Robert Soufer, MD
Professor of Medicine (Cardiology)Cards
Appointments
Additional Titles
Vice Chair for Clinical Research, Department of Internal Medicine
Associate Chief of Medicine for Faculty Development, Medicine
Contact Info
Appointments
Additional Titles
Vice Chair for Clinical Research, Department of Internal Medicine
Associate Chief of Medicine for Faculty Development, Medicine
Contact Info
Appointments
Additional Titles
Vice Chair for Clinical Research, Department of Internal Medicine
Associate Chief of Medicine for Faculty Development, Medicine
Contact Info
About
Titles
Professor of Medicine (Cardiology)
Vice Chair for Clinical Research, Department of Internal Medicine; Associate Chief of Medicine for Faculty Development, Medicine
Appointments
Cardiovascular Medicine
ProfessorPrimary
Other Departments & Organizations
- Cardiovascular Medicine
- Diabetes Research Center
- Internal Medicine
- Neurobehavioral
- Stress & Addiction Clinical Research Program
- Yale Stress Center
- Yale Ventures
Education & Training
- Research Fellow in Cardiology/Nuclear Medicine Resident
- Yale University School of Medicine (1985)
- Postgraduate Fellow in Cardiology
- Yale University School of Medicine (1984)
- Chief Medical Resident/Assistant Instructor in Medicine
- Downstate Medical Center Kings County Hospital, State University of New York (1982)
- Medical Resident
- Downstate Medical Center Kings County Hospital, State University of New York (1981)
- Straight Medical Intern
- Downstate Medical Center Kings County Hospital, State University of New York (1979)
- MD
- New York Medical College (1978)
- BA
- New York University/Uptown Campus, Chemistry/Philosophy (1975)
- Research Fellow
- Brigham and Women's Hospital/Harvard School of Medicine (1975)
Board Certifications
Nuclear Medicine
- Certification Organization
- AB of Nuclear Medicine
- Original Certification Date
- 1989
Cardiovascular Disease
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1989
Internal Medicine
- Certification Organization
- American Board of Internal Medicine
- Original Certification Date
- 1982
Research
Overview
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.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Matthew Burg, PhD
Frans Wackers, MD, PhD
Lawrence Staib, PhD
Judith Meadows, MD, MPH
Aseem Vashist, MD
Steven Pfau, MD
Stress, Psychological
Cardiovascular Diseases
Publications
2023
The Brain–Heart Axis: Neuroinflammatory Interactions in Cardiovascular Disease
Hu J, Abdullah A, Nanna M, Soufer R. The Brain–Heart Axis: Neuroinflammatory Interactions in Cardiovascular Disease. Current Cardiology Reports 2023, 25: 1745-1758. PMID: 37994952, PMCID: PMC10908342, DOI: 10.1007/s11886-023-01990-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricConceptsHeart-brain axisCardiovascular diseaseRenin angiotensin aldosteroneDevelopment of strokeBrain-heart axisAbnormal atrial substrateParasympathetic nervous systemNeuroimmune modulationNeuroinflammatory interactionsNeurogenic inflammationCardioembolic strokeNeurologic insultProinflammatory factorsCardiac dysfunctionAtrial fibrillationAfferent pathwaysAtrial substrateHypothalamus-pituitary axesSpinal injuryCommon disorderCommon conditionProinflammatory signalsNervous systemRecent FindingsAtPrototypical disorderPromoting Collaborative Scholarship During the COVID-19 Pandemic: Creation and Implementation of an Innovative COVID-19 Data Explorer and Repository (DOM- CovX) at Yale School of Medicine (Preprint)
Victoria-Castro A, Arora T, Simonov M, Biswas A, Alausa J, Subair L, Gerber B, Nguyen A, Hsiao A, Hintz R, Yamamoto Y, Soufer R, Desir G, Wilson F, Villanueva M. Promoting Collaborative Scholarship During the COVID-19 Pandemic: Creation and Implementation of an Innovative COVID-19 Data Explorer and Repository (DOM- CovX) at Yale School of Medicine (Preprint). JMIR Formative Research 2023 DOI: 10.2196/52120.Peer-Reviewed Original ResearchDelirium in older adults after percutaneous coronary intervention: Prevalence, risks, and clinical phenotypes
Park D, Jamil Y, Hu J, Lowenstern A, Frampton J, Abdullah A, Damluji A, Ahmad Y, Soufer R, Nanna M. Delirium in older adults after percutaneous coronary intervention: Prevalence, risks, and clinical phenotypes. Cardiovascular Revascularization Medicine 2023, 57: 60-67. PMID: 37414611, PMCID: PMC10730763, DOI: 10.1016/j.carrev.2023.06.010.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPercutaneous coronary interventionHospital mortalityHigher oddsOlder adultsHospital deliriumCoronary interventionAdverse health-related outcomesInpatient percutaneous coronary interventionNon-home dischargePeri-procedural settingAcute kidney injuryImpact of deliriumPost-procedural complicationsNational Inpatient SampleHealth-related outcomesDelirium preventionHospital complicationsMore comorbiditiesGastrointestinal hemorrhageKidney injuryAdverse eventsSecondary outcomesBlood transfusionPrimary outcomeIntracranial hemorrhage
2020
The Foundational Role of Cardiovascular Imaging in the Characterization of Mental Stress–Induced Myocardial Ischemia in Patients with Coronary Artery Disease
Meadows JL, Shah S, Burg MM, Pfau S, Soufer R. The Foundational Role of Cardiovascular Imaging in the Characterization of Mental Stress–Induced Myocardial Ischemia in Patients with Coronary Artery Disease. Current Cardiology Reports 2020, 22: 162. PMID: 33037938, DOI: 10.1007/s11886-020-01407-w.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsMeSH Keywords and ConceptsConceptsCoronary artery diseaseArtery diseaseMyocardial ischemiaMental Stress–Induced Myocardial IschemiaNon-obstructive coronary artery diseaseStable coronary artery diseaseHalf of patientsEpicardial coronary stenosisMental stress testingMyocardial oxygen demandUnderstanding of pathophysiologyCoronary macroAnginal symptomsCardiac eventsAdverse prognosisEarly mortalityIschemic phenomenaCoronary perfusionCoronary stenosisCoronary microvasculatureInvasive studiesClinical careMyocardial perfusionStress-mediated changesCardiac responseEffects of Psychological Stress on Vascular Physiology: Beyond the Current Imaging Signal
Shah SM, Meadows JL, Burg MM, Pfau S, Soufer R. Effects of Psychological Stress on Vascular Physiology: Beyond the Current Imaging Signal. Current Cardiology Reports 2020, 22: 156. PMID: 33037500, DOI: 10.1007/s11886-020-01406-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsPsychological stressCardiovascular diseaseMental stress-induced myocardial ischemiaStress-induced myocardial ischemiaMental stressVascular smooth muscleMental stress effectsVascular systemCardiovascular imaging modalitiesEntire vascular systemCardiovascular manifestationsVascular effectsMicrovascular resistanceMicrovascular responsesVascular changesVascular mechanismsVascular responsesCardiovascular responsesMyocardial ischemiaLong-term consequencesSmooth muscleMicrovascular compartmentTherapeutic interventionsReviewThis reviewStandardized psychological assessmentsRelationship Between Depressive Symptoms and Health Status in Peripheral Artery Disease: Role of Sex Differences
Jelani Q, Mena‐Hurtado C, Burg M, Soufer R, Gosch K, Jones PG, Spertus JA, Safdar B, Smolderen KG. Relationship Between Depressive Symptoms and Health Status in Peripheral Artery Disease: Role of Sex Differences. Journal Of The American Heart Association 2020, 9: e014583. PMID: 32781883, PMCID: PMC7660812, DOI: 10.1161/jaha.119.014583.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPeripheral artery diseaseDepressive symptomsHealth statusArtery diseaseEQ-5D visual analog scale scoresEQ-5D visual analog scaleVisual analog scale scoreGeneric health statusPeripheral Artery QuestionnaireVascular specialty clinicsAnalog scale scoreHealth status scoresPatient Health QuestionnaireSevere depressive symptomsVisual analog scaleHealth status outcomesWorse health statusAdjusted general linear modelSex differencesPORTRAIT registryPAD diagnosisPAD symptomsAnalog scaleConclusions WomenMean ageCardiovascular Imaging of Biology and Emotion
Meadows JL, Shah S, Burg MM, Pfau S, Soufer R. Cardiovascular Imaging of Biology and Emotion. Circulation Cardiovascular Imaging 2020, 13: e011054. PMID: 32762255, PMCID: PMC9261020, DOI: 10.1161/circimaging.120.011054.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsMental stressEpicardial coronary artery diseaseCoronary artery diseaseExercise-induced changesMicrovascular dysfunctionArtery diseaseObstructive diseaseClinical manifestationsVascular responsesCentral activationCardiovascular healthPathophysiologic changesCardiovascular responsesMyocardial ischemiaPeripheral vasculatureTreatment targetsVascular pathophysiologyPsychosocial determinantsCardiovascular imagingPsychosocial experiencesImplementation studyMS testingTriggers activationCardiovascular biologyDisease
2019
Effect of β-blockers on triggering of symptomatic atrial fibrillation by anger or stress
Lampert R, Burg MM, Jamner LD, Dziura J, Brandt C, Li F, Donovan T, Soufer R. Effect of β-blockers on triggering of symptomatic atrial fibrillation by anger or stress. Heart Rhythm 2019, 16: 1167-1173. PMID: 31171436, PMCID: PMC6759206, DOI: 10.1016/j.hrthm.2019.03.004.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAtrial fibrillationΒ-blockersAF episodesHistory of AFControl periodSymptomatic AF episodesSymptomatic atrial fibrillationΒ-blocker useExclusion of patientsPersistent atrial fibrillationHolter monitoringAF symptomsPatientsPatient exposureCase periodFibrillationMood statesEpisodesEvent monitorDeleterious physiological responsesExposurePhysiological responsesDiary dataSotalol
2017
The interface of emotion and biology in myocardial ischemia: Can we progress using the traditional paradigm?
Soufer R, Burg MM. The interface of emotion and biology in myocardial ischemia: Can we progress using the traditional paradigm? Journal Of Nuclear Cardiology 2017, 24: 783-787. PMID: 28155190, DOI: 10.1007/s12350-016-0762-2.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsBiology
2016
Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1&bgr; 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-1&bgr; Production. Arteriosclerosis Thrombosis And Vascular Biology 2016, 37: 328-340. PMID: 27834690, PMCID: PMC5269510, DOI: 10.1161/atvbaha.116.308507.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisCells, CulturedCoronary Artery DiseaseCoronary VesselsFemaleGenetic Predisposition to DiseaseHumansInflammation MediatorsInterleukin 1 Receptor Antagonist ProteinInterleukin-1betaMacrophagesMaleMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeuropeptidesPhenotypePlaque, AtheroscleroticPrognosisRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSignal TransductionTransfectionUp-RegulationVascular CalcificationConceptsCoronary calcium burdenIL-1β expressionCalcium burdenSerum IL-1β levelsElevated IL-1βIL-1β levelsCoronary artery diseaseInterleukin-1β expressionCalcified coronary arteryCardiovascular deathCardiovascular eventsArtery diseaseIndependent predictorsClinical outcomesVascular calcificationCoronary arteryIL-1βPlaque calciumAtherosclerotic calcificationExperimental atherogenesisInflammatory regulatorsMacrophage interleukinAtherosclerotic plaquesTherapeutic targetProgressive calcification
Links & Media
News
- September 28, 2020
CTRA-Created Yale DOM Covid Explorer Is Important Research Tool
- June 04, 2019Source: Science Blog
Beta Blockers Can Block The Effects Of Stress And Anger In Some Patients
- June 04, 2019Source: U.S. News & World Report
Another Use for Beta Blockers? Curbing A-fib
- June 04, 2019Source: MedPage Today
Stress, Anger Trigger Fewer Afib Episodes With Beta-Blocker Use