAD. 
if you have the remote, you can simply switch between the inputs by switching the configurations.