Intensification of pharmacological decongestion but not the actual daily loop diuretic dose predicts worse chronic heart failure outcome: insights from TIME-CHF

Background: Both loop diuretics (LDs) and congestion have been related to worse heart failure (HF) outcome. The relationship between the cause and effect is unknown. The aim of this study was to investigate the interaction between congestion, diuretic use and HF outcome.

Methods: Six hundred and twenty-two chronic HF patients from TIME-CHF were studied. Congestion was measured by means of a clinical congestion index (CCI). Loop diuretic dose was considered at baseline and month 6. Treatment intensification was defined as the increase in LD dose over 6 months or loop diuretic and thiazide or thiazide-like diuretic co-administration. The end-points were survival and HF hospitalisation-free survival.

Results: High-LD dose at baseline and month 6 (≥ 80 mg of furosemide per day) was not identified as an independent predictor of outcome. CCI at baseline remained independently associated with impaired survival [hazard ratio (HR) 1.34, (95% confidence interval) (95% CI) (1.20-1.50), p < 0.001] and HF hospitalisation-free survival [HR 1.09, 95% CI (1.02-1.17), p = 0.015]. CCI at month 6 was independently associated with HF hospitalisation-free survival [HR 1.24, 95% CI (1.11-1.38), p < 0.001]. Treatment intensification was independently associated with survival [HR 1.75, 95% CI (1.19-1.38), p = 0.004] and HF hospitalisation-free survival [HR 1.69, 95% CI (1.22-2.35), p = 0.002]. Patients undergoing treatment intensification resulting in decongestion had better outcome than patients with persistent (worsening) congestion despite LD dose up-titration (p < 0.001).

Conclusion: Intensification of pharmacological decongestion but not the actual LD dose was related to poor outcome in chronic HF. If treatment intensification translated into clinical decongestion, outcome was better than in case of persistent or worsening congestion.