Journal Article Ahead of print
PubMed: 42149589 DOI: 10.1093/ehjcvp/pvag019
Kidney function and acid-base status as gatekeepers of natriuretic and diuretic responsiveness in chronic HF: insights from the DEA-HF clinical trial.
Eur Heart J Cardiovasc Pharmacother
Authors: Ina Volis, Amit Gruber, Aharon Ronnie Abbo, Doron Aronson, Nicolas Girerd, Søren Lund Kristensen, Robert Zukermann, Natalia Alberkant, Elena Sitnitsky, Anton Kruger, Polina Khasis, Evgeny Bravo, Boaz Elad, Ludmila Helmer Levin, Oren Caspi
Affiliations
- The Heart Failure Unit, Department of Cardiology, Rambam Health Care Campus, Haifa 3109601, Israel.
- The Heart Failure Unit, Department of Cardiology, Rambam Health Care Campus, Haifa 3109601, Israel. The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa 3525433, Israel.
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa 3525433, Israel.
- Université de Lorraine, INSERM, Centre d'Investigations Cliniques-Plurithématique 1433, CHRU Nancy, and INSERM U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy 54000, France.
- Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen 2100, Denmark.
- Clinical Research Institute at Rambam (CRIR), Haifa 3109601, Israel.
Abstract
AIMS
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.
METHODS AND RESULTS
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.
CONCLUSION
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.
MeSH
Acetazolamide, Diuresis, Safety, Serum, Kidney, Natriuresis, Metolazone, Diuretics, Therapeutics, Furosemide