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How to assess and treat congestion in acute heart failure

Prof. Adriaan A. Voors, cardioloogUniversitair Medisch Centrum Groningen

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Disclosures• AAV received consultancy fees Novartis, and

Trevena.• AAV is supported by a grant from the European

Commission: FP7-242209-BIOSTAT-CHF• AAV is supported by research grants from the

Dutch Heart Foundation

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Congestion in Acute Heart Failure

• Congestion is the main reason for hospitalization for worsening HF1

• Most patients admitted to the hospital with ADHF do not achieve adequate relief of signs and symptoms of congestion2

• Patients with inadequate decongestion are known to be at higher risk of readmission for heart failure and mortality2

1. Gheorghiade et al. Eur J Heart Fail 2010; 12, 423–4332. Shakar et al. Curr Treat Options Cardio Med 2014;6:330

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More weight loss was associated with early dyspnea relief and reduced short-term mortality.

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How to assess congestion?

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Measurement of congestion• Bedside assessment

• Dyspnea (NYHA, Likert, VAS)• Orthopnea• Rales, Edema, JVP• Body weight

• Laboratory and Radiographic assessment• Natriuretic peptides, BUN, Hemoglobin• Chest X-ray

• Dynamic manoeuvres.• Orthostasis• Valsalva

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University Medical Center Groningen University of Groningen

Treatment of Congestion

ESC HF Guidelines 2012

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Treatment of Acute Heart Failure

ESC HF Guidelines 2012

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Total(n=5039)

<85 mmHg(n=90)

85-110mmHg(n-1169

>110 mmHg(n=3484)

I.v. Inotropes 11.9% 73.3% 22.3% 6.8%I.v. Nitrates 20.4% 10.0% 13.3% 23.0%I.v. Diuretics 81.5% 77.8% 82.9% 81.1%

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Goals of Treatment in AHF

McMurray et al. ESC-HF Guidelines; EJHF 2012

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Treatment of Acute Heart Failure

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PROTECT: design

Prospective, randomized, placebo-controlled study (Rolofylline vs. Placebo) with neutral results

2033 patients admitted with acute HF Daily assessments of diuretic dose and weight Diuretic response was defined as Δ weight kg/40

mg furosemide (or equivalent loop diuretic dose) up to Day 5

Massie et al. NEJM 2010

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Diuretic response and outcome in AHF

Diuretic response (kg/40mg furosemide) –1.7±1 –0.7±0.1 –0.4±0.1 –

0.2±0.1 0.1±0.3 P for trend*

N 349 349 351 347 349

WRF, day 7 21.9% 16% 18.2% 26.8% 25.1% 0.016Persistent WRF 11.7% 10.1% 10.3% 15.5% 17.6% 0.003Worsening heart failure 3.4% 4.9% 5.7% 14.1% 18.3% <0.001

Hemoconcentration on day 4 65.8% 66.4% 61.6% 55.7% 47.1% <0.001

180-day mortality 8.0% 12.6% 14.0% 21.9% 24.9% <0.001

60-day HF re-hospitalisation 7.4% 8.9% 15.7% 19% 23.2% <0.001

60-day death or renal or CV rehosp (%) 15.8% 19.2% 27.9% 35.2% 38.4% <0.001

Valente, et al. EHJ 2014

PROTECT: 2033 AHF patients; serial measurements

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ESC HF Guidelines 2012

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CARESS-HF• 188 patients hospitalized with acute

decompensated heart failure• Worsened Renal function (increase in serum

Creat >0.3 mg/dL) within 12 weeks before or 10 days after admission

• Signs of congestion• Serum creatinine > 3.0 g/dL excluded• 60 days follow-up• Primary endpoint: change in weight and change

in renal function

Bart et al. NEJM 2012

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CARESS-HF: primary endpoint

Bart et al. NEJM 2012

96 hours after randomization

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ESC HF Guidelines 2012

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ROSE-AHF methods• low-dose dopamine may increase urinary output and

preserve renal function in AHF patients

• Multicenter, double-blind, placebo-controlled clinical trial

• 360 hospitalized AHF patients and renal dysfunction (eGFR 15-60 mL/min/1.73m2)

• randomized < 24 hours of admission to low-dose dopamine (2 μg/kg/min)

• Co-primary end points • 72-hour cumulative urine volume (decongestion end point)

• Change in serum cystatin C from enrollment to 72 hours (renal function end point).

Chen et al. JAMA 2013

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ROSE-AHF: low dose dopamine in AHF

72 hour Urine volume

01,0002,0003,0004,0005,0006,0007,0008,0009,000

10,000

plac

ebo

Urin

ary

Out

put (

L)

P=0.59

dopa

min

edo

pam

ine

Change in Cystatin C

0

0.02

0.04

0.06

0.08

0.1

0.12

0.14

plac

ebo

dopa

min

edo

pam

ine

P=0.72

Mg/

dL

N=360 AHF patients with eGFR 15-60 ml/min

Chen et al. JAMA 2013

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Safety• No significant effect of dopamine on secondary

endpoints:• Decongestion• Renal function• Symptom relief

Safety Drug Tolerance Dopamine (n=122)

Placebo (n=119)

P-value

Study drug dose reduced of stopped because of hypotension

0.9% 10.4% <0.001

Study drug dose reduced or stopped because of tachycardia

7.2% 0.9% <0.001

Study drug discontinued due to any cause

23% 25% 0.72

Chen et al. JAMA 2013

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ESC HF Guidelines 2012

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How to overcome diuretic resistance?

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University Medical Center GroningenTer Maaten et al. Nat Rev Cardiol 2015

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Pre-discharge management

ESC HF Guidelines 2012

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Conclusions

• Congestion is the main reason for AHF• Loop diuretics: mainstay decongestion therapy• Inadequate decongestion = poor diuretic

response = poor prognosis• Strategies to improve diuretic response (e.g. add

thiazide, MRA) together with appropriate pre-discharge management may reduce the risk of re-hospitalization