William R Hiatt

University of Colorado at Boulder, Boulder, Colorado, United States

Are you William R Hiatt?

Claim your profile

Publications (285)2185.86 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.
    Full-text · Article · Feb 2016 · Thrombosis and Haemostasis
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD, while clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events.
    No preview · Article · Jan 2016
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF) patients are at high risk for thrombotic and vascular events related to their cardiac arrhythmia and underlying systemic atherosclerosis. Ankle-Brachial Index (ABI) is a non-invasive tool in evaluating systemic atherosclerosis, useful in predicting cardiovascular events in general population; no data are available in AF patients. ARAPACIS is a prospective multicentre observational study performed by the Italian Society of Internal Medicine, analysing association between low ABI (≤ 0.90) and vascular events in NVAF out- or in-patients, enrolled in 136 Italian centres. A total of 2,027 non-valvular AF (NVAF) patients aged > 18 years from both sexes followed for a median time of 34.7 (interquartile range: 22.0-36.0) months, yielding a total of 4,614 patient-years of observation. Mean age was 73 ± 10 years old with 55 % male patients. A total of 176 patients (8.7 %) experienced a vascular event, with a cumulative incidence of 3.81 %/patient-year. ABI≤ 0.90 was more prevalent in patients with a vascular event compared with patients free of vascular events (32.2 vs 20.2 %, p< 0.05). On Cox proportional hazard analysis, ABI≤ 0.90 was an independent predictor of vascular events (hazard ratio (HR): 1.394, 95 % confidence interval (CI): 1.042-1.866; p=0.02), vascular death (HR: 2.047, 95 % CI: 1.255-3.338; p=0.004) and MI (HR: 2.709, 95 % CI: 1.485-5.083; p=0.001). This latter association was also confirmed after excluding patients with previous MI (HR: 2.901, 95 % CI: 1.408-5.990, p=0.004). No association was observed between low ABI and stroke/transient ischaemic attack (p=0.91). In conclusion, low ABI is useful to predict MI and vascular death in NVAF patients and may independently facilitate cardiovascular risk assessment in NVAF patients.
    No preview · Article · Jan 2016 · Thrombosis and Haemostasis
  • Source
    Brendan M Everett · Robert J Smith · William R Hiatt
    [Show abstract] [Hide abstract]
    ABSTRACT: In early June, the Endocrinologic and Metabolic Drugs Advisory Committee of the Food and Drug Administration (FDA), on which we serve, met to consider marketing applications for the new molecular entities alirocumab and evolocumab on the basis of their ability to lower low-density lipoprotein (LDL) cholesterol levels and their effects on other lipid fractions in patients at risk for cardiovascular disease. These first-in-class medications are fully humanized monoclonal antibodies that inactivate proprotein convertase subtilisin-kexin type 9 (PCSK9). That inactivation results in decreased LDL-receptor degradation, increased recirculation of the receptor to the surface of hepatocytes, and consequent lowering of LDL cholesterol . . .
    Preview · Article · Oct 2015 · New England Journal of Medicine
  • Source

    Full-text · Conference Paper · Aug 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today. © The Author(s) 2015.
    No preview · Article · Aug 2015 · Journal of Endovascular Therapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: Randomized controlled trials (RCTs) in pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. Kids-DOTT is a multicenter RCT investigating non-inferiority of a 6-week (shortened) vs. 3-month (conventional) duration of anticoagulation in patients <21 years old with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically-relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded endpoint, parallel-cohort RCT design. No eligibility violations or randomization errors occurred. Of enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in pre-specified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Inter-observer agreement between local vs. blinded central determination of venous occlusion by imaging at 6 weeks post-diagnosis was strong (ĸ-statistic=0.75; 95% confidence interval [CI] 0.48-1.0). Primary efficacy and safety event rates were 3.3% (95% CI 0.3-11.5%) and 1.4% (0.03-7.4%). The P/F phase of Kids-DOTT has demonstrated validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention, and endpoint rates to inform the fully-powered RCT. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jun 2015 · Journal of Thrombosis and Haemostasis
  • Cecilia C Low Wang · Jeffrey L Galinkin · William R Hiatt
    [Show abstract] [Hide abstract]
    ABSTRACT: R118 is an experimental compound that completed preclinical development as a potential medical therapy for the exercise limitation in peripheral artery disease. Animal studies established that R118 provided partial and reversible mitochondrial complex I inhibition with consequent increases in AMP kinase activation in liver and skeletal muscle. After demonstration of improved exercise performance in a mouse model and safety in rodent and primate models, a Phase I trial was performed in 24 subjects randomized to R118 vs placebo (5:1) in escalating doses. Plasma lactic acid levels were transiently elevated in 20% of subjects at the lowest dose and in 100% of subjects using a different formulation at the highest dose, which was associated with hospitalization in all subjects and severe metabolic acidosis requiring prolonged intubation in 2 subjects. Thus inhibition of mitochondrial complex I with R118 resulted in severe lactic acidosis representing unacceptable toxicity from this mechanism of action. This article is protected by copyright. All rights reserved. © 2015 American Society for Clinical Pharmacology and Therapeutics.
    No preview · Article · Jun 2015 · Clinical Pharmacology &#38 Therapeutics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Patients with nonvalvular atrial fibrillation (AF) show high residual cardiovascular (CV) risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of CV events (CVEs), but its predictive value in patients with anticoagulated AF is unknown. Methods: A prospective single-center cohort study, including 837 patients with AF, was conducted. Mean time of follow-up was 30.0 months, yielding 2,062 person-years of observation. Urinary 11-dehydro-TxB2 was measured at baseline. The primary end point was the occurrence of a CVE including fatal/nonfatal myocardial infarction and ischemic stroke, transient ischemic attack, cardiac revascularization, and CV death. Results: Mean age of patients was 73.1 years, and 43.6% were women. Median 11-dehydro-TxB2 levels were 100 (interquartile range 50-187) ng/mg of urinary creatinine. Overall, the anticoagulation control was adequate (63.9% of mean time in therapeutic range). A CVE occurred in 99 (11.8%) patients, and 55 were CV deaths. At baseline, 11-dehydro-TxB2 levels were higher in patients with a CVE compared with those without (186 [107-400] vs 98 [52-170], P < .001). An increased rate of CVEs (log-rank test, P < .001) and CV deaths (P < .001) was observed across tertiles of 11-dehydro-TxB2. Cardiovascular events were associated with age (hazard ratios [HR] 1.72 per 1 SD, 95% CI 1.33-2.21, P < .001), diabetes mellitus (HR 1.89, 95% CI 1.20-2.96, P = .005), heart failure (HR 1.60, 95% CI 1.01-2.54, P = .044), history of stroke/transient ischemic attack (HR 1.96, 95% CI 1.25-3.06, P = .003), and 11-dehydro-TxB2 (HR 1.64 per 1 SD, 95% CI 1.42-1.89, P < .001). Conclusions: Urinary 11-dehydro-TxB2 levels are associated with a residual risk of CVEs and CV mortality in patients with AF despite anticoagulant treatment.
    Full-text · Article · May 2015 · American Heart Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the relationship between Ankle-Brachial Index (ABI) and renal function progression in patients with atrial fibrillation (AF). Observational prospective multicentre cohort study. Atherothrombosis Center of I Clinica Medica of 'Sapienza' University of Rome; Department of Medical and Surgical Sciences of University Magna Græcia of Catanzaro; Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study. 897 AF patients on treatment with vitamin K antagonists. The relationship between basal ABI and renal function progression, assessed by the estimated Glomerular Filtration Rate (eGFR) calculated with the CKD-EPI formula at baseline and after 2 years of follow-up. The rapid decline in eGFR, defined as a decline in eGFR >5 mL/min/1.73 m(2)/year, and incident eGFR<60 mL/min/1.73 m(2) were primary and secondary end points, respectively. Mean age was 71.8±9.0 years and 41.8% were women. Low ABI (ie, ≤0.90) was present in 194 (21.6%) patients. Baseline median eGFR was 72.7 mL/min/1.73 m(2), and 28.7% patients had an eGFR<60 mL/min/1.73 m(2). Annual decline of eGFR was -2.0 (IQR -7.4/-0.4) mL/min/1.73 m(2)/year, and 32.4% patients had a rapid decline in eGFR. Multivariable logistic regression analysis showed that ABI ≤0.90 (OR 1.516 (95% CI 1.075 to 2.139), p=0.018) and arterial hypertension (OR 1.830 95% CI 1.113 to 3.009, p=0.017) predicted a rapid eGFR decline, with an inverse association for angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (OR 0.662 95% CI 0.464 to 0.944, p=0.023). Among the 639 patients with AF with eGFR >60 mL/min/1.73 m(2), 153 (23.9%) had a reduction of the eGFR <60 mL/min/1.73 m(2). ABI ≤0.90 was also an independent predictor for incident eGFR<60 mL/min/1.73 m(2) (HR 1.851, 95% CI 1.205 to 2.845, p=0.005). In patients with AF, an ABI ≤0.90 is independently associated with a rapid decline in renal function and incident eGFR<60 mL/min/1.73 m(2). ABI measurement may help identify patients with AF at risk of renal function deterioration. NCT01161251. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · May 2015 · BMJ Open
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease. © 2015 American Heart Association, Inc.
    No preview · Article · Apr 2015 · Circulation Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite the global burden of cardiovascular disease, investment in cardiovascular drug development has stagnated over the past 2 decades, with relative underinvestment compared with other therapeutic areas. The reasons for this trend are multifactorial, but of primary concern is the high cost of conducting cardiovascular outcome trials in the current regulatory environment that demands a direct assessment of risks and benefits, using clinically-evident cardiovascular endpoints. To work toward consensus on improving the environment for cardiovascular drug development, stakeholders from academia, industry, regulatory bodies, and government agencies convened for a think tank meeting in July 2014 in Washington, DC. This paper summarizes the proceedings of the meeting and aims to delineate the current adverse trends in cardiovascular drug development, understand the key issues that underlie these trends within the context of a recognized need for a rigorous regulatory review process, and provide potential solutions to the problems identified. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · Journal of the American College of Cardiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The lack of consistent definitions and nomenclature across clinical trials of novel devices, drugs, or biologics poses a significant barrier to accrual of knowledge in and across peripheral artery disease therapies and technologies. Recognizing this problem, the Peripheral Academic Research Consortium, together with the U.S. Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, has developed a series of pragmatic consensus definitions for patients being treated for peripheral artery disease affecting the lower extremities. These consensus definitions include the clinical presentation, anatomic depiction, interventional outcomes, surrogate imaging and physiological follow-up, and clinical outcomes of patients with lower-extremity peripheral artery disease. Consistent application of these definitions in clinical trials evaluating novel revascularization technologies should result in more efficient regulatory evaluation and best practice guidelines to inform clinical decisions in patients with lower extremity peripheral artery disease. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Journal of the American College of Cardiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Supervised walking exercise is an effective treatment to improve walking ability of patients with peripheral artery disease (PAD), but few exercise programs in community settings have been effective. The aim of this study was to determine the efficacy of a community-based walking exercise program with training, monitoring and coaching (TMC) components to improve exercise performance and patient-reported outcomes in PAD patients. This was a randomized, controlled trial including PAD patients (n=25) who previously received peripheral endovascular therapy or presented with stable claudication. Patients randomized to the intervention group received a comprehensive community-based walking exercise program with elements of TMC over 14 weeks. Patients in the control group did not receive treatment beyond standard advice to walk. The primary outcome in the intent-to-treat (ITT) analyses was peak walking time (PWT) on a graded treadmill. Secondary outcomes included claudication onset time (COT) and patient-reported outcomes assessed via the Walking Impairment Questionnaire (WIQ). Intervention group patients (n=10) did not significantly improve PWT when compared with the control group patients (n=10) (mean±standard error: +2.1±0.7 versus 0.0±0.7 min, p=0.052). Changes in COT and WIQ scores were greater for intervention patients compared with control patients (COT: +1.6±0.8 versus -0.6±0.7 min, p=0.045; WIQ: +18.3±4.2 versus -4.6±4.2%, p=0.001). This pilot using a walking program with TMC and an ITT analysis did not improve the primary outcome in PAD patients. Other walking performance and patient self-reported outcomes were improved following exercise in community settings. Further study is needed to determine whether this intervention improves outcomes in a trial employing a larger sample size. © The Author(s) 2015.
    Preview · Article · Mar 2015 · Vascular Medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Society for Vascular Medicine was founded in 1989. During the subsequent 25 years, the Society has grown to approximately 500 members and has achieved international recognition while making important contributions to vascular disease education, clinical vascular medicine and biology research, and patient care. In celebration of the Society's 25th anniversary, its past and current presidents reflect on the Society's history, challenges, and achievements, and emphasize the vital role of the SVM in the discipline of vascular medicine. © The Author(s) 2015.
    No preview · Article · Feb 2015 · Vascular Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This White Paper provides a summary of presentations and discussions at a Cardiovascular Safety Outcome Trials Think Tank cosponsored by the Cardiac Safety Research Consortium, the US Food and Drug Administration, and the American College of Cardiology, held at American College of Cardiology's Heart House, Washington, DC, on February 19, 2014. Studies to assess cardiovascular (CV) risk of a new drug are sometimes requested by regulators to resolve ambiguous safety signals seen during its development or among other members of its class. Think Tank participants thought that important considerations in undertaking such studies were as follows: (1) plausibility-how likely it is that a possible signal indicating risk is real, based on strength of evidence, and/or whether a plausible mechanism of action for potential CV harm has been identified; (2) relevance-what relative and absolute CV risk would need to be excluded to determine that the drug had an acceptable benefit-to-risk balance for its use in the intended patient population; and (3) how plausibility and relevance influence the timing and approach to further safety assessment. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Jan 2015 · American Heart Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxia inducible factor (HIF) stabilization by HIF-prolyl hydroxylase (PHD) inhibitors may improve ischemic conditions such as peripheral artery disease (PAD). This multicenter, randomized, placebo-controlled study evaluated the safety and efficacy of GSK1278863 (an oral PHD inhibitor) in subjects with PAD. The study assessed two active treatment paradigms: single dosing and subchronic daily dosing (300 mg single dose and 15 mg daily for 14 days, respectively). Neither regimen improved exercise performance compared with placebo (change from baseline in the 6-minute walk test (6MWT; feet), (GSK1278863, placebo): single dose (-46, -44), p=0.96; repeat dose (9, 8), p=0.99; change in number of contractions to onset of claudication (goniometry): single dose (4, -1), p=0.053; repeat dose (-2, 1), p=0.08). A calf-muscle biopsy substudy showed no increases in mRNA or protein levels of HIF target genes. More subjects receiving GSK1278863 than placebo experienced adverse events, particularly following the 300 mg single dose. Thus, assessing the safety of GSK1278863 in this setting would require a larger population exposed to the agent for a longer duration. These data do not support a benefit of GSK1278863 in PAD using the regimens tested. ClinicalTrials.gov Identifier: NCT01673555.
    Full-text · Article · Nov 2014 · Vascular Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Although the relationship between physical activity and coronary heart disease is well characterized, a paucity of data exists on physical activity and vascular disease in other arterial territories. This study examined the prevalence of peripheral artery disease (PAD) and carotid artery stenosis (CAS) in association with physical activity. Approach and results: The association between physical activity and vascular disease was examined in >3 million self-referred US participants in the United States from 2003 to 2008 who completed a medical and lifestyle questionnaire in the Life Line screening program. All subjects were evaluated by screening ankle brachial indices <0.90 for PAD and ultrasound imaging for CAS >50%. Multivariable logistic regression modeling was used to estimate odds of disease. Among 3 250 350 subjects, 63% of the population engaged in some leisure time vigorous physical activity. After adjustment for age, sex, race/ethnicity, hypertension, hypercholesterolemia, smoking status, diabetes mellitus, body mass index, and family history of cardiovascular disease, subjects who reported any physical activity had a significantly lower odds of PAD (odds ratio, 0.64; 95% confidence interval, 0.63-0.65) and CAS (odds ratio, 0.80; 95% confidence interval, 0.79-0.81). The association between physical activity with PAD and CAS was robust when stratified by sex, race, and age categories. Physical activity intensity frequency was associated with lower PAD and CAS in a graded manner (P trend <0.0001 for both). Findings seemed unaffected by confounding by comorbidity or indication. Conclusions: In a large population-based study, higher levels of physical activity were independently associated with lower odds of vascular disease in the lower extremities and carotid arteries.
    Preview · Article · Oct 2014 · Arteriosclerosis Thrombosis and Vascular Biology
  • William R. Hiatt

    No preview · Article · Oct 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). Methods and results: We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. Conclusions: PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD.
    Full-text · Article · Sep 2014 · Circulation

Publication Stats

18k Citations
2,185.86 Total Impact Points


  • 2011-2015
    • University of Colorado at Boulder
      Boulder, Colorado, United States
    • National Research Center (CO, USA)
      Boulder, Colorado, United States
  • 1991-2015
    • University of Colorado
      • • Department of Medicine
      • • Division of Cardiology
      Denver, Colorado, United States
  • 1992-2014
    • University of Colorado Hospital
      • Department of Medicine
      Denver, Colorado, United States
  • 2012
    • Sapienza University of Rome
      • Department of Experimental Medicine
      Roma, Latium, Italy
  • 2009
    • University of Pennsylvania
      • Division of Cardiovascular Medicine
      Philadelphia, PA, United States
  • 2008
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2007
    • University of Washington Seattle
      Seattle, Washington, United States
  • 2006
    • Mental Health Center of Denver
      Denver, Colorado, United States
    • Colorado Center for Digestive Disorders
      Longmont, Colorado, United States
  • 2004
    • Harvard University
      Cambridge, Massachusetts, United States
    • Duke University
      • Department of Medicine
      Durham, North Carolina, United States
  • 2001-2004
    • University of California, San Diego
      • Department of Family and Preventive Medicine
      San Diego, California, United States
    • Mayo Clinic - Rochester
      Рочестер, Minnesota, United States
  • 2002
    • Uniformed Services University of the Health Sciences
      Maryland, United States
  • 1999
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
  • 1994
    • Case Western Reserve University
      • Department of Medicine (University Hospitals Case Medical Center)
      Cleveland, Ohio, United States