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Challenging Cases in Acute Heart Failure
Diuretic Resistance
Kevin Damman, MD, PhDUniversity Medical Center Groningen
Groningen, The Netherlands
Disclosures
Supported by the Netherlands Heart Institute (ICIN) and a HFA
Research Grant
Scope of the Problem
• Acute (Decompensated) Heart Failure patient
• Treatment with conventional methods:
i.v. Loop Diuretics
Oxygen, morfine if necessary, vasodilators
Either:
No improvement in symptoms/signs or worsening
No increase in diuresis
Increase in serum creatinine
Diuretic Resistance?
Contents
Diuretic Resistance
• Definition
• Epidemiology
• Pathyphysiology
• Possible treatments and caveats
Definition
No Consensus on definition of Diuretic Resistance
• “Poor response to diuretic therapy”
• Peristent signs and symptoms despite diuretic therapy
• Furosemide > 80mg daily (chronic HF)
• Fractional Sodium excretion < 0.2%
• Failure to excrete at least 90 mmol of sodium within 72h of a 160
mg oral furosemide dose given twice daily
• Lack of weight loss during i.v. loop diuretic therapy
• Lack of negative fluid balance during i.v. Loop diuretic therapy
Diuretic Response
No Consensus on definition of Diuretic Resistance
• It might be better to speak of the relative response to diuretics
Diuretic Response
Diuretic Efficacy
• Overcomes the problem of estalishing a ‘cut off’
• Highlights the importance of response to diuretics on a continuous
scale
Weight Change
Adapted from Fonarow et al Rev Cardiovasc Med 2003 (ADHERE)
Little / no weight loss or weight
increase~50%
Diuretic Response
Testani et al Circ Heart Fail 2014
Diuretic Response
Testani et al Circ Heart Fail 2014
Diuretic Response
Valente et al Eur Heart J 2014 (PROTECT)
Diuretic Response:
Weight Change (kg) / 40 mg Furosemide equivalent
Diuretic Response
Valente et al Eur Heart J 2014 (PROTECT)
Pathophysiology
Pathophysiology incompletely understood
• Diminished Reponsiveness to Diuretics in Heart failure
• Activation of RAAS by diuretics
• Decreased GFR and Renal Blood Flow
• Braking phenomenon
• Hypoalbuminemia (Furosemide) and Hyperalbuminuria
• High BUN
• Distal tubular Sodium Reabsorption
• (Renal) Venous congestion
Ter Maaten Nat Rev Cardiol 2015
Braking Phenomenon
Ellison et al Cardiology 2001
Dose Response
Felker Heart Fail Rev 2011
Pathophysiology
Ter Maaten Nat Rev Cardiol 2015
Diuretic Resistance and WRF
Increase in serum creatinine ≠ Diuretic Resistance
• Worsening Renal Function (WRF) occurs frequently in AHF
• WRF not always associated with poor outcome:
Pseudo WRF during adequate decongestion
Valente et al Eur Heart J 2014 (PROTECT)
Treatment
Most importantly: Identify patients experiencing poor diuretic
response early
If using only oral loop diuretics:
Dose appropriately (eGFR)
Consider changing loop diuretic:
Furosemide Bumetanide -> Torsemide
Add Thiazide
Add Mineralocorticoid receptor antagonist
Switch to intravenous loop diuretic
Treatment
Intravenous Loop Diuretics:
• Furosemide
be aware of albumin levels
consider switch to Bumetanide/Torsemide
• Dose properly: High dose in patients with low eGFR
I.V. Continuous/bolus
Lahav et al Chest 1992
I.V. Continuous/bolus
Felker et al NEJM 2011 (DOSE)
More WRF with high Dose
(despite similar outcome):
23% vs. 17%, P = 0.04
Treatment
Ter Maaten Nat Rev Cardiol 2015 / Verbrugge Cardiorenal Med 2014
Treatment
Thiazide Inhibits Na/Cl co-transporter distal tubules Increases fractional sodium excretion
Metolazone Inhibits Na/Cl co-transporter distal tubules
Increases diuresis, also in patients with low eGFR
Acetazolemide Carbon Anhydrase inhibitor proximal tubule
Inhibits proximal sodium reabsorptionIncreases diuresis, caution in low eGFR
Mannitol Inhibits water reabsorption Henle’s loop Increases free water excretion
MRA Competitive aldosterone antagonist distal tubules
In natriuretic doses, caution in low eGFR
Ter Maaten Nat Rev Cardiol 2015 / Verbrugge Cardiorenal Med 2014
Treatment
Ter Maaten Nat Rev Cardiol 2015
Consider Paracentesis
Mullens et al JACC 2008 and J Card Fail 2008
Hypertonic Saline
Ghandi IJC 2014
Mortality
HF Rehospitalisation
Ultrafiltration / Dopamine
Bart NEJM 2012 and Chen JAMA 2013
Not as universal therapy, may be considered in selected patients
Placebo Dopamine P-value
N 119 122
Urine volume (72h, mL) 8296 8524 0.59
Change in Cystatin C (mg/L) 0.11 0.12 0.72
Change in Creatinine (µmol/L) 1.8 0 0.78
WRF (%) 22 22 0.88
Sodium excretion (72h, mmol) 540 527 0.75
Weight change (72h, kg) -3.5 -3.3 0.82
CARRESS-HF ROSE-AHF
Diuretic Resistance and WRF
Damman and Testani Eur Heart J 2015
Diuretic Resistance
Diuretic Resistance / Poor Diuretic Response associated with
worse outcomes
• Early identification pivotal
Weight, fluid balance, signs/symptoms, electrolytes
• WRF ≠ Diuretic Resistance.
• Switch from oral to i.v.. Dose adequately (high in low eGFR)
• Combine diuretics: Acetolemide, Thiazides, MRA, Mannitol
• Some evidence on Hypertonic Saline
• In selected patients: Ultrafiltration, dopamine, inotropes
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