System Devices Panel
Proximal Anastomosis System
of myocardial perfusion due to CABG failure can result in incapacitating
symptoms, myocardial infarction, cardiac failure, or sudden death. The FDA recommends
that any clinical study of a device modifying the “gold standard” of
hand-sutured creation of a CABG conduit provide objective angiographic evidence
of patency at 6-months and 1 year.
sponsor presented data derived from two studies performed outside the United
States. Although a US Core Lab
evaluated the imaging studies, there was no formal DSMB or CEC to interpret
clinical events. Study 1 was a
prospective recruitment of patients for study of the PAS-Port device. Cohort
2 was a subset of patients from a separate study (Study 2) for which the
objective was to evaluate a different device, i.e., a distal coronary
anastomotic system called the C-Port.
Cohort 2 was created retrospectively from a subset
of patients in Study 2 who had a PAS-Port anastomosis performed based on
surgeons’ discretion and influenced by aortic disease state and preferred sequence
of graft anastomosis. Inclusion criteria were
different for studies that provided the patients constituting Study 1 and
- The sponsor did not
achieve the patency objective in pivotal Study I and is attempting to pool
data from a subset of Study 2 to remedy this failure. Please comment on the acceptability of
pooling data from Study 1 and Cohort 2, discussing any limitations of this
- Modifications were
made to the PAS Port device between Study 1 and Cohort 2. These modifications were made to
address failures in device deployment.
Do you have any concerns with the use of the combined data set
given the changes in device design?
- The primary effectiveness
endpoint for the combined data was the proportion of patent grafts at 6
months. Definition of patency is
less than 50% stenosis. FDA
recommends that the lower confidence limit of the 95% confidence interval
for the proportion of patent grafts be greater than 80%.
- In the per
protocol analysis, patency for 20 of 97 (20%) device patients who failed
to have an angiogram was imputed from MRI (5), CT (5), Stress ECG (4),
and absence of symptoms (3). One patient lost to follow-up and 2 deaths
were listed as occluded grafts. Please
discuss whether this is a sufficiently robust assessment for this device.
- In the intent to
treat analysis, 9 of the 12 patients who converted to hand-sewn
anastomoses following failed deployment of the device, had “patency”
imputed with data from stress-ECG in 7 cases and from absence of cardiac
symptoms in 2 cases. Insufficient
follow-up data were available for three patients and for that reason
imputed as “occluded.” Please
discuss whether this is an acceptable assessment of outcome for 12 of the
109 patients that constitutes the intent to treat cohort analyzed?
- Is device
effectiveness adequately demonstrated by the multiple angiographic and
- Please discuss
whether you believe the data provides reasonable assurance of safety for
the proposed indications. In your
discussion consider the critical importance of the aortic anastomosis to
the patency of the CABG conduit that requires careful scrutiny of adverse
events as they relate to the anastomotic device. Do you concur with the sponsor’s
assessment that the following adverse events were not device related:
a. ECG ischemia assessed as
unrelated to the device solely based on interpretation that the index graft did
not supply the region of myocardial ischemia;
b. Ischemia related to the
index graft that resolved over the course of the study was not considered significant for conduit patency irrespective
of coronary vessel bypassed;
in one case and interior myocardial infarction in a second case were assessed
as not device related although occurring in the region of index graft perfusion.
- Taking into account
all pertinent clinical information available as well as your responses to
the above questions, please comment on whether you believe the data
provides an overall risk/benefit ratio which supports marketing clearance
of the device in the United States for the proposed indication.
aspect of the 510(k) review of a new product is the review of its labeling. The
labeling must indicate which patients are appropriate for treatment, identify
potential adverse events with the use of the device, and explain how the
product should be used to maximize benefits and minimize adverse effects. Please address the following questions
regarding product labeling:
- The Indications state
that the PAS-Port System is intended to create an everting anastomosis
between the aorta and an autologous vein graft. The PAS-Port System has only been studied in CABG procedures
involving the unique coronary circulatory system. Please comment whether the indication should
be restricted solely to this use which is consistent with their
instructions for use (IFU)?
- The anstomosis
created with the PAS-Port device has many characteristics of endovascular
stenting, i.e., circumferential splinting and exposure of subintimal
tissue and of blood stream to bare metal.
The report of adverse events noted two episodes of conduit
thrombosis and the occurrence of distal anastomotic obstructions that
could reflect embolic episodes. Should
a regimen of antiplatelet coverage be advised with use of this device?
- The IFU indicates
that a mean arterial pressure of at least 50mmHg for deployment of the
device. This suggests the use during beating heart or off pump CABG or the
performance of all proximal anastamotic use before cross-clamping the
aorta. This will require estimation of conduit lengths for multiple CABG
procedures at an early stage of the operation, possibly compromising
by-pass grafting performed. Should
this potential problem be indicated with a warning in the labeling?
- The stented
circular anastomosis created with the device has an inherent propensity for
kinking. This is addressed
generically in the precaution section of labeling. This complication is particularly
problematic with right coronary revascularization. Should use of the device be restricted
for CABG procedures for the circumflex area of myocardial perfusion?
- Please provide any
other recommendations or comments regarding the labeling of this device.
- If the data
provided are not adequate to support safety and/or effectiveness, what
additional data, analyses, or study would you recommend?