Impella CP With VA ECMO for Cardiogenic Shock

Veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) is indicated as a haemodynamic
rescue strategy in decompensated acute or chronic heart failure presenting as cardiogenic
shock. It has been used across aeitologies including post-myocardial infarction, dilated
cardiomyopathy, acute myocarditis and in post-cardiotomy shock. VA ECMO has a number of
effects on the circulation including improved end-organ perfusion and possibly improved
coronary perfusion, and is a bridge to further therapies including permanent advanced
mechanical circulatory support, cardiac transplantation and to cardiac recovery.

Left ventricular assist devices (LVADs) provide long-term mechanical circulatory support and
also profoundly mechanically unload the left ventricle. Multiple clinical studies have
documented cardiac recovery using LVAD therapy, with a rate between 10-60% in selected
populations. A large body of basic science has documented the pivotal role of mechanical load
in determining ventricular contractile performance across species. Therefore both clinical
data and basic laboratory studies support the notion that profound ventricular unloading may
result in improved cardiac performance through a variety of mechanisms ranging from triggered
de novo cardiomyocyte proliferation, subcellular calcium handling reverse remodeling, changes
to the extracellular matrix of the heart, reverse remodeling of the neurohormal milleu,
amongst many others.

One of the major deficiencies of peripheral VA-ECMO is its lack of left ventricular
unloading, with associated pulmonary congestion, which can derail clinical improvement and
hamper cardiac recovery. Indeed, percutaneous VA-ECMO increases LV afterload due to the
retrograde blood flow, and because of the lack of venting, there may be progressive LV
distension. These conditions can result in a congested, pressure-overloaded ventricle, even
in the absence of echocardiographic ventricular distension. This may be ameliorated with the
addition of ventricular mechanical unloading using percutaneous therapies including the
percutaneous left ventricular device, Impella CP.

On the platform of VA-ECMO, the addition of an Impella device to reduce ventricular loading
results in improved survival and recovery of ventricular performance in the setting of
cardiogenic shock. In a number of small studies, the use of additional means to unload the
ventricle, principally Impella, results in cardiac recovery and less ventricular distension.
In chronic heart failure, direct ventricular unloading is critical to cardiac recovery.

The objective of this randomized study is to determine whether the addition of early direct
ventricular unloading using Impella CP leads to higher rates of cardiac recovery, defined as
survival free from mechanical circulatory support, heart transplantation or inotropic support
at thirty days. This study will also examine the clinical, biochemical, echocardiographic and
radiologic effects of VA ECMO with and without the addition of Impella CP to directly vent
the left ventricle to address adjunct important questions such as the effects on pulmonary
congestion.