Evaluation of a temporary pump in patients with decompensated heart failure.

Introduction:
Patients with heart failure have a diminished cardiac pump function. Severe
congestive heart failure is characterized by signs and symptoms of severe left
ventricular failure. Patients have fluid retention and other signs such as
right ventricular dysfunction, renal dysfunction or pulmonary congestion.
These patients are admitted to a heart failure clinic for weeks, and often
longer than one month. They are treated with (high dosages of) intravenous
diuretics. When basic treatment fails, mortality rates are high. Escalation
therapy includes administration of inotropic drugs (-> these enhance cardiac
contractility) such as enoximone or dobutamine. Guidelines note that initiation
of inotropic therapy *may be reasonable* in diuretic-resistant patients.
However, there are no data demonstrating an outcome benefit of inotropes in
this population, and some reports warn for the potential adverse events
including increased mortality. Moreover, inotropes also often fail to rapidly
improve the patient. In these patients, escalation towards mechanical
circulatory support such as an intra-aortic balloon pump, is necessary. When
right heart and kidney function deteriorate in case of failing therapy,
patients have contra-indications for implantation of a (permanent) left
ventricular assist device (LVAD) and/or heart transplantation.
Shortcomings of the current approach therefore include:
-> current treatment often fails;
-> it consumes at least weeks to learn if right ventricular and renal function
recover sufficiently in order to qualify for LVAD implantation, and
-> patients are thus admitted in the hospital for a long period of time.

Rationale:
In Erasmus MC, we treated several advanced heart failure patients with an
intra-aortic balloon pump (IABP). This IABP was used as a bridge to recovery
(ie, towards ambulant heart failure in good global condition), as a bridge to
implantation of LVAD or heart transplantation, or to palliative care. An IABP
is a pneumatic, helium gas driven balloon catheter, positioned in the
descending aorta to improve heart function.
Complication rates of this pump are low (<1%). In heart failure patients, I
observed a decrease in dyspnea and fluid retention after implantation of the
pump (Figure 2), which was also described in observational studies of other
investigators. The use of the IABP for diuretic-resistant heart failure however
remains controversial, mainly due to the lack of strong data. I would very much
like to investigate these observations more comprehensively and we urgently
need controlled trials in order to develop an evidence-based treatment
algorithm for tailored patient treatment.

Primary Objective: Evaluation of the benefit of IABP counterpulsation in
patients with diuretic-resistant congestive heart failure.

Secondary Objective(s):
- To lower the burden of disease/improve symptoms, to shorten duration of stay
in the hospital, to improve the function of other organs than the heart, and to
bridge patients faster to final treatment (medical vs. LVAD vs. transplantation
vs. palliative care).
- To create evidence based knowledge and gain better understanding of the
disease, resulting in tailor-made treatment.

Study design: Open-label randomized controlled parallel, partly cross-over,
study in patients with diuretic-resistant congestive heart failure (Figure 3).

Duration: Three years.

Setting: 12-bed Intensive Cardiac Care Unit at Erasmus MC.

Methods: Each patient will receive a pulmonary artery catheter to measure
intracardiac pressures. After informed consent, patients will be randomized
(Figure 3) to IABP (without inotrope, group I) or inotrope (without IABP, group
II).
After 48 hours, we aim at a negative fluid balance of at least 1 liter. If this
target (+ 1 other criterium; Table 2) is not reached, a patient is classified
as clinical *non-responder*by protocol. In these non-responders, a crossover of
the protocol will be performed using the same endpoints. After 48h (or 96h in
case of a non-responder), patients will receive routine treatment: in general
the pump or inotropes will bridge the patient towards recovery or LVAD
implantation.


TABLE 2. DEFINITION OF NON-RESPONDER, ASSESSED AT T=48H
FLUID BALANCE AT T=48H Less than 1 liter negative
AND 1 OTHER CRITERIUM:
- SVO2 (T=48H) <55%
- LACTATE (T=48H) >2.0 mmol/L.

Group 1 (IABP): An experienced interventional cardiologist will implant the
IABP in the catheterization laboratory. The IABP catheter will remain in situ
for at least 48h, unless complications occur or escalation of therapy is
necessary.

Group II (Inotrope): Enoximone will be started in a dose of 1 µg/kg/min. Before
starting the infusion, a bolus injection will be given equal to the volume of
the (central) venous line used. Target dose will be 0.5-2 µg/kg/min, based on
the following parameters:
- Cardiac index (if measured reliably; target >2.5 L/min/m2).
- SvO2 (target >55%)
- Lactate (target <2.0 mmol/L).
- Mean arterial pressure (MAP, target *60 mm Hg).
- Urine output (target >0.5 mL/kg/uur).
If necessary, dobutamine can be added in a dose of 1-10 µg/kg/min, dependent of
the parameters listed above, heart rate (target 60-120 bpm) and the occurrence
of arrhythmias.

Escalation of therapy (Table 3; Word file):
Escalation therapy is defined as (unintended) extension of therapy based on
clinical assessment of the patient after T=3h, but within T=48h.
In the IABP group (group I), escalation of therapy could be performed by
starting an inotropic agent (=enoximone or dobutamine), or norepinephrine.
Indication for starting inotropic therapy is failure of therapy, defined as
SvO2 <55% AND lactate *2.0 mmol/L AND low urine output (<0.5 mL/kg/h).
Indication for starting norepinephrine is prolonged hypotension (MAP <60 mm Hg
for at least 30 minutes) AND low urine production (<0.5 ml/kg/uur).
In the inotrope group (group II), escalation of therapy could be performed by
(a) starting norepinephrine and (b) implantation of an IABP.
Indication is failure of therapy, defined as SvO2 <55%, lactate *2.0 mmol/L,
prolonged hypotension (MAP <60 mm Hg for at least 30 minutes) AND low urine
production (<0.5 mL/kg/uur).
In both groups, escalation towards more potent circulatory support devices or
extracorporeal membrane oxygenation is always indicated in cases of evident
treatment failure, defined as progressively worsening SvO2 and lactate measures
despite high dosages of inotropic and vasopressor support, and IABP.

Therapy with inotropes as well as intra-aortic balloon pump support are
frequently used in patients with heart failure. Complication rates are low
(<1%). Decompensated heart failure is a CE-certified indication for an
intra-aortic balloon pump.