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Inotropes and Heart : When to Use and When Not to Use 521

ing heart which results in contractile dysfunction and HOME INOTROPIC SUPPORT
arrhythmia. Experimental models have proved when
SERCA2a expression is increased in cardiomyocytes SELECTION OF PATIENTS :
which can lead to restoration of intracellular calcium Patient preferences and goals of care should ideally
cycling there was demonstrable improvement in be determined prior to any initiation of intravenous
contractility, cardiac metabolism, and survival The inotropic therapy. This should involve direct conver-
CUPID (Calcium Up-regulation by Percutaneous ad- sations with the patient and family discussing the
ministration of gene therapy In cardiac Disease) trial, available treatment options and possible outcomes.
a multicenter open-label study designed to evaluate When one is unable to wean patients from inotropic
the safety profile and provide first-in-human data for support discharging a patient with home inotropic
the gene transfer of SERCA2a cDNA (adeno-associ- therapy [5] and patients should also be instructed
ated virus [AAV1]/SERCA2a). Three separate dosing that further hospitalization is likely even with home
regimens of AAVI/SERCA2a were tested and com- inotropic therapy.
pared to a placebo group, with the high-dose group
showing improvement or stabilization in each of the INOTROPES IN PATIENTS AWAITING
efficacy endpoints for the 6-month primary analysis.
AAV1/SERCA2a was well tolerated with no reported HEART TRANSPLANT —
adverse events. Thus The CUPID trial demonstrates
that SERCA2a is a potential therapeutic target in pa- BRIDGE THERAPY :
tients with heart failure and two clinical trials are cur- Patients with severe heart failure (HF) with reduced
rently targeting SERCA2a, one in patients implanted ejection fraction who are awaiting heart transplanta-
with left ventricular assist devices and another exam- tion constitute a unique population with respect to
ining the effect on cardiac remodeling. the role of therapy for hemodynamic support. In this
setting, the goal of HF management is to maintain
Istaroxime the patient’s clinical stability long enough to enable
the patient to undergo transplantation when a donor
Istaroxime is a novel intravenous drug which inhibits heart becomes available. A variety of approaches have
the activity of sodium-potassium ATPase and stimu- been used to “bridge” a patient to heart transplanta-
lates sarcoplasmic reticulum calcium ATPase isoform tion, including the use of mechanical ventricular as-
2a (SERCA2a). sist devices. Intravenous inotropic agents are another
This dual mechanism of action results in both inotro- option for the temporary hemodynamic support of a
pic action(by allowing the accumulation of cytosolic heart transplant candidate. The clinical improvements
calcium during contraction) and a lusitropic effect(by seen with inotropes (reduced hospitalization, less fre-
sequestering calcium during relaxation) and thus it quent worsening of HF) are beneficial because the
was found improve both systolic and diastolic dys- patient is maintained in an optimal clinical condition
function without an increased incidence of arrhyth- prior to surgery. The increased risk of sudden death
mias. The HORIZON-HF (Hemodynamic, Echocardio- associated with these agents can be mitigated with
graphic, and Neurohormonal Effects of Istaroxime, the use of an implantable cardioverter-defibrillator
a Novel Intravenous Inotropic and Lusitropic Agent: (ICD) and pharmacotherapy (usually amiodarone) for
a Randomized Controlled Trial in Patients Hospital- the suppression of ventricular arrhythmias.
ized with Heart Failure) study, a double-blind, place- The benefit of outpatient intravenous inotropic
bo-controlled trial in patients hospitalized with acute therapy as a bridge to heart transplantation was
heart failure, assessed the hemodynamic effects of illustrated in a report of 21 patients with severe
istaroxime which showed that there was reduction in HF treated for a mean duration of 146 days. All
the primary end point- reduction in pulmonary cap- but one of the patients received an ICD prior to
illary wedge pressure, was improved for all 3 doses hospital discharge. Intravenous inotropic therapy
compared to placebo. The distinguishing features resulted in significant improvements in functional ca-
from conventional agents included, a dose-depen- pacity, renal function, and hemodynamics as well as
dent reduction in heart rate, an increase in systolic a decrease in the number of hospitalizations.
blood pressure but no effect on neurohormones, re-
nal function, or troponin levels. Thus Istaroxime may Thus for patients awaiting transplant, inotropes are
be a potential inotrope which avoids the adverse ef- meant to maintain hemodynamics and end-organ
fects associated with conventional inotropes. function and alleviate symptoms as a bridge to trans-
plantation. For patients who are not likely to undergo
further advanced therapies, inotropic agents may al-

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