Editorial
When Fat Speaks: Decoding the Signals of Epicardial Adipose Tissue after Acute Coronary Syndrome
2026 年 33 巻 2 号 p. 117-119
詳細
2026 年 33 巻 2 号 p. 117-119
See article vol. 33: 120-130
Epicardial adipose tissue (EAT) has emerged as an active player in cardiovascular pathophysiology, particularly in the development and progression of heart failure (HF). Beyond being a passive fat depot, the EAT exerts paracrine and endocrine effects through the secretion of pro- and anti-inflammatory adipocytokines, modulation of myocardial metabolism, and mechanical influences on the myocardium and coronary arteries1). Previous studies have consistently linked increased EAT volume with coronary artery disease, atrial fibrillation, and HF with preserved ejection fraction (HFpEF), particularly in the obese phenotype1-4). However, the role of EAT in acute coronary syndrome (ACS) and its potential influence on subsequent left ventricular (LV) remodeling remain insufficiently understood.
In this issue of the Journal of Atherosclerosis and Thrombosis, Harada et al. prospectively evaluated the association between EAT volume in ACS and longitudinal changes in LV ejection fraction (LVEF) over three years5). The authors demonstrated that baseline EAT volume was not associated with subsequent changes in LVEF across the cohort. Nevertheless, patients who developed chronic HF with reduced ejection fraction (HFrEF) exhibited significantly higher baseline EAT volumes despite the absence of obesity, whereas in patients with HF with mildly reduced ejection fraction (HFmrEF) and HFpEF, EAT volume correlated positively with body mass index (BMI). These findings highlight the heterogeneity of EAT pathophysiology according to the HF phenotype.
Several aspects of this study should be emphasized. First, the observation that higher EAT volumes characterize patients with chronic HFrEF despite non-obesity suggests that mechanisms beyond systemic adiposity may drive EAT expansion in this group. Ischemia-induced inflammatory signaling, neurohormonal activation, and maladaptive paracrine activity from EAT could contribute to adverse remodeling, independent of BMI. Conversely, in HFpEF and HFmrEF, EAT reflects a systemic metabolic milieu and obesity-related inflammation, consistent with previous studies linking EAT accumulation to metabolic syndrome and HFpEF progression1, 3, 4). This divergence underscores the fact that the clinical significance of EAT differs between the reduced and preserved EF phenotypes.
Second, this study adds nuances to the ongoing debate on whether EAT should be viewed primarily as a risk marker or therapeutic target. Although EAT volume at ACS onset did not predict longitudinal EF decline, the finding of disproportionately elevated EAT in non-obese patients with HFrEF suggests that EAT may serve as a marker of susceptibility to maladaptive remodeling in selected patients. However, whether EAT contributes to post-ACS remodeling or merely reflects the extent of myocardial injury remains unclear. Animal data and translational studies have shown that pro-inflammatory cytokines secreted by EAT, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1), can exacerbate ischemia–reperfusion injury and fibrosis6, 7); however, anti-inflammatory adipokines, such as adiponectin and omentin, may exert counterbalancing protective effects8, 9). The balance between these opposing factors may explain the inconsistent overall association between the EAT volume and outcomes.
Clinically, the recognition that non-obese patients with ACS with a high EAT burden are at a greater risk of developing HFrEF has potential prognostic implications. This subgroup may benefit from closer follow-up and more aggressive preventive strategies. Furthermore, the advent of pharmacological agents with demonstrated effects on EAT reduction, such as sodium–glucose cotransporter-2 (SGLT2) inhibitors10), has opened new avenues for therapeutic exploration. Although SGLT2 inhibitors were not widely available during the study period, future research should examine whether the modulation of EAT by these agents can translate into improved post-ACS remodeling and long-term HF outcomes.
This study has some potential limitations. This was a single-center study with a modest sample size, particularly in the HFrEF subgroup, and only baseline EAT was quantified. The absence of serial EAT measurements precluded the assessment of temporal changes in fat volume relative to LV remodeling. Moreover, the participants were only Japanese patients, among whom the prevalence of obesity was lower and visceral adiposity distribution differed from that of Western populations. Previous data have suggested that Asians may accumulate more visceral fat at comparable BMI levels11); thus, the relationship between EAT and outcomes may vary across ethnicities. Larger multi-ethnic studies are required to validate and extend these findings.
Collectively, this prospective study provides valuable evidence that, although EAT volume at ACS presentation does not predict changes in LVEF over time, it distinguishes patients who eventually manifest HFrEF despite non-obesity. These results suggest that the role of EAT is phenotype-dependent; in HFpEF and HFmrEF, EAT correlates with obesity and metabolic burden, whereas in HFrEF, elevated EAT may signal unique inflammatory or ischemic pathways driving adverse remodeling. Future investigations integrating imaging, biomarker profiling, and interventional trials are needed to clarify whether targeting the EAT could emerge as a viable strategy in post-ACS care. This study advances our understanding of the complex interplay between the EAT and cardiac remodeling and provides a foundation for precise approaches to HF prevention.
TM declares no conflicts of interest. AT has received honoraria from Amgen, Otsuka, and Mochida and scholarship from Bristol-Myers Squibb. KN has received honoraria from MSD, AstraZeneca, Novartis, Novo Nordisk, Bayer, Kowa, Mochida, Otsuka, Daiichi Sankyo, Mitsubishi Tanabe, Eli Lilly Japan, and Boehringer Ingelheim Japan; research grant from Fuji, Astellas, Novartis, Bayer, and Mochida; scholarship from Abbott Medical, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Teijin Pharma, and Boehringer Ingelheim Japan.
During the preparation of this study, the authors used ChatGPT, a language model developed by OpenAI to improve the language and readability. Thereafter, the authors reviewed and edited the content as required and took full responsibility for its content.
