Cerebral Lesions and Outcome After Cardiac Surgery (CLOCS)

Objective. Cardiac surgery is the leading cause of iatrogenic stroke in the United States;
1% to 5% of patients undergoing CABG have a stroke, and 30% have clinically silent new
lesions that are detectable only on MRI. Cognitive dysfunction is also common after heart
surgery, and up to 40% have long-term cognitive impairment. The primary objective of this
study is to define the pre-operative risk profile that best predicts postoperative ischemic
or cognitive changes in patients undergoing heart surgery and to 1) establish a registry of
patients undergoing cardiac surgery to evaluate the relationship of new lesions on MRI,
blood biomarkers, neurological and neurocognitive outcome 2) identify the most significant
risk factors for post operative cerebral ischemic lesions 3) determine whether new ischemic
lesions on DWI are associated with subsequent neurological or cognitive impairment. The
objective of the genetics sub-study is to estimate the relative risk of specific
polymorphisms of genes of molecules involved in the inflammatory response and occurrence of
new ischemic lesions.

Study population. 363 patients (188 consecutive patients undergoing CABG and 175 patients
undergoing aortic or mitral valve replacement).

Design. Patients will have a pre-operative medical and neurological evaluation before
surgery and 24 and 48 hours after surgery. A brain MRI will be obtained preoperatively and
48 hours, 30 days, and 6 months after surgery. Blood drawn to quantify biomarkers will be
obtained before and immediately after surgery and 6, 24, 48 and 72 hours post-operatively.
Patients enrolled in the genetics sub-study will have additional blood drawn for sequencing
of inflammatory genes. Neuropsychological examinations will occur at 30 days and 6 months
after surgery.

Outcome measures. The primary outcome measure is the evidence of new ischemic lesions on the
48-hour DWI relative to pre-operative DWI. In addition, the following outcome measures will
be considered in exploratory analyses: 1) Any new ischemic lesion on 30 day DWI or FLAIR
relative to pre-op DWI or FLAIR; 2) Evidence of clinically definite ischemic stroke (focal
neurological deficits persisting for more than 24 hours) confirmed by non-investigational CT
or MRI (if protocol-required scans are not obtained) occurring within the first 30 days
(plus or minus 3 days) after surgery; 3) All cause mortality; 4) Encephalopathy; 5)
Cognitive decline at 30 days; 6) Cognitive decline at 6 months; 7) Evidence of reperfusion
injury on 48-hour post-gadolinium FLAIR; 8) New ischemic lesions on 6-month DWI or FLAIR; 9)
Changes in values of blood markers; 10) Number, volume, and location of new DWI or FLAIR
lesions.

- INCLUSION CRITERIA:

- Age 18 years or greater

- Neurologically and cognitively independent prior to surgery (mRS less than 2)

- CABG, aortic or mitral valve replacement, or a combined valve/CABG procedure
scheduled within one week

EXCLUSION CRITERIA:

- Planned concomitant carotid endarterectomy

- Concomitant medical disorders making clinical follow-up of at least 6 months unlikely
or impossible (e.g., neoplastic disease, hepatic failure)

- History of dementia, cognitive dysfunction (MMSE score less than 24) or psychotic
disorder

- Any current MRI contraindication (cardiac pacemaker or defibrillator, insulin pump,
aneurysmal clip, implanted neural stimulator, cochlear implant, metal shrapnel or
bullet, etc)

- Definite or possible pacemaker placement at the time of or after surgery

- Inability to give informed consent

- Pregnancy