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
- 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