Assistant Professor Akira Taruya, Professor Atsushi Tanaka, and their colleagues from the School of Medicine, Wakayama Medical University announced on December 1 that, in collaboration with eight medical facilities in Wakayama Prefecture, they demonstrated the effectiveness of treatment using the diabetes drug dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), in improving symptoms of earlier, subclinical heart failure. The treatment group showed a reduction in epicardial adipose tissue (EAT), improvement in myocardial fibrosis, and enhanced ventricular diastolic function. The researchers plan to clarify these mechanisms going forward. This result suggests early-intervention may maintain cardiac function before heart failure symptoms develop. Their findings were published in Circulation on November 9.
According to the latest guidelines of the Japanese Circulation Society, heart failure is defined as "a syndrome in which structural or functional abnormalities of the heart cause congestion, elevated intracardiac pressure, and/or reduced cardiac output or tissue hypoperfusion, resulting in symptoms such as dyspnea, edema, and fatigue, as well as reduced exercise tolerance."
The number of heart failure patients are increasing worldwide, with an estimated 1.2 million patients in Japan alone, creating a situation referred to as a "heart failure pandemic." Although numerous risk factors for heart failure onset have been identified, current treatment is generally initiated only after onset. Resultingly, pre-onset intervention is considered necessary to address this situation.
Recent research has revealed that increased EAT is deeply involved in the onset and progression of cardiac diseases, including heart failure, coronary artery disease, and atrial fibrillation. Previous reports also indicated that administration of SGLT2i, which had been shown to improve heart failure prognosis, reduces EAT. Although SGLT2i were originally developed as diabetes drugs, they have since been recognized for their improvements in heart failure prognosis and are now also approved for treatment after onset.
On the other hand, it remained unclear whether SGLT2i were effective for earlier, subclinical heart failure, and their use age this stage was left to physician discretion.
Therefore, the research group conducted the "DAPA-EAT trial," an investigator-initiated trial to verify whether SGLT2i administration reduces EAT in patients with earlier, subclinical heart failure (Stage B).
Specifically, eight medical facilities in Wakayama Prefecture participated: Arida Municipal Hospital, Kinan Hospital, Shingu Municipal Medical Center, Hashimoto Municipal Hospital, Hidaka Hospital, Minami Wakayama Medical Center, Wakayama Rosai Hospital, and Wakayama Medical University Hospital.
A total of 229 patients with Stage B heart failure who had been receiving cardioprotective drugs without changes for at least two weeks were randomly assigned to either an SGLT2i treatment group or a non-treatment group. The treatment group received SGLT2i (10 mg daily) in addition to standard therapy, while the non-treatment group received only standard therapy. Both groups were observed for 24 weeks, with the trial being conducted from August 2022 to May 2024.
The primary endpoint was the change in EAT volume, with myocardial fibrosis and diastolic function evaluated by CT and echocardiography. Cardiovascular event rates and safety were also examined.
The results showed a significant reduction in EAT within the treatment group, demonstrating that SGLT2i administration may reduce EAT before heart failure onset. Furthermore, the treatment group exhibited significant reductions in left ventricular (LV) myocardial fibrosis volume and LV myocardial volume, indicating possibility improvements in myocardial structure. The effects were further supported by analyses using a linear mixed-effects model.
There was no significant difference in cardiovascular event rates. Additionally, there were almost no adverse events from administration.
Echocardiography also demonstrated a substantial improvement in LV diastolic function amongst the treatment group.
Future research will continue to investigate whether there is a causal relationship between EAT volume reduction, fibrosis reduction, and myocardial volume reduction. The researchers also plan to verify, in clinical settings, whether administration reduces cardiovascular event rates.
Taruya commented: "Patients with asymptomatic heart failure appear healthy, but compared with normal individuals without heart failure, they have increased EAT, increased LV myocardial volume and fibrosis volume, and decreased LV compliance. Until now, the main treatment approach for heart failure has been to slow the rate of heart failure progression. We believe the results of this study suggest that dapagliflozin administration may improve the myocardial condition of at least early-stage heart failure patients."
Journal Information
Publication: Circulation
Title: Dapagliflozin Reduces Epicardial Adipose Tissue and Myocardial Fibrosis in Subclinical Heart Failure: The DAPA-EAT Trial
DOI: 10.1161/CIRCULATIONAHA.125.077630
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.