evolving concepts in the treatment of the patient with chf and ckd

1. Evolving Concepts in the Treatment of the Patient with CHF and CKD Scope of the problem Stage 3-4 CKD ACE inhibitors Diuretics Ultrafiltration ESRD ACE inihibition b blockers Ultrafiltration Transplantation

2. Scope of the Problem 20 million (10.8%) with CKD – 8 million with stage 3 or 4 CKD 400,000 (0.1%) with ESRD Incidence of CHF 1/100 over age of 65 CKD increases all cause mortality in CHF Worsening renal function in CHF predicts hospital death and complications

3. Prevalence of CHF in Prevalent Patients Point Prevalent General Medicare (age 66 & older) & ESRD Patients

5. Impact of Worsening Renal Function (WRF) Among Patients Hospitalized with Heart Failure (JACC 43:61-67, 2004) 1,004 consecutive patients with CHF WRF ( Scr > 0.3 mg/dL) occurred in 27% Risk factors – history of CHF, DM, Scr > 1.5 mg/dL, SBP > 160 mmHg WRF increased risk of: Complications – ARR 2.1 Hospitalization > 10 days – ARR 3.2 Hospital death – ARR 7.5

6. Case 1 A 70 y/o man with a 20-year history of Type II diabetes, a 7-year history of coronary artery disease (E.F. 25%), and diabetic nephropathy (Baseline creatinine 2.8 mg/dl) was admitted because the serum creatinine increased to 4.5 mg/dl after institution of lisinopril at a dose of 5 mg/dl. Medication on admission consisted of Glyburide 10 mg qd, Imdur 60 mg/qd, aspirin 81 mg qd, lisinopril 5 mg qd, and Lasix 80 mg qd. Physical examination revealed BP 102/50 mmHg, pulse 81, bilateral rales, S3 gallop, ascites and 3+ bilateral lower extremity edema. Labs – Na/K = 133/5.1, Cl/HCO3 = 101/17 BUN 76, creatinine 4.6 Duplex ultrasound – Widely patent renal arteries

7. The ACE inhibitor is discontinued. Over the next 3 days, the creatinine decreases to 3.8 mg/dl, his weight increases 2 kg, and he develops increasing dyspnea. A cardiology consultant recommends reinstitution of the ACE inhibitor for afterload reduction. To ameliorate this patient’s signs and symptoms of fluid overload, you should: A) add hydralazine B) intensify the diuretic regimen C) resume the ACE inhibitor D) perform isolated hemofiltration

8. Case 2 A 22 y/o woman with ESRD due to sickle cell nephropathy and a dilated cardiomyopathy (E.F. 20%) is admitted with fluid overload (10 kg above dry weight). Her interdialytic weight gains average 4.6 kg. Physical examination reveals BP 123/71, pulse 96, weight 59 kg, bilateral pleural effusions, S3 gallop, ascites, and 2+ lower extremity edema. An echocardiogram shows global hypokinesis with an E. F. of 20% but no pericardial effusion.

9. The house staff requests a cardiology consult who recommends institution of an ACE inhibitor. You should: A) begin an ACE inhibitor B) hemofiltrate the patient to her dry weight over several days C) begin hydrazaline for afterload reduction D) never call a cardiologist for a case like this

10. ACEI and Angiotensin II Antagonism in CHF

11. Influence of Renal Function on the Hemodynamic and Clinical Responses to Long-term Captopril Therapy in Severe Chronic Heart Failure 101 patients NYHA IV Stratified according to serum creatinine (Scr): Group I – Scr <1.4 mg/dL Group II – Scr 1.4-2.8 mg/dL Group III – Scr > 2.8 Captopril 1 to 3 months Hemodynamic and clinical assessment baseline and after ACEI (Packer et al, Ann. Intern. Med. 104:147-154 1986)

13. Clinical Benefit of ACEI Improvement of at least 1 NYHA functional class Related to pretreatment renal function (p < 0.005): Group I – 29/40 (73%) Group II – 29/49 (59%) Group III – 2/12 (17%)

14. ACEI in Older Patients with Heart Failure and Renal Dysfunction Prospective cohort study 10 community hospitals 1,076 patients discharged with diagnosis of CHF Follow up for 6 months Abnormal renal function – Scr > 2.0 mg/dL (Philbin et al., J. Am. Geriatr. Soc. 47:302-08, 1999)

15. Baseline Characteristics

16. Severity Adjusted Clinical Outcomes

17. The Association Among Renal Insufficiency, Pharmacotherapy and Outcomes in Patients with CHF and Coronary Disease (Ezekowitz et al. JACC 44:1587-92, 2004) Prospective cohort study 6427 patients with CHF and CAD One-year follow-up 39% with creatinine clearance < 60 ml/min Outcome – one-year mortality

20. Renal Insufficiency and Heart Failure (McAlister et al. Circulation 109:1004-09, 2004) Prospective cohort study 754 patients 2.5-year median follow-up 56% with creatinine clearance < 60 ml/min Outcome – survival one year

21. Potential Adverse Effects of ACEI in Patients with CHF and CKD Hyperkalemia Hypotension may limit fluid removal with diuretics Acute on chronic renal failure Older age Diuretic use Decrease in MAP

28. Diuretic Therapy Diuretic therapy improves signs and symptoms of CHF Chronic diuretic therapy decreases afterload and increases C.O. Intravenous diuretics: Improve signs and symptoms of CHF Neurohormonal activation Increase risk of AKI (? cardiorenal syndrome)

29. Effect of Diuresis on Cardiac Function, Weight, and Fluid Volumes in 6 Patients with Congestive Heart Failure

31. High-dose Furosemide Versus Low-dose Dopamine in the Treatment of Refractory CHF (Cotter et al. Clin. Pharmacol. Ther. 62:187-93, 1997) Randomized prospective trial 20 patients with refractory CHF: Group A – Dopamine (4 mcg/kg/min) plus oral furosemide (80 mg/day) Group B – Dopamine plus continuous IV furosemide (5 mg/kg/day) Group C – Continuous IV furosemide (10 mg/kg/day) 72-hour follow-up

32. Results

35. Ultrafiltration Improved neurohormonal profile compared with IV diuretics Greater weight loss and fluid removal Significant decrease in 90-day morbidity

37. Ultrafiltration Versus IV Diuretics for Acute Decompensated CHF(Costanzo et al. JACC 49:675-83, 2007) Prospective randomized trial 200 patients with CHF and fluid overload: Ultrafiltration up to 500 ml/hr or IV diuretics – at least twice previous oral dose Excluded – ACS, creatinine > 3.0, SBP < 90, Hct > 45, pressors

38. Results

40. CHF in ESRD 40-50% of patients with ESRD have CHF-mostly diastolic Limited data with respect to efficacy of ACEI/ARB or b blocker therapy Ultrafiltration mainstay of therapy Renal transplantation improves LVEF

41. Prescription Patterns for Systolic Dysfunction Among Hemodialysis Patients(Roy et al. Am. J. Kid. Dis. 48:645-651, 2006) Prospective cohort study 420 patients – 11% with LVEF < 40% Questionnaire regarding use/nonuse of ACEI or b blockers

42. Results 47 patients with EF < 40%: b blocker – 72% ACEI – 36% Both – 26% Reasons for not prescribing – concern regarding: Adverse reactions – 88% Adequate control with UF – 38% Unproven benefit – 25% Unfavorable risk/benefit – 17%

43. ACEI/ARB Therapy in ESRD Limited data Efrati et al (Am. J. Kid. Dis. 40:1023, 2002) Retrospective study ACEI – 60 patients, no ACEI – 66 patients 52% decrease in cardiovascular mortality Takahashi et al. (NDT 21:2507, 2006) Randomized trial Candesartan 4-8 mg – 43 patients, control – 37 patients 19-month follow-up CVEs and CV death significantly higher in control group

44. Carvedilol Increases Survival in Dialysis Patients with Dilated Cardiomyopathy (JACC 41:1438, 2003) Prospective placebo – controlled trial 114 patients with: NYHA class II or III CHF LVEF < 35% ACEI – 97% Two-year follow-up Primary endpoints – change in LVEDV, LVESV, LVEF Secondary endpoints – all cause mortality, CVEs

47. Results

49. Improvement in “Uremic” Cardiomyopathy by Persistent Ultrafiltration(Toz et al. Hemodialysis Int. 11:46, 2007) Prospective study – 20-120 days 12 patients with C/T > 0.54 and LVEF < 45% Dialysis regimen: 3 times/week, 4-5 hours No antihypertensive agents Isolated UF or post HD UF Results – weight loss – 12 kg, C/T 0.59-0.47

51. Effect of Kidney Transplantation on LV Systolic Dysfunction and CHF in Patients with ESRD(Wali et al. JACC 45:1051, 2005) Observational cohort study 103 recipients with EF <40% - MUGA 6 and 12 months and last follow-up Results: LVEF 32 to 55% 70% achieved EF > 50% 15% remained with EF <40%

52. Summary In stage 3-4 CKD and Chronic CHF: ACEI of limited hemodynamic and clinical benefit Loop-blocking diuretics decrease afterload, improve LV function and are a cornerstone of therapy In stage 3-4 CKD with acute decompensated CHF: IV diuretics can have a negative hemodynamic and neurohumoral impact Ultrafiltration should be considered as an alternative In patients with ESRD: Few data regarding the utility of ACEI/ARBs/b blockers Persistent ultrafiltration or transplantation clearly beneficial