Response by Dauw and Mullens to Letters Regarding Article, “Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response: The Multicenter ENACT-HF Study”

In Response: We thank all our colleagues for their interest in our study. 1 Dr Albulushi questions how patient selection might affect the generalizability of our results. A detailed description of the inclusion and exclusion criteria has been published previously. 2 Our study had a pragmatic design with the goal of mimicking real-life practice as much as possible. In essence, almost all patients with fluid overload on a daily loop diuretic dose of ≥40 mg of furosemide or equivalent with elevated natriuretic peptides could be included. Only patients in shock or impending shock and patients with a potential need for renal replacement therapy were excluded. As a result, the patient population in our study is comparable to that of recent registries of acute heart failure. 3 Of note, comor-bidities were highly prevalent, and almost half of the patients had chronic kidney disease (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m 2). Regarding arrhythmias, 54% of patients had a history of atrial fibrillation, and 45% were in atrial fibrillation at the time of admission. Therefore, our study population seems generalizable to real-world patients. Dr Albulushi was also interested in long-term data on readmission rates or mortality, but we did not collect data beyond discharge. Shahriar et al request more information on the diuretic response assessments after the first loop diuretic dose. Indeed, there were more patients with an insufficient urine output (UO; 19.6%) than an insufficient urinary sodium concentration (UNa; 12.6%) in the protocol arm. We performed additional analyses to provide more in-depth information: 36 (25.2%) patients had any sign of insufficient diuretic response. Of those, 8 (5.6%) only had UNa <50 mmol/L; 18 (12.6%) only had UO <100 mL/h, and 10 (7.0%) had both UNa <50 mmol/L and UO <100 mL/h. Thus, both measures can be incongruent and have additive value. Recent observational data in a small group of acute heart failure patients have already suggested that UNa and UO may differ. 4 When a threshold of UNa <70 mmol/L is applied, 60 (24.5%) patients in the standard of care group and 26 (18.3%) patients in the protocol group had an insufficient diuretic response. Potentially, a cutoff value of UNa <70 mmol/L might identify a larger group of patients with an insufficient diuretic response. A cutoff value of UNa <70 mmol/K was also used in the recent Pragmatic Urinary Sodium-Based Treatment Algorithm in Acute Heart Failure randomized trial. 5 In addition, the trial used a higher UO threshold with UO <150 mL/h. Again, the natriuresis-guided protocol performed better than the standard of care, but UNa and UO were not always congruent.