HCAR1-mediated lactate signaling modulates motor behavior and regulates spontaneous firing in Purkinje cells.

Heart failure (HF) is a clinical syndrome rather than a single disease entity. Contemporary European and North American documents define and classify HF using symptoms and signs, natriuretic peptides, structural or functional cardiac abnormalities, and left ventricular ejection fraction (LVEF) categories, including HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), preserved ejection fraction (HFpEF), and improved ejection fraction (HFimpEF) [,,,]. Despite major progress in guideline-directed medical therapy, HF remains highly heterogeneous. Patients with similar LVEF may differ substantially in inflammatory burden, fibrosis, pulmonary comorbidity, obesity, renal dysfunction, autonomic tone, and environmental vulnerability. This heterogeneity has encouraged endotyping approaches that seek biologically coherent subgroups with distinct symptom trajectories, biomarker patterns, decompensation triggers, and therapeutic opportunities. Inflammation and extracellular matrix remodeling are central to this endotyping perspective. HFpEF has been conceptualized as a comorbidity-driven syndrome in which systemic inflammation promotes coronary microvascular dysfunction, cardiomyocyte stiffness, and myocardial fibrosis; HFrEF also involves inflammatory activation during myocardial injury, repair, and adverse remodeling [,,,,,]. The immunoglobulin E (IgE) axis intersects with this biology. Experimental and clinical data suggest that total IgE and IgE-FcεRI signaling may participate in pathological cardiac remodeling, cardiac fibrosis, atherogenesis, and cardiovascular mortality, while newer work indicates that HF itself may influence IgE biology through spleen–heart immune communication and CD23-mediated pathways [,,,,,,]. Cardiac mast cells provide an additional link between allergic effector biology and cardiovascular remodeling because they can release vasoactive, proteolytic, profibrotic, and inflammatory mediators in the myocardium, vasculature, and right-ventricular–pulmonary interface [,,,]. Molecular allergology offers a more precise framework than crude extract testing. Component-resolved diagnosis (CRD) can distinguish genuine sensitization from cross-reactivity and refine clinical interpretation in polysensitized patients [,,]. In ragweed allergy, Amb a 1 is the dominant major allergen and accounts for a large proportion of ragweed-specific IgE reactivity in sensitized individuals. Ragweed pollen allergy is an important and expanding European public health problem driven by plant invasion, climate change, pollution, and regional exposure intensity. Clinical and molecular studies across Europe confirm clinically relevant ragweed rhinitis, conjunctivitis, asthma, and Amb a 1 sensitization [,,,,,,,,]. The geographical distribution of this burden is highly uneven and merits specification. Ragweed invasion in Europe is concentrated in the Pannonian Basin, encompassing Hungary, Serbia, Croatia, Slovakia, western Romania, and parts of Ukraine, with secondary foci in the Rhône Valley of France and the Po Valley of northern Italy [,,]. Sensitization rates track this distribution closely, ranging from below 2.5% in Finland to above 50% in established centers of infestation such as Szeged and Budapest in Hungary, with rates exceeding 50% also reported from parts of Serbia, Croatia, Bulgaria, and northern Italy and intermediate values in France and Austria [,]. Estimates for Europe as a whole indicate that approximately 13.5 million people are affected by ragweed allergy, a figure projected to rise with continued climate-driven range expansion [,]. Romania lies within the Pannonian focus, and the western part of the country in particular constitutes one of the most heavily exposed regions. In a pollen-exposed cohort from northern Italy, 66 Amb a 1-allergic participants showed significant associations between airborne ragweed pollen concentrations and daily ocular, nasal, and bronchial symptom severity []. Component-resolved studies in European cohorts have demonstrated IgE reactivity to Amb a 1 together with cross-reactive profilins, polcalcins, and homologous weed-pollen allergens [,,]. This regional concentration is central to the argument of the present review: the exposure-informed studies proposed below are feasible only in populations where both ragweed sensitization and heart failure are sufficiently prevalent for their overlap to be studied, and western Romania and the wider Pannonian Basin represent precisely such settings. Environmental and epidemiological studies also suggest that pollen exposure and allergic airway disease may intersect with cardiovascular outcomes, although the available findings are heterogeneous and often confounded by heat, air pollution, respiratory infections, and behavioral factors [,,,,,,,].