Read our latest analysis from the #ADVOR trial @JACCJournals. Deeper dive into the relationship of #natriuresis with decongestion & clinical outcomes after diuretic therapy in acute #heartfailure! Tweetorial below...
authors.elsevier.com/a/1h4wr2d9GHwT…
@PieterMartensMD @WilfriedMullens
First, look at detailed #ADVOR protocol below:
onlinelibrary.wiley.com/doi/full/10.10…
We did 2 consecutive urine collections:
1. Randomization => First morning (<24 h)
2. First morning => Second morning (=24 h)
If in those 2 collections, cumulative urine output <3.5 L ➡️ Failed decongestion!
Allocation to #acetazolamide clearly increased:
✅total urine output (+12.6%)
✅total natriuresis (+26.9%)
In relative terms: effect on natriuresis > urine output, UO🚫significant after 1st diuretic dose, natriuresis remained high!
*Normalized UO to 24 h for collection 1.
Moreover, allocation to #acetazolamide by a landslide strongest predictor of both urine #sodium concentration (UNa) AND total #natriuresis (molecules excreted)!
For instance, 5-8x bigger impact than an eGFR change of 10 mL/min/1.73m²
Be wary: total natriuresis and UNa not the same!
Total natriuresis tracks well with UO
➡️Amount of extracellular volume (ECV) DURABLY removed (150 mmol Na ~ 1 L ECV)
❗️Urine is usually HYPOTONIC (UNa <150 mmol/L)
➡️Part of UO reflects #dehydration rather than #decongestion
No such strong correlation between UNa & UO!
UNa:
➡️Only partly reflects decongestion
➡️Also reflects neurohumoral activation
➡️Best measurement of sodium avidity
Thus, #acetazolamide
✅Keeps sodium content of urine high, therefore allowing better decongestion for same UO!
Higher UNa & greater total natriuresis
✅Associated with higher chance of successful #decongestion (no more than trace edema and no ascites/pleural effusion)
From 1st morning, patients w higher UNa (less Na avidity): significantly greater clinical decongestion!
UNa ≥80 ideal cut-off, indicating excellent response!
❗️Intriguingly, effect of #acetazolamide on decongestion🚫significant after adjustment for natriuresis➡️Mediation?
Consequently, patients with better natriuresis has a shorter length of stay
✅4.5 days shorter for UNa ≥100 versus <50 mmol/L
As shown in other studies, better natriuretic response to #diuretics was associated with better clinical outcome (death or heart failure readmissions)
Now the intriguing part:
Good natriuretic response (UNa ≥80 mmol/L):
➡️Similar outcome loop diuretic monotherapy & combination with acetazolamide
❗️Many more patients with #acetazoalmide had UNa ≥80 mmol/L (NNT = only 7!)
Poor natriuretic response (UNa <80 mmol/L):
🪦 &🏥
Also, for people that are so concerned about the non-significantly🔼90-day 🪦 with #acetazolamide in #ADVOR:
* Notice LATE occurrence of this effect (45 days after randomization or >30 days after acetazolamide was stopped)
* Mostly in patients with a poor natriuretic response
My interpretation is that by the play of chance, patients in the #acetazolamide arm were probably slightly sicker.
Illustrated as well by slightly higher baseline dose of loop diuretics (80 vs. 60 mg furosemide equivalents).
Conclusion:
1. Upfront combination of #acetazolamide with loop diuretics in acute #heartfailure helps to keep sodium content of urine high.
2. Strong natriuresis ~ better (and more durable?) decongestion!
3. Natriuretic response ~ clinical outcomes
➡️UNa+ guided diuretic therapy
Also read this other analysis from the #ADVOR, eloquently discussed by my friend & partner in crime @PieterMartensMD :
It shows nicely that after 48 h treatment with monotherapy loop diuretics, almost every patient develops "contraction alkalosis"
We need to rename "contraction alkalosis" to "neurohumoral alkalosis", as it is not a sign of hypovolemia per se.
Thus:
➡️Minor congestion requiring 1 or 2 doses of diuretics probably does not need #acetazolamide
➡️In case of any prolonged treatment: UPFRONT!!!
This is a BIG difference with #thiazides, which have shown to break diuretic resistance, can wait until this occurs!
The effect of #acetazolamide resides in braking the neurohumoral system, so need to treat upfront rather than bail-out, which is how #ADVOR was set up!
For the #physiology fans, here's the paper in which we discussed the proximal nephron hypothesis, leading to the #ADVOR trial @ESC_Journals :
onlinelibrary.wiley.com/doi/full/10.10…
Doing a pilot on UNa guided therapy incorporating ALL diuretic classes (#DECONGEST):
clinicaltrials.gov/ct2/show/NCT05…
@SVanhentenrijk
Don't miss out on:
- ENACT-HF at #Heartfailure2023 in Prague
- PUSH-HF, by @jozinetm & @kevin_damman @escardio 2023 in Amsterdam
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