The discovery of an NRF2/β3-adrenergic receptor (β3AR) axis that orchestrates metabolic rewiring and antioxidant cellular mechanism under pressure overload represents a significant advancement in our understanding of cardiac adaptation. β3AR, selectively upregulated during early cardiac stress, promotes glucose flux through the pentose phosphate pathway, boosting NADPH production and redox homeostasis. This metabolic shift is accompanied by increased cardiac glucose uptake—readily visualized using ¹⁸F-FDG PET, a widely available clinical imaging modality. In the referenced study, β3AR overexpression correlated with enhanced FDG uptake, reflecting a protective, adaptive phenotype. While FDG-PET offers a global view of myocardial glucose metabolism, emerging β3AR-targeted PET tracers promise a more receptor-specific and mechanistic readout. Although β-adrenergic receptor imaging has been previously explored using [¹¹C]-CGP-12177 and [¹¹C]-CGP-12388 (targeting β₁/β₂), these early-generation tracers highlight both feasibility and limitations due to short half-lives and currently lack of β3-targeted PET tracers selectivity. The dynamic regulation of β3AR—upregulated in early disease, and whether its expression changes in late or end-stage heart failure—underscores its potential as a molecular marker for staging and therapy monitoring. Combining FDG-PET with future β3AR-specific tracers could enable a multimodal strategy to precisely diagnose, stratify, and monitor heart failure progression. This axis represents a compelling target for next-generation, receptor-guided imaging in precision cardiology.