Kidney function and acid–base status as gatekeepers of natriuretic and diuretic responsiveness in chronic HF: insights from the DEA-HF clinical trial

In chronic heart failure (HF), decongestion is hindered by reduced renal function and diuretic resistance. This study compared the effect of eGFR and serum bicarbonate on three diuretic regimens in congestion-refractory HF patients.

This is a prespecified post-hoc analysis of DEA-HF, a randomized, crossover trial (n = 42). Patients received, in random order, weekly treatments of IV furosemide 250 mg; oral metolazone 5mg + IV furosemide 250 mg; and IV acetazolamide 500mg + IV furosemide 250 mg. Primary endpoint: 6h-Natriuresis; secondary: 6h-diuresis and decongestion measures at 7 ± 3 days. Mixed models assessed effect modification by eGFR (≤30 vs. > 30 mL/min/1.73m²) and by serum bicarbonate (≤vs.> median-29.6 mmol/L). Higher eGFR was associated with greater natriuresis and diuresis (4735 mg vs. 3211 mg, P = 0.0004; 1.93L vs. 1.49L, P = 0.0078). In patients with eGFR > 30, addition of metolazone to furosemide led to higher natriuresis compared to acetazolamide addition (5525 mg vs. 4379 mg, P = 0.04) or to furosemide monotherapy (5525 mg vs. 4303 mg, P = 0.014); no regimen differences were observed at eGFR ≤ 30. Independently, higher serum bicarbonate predicted greater natriuresis and diuresis (4858 mg vs. 3576 mg, P = 0.0008; 1.99 vs. 1.56L, P = 0.0014). There was no difference in clinical decongestion measures. All regimens were well-tolerated with comparable safety concerns regarding renal function, electrolyte disturbances, or hypotension.

In ambulatory patients with congestion-refractory HF and eGFR > 30 mL/min/1.73m², natriuretic and diuretic responses are augmented across all regimens, with metolazone providing additional improvement in natriuresis. When eGFR ≤ 30 mL/min/1.73m², neither metolazone nor acetazolamide provides additional benefit. High serum bicarbonate predicts better natriuretic and diuretic response, as well as additional benefit from metolazone treatment. High-dose diuretics had comparable safety profiles across the eGFR spectrum.