Treatment of ADHF Cardiorenal syndrome Ultrafiltration versus IV diuretics

1. UF versus Diuretics in
management of ADHF

2. 1. Heart failure.
2. Cardiorenal syndrome.
3. Current practice and its limitations
4. UF : Could it help?
5. Plasma refill rate and its implications
6. Clinical trials.
7. Pros and Cons.
8. Questions and answers.
9. Questions with no answers.
10.Conclusion.

3.  Heart Failure (HF) is a major public health problem with
increasing prevalence owing to the substantial rise in
population aged over 65 years of age.
 Fluid overload and congestion are major characteristics of
HF and among the most important targets of treatment.
 Acute Cardiorenal syndrome (type 1) is worsening of renal
function in acute decompensated heart failure (ADHF).

4. IV Diuretics Diuretic resistance
Stepped Pharmacological approach
In case
Of renal
Impairment Ultrafiltration

6. Should we start treatment of CRS type 1 by UF ?

7. 1. Efficacy: In the ADHERE registry with over than 100000
patients enrolled, around half of the patients admitted
for ADHF were discharged with symptoms of congestion
after receiving conventional diuretic based therapy
2. Diuretic resistance: common in Heart failure (HF).
3. New onset AKI during hospital admission or worsening of
renal function.
4. Uncertainties about optimal dose, mode of
administration and stepped approach in resistant cases.
“Diuretic secretion is impaired in CKD”
5. Electrolyte abnormalities: (hypokalemia, etc.,,,)
6. Hypersensitivity and ototoxicity.

8. 1. Higher mass clearance of sodium for similar
volumes of fluid removal.
2. Rapid controlled fluid removal.
3. Decreased renal venous congestion.
4. Lack of neurohormonal activation.
5. No resistance to its action.
6. Low risk of electrolyte abnormalities.
7. Sustained clinical benefits.
8. Decreased hospital length of stay and
rehospitalization for HF.
9. Ability to restore diuretic sensitivity.

9.  15 hospitalizedADHF patients with presumed
diuretic resistance and clinical evidence of
volume overload.
 Urine electrolyte concentrations measured
after a dose of IVD.
 UF was then begun and ultrafiltrate
electrolyte concentrations were measured 8
hours later and compared to the initial urine
values.
Ali SS et al. Congest Heart Fail. 2009; 15: 1-4

10. 0
20
40
60
80
100
120
140
mg/dL URINE ELECTROLYTES AFTER INTRAVENOUS
DIURETICS OR ULTRAFILTRATION
IVD
UF
0
20
40
60
80
100
120
140
mg/dL URINE ELECTROLYTES AFTER INTRAVENOUS
DIURETICS OR ULTRAFILTRATION
IVD
UF
Sodium Potassium Magnesium
P= 0.000025
P= 0.000017
P= 0.017

12. Theoretical advantages should be proved in RCT
2 large RCTs
UNLOAD
CARRESS-HF

13. UF
Vascular
Space
Interstitial
Space (Edema)
Na
Na
Na
Na
K
P
H2O
K
P
PR
Ultrafiltration can remove fluid from the
blood at the same rate that fluid can be
naturally recruited from the tissue
The transient removal of blood elicits a
compensatory mechanism, called plasma
or intravascular refill (PR), aimed at
minimizing this reduction
The rate of plasma refill is important, for
if the ultrafiltration rate is too aggressive
intravascular volume may decrease
because the rate of refill from the
interstitial to the intravascular space is
exceeded.This in turn may lead to
hemodynamic instability and renal
dysfunction.

14. Marenzi GC et al. JACC 2001; 38:
963-968

15.  How to monitor PRR during UF?
 How to minimize extracorporeal blood
volume to minimize circulatory instability
during UF?

16. Ionometer

17.  Small sized portable devices.
 Adjustable blood flow rates
(10-40 ml/min).
 Small polysulphone filters
(0.12 m2).
 Small extracorporeal blood
volume of less than 50 ml.
 The ability to use peripheral
veins.
Aquadex FlexFlow
Gambro

18. Ultrafiltration versus IV Diuretics for Patients
Hospitalized for
Acute DecompensatedCongestive Heart Failure:
A Prospective RandomizedClinicalTrial
UNLOADTrial

19. randomized 200 patients with ADHF to
receive either UF therapy or standard
intravenous (IV) diuretic therapy. UF was
done at a rate up to 500 cc / hour, while
IV diuretics were given at least 2 times
the daily oral dose for the first 48 hours
as bolus or continuous infusion.

20. Weight and fluid loss were
greater in the UF group
without significant change in
blood pressure (BP) or serum
creatinine.
The ultrafiltration group
showed fewer patient
rehospitalizations for HF at
90 days.

21. 1. Patients with hemodynamic instability were
excluded, systolic BP of > 90 mmHg or requiring
IV vasopressors were excluded.This might be in
favor for the UF group as UF theoretically has
more hemodynamic instability.
2. Suboptimal use of diuretics at 48 hours made the
fluid loss greater in the UF group which had an UF
rate up to 500 cc / hour.
3. Higher serum creatinine in UF group although not
significant.

22. CARdiorenal REScue Study in Acute
Decompensated Heart Failure
(CARESS-HF)

23. randomized 188 patients with ADHF, worsened
renal functions and persistent congestion
despite standard therapy to receive stepped
pharmacological therapy or UF.

24. 1. UF didn’t show greater weight loss than stepped medical therapy
(5.7 kg for UF versus 5.5 kg for medical therapy; P=0.58).
2. Patients in UF group showed significant increase in serum
creatinine level (+0.23 mg/dl for UF group versus -0.04 mg/dl for
medical therapy group; P=0.003).
3. Higher rate of serious adverse events in UF group was also noted.
(72% vs 52%)
4. Significantly higher mortality in the ultrafiltration group at 60 day
observation (17% vs 13%)

26. 1. The addition of IV vasodilators or positive inotropic agents
was prohibited in the UF group unless indicated as a rescue
therapy, while it was allowed in the diuretic group
for patients in whom the target urine output (3-5 liters/day)
could not be attained.
2. Although the pharmacological approach was stepped up to
target urine output of 3-5 liters/day, UF was delivered in a
constant rate of 200 ml/hour. As discussed above the UF
rate should be adjusted according to the plasma refill rate,
but delivering a constant rate of UF to different patients
may contribute to the greater rise in serum creatinine in
this group.

27. 3. In the ultrafiltration group, most of the fluid removal was achieved with
ultrafiltration, which implied that less fluid was eliminated by the kidney
through glomerular filtration.
By contrast, in the pharmacologic-therapy group, the excess fluid was
eliminated exclusively through the kidney.
Since, according to the manufacturer, creatinine is not removed with the
Aquadex System 100 ultrafiltration procedure used in the study, it could
be anticipated that a smaller amount of creatinine was excreted through
glomerular filtration and tubular secretion.
Hence, besides being clinically irrelevant, the small increase in the serum
creatinine level in the ultrafiltration group, as compared with the
changes observed in the pharmacologic-therapy group, was nothing
other than the expected result given the choice of this primary end
point.

28. Heart Failure Hospitalizations after Aquapheresis
Therapy Compared to Intravenous (IV) Diuretic
Treatment
(AVOID-HF)

29.  Ongoing trial.
 to determine if patients have fewer Heart
Failure (HF) events after receiving
Aquapheresis (AQ) therapy compared to IV
diuretics up to 90 days of discharge from the
hospital.
 Heart Failure events are defined as returning
to the hospital, clinic or emergency
department (ED) for treatment of HF
symptoms.

30.  How to compare CARRESS-HF results to
UNLOAD results?
 How would we manage the patient then?
 What are the drawbacks of UF?

31. 1. Hypotension:The incidence of cardiovascular instability in UF &
the development of hypotension episodes is a frequent problem
during UF and can seriously affect long term outcome.
2. Effect on renal functions: Data are conflicting regarding the effect
of UF on renal functions. Studies have failed to show any
protective effects of UF.
3. Cost versus standard medical therapy is much higher. Studies to
impact that by proving the decrease incidence of rehospitalization.
4. No data regarding long term outcome.
5. Problems with vascular access, although peripheral veins may be
used.
6. Uncertainties regarding patient choice, UF rate and monitoring
efficacy.

32. 1. Which patient? Is UF better in CKD patients?
2. Rate and Duration of UF?
3. Monitoring?
4. When to stop?
5. Long term outcome? QOL ?

33. 1. Fluid overload and congestion are major
characteristics of HF and among the most
important targets of treatment.
2. Diuretics have many limitations including
resistance,WRF, electrolyte disturbance and
low effecacy.
3. UF could help, theoretically UF has many
advantages over diuretics in management of
ADHF.

34. 4. UNLOAD and CARRESS-HF have conflicting
results, New trials are needed to :
▪ Compare both strategies
▪ Compare long term outcome
5. Monitoring PRR during UF is still a point of
research, New technology may help in
stabilizing UFR with PRR.
6. UF advantage over diuretics is still unproven,
Current practice should be followed till new
evidence from RCTs show up.