Review
Nutrition & Dietetics
George A. Brooks
Summary: After years of misunderstanding, it is now recognized that lactate shuttling plays a crucial role in energy flux and metabolic regulation in vivo, especially during physical exercise. The complex series of events involved in lactate shuttling highlight its importance in energy substrate production and distribution, as well as cell signaling.
FRONTIERS IN NUTRITION
(2021)
Article
Cardiac & Cardiovascular Systems
Dylan Chase, Thomas R. Eykyn, Michael J. Shattock, Yu Jin Chung
Summary: This study aims to test whether EMPA directly alters cardiac ketone metabolism independent of supply.
CARDIOVASCULAR RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Milton Packer, Javed Butler, Faiez Zannad, Gerasimos Filippatos, Joao Pedro Ferreira, Stuart J. Pocock, Peter Carson, Inder Anand, Wolfram Doehner, Markus Haass, Michel Komajda, Alan Miller, Steen Pehrson, John R. Teerlink, Sven Schnaidt, Cordula Zeller, Janet M. Schnee, Stefan D. Anker
Summary: Empagliflozin significantly reduced the risk of heart failure-related inpatient and outpatient events in patients with heart failure with preserved ejection fraction, including cardiovascular death, heart failure hospitalization, and urgent visits, while also decreasing total heart failure hospitalizations and intensive care admissions. Patients receiving empagliflozin may experience improved New York Heart Association functional class levels.
Article
Cardiac & Cardiovascular Systems
Louise E. Bechmann, Frida Emanuelsson, Borge G. Nordestgaard, Marianne Benn
Summary: A functional genetic variant in SLC5A2, mimicking SGLT2-inhibition, was associated with a lower risk of heart failure, myocardial infarction, ischaemic heart disease, and all-cause mortality. However, the effects were minimally mediated through lower plasma glucose.
CARDIOVASCULAR RESEARCH
(2023)
Letter
Cardiac & Cardiovascular Systems
Bo Liang, Ning Gu
Summary: The 2022 AHA/ACC/HFSA guideline for heart failure management recommends the use of sodium-glucose co-transporter-2 inhibitors in patients with heart failure and type 2 diabetes to manage hyperglycemia and reduce heart failure-related morbidity and mortality. However, it should be noted that this recommendation is based on specific trials and does not include recently published studies.
CARDIOVASCULAR DIABETOLOGY
(2022)
Article
Medicine, General & Internal
Daria M. Keller, Natasha Ahmed, Hamza Tariq, Malsha Walgamage, Thilini Walgamage, Azad Mohammed, Jadzia Tin-Tsen Chou, Marta Kaluzna-Oleksy, Maciej Lesiak, Ewa Straburzynska-Migaj
Summary: SGLT2 inhibitors not only show excellent performance in improving glycemic control, but also have a positive impact on cardiovascular and renal outcomes. New guidelines recommend SGLT2 inhibitors as first-line treatment for heart failure patients, bringing new hope for the treatment of heart failure patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Milton Packer, Stefan D. Anker, Javed Butler, Gerasimos Filippatos, Joao Pedro Ferreira, Stuart J. Pocock, Peter Carson, Inder Anand, Wolfram Doehner, Markus Haass, Michel Komajda, Alan Miller, Steen Pehrson, John R. Teerlink, Martina Brueckmann, Waheed Jamal, Cordula Zeller, Sven Schnaidt, Faiez Zannad
Summary: Empagliflozin reduces the risk and total number of worsening heart failure events in patients with heart failure and reduced ejection fraction, with benefits seen early after treatment initiation and sustained throughout the therapy.
Review
Biology
Gassan Moady, Tuvia Ben Gal, Shaul Atar
Summary: SGLT2 inhibitors have positive effects on cardiovascular and renal outcomes, reducing heart failure hospitalization and improving cardiovascular outcomes. They also show beneficial effects in patients with chronic kidney disease. The drugs have an excellent safety profile.
Article
Cardiac & Cardiovascular Systems
Andrew N. Carley, Santosh K. Maurya, Matthew Fasano, Yang Wang, Craig H. Selzman, Stavros G. Drakos, E. Douglas Lewandowski
Summary: The study revealed that short-chain fatty acids (SCFAs) are oxidized more readily than ketones in failing hearts, serving as a potential unexplored carbon source for energy production. Despite both SCFAs and ketones bypassing reduced CPT1 activity, SCFAs show higher oxidation rates and may represent a promising alternative energy substrate for failing hearts.
Article
Biochemistry & Molecular Biology
Akira Sezai, Atsushi Tanaka, Takumi Imai, Keisuke Kida, Hisakuni Sekino, Toyoaki Murohara, Masataka Sata, Norio Suzuki, Koichi Node
Summary: There was no significant difference in the effects of canagliflozin, relative to glimepiride, on NT-proBNP concentrations irrespective of baseline obesity. The canagliflozin group was associated with significant reduction in BMI compared to the glimepiride group.
Article
Geriatrics & Gerontology
Adam Oesterle, Petra Buzkova, Cara N. Pellegrini, Calvin Hirsch, Russell P. Tracy, David S. Siscovick, Luc Djousse, Ken J. Mukamal, Jorge R. Kizer
Summary: Glucose, both fasting and post-load, is associated with incident heart failure, while non-esterified fatty acids (NEFA) are not. The association is particularly strong for post-load glucose, suggesting potential targets for HF prevention.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
E. Douglas Lewandowski
Summary: Cardiac function relies on efficient metabolic support, which is a dynamic process that adjusts to the demands of the heart. Flux through metabolic pathways provides energy and signaling molecules to meet these demands. Inability of metabolic flux to keep pace with cardiomyocyte demands leads to dysfunction and contributes to cardiac disease. Studying metabolic mechanisms as therapeutic targets and detecting metabolic flux in the heart will provide important insights into cardiac function and disease.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Review
Cell Biology
Tanawat Attachaipanich, Siriporn C. Chattipakorn, Nipon Chattipakorn
Summary: This review summarizes the current available evidence regarding the potential benefits of SGLT-2 inhibitors against cardiac arrhythmias, ranging from basic research to clinical reports. It comprehensively examines the effects of SGLT-2 inhibitors on cardiac action potential, cellular ion currents, calcium ion homeostasis, and cardiac mitochondrial function, as well as the association with arrhythmias such as atrial fibrillation and ventricular arrhythmias.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Kirtipal Bhatia, Vardhmaan Jain, Kartik Gupta, Agam Bansal, Arieh Fox, Arman Qamar, Kevin Damman, Muthiah Vaduganathan
Summary: The meta-analysis found that SGLT2i significantly reduces the risk of heart failure events across different risk groups, with greater benefits observed in patients with longer treatment exposure.
EUROPEAN JOURNAL OF HEART FAILURE
(2021)
Article
Cardiac & Cardiovascular Systems
Joao Pedro Ferreira, Joana Pimenta, Brenda Moura, Carlos Aguiar, Fatima Franco
Summary: This article reviews the potential utility of SGLT2 inhibitors in patients hospitalized for acute heart failure, highlighting that besides SGLT2 inhibitors, other drugs have failed to improve the prognosis of AHF patients.
Editorial Material
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Kenneth B. Margulies
CARDIOVASCULAR RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Mahesh K. Vidula, Philip Wiener, Senthil Selvaraj, Muhammad Shoaib Khan, Usman Abdul Salam, Chaitanya Rojulpote, Scott D. Metzler, Srinivas Denduluri, Marie Guerraty, Howard Julien, Paco E. Bravo
Summary: PET has higher diagnostic accuracy compared to SPECT for detecting obstructive CAD in patients with left bundle branch block (LBBB) or ventricular-paced rhythm (VPR).
JOURNAL OF NUCLEAR CARDIOLOGY
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Mahesh K. Vidula, Senthil Selvaraj, Marie A. Guerraty
JOURNAL OF NUCLEAR CARDIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Brian Claggett, Michelle C. Johansen, Jonathan W. Cunningham, Rebecca F. Gottesman, Bing Yu, Eric Boerwinkle, Thomas H. Mosley, Amil M. Shah, Scott D. Solomon
Summary: The genetic predisposition to Alzheimer's disease through APOEε4 is not associated with an increased prevalence of HF, HF hospitalization, myocardial remodeling, or biochemical evidence of HF.
JOURNAL OF CARDIAC FAILURE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Senthil Selvaraj, Kenneth B. Margulies, Supritha Dugyala, Erin Schubert, Ann Tierney, Zoltan Arany, Daniel A. Pryma, Svati H. Shah, J. Eduardo Rame, Daniel P. Kelly, Paco E. Bravo
Summary: This study examines whether exogenous ketone administration is noninferior to the ketogenic diet in achieving myocardial glucose suppression and whether serum beta-hydroxybutyrate levels can predict this suppression. The results suggest that exogenous ketones are less effective than the ketogenic diet, while serum BHB levels can predict myocardial glucose suppression.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Ray Hu, Mahesh K. Vidula, Supritha Dugyala, Ann Tierney, Bonnie Ky, Kenneth B. Margulies, Svati H. Shah, Daniel P. Kelly, Paco E. Bravo
Summary: This study assessed the effects of exogenous ketones on cardiac function in healthy participants. The results showed that cardiac function improved after ketone ester ingestion in healthy, fasting participants, similar to effects observed in heart failure patients.
JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
(2022)
Article
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Zhuxuan Fu, Philip Jones, Lydia C. Kwee, Sheryl L. Windsor, Olga Ilkayeva, Christopher B. Newgard, Kenneth B. Margulies, Mansoor Husain, Silvio E. Inzucchi, Darren K. McGuire, Bertram Pitt, Benjamin M. Scirica, David E. Lanfear, Michael E. Nassif, Ali Javaheri, Robert J. Mentz, Mikhail N. Kosiborod, Svati H. Shah
Summary: This study explored the effects of dapagliflozin on metabolic pathways in HFrEF patients, showing an increase in ketone-related and fatty acid metabolite clusters. It also identified metabolic biomarkers associated with adverse HFrEF outcomes, suggesting a potential role for altered ketone and fatty acid biology with sodium-glucose cotransporter-2 inhibitors.
Article
Cardiac & Cardiovascular Systems
Riccardo M. Inciardi, Brian Claggett, Masatoshi Minamisawa, Sung-Hee Shin, Senthil Selvaraj, Alexandra Goncalves, Wendy Wang, Dalane Kitzman, Kunihiro Matsushita, Narayana G. Prasad, Jimmy Su, Hicham Skali, Amil M. Shah, Lin Yee Chen, Scott D. Solomon
Summary: This study assessed the left atrial (LA) structure and function in older adults without prevalent heart failure (HF) and found that LA measures were associated with NT-proBNP and increased risk of incident HF or death. These measures, when added to traditional risk factors and NT-proBNP, improved the accuracy of predicting cardiovascular events.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Sara B. Seidelmann, Meshal Soni, Abhijit Bhattaru, Kenneth B. Margulies, Svati H. Shah, Supritha Dugyala, Chenao Qian, Daniel A. Pryma, Zolt Arany, Daniel P. Kelly, Julio A. Chirinos, Paco E. Bravo
Summary: This study aimed to assess the predictive utility of nutrient intake in achieving myocardial glucose suppression (MGS) during ketogenic diet (KD) treatment. The results showed that only about half of the patients met the strict carbohydrate goals during highly supervised, short-term KD. There are currently no clear thresholds for carbohydrate or fat intake that reliably predict MGS.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
(2022)
Article
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Deepak L. Bhatt, Ph Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Rebecca A. Juliano, Lixia Jiao, Jean-Claude Tardif, Christie M. Ballantyne
Summary: This study aimed to investigate the treatment effects of icosapent ethyl in patients with heart failure (HF). The results showed that icosapent ethyl reduced triglyceride and hs-CRP levels in patients with HF, and had similar cardiovascular risk reduction effects.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Letter
Cardiac & Cardiovascular Systems
Mahesh K. Vidula, Daniel P. Kelly, Zoltan Arany Md, Kenneth B. Margulies, Svati H. Shah, Thomas P. Cappola, Paco E. Bravo, Senthil Selvaraj
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Stephen J. Greene, Iyanuoluwa Ayodele, Brooke Alhanti, Larry A. Allen, Sabra C. Lewsey, Srinath Adusumalli, Nosheen Reza, Adrian F. Hernandez, Clyde W. Yancy, Anupam B. Jena, Gregg C. Fonarow, Deepak L. Bhatt
Summary: This study investigated the impact of patient age on quality of care in heart failure and found that discharge date relative to 80th birthday did not affect healthcare quality or outcomes.
CIRCULATION-HEART FAILURE
(2023)
Letter
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Scott D. Solomon
JACC-HEART FAILURE
(2023)
Letter
Cardiac & Cardiovascular Systems
Senthil Selvaraj, Mikhail N. Kosiborod, Svati H. Shah
Article
Cardiac & Cardiovascular Systems
John W. Ostrominski, Muthiah Vaduganathan, Senthil Selvaraj, Brian L. Claggett, Zi Michael Miao, Akshay S. Desai, Pardeep S. Jhund, Mikhail N. Kosiborod, Carolyn S. P. Lam, Silvio E. Inzucchi, Felipe A. Martinez, Rudolf A. de Boer, Adrian F. Hernandez, Sanjiv J. Shah, Magnus Petersson, Anna Maria Langkilde, John J. V. Mcmurray, Scott D. Solomon
Summary: This study analyzed the potential role of dapagliflozin in treating apparent treatment-resistant hypertension (aTRH) in heart failure patients. The results showed that dapagliflozin consistently improved cardiovascular outcomes and was well-tolerated in patients with aTRH.