BACKGROUND: Cardiac decompensation in aortic stenosis (AS) involves extra-valvular cardiac damage (CD) and progressive fluid overload (FO). FO can be objectively quantified using bioimpedance spectroscopy (BIS). We aimed to assess the prognostic value of FO beyond established cardiac damage markers to guide risk stratification.

METHODS: Consecutive patients with severe AS scheduled for transcatheter aortic valve implantation (TAVI) underwent BIS in addition to echocardiographic, clinical, and laboratory assessment. FO by BIS was defined as ≥1.0L (1-3L: mild FO; >3L: severe FO). The extent of CD was defined by echo according to an established staging classification (stage 0 or 1: no or isolated left ventricular CD; stage 2: left atrial or mitral CD; stage 3: pulmonary vasculature or tricuspid CD; stage 4: right ventricular CD). Right-sided CD (rCD) was defined as stage 3 or 4. Occurrence of heart failure hospitalization (HFH) and/or all-cause death served as primary endpoint. 

RESULTS: In total, 880 patients (81±7 y/o, 47% female) undergoing TAVI with valid BIS measurements were prospectively included. 360 (41%) had FO (274 mild FO, 86 severe FO). Overall, increasing fluid levels by BIS correlated with clinical signs of congestion, higher NT-proBNP levels, and increasing cardiac damage (all P<0.05).  Yet, clinical examination was unremarkable in >50% of those diagnosed with FO by BIS. Also, 25% had FO but no rCD (FO+/rCD-). Conversely, the discrepancy of FO-/rCD+ identified a “HFpEF” phenotype, characterised by better left ventricular function, less hypertrophy, lower NT-proBNP levels, but more coronary artery disease, arterial hypertension, mitral regurgitation and atrial fibrillation compared to FO+/rCD- (Figure 1A).

After 2.4±1.0 years, 236 patients (27%) had reached the primary endpoint (29 HFH, 194 deaths, 13 both). A stepwise increase in risk hazard was observed from mild FO (vs. no FO: adjusted hazard ratio [AHR] 1.34, 95% confidence interval [CI] 1.01-1.79) to severe FO (vs. no FO: AHR 1.37, 95% CI 1.11-1.69; Figure 2A). Quantitatively, every 1L increase in BIS was associated with a 13% (AHR 1.13, 95% CI 1.05-1.21, P<0.001) increase in event hazard, with a consistent effect across all subgroups, including cardiac damage stages (Figure 2B). Importantly, FO+/rCD- had significantly worse outcomes, but not FO-/rCD+ (Figure 1B). 

CONCLUSION: Quantitative assessment of FO enables a nuanced refinement of cardiac damage in severe AS. FO identifies phenotypes with higher or lower inherent risk, respectively, otherwise misclassified by the traditional staging classification. Hence, incorporation of FO improves risk stratification compared to currently established staging criteria. The hypothesis that FO could serve as a potential treatment target after TAVI is currently being tested in a randomised controlled trial (EASE-TAVR, NCT04556123).