28 CardioSource WorldNews: Interventions
had both. Mean exercise PCWP was significantly
lower at 6 months despite mean exercise duration being significantly increased.
The V-Wave Unidirectional Shunt System
was tested in a Canadian single-arm, singlecenter, proof-of-concept study that enrolled
10 patients with HFrEF.2 This study was led by
Josep Rodes-Cabau, MD, of the Quebec Heart
and Lung Institute, Laval University, Quebec
City, Canada. The device was implanted successfully with transesophageal echocardiographic (TEE) guidance in all patients, with no
procedural adverse events reported and shunt
patency confirmed by TEE at 1 month.
At 3 months, seven of nine patients (78%) had
improved their New York Heart Association functional class from class III to class II, and one patient
improved from class III to class I. In one patient,
no change was noted. Quality of life and 6-minute
walk distance were also significantly improved,
while mean PCWP was reduced from 23 mm Hg at
baseline to 17 mm Hg at 3 months (p = 0.035).
Patients were empirically treated with oral
anticoagulants (warfarin or another) and aspirin
for 3 months. No thrombotic complications were
observed.
Individuals with larger congenital atrial septal defects, usually more than 10 mm in diameter, can have left-to-right shunting that leads
to symptoms and signs of right ventricular volume overload and pulmonary hypertension. So
an obvious concern with these devices is that
they do not overload the right side of the heart.
The V-Wave shunt, for example, is designed to
create only a small left-to-right atrial shunt. The
device has a 5 mm minimum lumen diameter or
a 6.5 mm effective orifice diameter. In the Rodes-Cabau
study, there was a mild and nonsignificant increase in
pulmonary arterial pressures and pulmonary resistance,
but the evidence indicated that this was well tolerated by
the right ventricle and pulmonary vasculature.
Next Steps
“I think the proof of concept is there and we have shown
that some patients may benefit from this, now it’s time to
move ahead with larger studies,” said Dr. Rodes-Cabau.
He noted with interest that the proof of concept has been
accomplished with two somewhat mechanically different
devices that work similarly but were tested in two different patient populations. On the V-Wave device, he added,
they saw that the valve shunt remained open most of the
time, making the most obvious difference between the
two devices less meaningful.
Commenting on the trials, Patrick Rossignol, MD, PhD
(Inserm, Nancy, France), and Faiez Zannad, MD, PhD (Universite de Lorraine, Nancy, France), noted that, beyond the
significant amount of further clinical testing that is needed
to prove safety and efficacy, clinicians also need to understand whether the results have mechanistic plausibility.3
Courtesy V-Wave Ltd.
T
he closing of the foramen ovale ranks as one of the
miracles of birth; but when it doesn’t happen, then
new parents at least can take some comfort in the
miracle of repairing the defect. However, in patients with
heart failure (HF), there is some evidence to suggest that
shunting of blood from the left atrium to the right atrium
might actually be hemodynamically advantageous.
Could an intentional left-to-right atrial shunt work as
a decompression and decongestion security valve in individuals with increased left atrial pressure, high pulmonary
capillary wedge pressure (PCWP; either at rest or with
exercise), and heart failure (either with reduced or preserved ejection fraction)? Think of it is as kind of a detour
for blood that will otherwise put pressure on the lungs and
cause dyspnea, the main reason for hospital admission in
HF patients.
This possibility is being tested and the results look
exciting, particularly for those with HF with preserved ejection fraction (HFpEF), for whom no treatments have been
proven to reduce morbidity or mortality or even significantly improve symptoms or exercise capacity.
Two companies are currently testing left-to-right shunt
devices: V-Wave Medical of Caesaria, Israel, is assessing
its Unidirectional Shunt System, and Corvia Medical of
Tewkesbury, Massachusetts, has the InterAtrial Shunt Device (IASD®). Both devices are implanted percutaneously
via femoral venous access and a trans-septal puncture.
Furthermore, both are designed to create a controlled
atrial septal defect in symptomatic patients with HF.
The V-Wave device is placed across the fossa ovalis
and secured in place by its geometry with the wider entry
funnel deployed in the left atrium and a wider exit funnel in the right atrium. The exit funnel has three porcine
pericardial leaflets sutured to the frame that remain in the
open position and will close wh en the right atrial pressure
exceeds the left atrial pressure by 1 or 2 mm Hg.
The Corvia IASD device—which, by the way, is the first
transcatheter device designed to treat HFpEF (and only
HFpEF)—works less like a valve and more like a stent. The
mesh structure is deployed through a hole made in the
atrial septum and allows constant communication between
the left and right atria.
In the REDUCe Elevated Left Atrial Pressure in Patients
with Heart Failure (REDUCE LAP-HF) study, Gerd Hasenfuss, MD, of the Heart Centre at the George-August
Universitat, Gottingen, Germany, and colleagues from 21
centers in the Europe, Australia, and New Zealand, assessed the performance and safety of the IASD device in
patients with symptomatic HFpEF despite treatment and a
raised PCWP at rest or during exercise.1
In this single-arm, phase I study, there were no reports
of peri-procedural, major adverse cardiac, or cerebrovascular events in the 64 eligible patients who had successful
IASD placement, nor was there any need for surgical intervention for device-related complications within 6 months
of the procedure. Sustained device patency at 6 months
was confirmed by left-to-right shunting.
At 6 months, 52% of patients had a reduction in PCWP
at rest, 58% had a lower PCWP during exertion, and 39%
Courtesy Corvia Medical, Inc.
Might We Offer You a 5th Valve?
top: World’s First InterAtrial Shunt Designed to Treat HF
bottom: V-Wave shunt-image
“The mechanisms that lead from a modest hemodynamic change to the striking apparent clinical benefit
still need to be understood, particularly in heart failure
with reduced ejection fraction,” they wrote. As well, the
long-term effects on heart and large artery remodeling
need to be shown, along with clear impact on long-term
hard clinical outcomes.
In March of this year, Corvia Medical received an investigational device exemption approval from the Food and
Drug Administration for a multicenter study of the IASD. In
May they gained CE Mark approval. It has been reported
that they have inked a strategic agreement for a purchase
option with a secret partner.
For its part, the V-Wave shunt is currently under investigation in multiple clinical trials in North America, Europe,
and Israel. V-Wave Ltd. announced completion of a $28
million Series B financing deal with investors, including
Johnson & Johnson Innovation. ■
REFERENCES:
1. Hasenfuss G, Hayward C, Burkhoff D, et al. Lancet. 2016;387:1298-304.
2. Del Trigo M, Bergeron S, Bernier M, et al. Lancet. 2016;387:1290-97.
3. Rossignol P, Zannad F. Lancet. 2016;387:1253-55.
July/August 2016