Reply to the letter regarding the article 'Lower extremity lymphatic flow is associated with diuretic response in acute heart failure'

Aims: The dysfunctional lymphatic system appears to play an important role in the development and progression of congestion in heart failure. We hypothesized that in acute heart failure (AHF), diuretic efficacy is associated with peripheral lymph flow. Methods and results: We prospectively studied AHF patients who received protocolized diuretics followed by assessment of lower limb flow using indocyanine green lymphangiography (a validated method for visualization of lymphatic drainage). The lymph flow was defined as 'present' when it reached the ankle and 'significant' when it reached >10 cm within 10 min of dye injection, respectively. Based on diuretic efficacy (defined as cumulative diuresis and weight loss), patients were classified as diuretic responders vs. non-responders. Overall, 65 patients (mean age: 67 +/- 15 years, median [Q1-Q3] N-terminal pro-B-type natriuretic peptide: 6901 [4478-12 723] pg/ml) were examined. There were 43 (66%) diuretic responders and 22 (34%) non-responders who did not differ in baseline clinical/laboratory characteristics. Among the responders, there were more patients with lymph flow either 'present' or 'significant' (95% vs. 73% and 88% vs. 45% vs non-responders, respectively, p < 0.01). Responders had significantly longer median distance lymph reached within 10 min (50 [24-75] vs. 10 [3-38] cm; p < 0.0005). There was a significant association between lymph flow and 6-h diuresis with beta (standard error) of 0.45 (0.13) (p < 0.005). In the multivariable analyses, lymph flow distance (odds ratio 1.48, 95% confidence interval 1.08-2.03) independently predicted diuretic efficacy (p < 0.05). Conclusion: For the first time, faster lower limb lymph flow was linked with better diuretic efficacy in AHF. Studies are needed to determine whether the lymphatic system can become a therapeutic target for decongestion.