Robert Soufer
Yale University School of Medicine, Internal Medicine, Faculty Member
- Robert Soufer joined Yale as a Cardiology fellow and thereafter a Nuclear Medicine Residency. Upon completing his tra... moreRobert Soufer joined Yale as a Cardiology fellow and thereafter a Nuclear Medicine Residency. Upon completing his training, he became an Assistant Professor at Yale. Currently, he is Chief of the Cardiovascular Medicine Section at VA-CT Health Care Systems. Dr. Soufer’s research has been motivated by the pursuit of models for recurring clinical presentations lacking conceptual constructs. He first encountered patients with signs and symptoms of heart failure with normal left ventricular function. This resulted in his seminal publication concerning the description, frequency and mechanism of Diastolic Heart Failure, currently a major cohort of CHF patients. Thereafter he turned his attention to the mediation of emotions such as anger to the development of myocardial ischemia. He established the Yale/VA Positron Emission Tomography Center, one of the first multidisciplinary imaging centers of its kind, dedicated to clinical research and integration of scientists from varied disciplines/approach to answer similar clinical queries not addressed by extant efforts. During this period, he established Yale as one of the earliest centers engaged in CV metabolic imaging. Thereafter, working with the late Neuroscientist P.G. Rakic, he innovated techniques to simultaneously measure cerebral and myocardial blood during emotionally provocative interventions. This resulted in innovative publications of the first dynamic mappings of the brain during the transduction of myocardial ischemia in response to standardized emotionally stressful laboratory intervention in patients. This work shaped and broadened the conceptual construct in Neurocardiac interaction investigation. Specifically, paradigms of emotionally provoked myocardial ischemia, termed MSMI, (Mental Stress Induced Myocardial Ischemia)edit
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During hypoxia, the heart consumes glycogen to generate ATP. Tolerance of repetitive hypoxia logically requires prompt replenishment of glycogen, a process whose regulation is not fully understood. To examine this, we imposed a defined... more
During hypoxia, the heart consumes glycogen to generate ATP. Tolerance of repetitive hypoxia logically requires prompt replenishment of glycogen, a process whose regulation is not fully understood. To examine this, we imposed a defined hypoxic stimulus on the rat heart while varying its workload. In intact rats, hypoxia reduced myocardial glycogen approximately 30% and increased both the fraction of glycogen synthase in its physiologically active (GS I) form (from 0.24 +/- 0.06 to 0.82 +/- 0.07; P < 0.005) and glycogen synthesis (from 0.087 +/- 0.011 to 0.375 +/- 0.046 mumol.g-1.min-1; P < 0.005). Reducing cardiac work (with propranolol or heterotopic transplantation) reduced glycogen breakdown, glycogen synthase activation, and glycogen synthesis in parallel, stepwise fashion in intact rats. Correspondingly, hypoxia increased GS I activity in the perfused heart in vitro, but only under conditions where glycogen was consumed. This suggests myocardial glycogen synthase is activated by systemic hypoxia and catalyzes rapid posthypoxic glycogen synthesis. Hypoxic glycogen synthase activation appears to be a proportionate, wholly intrinsic response to local glycogenolysis, operating to preserve myocardial glycogen stores independent of any extracardiac mediator of carbohydrate metabolism.
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Background The association of depressive symptoms with health status in peripheral artery disease (PAD) is understudied. No reports of differential impact on women have been described. Methods and Results The PORTRAIT (Patient‐Centered... more
Background The association of depressive symptoms with health status in peripheral artery disease (PAD) is understudied. No reports of differential impact on women have been described. Methods and Results The PORTRAIT (Patient‐Centered Outcomes Related to Treatment Practices in Peripheral Artery Disease Investigating Trajectories) registry enrolled 1243 patients from vascular specialty clinics with new or worsening PAD symptoms. Depressive symptoms were assessed at baseline and 3 months using the 8‐Item Patient Health Questionnaire (score ≥10 indicating clinically relevant depressive symptoms). Disease‐specific and generic health status were measured by Peripheral Artery Questionnaire and EQ‐5D Visual Analogue Scale at baseline and 3, 6, and 12 months. An adjusted general linear model for repeated measures was constructed for baseline and 3‐, 6‐, and 12‐month health status outcomes by depressive symptoms at baseline. Differences by sex were tested with interaction effects. The mean ...
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The calcium composition of atherosclerotic plaque has predictive value for increased risk of cardiovascular events. Inflammation is associated with atherosclerotic calcification, but the immune signaling that regulates calcium... more
The calcium composition of atherosclerotic plaque has predictive value for increased risk of cardiovascular events. Inflammation is associated with atherosclerotic calcification, but the immune signaling that regulates calcium mineralization in plaque is minimally understood. The hematopoietic Rac family member, Rac2, modulates the activation of immune cells and has potential to influence plaque osteogenesis. Both aortic plaque from ApoE -/- mice fed a high fat diet and coronary plaque from patients revealed increased Rac1:Rac2 expression ratios, driven by dynamic Rac2 expression, to be associated with calcified plaque. On high fat diet, Rac2 -/- ApoE -/- mice demonstrated comparable serum cholesterol and plaque burden relative to ApoE -/- mice, but histology identified differences in plaque structure and cellularity. MicroCT and calcium-targeted imaging identified increased atherosclerotic calcification, which was associated with elevated expression of osteogenic transcription fact...
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The radionuclide assessment of ventricular performance provides relevant data concerning global and regional systolic and diastolic function, and right as well as left ventricular function. In addition, assessment may be made under... more
The radionuclide assessment of ventricular performance provides relevant data concerning global and regional systolic and diastolic function, and right as well as left ventricular function. In addition, assessment may be made under varying conditions such as exercise or pharmacologic intervention, and technology has been miniaturized such that ambulatory patients can be evaluated during routine activity. This review will address radionuclide cardiologic techniques for evaluating ventricular performance and focus specifically on their applicability to the clinical and investigative study of congestive heart failure.
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The ability of nuclear cardiology techniques to assess myocardial perfusion is vital in the cardiology consultants’ evaluation of patients with suspected or known coronary artery disease. This chapter will begin with a description of the... more
The ability of nuclear cardiology techniques to assess myocardial perfusion is vital in the cardiology consultants’ evaluation of patients with suspected or known coronary artery disease. This chapter will begin with a description of the physiologic principles underlying perfusion imaging. With this intellectual framework, the consultant can employ nuclear cardiology techniques to assist in the diagnosis of coronary artery disease, to assess cardiovascular prognosis and risk stratification, and to guide medical and revascularization strategies in the management of coronary artery disease. This chapter concludes with an overview of the performance of nuclear cardiology tests.
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Research Interests: Psychology, Forecasting, Nuclear medicine, Positron Emission Tomography, Medicine, and 15 moreHumans, Glucose, Fatty acids, Female, Animals, Dilated cardiomyopathy, Positron, Cardiomyopathies, Radioisotopes, Catecholamines, Positron Emission, Myocardial Ischemia, Neoplasm staging, Cardiovascular medicine and haematology, and Ovarian Neoplasms
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ABSTRACTBackgroundThe COVID-19 pandemic has led to an explosion of research publications spanning epidemiology, basic and clinical science. While a digital revolution has allowed for open access to large datasets enabling real-time... more
ABSTRACTBackgroundThe COVID-19 pandemic has led to an explosion of research publications spanning epidemiology, basic and clinical science. While a digital revolution has allowed for open access to large datasets enabling real-time tracking of the epidemic, detailed, locally-specific clinical data has been less readily accessible to a broad range of academic faculty and their trainees. This perpetuates the separation of the primary missions of clinically-focused and primary research faculty resulting in lost opportunities for improved understanding of the local epidemic; expansion of the scope of scholarship; limitation of the diversity of the research pool; lack of creation of initiatives for growth and dissemination of research skills needed for the training of the next generation of clinicians and faculty.ObjectivesCreate a common, easily accessible and up-to-date database that would promote access to local COVID-19 clinical data, thereby increasing efficiency, streamlining and d...
Research Interests: Medicine and Scholarship
BackgroundAnger and stress can trigger episodes of atrial fibrillation (AF) in patients with a history of AF.Objective:To determine whether beta-blockers can protect against emotionally-triggered AF.MethodsIn this prospective, controlled,... more
BackgroundAnger and stress can trigger episodes of atrial fibrillation (AF) in patients with a history of AF.Objective:To determine whether beta-blockers can protect against emotionally-triggered AF.MethodsIn this prospective, controlled, electronic-diary-based study of emotions preceding AF, patients with a history of paroxysmal or persistent AF, (N=91), recorded their rhythm on event-monitor at the time of AF symptoms, and completed a diary entry querying mood states (eg, anger, stress) for the preceding 30 minutes (pre-AF “case period”) for one year. Also, patients underwent monthly 24-hour holter-monitoring, during which they were prompted to complete a diary entry twice per hour. Diaries recorded during sinus comprise the controls. Patients’ exposure to each emotion was compared between the pre-AF case period and control periods using GEE modeling, and interactions between beta-blocker use and emotion tested.ResultsSixty percent were prescribed beta-blockers. 163 symptomatic AF episodes (in 34 patients) and 11,563 holter-confirmed sinus rhythm control periods had associated diary data. Overall, the likelihood of an AF episode was significantly higher during anger or stress. This effect however, was significantly attenuated in the patients on beta-blockers. (OR = 22.5, 95% CI 6.7–75.4, p<0.0001, for non-beta-blocked, versus OR = 4.0, 95% CI 1.7–9.5, p = 0.002 for those prescribed beta-blockers, p =0.02 for the interaction.) Exclusion of patients on sotalol did not impact findings.ConclusionsAnger or stress can trigger AF, but use of beta-blockers greatly attenuates this deleterious physiological response.
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Central activation in response to emotion and cognitive stress induces perturbations in the heart and the peripheral vasculature that differ in physiology and clinical manifestations when compared with exercise-induced changes. While our... more
Central activation in response to emotion and cognitive stress induces perturbations in the heart and the peripheral vasculature that differ in physiology and clinical manifestations when compared with exercise-induced changes. While our conventional framework of epicardial coronary artery disease is foundational in cardiology, an expanded paradigm is required to address the cardiovascular response to mental stress (MS) and its associated risks, thus addressing the intersection of the patient’s ecological and psychosocial experience with cardiovascular biology. To advance the field of MS in cardiovascular health, certain core challenges must be addressed. These include differences in the trigger activation between exercise and emotion, identification and interpretation of imaging cues as measures of pathophysiologic changes, characterization of the vascular response, and identification of central and peripheral treatment targets. Sex and psychosocial determinants of health are impor...
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The effect of positive end-expiratory pressure (PEEP) on right ventricular performance and myocardial blood flow was determined in 16 dogs before and after right coronary artery (RCA) occlusion. Right ventricular ejection fraction (RVEF),... more
The effect of positive end-expiratory pressure (PEEP) on right ventricular performance and myocardial blood flow was determined in 16 dogs before and after right coronary artery (RCA) occlusion. Right ventricular ejection fraction (RVEF), end-diastolic volume (EDV) and end-ejection volume were measured by thermodilution. Right ventricular end-ejection pressure-volume relations (RVEEPVR) were determined at baseline and at 20 cm H2O PEEP, both before and after RCA occlusion. In four of the dogs, RVEEPVR were also determined at 10 cm H2O PEEP after RCA occlusion. With intact RCA flow, RVEF declined with PEEP (37 +/- 5 to 19 +/- 6%) with no significant change in EDV (50 +/- 11 to 42 +/- 11 ml) or end-ejection volume (31 +/- 7 to 36 +/- 9 ml). RVEEPVR and right ventricular myocardial blood flow were also unchanged with PEEP. After RCA occlusion, RVEF declined with PEEP (27 +/- 4 to 15 +/- 5%) in association with a significant increase in end-ejection volume (39 +/- 8 to 49 +/- 10 ml), but no change in EDV (53 to 55 ml). In addition, RVEEPVR and myocardial blood flow declined with RCA occlusion, and declined further with 20 cm H2O, but not with 10 cm H2O PEEP, after RCA occlusion. Therefore, in this experimental model, right ventricular performance was adversely affected during PEEP when right coronary blood flow was limited.
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Evidence points to a significant role for psychological factors in the pathogenesis of cardiovascular disease (CVD). Mental stress, including psychological, psychosocial, or emotional stress, is recognized as a risk factor for the... more
Evidence points to a significant role for psychological factors in the pathogenesis of cardiovascular disease (CVD). Mental stress, including psychological, psychosocial, or emotional stress, is recognized as a risk factor for the development of CVD. It also seems to contribute to the onset of—and can directly precipitate acute—coronary syndromes (ACS), fatal arrhythmias, and acute heart failure.
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Studies suggest that men and women have important differences in specific cognitive functions. Men show superior spatial memory and women demonstrate superior verbal memory, and women rely on emotional content to a greater degree in the... more
Studies suggest that men and women have important differences in specific cognitive functions. Men show superior spatial memory and women demonstrate superior verbal memory, and women rely on emotional content to a greater degree in the processing of information. In spite of extensive research in neural correlates of human cognition, little is known about possible gender differences or the role of emotional content in the mediation of cognition. Two sets of lists of word pairs were developed, one with neutral (e.g., school-grocery) and the other with emotional (e.g., mutilate-beat) content. Male and female subjects were asked to rate emotions related to the words on several dimensions (e.g., nervous, fearful, happy). In a second experiment, men and women underwent positron emission tomographic (PET) measurement of brain blood flow during retrieval of word pairs. Words in the "emotional" category were rated more highly on the emotional dimensions, and women rated them as ha...
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The individual and additive effects of positive end-expiratory pressure (PEEP) and right coronary artery (RCA) occlusion on left ventricular end-diastolic pressure-volume relations (LVEDPVR) were examined in six anesthetized dogs. Right... more
The individual and additive effects of positive end-expiratory pressure (PEEP) and right coronary artery (RCA) occlusion on left ventricular end-diastolic pressure-volume relations (LVEDPVR) were examined in six anesthetized dogs. Right ventricular (RV) and left ventricular (LV) ejection fractions (EF), end-diastolic volume (EDV) and end-systolic volumes (ESV) were measured by thermodilution as PEEP was added before and after RCA occlusion. PEEP alone caused a decline in cardiac output, transmural left atrial pressure (LAP) (6.0 +/- 0.6 to 3.2 +/- 1.4 mm Hg, p less than 0.05), and LVEDV (49 +/- 3 to 36 +/- 4 ml, p less than 0.05). RVEDV, the mean slope (+/- SD) of the LVEDPVR (0.37 +/- 0.16 to 0.30 +/- 0.19) and LAP at a common LV volume (35 ml, V35) did not change with PEEP. RCA occlusion caused cardiac output and RVEF (38 +/- 5 to 27 +/- 5%, p less than 0.05) to decline and RVESV (25 +/- 4 to 33 +/- 6 ml, p less than 0.05) to increase. RVEDV, the slope of the LVEDPVR, and LAP at V...
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Background: Ability of patients (pts) to perform a regular symptom-limited exercise treadmill test (ETT) is well-known favourable predictor of prognosis. However, prognostic impact of the ability to perform an adjunctive low-level... more
Background: Ability of patients (pts) to perform a regular symptom-limited exercise treadmill test (ETT) is well-known favourable predictor of prognosis. However, prognostic impact of the ability to perform an adjunctive low-level exercise (Adeno-Walk) in pts referred to ...
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Research Interests: Cardiology, Risk assessment, Causality, Medicine, Comorbidity, and 13 moreHumans, Ischemia, Incidence, Risk factors, Left Ventricular Dysfunction, Nuclear Cardiology, Mental Stress, Risk Factors, Risk Assessment, Psychological Stress, Clinical Trials as Topic, Myocardial Ischemia, and Cardiovascular medicine and haematology
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The radionuclide measurement of diastolic performance may provide a rapid noninvasive index available in the clinical setting. These measurements may be used to detect coronary artery disease, manifestations of hypertensive heart disease,... more
The radionuclide measurement of diastolic performance may provide a rapid noninvasive index available in the clinical setting. These measurements may be used to detect coronary artery disease, manifestations of hypertensive heart disease, isolated diastolic heart failure, and hypertrophic cardiomyopathy. The various radionuclide methods to measure diastolic filling are influenced by technological considerations, as well as applying the results in the appropriate clinical context. The importance of these derived measurements and how they correspond to various pathophysiological presentations will be discussed.
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Background Experimental data have indicated that [ 99m Tc]- nitroimidazole (BMS-181321) is preferentially taken up in hypoxic tissue; its kinetics, however, has not been fully investigated. The purpose of this study was to address the... more
Background Experimental data have indicated that [ 99m Tc]- nitroimidazole (BMS-181321) is preferentially taken up in hypoxic tissue; its kinetics, however, has not been fully investigated. The purpose of this study was to address the relation between perfusate oxygen level and myocardial retention of [ 99m Tc]nitroimidazole. Methods and Results Bolus injection and constant infusion experiments were performed in Langendorff buffer–perfused rat hearts in normoxic and hypoxic conditions. Data were acquired with a pair of NaI detectors. The initial clearance rate of [ 99m Tc]nitroimidazole was approximately 20 seconds and independent of perfusate oxygen level. The slow clearance rate was greater than 3 hours in all perfusion conditions. The tissue retention of [ 99m Tc]nitroimidazole varied from 0.61±0.14% in normoxic conditions to 5.94±1.16% in the most severe hypoxic conditions. In addition, tissue retention was inversely proportional to perfusate oxygen level in a sigmoidal manner. ...
Research Interests: Hypoxia, Medicine, Isotopes, Animals, Male, and 15 moreExploration, Heart, Perfusion, Clinical Sciences, Isotope, Rats, Oxygen, Myocardium, Public health systems and services research, Rat, Circulation, Oxygen Consumption, Myocardial Ischemia, nitroimidazole, and Cardiovascular medicine and haematology
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Clinical congestive heart failure (CHF) is traditionally associated wtih significant left ventricular (LV) systolic dysfunction. Over a 1-year period, 58 patients with CHF and intact systolic function (LV ejection fraction [EF] 62 +/-... more
Clinical congestive heart failure (CHF) is traditionally associated wtih significant left ventricular (LV) systolic dysfunction. Over a 1-year period, 58 patients with CHF and intact systolic function (LV ejection fraction [EF] 62 +/- 11%) were identified. An objective clinical-radiographic CHF score was used to document the clinical impression. Based on radionuclide evaluation of peak filling rate, 38% of these patients were found to have a significant abnormality in diastolic function as measured by peak filling rate (less than 2.50 end-diastolic volume/s). An additional 24% of the patients had probable diastolic dysfunction with borderline abnormal peak filling rate measurements (2.5 to 3.0 end-diastolic volume/s). The disease states most frequently associated with CHF and intact systolic function were coronary artery disease and systemic hypertension. During a 3-month sampling period 42% of patients with clinical diagnosis of CHF referred to the nuclear cardiology laboratory were found to have intact systolic function; thus, intact systolic function is not uncommon in patients with clinical CHF. Abnormal diastolic function is the most frequently encountered mechanism for the occurrence of CHF. Definition of systolic and diastolic function appears relevant for development of optimal therapeutic strategies for the treatment of patients with CHF.
Research Interests: Cardiology, Medicine, Heart Failure, Humans, Internal Medicine, and 14 moreCongestive Heart Failure, Aged, Middle Aged, Adult, Cardiac Output Monitoring, Coronary Artery Disease, Ejection Fraction, Left Ventricular Function, Heart Ventricles, The American, Cardiac output, Diastole, systole, and Cardiovascular medicine and haematology
Research Interests: Cardiology, Surgery, Medicine, Humans, Derivation, and 14 moreInternal Medicine, Ischemia, Male, Heart, Artery, Myocardial Infarction, Adult, Coronary heart disease, Coronary Artery Disease, Heart Ventricles, Revascularization, Coronary artery bypass graft, Cardiovascular medicine and haematology, and Coronary Artery Bypass
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The calcium composition of atherosclerotic plaque is thought to be associated with increased risk for cardiovascular events, but whether plaque calcium itself is predictive of worsening clinical outcomes remains highly controversial.... more
The calcium composition of atherosclerotic plaque is thought to be associated with increased risk for cardiovascular events, but whether plaque calcium itself is predictive of worsening clinical outcomes remains highly controversial. Inflammation is likely a key mediator of vascular calcification, but immune signaling mechanisms that promote this process are minimally understood. Here, we identify Rac2 as a major inflammatory regulator of signaling that directs plaque osteogenesis. In experimental atherogenesis, Rac2 prevented progressive calcification through its suppression of Rac1-dependent macrophage interleukin-1β (IL-1β) expression, which in turn is a key driver of vascular smooth muscle cell calcium deposition by its ability to promote osteogenic transcriptional programs. Calcified coronary arteries from patients revealed decreased Rac2 expression but increased IL-1β expression, and high coronary calcium burden in patients with coronary artery disease was associated with sign...
Research Interests: Biology, Atherosclerosis, Inflammation, Calcium, Macrophages, and 15 moreMedicine, Neuropeptides, Humans, Macrophage, Female, Animals, Male, Phenotype, Clinical Sciences, Coronary Artery Disease, Aorta, Calcification, Cardiovascular medicine and haematology, Coronary Vessels, and Inflammation Mediators
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Research Interests: Psychology, Depression, Risk, Medicine, Psychosomatic Medicine, and 15 moreProspective studies, Humans, Internal Medicine, Male, Veterans, Follow-up studies, Aged, Middle Aged, Adult, Cardiovascular Diseases, Coronary artery bypass surgery, Postoperative Period, Psychology and Cognitive Sciences, Medical and Health Sciences, and Coronary Artery Bypass
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Although positron emission tomography (PET) provides important physiological information, a major limitation of this technique is poor anatomical resolution. Combining the superior anatomical resolution of magnetic resonance imaging (MRI)... more
Although positron emission tomography (PET) provides important physiological information, a major limitation of this technique is poor anatomical resolution. Combining the superior anatomical resolution of magnetic resonance imaging (MRI) with the physiologic information of PET could be an important advance for clinical and research applications of PET. The purpose of this study was to develop reliable methods for using MRI in the definition of brain regions of interest (ROIs) for application to coregistered PET brain images. First, specific criteria were developed for definition of ROIs on coregistered MRI using anatomical landmarks from a standard anatomical atlas. ROIs were then drawn by three independent raters using the criteria on 11 MRI scans, which had been coregistered to PET [(18)F]2-fluoro-2-deoxyglucose (FDG) brain scans. These MRI-based templates were used to determine activity in various brain regions on the PET scans, which were used in the determination of regional brain metabolic rates. There was a high level of agreement between raters for the measurement of regional metabolic rates, with intra-class correlation coefficients ranging from 0.63-0.98. These findings suggest that specific ROI criteria based on coregistered MRI are a reliable method of measuring activity from PET images. The use of a standard and widely available atlas and readily applicable criteria for ROIs should facilitate a standard method of measurement which can be applied in a similar manner at different PET sites.
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Positron emission tomography was used to quantify changes in myocardial blood flow during mental stress in patients with and without coronary artery disease. Blunted augmentation of myocardial blood flow during mental stress was observed... more
Positron emission tomography was used to quantify changes in myocardial blood flow during mental stress in patients with and without coronary artery disease. Blunted augmentation of myocardial blood flow during mental stress was observed in regions without significant epicardial stenosis.