Background: Calcific aortic stenosis(AS) is the leading valvular disease in the United States. The number of patients with this diagnosis and requiring aortic valve replacement(AVR) is growing rapidly with the aging of our population. Emboli are implicated in most strokes and in postopertive cognitive dysfunction(POCD) after heart surgery. Patients presenting for AVR for AS define a subgroup at """"""""extraordinary"""""""" risk(10%) for postoperative stroke, and 40% suffer multiple cerebral embolic events. These patients also are at risk for POCD and or vascular cognitive impairment secondary to these multiple cerebral infarctions in the short- term, and may be at risk for an acceleration toward long-term vascular dementia. This is a key population in which to study not only the pathogenesis of stroke and POCD, but also one in which the success or failure of neuroprotective interventions may be efficiently demonstrable.
Aims :
Aim -1) To determine the incidence the outcomes of stroke and cerebral transient ischemic events in an aged population, after AVR for AS;
Aim -2) To determine the validity of a surrogate imaging biomarkertor postoperative cerebral ischemic events after AVR, using pre and postoperative Diffusion-Weighted MRI(DWI);
Aim -3)Jo determine the change in cognitive performance in the aged patient after AVR for AS as compared to age/disease matched controls over time. Relevance:Post-surgical stroke portends a 5-10-fold increase in early mortality, while 69% suffer severe disability. Advances in the treatment of patients in the general stroke population, where early diagnosis, and an organized approach to early intervention has profoundly impacted outcome. Oddly, an organized approach to stroke surveillance after heart surgery, in a """"""""captured"""""""" population, where the occurrence of stroke is not only frequent but predictable, rarely exists. (The 5-fold variance in the reported incidence of stroke after AVR is very telling.) Conversely, with the opportunity for close surveillance, benefits of rapid intervention/neuroprotection could reasonably be expected to surpass those seen in the general population. Neuroprotection trials have failed at an alarming rate due to inadequate design. A key element in designing properly powered studies is knowing accurately the frequency of the outcome to be studied. An accurate accounting of the risk of two important ischemic endpoints, stroke and POCD, will serve as a foundation for future trials. Validation of a potential imaging surrogate for stroke after AVR, DWI-MRI lesions, may allow for the efficient conduct of """"""""proof of concept"""""""" studies in much smaller populations. Advanced imaging approaches paired with detailed cognitive analyses may allow us to deepen our understanding of the pathogenesis of POCD. Finally, the study database will allow us to closely examine the long-term risks for cognitive impairment &dementia from embolic processes during heart surgery..

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL084375-05
Application #
8128577
Study Section
Special Emphasis Panel (ZRG1-CND-L (03))
Program Officer
Desvigne-Nickens, Patrice
Project Start
2007-09-01
Project End
2013-12-31
Budget Start
2011-09-01
Budget End
2013-12-31
Support Year
5
Fiscal Year
2011
Total Cost
$740,419
Indirect Cost
Name
University of Pennsylvania
Department
Surgery
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Massaro, Allie; Messé, Steven R; Acker, Michael A et al. (2016) Pathogenesis and Risk Factors for Cerebral Infarct After Surgical Aortic Valve Replacement. Stroke 47:2130-2
Messé, Steven R; Acker, Michael A; Kasner, Scott E et al. (2014) Stroke after aortic valve surgery: results from a prospective cohort. Circulation 129:2253-61
Wang, Ping; Acker, Michael A; Bilello, Michel et al. (2010) Sex, aging, and preexisting cerebral ischemic disease in patients with aortic stenosis. Ann Thorac Surg 90:1230-5