Mihai Gheorghiade

Emory University, Atlanta, Georgia, United States

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Publications (714)4649.53 Total impact

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    ABSTRACT: The relationship between resting heart rate (RHR) and incident heart failure (HF) has been questioned. RHR was assessed at baseline in 7073 participants in 3 prospective cohorts (Cardiovascular Health Study, Health ABC study and Kuopio Ischemic Heart Disease Study) that recorded 1189 incident HF outcomes during 92 702 person-years of follow-up. Mean age of participants was 67 (9.9) years and mean RHR was 64.6 (11.1) bpm. Baseline RHR correlated (P<0.001) positively with body mass index (r=0.10), fasting glucose (r=0.18), and C-reactive protein (r=0.20); and inversely with serum creatinine (r=-0.05) and albumin (r=-0.05). Baseline RHR was non-linearly associated with HF risk. The age and sex-adjusted hazard ratio for HF comparing the top (>72 bpm) versus the bottom (<57 bpm) quartile of baseline RHR was 1.48 (95% confidence interval [CI] 1.26 to 1.74) and was modestly attenuated (1.30, 95% CI 1.10 to 1.53) with further adjustment for body mass index, history of diabetes, hypertension, smoking status, serum creatinine, and left ventricular hypertrophy. These findings remained consistent in analyses accounting for incident coronary heart disease, excluding individuals with prior cardiovascular events, or those taking beta-blockers; and in subgroups defined by several individual participant characteristics. In a pooled random effects meta-analysis of 7 population-based studies (43 051 participants and 3476 HF events), the overall hazard ratio comparing top versus bottom fourth of RHR was 1.40 (95% CI: 1.19 to 1.64). There is a non-linear association between RHR and incident HF. Further research is needed to understand the physiologic foundations of this association. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 12/2015; 4(1). DOI:10.1161/JAHA.114.001364
  • Stephen J Greene, Mihai Gheorghiade
    Journal of the American College of Cardiology 03/2015; 65(10):1061-1062. DOI:10.1016/j.jacc.2014.11.064 · 15.34 Impact Factor
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    ABSTRACT: The clinical characteristics, initial presentation, management, and outcomes of patients hospitalized with new-onset (first diagnosis) heart failure (HF) or decompensation of chronic HF are poorly understood worldwide. REPORT-HF (International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) is a global, prospective, and observational study designed to characterize patient trajectories longitudinally during and following an index hospitalization for HF. Data collection for the registry will be conducted at ∼300 sites located in ∼40 countries. Comprehensive data including demographics, clinical presentation, co-morbidities, treatment patterns, quality of life, in-hospital and post-discharge outcomes, and health utilization and costs will be collected. Enrolment of ∼20 000 adult patients hospitalized with new-onset (first diagnosis) HF or decompensation of chronic HF over a 3-year period is planned with subsequent 3 years follow-up. The REPORT-HF registry will explore the clinical characteristics, management, and outcomes of HF worldwide. This global research programme may have implications for the formulation of public health policy and the design and conduct of international clinical trials. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.
    European Journal of Heart Failure 03/2015; DOI:10.1002/ejhf.262 · 6.58 Impact Factor
  • Sadiya S Khan, Mihai Gheorghiade
    The Lancet 03/2015; DOI:10.1016/S0140-6736(14)62301-1 · 39.21 Impact Factor
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    ABSTRACT: -The prevalence of heart failure (HF) is expected to significantly rise unless high-risk patients are effectively screened and appropriate, cost-effective prevention interventions are implemented. -We performed a systematic review to evaluate the prediction characteristics of the published HF risk prediction models as of August 2014 using MEDLINE and EMBASE databases. Eligible studies reported the development, validation, or impact assessment of a model. Two investigators performed independent review to extract data on study design and characteristics, risk predictors, discrimination, calibration, and reclassification ability of models, as well as validation and impact analysis. We included 13 publications reporting on 28 HF risk prediction models. Models had acceptable-to-good discriminatory ability (c-statistics >0.70) in the derivation sample. Calibration was less commonly assessed, but was acceptable when it was. Only two models were externally validated more than once, displaying modest-to-acceptable discrimination (c-statistics 0.61-0.79). When assessed, novel blood and imaging markers modestly improved risk prediction. One model assessed the prediction properties in race-based subgroups while two models evaluated gender-based subgroups. Impact analysis found none of the models recommended for use in any clinical practice guideline. -Incident HF risk prediction remains at an early stage. The discrimination ability of current models is acceptable in derivation datasets but most models have not been externally validated. It remains unclear which models are cost-effective and best suit population screening needs. The attendant effects of models on clinical and preventative care requires further study.
    Circulation Heart Failure 03/2015; DOI:10.1161/CIRCHEARTFAILURE.114.001896 · 6.68 Impact Factor
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    ABSTRACT: Despite available therapy, mortality and readmission rates within 60-90 days of discharge for patients hospitalized with heart failure (HF) approach 15% and 30%, respectively. This early postdischarge period has been termed the 'vulnerable phase' and accounts for a disproportionate amount of the >US$30 billion spent annually on HF care in the USA. The pathophysiology underlying these early adverse events is likely associated with persistently elevated filling pressures at time of discharge and subsequent acute or subacute worsening of postdischarge haemodynamics. Despite limited proven strategies to reduce early adverse events, hospitals in the USA face penalties for 30-day readmission rates that exceed current expectations, and an urgent need exists for novel approaches to improve early postdischarge outcomes. The objective of this Review is to describe the early postdischarge problem among patients hospitalized for HF, the associated patient profile and pathophysiology, and the limitations of current postdischarge treatment strategies. We also identify therapeutic targets and outline a progressive management approach that should be considered by clinicians for reducing early postdischarge morbidity and mortality. Although these strategies require prospective validation, they are practical, affordable, and have the potential to improve patient outcomes substantially after HF hospitalization.
    Nature Reviews Cardiology 02/2015; DOI:10.1038/nrcardio.2015.14 · 10.40 Impact Factor
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    ABSTRACT: There are more than 1 million primary hospitalizations for heart failure (HF) annually in the USA alone, and post-discharge outcomes remain persistently poor despite available therapies and quality improvement initiatives. Recent international randomized clinical trials in hospitalized HF have repeatedly failed to improve this post-discharge event rate. A potential reason for this persistent lack of clinical trial success that has not previously received significant attention relates to site selection and the generally low level of patient enrollment from the USA. Only ~5 % of US hospitals participate in clinical trials, and in four recent randomized trials of hospitalized HF, only one-third of patients were enrolled in North America. This poor participation among US centers has necessitated disproportionate enrollment from non-US sites. Regional variations in HF patient characteristics and clinical outcomes are well documented, and a lack of US patient representation in clinical trials limits the generalizability of results and presents obstacles for US regulatory agency approval. There are multiple impediments to successful US enrollment including a lack of incentive for investigators and institutions, the relative value unit-based compensation system, poor institutional framework for identification of appropriate patients, and increasing liability to conduct trials. In this manuscript, we specifically identify barriers to successful hospitalized HF clinical trial participation in the USA and suggest possible solutions.
    Heart Failure Reviews 02/2015; DOI:10.1007/s10741-015-9473-z · 3.99 Impact Factor
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    ABSTRACT: The prevalence of patients with concomitant heart failure (HF) and diabetes mellitus (DM) continues to increase with the general aging of the population. In patients with chronic HF, prevalence of DM is 24% compared with 40% in those hospitalized with worsening HF. Patients with concomitant HF and DM have diverse pathophysiologic, metabolic, and neurohormonal abnormalities that potentially contribute to worse outcomes than those without comorbid DM. In addition, although stable HF outpatients with DM show responses that are similar to those of patients without DM undergoing evidence-based therapies, it is unclear whether hospitalized HF patients with DM will respond similarly to novel investigational therapies. These data support the need to re-evaluate the epidemiology, pathophysiology, and therapy of HF patients with concomitant DM. This paper discusses the role of DM in HF patients and underscores the potential need for the development of targeted therapies. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    02/2015; 3(2):136-145. DOI:10.1016/j.jchf.2014.08.004
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    ABSTRACT: To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal dysfunction. The MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF; NCT01807221) is a multicentre, randomized, double-blind, active-comparator-controlled, six-parallel-group, phase 2b dose-finding study. In total, 1060 patients with HFrEF and concomitant type 2 diabetes mellitus and/or chronic kidney disease (CKD) will be randomized within 7 days of emergency presentation to hospital for worsening chronic HF to receive finerenone (one of five doses in the range 2.5-20.0 mg once daily) or eplerenone (25 mg every second day to 50 mg once daily for 90 days). The primary objective is to investigate the safety and potential efficacy (measured as the percentage of individuals with a decrease in plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP] of more than 30% relative to baseline at day 90 ± 2) of different oral doses of finerenone compared with eplerenone. Other objectives are to assess the effects of finerenone on a composite clinical endpoint (death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic HF), and on changes in health-related quality of life from baseline. ARTS-HF is the first phase 2b clinical trial to investigate the effects of finerenone on plasma NT-proBNP in a high-risk population of patients who have worsening chronic HF with type 2 diabetes mellitus and/or CKD presenting at the emergency department. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.
    European Journal of Heart Failure 02/2015; 17(2):224-232. DOI:10.1002/ejhf.218 · 6.58 Impact Factor
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    ABSTRACT: AimsThe purpose of this study was to determine the prognostic significance and associated clinical profile of early post-discharge N-terminal pro-B-type natriuretic peptide (NT-proBNP) trajectory among patients hospitalized for worsening chronic heart failure (HHF).Methods and resultsThis post-hoc analysis of the Aliskiren Trial in Acute Heart Failure Outcomes (ASTRONAUT) included 1351 HHF patients with ejection fraction (EF) ≤40%, elevated B-type natriuretic peptide ≥400 pg/mL or NT-proBNP ≥1600 pg/mL at admission, and available NT-proBNP measurements (from a central core laboratory) at baseline (median 5 days after admission) and 1-month follow-up. The co-primary endpoints were all-cause mortality and cardiovascular mortality or HHF within 12 months. Median follow-up was 11.3 months. Patients with decreasing post-discharge NT-proBNP trajectory tended to be younger and have non-ischaemic HF aetiology. The presence of baseline atrial fibrillation was associated with high NT-proBNP at 1 month (i.e. above the median), regardless of the baseline value. After adjustment for patient characteristics and 1-month NT-proBNP level, every twofold increase in continuous NT-proBNP change from baseline to 1 month was predictive of increased cardiovascular mortality or HHF (hazard ratio 1.14; 95% confidence interval 1.02–1.26), but not all-cause mortality (hazard ratio 0.95; 95% confidence interval 0.81–1.11).Conclusion In this cohort of HHF patients with reduced EF, early post-discharge NT-proBNP trajectory was associated with a distinct clinical profile and carried independent prognostic value after adjustment for patient characteristics and absolute NT-proBNP level. Future prospective study of serial NT-proBNP measurement during the hospital and early post-discharge periods is warranted to validate these findings and evaluate post-discharge NT-proBNP trajectory as a therapeutic target.
    European Journal of Heart Failure 01/2015; 17(1). DOI:10.1002/ejhf.201 · 6.58 Impact Factor
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    ABSTRACT: Advances in medical therapies leading to improved patient outcomes are in large part related to successful conduct of clinical trials that offer critical information regarding the efficacy and safety of novel interventions. The conduct of clinical trials in the United States, however, continues to face increasing challenges with recruitment and retention. These trends are paralleled by an increasing shift toward more multinational trials where most participants are enrolled in countries outside the United States, bringing into question the generalizability of the results to the American population. This manuscript presents the perspectives and recommendations from clinicians, researchers, sponsors, and regulators who attended a meeting facilitated by the Food and Drug Administration to improve upon the current clinical trial trends in the United States. Copyright © 2014 Elsevier Inc. All rights reserved.
    American Heart Journal 12/2014; 169(3). DOI:10.1016/j.ahj.2014.12.001 · 4.56 Impact Factor
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    ABSTRACT: The aim of this study is to assess the impact of obstructive coronary artery disease (CAD) on outcomes after liver transplantation. Patients considered for liver transplantation are at an increased risk for CAD. Obstructive CAD is a contraindication for liver transplantation at most centres. However, the association between severity of CAD and liver transplantation outcomes remains poorly characterized. We retrospectively reviewed 386 consecutive liver transplantations performed between January 2001 and December 2005 at Northwestern Memorial Hospital (NMH). A comparative analysis was conducted for a national cohort (n = 23 820) from the United Network for Organ Sharing database. Outcome measures included patient and graft survival, rates of acute myocardial infarction and heart failure. Patient survival remained similar irrespective of CAD severity or cardiovascular risk index (CRI) in the NMH cohort. The CRI closely correlated with the presence of CAD in the NMH cohort [CRI 0, odds ratio (OR) 0.125, 95% confidence interval (95% CI) 0.02-0.61, P = 0.01; CRI 1, OR 1 reference; CRI ≥2, OR 2.28, 95% CI 1.09-4.75, P = 0.02]. In the national cohort using Cox regression, high (≥2) CRI (reference 0, hazard ratio 1.376, 95% CI 1.271-1.488, P < 0.0001) predicted patient mortality and exceeded established risk factors, including Hepatitis C virus (HCV) (hazard ratio 1.321, 95% CI 1.242-1.403, P < 0.0001), hepatocellular carcinoma (HCC) (hazard ratio 1.27, 95% CI 1.181-1.370, P < 0.0001) and diabetes (hazard ratio 1.241, 95% CI 1.160-1.326, P < 0.0001). Liver transplantation in patients with CAD is not associated with prohibitive risk for cardiac events and patient mortality. Appropriately treated CAD should therefore not represent a contraindication to liver transplantation.
    Journal of Cardiovascular Medicine 12/2014; DOI:10.2459/JCM.0000000000000207 · 1.41 Impact Factor
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    ABSTRACT: Background-Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome in need of improved phenotypic classification. We sought to evaluate whether unbiased clustering analysis using dense phenotypic data (phenomapping) could identify phenotypically distinct HFpEF categories. Methods and Results-We prospectively studied 397 patients with HFpEF and performed detailed clinical, laboratory, ECG, and echocardiographic phenotyping of the study participants. We used several statistical learning algorithms, including unbiased hierarchical cluster analysis of phenotypic data (67 continuous variables) and penalized model-based clustering, to define and characterize mutually exclusive groups making up a novel classification of HFpEF. All phenomapping analyses were performed by investigators blinded to clinical outcomes, and Cox regression was used to demonstrate the clinical validity of phenomapping. The mean age was 65 +/- 12 years; 62% were female; 39% were black; and comorbidities were common. Although all patients met published criteria for the diagnosis of HFpEF, phenomapping analysis classified study participants into 3 distinct groups that differed markedly in clinical characteristics, cardiac structure/function, invasive hemodynamics, and outcomes (eg, phenogroup 3 had an increased risk of HF hospitalization [hazard ratio, 4.2; 95% confidence interval, 2.0-9.1] even after adjustment for traditional risk factors [P<0.001]). The HFpEF phenogroup classification, including its ability to stratify risk, was successfully replicated in a prospective validation cohort (n=107). Conclusions-Phenomapping results in a novel classification of HFpEF. Statistical learning algorithms applied to dense phenotypic data may allow improved classification of heterogeneous clinical syndromes, with the ultimate goal of defining therapeutically homogeneous patient subclasses.
    Circulation 11/2014; 131(3). DOI:10.1161/CIRCULATIONAHA.114.010637 · 14.95 Impact Factor
  • Circulation Heart Failure 11/2014; 7(6):1042-9. DOI:10.1161/CIRCHEARTFAILURE.114.001276 · 5.95 Impact Factor
  • Stephen J Greene, Mihai Gheorghiade
    Journal of the American College of Cardiology 10/2014; 64(15):1599-601. DOI:10.1016/j.jacc.2014.06.1199 · 15.34 Impact Factor
  • The American Journal of Cardiology 10/2014; DOI:10.1016/j.amjcard.2014.09.040 · 3.43 Impact Factor
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    ABSTRACT: Heart failure (HF) is a public health problem of global proportions afflicting more than 25 million patients worldwide. Despite stable or declining per capita hospitalization rates in the USA and several European countries, there are over one million hospitalizations for HF annually in the USA, with similar numbers in Europe, accounting for 6.5 million hospital days and the majority of the approximately $40 billion spent each year on HF-related care. Moreover, clinical trial data suggest that post-discharge survival and readmissions have largely remained unchanged. Thus, understanding geographic and ethnic variations in HF is essential to formulating public policy at the local, national, regional, and international levels and setting the agenda for basic, translational, and clinical research endeavors. This paper aims to describe regional and ethnic variations in patient characteristics, management, and outcomes in hospitalized HF.
    Current Heart Failure Reports 09/2014; DOI:10.1007/s11897-014-0221-9
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    ABSTRACT: The objective of this study was to evaluate the clinical presentation, inpatient management, and in-hospital outcome of patients hospitalized for acute heart failure syndromes (AHFS) and classified as pulmonary edema (PE).
    Journal of Cardiovascular Medicine 09/2014; DOI:10.2459/JCM.0000000000000192 · 1.41 Impact Factor

Publication Stats

23k Citations
4,649.53 Total Impact Points

Institutions

  • 2012–2014
    • Emory University
      • Division of Cardiology
      Atlanta, Georgia, United States
  • 2001–2014
    • Northwestern University
      • • Center for Cardiovascular Innovation
      • • Feinberg School of Medicine
      • • Division of Cardiology (Dept. of Medicine)
      Evanston, Illinois, United States
  • 2013
    • Durham University
      Durham, England, United Kingdom
    • Vanderbilt University
      • Department of Emergency Medicine
      Nashville, Michigan, United States
    • Stanford Medicine
      • Department of Medicine
      Stanford, CA, United States
    • Harvard Medical School
      • Department of Medicine
      Boston, MA, United States
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2011–2013
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • National Research Council
      • Institute of Clinical Physiology IFC
      Roma, Latium, Italy
  • 1998–2013
    • University of California, San Francisco
      • • Division of Cardiology
      • • Division of Hospital Medicine
      San Francisco, CA, United States
  • 1994–2013
    • University of Illinois at Chicago
      • Section of Cardiology
      Chicago, Illinois, United States
  • 1999–2012
    • Duke University Medical Center
      • • Division of Cardiology
      • • Department of Medicine
      Durham, NC, United States
  • 2010–2011
    • Università degli Studi di Brescia
      • Department of Clinical and Experimental Sciences
      Brescia, Lombardy, Italy
    • Baylor Health Care System
      • Baylor Heart and Vascular Institute (BHVI)
      Dallas, Texas, United States
    • University of Wisconsin - Milwaukee
      Milwaukee, Wisconsin, United States
    • Medtronic
      Minneapolis, Minnesota, United States
    • Thomson Reuters
      New York City, New York, United States
  • 2007–2011
    • Tufts Medical Center
      • Division of Cardiology
      Boston, Massachusetts, United States
    • University of Texas at Dallas
      Richardson, Texas, United States
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
    • University of Alabama at Birmingham
      • Department of Medicine
      Birmingham, AL, United States
  • 1995–2011
    • University of Chicago
      • Department of Medicine
      Chicago, Illinois, United States
    • Henry Ford Health System
      Detroit, Michigan, United States
  • 2005–2010
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 1999–2010
    • Northwestern Memorial Hospital
      Chicago, Illinois, United States
  • 1992–2010
    • Wayne State University
      • Department of Emergency Medicine
      Detroit, MI, United States
  • 2008
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • Attikon University Hospital
      • Department of Cardiology
      Athínai, Attica, Greece
    • Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2004–2008
    • University of California, Los Angeles
      • Department of Medicine
      Los Angeles, CA, United States
    • Johns Hopkins Medicine
      • Department of Medicine
      Baltimore, MD, United States
    • Ochsner
      New Orleans, Louisiana, United States
  • 2006–2007
    • Campbell University
      North Carolina, United States
    • Medical University of Silesia in Katowice
      Catowice, Silesian Voivodeship, Poland
    • European Hospital
      Roma, Latium, Italy
    • The institute for clinical research and development
      San José, California, United States
    • Georgetown University
      Washington, Washington, D.C., United States
  • 1989–2007
    • Henry Ford Hospital
      • Department of Internal Medicine
      Detroit, Michigan, United States
    • Virginia Hospital Center
      Arlington, Virginia, United States
  • 2002–2006
    • University of North Carolina at Chapel Hill
      • Department of Medicine
      North Carolina, United States
    • Medical City Hospital, Dallas
      Dallas, Texas, United States
    • University of Texas Southwestern Medical Center
      • Department of Internal Medicine
      Dallas, TX, United States
  • 1998–2006
    • Sapienza University of Rome
      • Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences
      Roma, Latium, Italy
  • 2003–2004
    • Duke University
      • Department of Medicine
      Durham, North Carolina, United States
    • Boston University
      Boston, Massachusetts, United States
  • 2001–2003
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
  • 1997
    • Northeastern Illinois University
      Chicago, Illinois, United States
  • 1986
    • Baylor College of Medicine
      • Section of Cardiology
      Houston, Texas, United States
  • 1984
    • Providence Hospital
      Mobile, Alabama, United States