Presentation is loading. Please wait.

Presentation is loading. Please wait.

1 Treating Decompensated and Stage D Heart Failure Ronald S. Freudenberger, M.D. Medical Director, Center for Advanced Heart Failure, Lehigh Valley Hospital.

Similar presentations


Presentation on theme: "1 Treating Decompensated and Stage D Heart Failure Ronald S. Freudenberger, M.D. Medical Director, Center for Advanced Heart Failure, Lehigh Valley Hospital."— Presentation transcript:

1 1 Treating Decompensated and Stage D Heart Failure Ronald S. Freudenberger, M.D. Medical Director, Center for Advanced Heart Failure, Lehigh Valley Hospital & Health Network and Lehigh Valley Heart Specialists Professor of Medicine Penn State College of Medicine

2 Decongestion  Drugs  Monitoring devices  Ultrafiltration Devices for decompensation or end stage Transplantation

3 Inadequate Diuresis During ADHF Treatment Note: For the chart, n represents the number of patients who have both baseline and discharge weight, and the percentage is calculated based on the total patients in the corresponding population. Patients without baseline or discharge weight are omitted from the histogram calculations. ADHERE ® Database All Enrolled Discharges in Over 12 Months (01.01.2003–12.31.2003) Who Were Discharged Home (including home with additional and/or outpatient care) The Nation n=26,757, 68% Change in Weight From Admission to Discharge 7% 6% 13% 24% 30% 15% 3% 2% 0 10 20 30 40 50 Enrolled Discharges (%) (<-20)(-20 to -15)(-15 to -10)(-10 to -5)(-5 to 0)(0 to 5)(5 to 10)(>10) Change in Weight (lb) 20 % discharged without Wt Loss or with Wt gain

4 −25 −20 −15 −10 −5−5−5−5 0 5 101505001000150020002500 Urine Output (mL) 0–8 hours GFR (% Change) Placebo IV furosemide Gottlieb SS, Brater DC, Thomas I, et al. Circulation. 2002;105:1348-1353. Change in GFR After IV Furosemide 80 mg in HF Class III CHF n=16 mean age 61 LVEF.28 CAD 63 % Furosemide Monotherapy Causes Significant Decline in GFR

5 A1 Adenosine Antagonists in CHF* *Renal Function and Renal Output in Edematous Heart Failure Patients Treated with Furosemide (80 mg IV) and/or BG9719. Gottlieb SS et al. Circulation. 2002;105:1348-1353. -25 -15 -5 5 15 05001000150020002500 Placebo BG9719BG9719 + Furosemide GFR (% change) (1-8 hours) Furosemide Alone Urine Output (mL) (0-8 hrs, Day 1 – Baseline)

6 Vasopressin Levels in CHF n = 75 n = 50 Goldsmith et al, JACC 1983 p<0.01

7 Arginine Vasopressin V 1a Blood vessels Myocardium V2V2 Renal tubules Tolvaptan 0 1 2 3 4 Median Plasma AVP (pg/mL) in SOLVD Trial 1 Control Prevention Treatment (1.4-2.3) (1.7-3.0) (2.3-4.4) Francis et al. Circulation 1990;82:1724-1729. Conivaptan

8 Effects of Tolvaptan and Furosemide on GFR, ERPF and RBF % Change vs Placebo * * * ** * p<0.05 vs Placebo; **p<0.001 vs Placebo Burnett et al, AHA 2003

9 Effect of Tolvaptan in HF With Hyponatremia (Serum Na + < 136 mEq/L) * * * ** * * p<0.01 low Gheorghiade M et al, Circulation 2003

10 Composite Components (Day 7 or Discharge) Change in Body Weight Trial ATrial B mm 0 5 10 15 20 P=ns Change in Global Clinical Status No significant difference in GCS improvement Additional weight loss 0.6 kg0.9 kg Trial A Trial B kg -5 -4 -3 -2 0 1 P<0.0001 n=997 n=1007 n=1031 n=1008 n=903n=910n=931n=900 TolvaptanPlacebo Gheorghiade M, et al. JAMA. 2007;297:1332-1343.

11 TLV PLC Peto-Peto Wilcoxon Test: P=0.68 TLV 30 mg PLACEBO Proportion Alive 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Months In Study 03691215182124 2072181214461112 859 589 404 239 97 2061178114401109 840 580 400 233 95 HR 0.98; 95%CI (.87-1.11) Meets criteria for non-inferiority Peto-Peto Wilcoxon Test: P=0.55 TLV PLC Proportion Without Event 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 03691215182124 207215621146 834 607 396 271 149 58 206115321137 819 597 385 255 143 55 HR 1.04; 95%CI (.95-1.14) TLV 30 mg PLACEBO Months In Study Konstam MA, et al. JAMA. 2007;297:1319-31. CV Mortality or HF Hospitalization All-Cause Mortality EVEREST: Primary End Points

12 Istaroxime New combined inotropic and lusiotropic agent New combined inotropic and lusiotropic agent Mechanism of action: inhibition of Na+/K+ ATPase (digoxin-like) and stimulation of SR Ca++ ATPase (increase SERCA 2a activity) Mechanism of action: inhibition of Na+/K+ ATPase (digoxin-like) and stimulation of SR Ca++ ATPase (increase SERCA 2a activity) Hemodynamic properties: lowers PCWP; increases CI; decreases HR and increases BP Hemodynamic properties: lowers PCWP; increases CI; decreases HR and increases BP Lowers LVED volumes and improves diastolic acceleration time Lowers LVED volumes and improves diastolic acceleration time Gheorghiade M et al. JACC 2008;51:2276-85

13 Hemodynamic effects of Istaroxime Gheorghiade M et al. JACC 2008;51:2276-85

14 Echocardiographic descriptions of Istaroxime Effects on LV parameters

15

16

17 Ultrafiltration and Renal Function Jaski et al reported no difference in mean creatinine before UF (1.6mg/dL +/- 0.6mg/dL) and 24 h after UF (1.7 mg/dL +/- 0.6 mg/dL) Jaski et al reported no difference in mean creatinine before UF (1.6mg/dL +/- 0.6mg/dL) and 24 h after UF (1.7 mg/dL +/- 0.6 mg/dL) Bart et al reported an average pre-UF creatinine of 1.6 mg/dL and 48 h post-UF creatinine of 1.9 mg/dL, which was not statistically significant Bart et al reported an average pre-UF creatinine of 1.6 mg/dL and 48 h post-UF creatinine of 1.9 mg/dL, which was not statistically significant Costanzo et al reported no change in creatinine pre- and post-UF in both the EUPHORIA and UNLOAD trials Costanzo et al reported no change in creatinine pre- and post-UF in both the EUPHORIA and UNLOAD trials Marenzi et al reported no change in creatinine when utilizing UF in volume-overloaded patients Marenzi et al reported no change in creatinine when utilizing UF in volume-overloaded patients

18 Costanzo MR, et al. J Amer Coll Cardiol. 2007;49:675-83. 6 5 4 3 2 1 0 Ultrafiltration ArmStandard Care Arm m =5.0, CI ± 0.68 kg (N = 83) m =3.1, CI ± 0.75 kg (N = 84) p = 0.001  Weight Loss (kg) A 6 5 4 3 2 1 Ultrafiltration Arm Dyspnea Score B Standard Care Arm m =6.4, CI ± 0.11 kg (N = 80) m = 6.1, CI ± 0.15 (N = 83) p = 0.35  7 UNLOAD Primary Efficacy Endpoints: Ultrafiltration

19 Costanzo MR, et al. J Amer Coll Cardiol. 2007;49:675-683. Ultrafiltration arm (16 events) 100 80 60 40 20 0 0 10 20 30 40 50 60 70 80 90 Days #of patients at risk Ultrafiltration arm 88 85 80 77 75 72 70 66 64 45 Standard care arm 86 83 77 74 66 63 59 58 52 41 Standard care arm (28 events) P = 0.037 Patients free from re-hospitalization (%) UNLOAD: Freedom from Re-hospitalization

20

21 RVDP ePAD RVSP PEI STI HR RV Pressure RV dP/dt Timing intervals V. Sense EGM

22

23

24

25

26 REducing Decompensation events Utilizing intraCardiac prEssures in patients with chronic HF CONFIDENTIAL- Medtronic, Inc.

27

28 HYPERVOLEMIC

29 Monitoring-CHAMPION Cardiomems Heart sensor Allows Measurement of Pressure to Improve Outcomes in NYHA Class III HF Patients

30 Cancion System for Aortic Flow Therapy

31 Aortic Flow Therapy Backflow against the aortic wall Forward flow in the center of the aorta Early Diastole With AFT

32

33 1) Technical (device group only)- insertion and attainment of flow 1 L/min for 24 hours 2) Hemodynamic -mean PCWP decrease from baseline of 5 mm Hg calculated as the average of values at 72 to 96 hours 3) Clinical any of the following: 10 consecutive days alive out of hospital, no alternative mechanical support, absence of death, and absence of readmission for HF. ( days 1 to 35 after randomization) Primary end point overall success composite

34 Copyright ©2008 American Heart Association Greenberg, B. et al. Circulation 2008;118:1241-1249 Percentage of patients with PCWP and clinical success 13.6% of the control group and 17.4% of the device group patients (P=0.45 )

35 Copyright ©2008 American Heart Association Greenberg, B. et al. Circulation 2008;118:1241-1249 PCWP and CI at baseline (prerandomization) and at sequential postrandomization time points (mean{+/-}SEM)

36

37 *Use as an alternative to transplant is currently under clinical investigation in the US. The HeartMate ® Left Ventricular Assist System (LVAS) Bridge to Transplant Bridge to Transplant Destination* Therapy for Non-Transplant Candidates Destination* Therapy for Non-Transplant Candidates

38 HeartMate ® XVE LVAD

39 REMATCH Inclusion Criteria Original Criteria (124/129 pts) Ineligible for cardiac transplantation Ineligible for cardiac transplantation NYHA Class IV > 90 days (70% on inotropes) NYHA Class IV > 90 days (70% on inotropes) Intensive medical therapy Intensive medical therapy LVEF < 25% LVEF < 25% VO 2 max <12 ml/kg/min VO 2 max <12 ml/kg/min

40 Cardiac Mortality

41 Improved Outcomes in 2-Year LVAD Survival

42 LVAD Survival Mechanical Circ Support Registry ISHLT 2005

43 CMS Decision One year following REMATCH CMS approved the use of the HeartMate LVAD as an alternative to heart transplant. One year following REMATCH CMS approved the use of the HeartMate LVAD as an alternative to heart transplant. Required the patient have been evaluated and rejected for transplant Required the patient have been evaluated and rejected for transplant Have Stage D HF for over 90 days Have Stage D HF for over 90 days Presumed survival of less than 50% at 1 year Presumed survival of less than 50% at 1 year Expected benefit from LVAD therapy Expected benefit from LVAD therapy

44 NUMBER OF HEART TRANSPLANTS REPORTED BY YEAR ISHLT 2007 NOTE: This figure includes only the heart transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as evidence that the number of hearts transplanted worldwide has declined in recent years. J Heart Lung Transplant 2007;26: 769-781

45 HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2005) ISHLT 2007 N at risk at 22 years: 33 HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2005) J Heart Lung Transplant 2007;26: 769-781

46 The Randomized Trial We think that everyone might benefit the most if the Most radical protagonists of evidence based medicine Organized and participated in a double blind, Randomized, placebo controlled, crossover trial of the parachute.

47 Optimal Medical Treatment Transplant Dead Class I CHF Class II CHF Class III CHF Class IV CHF Post-Transplant Well PT-CAD PT-Malignancy PT-Renal Failure PT-CAD+Malignancy PT-CAD+Renal Failure PT-Malignancy+Renal Failure PT-CAD+Malignancy+Renal Failure Medical Subtree Post-transplant Subtree Markov Node LVAD Markov Node Dead Dead post-LVAD Postop_Hemorrhage Postop_Thrombotic_CVA Postop_Hemorrhagic_CVA Post_LVAD_Well Post-LVAD subtree Modified from Freudenberger,RS Circulation. 2006 Jul 4

48

49


Download ppt "1 Treating Decompensated and Stage D Heart Failure Ronald S. Freudenberger, M.D. Medical Director, Center for Advanced Heart Failure, Lehigh Valley Hospital."

Similar presentations


Ads by Google