Fluid status established by bioimpedance vector analysis (BIVA) at diagnosis of wild-type transthyretin amyloidosis is associated with patient survival

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Abstract Background Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is an increasingly recognised cause of heart failure. It is progressive and fatal if untreated (1) and characterised by the deposition of insoluble amyloid fibrils in the myocardium, causing a restrictive cardiomyopathy. Recent therapeutic advances have transformed outcomes in ATTR-CM (2). However, therapies do not reverse cardiomyopathy and patients in advanced disease stages at diagnosis still experience substantial morbidity from heart failure and require meticulous management of fluid balance. BIVA has been validated in cardiovascular disease and provides valuable data on fluid status and cachexia (3,4) but has not been evaluated in ATTRwt-CM. Purpose To evaluate the association between fluid status at diagnosis, measured as extracellular body water/total body water ratio (ECW/TBWr) via BIVA, and survival in ATTRwt-CM. Methods Retrospective analysis of 879 patients with newly diagnosed ATTRwt-CM between March 2016 and March 2020 was performed. Data collected at baseline included demographics, biochemistry, echocardiography and functional capacity assessment via six-minute walk test (6MWT) together with BIVA on body composition, namely ECW/TBWr as an indicator of fluid status and skeletal muscle index (SMI) for sarcopenia. Kaplan-Meier survival analyses at 5-year follow-up was performed to assess the association between baseline fluid status and mortality, with ECW/TBWr categorised as no volume overload (≤0.39), mild/moderate volume overload (>0.39-0.41) and severe volume overload (>0.41). Results Baseline characteristics are summarised in Table 1. Most patients were male (92.6%) and median age was 79.7 (74.7-84.6) years. Baseline NT-proBNP was raised with a median of 2798ng/l (1404.5-5019.3), with impaired global longitudinal strain (GLS) (median GLS -11% (-8.7 - -13.9%)) and impaired functional capacity via 6MWT (average distance 74%, predicted range 3-141%). 88.3% of patients had BIVA evidence of fluid overload at diagnosis, categorised as mild/moderate in 64.4% and severe in 23.9% and 59.4% of patients were sarcopenic. Kaplan-Meier survival analysis stratified by volume status at diagnosis demonstrated that increasing volume overload at diagnosis was predictive of mortality (Figure, p<0.001). Mild/moderate fluid overload and severe fluid overland were associated with increased risk of mortality (hazard ratio [HR] 3.04, 95% confidence interval [CI] 1.99-4.65, p <0.001 and HR 6.46, 95% CI 4.17-10.00, p <0.001, respectively) independently of NAC ATTR Stage at diagnosis. Bivariable Cox regression analyses showed that the prognostic significance of volume status by BIVA at diagnosis was maintained when adjusted for NT-proBNP, GLS, or 6MWT. Conclusions Fluid status at diagnosis in wtATTR-CM is associated with survival independent of disease severity. Further analysis will determine whether change in fluid status as a result of diuresis prolongs patient survival.Baseline Clinical Characteristics Kaplan-Meier Survival Analysis

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