Robert J Mentz

North Carolina Clinical Research, Raleigh, North Carolina, United States

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Publications (112)726.98 Total impact

  • Pablo F. Castro · Naoki Sato · Robert J. Mentz · Ovidiu Chioncel
    Heart Failure Clinics 10/2015; 11(4):i. DOI:10.1016/S1551-7136(15)00095-1 · 1.84 Impact Factor
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    ABSTRACT: Aim: The authors assessed the comparative effectiveness of torsemide versus furosemide in the PROTECT trial. Methods: The authors assessed the relationship between loop diuretic at discharge and death or cardiovascular/renal hospitalization within 30 days, and death through 150 days postdischarge using inverse probability weighting. Results: Out of 1004 patients, 83.5% received furosemide and 16.5% torsemide. Torsemide patients had higher blood urea nitrogen, and more in-hospital worsening heart failure. Following adjustment, torsemide was associated with similar 30-day outcomes compared with furosemide (p = 0.93), but remained associated with increased 150-day death (hazard ratio: 2.26; 95% CI: 1.40-3.66; p < 0.001). Conclusion: Patients treated with torsemide had features of greater disease severity, similar 30-day outcomes but increased 150-day mortality. Prospective randomized trials are needed to investigate the effect of torsemide versus furosemide.
    Future Cardiology 09/2015; DOI:10.2217/fca.15.56
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    ABSTRACT: Congestion is a primary reason for hospitalization in patients with acute heart failure (AHF). Despite inpatient diuretics and vasodilators targeting decongestion, persistent congestion is present in many AHF patients at discharge and more severe congestion is associated with increased morbidity and mortality. Moreover, hospitalized AHF patients may have renal insufficiency, hyponatremia, or an inadequate response to traditional diuretic therapy despite dose escalation. Current alternative treatment strategies to relieve congestion, such as ultrafiltration, may also result in renal dysfunction to a greater extent than medical therapy in certain AHF populations. Truly novel approaches to volume management would be advantageous to improve dyspnea and clinical outcomes while minimizing the risks of worsening renal function and electrolyte abnormalities. One effective new strategy may be utilization of aquaretic vasopressin antagonists. A member of this class, the oral vasopressin-2 receptor antagonist tolvaptan, provides benefits related to decongestion and symptom relief in AHF patients. Tolvaptan may allow for less intensification of loop diuretic therapy and a lower incidence of worsening renal function during decongestion. In this article, we summarize evidence for decongestion benefits with tolvaptan in AHF and describe the design of the Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure Study (TACTICS) and Study to Evaluate Challenging Responses to Therapy in Congestive Heart Failure (SECRET of CHF) trials.
    Circulation Heart Failure 09/2015; 8(5):997-1005. DOI:10.1161/CIRCHEARTFAILURE.115.002259 · 5.89 Impact Factor
  • Robert J Mentz · Christopher M O'Connor
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    ABSTRACT: Acute heart failure (AHF) is a complex syndrome characterized by worsening heart failure (HF) symptoms that requires escalation of therapy. Intrinsic cardiac abnormalities and comorbid conditions, including lung and renal disease, and sleep-disordered breathing, can contribute to the development of AHF. In this Review, we summarize and discuss the literature on the clinical evaluation and underlying pathophysiology of AHF. Important features of AHF evaluation include identification of precipitating factors to the disease, and assessment of circulatory-renal limitations associated with use of HF medications, prior HF hospitalizations, congestion and perfusion profiles, and end-organ dysfunction. The pathophysiological contributions of endothelial dysfunction, neurohormonal activation, venous congestion, and myocardial injury to the development of AHF are also discussed. These potential causative mechanisms provide a framework for clinicians to evaluate and manage patients with AHF and highlight possible future targets for therapies designed to improve clinical outcomes.
    Nature Reviews Cardiology 09/2015; DOI:10.1038/nrcardio.2015.134 · 9.18 Impact Factor
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    ABSTRACT: Nuclear imaging data demonstrate that revascularisation leads to favourable effects on ischaemia burden and improved outcomes compared with medical therapy (MT). In patients with heart failure (HF), the effects of MT versus revascularisation on ischaemia change and its independent prognostic significance requires investigation. From the Duke Databank, we performed a retrospective analysis of 278 consecutive patients with coronary artery disease (CAD) and ejection fraction (EF) ≤40%, who underwent 2 serial myocardial perfusion scans between 1993 and 2009. Ischaemia change was calculated for patients undergoing MT alone, or revascularisation. Cox proportional hazards regression modelling was used to identify factors associated with death/myocardial infarction (MI). The magnitude of ischeamia reduction was greater with revascularisation than with MT alone (median change of -6% vs 0%, p<0.001). With revascularisation, more patients experienced ≥5% ischaemia reduction compared with MT (52% vs 25%, p<0.01) and a similar percentage experienced ≥5% ischaemia worsening (13% vs 18%, p=0.37). After risk adjustment, ≥5% ischaemia worsening was associated with decreased death/MI (HR=0.58; 95% CI 0.36 to 0.96). In patients with HF with CAD, revascularisation improves long-term ischaemia burden compared with MT. Ischaemia worsening on nuclear imaging was associated with reduced risk of death/MI, potentially related to development of ischaemic viable myocardium as opposed to scar tissue.
    09/2015; 2(1):e000284. DOI:10.1136/openhrt-2015-000284
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    ABSTRACT: Troponin elevation is common in acute heart failure (AHF) and may be useful for prognostication; however, available data are mixed and many previous studies used older, less sensitive assays. We examined the association between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and outcomes in RELAX-AHF. Hs-cTnT was measured at baseline and days 2, 5, and 14. We assessed the relationship between baseline, peak and peak change hs-cTnT with dyspnoea relief by visual analogue scale, cardiovascular death, or HF/renal hospitalization to 60 days and cardiovascular mortality to 180 days. Models were adjusted for clinical variables and treatment assignment. Whether baseline troponin status affected the treatment effect of serelaxin was assessed using interactions terms. In 1074 patients, the median baseline troponin was 0.033 µg/L, and 90% of patients were above the 99th upper reference limit (URL). Patients with hs-cTnT >median were more likely to be men with ischaemic heart disease, worse renal function, and higher N-terminal pro-brain natriuretic peptide. Higher baseline or peak hs-cTnT and greater peak change were associated with worse outcomes independent of adjustment for covariates, but relationships were generally strongest for 180-day cardiovascular mortality (hazard ratio per doubling of baseline hs-cTnT = 1.36, 95% confidence interval 1.15-1.60). Troponin was most strongly associated with death from heart failure or from other cardiovascular causes. The treatment effect of serelaxin did not differ by baseline troponin levels. Hs-cTnT was elevated above the 99% URL in the majority of AHF patients. Baseline, peak, and peak change hs-cTnT were associated with worse outcomes, with the strongest relationship with 180-day cardiovascular mortality. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.
    European Journal of Heart Failure 09/2015; DOI:10.1002/ejhf.341 · 6.53 Impact Factor
  • Jonathan Buggey · Robert J. Mentz · Anthony N. Galanos
    Heart Failure Clinics 08/2015; DOI:10.1016/j.hfc.2015.07.001 · 1.84 Impact Factor
  • Heart Failure Clinics 08/2015; DOI:10.1016/j.hfc.2015.07.003 · 1.84 Impact Factor
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    ABSTRACT: Acute heart failure (AHF) is a complex syndrome with presentations ranging from hypotensive cardiogenic shock to hypertensive emergency with pulmonary edema. Most patients with AHF present with worsening of chronic HF signs and symptoms over days to weeks, and significant heterogeneity exists. It can, therefore, be challenging to characterize the overall population. The complexity of defining the AHF phenotype has been cited as a contributing cause for neutral results in most pharmacologic trials in patients with AHF. Dyspnea has been a routine inclusion criterion for AHF for over a decade, but the utility of current instruments for dyspnea assessment has been called into question. Furthermore, the threshold of clinical severity that prompts patient admission of an HF clinic visit may vary substantially across regions in global trials. Therefore, the inclusion of cardiac-specific biomarkers has been incorporated into AHF trials as 1 strategy to support inclusion of the target patient population and potentially enrich the population with patients at risk for clinical outcomes. In conclusion, we discuss strategies to support appropriate patient selection in AHF trials with an emphasis on using biomarker criteria that may improve the likelihood of success with future AHF clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American journal of cardiology 07/2015; DOI:10.1016/j.amjcard.2015.07.049 · 3.28 Impact Factor
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    ABSTRACT: We aimed to characterize the independent predictors of LVT following STEMI and the association with outcomes. The clinical predictors of left ventricular thrombus (LVT) formation after ST-segment elevation myocardial infarction (STEMI) are not well-defined in the contemporary era. We performed a retrospective analysis of STEMI patients at Duke from 2000 to 2011 who had a transthoracic echocardiogram within 90 days post-STEMI and compared patients with and without LVT (LVT+ vs. LVT-). Univariate Cox proportional hazards regression models of baseline characteristics were examined and significant variables were used in a multivariable model to assess adjusted relationships with LVT. A multivariable Cox PH survival model with covariate adjustments was used for assessment of LVT and long-term mortality. Of all eligible patients, 1734 patients met inclusion criteria and 4.3 % (N = 74) had a LVT. LVT+ patients tended to have a history of heart failure (HF) and higher initial troponin compared to LVT- patients. After adjustment, higher heart rate, non-white race, HF severity, and presence of left anterior descending artery (LAD) disease were independent predictors of LVT. There was a trend toward an association between LVT and increased all-cause mortality (HR 1.36; 95 % CI 0.84-2.21, P = 0.22), however this was not statistically significant. LVT was seen in over 4 % of this contemporary post-STEMI population. Several baseline characteristics were independently associated with LVT: Heart rate, HF severity, LAD disease, and non-white race. Prospective studies are warranted to determine whether anticoagulation in patients at increased risk for LVT improves outcomes.
    Journal of Thrombosis and Thrombolysis 07/2015; DOI:10.1007/s11239-015-1252-0 · 2.17 Impact Factor
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    ABSTRACT: Heart failure (HF) is an increasingly common syndrome associated with high mortality and economic burden, and there has been a paucity of new pharmacotherapies that improve outcomes over the past decade. However, recent data from a large, randomized controlled trial compared the novel agent LCZ696, a dual acting angiotensin receptor blocker and neprilysin inhibitor (ARNi), to the well-established angiotensin-converting enzyme (ACE) inhibitor enalapril and found significant reduction in mortality among the chronic, reduced ejection fraction HF population. Preclinical and clinical data suggest that neprilysin inhibition provides beneficial outcomes in HF patients by preventing the degradation of natriuretic peptides thereby promoting natriuresis, vasodilatation, and counteracting the negative cardiorenal effects of the up-regulated renin-angiotensin-aldosterone system. Agents such as omapatrilat combined neprilysin and ACE inhibition but had increased rates of angioedema. Goals of an improved safety profile provided the rationale for the development of the ARNi LCZ696. Along with significant reductions in mortality and hospitalizations, clinical trials suggest LCZ696 may improve surrogate markers of HF severity. In this paper, we review the preclinical and clinical data that has led to the development of LCZ696 and the understanding of the underlying mechanistic action and the robust clinical impact that LCZ696 may have in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of cardiac failure 07/2015; 21(9). DOI:10.1016/j.cardfail.2015.07.008 · 3.05 Impact Factor
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    ABSTRACT: Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality.
    Expert Review of Cardiovascular Therapy 07/2015; 13(7):799-809. DOI:10.1586/14779072.2015.1053872
  • Robert J Mentz · Michel G Khouri
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    ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) represents approximately 50% of the overall heart failure (HF) population(1), yet relatively few prognostic markers are used in routine clinical practice. Clinicians commonly assess symptom severity, prior HF hospitalizations, natriuretic peptide levels and comorbidity burden to characterize disease trajectory. Furthermore, without disease-modifying agents, the management of HFpEF is largely limited to optimization of volume status and comorbid conditions(2). In contrast, for patients with HF with reduced EF (HFrEF), clinicians incorporate an array of data from clinical evaluation and diagnostic testing to risk-stratify patients, individualize guideline-based medication regimens and determine optimal timing for implantable devices and advanced therapies. For instance, thresholds for echocardiographic and exercise testing parameters (e.g., EF and maximal oxygen consumption) are central components of the decision-making process for defibrillator implantation and advanced therapies such as ventricular assist devices(2). An equivalent prognostic marker to EF has not been identified for HFpEF patients despite the similarly high event rate compared to HFrEF cohorts(3, 4).
    Circulation 06/2015; 132(5). DOI:10.1161/CIRCULATIONAHA.115.017683 · 14.43 Impact Factor
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    ABSTRACT: Worsening heart failure (WHF) symptoms despite initial therapy during admission for acute heart failure (AHF) is associated with worse outcomes. The association between the time of the WHF event and the intensity of WHF therapy with outcomes is unknown. In the PROTECT trial of 2033 AHF patients, we investigated the association between time of occurrence of WHF and intensity of therapy, with subsequent outcomes. WHF was defined by standardized, physician-determined assessment. Early WHF was defined as occurring on days 2-3 and late on days 4-7. Low intensity included restarting/increasing diuretics or vasodilators and high intensity included initiation of inotropes, vasopressors, inodilators, or mechanical support. Outcomes were death or cardiovascular/renal hospitalization over 60 days and death over 180 days. Of the 1879 patients with complete follow-up after day 7, 12.7% (n = 238) experienced WHF: 47.9% early and 52.1% late. Treatment intensity was low in 72.3% and high in 24.8% (2.9% missing). After adjusting for baseline predictors of outcome, WHF was associated with a trend toward increased 60-day death or cardiovascular/renal hospitalization [hazard ratio (HR) 1.26; 95% confidence interval (CI) 0.99-1.60; P = 0.063] and increased 180-day death (HR 1.77; 95% CI 1.33-2.34; P < 0.001). There was no evidence of a differential association between the time of occurrence of WHF and outcomes. High-intensity therapy was not significantly associated with increased event rates (180-day mortality: HR 1.44; 95% CI 0.80-2.59 vs. low). Inhospital WHF was associated with increased 180-day death. The time of occurrence and intensity of WHF therapy may provide less prognostic information than whether or not WHF occurred. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.
    European Journal of Heart Failure 06/2015; 17(7). DOI:10.1002/ejhf.308 · 6.53 Impact Factor
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    ABSTRACT: -Congestion is the most frequent cause for hospitalization in acute decompensated heart failure (ADHF). Although decongestion is a major goal of acute therapy, it is unclear how the clinical components of congestion (e.g., peripheral edema, orthopnea) contribute to outcomes after discharge or how well decongestion is maintained. -A post-hoc analysis was performed of 496 patients enrolled in the DOSE-AHF and CARRESS-HF trials during hospitalization with ADHF and clinical congestion. A simple "orthodema" congestion score was generated based on symptoms of orthopnea (≥2 pillows=2 points, <2 pillows=0 points) and peripheral edema (trace=0 points, moderate=1 point, severe=2 points) at baseline, discharge, and 60-day follow-up. Orthodema scores were classified as absent (score of 0), low-grade (score of 1-2), and high-grade (score of 3-4), and the association with death, rehospitalization or unscheduled medical visits through 60 days was assessed. At baseline, 65% of patients had high-grade orthodema and 35% had low-grade orthodema. At discharge, 52% patients were free from orthodema at discharge (score = 0) and these patients had lower 60-day rates of death, rehospitalization, or unscheduled visits (50%) compared to those with low-grade or high-grade orthodema (52% and 68%, respectively, p=0.038). Of the patients without orthodema at discharge, 27% relapsed to low-grade orthodema and 38% to high-grade orthodema at 60-day follow-up. -Increased severity of congestion by a simple orthodema assessment is associated with increased morbidity and mortality. Despite intent to relieve congestion, current therapy often fails to relieve orthodema during hospitalization or to prevent recurrence after discharge. Clinical Trial Registration-URL: Unique identifiers: NCT00608491, NCT00577135.
    Circulation Heart Failure 06/2015; DOI:10.1161/CIRCHEARTFAILURE.114.001957 · 5.89 Impact Factor
  • Anuradha Lala · Robert J Mentz
    Journal of the American College of Cardiology 06/2015; 65(21):2348-51. DOI:10.1016/j.jacc.2015.04.016 · 16.50 Impact Factor
  • Robert J Mentz
    Journal of Cardiovascular Medicine 06/2015; 16(6):401-3. DOI:10.2459/JCM.0000000000000194 · 1.51 Impact Factor
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    ABSTRACT: Furosemide has historically been the primary loop diuretic in heart failure patients despite data suggesting potential advantages with torsemide. We used the Duke Echocardiography Lab Database to investigate patients admitted with heart failure to Duke Hospital from 2000 to 2010 who were discharged on either torsemide or furosemide. We described baseline characteristics based on discharge diuretic and assessed the relationship with all-cause mortality through 5 years. Of 4580 patients, 86% (n = 3955) received furosemide and 14% (n = 625) received torsemide. Patients receiving torsemide were more likely to be female and had more comorbidities compared with furosemide-treated patients. Survival was worse in torsemide-treated patients [5-year Kaplan–Meier estimated survival of 41.4% (95% CI: 36.7–46.0) vs. 51.5% (95% CI: 49.8–53.1)]. After risk adjustment, torsemide use was no longer associated with increased mortality (hazard ratio 1.16; 95% CI: 0.98–1.38; P = 0.0864). Prospective trials are needed to investigate the effect of torsemide versus furosemide because of the potential for residual confounding.
    Journal of Cardiovascular Pharmacology 05/2015; 65(5):438-443. DOI:10.1097/FJC.0000000000000212 · 2.14 Impact Factor
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    ABSTRACT: Mortality from cardiovascular diseases (CVD) represents the primary cause of death worldwide. Prevention or treatment of atherosclerosis and its clinical sequelae is a central goal in the management of patients with established vascular disease or those at high-risk for vascular events. This paper provides a review of the contemporary pharmacological armamentarium targeting atherosclerosis and also highlights strategies to support future clinical trial design. Powering future trials targeting LDL-cholesterol to its absolute reduction and including patients with a higher LDL-C despite optimal medical therapy (or unable to tolerate statins) will increase the odds of meaningful results. Mendelian randomization studies may identify new causal risk factors for CVD that would help in the selection of the patients most likely to benefit from a specific new compound. Furthermore, imaging techniques integrating a morphological and functional assessment such as IVUS, OCT, PET/CT and PET/MRI may represent in a near future robust "soft" endpoints to support successful translation of early research into meaningful phase III clinical outcome trials. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 05/2015; 192. DOI:10.1016/j.ijcard.2015.05.013 · 4.04 Impact Factor
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    ABSTRACT: Recent clinical trials in patients with heart failure with preserved ejection fraction (HFpEF) have provided important insights into participant selection strategies. Historically, HFpEF trials have included patients with relatively preserved left ventricular ejection fraction ranging from 40% to 55% and a clinical history of heart failure. Contemporary HFpEF trials have also incorporated inclusion criteria such as hospitalization for HFpEF, altered functional capacity, cardiac structural and functional abnormalities, and abnormalities in neurohormonal status (e.g., elevated natriuretic peptide levels). Careful analyses of the effect of these patient selection criteria on outcomes in prior trials provide valuable lessons for future trial design. We review recent and ongoing HFpEF clinical trials from a patient selection perspective and appraise trial patient selection methodologies in relation to outcomes. This review reflects discussions between clinicians, scientists, trialists, regulators, and regulatory representatives at the 10th Global CardioVascular Clinical Trialists Forum in Paris, France, on December 6, 2013. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 04/2015; 65(16):1668-1682. DOI:10.1016/j.jacc.2015.03.043 · 16.50 Impact Factor

Publication Stats

493 Citations
726.98 Total Impact Points


  • 2015
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
  • 2012–2015
    • Duke University
      • Department of Medicine
      Durham, North Carolina, United States
  • 2011–2015
    • Duke University Medical Center
      • • Division of Cardiology
      • • Duke Clinical Research Institute
      Durham, North Carolina, United States
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2014
    • Aalborg University
      Ålborg, North Denmark, Denmark
  • 2013
    • Durham University
      Durham, England, United Kingdom