TITLE: Atrial Fibrillation Precursors May Be Novel Stroke Risk Factors PROJECT SUMMARY/ABSTRACT This is a K23 resubmission application for Dr. Hooman Kamel, a neurologist and young investigator pursuing patient-oriented clinical research on ischemic stroke caused by cardiac arrhythmias. A K23 award will provide him with the means to acquire critical skills in three key career development areas: 1) epidemiology and clinical trial design, 2) cardiac diagnostic techniques, and 3) biomarker development and assessment. By acquiring these skills, Dr. Kamel will fulfill his long-term career goal of becoming an independent clinical investigator. To pursue this goal, Dr. Kamel has recruited a primary mentor, Dr. Richard Devereux, a cardiologist with expertise in cardiovascular epidemiology and cardiac diagnostic techniques, and two co- mentors, Dr. Mitchell Elkind, a neurologist with expertise in stroke epidemiology and clinical trial design, and Dr. Costantino Iadecola, a neurologist with expertise in ischemic brain injury and biomarkers. Based on recent evidence and his own preliminary data, Dr. Kamel's central hypothesis is that supraventricular arrhythmias increase stroke risk even before the development of atrial fibrillation/flutter (AF), which is currently the only cardiac arrhythmia thought to cause stroke. Testing this hypothesis will address a fundamental gap in knowledge about which supraventricular arrhythmias cause stroke. Until this knowledge gap is filled, optimal strategies for preventing stroke from cardiac disease cannot be fully determined. By pursuing the following specific aims, the applicant will test his hypothesis and gather data for a population- based study of stroke risk from supraventricular arrhythmias (to be proposed in an R01 application during the K23 award period).
Specific Aim 1 will test the hypothesis that electrocardiographic P-wave dispersion, an early marker of atrial electrical dysfunction and predisposition to supraventricular arrhythmias, is associated with an increased risk of stroke.
This aim will be pursued by analyzing a cohort without AF enrolled in the Strong Heart Study, a population-based epidemiological study with baseline electrocardiographic data and >375 adjudicated and classified cases of stroke.
Specific Aim 2 will test the hypothesis that supraventricular ectopy is associated with cryptogenic stroke. In a prospectively enrolled series of patients, rates of supraventricular ectopy during cardiac monitoring will be compared between 75 patients with cryptogenic stroke and 75 patients with stroke from small-vessel occlusion or large-artery atherosclerosis. Secondary analyses will compare biomarkers of cardiac embolism between the two groups, and correlate rates of supraventricular ectopy with these biomarkers.
Specific Aim 3 will test the hypothesis that clinical diagnoses of paroxysmal supraventricular tachycardia are associated with the risk of stroke after transient ischemic attack.
This aim will be pursued using a validated ICD-9-CM code for paroxysmal supraventricular tachycardia and linked medical records from the California State Inpatient Database and Emergency Department Database. The proposed research is significant because positive results will uncover novel stroke risk factors, while negative results will counter the increasing off-label use of unproven anticoagulant therapy for nonspecific supraventricular arrhythmias after cryptogenic stroke. The proposed research is innovative because it seeks to shift current research and clinical practice paradigms by identifying a large new class of patients who are at high risk for stroke and may benefit from existing anticoagulant drugs, and also seeks to bridge cardiology and neurology via the new application of cardiology tools to stroke research.

Public Health Relevance

Atrial Fibrillation Precursors May Be Novel Stroke Risk Factor. The proposed research is relevant to public health because the discovery of novel cardiac risk factors for ischemic stroke will ultimately improve risk factor screening and stroke prevention efforts, thereby reducing the incidence of a disabling and lethal disease. Thus, the proposed research is relevant to the part of the NINDS's mission that involves reducing the burden of neurological disease by fostering research on the causes and prevention of stroke.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23NS082367-01A1
Application #
8634871
Study Section
NST-2 Subcommittee (NST)
Program Officer
Moy, Claudia S
Project Start
2013-09-01
Project End
2018-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$187,483
Indirect Cost
$13,888
Name
Weill Medical College of Cornell University
Department
Neurology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Chen, Monica Lin; Gupta, Ajay; Chatterjee, Abhinaba et al. (2018) Association Between Unruptured Intracranial Aneurysms and Downstream Stroke. Stroke 49:2029-2033
Kamel, Hooman; Bartz, Traci M; Elkind, Mitchell S V et al. (2018) Atrial Cardiopathy and the Risk of Ischemic Stroke in the CHS (Cardiovascular Health Study). Stroke 49:980-986
Murthy, Santosh B; Cushman, Mary; Bobrow, Dylan et al. (2018) Ability of the Khorana score to predict recurrent thromboembolism in cancer patients with ischemic stroke. J Clin Neurosci 57:111-115
Merkler, Alexander E; Gialdini, Gino; Lerario, Michael P et al. (2018) Population-Based Assessment of the Long-Term Risk of Seizures in Survivors of Stroke. Stroke 49:1319-1324
Alkhachroum, Ayham M; Rubinos, Clio; Kummer, Benjamin R et al. (2018) Risk of seizures and status epilepticus in older patients with liver disease. Epilepsia 59:1392-1397
Morris, Nicholas A; May, Teresa L; Motta, Melissa et al. (2018) Long-term risk of seizures among cardiac arrest survivors. Resuscitation 129:94-96
Merkler, Alexander E; Gialdini, Gino; Kamel, Hooman (2018) Response by Merkler et al to Letter Regarding Article, ""Safety Outcomes After Percutaneous Transcatheter Closure of Patent Foramen Ovale"". Stroke 49:e17
Parikh, Neal S; Merkler, Alexander E; Kummer, Benjamin R et al. (2018) Ischemic Stroke After Emergency Department Discharge for Symptoms of Transient Neurological Attack. Neurohospitalist 8:135-140
Chatterjee, Abhinaba; Chen, Monica; Gialdini, Gino et al. (2018) Trends in Tracheostomy After Stroke: Analysis of the 1994 to 2013 National Inpatient Sample. Neurohospitalist 8:171-176
Liberman, Ava L; Gialdini, Gino; Bakradze, Ekaterina et al. (2018) Misdiagnosis of Cerebral Vein Thrombosis in the Emergency Department. Stroke 49:1504-1506

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