5. Class I Indications for Cardiac
Transplantation
• Cardiogenic shock requiring mechanical assistance.
• Refractory heart failure with continuous inotropic infusion.
• NYHA functional class 3 and 4 with a poor 12 month
prognosis.
• Progressive symptoms with maximal therapy.
• Severe symptomatic hypertrophic or restrictive
cardiomyopathy.
• Medically refractory angina with unsuitable anatomy for
revascularization.
• Life-threatening ventricular arrhythmias despite aggressive
medical and device interventions.
• Cardiac tumors with low likelihood of metastasis.
• Hypoplastic left heart and complex congenital heart disease.
6. American College of Cardiology Foundation/American Heart
Association 2013 (Yancy, Jessup et al. 2013)
To maintain systemic perfusion and preserve end-
organ performance in low output syndrome
Strength Level of
Evidenc
e
Temporary support in cardiogenic shock I C
Continuous intravenous support as “bridge therapy” to VAD or
transplantation
IIA B
Short-term support in hospitalized patients with severe systolic
dysfunction with low blood pressure and significantly depressed
cardiac output
IIB B
Long-term, continuous support as palliative therapy for symptom
control if not eligible for VAD/ transplant
IIB B
Long-term use in the absence of specific indications is potentially
harmful
III B
Use in hospitalized patients without documented severe systolic
dysfunction, low blood pressure, or impaired perfusion, and evidence
of significantly depressed cardiac output is potentially harmful .
III B
7. OPTIME-CHF
• Randomized, controlled, double-blind trial
• Patients admitted with acute HF and systolic
dysfunction
• A 48-hour infusion of milrinone (0.5 mg/kg/min)
or placebo
• The primary end point: CV rehospitalization
within 60 days.
9. Patients were ineligible if
• Systolic blood pressure< 80
• Creatinine> 3
• the treating physician judged
that intravenous inotropic
therapy was essential
Cuffe et al. 2003, JAMA 2002;287:1541-1547
12. Clinical Trial
• Question: do inotropes increase mortality
in HF?
• Randomized: placebo vs inotrope
• After 2005 (AICD)
• Inotrope: Dobutamine or Milrinone
• Low output syndrome (evidence of
decreased CI and/or poor organ perfusion)
13. Source, design Inotrope Cardiac index
Cohn, 1998 Vesnarinone Not reported
Cowley, 1994 Enoximone Not reported
Uretsky,1990 Enoximone Not reported
Hampton, 1997 Ibopamine Not reported
Packer, 1991 Oral milrinone Not reported
The Xamoterol, 1990 Xamoterol Not reported
Cuffe, 2002 IV milrinone Not reported
Metra, 2009 Enone Not reported
Colucci, 1993 Milrinone, oral Not reported
Dibianco, 1984 Amrinone Not reported
Elis, 1998 Dobutamine IV Not reported
Erlemeier, 1992 Dobutamine IV Not reported
Oliva, 1999 IV dobutamine 1.89 +/- 0.1 L/min/m(2)
Massie, 1985 Amrinone Not reported
Narahara, 1991 Enoximone Not reported
Van Veldhuisen, 1993 Ibopamine Not reported
Dubourg, 1990 Enoximone 2.17 +/- 0.7 L/min/m2
Feldman, 2007 Enoximone Not reported
Feldman, 1993 Vesnarinone Not reported
Nanas, 2004 Dobutamine, IV 2.3 ± 0.7 L/min/m(2)
Likoff, 1984 Amrinone 1.9+/-0.2L/min/m2
Khalife, 1987 . Enoximone 2.76 +/- 0.63
14. Randomized trials with inotropes
• They were performed with inotropes that are
currently not in use.
• They were performed in the years when
AICDs were not recommended for primary
prevention
• They were performed on patients who did not
have any evidence of low output syndrome
and therefore did not have indications for
inotropes.
16. Inotropes do not increase mortality
in advanced heart failure.
Guglin M, Kaufman M.
Int J Gen Med. 2014 May 20;7:237-51
17. Inotropes Do Not Increase Mortality in
Advanced Heart Failure
REBUTTAL
18. Inotrope Dependence
• Patients are inotrope dependent if they
cannot be weaned off inotropes at an
experienced HF center
Lindenfeld J et al, HFSA Guidelines 2010
19. Inotropic Dependence
“failure to wean from inotropes because of
imminent (minutes to hours) worsening of the
patient’s clinical status (combined objective
[eg, blood pressure, level of consciousness,
confusion, change in creatinine, oxygenation]
and subjective [eg, dyspnea, confusion,
weakness]), such that death appeared
imminent, and the patient was deemed highly
unlikely to survive inotrope withdrawal to
permit hospital discharge”.
Hershberger RE et al J Card Fail. 2003;9:180-187
20. Patients will die if we discontinue the
medication which increases mortality!
21.
22. • For example, the FIRST trial was a RCT, designed to
test the effects of continuous intravenous
epoprostenol plus conventional therapy versus
conventional therapy alone in patients with advanced
HF. Some patients who entered the trial were also on
intravenous dobutamine.59 The analysis of the
outcomes depending on the use of dobutamine is
therefore flawed because the patients who required
inotropes were sicker (89% in NYHA IV) than those
who did not (53%).
23. Colucci et al J Clin Invest. 1988 Apr; 81(4): 1103–1110.
24. “Despite improving hemodynamic
compromise, positive inotropic
agents have not demonstrated
improved outcomes in patients with
HF in either the hospital or
outpatient setting”.
ACCF/AHA 2013 HF Guidelines (Yancy, Jessup et al. 2013)
25. Oliva et al.,
1999
DICE
(Dobutamina
ne
ll'Insufficienz
a Cardiaca)
trial:
Dobutamine
vs standard
treatment
38 6
mon
ths
IV
dobuta
mine,
intermi
ttent
48
hours
/week
1.89
+/- 0.1
L/min
/m(2)
Dobutamine:
5 deaths,
2 heart
transplants
Standard
treatment:
3 deaths.
No difference
Hospitalization
s for all
causes: no
difference
Dobutamine:
11 (7 for HF)
Standard
treatment: 17
(11 for HF)
No difference
in NYHA class
and in 6-
minute
walking test.
American heart journal. 1999;138:247-253
