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Hampered by an ankle injury suffered on Wednesday, Roddick, ranked 17th in the world, was second best against his 61st ranked opponent and fell to defeat inside 76 minutes on the indoor hard court.
Istomin broke Andy Roddick three times and did not lose his serve. Denis served six aces and made no double faults. Meanwhile, Andy Roddick recorded five aces and had no double faults.
Istomin, aiming for his first ATP Tour title, will play fifth seed Julien Benneteau of France in the semi-finals after the Frenchman rallied to defeat Belgian Steve Darcis 3-6 6-1 6-2.