Prognostic impact of an extravascular congestion score and its interaction with SGLT2 inhibitor therapy in patients hospitalized for acute heart failure

INTRODUCTION AND OBJECTIVES Congestion is the main driver of hospitalization and adverse outcomes in acute heart failure (AHF), with tissue-predominant volume expansion frequently persisting despite loop diuretic therapy. We evaluated whether an extravascular congestion score (ECS) identifies high-risk patients and modifies the prognostic effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i). METHODS We prospectively studied 821 patients hospitalized for AHF. ECS at discharge was defined as the sum of 3 variables: antigen carbohydrate 125 > 35 U/mL, peripheral edema, and pleural effusion (range 0-3). The primary endpoint was a composite of all-cause mortality or heart failure rehospitalization at 1 year. Multivariable Cox models assessed associations between ECS and outcomes and tested the interaction with SGLT2i use at discharge. RESULTS During follow-up, the primary endpoint occurred in 436 patients (53.5%). Higher ECS was associated with a stepwise increase in risk. Compared with ECS 0, adjusted HRs were 1.72 (95%CI, 1.04-2.85; P = .034) for ECS 1 and 2.39 (95%CI, 1.29-4.43; P = .006) for ECS 2. A significant interaction was observed between ECS and SGLT2i use (P for interaction = .029). SGLT2i use was not associated with improved outcomes in ECS 0 (HR, 1.21; P = .462) but was associated with numerically lower risk in ECS 1 (HR, 0.76; P = .065), and with a marked risk reduction in ECS 2 (HR, 0.45; P = .003). CONCLUSIONS ECS identifies AHF patients at high risk due to residual tissue congestion. The association between SGLT2i use and improved outcomes was more pronounced with increasing extravascular congestion burden.