Andrea,
I suggest you leverage Progression Statuses which are part of programs. You can read up on some background info in this
article -- go about halfway down to the section called Progressions.
So, in the campaign used to email out the initial invite to the webinar, make sure you include the flow action to change the Progression Status of all the leads to Webinar > Invited.
For those who register for the webinar, make sure you change their Progression Status to Webinar > Registered.
Then, in your campaign to send out a follow-up email to leads who haven't registered for the webinar, you can use the "Member of Program" filter with the added constraint of "Progression Status" for your smart list: