Thread by @PieterMartensMD

Hot-of-the press sub-analysis of ADVOR trial looking at HCO3 levels and decongestive response @ESC_Journals #EHJ. A short 🧵 on the rational, findings and clinical translation of the paper. @FH_Verbrugge , @WilfriedMullens , @AlexMebazaa , @kevin_damman

doi.org/10.1093/eurhea…

The rational= old forgotten concept (fig). AT II stimulates prox nephron Na/HCO3. Exact stoichiometry might differ but per Na retained +/- 3 HCO3 are retained. HCO3 levels can indicate neurohormonal activation. HCO3 levels can predict development of HF (pubmed.ncbi.nlm.nih.gov/25896890/ )

If HCO3 levels in HF reflect prox nephron activation through NHE3 stimulation, patients might benefit more from decongestive effects of acetazolamide. + loop diuretics inhibit NKCC on macula densa ➡️ATII➡️HCO3 elevations during decongestion.

HCO3 levels are often elevated in AHF. In analysis of DOSE-AHF, ROSE-AHF and CARRESS-HF median HCO3 = 28 mEq/L. These pts are sicker and increase in HCO3 did not reflect better decongestion. @robmentz
pubmed.ncbi.nlm.nih.gov/26777758/

Elevated HCO3 is often termed inappropriate a contraction alkalosis. But pts in ADVOR with HCO3≥27 had most signs of volume overload.

Often we get a consult for RHC on AHF pt and elevated HCO3 + diuretic resistance with believe pt must be intravasc dry, but we find MAP, RAP, PCWP well elevated. Not intravascular dry but proximal nephron NaHCO3 retention is the cause of the diuretic resistance @RyanTedfordMD

In ADVOR pts with HCO3≥27 had better decongestive response on numerous metrics. Suggesting that how acetazolamide works overlaps with reason why HCO3 was elevated

Pts Rx with acetazolamide had a stable HCO3 during the treatment. While patients with loop diuretics only treatment had significant increase in HCO3. Remember loop diuretics➡️ATII➡️prox nephron activation ➡️HCO3 goes up and less Na presentation in loop of Henle for loop diuretics

Loop diuretics induce their own resistance which can be seen in the event rate in the loop only arm (red boxes) and is prevented by acetazolamide. Indeed the treatment effect of acetazolamide becomes bigger every day due acquired diuretic resistance in the loop only arm

bottomline:
1) HCO3 elevation in AHF = sign of prox nephron NaHCO3 retention
2) Acetazolamide works even more potent in this setting
3) Acetezolamide prevents loop induced HCO3 increase and the associated resistance