Khan, who had served as Minister of State under the late Prime Ministers Indira Gandhi and Rajiv Gandhi, was admitted to a private hospital here six days ago after he complained of chest pain.
Dr TS Kler, Executive Director of cardiac sciences department, Escorts Hospital, said that Khan was admitted with fever and chest infection.
"But he already had a major problem of Aortic Stenosis (AS), a disease of the heart valves. He (breathed his last) at around 3 A.M. Today," Kler said.
Born in Pitaura village in Farrukhabad district of Uttar Pradesh, he had represented Farrukhabad in Lok Sabha between 1984 and 1989.
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Son-in-law of the late President Zakir Hussain, Khan served as Member of Parliament for 15 years. He was in Rajya Sabha from 1974 to 1984.
He resigned from the Lok Sabha in July 1989 Governor of Goa. Then he shifted to Karnataka in 1991. As union minister, he had held portfolios of education, textiles, tourism, transport besides external affairs.
Condoling his death, Prime Minister Manmohan Singh said that India had lost a true son and servant of the nation.
The Prime Minister said Khan had served the nation with distinction throughout his life and in many capacities. His death was an "irreparable loss".
"His leadership in India's foreign policy, education system and legislative affairs contributed immensely to the country's modern, liberal and democratic polity.
"His commitment to the nation was deeply rooted in the abiding values of our Constitution and the idea of an India envisioned by our founding fathers," the Prime Minister added.