F J Wackers

Yale-New Haven Hospital, New Haven, Connecticut, United States

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Publications (199)1281.25 Total impact

  • Frans J Th Wackers
    Journal of Nuclear Cardiology 04/2014; · 2.85 Impact Factor
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    Frans J Th Wackers, Jeffrey A Leppo
    Journal of Nuclear Cardiology 12/2012; · 2.85 Impact Factor
  • Frans J Th Wackers
    Journal of Nuclear Cardiology 01/2012; 19(2):220-3. · 2.85 Impact Factor
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    ABSTRACT: Gender differences in cardiovascular outcomes were compared in asymptomatic men and women with type 2 diabetes (T2DM) in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Of 1123 participants, 290 men and 271 women were randomised to screening with stress myocardial perfusion imaging (MPI); 311 men and 251 women were randomised to no screening. Follow-up was 4.8±0.9 years for the occurrence of cardiac events (CE; cardiac death or non-fatal myocardial infarction). The frequency of abnormal screening was similar in men (24%) and women (19%), (p=0.2), although women trended to have smaller MPI abnormalities. CE rates were lower in women than men (1.7% vs. 3.8%, p=0.04). No CEs occurred in 17 high-risk (UKPDS risk engine) women, whereas 14 (11.2%) occurred in 125 high-risk men. Asymptomatic women with T2DM have significantly better cardiac outcomes than their male counterparts and represent a subgroup for which screening for coronary artery disease does not appear warranted.
    Diabetes & Vascular Disease Research 01/2012; 9(2):124-30. · 2.59 Impact Factor
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    Frans J Th Wackers
    Journal of the American College of Cardiology 05/2010; 55(18):1975-8. · 14.09 Impact Factor
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    Frans J Th Wackers
    Journal of the American College of Cardiology 09/2009; 54(6):546-8. · 14.09 Impact Factor
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    Frans J Th Wackers, Lawrence H Young
    Journal of Nuclear Cardiology 09/2009; 16(6):855-9. · 2.85 Impact Factor
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    Journal of Nuclear Medicine Technology 10/2008; 36(3):155-61.
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    ABSTRACT: We sought to assess prospectively the evidence for silent coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes mellitus by stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging, coronary artery calcium (CAC) scoring, and multislice computed tomographic (MSCT) coronary angiography. One hundred asymptomatic patients (aged 30 to 72 years) with type 2 diabetes mellitus and one or more risk factors for CAD were prospectively recruited from an outpatient diabetes clinic. All patients underwent adenosine technetium-99m sestamibi SPECT imaging, CAC scoring, and 64-slice MSCT coronary angiography. Twenty-three patients (23%) had abnormal stress SPECT imaging, consistent with inducible myocardial ischemia, whereas 60 patients (60%) had positive CAC scoring (18 patients [18%] with significant CAC >401), and 70 patients (70%) had abnormal MSCT coronary angiography (24 patients [24%] with significant, >or=50% stenosis). Of 77 patients with normal SPECT, 44 had a positive CAC score (10 patients [13%] >401), and 54 showed CAD on MSCT angiography (16 patients [21%] with >or=50% stenosis). Of 23 patients with an abnormal SPECT, 16 patients had a positive CAC score (8 patients [35%] >401), and 16 patients had CAD on MSCT angiography (8 patients [35%] with >or=50% stenosis). Overall, 17 patients (17%) had more than 2 significantly abnormal diagnostic test results, and 5 patients had three tests with significantly abnormal results. In this cohort of asymptomatic patients with type 2 diabetes mellitus, different modalities visualized different aspects of silent coronary atherosclerosis. Anatomic evidence of coronary atherosclerosis (CAC and MSCT) occurred more frequently than functional evidence (stress SPECT). However, clinically significant manifestations of CAD were observed in about one-quarter to one-fifth of patients by each modality, either separately or combined. The relative prognostic value of each modality needs to be determined by a follow-up of this cohort.
    Journal of Nuclear Cardiology 01/2008; 15(4):503-9. · 2.85 Impact Factor
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    Todd D Miller, Rita F Redberg, Frans J T Wackers
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    ABSTRACT: Given the elevated risk of cardiovascular events and the higher prevalence of silent coronary artery disease (CAD) in diabetic versus non-diabetic patients, screening asymptomatic diabetic patients for CAD is an appealing concept. However, many factors argue against implementing a broad-based screening program at the present time. Foremost is the lack of any published data demonstrating that a prospectively applied screening program improves outcome in asymptomatic diabetic patients. The true prevalence of CAD, and in particular prognostically important CAD, in this population is uncertain. Consensus documents recommend more aggressive treatment of hypertension and hyperlipidemia solely on the basis of diabetes status, without differentiation based on the presence or absence of identifiable CAD. There is no evidence that use of anti-ischemic medication can alter the natural history of CAD in these patients. Retrospectively performed studies using stress single-photon emission computed tomography (SPECT) imaging have reported that approximately 50% and 20% of patients have abnormal and high-risk images, respectively. However, the only prospectively designed study, the DIAD (Detection of Ischemia in Asymptomatic Diabetics) study, reported a much lower percentage of abnormal SPECT images (16%) and images with a very large (>/=10% of the left ventricle) defect (1%). The financial implications of screening all asymptomatic diabetic patients determined to be at intermediate and high risk by clinical scoring systems is enormous. Clearly more data are needed to address this issue. Future studies should consider possible methods to enrich the patient subset that might benefit from screening and should include carefully performed cost-effective analyses.
    Journal of the American College of Cardiology 08/2006; 48(4):761-4. · 14.09 Impact Factor
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    ABSTRACT: Objective: The aim of this multicenter study was to evaluate the diagnostic performance of a hybrid SPECT/CT attenuation correction system for the detection of angiographic coronary artery disease (CAD).Methods: One hundred and fifty-two patients were included in this study. Eighty-three had angiographic CAD ≷50%, 32 patients (pts) had angiographic insignificant CAD (of whom 24 pts had 0% stenosis), and 37 subjects were normal volunteers with < 3% likelihood of CAD. All pts had exercise-rest Tc-99m-Sestamibi SPECT imaging using a hybrid SPECT/CT gamma camera system. SPECT and CT images were acquired sequentially without patient movement. Images were reconstructed using filtered back projection method without attenuation correction (NC) and ordered subset expectation maximization method with non-uniform attenuation correction (AC). Reconstructed images were smoothed using a conventional Butterworth filter. All images were interpreted by two expert readers (GD, RT) who were blinded to the pts' clinical information. Images were scored by consensus on a 5-point scale (1:definitely normal; 5:definitely abnormal) for construction of receiver operating characteristic (ROC) curves. Coronary stenosis ≷50% was considered abnormal (CAD+) and < 50% normal (CAD-). Normalcy rate was determined in the normal volunteers (NL).Results: Fig. 1 shows the ROC analysis for NC and AC. Using NL as normal reference, specificity was higher as compared to CAD- as normal. Sensitivity, specificity, predictive accuracy and normalcy were improved using AC (Fig. 2>). However, specificity was relative low due to referral bias.Conclusion: CT-based AC SPECT performs better in detecting CAD than NC SPECT, with improved specificity and normalcy rate and preserved sensitivity and predictive accuracy. Figure 1.
    Journal of Nuclear Cardiology 01/2004; 11(4). · 2.85 Impact Factor
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    ABSTRACT: Background: Many patients with type 2 Diabetes Mellitus (T2DM) have cardiac autonomic neuropathy (CAN), which has been associated with poor outcome. CAN is also associated with blunted heart rate response (HRR) to dipyridamole infusion. Furthermore in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study CAN was associated with moderate and large myocardial perfusion defects. Therefore, we hypothesized that blunted HRR during adenosine infusion is associated with myocardial perfusion abnormalities and silent myocardial ischemia.Methods: 442 asymptomatic patients with T2DM, without known coronary artery disease who were enrolled in DIAD study, had quantitative adenosine-Tc-99m-Sestamibi SPECT imaging. Heart rate response to adenosine infusion was assessed as the ratio between baseline HR and HR at end of adenosine infusion. Myocardial perfusion defects were quantified and categorized as small, moderate and large.Results: Mean age of patients was 60.5± 6.8 years; females 47%; males 53%; T2DM duration 8.1 ± 7.1 years. 7% of the patients had either moderate or large perfusion abnormalities. Patients in the lowest decile of HRR (< 1.10), the cut point used to define an abnormal response, were more likely to have moderate or large perfusion abnormalities (OR=3.0, 95% CI 1.2, 7.0; p = .01). The sensitivity of lower HRR to predict moderate to large myocardial perfusion defects was 24% and specificity was 90%. The negative predictive value was 94%.Conclusion: In asymptomatic patients with T2DM a blunted HRR to adenosine infusion is a simple marker with high negative predictive value and high specificity for moderate and large silent myocardial ischemia.
    Journal of Nuclear Cardiology 01/2004; 11(4). · 2.85 Impact Factor
  • Yi-Hwa Liu, D. Khaimov, A.J. Sinusas, F.J.Th. Wackers
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    ABSTRACT: We present a novel counts- and geometry-based method for gated single photon emission computerized tomography (SPECT) quantification to assess myocardial thickness, left ventricular (LV) volumes and ejection fraction (EF). A median search approach and integrated counts strategy were used to determine the endo- and epi-cardial boundaries of the LV. The method was validated using 6 cardiac phantoms with a wide range of wall thicknesses from 6 mm to 16 mm and LV volumes from 33 mL to 128 mL. Tc-99m radioactive isotope with a concentration of 2.5 μCi/mL was injected into the phantoms to simulate normal myocardial perfusion. Two solid plastic inserts were placed in the simulated myocardium of phantoms to mimic dense perfusion defect. Phantom was submerged into a cylindrical tank filled with water to simulate photon attenuation of the human body. A total of 72 image acquisitions were acquired. Images were reconstructed, filtered, reorientated, aligned and computer animated to generate an 11-bin image sequence of simulated gated SPECT. Phantom wall thickness, volumes, and ejection fraction were calculated from the simulated gated SPECT. Correlations between SPECT quantified and actual values of thickness, volume and ejection fraction simulated by the phantoms were excellent. The quantitative results were not significantly affected by the dense perfusion defects simulated. In conclusion, the method developed is feasible to detect the LV boundaries and allows for precise estimation of myocardial thickness, LV volumes and ejection fraction as simulated by phantoms. Further patient validation for the method is warranted for clinical application.
    Nuclear Science Symposium Conference Record, 2003 IEEE; 11/2003
  • Sachin M Navare, Frans J T Wackers, Yi-Hwa Liu
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    ABSTRACT: Electrocardiographic (ECG) gated single-photon emission tomography (SPET) allows for simultaneous assessment of myocardial perfusion and left ventricular (LV) function. Presently 8-frame per cardiac cycle ECG gating of SPET images is standard. The aim of this study was to compare the effect of 8-frame and 16-frame gated SPET on measurements of LV volumes and to evaluate the effects of the presence of myocardial perfusion defects and of radiotracer dose administered on the calculation of LV volumes. A total of 86 patients underwent technetium-99m SPET myocardial perfusion imaging using 16-frame per cardiac cycle acquisition. Eight-frame gated SPET images were generated by summation of contiguous frames. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were calculated from the 16-frame and 8-frame data sets. The patients were divided into groups according to the administered dose of the radiotracer and the size of the perfusion defect. Results. Sixteen frame per cardiac cycle acquisition resulted in significantly larger EDV (122+/-72 ml vs 115+/-68 ml, P<0.0001), smaller ESV (64+/-58.6 ml vs 67.6+/-59.5 ml, P<0.0001), and higher LVEF (55.3%+/-18% vs 49%+/-17.4%, P<0.0001) as compared to 8-frame SPET imaging. This effect was seen regardless of whether a high or a low dose was administered and whether or not significant perfusion defects were present. This study shows that EDV, ESV and LVEF determined by 16-frame gated SPET are significantly different from those determined by 8-frame gated SPET. The radiotracer dose and perfusion defects do not affect estimation of LV parameters by 16-frame gated SPET.
    European journal of nuclear medicine and molecular imaging 10/2003; 30(10):1330-7. · 5.11 Impact Factor
  • Frans J Th Wackers
    Journal of Nuclear Cardiology 07/2002; 9(4):438-40. · 2.85 Impact Factor
  • Frans J T Wackers
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    ABSTRACT: The development of reliable and accurate devices for the correction of nonuniform soft tissue attenuation is essential for the future clinical use of SPET myocardial perfusion imaging. In addition to abolishing false-positive defects, which is the chief goal, such corrected SPET images may allow for improved detection of coronary artery disease and perhaps ultimately for true quantification of regional myocardial blood flow. Although progress has been made, most existing attenuation correction devices are not yet ready for prime time. To date the literature shows as many positive results as negative results. There is considerable uncertainty, confusion, and skepticism about the true reliability and value of currently available attenuation correction packages. Although commonly referred to as "attenuation correction devices," these packages are in fact much more complex systems and contain novel mechanical designs, novel image acquisition and image reconstruction algorithms, scatter correction, and depth-dependent resolution compensation, in addition to attenuation correction. Each of these variables needs to be better understood and tested prior to clinical implementation. Although the general concepts are shared, there are as may different approaches to attenuation correction as there are vendors. In order to minimize the confusion of potential buyers about such complex systems, it is desirable that, before attenuation correction is implemented in routine clinical practice, each attenuation correction device is rigorously tested using a standardized testing protocol. Potential buyers of equipment should be able to compare the results of testing with various devices against predefined criteria in order to make an educated decision. Such standards have as yet not been developed. At the present time it is unclear whether attenuation correction of cardiac SPET will remain the emperor's new clothes or will develop into a fashionable Armani suit. Until further progress has been made, one cannot recommend attenuation correction devices for routine clinical practice.
    European journal of nuclear medicine and molecular imaging 04/2002; 29(3):412-5. · 5.11 Impact Factor
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    ABSTRACT: Insulin-induced hypoglycemia occurs commonly in intensively treated patients with type 1 diabetes, but the cardiovascular consequences of hypoglycemia in these patients are not known. We studied left ventricular systolic [left ventricular ejection fraction (LVEF)] and diastolic [peak filling rate (PFR)] function by equilibrium radionuclide angiography during insulin infusion (12 pmol. kg(-1). min(-1)) under either hypoglycemic (approximately 2.8 mmol/l) or euglycemic (approximately 5 mmol/l) conditions in intensively treated patients with type 1 diabetes and healthy nondiabetic subjects (n = 9 for each). During hypoglycemic hyperinsulinemia, there were significant increases in LVEF (DeltaLVEF = 11 +/- 2%) and PFR [DeltaPFR = 0.88 +/- 0.18 end diastolic volume (EDV)/s] in diabetic subjects as well as in the nondiabetic group (DeltaLVEF = 13 +/- 2%; DeltaPFR = 0.79 +/- 0.17 EDV/s). The increases in LVEF and PFR were comparable overall but occurred earlier in the nondiabetic group. A blunted increase in plasma catecholamine, cortisol, and glucagon concentrations occurred in response to hypoglycemia in the diabetic subjects. During euglycemic hyperinsulinemia, LVEF also increased in both the diabetic (DeltaLVEF = 7 +/- 1%) and nondiabetic (DeltaLVEF = 4 +/- 2%) groups, but PFR increased only in the diabetic group. In the comparison of the responses to hypoglycemic and euglycemic hyperinsulinemia, only the nondiabetic group had greater augmentation of LVEF, PFR, and cardiac output in the hypoglycemic study (P < 0.05 for each). Thus intensively treated type 1 diabetic patients demonstrate delayed augmentation of ventricular function during moderate insulin-induced hypoglycemia. Although diabetic subjects have a more pronounced cardiac response to hyperinsulinemia per se than nondiabetic subjects, their response to hypoglycemia is blunted.
    AJP Endocrinology and Metabolism 11/2001; 281(5):E1029-36. · 4.51 Impact Factor
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    ABSTRACT: Emergency department chest pain centers (CPCs) vary in their approach to patients with chest pain and nonischemic electrocardiograms (ECG). Although single-photon emission computed tomography (SPECT) myocardial perfusion imaging has been evaluated in this setting, both acutely at rest and after stress, we questioned its application in all patients. We prospectively evaluated the utility of selective SPECT imaging in a CPC (i.e., rest SPECT for ongoing pain, stress SPECT if unable to undergo exercise electrocardiography) and its impact on the overall disposition of all emergency department chest pain patients. Over 3 years, 2,601 patients were evaluated in a CPC (2,211 [85%] were sent home, 390 [15%] were hospitalized). Of 390 CPC patients hospitalized, 182 (47%) were diagnosed with coronary artery disease at the time of hospital discharge. Only 28 patients (1.1%) had an acute myocardial infarction. After 3 years, the proportion of all chest pain patients hospitalized and those diagnosed as "rule-out myocardial infarction" decreased from 53% to 41% and 32% to 18% of all chest pain patients, respectively (both p <0.0001). Overall, 906 patients (35%) required SPECT imaging to complete the CPC evaluation. Had SPECT imaging not been performed selectively, and all 906 patients been admitted, 762 (29%) would have been hospitalized unnecessarily based on the final diagnoses. Alternatively, sending all these patients home would have resulted in 144 (6%) inappropriate discharges of patients with coronary artery disease. A CPC protocol using the selective use of SPECT imaging permits the complete evaluation of all patients in the CPC, significantly reduces hospitalizations for chest pain, and restricts hospital admission to more appropriate patients.
    The American Journal of Cardiology 06/2001; 87(12):1351-5. · 3.21 Impact Factor
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    ABSTRACT: The prognosis of patients with severe non-ischaemic dilated cardiomyopathy is variable. The predictive value of currently utilized tests is suboptimal. The purpose of this study was to determine the prognostic value of dobutamine-induced augmentation of left ventricular ejection fraction in patients with non-ischaemic dilated cardiomyopathy. Sixty-two patients with left ventricular ejection fraction < or =0.30 underwent exercise testing with gas exchange analysis and assessment of left ventricular ejection fraction at rest and after a 10-min intravenous infusion of dobutamine at 10 microg x kg(-1) x min(-1), using equilibrium radionuclide ventriculography. Age was 48+/-11 years, 32% females, functional class 2.6+/-0.6, resting left ventricular ejection fraction 0.20+/-0.06, and peak exercise oxygen consumption (mVO2) 19+/-6 ml x kg(-1) x min(-1). Mean dobutamine-induced augmentation of left ventricular ejection fraction (DeltaLVEF) was 0.09+/-0.06 (median 0.08, range -0.03 to 0.26). Follow-up was 25+/-15 months during which there were 12 deaths and five transplantations. Patients were divided into two groups based on median DeltaLVEF. The transplant-free survival was better in the group with higher DeltaLVEF (94% vs 64%, P<0.008). In multivariate analysis incorporating age, gender, duration of chronic heart failure, functional class, right and left ventricular ejection fraction, DeltaLVEF, left ventricular end-diastolic volume index, and mVO2, only DeltaLVEF was predictive of 1-year, 3-year, and overall transplant-free survival (RR 0.09, 0.03, and 0.13;P 0.03, 0.09, and 0.08 respectively). The linear correlation between DeltaLVEF and mVO2(r=0.3) and between DeltaLVEF and left ventricular ejection fraction (r=0.5) was weak. Dobutamine-induced augmentation of left ventricular ejection fraction is a strong prognostic variable, independent of exercise capacity and resting ventriculographic variables, in severe non-ischaemic systolic dysfunctional heart failure.
    European Heart Journal 05/2001; 22(10):849-56. · 14.10 Impact Factor
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    ABSTRACT: OBJECTIVESThe purpose of this study was to determine whether higher left ventricular inotropic reserve, defined as the increase in left ventricular ejection fraction (LVEF) in response to intravenous dobutamine infusion, or other ventriculographic variables predict the increase in LVEF after beta-blocker therapy in patients with nonischemic cardiomyopathy (NICM).BACKGROUNDLong-term beta-blocker therapy increases LVEF in some patients with NICM. Other than dose, there are no definite predictors of LVEF increase.METHODSThirty patients with LVEF ≤0.35 and NICM underwent assessment of LVEF at rest and after a 10-min intravenous infusion of dobutamine at 10 μg/kg/min, using equilibrium radionuclide ventriculography. Age was 49 ± 11 years, 33% women, functional class 2.6 ± 0.5, duration of chronic heart failure 3.2 ± 2.9 years, LVEF 0.21 ± 0.07, left ventricular end-diastolic volume index 180 ± 64 ml/m2. Right ventricular ejection fraction (RVEF) was abnormal in 37%. Mean dobutamine-induced augmentation of LVEF (DoΔLVEF) was 0.12 ± 0.08. Patients were started on one of three beta-blockers (carvedilol, bucindolol or metoprolol) and the dose was advanced to the maximum tolerated.RESULTSLeft ventricular ejection fraction, reassessed 7.4 ± 5.9 months after maximum beta-blocker dose was reached, increased to 0.34 ± 0.13 (p = 0.0006). The following baseline variables correlated with improvement of LVEF: DoΔLVEF (p = 0.001), RVEF (p = 0.005), systolic blood pressure at end of dobutamine infusion (p = 0.02) and dose of beta-blocker (p = 0.07). In a multivariate analysis, only DoΔLVEF (p = 0.0003) and RVEF (p = 0.002) were predictive of the increase in LVEF.CONCLUSIONSPatients with nonischemic cardiomyopathy who have higher left ventricular inotropic reserve and normal RVEF derive higher increase in LVEF from beta-blocker therapy.
    Journal of the American College of Cardiology 03/2001; · 14.09 Impact Factor

Publication Stats

4k Citations
1,281.25 Total Impact Points


  • 1979–2010
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
  • 1980–2009
    • Yale University
      • • Section of Cardiovascular Medicine
      • • Department of Diagnostic Radiology and Pediatric Diagnostic Radiology
      • • Department of Internal Medicine
      • • School of Medicine
      New Haven, CT, United States
  • 2008
    • Leiden University Medical Centre
      • Department of Cardiology
      Leiden, South Holland, Netherlands
  • 1993–2006
    • Mayo Clinic - Rochester
      • Department of Cardiovascular Diseases
      Rochester, MN, United States
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
    • University of Rochester
      Rochester, New York, United States
  • 1998
    • Hartford Hospital
      Hartford, Connecticut, United States
  • 1996
    • Good Samaritan Hospital Los Angeles
      Los Angeles, California, United States
  • 1995
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 1994
    • Aurora St. Luke's Medical Center
      Milwaukee, Wisconsin, United States
  • 1990–1991
    • University of New Haven
      New Haven, Connecticut, United States
    • Greater Baltimore Medical Center
      Baltimore, Maryland, United States
  • 1989
    • Mayo Foundation for Medical Education and Research
      • Division of Cardiovascular Diseases
      Scottsdale, AZ, United States
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 1984–1987
    • University of Vermont
      • Department of Radiology
      Burlington, Vermont, United States
  • 1976
    • University of Amsterdam
      • Department of Cardiology
      Amsterdamo, North Holland, Netherlands