Beth Davidson DNP, ACNP, CCRN Kristi Hayes MSN, FNP St. Thomas Hospital Nashville, TN

1. Ultrafiltration as a Therapy Option for Diuretic Resistance: Inpatient & Outpatient Case Studies Beth Davidson DNP, ACNP, CCRN Kristi Hayes MSN, FNP St. Thomas Hospital Nashville, TN

2. Objectives Review the epidemiology and pathophysiology of diuretic-resistant, acute heart failure Identify volume overload treatment options Review/discuss case studies of diuretic-resistance and use of ultrafiltration for volume removal

3. Heart failure is a major public health problem resulting in substantial morbidity and mortality Major cost-driver of HF is high incidence of hospitalizations JCAHO has initiated quality care indicators for hospitalized HF patients CMS reimbursement for readmission < 30 days = $ 0 Epidemiology of Heart Failure (HF)

4. Decompensated Heart Failure Insult Cardiac Dysfunction LV Remodeling Neurohormonal Activation  RAAS/SNS  Catecholamine  Endothelin Hemodynamic Decompensation  Preload  Afterload ↓ Cardiac Output FluidOverload Symptoms Morbidity Death Renal Vasoconstriction/ Fluid Retention

5. ACC/AHA Guidelines:Management of Fluid Status Patients should not be discharged from the hospital until a stable and effective diuretic regimen is established, and ideally, not until euvolemia is achieved Patients who are sent home before these goals are reached are at high risk of recurrence of fluid retention and early readmissionbecause unresolved edema may itself attenuate the response to diuretics

6. Diuretics • Diuretics… More diuretics... Still more diuretics… Current “Standard of Care”

7. Change in Weight During HospitalizationOutcomes with Standard Care Evidence of Incomplete Relief From Congestion Nearly 50% of ADHF patients discharged with weight gain or losing less than 5 lbs 27% 30 26% 25 20 Enrolled Discharges(%) 13% 15 16% 7% 6% 10 3% 2% 5 0 (<-20) (–20 to –15) (-15 to –10) (–10 to –5) (–5 to 0) (0 to 5) (5 to 10) (>10) Change in Weight (lbs)

8. Outcomes with Standard Care Hospital Readmissions Mortality 50% 50% 33% 37% 20% 12% 30 Days 3 Months 6 Months 30 Days 12 Months 5 Years Patients have persistently high event rates despite use of evidence-based therapies…

9. CARDIACFAILURE Left Ventricular Dysfunction Loop Diuretic Inhibition of Macula Densa Cardiac Remodeling and Fibrosis Increased Renin-Angiotensin Increased Aldosterone Effect of Loop Diuretics on RAAS in Cardiac Failure

10. Current Options May Have Undesirable Clinical Impacts • Favorable aspects of diuretic therapy • Increases urine output; reduces total body volume • Adverse aspects of diuretic therapy • Direct activation of renin-angiotensin-aldosteronesystem • Enhanced myocardial aldosteroneuptake • Loss of K, Mg, Ca, secondary myocyte Ca loading • Indirect reduction of cardiac output • Increased total systemic vascular resistance • Reduced natriuresisand GFR • Associated with increased morbidity and mortality

11. Diuretics and ADHF 14):39-42. • No consensus dosing guidelines • No common definition of diuretic resistant • No long-term studies of diuretic therapy for the treatment of heart failure • No outcomes data regarding morbidity and mortality

12. Diuretic Resistance Can be described as a clinical state in which the diuretic response is diminished or lost before the therapeutic goal of relief from edema has been reached Affects 20%–30% of patients with HF

13. Diuretic Resistance: Two Types • “Braking” phenomenon • A decrease in response to a diuretic after the first dose has been administered • Long-term tolerance • Tubular hypertrophy to compensate for salt loss

14. Diuretic Therapeutic Dilemma Diminished renal function and concurrent sodium and water retention in ADHF presents a therapeutic dilemma with regard to sub-maximal diuretic therapy Fluid removal by ultrafiltration may be recommended in this clinical setting

15. What is Aquapheresis? • Method to safely achieve euvolemia • Simplified form of ultrafiltration • Inpatient or outpatient settings • ICU, CCU, MICU, telemetry, step-down, observation, ED, outpatient clinics • Peripheral or central venous access • Flexible access sites and catheters • Diverse physician prescription • Highly automated operation • No clinically significant impact on electrolyte balance, blood pressure, or heart rateor heart rate*

16. Fluid Removal by Ultrafiltration • 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 illicits compensatory mechanisms, termed plasma or intravascular refill (PR), aimed at minimizing this reduction Interstitial Space (edema) Na P H2O Na K UF K PR P Vascular Space Na Vascular Space Na

17. The EUPHORIA Study • Single center, prospective study, 20 patients • Initial UF within 12 hours of hospitalization and before any significant administration of IV diuretics and/or vasoactive drugs • Results • Removed an average of 8.6 liters of fluid • 60% of patients were discharged in ≤ 3 days • Average hospitalization was 3.7 days

18. The EUPHORIA Study • Rehospitalization • In the three months preceding ultrafiltration: 10 hospitalizations in 9 patients • After ultrafiltration: 1 readmission for ADHF within 30 days

19. The UNLOAD Study • 200 patients (100 each arm) randomized, multi-center study comparing ultrafiltration versus standard care for acutely decompensated patients • Superior salt & water removal/weight loss • At 48 hours, ultrafiltration demonstrated • 38% greater weight loss • 28% greater net fluid loss • At 90 days, reduced readmissions • 50% reduction in re-hospitalization episodes • 63% reduction in total re-hospitalized days • 52% reduction in emergency department or clinic visits

20. ACC/AHA Guidelines: Class IIa, Level of Evidence B I IIa IIb III B Ultrafiltration is reasonable for patients with refractory congestion not responding to medical therapy Aquapheresis is now ranked HIGHER in the Level of Evidence than: - salt restriction - strict I/Os - higher doses of loop diuretics - addition of a second diuretic - continuous infusion of a loop diuretic - vasodilators – IV nitroglycerin, nesiritide - IV inotropes All of these are Level of Evidence: C

21. Case Study • 68 yo WM • Diastolic heart failure • Ischemic heart disease • CAB 4/06 • HTN • Afibrillation/flutter • Anemia • Hospitalized every 6 months for exacerbation

22. Case Study: Inpatient Therapy • Inpatient ultrafiltration – January 2010 • Access issues – extended length catheter (ELC) • Creatinine 1.5 2.9 after 48 hrs of treatment • Creatinine 1.6 at discharge • Therapy/ACEI discontinued • Diuresed with IV lasix continuous infusion • LOS = 5 days • Net volume loss = 7 kgs

23. Case Study: Outpatient Therapy • 1st treatment- 2/22/10 • ELC catheter • 1850 cc ultrafiltrate over 7 hrs • Wt loss = 2 lbs • Serum Cre = 1.8 pre and at termination of therapy • Hct 29 – sent home with hemoccult cards • Positive x 3- referred to PCP – no follow-up

24. Case Study: Outpatient Therapy • 2nd treatment – 3/26/10 • ELC catheter and 18 g peripheral IV • Access issues! • 2130 ultrafiltrate over 6.5 hrs • Also treated with Lasix 240mg IV due to loss of time waiting for access • Serum Cre = 1.7 pre and post termination of therapy • Hct 26 - referred to Hematology

25. Saint Thomas Hospital:Inpatient Outcomes 54 UF treatments from 5/1/08 – 6/1/10 Average treatment time = 37 hours, 28 minutes Average fluid removal = 6.15 liters/circuit Minimal adverse events 9 episodes of worsening renal insufficiency No significant electrolyte disturbances No significant hypotension 1 asymptomatic, small apical pneumothorax 6 minor bleeding episodes – epistaxis, line insertion site, generalized “oozing”

26. Saint Thomas Hospital:Inpatient Outcomes • Readmissions < 30 days • 1 re-admitted with LOC changes • 2 discharged to hospice • ultrafiltration for palliation • 1 patient, 5 re-admissions • now on dialysis for volume control • no readmits since dialysis except for recent hip fracture • 1 expired within 90 days of readmission • 1 patient, 2 re-admissions • suspect non-compliance – eating Whopper at discharge!

27. 1st outpatient treatment – January 19, 2010 13 treatments – 7 pts avg treatment time 5.79 hrs avg volume removal 1.49 L 1 repeated hospitalization now on peritoneal dialysis 1 deceased 1 ARF patient did not follow medication discharge instructions Effective in keeping pts out of hospital > 30 days Need more data Pt satisfaction and QOL are most important! Saint Thomas Hospital:Outpatient Outcomes

28. Advanced Heart Failure ClinicSaint Thomas Hospital

29. Another satisfied customer…

30. Challenges andOpportunities for Improvement • Early identification of patients that could benefit from outpatient therapy to decrease readmission within 30 days • Process improvement – timely, efficient IV access to allow faster initiation of therapy • Patient education – medications, line care, follow-up appointments, etc… • Anticoagulation – preserve integrity of circuit

31. Any questions?

32. Contact Information Beth Davidson DNP, ACNP bethdavidsondnp@comcast.net Kristi Hayes MSN, FNP khayes@stthomas.org