The 1st Kuwait-North American Update in Internal Medicine
Acute Decompensated Heart Failure in
Hospitalized Patients
Michael M. Givertz, M.D.
Medical Director, Heart Transplant/Mechanical Circulatory Support
Brigham and Women’s Hospital
Associate Professor of Medicine
Harvard Medical School
Boston, MA
Heart Failure is a Progressive Disease
The Course of Heart Failure
Goodlin et al., J Am Coll Cardiol 2009;54:386
Trends in ADHF Morbidity/Mortality
Mortality
09
20
08
20
07
20
06
20
05
20
04
20
03
20
02
20
01
20
00
20
99
35
30
25
20
15
10
5
0
19
Hosp Rate per 1000
1-Yr Mortality, %
HF Hosp
Year
Chen et al., JAMA 2011;306:1669
Markers of Advanced Disease and
Poor Prognosis
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Severe (objective) exercise intolerance
ACE inhibitor or β-blocker intolerance
High-dose diuretics
RV failure, 2 pulmonary hypertension
Hyponatremia, anemia, hyperuricemia
Chronic kidney disease (CKD)
Cardiac cachexia
Muscle Wasting in Heart Failure
Repeat Hospitalizations and Death
6-12 months
Setoguchi et al., Am Heart J 2007;154:260
ADHF: Who are They?
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Older (mean age 70s)
≈50% women
40-50% preserved EF
Over 85% with chronic HF
Multiple co-morbidities
– Hypertension
– Diabetes
– Chronic kidney disease
Shortness of Breath is the Main Reason
for HF Hospitalization
Congestion (Not Low Output) is the
Main Finding in Hospitalized Patients
Systolic blood pressure (%)1
> 140 mm Hg
50
90 – 140 mm Hg
48
< 90 mm Hg
2
Mean heart rate (bpm)2
PCWP (mm Hg)2
Cardiac index2
1Fonarow
≈90
25 – 30
Usually preserved
et al. Rev Cardiovasc Med 2003;4 Suppl 7:S21
2VMAC Investigators. JAMA 2002;287:1531
Congestion is Often Unrecognized and
Precedes Hospitalization
PASP
PADP
HR
Adamson et al., J Am Coll Cardiol 2003;41:565
Yu et al., Circulation 2005;112:841
CardioMEMS:
Pressure Measurement System
Dear Michael M. Givertz, MD
A new reading has come in for your patient, 31-003 C-Z which violated the
alert threshold set up for "Mean Pressure above 20.0 mmHg". The reading
was taken on 25 Jan 04:06 EST.
Systolic: 89
Diastolic: 51
Mean: 66
Heart Rate: 91
Pressure waveform is attached.
Thank you,
CardioMEMS Alert System
CHAMPION Study: HF Hospitalizations
260
HF Hospitalizations, no.
240
Treatment
Control
220
p < 0.001, based on Negative
Binomial Regression
200
180
160
140
120
100
80
60
40
6 Months
15 Months
20
At Risk
0
Treatment
0 270
Control
280
90 262
267
180 244
252
270 209
215
360 168
179
450 130
138
540 107
105
630 81
67
720 28
25
810 5
10
900 1
0
ACC/AHA Guidelines for ADHF
Guidelines
N=25
Class I
N=18
Class II
N=5
Evidence A
N=1
IIa
N=4
Class III
N=2
IIb
N=1
Evidence B
N=2
Consensus opinion 72%, “Evidence” 28%
Evidence B
N=3
Evidence B
N=1
Evidence C
N=14
Evidence C
N=3
Evidence C
N=1
Class I, Level of Evidence A
•
Concentrations of BNP1 or NT-proBNP2
should be measured in patients being evaluated
for dyspnea in which the contribution of HF is
not known.
diagnosis
requires
Unfortunately,
theFinal
routine
use of serial
natriuretic
interpreting
these results
in thehemodynamics
context of all has
peptide
measurements
to monitor
available
clinical
andinought
not to the
be
not been
shown
to be data
helpful
improving
considered
stand alone patient
test. with HF
outcomes
of theahospitalized
(ACC/AHA)
1Maisel
et al., N Engl J Med 2002;347:161 (BNP Study)
2Januzzi et al., Am J Cardiol 2005;95:948 (PRIDE Study)
Diuretics for ADHF and Fluid Overload
• Treatment with IV loop diuretics should begin
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in the ED without delay, as early intervention
may be associated with better outcomes (Level
of evidence B).
If patients are already receiving loop diuretics,
initial IV dose should equal or exceed chronic
oral dose (Level of evidence C).
When a patient with congestion fails to
respond to IV diuretics, consider increased
dose of loop diuretic, addition of second
diuretic, continuous infusion of loop diuretic
(Level of evidence C)
DOSE Study
Felker et al., N Engl J Med 2011;364:797
DOSE Study
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308 patients with ADHF
Randomized 2x2 to low vs. high-dose
furosemide and IV bolus vs. continuous
infusion
No differences at 72 hours in:
– Global symptom assessment (1° efficacy endpoint)
– Change in renal function (1° safety endpoint)
Felker et al., N Engl J Med 2011;364:797
Death, Rehospitalization, or ED Visit
Felker et al., N Engl J Med 2011;364:797
Secondary Endpoints: Low vs. High
Dose Strategy
Low
High
P value
Dyspnea VAS AUC at 72 hours
4478
4668
0.041
% free from congestion at 72 hrs
11%
18%
0.091
Change in weight at 72 hrs
-6.1 lbs
-8.7 lbs
0.011
Net volume loss at 72 hrs
3575 mL
4899 mL
0.001
Change in NTproBNP at 72 hrs (pg/mL)
-1194
-1882
0.06
% Treatment failure
37%
40%
0.56
% with Cr increase > 0.3 mg/dL
within 72 hrs
14%
23%
0.041
6
5
0.55
Length of stay, days (median)
Cardiorenal Syndrome: Worsening Renal
Function During Treatment of ADHF
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Increase in creatinine ≥ 0.3 mg/dl
Occurs in 15-30% of admissions
Risk factors:
– Older age
– HTN, DM
– Baseline renal dysfunction
•
May be associated with adverse outcomes during
the hospitalization and post-discharge
Gottlieb et al., J Card Fail 2002;8:136
Forman et al., J Am Coll Cardiol 2004;43:61
Transient vs. Persistent Worsening
Renal Function
N = 467 with ADHF, WRF in 115 (24%)
+1.17
+0.60
Aronson et al., J Card Fail 2010;16:541
Ultrafiltration:
An Attractive Alternative to Diuretics
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More effective way to restore sodium balance1
– removal of isotonic vs. hypotonic saline
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No effect on serum electrolytes
Rapid and predictable fluid removal
Does not stimulate neurohormones
May restore diuretic responsiveness and
improve long-term outcomes2
1Jessup
and Costanzo, J Am Coll Cardiol 2009;53:597
2Agostoni et al., J Am Coll Cardiol 1993;21:424
Minimally Invasive Ultrafiltration
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FDA approved, portable device
Non-ICU, routine nursing
PICC or central line
UNLOAD (sponsor-initiated)
– Greater weight loss at 48 hours
compared to IV diuretics (5 vs.
3.1 kg; p < 0.001)
– Decreased HF hospitalization at
90 days
Costanzo et al., J Am Coll Cardiol 2007;49:675
CARRESS Study
N = 188 with ADHF, Cre ↑ ≥ 0.3, persistent congestion
Randomized to UF vs. stepped pharmacologic care
Bart et al., N Engl J Med 2012;367:2296
CARRESS Study: Primary Endpoint
Cre ↑ 0.23
Cre ↓ 0.04
Bart et al., N Engl J Med 2012;367:2296
CARRESS: Adverse Events
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More patients in UF group (72%) had SAEs
compared to stepped pharmacologic care (57%)
– Renal failure
– Bleeding
– IV catheter-related
•
No difference in 60-day mortality or rate of
death or HF rehospitalization
Bart et al., N Engl J Med 2012;367:2296
Options for Diuretic Resistant Patients
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Vasodilators
– IV Nitroprusside, nitroglycerin
– Hydralazine/nitrates
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Positive inotropes
– Dobutamine
– Milrinone
– Dopamine (renal-dose vs. higher doses)
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Mechanical circulatory support
Dobutamine: Interpatient Variability
Colucci et al., Circulation 1986;73:III175
Tolerance to (Not All) Inotropes
N = 20, severe chronic HF, CI 1.63 L/min/m2
Mager et al., Am Heart J 1991;121:1974
Is There Really a Role for Low-Dose
Dopamine?
N = 380 with ADHF and estimated GFR 15-60 ml/min
Randomized to dopamine 2 mcg/kg/min vs. placebo
Chen et al., JAMA 2013:310:2533
Low Dose Dopamine:
Co-primary
End-points
ROSE
Study
72 Hour Urine
Volume
Change in
Cystatin-C
No effect on symptoms, 60-day readmission or 180-day mortality
More tachycardia
Chen et al., JAMA 2013:310:2533
Worst Prognosis with Inotrope
Dependence
Community-based
Clinical trial
Hershberger, J Card Fail 2003;9:180
Rogers, J Am Coll Cardiol 2007;50:741
ADHF is a Good Time to Address
Risks and Co-Morbidities
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Arrhythmias or conduction disease
– consider ICD for primary prevention
– AF: consider amiodarone/CV, ablation
– LBBB: consider CRT*
Risk of thromboembolism: need for
anticoagulation or anti-platelet therapy
Anemia, diabetes, obesity, sleep apnea
Advanced directives
*should NOT be used as a “bail-out”
Dying with HF is Rarely Unexpected
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N = 160
Mean age 60, 74% male
Mean duration of HF: 5 years
40% died in hospital, 10% with hospice
Within 6 months of death:
– 93% NYHA class III or IV
– 74% hospitalized at least once
– mean Na 128, Cre 3.1, Hct 30
Teuteberg et al, J Card Fail 2006;12:47
Comprehensive Discharge Instructions
Six key aspects of care
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Diet
Medications (adherence and uptitration)
Activity level
Follow-up appointments
Daily weights
What to do if HF worsens?
Thank you for your attention