Randall C. Starling, M.D., MPH, FACC,FESCProfessor Of Medicine

Vice Chairman, Cardiovascular MedicineSection of Heart Failure and Cardiac Transplant Medicine

Department of Cardiovascular MedicineKaufman Center for Heart Failure

Heart and Vascular InstituteCleveland Clinic

Cleveland Ohio USA

Acute Heart FailureRenal Replacement Therapy

RANDALL C STARLING NONE

DISCLOSURES

Outline

• Worsening renal failure in acute heart failure• Diuretic resistance• Strategies for decongestion• Guidelines recommendations: renal

replacement therapy• Clinical trials renal replacement• Summary

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?

Complex Interplay Worsening Renal Function does not EQUAL

adequate decongestion

Tang & Mullens, Heart 2010

1

2

3

“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 2007Damman K et al, Eur Heart J (2014) 35 (7): 455-469.

23% WRF

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

Abdominal Contribution to Cardio-Renal Dysfunction: right heart failure, TR

Verbrugge et al, JACC 2013; Fallick et al, CircHF 2011

Venous Congestion and Renal Function in ADHF:measured on presentation to hospital

Mullens et al, JACC 2008

Strategies

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.govGoodfriend TL Life Sci 63:1998.Clin J Am Soc Nephrol 4: 2013–2026, 2009

Failed Trials to Preserve Renal Function and Improve Diuresis

• Nesiritide ASCEND HF• Ultrafiltration CARRESS• Dopamine ROSE, DAD HF II• Rolofylline PROTECT• Serelaxin RELAX AHF

ACC AHA HF GUIDELINES

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 UFDYSPNEA NO BETTER

Freedom From Heart Failure Rehospitalization

Costanzo MR, et al. J Am Coll Cardiol 2007;49:675–83

Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS)RRESS STUDYChanges 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

59% in hosp RRT14% home RRT30% mortality

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

Systolic perfusion pressure (Systolic BP – CVP)

• May be modifiable to reduce morbidity of SCUF• At initiation of SCUF > 90 mm hg

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