Discussion
congestion, AHF, acute heart failure, left ventricular systolic function
FLUID OVERLOAD, INFLAMMATION, CONGESTION, SYNDROME, ACUTE HEART FAILURE
In this study that enrolled patients with stable HFrEF, dapagliflozin treatment was associated with a significant short-term reduction of circulating CA125 but not NT-proBNP. Furthermore, changes in CA125 were more remarkable in patients at higher values at baseline. Interestingly, changes in CA125 mediated the increase in peakVOThe natriuresis and osmotic diuresis associated with SGLT2 inhibition have been shown in some studies to be associated with an increased plasma osmolarity and a modest decrease in plasma volumeCA125, also known as mucin 16 (MUC16), is a complex glycoprotein primarily produced by mesothelial cells in the pericardium, pleura, or peritoneum in response to tissue congestion or inflammationHowever, CA125 is upregulated in two-thirds of patients with AHF syndrome regardless of left ventricular systolic function and is associated with clinical congestion, especially tissue and third-space fluid accumulationRegarding changes in NT-proBNP, in the current study, we found a non-significant reduction of − 10.4% at 3-month in those allocated to dapagliflozin. It is consistent with previous results of the DAPA-HF and EMPEROR-reduced trial in which the authors reported a 8 and 12-month reduction of about 10%Further studies in acute heart failure scenarios are warranted. We speculate that changes in CA125 in response to decongestive therapies, including SGLT2i and renewed drugs such as acetazolamideInterestingly, the greater magnitude of CA125 changes was found in those patients with higher values at baseline, suggesting this effect is mainly found in those with residual fluid overload. Similar findings, in terms of greater reduction in those with higher baseline values, were also reported by our group in daily clinical practiceBeyond emerging as a reliable parameter of tissue congestion, some other advantages, such as low-cost, wide availability, and circulating levels not influenced by renal function and left ventricular ejection fraction, deserve to be highlightedFurther studies are required to unravel the exact mechanisms behind these findings. For instance, CA125 is also a proxy of inflammation. Thus, the effect attributable to dapagliflozin may also be capturing information about the antiinflammatory properties of this agent. Lastly, further trials are warranted to explore CA125 changes induced by SGLT2i in patients with greater fluid overload.