1. The document discusses different treatments for relieving congestion in acute heart failure, including diuretics, vasodilators, inotropes, and ultrafiltration. 2. A clinical trial found that higher versus lower doses of intravenous diuretics resulted in similar outcomes for patients with acute heart failure. 3. Nitrates have not been shown to definitively reduce mortality or rehospitalization when used to treat acute heart failure. 4. More aggressive decongestion as measured by hemoconcentration, albumin, and total protein levels was associated with improved outcomes, suggesting the importance of fully relieving congestion.

1. Congestion in Acute Heart
Failure: Does it Matter How It
Is Relieved?
Peter S. Pang MD MSc
FACEP FAAEM FAHA FACC
Associate Professor | Emergency Medicine
Associate Director | Clinical Research
Affiliated Regenstrief Scientist

2. Disclosures
• Consultant and/or honoraria from: Cardioxyl,
Janssen, Medtronic, Novartis, Relypsa, Roche
Diagnostics, Trevena, scPharmaceuticals
• Will NOT discuss anything off-label

3. Congestion
• Symptoms and signs of heart failure drive
admission and re-admission
• Alleviating congestion is a major goal of
therapy
• Failure to decongest adequately is associated
with worse outcomes
Kociol et.al. Circ Heart Failure 2013
Harjola et.al. EJHF 2010
Picano E et.al. Heart Failure Rev 2010
Gheorghiade et.al. EJHF 2010
Mebazaa et.al. Crit Care Med, 2008

4. Overview
1. Congestion is bad
2. A ‘right’ way implies measurement

5. “…there is no established algorithm for the
assessment of congestion.”

6. 27%

7. Ready…… Fire…. Aim….

8. The Unmet Need(s)
• How do you fix what you cannot measure?
• Is treating the ‘fever’ enough?
• Theory vs. Practice
• Destination vs. Journey

9. McMurray et.al. ESC Guidelines
2012
Diuretics
Vasodilator
NIV
Oxygen
Opiates
Inotrope

10. The National Institute for Health and
Care Excellence (NICE)
Clinical Guidelines
• Do not routinely offer opiates to people with acute heart failure
• Offer intravenous diuretic therapy to people with acute heart failure
• Do not routinely offer nitrates to people with acute heart failure
• If intravenous nitrates are used in specific circumstances, such as for people with
concomitant myocardial ischaemia, severe hypertension or regurgitant aortic or
mitral valve disease, monitor blood pressure closely in a setting where at least
level 2 care can be provided
• Do not offer sodium nitroprusside to people with acute heart failure
• Do not routinely offer inotropes or vasopressors to people with acute heart
failure
• Do not routinely offer ultrafiltration to people with acute heart failure
• Consider ultrafiltration for people with confirmed diuretic resistance
http://www.nice.org.uk/Guidance/CG187

11. IV Therapies
ADHERE, EHFS-II, EURObservational
Diuretic Nesir NTG Nipride Dobut Dopa Mil/Lev
0
10
20
30
40
50
60
70
80
90
100
ADHERE HfPEF ADHERE HfREF EHFS-II Eur
Yancy et.al. JACC 2006, Nieminen et.al. EHJ 2006, Maggioni et.al. EJHF 2010

12. Trick Question
Which of the following drugs given during
hospitalization for acute heart failure
definitively reduces mortality and/or re-
hospitalization safely?
A. Loop diuretics
B. Nitroglycerin
C. Dobutamine (or any other inotrope)

13. vs.

14. Acute Heart Failure (1 symptom AND 1 sign)
Home diuretics dose ≥ 80 mg and ≤240 mg furosemide
<24 hours after admission
2x2 factorial randomization
High Dose (2.5x oral)
Continuous infusion
48 hours
1) Change to oral
2) continue current dose
3) 50% increase in dose
Low Dose (1x oral)
Continuous infusion
High Dose (2.5x oral)
Q12 IV bolus
Low Dose (1 x
oral)
Q12 IV bolus
Felker et al. N Engl J Med 2011;364:797-805.

15. Global Assessment
Bolus vs. Continuous
Felker et al. N Engl J Med 2011;364:797-805.

16. Global Assessment
High vs. Low Dose
Felker et al. N Engl J Med 2011;364:797-805.

17. Death, Re-hospitalization,
or ED Visit
Felker et al. N Engl J Med 2011;364:797-805.

18. Secondary Endpoints
Felker et al. N Engl J Med 2011;364:797-805.
1.Dyspnea @ 72 hr
2.Change in weight
3.Net fluid loss
4.Change in NT-proBNP (p=.06)

20. • Objectives: To quantify the effect of different
nitrate preparations (isosorbide dinitrate and
nitroglycerin) and the effect of route of
administration of nitrates on clinical outcome,
and to evaluate the safety and tolerability of
nitrates in the management of AHF.
• Selection criteria: Randomised controlled
trials comparing nitrates with alternative
interventions in the management of AHF in
adults aged 18 and over.

21. Results
• 4 studies (n=634)
• Two included ONLY post-MI
• One excluded MI
• One included both
NO Difference

22. • IV ISDN 3 mg q 5 min (n = 52) vs.
IV furosemide (N = 52) 80 mg q 15 min
– Mean dose ISDN = 11.4 (± 6.8) mg
– Mean dose furosemide = 200 (± 65) mg
Cotter et al. Lancet 1998:351:389-3.

23. Nitrates in AHF
*
*
*
Cotter G, et al. Lancet. 1998;35:389.
*P<.05
Patients with AHF (LVEF = 42%-43%)

24. Rotating Tourniquets?

25. Primary: Bivariate change in weight and creatinine at 96 hours.
Followed for 60 days
N=188 patients
Had to have worsening renal function and persistent congestion
1. No differences in weight loss
2. Higher creatinine
3. More serious adverse events

26. Bart et.al. NEJM 2013

27. • No differences in the co-primary end points of urine
volume and change in cystatin C at 72 hours
• AHF patients, enrolled within 24 hours of
presentation, with eGFR between 15-60
• N=360

28. It’s the Destination…
NOT the journey

29. Suggesting that more aggressive decongestion, defined by
hemoconcentration, albumin, and total protein, was
associated with improved outcomes in patients with AHF
from the ESCAPE trial
Testani et.al. 2010

30. Metra et.al. Circulation: HF 2011

31. WRF/Cong
No WRF/Cong
No WRF/ No Cong
WRF/ No Cong
n=599

32. Congestion Sub-Types
Clinical
• Hemodynamic
• Total volume overload
• Volume redistribution

33. Present & Future
• Destination matters more than the journey
• Measurement
• Tailored (at both the type of congestion and
the reason for congestion)

34. Thank You

35. Testani et.al. JACC, 2013
Late
Early

36. Adamson PB et.al. JACC 2003

37. ePAD(mmHg)
Intra-cardiac pressures do
increase prior to HFRE
Zile et al. Circulation 2008 118:1433-1441
Chronicle device
(COMPASS-HF study)
BodyWeight(kg)
In the absence of weight gain!