Research Departments & Organizations
Dr. Soufer’s research effort deals with the elucidation of the interaction between the brain and the heart. His research integrates Cardiology, Neurobiology, Psychology and Nuclear Medicine. Specifically, he and his colleagues have elucidated Brain and Heart interactions of emotion and stress culminating in progressive myocardial ischemia (“low blood flow”) resulting in myocardial infarction (“heart attack”). His research efforts aresingular in methodology which simultaneously measures brain activation and myocardial perfusion and function with Positron Emission Tomography during a laboratory stress intervention. His group was the first to establish specific brain activation patterns associated with myocardial ischemia, which results from emotional provocation.
Specialized Terms: Neurobehavioral Correlates of Mental Stress in Cardiovascular Disease; Neuro-Cardiac Interaction; Mental Stress; Myocardial Blood Flow
Extensive Research Description
Data show that psychological factors play an important role in acute coronary syndromes. We and others, have found mentally demanding tasks such as mental arithmetic to provoke ischemia in approximately 50% of patients with ischemic heart disease. We have also found a specific psychological profile, characterized by emotional reactivity, and easily aroused anger and hostility, to be associated with this “mental stress ischemia”; conversely, we have not found an association between this profile and exercise ischemia. Follow up of these mental stress positive patients reveal a significantly poorer 1-2 year prognosis. Hence, mental stress ischemia may be a distinct phenomenon with unique risk factors and prognosis. The mechanisms of mental stress ischemia are, however, not well understood. Critical questions remain regarding the ways by which mental and psychological factors contribute to coronary syndromes. We believe that psychological, neurobiological and coronary vasomotor processes are key factors, expanding upon our pilot work, conducted in the context of our current funding. We are examining the functional CNS correlates of mental stress ischemia; these CNS correlates will be defined by positron emission tomography (PET) conducted while patients perform an arithmetic task that we have found to reliably provoke ischemia in half of those we have studied. This approach will illuminate CNS processes that may be serving to transduce mental stress susceptibility into risk for acute coronary events. Specific issues concerning gender interaction and relationship to psychological profiles/coping styles are currently being explored.
The overarching research theme of our research is the elucidation of those mechanisms, which transduce cognitive stress as a provocation of myocardial ischemia. Specifically, we are interested in the neurobiology and coronary flow dynamics that results from mentally stressful tasks. Our work utilizes simultaneous measurements of brain activation and myocardial function/coronary flow with PET imaging, echocardiography and pulse arterial tonometry during laboratory mental stress. We are developing conceptual constructs based upon our previous work, which support a model that suggests certain regional and global brain activation maps are associated with coronary flow responses specific to psychosocial stress.
Our goal for the next academic year is to describe the pathophysiologic mechanisms of mental stress induced myocardial ischemia that differs from those that are a result of exercise. We have the largest series of subjects to date (n=138) undergoing simultaneous imaging with PET during Mental Stress and then again with dobutamine as a surrogate for exercise in a population of CAD subjects. Our results thus far support our hypothesis of regional activation in the brain that promote parasympathetic withdrawal, increase in sympathetic tone and decrease LV flow/ function that is not observed in the dobutamine group (exercise surrogate) is thus far confirmed. A manuscript based on these results is in preparation. We have studies that show a gender interaction that has just been analyzed and these data will be prepared and submitted afterwards.
An individual’s biological substrate interacts within this neurobehavioral context thru genetic, endocrine, immune and neural processes. Many of these processes are shape by inflammatory responses. Our previous published reports reinforced the principle that inflammatory processes may also be associated with other dimensions of CAD expression. In this past year we have expanded our constructs regarding the role of other vascular factors, which may be operative during Mental Stress Ischemia. Specifically our recent data suggests an up regulation of ET-1 among CAD patients who are subjected to a standardized Anger recall paradigm. We have also described these findings in the context of the parasympathetic inflammatory response, which predicts such increases in response to w withdrawal of parasympathetic tone, a cardinal feature of Mental Stress Induced Myocardial Ischemia. We have observed an inverse relationship of TNF-alpha and parasympathetic withdrawal in subjects who become ischemic and have specific regional brain activation coincident with this process. Finally, we have developed and published a noninvasive stress test to index those most vulnerable to Mental Stress Ischemia.
Title: Depression and Coronary Disease: Prognosis and Mechanisms.The objectives of this project are to explore prognosis in subjects with CAD and depression after percutaneous intervention.
Title: Neurobehavioral Correlates of Mental Stress Ischemia. The objectives of this project are to examine CNS involvement in mental stress ischemia, using a combination of modalities, including positron emission tomography and echocardiography.
Title: Neurobehavioral Correlates of Mental Stress Ischemia: Supplement for Serological Core Lab.
The objectives of this project are to examine the inflammatory underpinnings of MSI.
Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1β Production.
Ceneri N, Zhao L, Young BD, Healy A, Coskun S, Vasavada H, Yarovinsky TO, Ike K, Pardi R, Qin L, Qin L, Tellides G, Hirschi K, Meadows J, Soufer R, Chun HJ, Sadeghi M, Bender JR, Morrison AR. Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1β Production. Arteriosclerosis, Thrombosis, And Vascular Biology 2017, 37:328-340. 2017
Body Mass Index and Risk for Mental Stress Induced Ischemia in Coronary Artery Disease.
Soufer R, Fernandez AB, Meadows J, Collins D, Burg MM. Body Mass Index and Risk for Mental Stress Induced Ischemia in Coronary Artery Disease. Molecular Medicine (Cambridge, Mass.) 2016, 22:286-291. 2016
Post-traumatic Stress Disorder and Cardiovascular Disease.
Burg MM, Soufer R. Post-traumatic Stress Disorder and Cardiovascular Disease. Current Cardiology Reports 2016, 18:94. 2016
Confluence of depression and acute psychological stress among patients with stable coronary heart disease: effects on myocardial perfusion.
Burg MM, Meadows J, Shimbo D, Davidson KW, Schwartz JE, Soufer R. Confluence of depression and acute psychological stress among patients with stable coronary heart disease: effects on myocardial perfusion. Journal Of The American Heart Association 2014, 3:e000898. 2014
Triggering of symptomatic atrial fibrillation by negative emotion.
Lampert R, Jamner L, Burg M, Dziura J, Brandt C, Liu H, Li F, Donovan T, Soufer R. Triggering of symptomatic atrial fibrillation by negative emotion. Journal Of The American College Of Cardiology 2014, 64:1533-4. 2014
Therapy for Mental Stress-Induced Myocardial Ischemia
Burg M, Soufer, R. Therapy for Mental Stress-Induced Myocardial Ischemia. JAMA 2013;310(13):1400-1401. 2013
Autonomic contribution to endothelin-1 increase during laboratory anger-recall stress in patients with coronary artery disease.
Burg MM, Soufer A, Lampert R, Collins D, Soufer R. Autonomic contribution to endothelin-1 increase during laboratory anger-recall stress in patients with coronary artery disease. Molecular Medicine (Cambridge, Mass.) 2011, 17:495-501. 2011
Mechanistic and Methodological Considerations for the Imaging of Mental Stress Ischemia. Chapter in Clinical Nuclear Cardiology: State of the Art and Future Directions, 4rd Edition.
Soufer R, Burg M, Fernandez A. Mechanistic and Methodological Considerations for the Imaging of Mental Stress Ischemia. Chapter in Clinical Nuclear Cardiology: State of the Art and Future Directions, 4rd Edition, 2010; Ed Zaret and Beller. 2010
Anger-induced T-wave alternans predicts future ventricular arrhythmias in patients with implantable cardioverter-defibrillators.
Lampert R, Shusterman V, Burg M, McPherson C, Batsford W, Goldberg A, Soufer R. Anger-induced T-wave alternans predicts future ventricular arrhythmias in patients with implantable cardioverter-defibrillators. Journal Of The American College Of Cardiology 2009, 53:774-8. 2009
C-reactive protein and vulnerability to mental stress-induced myocardial ischemia.
Shah R, Burg MM, Vashist A, Collins D, Liu J, Jadbabaie F, Graeber B, Earley C, Lampert R, Soufer R. C-reactive protein and vulnerability to mental stress-induced myocardial ischemia. Molecular Medicine (Cambridge, Mass.) 2006, 12:269-74. 2006
Quantitative myocardial blood flow response to mental stress in patients with chronic coronary artery disease: Correlation with coronary angiography and comparison with flow responses in normals
Arrighi JA, Burg MM, Cohen IS, Kao AH, Pfau S, Caulin-Glaser T, Zaret BL, and Soufer R. “Quantitative myocardial blood flow response to mental stress in patients with chronic coronary artery disease: Correlation with coronary angiography and comparison with flow responses in normals.” Lancet 2000; 356:310-311. 2009
Cerebral cortical Hyper activation in response to mental stress patients with coronary artery disease
Soufer R, Bremner JD, Arrighi JA, Cohen I, Zaret BL, and Goldman-Rakic P. “Cerebral cortical Hyper activation in response to mental stress patients with coronary artery disease.” Proc. Natl. Acad. Sci. USA 1998; 95:6454-6459. 1998