Challenging Cases in Acute Heart Failure

Diuretic Resistance

Kevin Damman, MD, PhDUniversity Medical Center Groningen

Groningen, The Netherlands

k.damman@umcg.nl

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

Thank you for your attention!k.damman@umcg.nl