Volume 06 · Issue 03 · 2026

HFpEF represents a growing clinical and therapeutic challenge in the current clinical setting, as it is difficult to diagnose and lacks consistently effective management guidelines.^[1,2]Despite accounting for over half of all heart failure cases, HFpEF remains notoriously difficult to treat, with most therapeutic options demonstrating limited efficacy.^[3]Unlike heart failure with reduced ejection fraction (HFrEF), where neurohormonal blockade and inotropic agents have led to significant clinical advances and clarity of mechanisms,^[4]HFpEF lacks clearly defined molecular targets, in part due to its heterogeneity. Multiple factors have been implicated in HFpEF pathogenesis, including systemic inflammation, endothelial dysfunction, myocardial fibrosis, microvascular rarefaction, and altered cardiomyocyte stiffness.^[5]However, a unifying mechanistic framework has proven elusive. Among the emerging hallmarks of HFpEF is metabolic dysregulation,^[6]particularly in the context of obesity, insulin resistance, and hypertension—key comorbidities that dominate the HFpEF phenotype. Metabolism is fundamental to cardiovascular homeostasis; it governs the energetic demands of cardiomyocytes, the inflammatory tone of immune cells, and increasingly, the behavior of vascular and lymphatic endothelium.^[7]Disrupted metabolic pathways—ranging from glucose and fatty acid oxidation to amino acid catabolism—can perturb cellular signaling, redox balance, and structural remodeling, all of which contribute to disease progression.^[7]In this context, the recent work by Guo et al^[1]is especially noteworthy for spotlighting a previously overlooked metabolic pathway—branched-chain amino acid (BCAA) catabolism in lymphatic endothelial cells (LECs)—and demonstrating its pivotal role in maintaining cardiac lymphatic integrity and preventing HFpEF. Their findings not only introduce a novel metabolic-vascular axis but also offer actionable insights into therapeutic intervention, potentially redefining our understanding of HFpEF pathobiology.

For more than 30 years, the terminology of acute myocardial infarction has been dominated by a deceptively simple binary classification: ST-segment elevationvs.non-ST-segment elevation myocardial infarction (STEMI/NSTEMI).^[1]STEMI implied emergency reperfusion, whereas NSTEMI implied risk stratification with troponin measurements, risk scores, and usually a "next-day" invasive strategy. The widespread adoption of this framework is understandable. Millimeter-based STEMI criteria were definitive, easy to follow, and historically transformative. The system was objective, reproducible, and protective against indiscriminate catheterization. In this view, broadening the emergency reperfusion gate beyond STEMI raises concerns about overdiagnosis, unnecessary catheterization laboratory activation, avoidable contrast exposure, and the loss of a simple universal protocol. Yet, it also masked a conceptual error: the disease we urgently seek is not ST-segment elevation, but acute coronary occlusion (ACO).

For more than 2 decades, risk stratification has served as the cornerstone of decision-making in non-ST-segment elevation myocardial infarction (NSTEMI). Both the 2023 European Society of Cardiology guidelines and the 2025 American College of Cardiology/American Heart Association guidelines endorse a risk-adapted invasive strategy: immediate angiography within 2 h for very high-risk patients, early invasive strategy within 24 h for high-risk patients, and selective or conservative management for the remainder.^[1,2]

Cardiovascular disease (CVD), particularly coronary artery disease (CAD), remains the leading cause of global mortality and is characterized by atherosclerotic plaque formation. Plaque rupture or erosion promotes thrombosis, leading to ischemia, necrosis, and clinical events such as myocardial infarction. Despite decades of research and advances in CAD treatment, its incidence and mortality remain high.^[1]Between 2000 and 2019, global CVD deaths increased by 25%, with the greatest rise observed in the Western Pacific region, where China bears a substantial share of mortality and disability-adjusted life years.^[2]This burden reflects not only demographic changes, such as population aging, but also the complex pathogenesis of CAD and persistent gaps in prevention and treatment.