Establishing Clinical Trail End Points for Neurologic Injury in Cardiac Procedures

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The recommendations are not intended for acute stroke intervention trials.
The recommendations are not intended for acute stroke intervention trials.

The Neurologic Academic Research Consortium (NeuroARC) proposed a set of standardized clinical trial end points for assessing neurologic injury related to surgical and catheter-based cardiovascular procedures. This initiative was published in the Journal of the American College of Cardiology.1

“Stroke is a devastating complication of life-saving cardiovascular procedures. Currently, clinical trials report only the most extreme disabling strokes, but this is [just] the tip of the iceberg,” Alexandra J. Lansky, MD, from Yale School of Medicine in New Haven, Connecticut, told Cardiology Advisor.

According to Dr Lansky, even “silent” cerebral infarcts, which are acutely asymptomatic and are only detectable on magnetic resonance imaging (MRI), may lead to long-term deficits.2,3 “Evidence suggests a possible causal link between silent brain injury and delayed cognitive impairment that is only detected after the patient goes home,” she said. Cognitive dysfunction may manifest as memory loss, inability to concentrate, loss of executive function, and even dementia in the longer term.4,5

Dr Lansky indicated that silent cerebral infarcts are particularly concerning, since they occur as the result of embolization of debris in more than 95% of patients undergoing cardiac procedures, such as aortic valve replacement. In the United States, up to 600,000 patients per year may be affected by brain injury after a cardiac procedure.6

“Standardizing neurological definitions for our clinical trials will ensure reporting of the full spectrum of neurologic injury to provide a better understanding of the clinical consequences, including the impact on longer-term cognitive function and quality of life,” Dr Lansky said. “These definitions will improve our ability to evaluate the risks of cardiovascular procedures and the safety and effectiveness of preventive therapies.”

The NeuroARC initiative, led by Dr Lansky and her colleagues, proposed standardized definitions for neurological injury, such as stroke, hypoxic-ischemic injury, and cerebral hemorrhage; assessments for neurologic injury according to device and procedure type; and assessments for neurologic dysfunction, disability, and cognitive impairment. The initiative also made recommendations for the use of neuroimaging modalities, including MRI, computed tomography, and transcranial doppler.

The writing committee noted that the NeuroARC recommendations were developed for trials evaluating cardiac procedures, such as catheter-based interventions and surgical procedures, and were not intended for acute stroke intervention trials.

Dr Lansky hopes that the initiative will enhance efforts to address evidence gaps regarding the link between procedure-related silent brain injury and long-term neurologic and cognitive outcomes.

“Defining the full spectrum of neurovascular injury may improve our ability to determine which findings are incidental and which are clinically meaningful,” she said.

Disclosures: Dr Lansky has received grant support and fees from Keystone Heart, NeuroSave Inc., and Boston Scientific.

References

  1. Lansky AJ, Messé SR, Brickman AM, et al. Proposed standardized neurological endpoints for cardiovascular clinical trials: an academic research consortium initiative. J Am Coll Cardiol. 2017;69(6):679-691. doi: 10.1016/j.jacc.2016.11.045
  2. Messe SR, Acker MA, Kasner SE, et al; for the Determining Neurologic Outcomes from Valve Operations (DeNOVO) Investigators. Stroke after aortic valve surgery: results from a prospective cohort. Circulation. 2014;129:2253-2261. doi: 10.1161/CIRCULATIONAHA.113.005084
  3. Bonati LH, Jongen LM, Haller S, et al; for the ICSS-MRI Study Group. New ischemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS). Lancet Neurol. 2010;9(4):353-362. doi:10.1016/S1474-4422(10)70057-0
  4. Garrett KD, Browndyke JN, Whelihan W, et al. The neuropsychological profile of vascular cognitive impairment — no dementia: comparisons to patients at risk for cerebrovascular disease and vascular dementia. Arch Clin Neuropsychol. 2004;19(6):745-757. doi:10.1016/j.acn.2003.09.008
  5. Vasquez BP, Zakzanis KK. The neuropsychological profile of vascular cognitive impairment not demented: a meta-analysis. J Neuropsychol. 2015;9(1):109-136. doi: 10.1111/jnp.12039
  6. Gress DR. The problem with asymptomatic cerebral embolic complications in vascular procedures: what if they are not asymptomatic? J Am Coll Cardiol. 2012;60(17):1614-1616. doI: 10.1016/j.jacc.2012.06.037
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