S J Marble

Beth Israel Deaconess Medical Center, Boston, MA, United States

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Publications (48)227 Total impact

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    ABSTRACT: Although percutaneous coronary intervention restores optimal epicardial blood flow in most cases, abnormal myocardial perfusion may still persist. This might be as a result of macro and microembolization, neutrophil plugging, vasoconstriction, myocyte contracture, local intracellular and interstitial edema, intramural haemorrhage, and endothelial blistering. Local delivery of intracoronary pharmacotherapy via the coronary arteries may increase local drug concentration several fold, and may improve drug efficacy. Several pharmacological agents such as adenosine, calcium channel blockers, alpha blockers, beta2 receptor activators, vasodilators, antithrombotics, and antiplatelet agents have been used to treat coronary microvascular dysfunction. This article reviews the results of trials of intracoronary pharmacotherapy to date.
    Journal of Thrombosis and Thrombolysis 10/2008; 26(3):234-42. · 1.99 Impact Factor
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    ABSTRACT: Potent antiplatelet and antithrombotic agents have significantly reduced mortality in the setting of acute coronary syndromes and percutaneous coronary intervention. However these agents are associated with increased bleeding which is in turn associated with adverse clinical outcomes. In many centers, transfusion is often used to correct for blood loss. Blood transfusion in the setting of acute coronary syndrome has been associated with adverse clinical outcomes including increased mortality. Transfusion associated microchimerism (TA-MC) is a newly recognized complication of blood transfusion. There is engraftment of the donor's hematopoietic stem cells in patients who then develop microchimerism. This article discusses the association of bleeding/blood transfusion with adverse outcomes and the potential role of TA-MC in clinical outcomes.
    Journal of Thrombosis and Thrombolysis 10/2008; 27(1):57-67. · 1.99 Impact Factor
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    ABSTRACT: Since its introduction, the TIMI frame count method has contributed to the understanding of the pathophysiology of coronary artery disease. In this article, the evolution of the TFC method and its applicability in the assessment of various therapeutic modalities are described.
    Journal of Thrombosis and Thrombolysis 05/2008; 27(3):316-28. · 1.99 Impact Factor
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    ABSTRACT: Administration of fibrinolytic, antiplatelet, and antithrombotic agents by the intracoronary route may disaggregate clot, but the potential role of the mechanical force of the injection itself in decreasing clot burden has not been studied. Patients with ST-segment elevation myocardial infarction who were pretreated in the emergency room (ER) with unfractionated heparin and aspirin in the TITAN-TIMI 34 study were randomized to treatment with eptifibatide in the ER (n = 131) versus after diagnostic catheterization (n = 150). Quantitative coronary angiography was used to assess change in diameter stenosis from time of first contrast injection to injection before percutaneous coronary intervention (PCI) immediately preceding wire placement down the culprit artery in a matching view. Successful perfusion of the myocardium was assessed after PCI by the presence of Thrombolysis In Myocardial Infarction myocardial perfusion grade of 2 or 3. In patients treated with eptifibatide in the ER, there was a 1.3% absolute improvement in diameter stenosis from the first injection to the injection before PCI (p = 0.02), whereas there was no change in diameter stenosis in patients not treated with eptifibatide in the ER (0.0%, p = NS). Each 1% improvement in percent diameter stenosis during diagnostic injections before PCI was strongly correlated with an open muscle after PCI (adjusted odds ratio 1.09, 95% confidence interval 1.02 to 1.16, p = 0.012). In conclusion, the mechanical force of a contrast injection decreases thrombotic burden in patients with ST-segment elevation myocardial infarction pretreated with eptifibatide but not with placebo. Future trials of intracoronary pharmacotherapies should include a control arm in which saline is injected to account for the potential clot disaggregation that occurs as a result of iodinated contrast injections, particularly if the patient has been pretreated with aggressive pharmacotherapy.
    The American Journal of Cardiology 08/2007; 100(1):13-7. · 3.21 Impact Factor
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    ABSTRACT: The current method of analyzing coronary flow data is the TIMI flow grade method. This method is convenient and easy to apply, but there are limitations to this categorical method of analyzing coronary artery flow. We have developed a new method of analyzing coronary blood flow called the “TIMI frame count.” Using the TIMI frame counting method, we have shown that the flow in the coronary arteries is in fact distributed as a continuous variable and that there are nondiscrete categories of slow and fast flow. This article discusses the statistical basis for the development of this new, simple, and continuous index of coronary flow and provides a “how-to manual“ describing the practical implementation of the new TIMI frame count method. We also describe simple new techniques for measuring the distance to the landmark used for TIMI frame counting. Knowing the distance and the time from the TIMI frame count, velocity can easily be calculated. Tables are provided that can be used for these calculations on-line in the cardiac catheterization laboratory. If the diameter is known, flow can also be calculated from these tables. We also describe new applications of marker wires to measure distance and velocity.
    Journal of Interventional Cardiology 06/2007; 9(6):429 - 444. · 1.50 Impact Factor
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    ABSTRACT: This is the first study to demonstrate the appearance of the Fibonacci Cascade within the distribution of coronary artery lesions in the human heart. The propensity for this ratio to appear in nature may also be because this ratio optimizes the efficiency of packing structures in a limited space in such a way that wasted space is minimized and the supply of energy or nutrients is optimized.
    The American Journal of Cardiology 10/2003; 92(5):595-7. · 3.21 Impact Factor
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    ABSTRACT: Although the time for contrast material to fill the epicardial artery in the setting of acute coronary syndromes has been studied extensively, the time for contrast material to fill the myocardium has not been evaluated. We compared differences in myocardial contrast material transit among patients with unstable angina pectoris/non-ST-elevation acute myocardial infarction (UAP/NSTEAMI) with patients with ST-elevation acute myocardial infarction (STEAMI). The time it took for contrast material to first appear and to arrive at peak intensity in the myocardium was compared in 224 patients with STEAMI enrolled in the LIMIT-AMI study versus 430 patients with UAP/NSTEAMI enrolled in the TACTICS-TIMI 18 trial. In patients with STEAMI, there was a delay in both the time for contrast material to first enter the myocardium (5,619 +/- 1,789 vs 4,663 +/- 1,626 ms, p <0.0001) and the time from entrance to peak blush intensity (2,387 +/- 1,359 vs 1,959 +/- 1,244 ms, p = 0.003) compared with patients with UAP/NSTEAMI. STEAMI remained significantly associated with impaired entrance of contrast material into the myocardium (p <0.0001) in a multivariate model controlling for known correlates of impaired epicardial flow (presence of thrombus, percent diameter stenosis, left anterior descending artery location, and contrast material inflow in the epicardial artery [corrected TIMI frame count]). The time for contrast material to enter the myocardium is impaired to a greater degree in STEAMI compared with UAP/NSTEAMI, even after adjusting for other variables known to delay flow in the epicardial artery. These data provide insight into potential mechanistic differences between these 2 clinical syndromes.
    The American Journal of Cardiology 05/2003; 91(10):1163-7. · 3.21 Impact Factor
  • The American Journal of Cardiology 05/2003; 91(8):976-8, A4. · 3.21 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2003; 41(6):322-322.
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    ABSTRACT: Improved microvascular perfusion using the TIMI myocardial perfusion grade (TMPG) has been related to reduced in hospital, 30-day and 2-year mortality following thrombolytic administration. We sought to validate this measure using the more quantitative technique of digital subtraction angiography (DSA) and to correlate TMPG with ST segment resolution. DSA was used to analyze films from the LIMIT AMI acute myocardial infarction trial of front loaded r-tPA and rhuMAb CD18. Dye kinetics were also characterized using DSA in 88 arteries from patients without acute coronary syndromes in the absence of an obstructive lesion. Compared to normal patients, microvascular perfusion was reduced in acute myocardial infarction patients on DSA as demonstrated by a reduction in peak Gray (brightness) (p < 0.0001), the rate of rise in Gray/sec (p < 0.0001), the blush circumference (p < 0.0001), and the rate of growth in circumference (cm/sec) (p < 0.0001). However, while DSA perfusion was impaired overall in the setting of acute myocardial infarction, TMPG grade 3 in the setting of acute myocardial infarction did not differ from that in normal patients when studied quantitatively as shown by similar rates of growth in brightness and circumference (p = NS). ST resolution and the TMPG were significantly associated (p = 0.04). Compared to normal patients, acute myocardial infarction reduces the peak brightness of the myocardium, the rate of rise in brightness, the circumference of blush and the rate of growth in circumference as assessed using digital subtraction angiography. However, acute myocardial infarction patients with TMPG 3 had rates of growth in brightness and circumference that were nearly identical to normal patients. Thus, DSA validates that TMPG 3 is associated with normal kinetics of myocardial perfusion, and this likely accounts for the low (0.7%) 30 day mortality observed among those patients with TFG 3 and TMPG 3.
    Journal of Thrombosis and Thrombolysis 12/2002; 14(3):233-7. · 1.99 Impact Factor
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    ABSTRACT: Patients with diabetes are at increased risk of death after acute myocardial infarction, independent of other baseline risk factors and more severe coronary artery disease. We studied the angiographic and electrocardiographic responses to thrombolytic agents in patients with diabetes; in particular ST-segment resolution as a measure of microvascular flow. Angiography was performed in 2588 patients at 90 minutes after thrombolytic agent administration as well as after percutaneous coronary intervention (PCI) in the Thrombolysis In Myocardial Infarction (TIMI) 4, 10A, 10B, and 14 trials. Electrocardiographic parameters were assessed at baseline and at 90 minutes in the TIMI 14 trial. Compared with those without diabetes, patients with diabetes (347/2588 [13.4%]) were older, more often female, heavier, and less often smokers, and they had higher systolic blood pressure on admission. At angiography, they more frequently had 3-vessel disease, well-developed collateral vessels, more distal culprit lesions, and smaller reference segment diameters. In the infarct-related artery, there was no relationship between diabetes and TIMI 3 flow at 90 minutes (55.4% vs 59.0% without diabetes) or after PCI, (83.7% vs 84.2%, both P = NS). Corrected TIMI frame counts were also similar at both time points. However, there was less frequent complete ST-segment resolution among diabetic patients after thrombolysis (38.6% vs 49.2%, adjusted P =.04). Thrombolysis and adjunctive/rescue PCI achieved equal rates of epicardial flow in patients with and without diabetes. However, diabetic patients had less complete ST-segment resolution, suggesting impaired microvascular flow. Abnormal microvascular flow may contribute at least in part to the poorer outcomes observed in patients with diabetes and acute myocardial infarction.
    American heart journal 11/2002; 144(4):649-56. · 4.65 Impact Factor
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    ABSTRACT: Slower blood flow in the setting of acute myocardial infarction (MI) has been related to adverse outcomes, but the relationship of coronary blood flow after percutaneous transluminal coronary angioplasty (PTCA) in the setting of acute coronary syndromes to adverse outcomes and restenosis has not been well described. We sought to evaluate the correlates of pre- and post-PTCA coronary blood flow to shed light on potential modifiable determinants. The RESTORE trial (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing balloon angioplasty or directional atherectomy within 72 hours of occurrence of either unstable angina pectoris or acute MI. Coronary blood flow was assessed with the corrected TIMI frame count (CTFC), and clinical outcomes were assessed at 30 days. In addition to tighter and longer minimum lumen diameters (MLDs), the multivariate correlates of slower flow before PTCA also included the presence of thrombus, collaterals, left coronary artery lesion location, acute MI, and >8F catheter size. As well as the above variables, type C and D dissection grades were related to slower post-PTCA CTFC. Death, or the composite of death/MI/coronary artery bypass graft at 30 days, was more frequent among patients with slower post-PTCA CTFCs and those with post-PTCA thrombus. In a multivariate model correcting for reference segment diameter and MLD, the post-PTCA CTFC was an independent predictor of late lumen loss and the follow-up MLD at 6 months. As a single index that integrates functional and anatomical aspects of the post-PTCA results, the ratio of CTFC/MLD was associated with death/MI by 30 days. In addition to MLD, variables such as the presence of thrombus, left coronary artery lesion location, and dissection grade also are associated with slower coronary blood flow after PTCA. In turn, post-PTCA CTFCs were an independent predictor of late lumen loss and follow-up MLDs. Furthermore, patients who die or who sustain other adverse cardiac events have slower coronary blood flow and greater thrombus burden after PTCA.
    American heart journal 07/2002; 144(1):130-5. · 4.65 Impact Factor
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    ABSTRACT: Although 90-minute TIMI flow grades (TFGs), corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grades (TMPGs) have been associated with 30-day outcomes, we hypothesized that these indices would be related to long-term outcomes after thrombolytic administration. As a substudy of the TIMI 10B trial (tissue plasminogen activator versus tenecteplase), 49 centers carried out 2-year follow-up. TIMI grade 2/3 flow (Cox hazard ratio [HR] 0.41, P=0.001), reduced CTFCs (faster flow, P=0.02), and an open microvasculature (TMPG 2/3) (HR 0.51, P=0.038) were all associated with improved 2-year survival. Rescue percutaneous coronary intervention (PCI) of closed arteries (TFG 0/1) at 90 minutes was associated with reduced mortality (P=0.03), and mortality trended lower with adjunctive PCI of open (TFG 2/3) arteries (P=0.11). In a multivariate model correcting for previously identified correlates of mortality (age, sex, pulse, left anterior descending coronary artery infarction, and any PCI during initial hospitalization), patency (TFG 2/3) (HR 0.32, P<0.001), CTFC (P=0.01), and TMPG 2/3 remained associated with reduced mortality (HR 0.46, P=0.02). Both improved epicardial flow (TFG 2/3 and low CTFCs) and tissue-level perfusion (TMPG 2/3) at 90 minutes after thrombolytic administration are independently associated with improved 2-year survival, suggesting complementary mechanisms of improved long-term survival. Although rescue PCI reduced long-term mortality, improved microvascular perfusion (TMPG 2/3) before PCI was also related to improved mortality independently of epicardial blood flow and the performance of rescue or adjunctive PCI. Further prospective trials are warranted to re-examine the benefit of early PCI with thrombolysis.
    Circulation 04/2002; 105(16):1909-13. · 15.20 Impact Factor
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    ABSTRACT: Anterior precordial ST-segment depression (APSTD) is common in the setting of inferior myocardial infarction (IMI). The presence of APSTD correlates with increased risk of adverse outcomes in patients with acute IMI as well as more myocardium at risk as assessed by sestamibi, larger infarcts, lower ejection fractions, and more severe wall motion abnormalities in the infarct region. The ECG leads associated with APSTD (V1-V3) are generally thought to represent electrical activity subtended by the anterior myocardium, which is perfused by the left anterior descending artery (LAD). To determine whether APSTD is associated with abnormal blood flow in the uninvolved or non-culprit LAD, we assessed TIMI flow grades and corrected TIMI frame counts (CTFC) in both the culprit and non-culprit arteries of IMI patients. Data were drawn from the TIMI 10B trial of tenecteplase versus front-loaded tissue plasminogen activator in acute MI. Baseline ECGs were obtained within 12 hours of symptom onset, and angiography was performed 90 minutes following thrombolytic administration. A patient was considered to have precordial ST-segment depression if any ST-segment depression was present in any of leads V1-V3. The majority of IMI's were due to right coronary artery occlusions, both in patients with APSTD (79.6%) and without APSTD (77.9%). In patients in whom the LAD was not the culprit artery but with APSTD were significantly less likely to have TIMI 3 flow at 90 minutes and more likely to have TIMI 2 flow. There was a trend toward slower CTFC in APSTD patients (27.2 +/- 13.4 vs. 22.6 +/- 8.5 frames/sec, p = 0.07). Among patients with acute IMI associated with precordial ST-segment depression, flow in the non-culprit left anterior descending artery was slower than that in patients without APSTD. This finding may partially explain the occurrence of APSTD in IMI.
    Journal of Thrombosis and Thrombolysis 03/2002; 13(1):9-12. · 1.99 Impact Factor
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    ABSTRACT: The etiology of creatine kinase-myocardial band (CK-MB) release after percutaneous coronary intervention (PCI) remains unclear. The goal of this study was to evaluate the relationship of both epicardial and tissue level perfusion at the completion of stent placement to CK-MB release after the procedure. Given the high rates of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow after PCI, we hypothesized that abnormalities in tissue level perfusion would instead explain CK-MB release. Data were drawn from the angiographic substudy of the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) trial of eptifibatide versus placebo in patients undergoing planned coronary stent implantation. In the substudy, cinefilms of 65 patients were analyzed by an angiographic core laboratory blinded to enzymatic and clinical outcomes. The release of CK-MB was not associated with TIMI grade 3 flow or the corrected TIMI frame count; 100% of patients had TIMI grade 3 flow at the completion of PCI. In contrast, tissue level perfusion using the TIMI myocardial perfusion grade (TMPG) was related to postintervention CK-MB release: patients with a closed myocardium (TMPG 0/1) or delayed myocardial perfusion (TMPG 2) had an average CK-MB release 2.2 +/- 2.7 times the upper limit of normal (n = 34), whereas those patients with normal myocardial perfusion (TMPG 3, n = 24) had CK-MB 0.8 +/- 0.6 times the upper limit of normal (P =.01). Although no patients with TMPG 3 sustained death/myocardial infarction/urgent target vessel revascularization or thrombotic bailout, 17.7% of patients with TMPG 0/1/2 did by 48 hours (P =.037). Impaired tissue level perfusion as assessed by the TMPG and not epicardial coronary blood flow is associated with CK-MB elevation after PCI. These data provide a pathophysiologic link between impaired tissue level perfusion, post-PCI infarction, and adverse clinical outcomes.
    American heart journal 02/2002; 143(1):106-10. · 4.65 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2002; 39:302-302.
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    ABSTRACT: Background and Objectives Slower blood flow in the setting of acute myocardial infarction (MI) has been related to adverse outcomes, but the relationship of coronary blood flow after percutaneous transluminal coronary angioplasty (PTCA) in the setting of acute coronary syndromes to adverse outcomes and restenosis has not been well described. We sought to evaluate the correlates of pre- and post-PTCA coronary blood flow to shed light on potential modifiable determinants. Methods The RESTORE trial (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing balloon angioplasty or directional atherectomy within 72 hours of occurrence of either unstable angina pectoris or acute MI. Coronary blood flow was assessed with the corrected TIMI frame count (CTFC), and clinical outcomes were assessed at 30 days. Results In addition to tighter and longer minimum lumen diameters (MLDs), the multivariate correlates of slower flow before PTCA also included the presence of thrombus, collaterals, left coronary artery lesion location, acute MI, and >8F catheter size. As well as the above variables, type C and D dissection grades were related to slower post-PTCA CTFC. Death, or the composite of death/MI/coronary artery bypass graft at 30 days, was more frequent among patients with slower post-PTCA CTFCs and those with post-PTCA thrombus. In a multivariate model correcting for reference segment diameter and MLD, the post-PTCA CTFC was an independent predictor of late lumen loss and the follow-up MLD at 6 months. As a single index that integrates functional and anatomical aspects of the post-PTCA results, the ratio of CTFC/MLD was associated with death/MI by 30 days. Conclusions In addition to MLD, variables such as the presence of thrombus, left coronary artery lesion location, and dissection grade also are associated with slower coronary blood flow after PTCA. In turn, post-PTCA CTFCs were an independent predictor of late lumen loss and follow-up MLDs. Furthermore, patients who die or who sustain other adverse cardiac events have slower coronary blood flow and greater thrombus burden after PTCA. (Am Heart J 2002;144:130-5.)
    American Heart Journal - AMER HEART J. 01/2002; 144(1):130-135.
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    M.D. C. Michael Gibson M.S, Susan J. Marble
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    ABSTRACT: While thrombolytic agents have demonstrated improved mortality over the use of placebo, this has come at the expense of bleeding complications such as intracranial hemorrhage (ICH). Tenecteplase (TNK-tPA) is a novel thrombolytic agent engineered to improve upon the ease of use and safety of alteplase (t-PA). Given its longer half-life, TNK-tPA can be administered as a single bolus. The dosing of TNK-tPA has been weight optimized to enhance both safety and efficacy outcomes. Weight-optimized TNK-tPA dosing requires body weight estimation, which may introduce the potential for medication error. However, data from TNK-tPA clinical trials suggest that body weight estimates can err by up to 20 kg (44 lb) without an increased risk of ICH or death. Furthermore, the results of TNK-tPA clinical trials showed that even at the highest weight-optimized dosage of 50 mg, ICH rates were among the lowest reported in clinical trials of thrombolytics for acute myocardial infarction. in elderly female patients of low body weight, the use of weight-optimized TNK-tPA lowered the risk of ICH compared with the use of t-PA, expanding the potential use of thrombolytics to this high-risk patient population. Tenecteplase has demonstrated clinical equivalence to t-PA, but with a wider therapeutic margin of safety.
    Clinical Cardiology 08/2001; 24(9):577 - 584. · 1.83 Impact Factor
  • The American Journal of Cardiology 07/2001; 87(11):1293-5. · 3.21 Impact Factor
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    ABSTRACT: The goal of this study was to examine the relationship between contrast agent type (ionic vs. nonionic) and angiographic, electrocardiographic, and clinical outcomes after thrombolytic administration. Ionic or nonionic contrast agents were selected in a nonrandomized fashion for 90-min angiography and percutaneous coronary intervention (PCI) following thrombolytic administration in the TIMI 14 trial [tissue plasminogen activator (tPA) or reteplase (rPA) vs. low-dose lytic + abciximab]. There was no relationship between contrast agent type and overall patency, rate of TIMI grade 3 flow, or corrected TIMI frame counts (CTFCs) in open culprit arteries and in post-PCI patency rates or post-PCI CTFCs. In patients treated with ionic contrast, ejection fractions at 90 min were slightly but significantly lower (56.2 +/- 16.5, n = 122, vs. 59.8 +/- 14.4, n = 322; P = 0.02), chest pain duration was longer (2.8 +/- 4.1 hr, n = 255, vs. 1.7 +/- 3.6, n = 550; P = 0.0003), and complete ST segment resolution was less frequent (41.5% vs. 50.8%; P = 0.04). While there was no difference in epicardial blood flow, ionic contrast agent use was associated with poorer ST segment resolution, longer chest pain duration, and poorer ejection fractions, perhaps as a result of microvascular dysfunction.
    Catheterization and Cardiovascular Interventions 06/2001; 53(1):6-11. · 2.51 Impact Factor

Publication Stats

2k Citations
227.00 Total Impact Points

Institutions

  • 2003–2008
    • Beth Israel Deaconess Medical Center
      • Department of Medicine
      Boston, MA, United States
  • 2001–2003
    • Boston Biomedical Research Institute
      Boston, Massachusetts, United States
  • 1996–2003
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 1999–2002
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
    • Allegheny General Hospital
      Pittsburgh, Pennsylvania, United States