The 67-year-old leader, who suffered a massive cardiac arrest on Sunday evening, passed away at 11:30 pm tonight, after battling for life for 75 days, the Apollo Hospitals said in a statement.
Two hours after the announcement of her death, in a swift political transition, her loyalist O Panneerselvam was sworn in as Chief Minister at a sombre ceremony at the Raj Bhawan along with all the ministers in the erstwhile Jayalalithaa Cabinet.
Even as her death was announced, the AIADMK MLAs met at the party headquarters to elect Panneerselvam as the successor to Jayalalithaa.
Jayalalithaa, who scored a historic win in the assembly elections in the state little over six months ago, was admitted to Apollo Hospitals on September 22 with fever and dehydration but she could never recover.
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A tinsel heroine, who inherited the legacy of her mentor late MGR, had entered politics in the early 1980s as the propaganda secretary of AIADMK and was made the incharge of the noon meal scheme undertaken by the MGR government.
She practised politics on her own terms and was one of the two poles in the state for nearly 30 years fighting the DMK headed by redoubtable M Karunanidhi.
Only hours earlier in the evening, the hospital had denied reports that Jayalalithaa had died as "baseless and false" when TV channels said she was no more.
"It is with indescribable grief, we announce the sad demise of our esteemed Honourable Chief Minister of Tamil Nadu Puratchi Thalaivi Amma at 11.30 PM today," Apollo Hospitals said in a statement.
"On this basis, honourable Chief Minister was shifted from the Advanced Critical Care Unit to the High Dependency Unit, where her health and vitals continued to improve under the close monitoring by our expert panel of specialists."
ECMO is the most advanced treatment currently available
internationally. Every possible clinical attempt was made to sustain her revival. However, despite our best efforts, the Chief Minister's underlying conditions rendered her unable to recover and she passed away at 11:30 pm on Monday, the release said.
She also opened a series of public welfare schemes under brand Amma, as she was popularly called, like 'Amma canteens' to low-priced food to the urban poor. There were similar schemes for the poor like 'Amma salt' 'Amma water' and 'Amma medicines'.
Jayalalithaa also attracted investment, especially from abroad, in sectors like automobile and IT.
A host of leaders including President Pranab Mukherjee, Vice President Hamid Ansari, Prime Minister Narendra Modi, Congress chief Sonia Gandhi, vice president Rahul, Home Minister Rajnath Singh and a number of film personalities expressed grief over her death.
"I will always cherish the innumerable occasions when I had the opportunity to interact with Jayalalithaa Ji. May her soul rest in peace," he said.