Assessment of Neurologic Injury Subsequent to Transcatheter Aortic Valve Replacement: A Feasibility Study

Nearly 1 in 10 adults over 65 years have aortic valve stenosis (AS), defined as an
obstruction of blood flow across the aortic valve.(Faggiano, Antonini-Canterin et al. 2006)
AS is a life-threatening disease, and one whose incidence increases with age. Natural
history studies suggest that the long-term survival among patients with severe AS is
unfavorable, even among patients who are asymptomatic, with event-free survival for AS being
64% at 1-year, 36% at 2-years, 12% at 4-years, and 3% at 6-years.(Rosenhek, Zilberszac et
al. 2010) Until recently surgery has been the gold standard approach for treatment for
severe AS. Recently, a less invasive approach, transcathether aortic valve replacement
(TAVR) has emerged as a viable treatment alternative, including among those previously not
thought of as suitable candidates for surgery. Unlike its surgical counterpart that utilizes
cardiopulmonary bypass and direct vision by a cardiothoracic surgeon, TAVR is performed (by
a surgeon in conjunction with an interventional cardiologist) by threading a wire mesh valve
through a catheter using fluoroscopy while the heart is still beating. Concern regarding
broader adoption of TAVR often revolves around the higher stroke rate relative to surgery
(5.5% vs. 2.4%, p = 0.04).(Leon, Smith et al. 2010) Much of the risk associated with
neurologic injuries (whether stroke, neurocognitive deficits or silent infarcts) revolves
around embolically-generated sources, including: threading a guidewire across diseased
vessels, removal of the native valve, or insertion/expansion of the new valve.(Miller,
Blackstone et al. 2012) Among 47 patients studied by Miller within a neurologic sub-study of
the PARTNER Trial, there were 49 (n=31 TAVR, 16 AVR) neurologic events (defined as a
transient ischemic attack or stroke).(Miller, Blackstone et al. 2012) In a recent review
article, Daneault cited risk of post-procedural cerebral infarcts within 5-7 days (using
Diffusion-weighted MRI) of 38-47% with standard aortic valve surgery vs. 68-84% with
TAVR.(Daneault, Kirtane et al. 2011) Given the growing interest and anticipated broadening
of indications for TAVR in and outside of the United States, it is increasingly important to
develop a sound methodological approach for evaluating the safety and effectiveness of this
emerging treatment modality. In the absence of such information, it is impossible for a
patient or clinician to estimate the likelihood for developing a neurologic injury
subsequent to TAVR. Additionally, linkage of processes of care with embolism detection
(through transcranial Doppler) would provide evidence to support targeted quality
improvement efforts. Such a strategy has been useful in prior studies applied to coronary
artery bypass grafting (CABG) surgery.(Groom, Quinn et al. 2009) Indeed, early studies
evaluating TAVR have found periods of the TAVR procedure which may be more prone to the
generation of embolic debris, although they have used varied methodological approaches.
Importantly, the relationship between these emboli and development of neurobehavioral or
ischemic lesions has not been explored in this setting.

The overlap between sleep disorders and stroke is an emerging field. Sleep apnea is a
serious medical condition that is very common after stroke, affecting over half of acute
ischemic stroke patients. (Broadley, Jorgensen et al. 2007) Recently, sleep apnea has been
recognized as an independent risk factor for stroke. (Munoz, Martinez-Vila et al. 2006;
Redline, Gottlieb et al. 2010; Yaggi, Kernan et al. 2005) Furthermore, sleep apnea has been
identified as an important predictor of both poor functional outcome and death following
stroke. (Sahlin, Sandberg et al. 2008; Turkington, Allgar et al. 2004) There remains
controversy over whether OSA predates stroke, whether stroke predates sleep apnea, and
whether stroke exacerbates sleep apnea severity. To answer the questions definitely, sleep
apnea testing would have to be performed just prior to and again after stroke. Because
stroke is typically unpredictable, this has been logistically challenging to pursue. The
current study however provides a rare opportunity to study patients for sleep-disordered
breathing just prior to and after a type of procedure that has an association with acute
cerebral infarction identified on MRI. (Kalert, Knipp et al. 2010) Within this context, we
seek to determine the feasibility of assessing neurologic injuries subsequent to TAVR. Such
a model has been applied previously by the principal investigator to assess and improve
neurologic outcomes for other cardiac surgical procedures.(Groom, Quinn et al. 2009) We
shall assess patients during the following intervals: pre-procedure, within 72-96 hours
post-procedure, and 3 months post-procedure (see Appendix). Case videos will be established
to assist in identifying and associating emboli (using transcranial Doppler) and processes
of clinical care during the TAVR procedure. Neurologic injury will be assessed in the
following ways: stroke (neurologic exam, NIH Stroke Scale), silent infarcts
(diffusion-weighted MRI, diffusion-tensor imaging), and neurobehavioral deficits (a battery
of neuropsychological tests). Secondly, we will investigate changes in the apnea-hypopnea
index (AHI), a measure of sleep-disordered breathing, before vs after surgery between those
subjects who develop post-operative acute brain infarction and those who do not. We
hypothesize that subjects who develop acute brain infarction will have an increase in AHI
between baseline and post-op measurements compared with those subjects who do not develop
acute brain infarction. A research coordinator will coordinate the testing.

Inclusion Criteria:

1. Adults > age 18 years old

2. Able to give informed consent

3. Meets criteria for implant of Sapien Aortic Valve

4. Availability of transtemporal windows

Exclusion Criteria:

1. Pregnancy

2. Having a metallic foreign body in orbit

3. Previous aneurysm surgery

4. Unable or unwilling to give informed consent and follow up with study activities