See latest updates on Pitt's response to the COVID-19 outbreak. 

Developing Goal-directed Perfusion Therapy in SAH Neurocardiac Injury

Project Leader: Marilyn Hravnak

Funding Agency: NIH/National Institute of Nursing Research 

Description: Up to 46% of patients surviving aneurysmal subarachnoid hemorrhage (aSAH) experience significant long- term disability. Emerging evidence suggests that post-aSAH myocardial injury (SAHMI), also called "neurocardiac injury" contributes to the development of secondary insult and therefore poorer outcomes. Improved ability to recognize and manage this complication could reduce the likelihood of adverse consequences. In prior work, we demonstrated that 31% of post-aSAH patients exhibit early elevated cardiac troponin I (cTnI) that is incrementally related to aSAH severity, and associated with myocardial regional wall motion abnormality (RWMA), depressed ejection fraction (EF), and dynamic cardiac arrhythmia that persists to some extent during hospitalization in over half of affected patients. We further determined that early elevated cTnI is associated with physical and neuropsychologic disability. We hypothesize that SAHMI blunts dynamic systemic and cerebral perfusion, producing a period of additive perfusion shortfall which contributes to poorer short and long term physical and neuropsychologic functional outcomes. Nurses are responsible for hemodynamic and neurologic monitoring of aSAH patients, but there are no evidence based recommendations driving clinical decisions for SAHMI perfusion support. We propose to utilize newer noninvasive macro and microcirculatory perfusion monitoring to determine SAHMI perfusion impact and develop perfusion supportive recommendations. Our study goal is to develop perfusion goal-directed therapeutic recommendations for SAHMI patients based upon the optimal perfusion parameters associated with better patient functional outcomes. We will determine the influence of SAHMI on dynamic systemic and cerebral perfusion, functional recovery, and SAHMI recovery trajectory. We will recruit 200 patients with aSAH (ages >21-75 years), and assess them for elevated cardiac troponin I, regional wall motion abnormalities and depressed ejection fraction on echocardiogram, and dynamic ectopy and arrhythmia via Holter monitoring. We will also utilize novel yet FDA-approved technologies to assess macro and microcirculatory perfusion impact. This will be accomplished with continuous noninvasive cardiac output monitoring (NICOM), peripheral microcirculatory (near-infrared spectroscopy [NIRS]), cerebral macro circulatory (cerebral perfusion pressure) and cerebral microcirculatory [cerebral NIRS]) perfusion monitoring in SAHMI and no-SAHMI subjects. We will also determine the impact SAHMI has on physical function as well as neuropsychologic function-a more sensitive measure of recovery and reintegration and therefore more reflective of the true burden imposed by SAHMI. We will then use this evidence to guide our development of clinically practicable perfusion goal-directed therapeutic recommendations. Analyses will include various regression modeling approaches as well as classification and regression trees. The application of targeted perfusion therapy at the bedside has the potential to improve outcomes and reduce aSAH burden on patients, the care system, and society.

Public Health Relevance: Data from the proposed study will serve to increase understanding of the complication of myocardial injury after subarachnoid hemorrhage (SAHMI) and its consequences, and permit our development of clinically practicable perfusion goal-directed therapeutic recommendations to support patients and minimize the development of physical and neuropsychological functional disability.