Mihai Gheorghiade

University of Illinois at Chicago, Chicago, Illinois, United States

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Publications (598)3302.65 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: The present study aims to describe the epidemiology, baseline clinical characteristics, in-hospital management, and outcome of patients hospitalized for heart failure admitted directly or transferred to the ICU. The Romanian Acute Heart Failure Syndromes (RO-AHFS) registry prospectively enrolled 3224 consecutive patients between January 2008 and May 2009 admitted with a primary diagnosis of heart failure. Participants were classified by ICU admission status (i.e. ICU+/ICU-). Independent clinical predictors of ICU admission and in-hospital mortality were identified using multivariable logistic regression analysis. Overall, 10.7% of patients required ICU level care, 32% as a direct ICU admission, with 68% as an ICU transfer during hospitalization. Patients admitted to the ICU had a mean age of 68.1 ± 11.3 years, 61% were men, 67% had an ischemic cause, and 44% presented with de-novo heart failure. ICU+ patients more frequently presented with low SBP and pulse pressure and abnormal renal function. Mechanical ventilation was required in 32.7% and intravenous inotropes were administered to 56.7% of ICU+ patients. ICU+ patients had higher in-hospital mortality compared to ICU- patients (17.3 vs. 6.5%). Patients admitted directly to the ICU had a 15.3% mortality rate compared to 18.4% in those transferred after admission. Age, serum sodium, SBP below 110 mmHg, and left-ventricular ejection fraction less than 45% were predictive of ICU admission, whereas for ICU+ patients, age, vasopressor, and mechanical ventilation utilization were predictive of mortality. Patients admitted directly or transferred to the ICU are at a high risk of in-hospital mortality. Clinical variables commonly measured at the time of admission may facilitate disposition decision-making including early triage to the ICU.
    Journal of Cardiovascular Medicine 04/2014; · 2.66 Impact Factor
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    ABSTRACT: The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.
    JACC. Heart failure. 04/2014; 2(2):97-112.
  • Javed Butler, Gregg C Fonarow, Mihai Gheorghiade
    JAMA The Journal of the American Medical Association 03/2014; 311(11):1160-1161. · 29.98 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: We examined the clinical effectiveness of beta-blockers considered evidenced-based to heart failure and reduced ejection fraction (HFrEF) and their recommended target doses in older adults with HF and preserved ejection fraction (HFpEF). In OPTIMIZE-HF (2003-2004) linked to Medicare (2003-2008), of the 10,570 older (age≥65 years, mean, 81years) adults with HFpEF (EF≥40%, mean 55%), 8373 had no contraindications to beta-blocker therapy. After excluding 4614 patients receiving pre-admission beta-blockers, the remaining 3759 patients were potentially eligible for new discharge prescriptions for beta-blockers and 1454 received them. We assembled a propensity-matched cohort of 1099 pairs of patients receiving beta-blockers and no beta-blockers, balanced on 115 baseline characteristics. Evidence-based beta-blockers for HFrEF, namely, carvedilol, metoprolol succinate, and bisoprolol and their respective guideline-recommended target doses were 50, 200, and 10mg/day. During 6years of follow-up, new discharge prescriptions for beta-blockers had no association with the primary composite endpoint of all-cause mortality or HF rehospitalization (hazard ratio, 1.03; 95% confidence interval {CI}, 0.94-1.13; p=0.569). This association did not vary by beta-blocker evidence class or daily dose. Hazard ratios for all-cause mortality and HF rehospitalization were 0.99 (95% CI, 0.90-1.10; p=0.897) and 1.17 (95% CI, 1.03-1.34; p=0.014), respectively. The latter association lost significance when higher EF cutoffs of ≥45%, ≥50% and ≥55% were used. Initiation of therapy with beta-blockers considered evidence-based for HFrEF and in target doses recommended for HFrEF had no association with the composite or individual endpoints of all-cause mortality or HF rehospitalization in HFpEF.
    International journal of cardiology 03/2014; · 7.08 Impact Factor
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    ABSTRACT: Congestion is a major reason for hospitalization in acute heart failure (HF). Therapeutic strategies to manage congestion include diuretics, vasodilators, ultrafiltration, vasopressin antagonists, mineralocorticoid receptor antagonists, and potentially also novel therapies such as gut sequesterants and serelaxin. Uncertainty exists with respect to the appropriate decongestion strategy for an individual patient. In this review, we summarize the benefit and risk profiles for these decongestion strategies and provide guidance on selecting an appropriate approach for different patients. An evidence-based initial approach to congestion management involves high-dose i.v. diuretics with addition of vasodilators for dyspnoea relief if blood pressure allows. To enhance diuresis or overcome diuretic resistance, options include dual nephron blockade with thiazide diuretics or natriuretic doses of mineralocorticoid receptor antagonists. Vasopressin antagonists may improve aquaresis and relieve dyspnoea. If diuretic strategies are unsuccessful, then ultrafiltration may be considered. Ultrafiltration should be used with caution in the setting of worsening renal function. This review is based on discussions among scientists, clinical trialists, and regulatory representatives at the 9th Global Cardio Vascular Clinical Trialists Forum in Paris, France, from 30 November to 1 December 2012.
    European Journal of Heart Failure 03/2014; · 5.25 Impact Factor
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    ABSTRACT: Lower serum lipid levels are paradoxically predictive of poor clinical outcomes in hospitalized and ambulatory patients with heart failure (HF). In large randomized controlled trials, statins did not demonstrate an overall mortality benefit in chronic HF patients. We currently lack adequate prospective data that aggressive lipid management in HF truly alters disease course and progression. Despite their traditional use as lipid-lowering agents, hypothesis-generating works have suggested that statins may show benefit in specific enriched HF subgroups. Given that patients hospitalized for HF continue to face a high post-discharge event rate and that statins are increasingly inexpensive, widely available, and generally well tolerated, it is imperative that we identify those HF patients most likely to benefit and reconsider testing these agents in specific subpopulations.
    Heart Failure Reviews 02/2014; · 4.45 Impact Factor
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    ABSTRACT: Heart Failure (HF) is a global pandemic affecting an estimated 26 million people worldwide and resulting in more than 1 million hospitalizations annually in both the United States and Europe. Although the outcomes for ambulatory HF patients with a reduced ejection fraction have improved with the discovery of multiple evidence-based drug and device therapies, hospitalized HF (HHF) patients continue to experience unacceptably high post-discharge mortality and readmission rates that have not changed in the last two decades. HHF registries have significantly improved our understanding of this clinical entity and remain an important source of data shaping both public policy and research efforts. This paper reviews global HHF registries to describe the patient characteristics, management, outcomes and their predictors, quality improvement initiatives, regional differences, and limitations of the available data. Moreover, based on the lessons learned, we also propose a roadmap for the design and conduct of future HHF registries.
    Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
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    ABSTRACT: New therapeutic targets, agents, and strategies are needed to prevent and treat heart failure (HF) after a decade of failed research efforts to improve long term patient outcomes, especially in patients following hospitalization for heart failure (HHF). Conceptually, an accurate assessment of left ventricular (LV) structure is an essential step in the development of novel therapies because heterogeneous pathophysiologies underlie chronic HF and HHF. Improved LV characterization permits the identification and targeting of the intrinsic fundamental disease modifying pathways that culminate in HF. “Interstitial heart disease” is one such pathway, characterized by extracellular matrix (ECM) expansion that is associated with mechanical, electrical, and vasomotor dysfunction and adverse outcomes. Previous landmark trials that appear to treat “interstitial heart disease” have been effective in improving outcomes. Advances in cardiovascular magnetic resonance now enable clinicians and researchers to assess the interstitium and quantify ECM expansion using extracellular volume fraction (ECV) measures, and other derangements in cardiovascular structure. These capabilities may provide a mechanistic platform to advance understanding of the role of the ECM, foster the development of novel therapeutics, and target specific disease modifying pathways intrinsic to the ventricle. Refocusing on the interstitium may potentially improve care through the identification and targeted treatment of key patient subgroups.
    Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
  • The American journal of medicine 01/2014; · 4.47 Impact Factor
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    ABSTRACT: Digoxin is the oldest cardiac drug still in contemporary use, yet its role in the management of patients with heart failure (HF) remains controversial. A purified cardiac glycoside derived from the foxglove plant, digoxin increases ejection fraction (EF), augments cardiac output, and reduces pulmonary capillary wedge pressure without causing deleterious increases in heart rate or decreases in blood pressure. Moreover, it is also a neurohormonal modulator at low doses. In the pivotal Digitalis Investigation Group (DIG) trial, digoxin therapy was shown to reduce all-cause and HF-specific hospitalizations but had no effect on survival. With the discovery of neurohormonal blockers capable of reducing mortality in HF with a reduced EF, the results of the DIG trial were viewed as neutral and its use declined precipitously. Although modern drug and device-based therapies have dramatically improved the survival of ambulatory HF patients, outcomes for patients with worsening chronic HF, defined as deteriorating signs and symptoms on standard therapy often leading to unscheduled clinic or emergency room visits or hospitalization, have largely remained unchanged over the last two decades. We critically review the evidence for digoxin, including its limitations, and provide a conceptual framework for future research.
    Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
  • Ali Ahmed, Mihai Gheorghiade, Gregg C Fonarow
    The American journal of medicine 12/2013; · 4.47 Impact Factor
  • Sean Collins, Philip Levy, Peter Pang, Mihai Gheorghiade
    American heart journal 12/2013; 166(6):e47. · 4.65 Impact Factor
  • Journal of the American College of Cardiology 11/2013; · 14.09 Impact Factor
  • Javed Butler, Gregg C Fonarow, Mihai Gheorghiade
    JAMA The Journal of the American Medical Association 11/2013; 310(19):2035-6. · 29.98 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: -Many clinical trials have demonstrated a benefit for cardiac resynchronization (CRT) and implantable cardioverter-defibrillator (ICD) therapies in patients with heart failure (HF) and reduced ejection fraction (EF), yet questions have been raised with regard to the benefit of ICDs for women. The purpose of this study was to determine the clinical effectiveness of CRT and ICD therapy as a function of sex in outpatients with HF and reduced EF (≤35%). -Data from IMPROVE HF were analyzed by device status and sex among guideline-eligible patients for vital status (alive/dead) at 24 months. Multivariate Generalized Estimating Equations analyses were conducted adjusting for baseline patient and practice characteristics. In the ICD/CRT-D eligible cohort (n=7748), there were 5,485 (71%) men and 2,261 (29%) women. In the CRT-P/CRT-D eligible cohort (n=1188) there were 824 (69%) men and 364 (31%) women. The clinical benefit associated with ICD/CRT-D therapy was similar in both men and women (men adjusted OR 0.71, 95% CI 0.57-0.87, p=0.0012; women adjusted OR 0.65, 95% CI 0.49-0.85, p=0.0019). For CRT-P/CRT-D, the associated benefits showed no significant heterogeneity (men adjusted OR 0.59, 95% CI 0.331.06, p=0.0793; women adjusted OR 0.44, 95% CI 0.22-0.90, p=0.0243). The device*sex interactions were not significant (p=0.4441 for CRT-P/CRT-D and p=0.5966 for ICD/CRT-D). -The use of guideline-directed CRT and ICD therapy was associated with substantially reduced 24 month mortality in eligible men and women with HF and reduced EF. Device therapies should be offered to all eligible HF patients, without modification based on sex.
    Circulation Heart Failure 10/2013; · 6.68 Impact Factor
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    ABSTRACT: Serum magnesium levels may be impacted by neurohormonal activation, renal function, and diuretics. The clinical profile and prognostic significance of serum magnesium level concentration in patients hospitalized for heart failure (HF) with reduced ejection fraction is unclear. In this retrospective analysis of the placebo group of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, we evaluated 1,982 patients hospitalized for worsening HF with ejection fractions ≤40%. Baseline magnesium levels were measured within 48 hours of admission and analyzed as a continuous variable and in quartiles. The primary end points of all-cause mortality (ACM) and cardiovascular mortality or HF rehospitalization were analyzed using Cox regression models. Mean baseline magnesium level was 2.1 ± 0.3 mg/dl. Compared with the lowest quartile, patients in the highest magnesium level quartile were more likely to be older, men, have lower heart rates and blood pressures, have ischemic HF origin, and have higher creatinine and natriuretic peptide levels (all p <0.003). During a median follow-up of 9.9 months, every 1-mg/dl increase in magnesium level was associated with higher ACM (hazard ratio [HR] 1.77; 95% confidence interval [CI] 1.35 to 2.32; p <0.001) and the composite end point (HR 1.44; 95% CI 1.15 to 1.81; p = 0.002). However, after adjustment for known baseline covariates, serum magnesium level was no longer an independent predictor of either ACM (HR 0.94, 95% CI 0.69 to 1.28; p = 0.7) or the composite end point (HR 1.01, 95% CI 0.79 to 1.30; p = 0.9). In conclusion, despite theoretical concerns, baseline magnesium level was not independently associated with worse outcomes in this cohort. Further research is needed to understand the importance of serum magnesium levels in specific HF patient populations.
    The American journal of cardiology 10/2013; · 3.58 Impact Factor
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    ABSTRACT: The last decade of acute heart failure (HF) research is characterized by disappointments in large phase 2 and 3 pharmacologic studies of therapeutics including calcium-sensitizing agents and antagonists of endothelin, vasopressin, and adenosine. As a result, pharmacologic management for acute HF has changed little in recent years, and adverse event rates remain higher than in chronic HF. Despite neutral results in many acute HF trials, recent studies including RELAX-AHF, ASTRONAUT, and PRONTO have highlighted the role of appropriate timing of patient enrollment, targeting the "right" patients, and selecting appropriate end points and sites. We describe lessons learned from recent trials in acute HF and outline strategies to improve the potential for success in future trials. This review is based on discussions between scientists, clinical trialists, and regulatory representatives at the 9th Global Cardio Vascular Clinical Trialists Forum in Paris, France, from November 30 to December 1, 2012.
    American heart journal 10/2013; 166(4):629-635. · 4.65 Impact Factor
  • Robert O Bonow, Mihai Gheorghiade
    Journal of the American College of Cardiology 09/2013; · 14.09 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in postdischarge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-Btype natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkerswere collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P ¼ 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80,95% CI: 0.64–0.99;DM:HR: 1.16,95% CI: 0.91–1.47; P ¼ 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50–0.94; DM: HR: 1.64, 95% CI: 1.15–2.33; P , 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71–1.93; DM: HR: 2.39, 95% CI: 1.30–4.42; P ¼ 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.
    European Heart Journal 09/2013; · 14.10 Impact Factor
  • Expert Review of Cardiovascular Therapy 09/2013; 11(9):1079-83.

Publication Stats

13k Citations
3,302.65 Total Impact Points


  • 1993–2014
    • University of Illinois at Chicago
      • Section of Cardiology
      Chicago, Illinois, United States
  • 2013
    • University at Buffalo, The State University of New York
      Buffalo, New York, United States
    • New York Medical College
      New York City, New York, United States
    • Stanford Medicine
      • Department of Medicine
      Stanford, CA, United States
    • University of Groningen
      • Department of Cardiology
      Groningen, Province of Groningen, Netherlands
  • 2012–2013
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • Centre Hospitalier Universitaire de Poitiers
      • Department of Cardiology
      Poitiers, Poitou-Charentes, France
    • Massachusetts General Hospital
      • Department of Medicine
      Boston, MA, United States
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
    • Stanford University
      • Department of Medicine
      Stanford, CA, United States
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
  • 2011–2013
    • Emory University
      • Division of Cardiology
      Atlanta, GA, United States
    • Vanderbilt University
      • Department of Emergency Medicine
      Nashville, Michigan, United States
    • Wilford Hall Ambulatory Surgery Center
      Lackland Air Force Base, Texas, United States
    • University of Chicago
      Chicago, Illinois, United States
    • Institute for Cardiovascular Diseases
      Socola, Iaşi, Romania
  • 2010–2013
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • Brescia University
      Chicago, Illinois, United States
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
    • Wayne State University
      • Department of Emergency Medicine
      Detroit, MI, United States
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2006–2013
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • University of Colorado
      Denver, Colorado, United States
    • Biomedical Research Institute, Rockville
      Maryland, United States
    • Ospedale Pediatrico Bambino Gesù
      • Division of Cardiac Surgery
      Roma, Latium, Italy
  • 2004–2013
    • University of Alabama at Birmingham
      • Department of Medicine
      Birmingham, AL, United States
    • Johns Hopkins Medicine
      • Department of Medicine
      Baltimore, MD, United States
    • Ochsner
      New Orleans, Louisiana, United States
  • 2001–2013
    • Duke University
      Durham, North Carolina, United States
  • 1998–2013
    • University of California, San Francisco
      • • Division of Cardiology
      • • Division of Hospital Medicine
      San Francisco, CA, United States
    • St. George's School
      • Department of Cardiological Sciences
      Middletown, Rhode Island, United States
  • 2002–2012
    • Duke University Medical Center
      • • Division of Cardiology
      • • Duke Clinical Research Institute
      • • Department of Medicine
      Durham, NC, United States
  • 1993–2012
    • Northwestern University
      • • Division of Cardiology (Dept. of Medicine)
      • • Department of Emergency Medicine
      • • Feinberg School of Medicine
      • • Department of Medicine
      • • Department of Preventive Medicine
      Evanston, IL, United States
  • 1987–2012
    • Henry Ford Hospital
      • Department of Internal Medicine
      Detroit, Michigan, United States
  • 2009–2011
    • University of Maryland, Baltimore
      • Division of Cardiology
      Baltimore, MD, United States
    • San Francisco VA Medical Center
      San Francisco, California, United States
    • University of South Florida
      Tampa, Florida, United States
    • Kerckhoff Klinik
      Stadt Bad Nauheim, Hesse, Germany
    • Baylor Hamilton Heart and Vascular Hospital
      Dallas, Texas, United States
    • National Research Council
      • Institute of Clinical Physiology IFC
      Roma, Latium, Italy
  • 2008–2011
    • Università degli Studi di Brescia
      • Department of Clinical and Experimental Sciences
      Brescia, Lombardy, Italy
    • The Ohio State University
      • Division of Cardiovascular Medicine
      Columbus, OH, United States
    • University of Texas Medical School
      • Department of Internal Medicine
      Houston, TX, United States
    • Attikon University Hospital
      • Department of Cardiology
      Athens, Attiki, Greece
    • University of Southern California
      Los Angeles, California, United States
  • 2007–2011
    • Tufts Medical Center
      • Division of Cardiology
      Boston, Massachusetts, United States
    • University of South Carolina
      Columbia, South Carolina, United States
    • University of California, San Diego
      San Diego, California, United States
    • University of Texas Southwestern Medical Center
      • Department of Internal Medicine
      Dallas, TX, United States
    • Louisiana State University Health Sciences Center Shreveport
      Shreveport, Louisiana, United States
    • Athens State University
      Athens, Alabama, United States
  • 1998–2011
    • University of California, Los Angeles
      • • Department of Medicine
      • • Division of Cardiology
      Los Angeles, CA, United States
  • 2008–2010
    • University of Cincinnati
      • Department of Emergency Medicine
      Cincinnati, OH, United States
    • Northwestern Memorial Hospital
      • Bluhm Cardiovascular Institute
      Chicago, Illinois, United States
    • Baylor Health Care System
      • Baylor Heart and Vascular Institute (BHVI)
      Dallas, Texas, United States
  • 2007–2010
    • Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2005–2010
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States
  • 1993–2010
    • Sapienza University of Rome
      • Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences
      Roma, Latium, Italy
  • 2008–2009
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
  • 2006–2008
    • European Hospital
      Roma, Latium, Italy
  • 2001–2006
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
  • 2002–2005
    • University of North Carolina at Chapel Hill
      • Department of Medicine
      Chapel Hill, NC, United States
  • 2003
    • Advocate Illinois Masonic Medical Center
      Chicago, Illinois, United States
  • 1995
    • Henry Ford Health System
      Detroit, Michigan, United States
  • 1989
    • Virginia Hospital Center
      Arlington, Virginia, United States
  • 1984
    • Providence Hospital
      Mobile, Alabama, United States