Marvin A Konstam

Tufts University, Бостон, Georgia, United States

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Publications (408)3386.72 Total impact

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    ABSTRACT: Serum osmolality may fluctuate with neurohormonal activation and with therapies targeting it in patients with heart failure (HF). The clinical relevance of osmolality among patients with HF has not been defined. In this post hoc analysis of the EVEREST trial, we analyzed serum osmolality measured at discharge in 3,744 patients hospitalized for HF and reduced ejection fraction (EF≤40%). Median follow-up was 9.9 months. The association between discharge osmolality and all-cause mortality (ACM) and composite cardiovascular mortality or HF hospitalization was non-linear and thus patients were divided into low (≤284), normal (285-300), and high (≥300mOsm/kg) osmolality. Median serum osmolality at discharge was 297 (290-304) mOsm/kg. Patients in the low osmolality group (n=454,12.1%) were more likely to be younger, male, have lower rates of hypertension, coronary artery disease, chronic kidney disease, diabetes, and have lower serum sodium, creatinine, systolic blood pressure, and EF (all p<0.001). Low discharge osmolality was associated with higher ACM (low 29.3%; normal 23.6%; high 25.2%; p=0.04) and the composite endpoint (low 45.6%; normal 39.3%; high 41.8%; p=0.04). After risk adjustment, a 15 mOsm/kg decrease in osmolality was predictive of higher ACM (HR 1.61, 95%CI 1.19-2.17) and the composite endpoint (HR 1.37, 95%CI 1.06-1.75) in the low osmolality group. These associations were not seen among patients with normal or high osmolality. Interaction analyses for tolvaptan treatment were non-significant (p>0.4). In conclusion, low discharge serum osmolality was independently predictive of worse post-discharge mortality and readmission. Further study is required to clarify the clinical utility of serum osmolality in hospitalized HF patients.
    No preview · Article · Jan 2016 · The American journal of cardiology
  • Marvin A. Konstam · Jenica Upshaw

    No preview · Article · Dec 2015 · JACC: Heart Failure
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    ABSTRACT: In observational studies of patients hospitalized for heart failure (HHF), risk of death is highest immediately after discharge and decreases over time. It is unclear whether this population risk trajectory reflects (1) lowering of individual patient mortality risk with increasing time from index hospitalization or (2) temporal changes in population case-mix with earlier postdischarge death for "sicker" patients. Survival rate and longitudinal models were used to estimate temporal changes in postdischarge all-cause mortality risk in 3,993 HHF patients discharged alive in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. After median follow-up of 9.9 months, 971 patients died (24.2%). Predicted mortality rate decreased from 15.9 per 100 patient-years immediately after discharge to 13.4 at 30 days and 12.8 at 90 days; mortality rate increased steadily thereafter. Risk variation between quintiles of risk was considerably larger than the temporal variation within risk strata. In a longitudinal model serially reassessing predicted patient mortality risk after each follow-up visit using data collected at these visits, predicted mortality risk increased during the 90 days preceding subsequent heart failure readmission and then followed a postdischarge trajectory similar to the index admission. In conclusion, although there is transiently elevated individual patient risk in the 90 days before and after discharge, the patient's individual risk profile, rather than temporal change in risk relative to hospitalization, remains the main determinant of mortality. For purposes of reducing all-cause mortality in HF patients, preventative and therapeutic measures may be best implemented as long-term interventions for high mortality risk patients based on serial risk assessments, irrespective of recent hospitalization.
    No preview · Article · Dec 2015 · The American journal of cardiology
  • Marvin A Konstam

    No preview · Article · Oct 2015 · European Journal of Heart Failure
  • Marvin A. Konstam

    No preview · Article · Oct 2015
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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.
    No preview · Article · Sep 2015 · Circulation Heart Failure
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    ABSTRACT: Background: In the current era, where advanced heart failure (AHF) has become an American Board of Internal Medicine (ABIM) certified subspecialty, new data are needed to benchmark and value levels of clinical effort performed by AHF specialists (AHFMDs). Methods and results: A 36-question survey was sent to 728 AHFMDs members of the Heart Failure Society of America, and 224 (31% responded). Overall, 56% worked in academic medical centers (AMCs) and were younger (48 ± 9 years vs. 52 ± 10 years, p < 0.01) and had a higher proportion of women (34% vs. 21%, p < 0.01) compared to non-AMCs. The percentage of time in clinical care was lower in AMC (64 ± 19% vs. 78 ± 18 %, p = 0.002), with similar concentration on E&M services (79 ± 18 % in AMC vs. 72 ± 18 % in non-AMC, p = NS). The majority of non-clinical time was spent in program administration (10% in both AMCs and non-AMCs) and education/ research (15% in AMC vs. 5% in non-AMCs). Although 69% of respondents were compensated by work relative value units (wRVUs), only a small percentage knew their target or the amount of RVU generated. The mean annual wRVUs generated were lower in AMC compared to non-AMC (5452 ±1961 vs. 9071 ± 3484), p < 0.001). The annual compensation in AMC was lower than non-AMC (45% vs. 10% below $250,000 and 17% vs. 61% over $350,000, p < 0.001) and the satisfaction with compensation was higher in non-AMCs. Conclusions: AHFMDs compensation is largely dependent by practice type (AMC vs. non-AMC) and clinical productivity, as measured by wRVUs. These data provide an opportunity for benchmarking work effort and compensation for AHFMDs, allowing distinction from segments of cardiologists with greater opportunity to accrue procedural wRVUs. They also show several differences between AMC and non-AMC that should be considered when formulating work assignment and compensation for AHFMDs.
    No preview · Article · Sep 2015 · Journal of cardiac failure

  • No preview · Article · Aug 2015
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    ABSTRACT: Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes. We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction ≤40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with placebo (treatment difference, -4.2 [-4.9, -3.5] mg/dL and -3.5 [-4.2, -2.7] mg/dL at 12 and 24 weeks, respectively, both P<0.0001). At 24 weeks, there was no significant difference in clinical status between the allopurinol- and placebo-treated patients (worsened 45% versus 46%, unchanged 42% versus 34%, improved 13% versus 19%, respectively; P=0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P=0.01), but there was no difference in serious adverse event rates between the groups (20% versus 15%, P=0.36). In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or left ventricular ejection fraction at 24 weeks. URL: Unique identifier: NCT00987415. © 2015 American Heart Association, Inc.
    Full-text · Article · May 2015 · Circulation
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    ABSTRACT: Previous reports have provided conflicting data regarding the relationship between length of stay (LOS) and subsequent readmission risk among patients hospitalized for heart failure (HF). We performed a post-hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial to evaluate the differences in LOS overall and between geographic regions (North America, South America, Western Europe, and Eastern Europe) in association with all-cause and cause-specific [HF, cardiovascular (CV) non-HF, and non-CV] readmissions within 30 days of discharge after HF hospitalization. The present analysis included 4020 patients enrolled from 20 countries who were alive at discharge. Median [interquartile range (IQR)] LOS was 8 (4-11) days. The 30-day readmission rates were 15.7% [95% confidence interval (CI) 14.6-16.8] for all-cause; 5.6% (95% CI 4.9-6.3) for HF; 4.4% (95% CI 3.8-5.1) for CV non-HF; and 5.8% (95% CI 5.1-6.6) for non-CV readmissions. There was a positive correlation between LOS and all-cause readmissions (r = 0.09, 95% CI 0.06-0.12). The adjusted odds ratio for the top (≥14 days) vs. the bottom (≤3 days) quintile for LOS was 1.39 (95% CI 0. 92-2.11) for all-cause readmissions, 0.43 (95% CI 0.24-0.79) for HF, 2.99 (95% CI 1.49-6.02) for CV non-HF, and 1.72 (95% CI 1.05-2.81) for non-CV readmissions. With the exception of Western Europe, these findings remained largely consistent across geographic regions. In this large multinational cohort of hospitalized HF patients, longer LOS was associated with a higher risk for all-cause, CV non-HF, and non-CV readmissions, but a lower risk of HF readmissions within 30 days of discharge. These results may inform strategies to reduce readmissions. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.
    No preview · Article · May 2015 · European Journal of Heart Failure
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    P. u Rossignol · N Girerd · D Gregory · J Massaro · M.A. Konstam · F Zannad
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    ABSTRACT: Recent data have highlighted shortcomings of the usual blood pressure (BP) hypothesis in several populations, and emphasized the importance of visit-to-visit variability of BP in predicting cardiovascular events. Herein, we aimed at assessing the association between visit-to-visit BP variability and outcomes in chronic heart failure (CHF) patients enrolled in the Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan (HEAAL). The HEAAL study randomized 3834 patients with HF and reduced ejection fraction administered 150mg or 50mg losartan daily in a double blind, randomized, controlled trial. The patients were followed up for up to 6.8years after randomization, and BP was measured at 3 time points in the first year and at semi-annual visits in the years thereafter. Three measures of visit-to-visit BP variability were computed for each subject: the standard deviation, the coefficient of variation and the average absolute visit-to-visit variation. Cox proportional hazard models were used to investigate the relationship between variations in systolic blood pressure, baseline covariates and the time to death or heart failure hospitalization (i.e. primary outcome). In multivariate analyses stratified on baseline BP, the patients with higher visit-to visit BP variability exhibited poorer outcomes (average absolute difference in SBP in mmHg:hazard ratio: 1.023 [95% CI (1.013, 1.034), P<0.0001]), independent from high dose losartan (still beneficial). For the first time, visit-to-visit BP variability was found elevated in CHF patients with reduced ejection fraction, and associated with poorer cardiovascular outcomes. Such assessments should be prioritized for testing prevention strategies in CHF. This study is registered with the, number NCT00090259. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Mar 2015 · International journal of cardiology

  • No preview · Article · Mar 2015 · Journal of the American College of Cardiology
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    ABSTRACT: Objectives: This study investigated the dose-related effect of losartan on changes in renal function using datafromthe HEAAL (Heart failure Endpoint evaluation of Angiotensin II Antagonist Losartan) trial. Background: Angiotensin receptor blockers adversely affect renal function in patients with heart failure (HF). Thetime course and dose dependency of this time course, as well as the clinical implications of these changes in renalfunction, are not well described. Methods: Subjects in the HEAAL dataset (n= 3,843) were studied. Changes in estimated glomerular filtration rate (eGFR) over time were compared between dose groups. The association between the timing of incident increases in serum creatinine (SCr) >0.3 mg/dl and clinical outcomes was explored. Results: Compared with 50 mg, 150 mg losartan led to a greater reduction in eGFR across time (mean difference: -3.79 ml/min/1.73 m2; p< 0.0001). This difference was driven by early changes, and differences in eGFR after 4 months were not significant (mean difference: 0.40 ml/min/1.73 m2; p= 0.16). Although an increase in SCr >0.3 mg/dl from baseline was associated with increased risk of death or hospitalization for HF (hazard ratio [HR]: 1.36; p<0.0001), the relationship was not significant if the change occurred before 4 months (HR: 1.09; p= 0.20). Despite increased risk of worsening renal function, 150 mg losartan was associated with reduced risk of death or hospitalization for HF compared with 50 mg (HR: 0.85; p< 0.0001). Conclusions: Compared with 50 mg, 150 mg losartan is associated with an increased risk of acute rise in SCr, as well as with greater long-term reductions in eGFR. Despite these effects, high-dose losartan retains its net clinical benefit andis associated with reduced risk of death or hospitalization for HF. (Study to Evaluate Potential Decrease in Hospitalization Events, Time Between Events, and Increasing Longevity in Patients With Symptomatic Heart Failure; NCT00090259).
    No preview · Article · Mar 2015 · JACC: Heart Failure
  • Marwan F Jumean · Marvin A Konstam
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    ABSTRACT: Evidence-based management of heart failure with preserved left ventricular ejection fraction (LVEF; HFpEF) remains a major gap in the care of patients with HF. Clinical trials directed toward the population with HFpEF have been disappointing, although renin-angiotensin-aldosterone system blockade appears to prevent HF in populations pre-disposed to HFpEF. This paradox may partly be due to inhomogeneity within the HF populations studied. Although the term HFpEF is often used to imply a specific diagnosis, in fact this constellation may be due to a large variety of disease states with different underlying pathophysiologic mechanisms. Furthermore, in patients with HF, regardless of LVEF, myocardial dysfunction is common during both systole and diastole, and LVEF is influenced at least as much by the pattern of LV remodeling as it is by myocardial contractility. The most common clinical-pathologic syndrome responsible for HFpEF is strongly associated with hypertension, with the metabolic syndrome, and with older age. Recent findings support that this condition is mediated via endothelial dysfunction, inflammation, oxidative stress, myocyte hypertrophy and altered collagen turnover. We therefore propose the terms "metabolic heart failure" and "senile heart failure" to describe this specific disease state. The search for therapies designed to prevent, halt, or reverse HF should more strongly focus on populations carefully selected to represent specific underlying cardiovascular disease states.
    No preview · Article · Feb 2015 · Cardiology in Review
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    ABSTRACT: We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) ≤40%, with specific focus on gender, race, and renal function based interactions. In 3,955 of 4,133 patients (96%) with baseline sUA data, clinical characteristics and outcomes were compared across sUA quartiles. The primary end points were all-cause mortality and a composite of cardiovascular mortality or heart failure hospitalization. Interaction analyses were performed for gender, race, and baseline renal function. Median follow-up was 9.9 months. Mean sUA was 9.1 ± 2.8 mg/dl and was higher in men than in women (9.3 ± 2.7 vs 8.7 ± 3.0 mg/dl, p <0.001) and in blacks than in whites (10.0 ± 2.7 vs 9.0 ± 2.8 mg/dl, p <0.001). Higher sUA was associated with lower systolic blood pressure and EF, higher natriuretic peptides, and more impaired renal function. After accounting for 24 baseline covariates, in patients with enrollment estimated glomerular filtration rate ≥30 ml/min/1.73 m(2), sUA was strongly associated with increased all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.22 to 1.69, p <0.001) and the composite end point (hazard ratio 1.44, 95% confidence interval 1.26 to 1.64, p <0.001). However, in patients with estimated glomerular filtration rate <30 ml/min/1.73 m(2), sUA was not related with either end point (both p >0.4). Adjusted interaction analyses for gender, race, and admission allopurinol use were not significant. In conclusion, sUA is commonly elevated in patients hospitalized for worsening chronic heart failure and reduced EF, especially in men and blacks. The prognostic use of sUA differs by baseline renal function, suggesting different biologic and pathophysiologic significance of sUA among those with and without significant renal dysfunction.
    No preview · Article · Sep 2014 · The American Journal of Cardiology
  • Alanna A Morris · Javed Butler · Marvin A Konstam

    No preview · Article · Aug 2014 · Journal of cardiac failure

  • No preview · Article · Aug 2014 · Journal of Cardiac Failure

  • No preview · Article · Aug 2014 · Journal of Cardiac Failure
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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.
    No preview · Article · Jun 2014 · The American Journal of Cardiology
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    ABSTRACT: Angiotensin receptor antagonists (ARBs) improve outcomes in patients with heart failure (HF) with reduced left ventricular ejection fraction, but may induce hyperkalemia (HK) and/or a worsening of renal function (WRF). The incidence and risk factors of HK and its inter-relationship with WRF, as well as associations with clinical outcome (death or admission for HF i.e. the primary outcome) in 3846 HF patients enrolled in the double blind HEAAL trial (losartan 150mg/d vs. 50mg/d) were assessed. Worsening of renal function was defined as a decrease in eGFR >20% from baseline and HK as serum K >5.5 or >5mmol/L. Higher dose of losartan increased serum potassium. Episodes of HK >5mmol/L or WRF occurred at least once in about half of the patients. WRF was associated with higher occurrence of HK (HR 1.19 (1.06-1.34)) and vice versa (HR 1.35 (1.19-1.53)), but preceded HK in only about half of the events. High dose losartan improved outcome despite more frequent WRF and HK, both being independently associated with adverse outcomes in multivariate analyses. HK and WRF are common in HF patients. Both can be predicted from baseline risk factors and are therefore potentially preventable. Although associated with worse outcome, occurrence of any does not hinder the efficacy of high dose losartan. HK was associated with WRF and worse outcomes. Whether therapy targeting specifically HK may maximize the survival benefit derived from renin angiotensin aldosterone inhibitor use should be appropriately tested in future trials.
    Full-text · Article · Feb 2014 · International journal of cardiology

Publication Stats

23k Citations
3,386.72 Total Impact Points


  • 1984-2015
    • Tufts University
      • • Division of Cardiology
      • • Department of Medicine
      • • Tufts Center for Conservation Medicine
      • • Division of Hematology/Oncology
      Бостон, Georgia, United States
  • 1983-2015
    • Tufts Medical Center
      • • Division of Cardiology
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 2013
    • American University Washington D.C.
      Washington, Washington, D.C., United States
    • University of Texas Southwestern Medical Center
      • Department of Clinical Sciences
      Dallas, Texas, United States
    • American College of Cardiology
      Washington, Washington, D.C., United States
  • 2012
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 1985-2012
    • University of Massachusetts Boston
      • Department of Counseling and School Psychology
      Boston, Massachusetts, United States
  • 2010
    • University of Wisconsin - Milwaukee
      Milwaukee, Wisconsin, United States
  • 1983-2010
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 2009
    • Rutgers New Jersey Medical School
      Newark, New Jersey, United States
  • 2007
    • Treatment Research Institute, Philadelphia PA
      Filadelfia, Pennsylvania, United States
    • Northwestern University
      • Division of Gastroenterology and Hepatology
      Evanston, Illinois, United States
  • 1998-2006
    • New England Baptist Hospital
      Boston, Massachusetts, United States
  • 2005
    • Blue Water Task Force
      Big Sky, Montana, United States
  • 2004
    • Medical University of South Carolina
      Charleston, South Carolina, United States
  • 2003
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1981-2003
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2002
    • Baylor College of Medicine
      Houston, Texas, United States
  • 1994-2000
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 1984-1996
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1995
    • U.S. Department of Health and Human Services
      Washington, Washington, D.C., United States
    • University of North Carolina at Chapel Hill
      • Department of Biostatistics
      North Carolina, United States
  • 1992
    • University of Texas Health Science Center at Houston
      • Medical School
      Houston, Texas, United States
  • 1990
    • Good Samaritan Hospital
      Cincinnati, Ohio, United States