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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
The Unmet Need(s)
• How do you fix what you cannot measure?• Is treating the ‘fever’ enough?• Theory vs. Practice• Destination vs. Journey
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)
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.
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%)
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
• 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
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
Present & Future
• Destination matters more than the journey• Measurement• Tailored (at both the type of congestion and
the reason for congestion)
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!