Congestion in Acute Heart Failure: Does it Matter How It

Is Relieved?

Peter S. Pang MD MSc FACEP FAAEM FAHA FACC

Associate Professor | Emergency MedicineAssociate Director | Clinical Research

Affiliated Regenstrief Scientist

Disclosures• Consultant and/or honoraria from: Cardioxyl,

Janssen, Medtronic, Novartis, Relypsa, Roche Diagnostics, Trevena, scPharmaceuticals

• Will NOT discuss anything off-label

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 2013Harjola et.al. EJHF 2010Picano E et.al. Heart Failure Rev 2010Gheorghiade et.al. EJHF 2010Mebazaa et.al. Crit Care Med, 2008

Overview

1. Congestion is bad2. A ‘right’ way implies measurement

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

27%

Ready…… Fire…. Aim….

The Unmet Need(s)

• How do you fix what you cannot measure?• Is treating the ‘fever’ enough?• Theory vs. Practice• Destination vs. Journey

McMurray et.al. ESC Guidelines 2012

Diuretics

Vasodilator

NIV

Oxygen

Opiates

Inotrope

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

IV TherapiesADHERE, EHFS-II, EURObservational

Diuretic Nesir NTG Nipride Dobut Dopa Mil/Lev0

10

20

30

40

50

60

70

80

90

100ADHERE HfPEF ADHERE HfREF EHFS-II Eur

Yancy et.al. JACC 2006, Nieminen et.al. EHJ 2006, Maggioni et.al. EJHF 2010

Trick QuestionWhich of the following drugs given during hospitalization for acute heart failure definitively reduces mortality and/or re-hospitalization safely?

A. Loop diureticsB. NitroglycerinC. Dobutamine (or any other inotrope)

vs.

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 hours1) Change to oral2) continue current dose3) 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.

Global AssessmentBolus vs. Continuous

Felker et al. N Engl J Med 2011;364:797-805.

Global AssessmentHigh vs. Low Dose

Felker et al. N Engl J Med 2011;364:797-805.

Death, Re-hospitalization, or ED Visit

Felker et al. N Engl J Med 2011;364:797-805.

Secondary Endpoints

Felker et al. N Engl J Med 2011;364:797-805.

1.Dyspnea @ 72 hr2.Change in weight3.Net fluid loss4.Change in NT-proBNP (p=.06)

• 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.

Results

• 4 studies (n=634)• Two included ONLY post-MI• One excluded MI• One included both

NO Difference

• 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.

Nitrates in AHF

* *

*

Cotter G, et al. Lancet. 1998;35:389.

*P<.05

Patients with AHF (LVEF = 42%-43%)

Rotating Tourniquets?

Primary: Bivariate change in weight and creatinine at 96 hours. Followed for 60 daysN=188 patientsHad to have worsening renal function and persistent congestion1. No differences in weight loss2. Higher creatinine3. More serious adverse events

Bart et.al. NEJM 2013

• 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

It’s the Destination…NOT the journey

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

Metra et.al. Circulation: HF 2011

WRF/Cong

No WRF/Cong

No WRF/ No Cong

WRF/ No Cong

n=599

Congestion Sub-Types

Clinical• Hemodynamic• Total volume overload• Volume redistribution

Present & Future

• Destination matters more than the journey• Measurement• Tailored (at both the type of congestion and

the reason for congestion)

Thank You

Testani et.al. JACC, 2013

Late

Early

Adamson PB et.al. JACC 2003

ePA

D (m

m H

g)

Intra-cardiac pressures do increase prior to HFRE

Zile et al. Circulation 2008 118:1433-1441

Chronicle device (COMPASS-HF study)

Bod

y W

eigh

t (kg

)

In the absence of weight gain!