Acute Heart Failure Renal Replacement Therapy

1. Randall C. Starling, M.D., MPH, FACC,FESC
Professor Of Medicine
Vice Chairman, Cardiovascular Medicine
Section of Heart Failure and Cardiac Transplant Medicine
Department of Cardiovascular Medicine
Kaufman Center for Heart Failure
Heart and Vascular Institute
Cleveland Clinic
Cleveland Ohio USA
Acute Heart Failure
Renal Replacement Therapy

2. RANDALL C STARLING
NONE
DISCLOSURES

3. Outline
• Worsening renal failure in acute heart failure
• Diuretic resistance
• Strategies for decongestion
• Guidelines recommendations: renal
replacement therapy
• Clinical trials renal replacement
• Summary

5. What is Euvolemia???
• Difficult to determine clinically
• Does not equate with weight loss
– Redistribution of fluid in the body
• Does not equate with hemodynamics
– Not related to cardiac output directly
• Does not equate with biomarkers
• “over diuresis” may precipitate worsening
renal function?

6. Complex Interplay
Worsening Renal Function does not EQUAL
adequate decongestion
Tang & Mullens, Heart 2010
1
2
3

7. “Worsening Renal Function”
• Serum creatinine  0.3 mg/dL:
• In-hospital mortality:
- Sensitivity of 65%
- Specificity of 81%
• 2.3 days  length of stay
• 67%  risk of death within 6
months after discharge
• 33%  risk for readmission
• Risk factors:
- Co-morbidities (diabetes)
- Age
- CKD (admit Cr >2.5 mg/dL)
- Nephrotoxic drugs
Krumholz et al, Am J Cardiol 2000; Smith et al, J Card Fail 2003;
Gottlieb et al, J Card Fail 2002; Metra et al, Eur J Heart Fail 2007
Damman K et al, Eur Heart J (2014) 35 (7): 455-469.
23% WRF

8. Diuretic Resistance….mechanisms?
• Decreased GFR
• Increased activation of RAAS
• Hypertrophy of distal tubule epithelial cells
• Decreased intestinal absorption of drug
• Altered pharmokinetics;
– impaired concentration of drug in renal tubule

9. Abdominal Contribution to Cardio-Renal Dysfunction:
right heart failure, TR
Verbrugge et al, JACC 2013; Fallick et al, CircHF 2011

10. Venous Congestion and Renal Function in ADHF:
measured on presentation to hospital
Mullens et al, JACC 2008

11. Strategies

12. Strategies to Address Diuretic
Resistance
• Change loop diuretics
• Torsemide inhibits aldosterone secretion of adrenal
cells
• Add a second agent to block distal tubule;
chlorothiazide, metolazone
• MRA: use natriuretic dose (> 25 mg spironolactone).
Peak effect 48 hours; use with loop diuretic*
• Paracentesis?
*ATHENA HF Network www.clinicaltrials.gov
Goodfriend TL Life Sci 63:1998.
Clin J Am Soc Nephrol 4: 2013–2026, 2009

13. Failed Trials to Preserve Renal
Function and Improve Diuresis
• Nesiritide ASCEND HF
• Ultrafiltration CARRESS
• Dopamine ROSE, DAD HF II
• Rolofylline PROTECT
• Serelaxin RELAX AHF

15. ACC AHA HF GUIDELINES

18. Ultrafiltration vs. IV Diuretics for
Patients Hospitalized for ADHF
Costanzo MR, et al.
J Am Coll Cardiol 2007;49:675–83
Two hundred patients (63± 15 years, 69%
men, 71% LVEF ≤40%) hospitalized for HF with
2 signs of hypervolemia were randomized to
ultrafiltration or intravenous diuretics.
Primary end points were weight loss and
dyspnea assessment at 48 h after
randomization.
WEIGHT LOSS FAVORS UF
DYSPNEA NO BETTER

19. Freedom From Heart
Failure Rehospitalization
Costanzo MR, et al. J Am Coll Cardiol 2007;49:675–83

20. Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS)RRESS
STUDY
Changes in Serum Creatinine and Weight at 96 Hours
Bart BA et al. N Engl J Med 2012;367:2296-2304
Primary Endpoint NOT met:
UF potential HARM
Bart BA et al. N Engl J Med 2012;367:2296-2304
serious adverse event
72% vs 57%; P = .03

21. 59% in hosp RRT
14% home RRT
30% mortality

22. LONG TERM OUTCOMES
• Three month mortality
was 81% vs 15% (P
<.001) in patients who
were moved to dialysis
versus those who were
not
• 12-month mortality was
95% vs 35%, respectively
(P < .001).
OBSERVATIONS
• More weight loss in non
dialysis group
• UF correlated with systolic
BP and systolic perfusion
pressure
• At SCUF initiation cr 2.5 vs
1.6 UF group
• Systolic perfusion pressure
and systolic BP > at baseline
in non dialysis groups

23. Systolic perfusion pressure
(Systolic BP – CVP)
• May be modifiable to reduce morbidity of SCUF
• At initiation of SCUF > 90 mm hg

24. Summary
• Current approach with diuretics associated with WRF,
neurohormonal activation, increased mortality and
readmission rate
• Lack of response to diuretics independently predicts adverse
outcomes
• Diuretic resistance is multifactorial, related to intrinsic renal
substrate, physiology, age and comorbidities
• Renal replacement therapy has not been shown to be safe or
effective in patients that are diuretic resistant
• The need for renal replacement therapy is associated with
high mortality
• Renal replacement therapy is palliative