Decongestion Strategies and Renin-Angiotensin-Aldosterone System Activation in Acute Heart Failure

Abstract

Background High dose diuretics in patients with acute heart failure (AHF) are thought to activate the renin-angiotensin-aldosterone system (RAAS), and alternative decongestion strategies, such as ultrafiltration (UF), have been proposed to mitigate this RAAS activation. Methods We analyzed 427 AHF patients enrolled in the DOSE-AHF and CARRESS-HF trials. We assessed the relationship between two markers of RAAS activation (plasma renin activity [PRA] and aldosterone) from baseline to 72-96h and decongestion strategy; high vs. low-dose and continuous infusion vs. bolus furosemide for DOSE-AHF and UF vs. stepped pharmacologic care for CARRESS-HF. We determined the relationship between RAAS biomarkers and 60-day outcomes. Results Patients with greater RAAS activation at baseline had lower blood pressures, lower serum sodium, and higher BUN. Continuous infusion furosemide and UF were associated with greater PRA increases (median +1.66 vs. +0.66 ng/mL/h with continuous vs. bolus, P=0.021; +4.05 vs. +0.56 ng/mL/h with UF vs. stepped care, P=0.014). There was no significant difference in RAAS biomarker change with high vs. low-dose diuretics (both P>0.5). Neither baseline log PRA nor log aldosterone was associated with increased death/HF hospitalization (HR for a doubling 1.05; 95% CI: 0.98-1.13, P=0.18 and HR 1.13; 95% CI: 0.99-1.28, P=0.069, respectively). The change in RAAS biomarkers from baseline to 72-96 h was not associated with outcomes (both P>0.5). Conclusions High-dose loop diuretics did not result in greater RAAS activation than low-dose diuretics. UF resulted in greater PRA increase than stepped pharmacologic care. Neither PRA nor aldosterone was significantly associated with short-term outcomes in this cohort.

Blood urea nitrogen-to-creatinine ratio in the general population and in patients with acute heart failure

“…Takaya et al 9 showed baseline BUN/creatinine ratio in AHF was not associated with acute kidney injury within 48 hours defined by serum creatinine increase ≥0.3 mg/dL or 50% from baseline. In another AHF study, the incidence of WRF was similar in patients with AHF with high/low plasma renin and aldosterone activity at baseline 30. These findings imply a complex and multifactorial pathophysiological background of WRF in patients with AHF.…”

“…In 427 patients enrolled in the Diuretic Optimization Strategies Evaluation (DOSE) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS) HF trials, low blood pressure, low ejection fraction, low sodium and high BUN levels are associated with the above-median levels of plasma renin or plasma aldosterone of renin-angiotensin-aldosterone activity 30. This finding supports our speculation that higher than normal range of BUN/creatinine ratio represents highly activated neurohormonal status in patients with AHF.…”

More Efficient Sodium Removal by Ultrafiltration Compared to Diuretics in Acute Heart Failure; Underexplored and Overstated

“…The mechanistic basis for UF fluid removal from the venous pool leading to interstitial decongestion is progressive intravascular volume contraction. In support of this concept, a recent study by Mentz et al [6] showed that contrary to what was suggested by earlier studies, UF therapy is associated with even more pronounced elevation in plasma renin activity compared with diuretics, possibly due to lowered intravascular volume and decreased intracellular chloride in macula densa triggering renin release. During UF therapy, the increase in filtration fraction (i.e., the ratio of glomerular filtration rate to renal blood flow) could lead to enhanced proximal tubular sodium reabsorption.…”

Current and Potential Therapeutic Strategies for Hemodynamic Cardiorenal Syndrome

“…Given the risk of adverse events and RAAS activation [55], the available evidence does not appear to support the implementation of a mechanical fluid removal strategy for ADHF or CRS when an adequate amount of urine volume is anticipated with available pharmacologic therapy. This is consistent with the statement in the 2013 ACCF/AHA HF guidelines [19].…”