1. Acute Decompensated Heart Failure - Medical Management or Device?
Timothy M. Hoffman, MD, FACC, FAHA Medical Director, Heart Transplant and Heart Failure Program Associate Medical Director, Division of Cardiology Professor of Pediatrics

2. Presenter Disclosure Information
Session: Heart Failure/Transplant
Presenter: Timothy M. Hoffman, MD
Title: Acute Decompensated Heart Failure - Medical Management or Device?
Financial Disclosure:
There are no relationships that exist related to this presentation

3. How Do We Answer the Question?
Describe Acute Decompensated Heart Failure in Pediatrics
Review Care Algorithms and Collective Experiences
Review Adult and Pediatric Guidelines

4. Adapted from Gheorghiade M, et al. Circulation 2005;112:3958-3968
What Don’t We Know
What are the pathophysiological differences (if any) between acute and chronic HF?
What is the difference (if any) between acute decompensated HF versus acute on chronic HF?
Adapted from Gheorghiade M, et al. Circulation 2005;112:

5. Adapted from Gheorghiade M, et al. Circulation 2005;112:3958-3968
What Don’t We Know
What is the contribution of different organs or systems to the pathophysiology of acute HF?
Kidney
Liver
Peripheral vasculature
What is unique to the pediatric patient population?
Adapted from Gheorghiade M, et al. Circulation 2005;112:

6. Kantor PF, et al. Can J Cardiol 2013;29:1535-1552

7. Acute Changes & Incomplete Compensation
Mancini D, et al. Circulation 2005;112:

8. Goal of Medical or Device Therapy
Mancini D, et al. Circulation 2005;112:

9. Adult and Pediatric Guidelines

10. Yancy CW, et al. Circulation 2013;28:e240-e327

11. Treatment of Stages A to D
Adult Guidelines
Inotropic Support

12. Inotropic Support I
IIa
IIb
III
Until definitive therapy (e.g., coronary revascularization, MCS, heart transplantation) or resolution of the acute precipitating problem, patients with cardiogenic shock should receive temporary intravenous inotropic support to maintain systemic perfusion and preserve end-organ performance. Continuous intravenous inotropic support is reasonable as “bridge therapy” in patients with stage D refractory to GDMT and device therapy who are eligible for and awaiting MCS or cardiac transplantation. I
IIa
IIb
III B

13. Inotropic Support (cont.)
IIa
IIb
III B
Short-term, continuous intravenous inotropic support may be reasonable in those hospitalized patients presenting with documented severe systolic dysfunction who present with low blood pressure and significantly depressed cardiac output to maintain systemic perfusion and preserve end-organ performance. Long-term, continuous intravenous inotropic support may be considered as palliative therapy for symptom control in select patients with stage D despite optimal GDMT and device therapy who are not eligible for either MCS or cardiac transplantation. I
IIa
IIb
III B

14. Inotropic Support (cont.)
IIa
IIb
III B
Long-term use of either continuous or intermittent, intravenous parenteral positive inotropic agents, in the absence of specific indications or for reasons other than palliative care, is potentially harmful in the patient with HF. Use of parenteral inotropic agents in hospitalized patients without documented severe systolic dysfunction, low blood pressure, or impaired perfusion, and evidence of significantly depressed cardiac output, with or without congestion, is potentially harmful.
Harm I
IIa
IIb
III B
Harm

15. Elkayam U, et al. Am Heart J 2007;153:98-104
All Cause Mortality
Kaplan-Meier survival curve for all-cause mortality by intravenous vasoactive medication use.
Elkayam U, et al. Am Heart J 2007;153:98-104

16. Treatment of Stages A to D Mechanical Circulatory Support
Adult Guidelines
Mechanical Circulatory Support

17. Mechanical Circulatory Support
IIa
IIb
III B
MCS use is beneficial in carefully selected* patients with stage D HFrEF in whom definitive management (e.g., cardiac transplantation) or cardiac recovery is anticipated or planned. Nondurable MCS, including the use of percutaneous and extracorporeal ventricular assist devices (VADs), is reasonable as a “bridge to recovery” or a “bridge to decision” for carefully selected* patients with HFrEF with acute, profound hemodynamic compromise. Durable MCS is reasonable to prolong survival for carefully selected* patients with stage D HFrEF. I
IIa
IIb
III B I
IIa
IIb
III B

18. McMurray J, et al. Eur J Heart Fail 2012;14:803-869

19. Pediatric Guidelines

20. ISHLT Practice Guidelines
Inotropic Support
All recommendations LOE C
Class I:
Inotropic support can be used in AHF presenting as cardiogenic shock (poor perfusion)
Class IIa:
Inotropic support may be temporarily used in AHF with hypotension and low cardiac output
Kirk R, Dipchand AI, Rosenthal D, et al. ISHLT Monograph Series 2014

21. ISHLT Practice Guidelines
Class IIa:
Inotropic support choice depends on clinical presentation. Milrinone and/or dobutamine can be used as first-line rescue therapy with epinephrine playing a role in refractory hypotension
Class IIb:
Levosimendan may be considered in AHF unresponsive to traditional inotropic support
Kirk R, Dipchand AI, Rosenthal D, et al. ISHLT Monograph Series 2014

22. ISHLT Practice Guidelines
Mechanical Circulatory Support
All recommendations LOE C
Class IIa:
For a child in cardiac arrest/cardiogenic shock with pulmonary compromise, ECMO should be considered
For a child with AHF that is believed to be reversible, either ECMO or a temporary VAD may be considered as a temporizing measure.
Kirk R, Dipchand AI, Rosenthal D, et al. ISHLT Monograph Series 2014

23. ISHLT Practice Guidelines
Class IIa:
For a child with cardiogenic shock that is not believed to be due to a reversible underlying cause, consideration should be given to use of a temporary VAD or ECMO for resuscitation of end organ function rather than directly implanting a chronic VAD system
Kirk R, Dipchand AI, Rosenthal D, et al. ISHLT Monograph Series 2014

24. Kantor PF, et al. Can J Cardiol 2013;29:1535-1552

25. Kantor PF, et al. Can J Cardiol 2013;29:1535-1552

26. Kantor PF, et al. Can J Cardiol 2013;29:1535-1552

27. Kantor PF, et al. Can J Cardiol 2013;29:1535-1552
∙ Circulatory support
Kantor PF, et al. Can J Cardiol 2013;29:

28. Care Algorithms and Collective Experiences

29. Can We Predict the Outcome?
ADHERE Trial Analysis
Yancy CW, et al. J Am Coll Cardiol 2006;47:76-84

30. Seattle Heart Failure Score
Figure 6. The Seattle Heart Failure Model has been implemented as an interactive program that employs the Seattle Heart Failure Score to estimate mean, 1-, 2-, and 5-year survival and the benefit of adding medications and/or devices for an individual patient. This model is available at ACE-I indicates ACE inhibitor; ARB, angiotensin receptor blocker; HCTZ, hydrochlorothiazide; Hgb, hemoglobin; and BiV, biventricular.
Levy W C et al. Circulation. 2006;113:
Copyright © American Heart Association, Inc. All rights reserved.

31. Seattle Heart Failure Score
Figure 2. The final variables and their contribution to the predictive power of the model in PRAISE1 are shown. Lymph indicates lymphocytes; Hgb, hemoglobin.
Levy W C et al. Circulation. 2006;113:
Copyright © American Heart Association, Inc. All rights reserved.

32. Predicted Effects on Survival
Figure 5. The predicted effects on survival of sequentially adding medications and an ICD for a heart failure patient with an annual mortality of 20% and a mean survival of 4.1 years at baseline. Adding an ACE inhibitor (ACEI), a β-blocker, an aldosterone (Aldo) blocker, and an ICD decreases the annual mortality by 70% (20% to 6%) and increases the mean survival by 5.6 years (mean survival 4.1, 5.0, 6.6, 8.2, and 9.7 years, respectively).
Levy W C et al. Circulation. 2006;113:
Copyright © American Heart Association, Inc. All rights reserved.

33. REMATCH Trial: Subset Analysis
Figure 1. Four Kaplan-Meier survival curves stratified by randomization to LVAD and OMM and by intravenous inotropic infusions at the time of randomization. For the 91 patients on intravenous inotropic (INO) therapy at randomization, major survival benefit was seen with LVAD compared with OMM (bottom line), with 49% versus 24% survival at 1 year and 28% versus 11% at 2 years (P=0.0014, log rank). For the 38 patients not on baseline inotropic infusions (NO INO), survival at 2 years was 22% with LVAD and 16% with OMM (P=0.55).
Stevenson L W et al. Circulation. 2004;110:
Copyright © American Heart Association, Inc. All rights reserved.

34. Improvement in Minnesota Living with Heart Failure Score
Figure 3. Bar graphs demonstrating improvement in Minnesota Living With Heart Failure questionnaire scores for survivors from time of randomization to 12 months. Scale is from 0 to 105, with higher scores representing more severe limitation. Ino indicates intravenous inotropic therapy.
Stevenson L W et al. Circulation. 2004;110:
Copyright © American Heart Association, Inc. All rights reserved.

35. LVAD survival benefit
Stevenson L W et al. Circulation. 2004;110:

36. % of Patients with VAD as BTT
Figure 1. Percentage of patients with VAD implantation as a bridge to heart transplantation.
Blume E D et al. Circulation. 2006;113:
Copyright © American Heart Association, Inc. All rights reserved.

37. How Many Recovered?
Figure 1. Percentage of patients with VAD implantation as a bridge to heart transplantation.
Blume E D et al. Circulation. 2006;113:
Copyright © American Heart Association, Inc. All rights reserved.

38. Device Types
Device diagrams. Reprinted with permission from Thoratec and from CardiacAssist.
Peura J L et al. Circulation. 2012;126:
Copyright © American Heart Association, Inc. All rights reserved.

39. Device Selection Flow Chart
Device selection flow chart. OHTx indicates orthotopic heart transplantation; IABP, intra-aortic balloon pump; ECMO, extracorporeal membrane oxygenation; pVAD, Paracorporeal Ventricular Assist Device; BTT, bridge to transplantation; DT, destination therapy; and BTD, bridge to decision.
Peura J L et al. Circulation. 2012;126:
Copyright © American Heart Association, Inc. All rights reserved.

40. Optimal Timing for MCS
Optimal Timing for mechanical circulatory support. NYHA indicates New York Heart Association; IM, INTERMACS level.
Peura J L et al. Circulation. 2012;126:
Copyright © American Heart Association, Inc. All rights reserved.

41. Optimal Timing for MCS
Optimal Timing for mechanical circulatory support. NYHA indicates New York Heart Association; IM, INTERMACS level.
Peura J L et al. Circulation. 2012;126:
Copyright © American Heart Association, Inc. All rights reserved.

42. Optimal Timing for MCS
Optimal Timing for mechanical circulatory support. NYHA indicates New York Heart Association; IM, INTERMACS level.
Peura J L et al. Circulation. 2012;126:
Copyright © American Heart Association, Inc. All rights reserved.

43. Device Types
Device diagrams. Reprinted with permission from Thoratec and from CardiacAssist.
Peura J L et al. Circulation. 2012;126:
Copyright © American Heart Association, Inc. All rights reserved.

44. Simon MA, et al. Circulation 2005;112[suppl I]:I-32-I-36
Bridge to Recovery
Simon MA, et al. Circulation 2005;112[suppl I]:I-32-I-36

45. Simon MA, et al. Circulation 2005;112[suppl I]:I-32-I-36
Bridge to Recovery
Simon MA, et al. Circulation 2005;112[suppl I]:I-32-I-36

46. Simon MA, et al. Circulation 2005;112[suppl I]:I-32-I-36
Bridge to Recovery
Ejection Fraction
= non-ischemic CM
Simon MA, et al. Circulation 2005;112[suppl I]:I-32-I-36

47. Kaplan-Meier survival curve for all-cause mortality by intravenous vasoactive medication use.

48. Cavigelli-Brunner A, et al. Pediatrics 2014;134:e894
Clinical Scenario
8 year old (25 kg, BSA 0.97 m2)
Bone sarcoma
Doxorubicin 450 mg/m2 cumulative dose
SF 15%, EF 25%
Inotropic and mechanical ventilatory support
Ongoing deterioration
149 device days total
90 days in hospital
Cavigelli-Brunner A, et al. Pediatrics 2014;134:e894

49. Catheterization/Balloon Occlusion of Outflow Graft
Kaplan-Meier survival curve for all-cause mortality by intravenous vasoactive medication use.
Cavigelli-Brunner A, et al. Pediatrics 2014;134:e894

50. Cavigelli-Brunner A, et al. Pediatrics 2014;134:e894
HeartWare
Kaplan-Meier survival curve for all-cause mortality by intravenous vasoactive medication use.
Cavigelli-Brunner A, et al. Pediatrics 2014;134:e894

51. Siegenthaler MP, et al. J Thorac Cardiovasc Surg 2004;127:812-22
Impella Recover LVAD
Kaplan-Meier survival curve for all-cause mortality by intravenous vasoactive medication use.
Siegenthaler MP, et al. J Thorac Cardiovasc Surg 2004;127:812-22

52. Impella Recover LVAD
Kaplan-Meier survival curve for all-cause mortality by intravenous vasoactive medication use.

53. Acute Decompensated Heart Failure - Medical Management or Device?
Answer is …
Interpreting the current guidelines and reviewing the collective experiences…
Optimal medical management is acceptable as initial therapy for most patients
For fulminant myocarditis, early device use is acceptable as a bridge to decision

54. Acute Decompensated Heart Failure - Medical Management or Device?
The decision to implant a device takes into account:
Disease process (reversibility, pathophysiology)
Patient size
Available devices
Program experience and infrastructure
What works best within the program’s system

55. Future Directions
Can we predict outcome in acute heart failure in children?
Can device technology improve in pediatrics for specific clinical scenarios?
Can we develop practice models for pediatric heart failure?

56. Future Directions Paradigm
ISHLT Workforce
AHA CVDY Committee
National Registry
Targeted Therapies
Link phenotype and genotype data
Develop practice models