Robert J Mentz

Duke University, Durham, North Carolina, United States

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Publications (59)258.91 Total impact

  • Journal of cardiac failure. 08/2014; 20(8S):S95.
  • Journal of cardiac failure. 08/2014; 20(8S):S49.
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    ABSTRACT: Despite the well-established benefits of mineralocorticoid receptor agonists (MRAs) in heart failure with reduced ejection fraction, safety concerns remain in patients with concomitant diabetes mellitus (DM) because of common renal and electrolyte abnormalities in this population. We analyzed all-cause mortality and composite cardiovascular mortality and HF hospitalization over a median 9.9 months among 1,998 patients in the placebo arm of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial by DM status and discharge MRA use. Of the 750 patients with DM, 59.2% were receiving MRAs compared with 62.5% in the non-DM patients. DM patients not receiving MRAs were older, more likely to be men, with an ischemic heart failure etiology and slightly worse renal function compared with those receiving MRAs. After adjustment for baseline risk factors, among DM patients, MRA use was not associated with either mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.75 to 1.15) or the composite end point (HR 0.94; 95% CI 0.80 to 1.10). Similar findings were seen in non-DM patients (mortality [HR 1.01; 95% CI 0.84 to 1.22] or the composite end point [HR 0.98; 95% CI 0.85 to 1.13] [p >0.43 for DM interaction]). In conclusion, in-hospital initiation of MRA therapy was low (15% to 20%), and overall discharge MRA use was only 60% (with regional variation), regardless of DM status. There does not appear to be clear, clinically significant in-hospital hemodynamic or even renal differences between those on and off MRA. Discharge MRA use was not associated with postdischarge end points in patients hospitalized for worsening heart failure with reduced ejection fraction and co-morbid DM. DM does not appear to influence the effectiveness of MRA therapy.
    The American Journal of Cardiology 06/2014; · 3.21 Impact Factor
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    ABSTRACT: Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.
    JACC. Heart failure. 06/2014;
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    ABSTRACT: AimsThe impact of refractory angina pectoris (AP) in patients with ischaemic cardiomyopathy (ICM) is unknown. We investigated the characteristics and outcomes of ICM patients with persistent AP following cardiac catheterization.Methods and resultsPatients who underwent coronary angiography at Duke from 2000 to 2009 with an EF <40% and ICM with persistent AP were compared with similar patients without persistent AP. Persistent AP was defined by patient report of ischaemic symptoms within 1 year of index catheterization. Time-to-event was examined using Kaplan–Meier or cumulative incidence and Cox proportional hazards modelling methods for death/myocardial infarction (MI)/revascularization [i.e. major adverse cardiac events (MACE)], death/MI, death, and cardiovascular death/hospitalization. Of 965 ICM patients, 298 (31%) had persistent AP. These patients were younger and had more previous revascularization than patients without persistent AP. Both groups had high use of aspirin, beta-blockers, ACE inhibitors, and statins, but modest nitrate use. Over a median follow-up of >5 years, patients with persistent AP had increased rates of MACE, and cardiovascular death/hospitalization compared with patients without persistent AP [5-year cumulative event rates of 53% vs. 46% (P = 0.013) and 73% vs. 60% (P < 0.0001), respectively], but similar rates of death (P = 0.59) and death/MI (P = 0.50). After multivariable adjustment, persistent AP remained associated with increased MACE [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.08–1.57], and cardiovascular death/hospitalization (HR 1.36; 95% CI 1.14–1.62).Conclusion Persistent AP is common despite medical therapy in patients with ICM and is independently associated with increased long-term MACE and rehospitalization. Future prospective studies of persistent AP in ICM patients are warranted.
    European Journal of Heart Failure 06/2014; · 5.25 Impact Factor
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    ABSTRACT: -Anemia has been associated with worse outcomes in patients with chronic heart failure (HF). We aimed to characterize the clinical profile and post-discharge outcomes of hospitalized HF (HHF) patients with anemia at admission and/or discharge. -An analysis was performed on 3731/4133 (90%) of HHF patients with ejection fraction <40% enrolled in the EVEREST trial with baseline hemoglobin data, comparing the clinical characteristics and outcomes [all-cause mortality (ACM) and cardiovascular mortality (CVM) or HF hospitalization] of patients with and without anemia (hemoglobin <12g/dL for females and <13g/dL for males) on admission and/or discharge/day 7. Overall, 1277 patients (34%) were anemic at baseline, which persisted through discharge in 73% and resolved in 27%; 6% of patients without baseline anemia developed anemia by discharge/day 7. Patients with anemia were older, with lower blood pressure, and higher creatinine and natriuretic peptide levels compared to those without anemia (all P<0.05). After risk adjustment, anemia at discharge, but not admission was independently associated with increased ACM (Hazard Ratio [HR] 1.30; 95% Confidence Interval [CI], 1.05-1.60, P=0.015; and HR 0.94; 95% CI, 0.76-1.15, P=0.53, respectively) and CVM+HF hospitalization early post-discharge (≤100 days) (HR 1.73; 95% CI, 1.37-2.18, P=<0.001; and HR 0.92; 95% CI, 0.73-1.16, P=0.47, respectively). Neither baseline nor discharge anemia was associated with long-term CVM+HF hospitalization (>100 days) on adjusted analysis (both P>0.1). -Among HHF patients with reduced EF, modest anemia at discharge but not baseline was associated with increased ACM and short-term CVM+HF hospitalization. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00071331.
    Circulation Heart Failure 04/2014; · 6.68 Impact Factor
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    ABSTRACT: AimsThe implications of geographical variation are unknown following adjustment for hospital length of stay (LOS) in heart failure (HF) trials that included patients whether or not they had systolic dysfunction. We investigated regional differences in an international acute HF trial.Methods and resultsThe PROTECT trial investigated 2033 patients with acute HF and renal dysfunction hospitalized at 173 sites in 17 countries with randomization to rolofylline or placebo. We grouped enrolling countries into six regions. Baseline characteristics, in-hospital management, and outcomes were explored by region. The primary study outcome was 60-day mortality or cardiovascular/renal hospitalization. Secondary outcomes included 180-day mortality. Of 2033 patients, 33% were from Eastern Europe, 19% from Western Europe, 16% from Israel, 15% from North America, 14% from Russia, and 3% from Argentina. Marked differences in baseline characteristics, HF phenotype, in-hospital diuretic and vasodilator strategies, and LOS were observed by region. LOS was shortest in North America and Israel (median 5 days) and longest in Russia (median 15 days). Regional event rates varied significantly. Following multivariable adjustment, region was an independent predictor of the risk of mortality/hospitalization at 60 days, with the lowest risk in Russia (hazard ratio 0.39, 95% confidence interval 0.23–0.64 vs. Western Europe) due to lower rehospitalization; mortality differences were attenuated by 180 days.Conclusions In an international HF trial, there were differences in baseline characteristics, treatments, LOS, and rehospitalization amongst regions, but little difference in longer term mortality. Rehospitalization differences exist independent of LOS. This analysis may help inform future trial design and should be externally validated.
    European Journal of Heart Failure 04/2014; · 5.25 Impact Factor
  • Robert J Mentz, Mona Fiuzat
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    ABSTRACT: Sleep-disordered breathing (SDB) is prevalent in patients with heart failure, and is associated with increased morbidity and mortality. SDB is proinflammatory, with nocturnal oxygen desaturations and hypercapnia appearing to play a pivotal role in the development of oxidative stress and sympathetic activation. Preliminary data suggest that attention to the diagnosis and management of SDB in patients with heart failure may improve outcomes. Ongoing research into the roles of comorbidities such as SDB as a treatment target may lead to better clinical outcomes and improved quality of life for patients with heart failure.
    Heart Failure Clinics 04/2014; 10(2):243-250.
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    ABSTRACT: Despite advances in medical therapy for chronic heart failure (HF), advanced HF carries a dismal prognosis. Options such as transplantation and durable mechanical circulatory support have greatly improved outcomes for these patients, but their introduction has introduced significant complexity to patient management. Although much of this management occurs at specialized heart transplant centers, it is the responsibility of the primary cardiologist of the patient with advanced HF to refer patients at the appropriate time and to help them navigate the difficult decisions related to the pursuit of advanced therapies. We present a unique pathway that incorporates guidelines, recent data, and expert opinion to help general cardiologists determine which patients should be referred for transplantation or durable mechanical circulatory support, and when they should be referred. Decision making on referral to the heart transplant center is also summarized.
    Critical pathways in cardiology 03/2014; 13(1):1-5.
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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
  • Adam D Devore, Robert J Mentz, Chetan B Patel
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    ABSTRACT: The prevalence of patients living with advanced heart failure continues to rise. For a subset of these patients, continuous-flow left ventricular assist devices (LVADs) are a life-saving therapy. Given the efficacy and durability of contemporary LVAD devices, their use has increased exponentially in recent years. The medical management of patients with an LVAD is an area of expertise for advanced heart failure clinicians, but a general understanding of the initial approach to, and stabilization of, LVAD patients is an important skillset for many health care providers. The rapidly changing field of the medical management of LVAD patients is largely based on clinical experience and limited published data. In this manuscript, we integrate the available published data on the medical management of LVAD patients with the growing clinical experience.
    Current Treatment Options in Cardiovascular Medicine 02/2014; 16(2):283.
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    ABSTRACT: Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high post-discharge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible contributors to the lack of success in HHF outcome trials include challenges in selecting clinical sites capable of 1) providing adequate numbers of appropriately selected patients and 2) properly executing the study protocol. We propose a “pre-trial” registry as a novel tool for improving the efficiency and quality of international HHF trials by focusing on the selection and cultivation of high quality sites. A pre-trial registry may help assess a site’s ability to achieve adequate enrollment of the target patient population, integrate protocol requirements into clinical workflow, and accomplish appropriate follow-up. While such a process would be associated with additional upfront resource investment, this appropriation may be modest in comparison to the downstream costs associated with maintenance of poorly performing sites, failed clinical trials, and the global health and economic burden of HHF. This review is based on discussions between scientists, clinical trialists, and regulatory representatives regarding methods for improving international HHF trials that took place at the US Food and Drug Administration (FDA) on January 12th 2012.
    American Heart Journal. 01/2014;
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    ABSTRACT: A subset of patients hospitalized with acute heart failure experiences worsening clinical status and requires escalation of therapy. Worsening heart failure is an end point in many clinical trials, but little is known about its prevalence in clinical practice and its associated outcomes.
    Journal of the American Heart Association. 01/2014; 3(4).
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    ABSTRACT: The progressive nature of heart failure (HF) coupled with high mortality and poor quality of life mandates greater attention to palliative care as a routine component of advanced HF management. Limited evidence exists from randomized, controlled trials supporting the use of interdisciplinary palliative care in HF. Methods The Palliative Care in Heart Failure trial (PAL-HF) is a prospective, controlled, unblinded, single-center study of an interdisciplinary palliative care intervention in 200 patients with advanced HF estimated to have a high likelihood of mortality or re-hospitalization in the ensuing 6 months. The 6-month PAL-HF intervention focuses on physical and psychosocial symptom relief, attention to spiritual concerns and advanced care planning. The primary endpoint is health-related quality of life measured by the Kansas City Cardiomyopathy Questionnaire and the Functional Assessment of Chronic Illness Therapy with Palliative Care Subscale score at 6 months. Secondary endpoints include changes in anxiety/depression, spiritual well-being, caregiver satisfaction, cost and resource utilization, and a composite of death, HF hospitalization and quality of life. Conclusions PAL-HF is a randomized, controlled clinical trial that will help evaluate the efficacy and cost-effectiveness of palliative care in advanced HF using a patient-centered outcome as well as clinical and economic endpoints.
    American Heart Journal. 01/2014;
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    ABSTRACT: We aimed to investigate the characteristics and outcomes of patients with heart failure with preserved ejection fraction (HFpEF) and angina pectoris (AP). AP is a predictor of adverse events in patients with heart failure with reduced EF. The implications of AP in HFpEF are unknown. We analyzed HFpEF patients (EF≥50%) who underwent coronary angiography at Duke University Medical Center from 2000-2010 with and without AP in the previous 6 weeks. Time to first event was examined using Kaplan-Meier methods for the primary endpoint of death/myocardial infarction (MI)/revascularization/stroke (i.e., MACE) and secondary endpoints of death/MI/revascularization, death/MI/stroke, death/MI, death and cardiovascular death/cardiovascular hospitalization. In the Duke Databank, 3517 patients met criteria for inclusion and 1402 (40%) had AP. Those with AP were older with more comorbidities, and prior revascularization vs. non-AP patients. AP patients more often received beta-blockers, ACE-inhibitors, nitrates, and statins (all P<0.05). In unadjusted analysis, AP patients had increased MACE and death/MI/revascularization (both P <0.001), lower rates of death and death/MI (both P<0.05), and similar rates of death/MI/stroke and cardiovascular death/cardiovascular hospitalization (both P>0.1). After multivariable adjustment, those with AP remained at increased risk for MACE (Hazard Ratio [HR] 1.30; 95% Confidence Interval [CI], 1.17-1.45) and death/MI/revascularization (HR 1.29; 95% CI, 1.15-1.43), but were at similar risk for other endpoints (P>0.06). AP in HFpEF patients with a history of coronary artery disease is common despite medical therapy and is independently associated with increased MACE due to revascularization with similar risk of death, MI, and hospitalization.
    Journal of the American College of Cardiology 10/2013; · 14.09 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
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    ABSTRACT: The strength of race as an independent predictor of long-term outcomes in a contemporary chronic heart failure (HF) population and its association with exercise training response have not been well established. We aimed to investigate the association between race and outcomes and to explore interactions with exercise training in patients with ambulatory HF. We performed an analysis of HF-ACTION, which randomized 2331 patients with HF having an ejection fraction ≤35% to usual care with or without exercise training. We examined characteristics and outcomes (mortality/hospitalization, mortality, and cardiovascular mortality/HF hospitalization) by race using adjusted Cox models and explored an interaction with exercise training. There were 749 self-identified black patients (33%). Blacks were younger with significantly more hypertension and diabetes, less ischemic etiology, and lower socioeconomic status versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at baseline. Over a median follow-up of 2.5 years, black race was associated with increased risk for all outcomes except mortality. After multivariable adjustment, black race was associated with increased mortality/hospitalization (hazard ratio [HR] 1.16, 95% CI 1.01-1.33) and cardiovascular mortality/HF hospitalization (HR 1.46, 95% CI 1.20-1.77). The hazard associated with black race was largely caused by increased HF hospitalization (HR 1.58, 95% CI 1.27-1.96), given similar cardiovascular mortality. There was no interaction between race and exercise training on outcomes (P > .5). Black race in patients with chronic HF was associated with increased prevalence of modifiable risk factors, lower exercise performance, and increased HF hospitalization, but not increased mortality or a differential response to exercise training.
    American heart journal 09/2013; 166(3):488-495.e1. · 4.65 Impact Factor
  • Robert J Mentz, Richard C Becker
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    ABSTRACT: Contemporary cardiovascular research offers junior investigators the opportunity to explore the gamut of biomedical questions. Despite the recent reduction in the availability of funding mechanisms that have historically served as the primary pathways for investigators in the early stages of career development, there remain numerous traditional and non-traditional funding opportunities. This article highlights these opportunities in order to assist early career investigators in the development of a personalized research trajectory, which optimizes the potential for career success.
    Journal of Thrombosis and Thrombolysis 07/2013; · 1.99 Impact Factor
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    ABSTRACT: Haemoconcentration has been studied as a marker of decongestion in patients with hospitalization for heart failure (HHF). We describe the relationship between haemoconcentration, worsening renal function, post-discharge outcomes, and clinical and laboratory markers of congestion in a large multinational cohort of patients with HHF. In 1684 patients with HHF with ejection fraction (EF) ≤40% assigned to the placebo arm of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, absolute in-hospital haematocrit change was calculated as the change between baseline and discharge or day 7 (whichever occurred first). Patient characteristics, changes in renal function, and outcomes over a median follow-up of 9.9 months were compared by in-hospital haematocrit change. Overall, 26% of patients had evidence of haemoconcentration (i.e. ≥3% absolute increase in haematocrit). Patients with greater increases in haematocrit tended to have better baseline renal function. Haemoconcentration correlated with greater risk of in-hospital worsening renal function, but renal parameters generally returned to baseline within 4 weeks post-discharge. Patients with haemoconcentration were less likely to have clinical congestion at discharge, and experienced greater in-hospital decreases in body weight and natriuretic peptide levels. After adjustment for baseline clinical risk factors, every 5% increase of in-hospital haematocrit change was associated with a decreased risk of all-cause death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.70-0.95]. Haematocrit change was also associated with decreased cardiovascular mortality or heart failure (HF) hospitalization at ≤100 days post-randomization (HR 0.73, 95% CI 0.71-0.76). In this large cohort of patients with HHF with reduced EF, haemoconcentration was associated with greater improvements in congestion and decreased mortality and HF re-hospitalization despite an increased risk of in-hospital worsening renal function.
    European Journal of Heart Failure 07/2013; · 5.25 Impact Factor

Publication Stats

182 Citations
258.91 Total Impact Points

Institutions

  • 2012–2014
    • Duke University
      Durham, North Carolina, United States
    • Emory University
      • Division of Cardiology
      Atlanta, Georgia, United States
    • Northwestern University
      • Division of Cardiology (Dept. of Medicine)
      Evanston, IL, United States
  • 2011–2014
    • Duke University Medical Center
      • Division of Cardiology
      Durham, North Carolina, United States
    • Brigham and Women's Hospital
      • Division of General Internal Medicine and Primary Care
      Boston, MA, United States
  • 2013
    • Stanford Medicine
      • Department of Medicine
      Stanford, CA, United States
  • 2012–2013
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States