Researchers at the Icahn School of Medicine at Mount Sinai have demonstrated that the recently developed antidiabetic drug empagliflozin can treat and reverse the progression of heart failure in non-diabetic animal models. Their study also shows that this drug can make the heart produce more energy and function more efficiently. The results were published in the April 23 issue of the Journal of American College of Cardiology.
“This drug could be a promising treatment for heart failure in both non-diabetic and diabetic patients,” said lead author Juan Badimon, MD, Professor of Cardiology and Director of the Atherothrombosis Research Unit at the Cardiovascular Institute at the Icahn School of Medicine at Mount Sinai. “Our research can lead to a potential application in humans, save lives, and improve quality of life.”
Empagliflozin was approved by the U.S. Food and Drug Administration in 2014. It limits renal sugar resorption and is the first drug in the history of type 2 diabetes proven to prolong survival. While diabetes patients are typically at higher risk of heart failure, past studies have suggested that those who take empagliflozin don’t commonly develop heart failure. Those observations led a team of researchers to question if the drug contains a mechanism, independent of anti-diabetic activity that is linked to heart failure prevention, and whether it could have the same impact on non-diabetics.
Investigators from the Atherothrombosis Research Unit tested the hypothesis by inducing heart failure in 14 non-diabetic pigs. For two months, they treated half of the animals with empagliflozin and the other group with a placebo. The team evaluated the pigs with cardiac magnetic resonance, 3D-echocardiography, and invasive catheterization at three different points in the study (before inducing, one day after inducing, and at the two-month mark). At two months, all animals in the group treated with empagliflozin experienced improved heart function. Specifically, those pigs had less water accumulation in the lungs (less pulmonary congestion, which is responsible for causing shortness of breath) and lower levels of biomarkers of heart failure. Importantly, the left ventricles had stronger contractions (enhanced systolic function), got smaller (less dilated), and were less thick (less hypertrophy), and the heart was a normal shape (less architectural remodeling).
The researchers also found that the drug addressed heart failure by improving cardiac metabolism. The hearts of pigs on the medication were consuming more fatty acids and ketone bodies (three related compounds–acetone, acetoacetic acid, and beta-hydroxybutyric acid–produced during the metabolism of fats) and less glucose, as contrasted with heart failure patients (diabetic and non-diabetic), whose hearts consume more glucose and almost no fatty acids and produces less energy. This boost in metabolism helped the hearts produce more energy and function more strongly and efficiently.
“This study confirmed our hypothesis that empagliflozin is an incredibly effective treatment for heart failure and not only an antidiabetic drug. Moreover, this study demonstrated that empagliflozin is useful for heart failure independently of a patient’s diabetic status. Importantly, empagliflozin switches cardiac metabolism toward fatty acid and ketone body consumption, thus allowing the production of more energy in the heart,” explained co-lead author Carlos Santos-Gallego, MD, postdoctoral fellow at the Icahn School of Medicine at Mount Sinai. “Empagliflozin may be a potentially effective treatment for heart failure patients. This is extremely important because heart failure is a disease with a mortality above 50 percent at 5 years. This study offers a new therapeutic strategy in heart failure, something badly needed given that there have not been new effective drugs for heart failure since the 1990s.”
The authors are currently studying whether empagliflozin is an effective heart failure treatment in non-diabetic human patients in the EMPATROPISM clinical trial.
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Mount Sinai Heart is one of the nation’s top 10 hospitals in Cardiology/Heart Surgery
The Mount Sinai Health System is New York City’s largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai’s vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report’s “Best Medical Schools”, aligned with a U.S. News & World Report’s “Honor Roll” Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report’s “Honor Roll” of top U.S. hospitals; it is one of the nation’s top 20 hospitals in Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 “Best Hospitals” issue. Mount Sinai’s Kravis Children’s Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke’s, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City’s largest integrated delivery system encompassing (with the addition of South Nassau Communities Hospital) eight hospital campuses, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai’s vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report’s “Best Medical Schools”, aligned with a U.S. News & World Report’s “Honor Roll” Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report’s “Honor Roll” of top U.S. hospitals; it is one of the nation’s top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 “Best Hospitals” issue. Mount Sinai’s Kravis Children’s Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke’s, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.
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