Heroin overdoses are most commonly caused by respiratory failure. This results from high doses of most opioids, because they slow your breathing as well as your heart rate. The dose at which this occurs with heroin is approx. 400mg for a non-tolerant user.
Mixing heroin with other drugs or alcohol may increase the risk of overdose.

http://www.thegooddrugsguide.com/heroin/overdose.htm
http://www.peele.net/lib/heroinoverdose.html
http://bmj.bmjjournals.com/cgi/conte...316/7128/327/i