James L Januzzi

Harvard Medical School, Boston, Massachusetts, United States

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Publications (68)580.67 Total impact

  • James L Januzzi · Douglas L Mann

    No preview · Article · Aug 2015
  • Nasrien Ibrahim · James L Januzzi
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    ABSTRACT: Heart failure (HF) is a complex disease process that is challenging to diagnose and manage. For more than 15 years, biomarkers have been used to diagnose and the guide the management of patients with this disease. The gold standard biomarkers for HF are B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP); both are used for diagnosis and prognosis. More recently, there has been an interest in use of BNP and NT-proBNP for HF management as well. Important aspects regarding production and clearance of BNP and NT-proBNP exist, which are vital for the clinician to understand. Beyond BNP or NT-proBNP, other newer biomarkers such as mid-regional pro-atrial natriuretic peptide, soluble ST2, highly sensitive troponin and renal biomarkers may add value for prognostication and possibly, patient management. In this article, the authors will discuss the established and evolving role of BNP and NT-proBNP in HF, along with consideration of select newer biomarkers in this setting.
    No preview · Article · Jul 2015 · Expert Review of Cardiovascular Therapy
  • Aditi Mallick · James L. Januzzi
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    ABSTRACT: A member of the interleukin-1 receptor family, soluble ST2 (sST2), is a powerful marker of myocyte strain and vascular stress in heart failure and acute coronary syndrome, as well as numerous other cardio-pulmonary disease states. It is clinically useful in both the emergency department and hospital setting for predicting disease prognosis and mortality. Together with patient-specific characteristics, sST2 also has an increasing role to play as a tool to guide therapeutic interventions. We will discuss where this important new biomarker fits in now and its promise for the future.
    No preview · Article · Jun 2015
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    ABSTRACT: To evaluate the associations of soluble ST2 (sST2) and galectin-3 with death relative to renal function in patients with heart failure (HF). Eleven-hundred-and-sixty-one patients hospitalized for HF with 1-year follow up were enrolled for biomarkers analysis. Patients were divided into two groups based on eGFR of either > or ≤60 ml/min/1.73 m(2). sST2 was independently associated with death in both categories of renal function, while galectin-3 lost this significance after addition of NT-proBNP to the model of patients with eGFR ≤60 ml/min/1.73 m(2). In patients with HF, sST2 improved prediction for death beyond risk factors without being influenced by renal function, however, the prognostic value of galectin-3 is less clear below an eGFR of 60 ml/min/1.73 m(2).
    No preview · Article · May 2015 · Biomarkers in Medicine
  • James L Januzzi

    No preview · Article · Apr 2015 · Journal of the American College of Cardiology
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    ABSTRACT: Arterial hypertension is a main determinant of arterial remodelling and atherosclerosis. Coronary artery calcium score and carotid intima-media thickness are recognized indices of vascular remodelling. Established biohumoral markers for the diagnosis of atherosclerosis are still lacking in asymptomatic subjects with hypertension. We aimed to test the association of plasma N-terminal pro B-type natriuretic peptide concentrations with either coronary artery calcium score or carotid intima-media thickness in asymptomatic hypertensive subjects. We conducted a case-control study on 436 hypertensi.ve and 436 age/sex-matched normotensive subjects from the population of the Montignoso HEart and Lung Project, a community-based study of asymptomatic general population ≥45 years. Subjects underwent N-terminal pro B-type natriuretic peptide measurement, echocardiography and evaluation of coronary artery calcium score and carotid intima-media thickness. Hypertensive subjects had higher median coronary artery calcium score (60 (interquartile range, 30-112) vs. 15 (interquartile range 3-70) Agatson units, p = 0.007), carotid intima-media thickness (8.6 (interquartile range 7.5-9.1) vs. 7.9 (7.1-8.4) µm, p < 0.001) and indexed left ventricular mass (101 (interquartile range 82-126) vs. 87 (63-91) mg/m2, p = 0.03) than controls, with no differences in left ventricular ejection fraction, diameters, E/E', left atrial area. N-terminal pro B-type natriuretic peptide concentrations were higher in hypertensive subjects with either coronary artery calcium score (p = 0.008) or carotid intima-media thickness >75th (p < 0.006) percentile and highest in combined coronary artery calcium score/carotid intima-media thickness >75th percentile (p = 0.021). In multivariable analysis, N-terminal pro B-type natriuretic peptide independently predicted either coronary artery calcium score or carotid intima-media thickness >75th percentile, but only in hypertensive subjects (odds ratio = 1.87, 95% confidence interval 1.30-2.74, p = 0.001 and odds ratio = 1.99, 95% confidence interval 1.43-2.76, p = 0.001). In asymptomatic subjects with hypertension, N-terminal pro B-type natriuretic peptide is a marker of hypertension-mediated preclinical vascular disease. © The European Society of Cardiology 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    No preview · Article · Feb 2015 · European Journal of Preventive Cardiology
  • Domingo A Pascual-Figal · James L Januzzi
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    ABSTRACT: ST2 is a member of the Interleukin-1 receptor family with two main isoforms: transmembrane or cellular (ST2L) and soluble or circulating (sST2) forms. ST2 is the receptor of the IL-33, which is an IL-1 like cytokine that can be secreted by living cells in response to cell damage. IL-33 exerts its cellular functions by binding a receptor complex composed of ST2L and IL-1R accessory protein. The IL-33/ST2 system is up-regulated in cardiomyocytes and fibroblasts as response to mechanical stimulation or injury. The interaction between IL33 and ST2L has been demonstrated to be cardioprotective: in experimental models, this interaction reduces myocardial fibrosis, prevents cardiomyocyte hypertrophy, reduces apoptosis and improves myocardial function. The beneficial effects of IL-33 are specifically through the ST2L receptor. sST2 avidly binds IL-33 which results in interruption of the interaction between IL-33/ST2L and consequently eliminates the anti-remodeling effects; thus sST2 is viewed as a decoy receptor. In recent years, knowledge about ST2 role in the pathophysiology of cardiovascular diseases has broadly expanded, with strong links to myocardial dysfunction, fibrosis, and remodeling. Beyond its myocardial role, the IL-33/ST2 system could have an additional role in the development and progression of atherosclerosis. In conclusion, IL-33/ST2L signaling is a mechanically activated, cardioprotective fibroblast-cardiomyocyte paracrine system, which may have therapeutic potential for beneficially regulating the myocardial response to overload and injury. In contrast, sST2 acts as a decoy receptor and, by sequestering IL-33, antagonizes the cardioprotective effects of IL-33/ST2L interaction.
    No preview · Article · Jan 2015 · The American Journal of Cardiology
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    ABSTRACT: Natriuretic peptides and suppression of tumorigenicity 2 (ST2) represent two different physiopathological pathways. We evaluated the prognostic accuracy and complementarity of B-type natriuretic peptide (BNP) and soluble ST2 (sST2) plasma levels at discharge from a hospital admission for acute heart failure, both in patients with preserved (HFpEF) and depressed (HFrEF) systolic function. We enrolled 195 consecutive patients discharged alive and followed them prospectively for 6 months. The endpoint was all-cause death or hospital readmission for heart failure. Seventy-six patients had HFpEF and 119 had HFrEF, of whom 23 (30.3 %) and 43 (36.1 %) reached the combined endpoint, respectively. In both HFpEF and HFrEF, having the two biomarkers into account added prognostic information, with the highest risk in patients with both biomarkers above the median in their group (approximately 40 % hospitalization-free survival in both groups at 6 months). These associations translated into a significant fourfold increase in risk of the endpoint for one elevated biomarker and sevenfold for both biomarkers elevated in HFrEF, and no association for one elevated biomarker and fivefold increase in risk for both biomarkers elevated in HFpEF. Considering the reclassification of risk added to BNP by measurement of sST2, net reclassification index was 0.31 (p = 0.21) among patients with HFpEF and 0.70 (p < 0.001) among patients with HFrEF. sST2 provides robust prognostic information in acute heart failure with HFrEF, while this pattern was less clear in HFpEF. When sST2 was measured together with BNP, it improved prognostic accuracy in both groups, more clearly in HFrEF.
    No preview · Article · Jan 2015 · Clinical Research in Cardiology
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    ABSTRACT: Background sST2 has been shown to be a risk predictor in heart failure (HF). Our aim was to explore the characteristics and prognostic value of soluble ST2 (sST2) in hospitalized Chinese patients with HF. Methods and Results We consecutively enrolled 1528 hospitalized patients with HF. Receiver operating characteristic (ROC) and multivariable Cox proportional hazards analysis were used to assess the prognostic values of sST2. Adverse events were defined as all-cause death and cardiac transplantation. During a median follow-up of 19.1 months, 325 patients experienced adverse events. Compared with patients free of events, sST2 concentrations were significantly higher in patients with events (P<0.001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with adverse events (per 1 log unit, adjusted hazard ratio 1.52, 95% confidence interval: 1.30 to 1.78, P<0.001). An sST2 concentration in the highest quartiles (>55.6 ng/mL) independently predicted events in comparison to the lowest quartile (≤25.2 ng/mL) when adjusted by multivariable model. In ROC analysis, the area under the curve for sST2 was not different from that for NT-proBNP in short and longer term. Over time, sST2 also improved discrimination and reclassification of risk beyond NT-proBNP. Conclusions sST2 is a strong independent risk predictor in Chinese patients hospitalized with HF and can significantly provide additional prognostic value to NT-proBNP in risk prediction.
    Preview · Article · Oct 2014 · PLoS ONE
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    ABSTRACT: No published information exists to support the safe use of ticagrelor in patients with a clopidogrel allergy. This study involved an institutional review board-approved retrospective review of patients with a documented clopidogrel allergy who subsequently received ticagrelor between July 2011 and February 2014. We report the cases of two patients with a history of hypersensitivity to clopidogrel in whom ticagrelor was used successfully without documented incident. In addition, principles suggesting a lack of cross-sensitivity between ticagrelor and clopidogrel are reviewed. These cases combined with theoretical evidence support the use of ticagrelor in patients with hypersensitivity to clopidogrel.
    No preview · Article · Aug 2014 · Pharmacotherapy
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    ABSTRACT: Background Rehospitalization is a major cause for heart failure (HF) related morbidity, and is associated with considerable loss of quality of life and costs. The rate of unplanned rehospitalization in HF patients is unacceptably high; current risk stratification to identify patients at risk for rehospitalization is inadequate. We evaluated whether measurement of galectin-3 would be helpful in identifying patients at such risk. Methods We analyzed pooled data from patients (N=902) enrolled in 3 cohorts (COACH, N=592; PRIDE, N=181; and UMD H-23258, N=129) originally admitted because of HF. Mean patient age was between 61.6 and 72.9 years across the cohorts, with a wide range of left ventricular ejection fraction. Galectin-3 levels were measured during index admission. We used fixed and random effects models, as well as continuous and categorical reclassification statistics to assess the association of baseline galectin-3 levels with risk of post-discharge rehospitalization at different time points and the composite endpoint all cause mortality and rehospitalization. Results Compared to patients with galectin-3 concentrations below 17.8 ng/mL, those with results exceeding this value were significantly more likely to be rehospitalized for HF at 30, 60, 90 and 120 days after discharge; odds ratios (OR) 2.80 (95% CI: 1.41-5.57), 2.61 (95% CI: 1.46-4.65), 3.01 (95% 1.79-5.05) and 2.79 (95% 1.75-4.45), respectively. After adjustment for age, gender, NYHA class, renal function (eGFR), LVEF, and BNP, galectin-3 remained an independent predictor of HF rehospitalization. Addition of galectin-3 to risk models significantly reclassified patient risk of post-discharge rehospitalization and fatal event at each time point (continuous NRI at 30 days of +42.6% (95% CI: +19.9-65.4%), P <0.001). Conclusions Among patients hospitalized for HF, plasma galectin-3 concentration is useful for the prediction of near-term rehospitalization.
    Full-text · Article · Jun 2014 · American Heart Journal
  • Parul U Gandhi · James L Januzzi

    No preview · Article · May 2014 · European Heart Journal
  • James L Januzzi · Paul J Hauptman

    No preview · Article · May 2014 · Circulation Heart Failure
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    Preview · Article · Apr 2014 · Clinical Chemistry
  • Richard Troughton · G. Michael Felker · James L Januzzi
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    ABSTRACT: The natriuretic peptides are important tools to establish diagnosis and prognosis in heart failure (HF). With application of therapies for HF, changes in both B-type natriuretic peptide (BNP) and its amino terminal cleavage fragment (NT-proBNP) parallel the benefits of the HF therapy applied. This dynamic nature of BNP and NT-proBNP relative to therapeutic intervention in HF has led to the concept of using the biomarkers as a 'guide' for intensification of HF care with a goal of not only achieving guideline-directed medical therapy goals accompanied by targeted natriuretic peptide suppression below prognostic thresholds. In studies achieving this combination of therapy optimization and BNP/NT-proBNP suppression, superior outcomes have been observed, and the approach was well tolerated. Natriuretic peptide-guided HF therapy has recently been given a recommendation in US HF guidelines to achieve guideline-directed medical therapy (Class IIa) and possibly improve outcome (Class IIb), while other clinical practice guidelines (including those from the European Society of Cardiology) await results from emerging clinical trial data. We will review lessons learned in the past regarding this novel concept of biomarker guided HF care, and discuss future directions for the approach.
    No preview · Article · Nov 2013 · European Heart Journal
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    James L Januzzi · Roland Rj van Kimmenade
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    ABSTRACT: Following the introduction of B-type natriuretic peptide (BNP) and its amino-terminal equivalent (NT-proBNP), the use of biomarkers for the evaluation and management of heart failure (HF) has grown. Indeed, natriuretic peptide testing for diagnosis and prognosis recently earned a Class I Level of Evidence: A in the 2013 American Heart Association/American College of Cardiology clinical practice guidelines for HF (2). Although it took years to develop such support, this is indeed the proper recognition of the clinical role played by these important biomarkers.
    Preview · Article · Sep 2013 · Journal of the American College of Cardiology
  • Noreen P Kelly · James L Januzzi
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    ABSTRACT: Opinion statement: While heart failure (HF) treatment guidelines exist, there are significant gaps in their implementation owing in part to the lack of objective data to help guide clinicians in their medical decision-making. B-type natriuretic peptide (BNP) and its amino-terminal equivalent (NT-proBNP) are objective markers of HF prognosis, are useful to monitor response to treatment in outpatients with HF, and may have a role in "guiding" HF care as well. Successful BNP or NT-proBNP guided HF treatment requires regular attempts to reach and maintain target values (BNP ≤ 125 pg/mL or NT-proBNP ≤ 1000 pg/mL). This may be achieved through lifestyle modifications, exercise programs, medication adjustments, and therapeutic interventions shown to reduce morbidity and mortality in HF patients. Failure to achieve biomarker targets portends a worse prognosis, proportional to the lowest achieved natriuretic peptide concentration; in those with significant biomarker "nonresponse," prognosis is poor, and alternative therapeutic strategies should be considered.
    No preview · Article · May 2013 · Current Treatment Options in Cardiovascular Medicine
  • James L Januzzi
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    ABSTRACT: Following the initial discovery of a natriuretic and diuretic peptide factor present in atrial myocardial tissue homogenates, subsequent elucidation of the natriuretic peptide (NP) family has led to substantial advances in the understanding of the autocrine, paracrine, and endocrine regulation of the cardiovascular system. Furthermore, with the development of assays for the measurement of the NPs, these important biomarkers have gone from being regarded as biological mediators of the cardiovascular system to now represent important clinical tools for the diagnostic and prognostic evaluation of patients with heart failure and may have potential as a therapeutic target in this setting as well. An historical perspective on the NPs from bench to bedside translation will be discussed.
    No preview · Article · May 2013 · Journal of Investigative Medicine
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    ABSTRACT: Background: Soluble ST2 (sST2) is an emerging prognostic biomarker in patients with existing cardiovascular disease. ST2 and its ligand, interleukin-33 (IL-33), are expressed in endothelial cells, and may play an important role in the development of early atherosclerosis and vascular biology. We sought to investigate the association of sST2 and progression of blood pressure (BP), as well as the development of hypertension. Methods: Circulating sST2 concentrations were measured in 1834 participants (mean age 56 years, 57% women) of the community-based Framingham Offspring study. Participants were free of hypertension at baseline. Multivariable linear and logistic regression models were used to evaluate the association of sST2 concentrations and subsequent BP outcomes. Results: Higher sST2 concentrations were associated with incident hypertension over 3 years of follow-up [multivariable-adjusted odds ratio per 1 standard deviation increase in sST2 1.22, 95% confidence interval 1.05-1.42, P=0.01]. Individuals in the upper sST2 quartile had a 2.6 mmHg greater increase in SBP compared with those in the lowest quartile (P for trend across quartiles 0.002) and a 1.8 mmHg greater increase in pulse pressure (P for trend 0.005). In contrast, sST2 concentrations were not associated with changes in DBP (P=0.27). Conclusion: These findings suggest that sST2 concentrations predict changes in BP physiology typically seen with aging and progressive arterial stiffness. Further studies are needed to elucidate underlying mechanisms by which the ST2/IL-33 pathway may contribute to BP physiology.
    No preview · Article · Apr 2013 · Journal of Hypertension
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    ABSTRACT: Objective: To evaluate soluble (s) ST2 as a biomarker of rejection, allograft vasculopathy and mortality after orthotopic heart transplantation (OHT). Methods: sST2 concentrations were measured in 241 patients following OHT. Results: Elevated sST2 was associated with cellular rejection (CR) ≥ 1R, with highest rates of CR in the 4th sST2 quartile (p = 0.003). No significant association between sST2 and antibody-mediated rejection or allograft vasculopathy was found. sST2 ≥ 30 ng/mL independently predicted death over 7-year follow-up (HR = 2.01; 95% CI 1.15-3.51; p = 0.01). Conclusion: Concentrations of sST2 are associated with the presence of CR and predict long-term mortality following OHT.
    No preview · Article · Apr 2013 · Biomarkers

Publication Stats

2k Citations
580.67 Total Impact Points


  • 2015
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2008-2015
    • Massachusetts General Hospital
      • Division of Cardiology
      Boston, Massachusetts, United States
  • 2008-2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2013
    • Boston University
      Boston, Massachusetts, United States
  • 2011
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2006
    • University of California, Davis
      Davis, California, United States