Antonio Abbate

Richmond VA Medical Center, Richmond, Virginia, United States

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Publications (276)1698.06 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite momentous breakthroughs in unraveling the pathophysiology of many chronic conditions and developing novel therapeutic agents, everyday clinical practice is still fraught with inadequate or inappropriate use of treatments with proven benefits. Aspirin is a paradigmatic example, as it is used for the primary and secondary prevention of cardiovascular disease and appears to have a beneficial impact on cancer risk. Yet, underuse, non-compliance or cessation of aspirin are not uncommon, may have an important clinical impact, and are not aggressively prevented or managed. Increasing the awareness of the extent and impact of aspirin underuse, non-compliance or cessation, and intensifying efforts at preventing them are worthy goals likely to yield significant benefits on cardiovascular morbidity and mortality worldwide, and possibly also on cancer outcomes.
    International Journal of Cardiology 03/2015; 182. · 6.18 Impact Factor
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    ABSTRACT: Abstract Clinical decision-making requires synthesis of an often complex evidence base. Novel tools have been developed building upon the historical approach of reviewing the literature focusing on a specific topic. Stemming from qualitative reviews, systematic reviews of randomized clinical trials, typically encompassing statistical pooling with pairwise meta-analysis, have been devised and are now considered one of the uppermost ladders in the hierarchy of clinical evidence. In the last decade, the exponential growth in randomized trials and the introduction of original computational methods have created the novel opportunity to compare indirectly competing treatments, as well as combining effect estimates stemming from head-to-head trials with those obtained by indirect comparisons. These methods include adjusted indirect comparison meta-analysis, network meta-analysis, and mixed treatment comparison. While still the focus of intense research and debate, they represent a powerful tool for evidence synthesis and comparative effectiveness in cardiovascular research, and thus are likely to become increasingly popular and impactful in shaping research agenda and clinical practice. This is clearly highlighted by a number of recent landmark network meta-analyses on smoking cessation therapies, coronary stents, and management of patent foramen ovale in patients with history of cryptogenic stroke. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved. KEYWORDS: Adjusted indirect comparison meta-analysis; Evidence-based medicine; Mixed treatment comparison; Network meta-analysis; Systematic review PMID: 25585376 [PubMed - as supplied by publisher]
    International Journal of Cardiology 01/2015; · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical decision-making requires synthesis of an often complex evidence base. Novel tools have been developed building upon the historical approach of reviewing the literature focusing on a specific topic. Stemming from qualitative reviews, systematic reviews of randomized clinical trials, typically encompassing statistical pooling with pairwise meta-analysis, have been devised and are now considered one of the uppermost ladders in the hierarchy of clinical evidence. In the last decade, the exponential growth in randomized trials and the introduction of original computational methods have created the novel opportunity to compare indirectly competing treatments, as well as combining effect estimates stemming from head-to-head trials with those obtained by indirect comparisons. These methods include adjusted indirect comparison meta-analysis, network meta-analysis, and mixed treatment comparison. While still the focus of intense research and debate, they represent a powerful tool for evidence synthesis and comparative effectiveness in cardiovascular research, and thus are likely to become increasingly popular and impactful in shaping research agenda and clinical practice. This is clearly highlighted by a number of recent landmark network meta-analyses on smoking cessation therapies, coronary stents, and management of patent foramen ovale in patients with history of cryptogenic stroke. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology. 01/2015; 182C:309-314.
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    ABSTRACT: The NLRP3 inflammasome is activated in the ischemic heart promoting caspase-1 activation, inflammation and cell death. Ischemic injury establishes both a priming signal (transcription of inflammasome components) and a trigger (NLRP3 activation). Whether NLRP3 activation, without priming, induces cardiac dysfunction and/or failure is unknown. The aim of the current study was to assess the independent and complementary roles of the priming and the triggering signals in the heart, in absence of ischemia or myocardial injury. We used mice with mutant NLRP3 (constitutively active), NLRP3-A350V, under the control of tamoxifen-driven expression of the Cre recombinase (Nlrp3-A350V/CreT mice). The mice were treated for ten days with tamoxifen before measuring the activity of caspase-1, the effector enzyme in the inflammasome. Tamoxifen treatment induced the inflammasome in the spleen but not in the heart, despite expression of the mutant NLRP3-A350V. The components of the inflammasome was significantly less expressed in the heart compared to the spleen. Subclinical low dose LPS (2 mg/Kg) in Nlrp3-A350V/CreT mice induced the expression of the components of the inflammasome (priming), measured using real-time PCR and Western blot, leading to the formation of an active inflammasome (caspase-1 activation) in the heart and LV systolic dysfunction while low dose LPS was insufficient to induce LV systolic dysfunction in wild type mice (all P<0.01 for mutant vs wild type mice). The signaling pathway governing the inflammasome formation in the heart requires a priming signal in order for an active NLRP3 to induce caspase-1 activation and LV dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.
    Cardiovascular Research 12/2014; · 5.81 Impact Factor
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    ABSTRACT: ITF2357 (generic givinostat) is an orally active, hydroxamic-containing histone deacetylase (HDAC) inhibitor, with broad anti-inflammatory properties and which has been used to treat children with systemic juvenile idiopathic arthritis. ITF2357 inhibits both Class I and II HDACs, reduces caspase 1 activity in human peripheral blood mononuclear cells (PBMC) and the secretion of IL 1β and other cytokines at 25-100 nM; at concentrations >200nM, ITF2357 is toxic in vitro. ITF3056, an analogue of ITF2357, inhibits only HDAC8 (IC50 285 nM). Here we compared the production of IL 1β, IL 1α, TNFα and IL 6 by ITF2357 to that of ITF3056 in PBMC stimulated with lipopolysaccharide (LPS), heat-killed Candida albicans or anti-CD3/anti-CD28 antibodies. ITF3056 reduced LPS-induced cytokines from 100 to 1000 nM; at 1000 nM, the secretion of IL 1β was reduced by 76%, TNFα by 88% and IL 6 by 61%. The intracellular levels of IL 1α were 30% lower. There was no evidence of cell toxicity at concentrations of ITF3056 (100 to 1000nM). Gene expression of TNFα was markedly reduced (80%) whereas IL 6 gene expression was 40% lower. Although anti-CD3/28 and Candida stimulation of IL 1β and TNFα was modestly reduced, IFNγ production was 75% lower. Mechanistically, ITF3056 reduced the secretion of processed IL 1β independent of inhibition of caspase 1 activity; however, synthesis of the IL 1β precursor was reduced by 40% without significant decrease in IL 1β mRNA levels. In mice, ITF3056 reduced LPS-induced serum TNFα by 85% and IL 1β by 88%. These data suggest that specific inhibition of HDAC8 results in reduced inflammation without cell toxicity. Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 12/2014; · 4.60 Impact Factor
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    ABSTRACT: Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of exercise intolerance and/or congestion, in the presence of a left ventricular (LV) ejection fraction within the normal limits (i.e. LVEF>50%). Determining the presence of impaired LV relaxation and/or filling (diastolic dysfunction) in HFpEF is needed to pragmatically to distinguish it from other cardiac and non-cardiac conditions where symptoms are not due to HF. There are multiple mechanisms for diastolic dysfunction ranging from structural abnormalities to functional derangements in HFpEF yet tailored therapies are lacking. Treatments proven effective in HF with systolic dysfunction have failed to show significant benefit in patients with HFpEF, which prognosis remains poor. This review will discuss the challenges inherent to the use of diagnostic criteria for HFpEF, differential diagnosis, prognostic evaluation, and treatment, highlighting the need for more research in this field. Copyright © 2014. Published by Elsevier Ireland Ltd.
    International Journal of Cardiology 11/2014; · 6.18 Impact Factor
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    ABSTRACT: Two pilot studies of interleukin-1 (IL-1) blockade in ST-segment elevation myocardial infarction (STEMI) showed blunted acute inflammatory response and overall favorable outcomes at 3 months follow-up. We hereby present a patient-level pooled analysis with extended follow-up of 40 patients with clinically stable STEMI randomized to anakinra, a recombinant IL-1 receptor antagonist, 100 mg/day for 14 days or placebo in a double-blinded fashion. End points included death, cardiac death, recurrent acute myocardial infarction (AMI), stroke, unstable angina, and symptomatic heart failure. Median follow-up was 28 (interquartile range 3 to 38) months. Sixteen patients (40%) had a total of 22 adverse cardiovascular events: 1 cardiac death, 4 recurrent AMI, 5 episodes of unstable angina pectoris requiring hospitalization and/or urgent revascularization, and 11 new diagnoses of heart failure. Treatment with anakinra was associated with a hazard ratio of 1.08 (95% confidence interval 0.31 to 3.74, p = 0.90) for the combined end point of death, recurrent AMI, unstable angina pectoris, or stroke and a hazard ratio of 0.16 (95% confidence interval 0.03 to 0.76, p = 0.008) for death or heart failure. In conclusion, IL-1 blockade with anakinra for 2 weeks appears, therefore, to have a neutral effect on recurrent ischemic events, whereas it may prevent new-onset heart failure long term after STEMI. Copyright © 2014 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 11/2014; · 3.43 Impact Factor
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    ABSTRACT: Abstract INTRODUCTION: Surgical replacement for aortic stenosis is fraught with complications in high-risk patients. Transcatheter techniques may offer a minimally invasive solution, but their comparative effectiveness and safety is uncertain. We performed a network meta-analysis on this topic. METHODS: Randomized trials on transcatheter aortic valve replacement vs surgery were searched. The primary outcome was all cause death. Risk estimates were obtained with Bayesian network meta-analytic methods. RESULTS: Four trials with 1,805 patients were included. After a median of 8 months, risk of death and myocardial infarction was not different when comparing surgery versus transcatheter procedures, irrespective of device or access. Conversely, surgery was associated with higher rates of major bleeding (odds ratio vs CoreValve=3.03 [95% credible interval: 2.23-4.17]; odds ratio vs transfemoral Sapien =1.82 [1.21-2.70]; odds ratio vs transapical Sapien =2.08 [1.20-3.70]), and acute kidney injury (odds ratio vs CoreValve =2.08 [1.33-3.32]; odds ratio vs transapical Sapien =2.78 [2.21-99.80]), but lower rates of pacemaker implantation (odds ratio vs CoreValve =0.41 [0.28-0.59]), and moderate or severe aortic regurgitation (odds ratio vs CoreValve =0.06 [0.02-0.27]; odds ratio vs Sapien=0.17 [0.02-0.76]). Strokes were less frequent with CoreValve than with transfemoral Sapien (odds ratio =0.32 [0.13-0.73]) or transapical Sapien (odds ratio =0.33 [0.10-0.93]), whereas pacemaker implantation was more common with CoreValve (odds ratio vs surgery =2.46 [1.69-3.61]; odds ratio vs transfemoral Sapien =2.22 [1.27-3.85]). CONCLUSIONS: Survival after transcatheter or surgical aortic valve replacement is similar, but there might be differences in the individual safety and effectiveness profile between the treatment strategies and the individual devices used in transcatheter aortic valve implantation. KEYWORDS: TAVI; TAVR; aortic stenosis; mixed treatment comparison; network meta-analysis; transcatheter aortic valve implantation; transcatheter aortic valve
    Heart, lung and vessels. 11/2014; 6(4):232-243.
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    ABSTRACT: Significance. An inflammatory response follows an injury of any nature, and while such response is an attempt to promote healing, it may itself result in further injury. Recent Advances. The inflammasome is a macromolecular structure recently recognized as a central mediator in the acute inflammatory response. The inflammasome senses the injury and it amplifies the response by leading to the release of powerful pro-inflammatory cytokines, Interleukin-1β (IL-1β) and IL-18. Critical Issues. The activation of the inflammasome in the heart during ischemic and non-ischemic injury represents an exaggerated response to sterile injury and promotes adverse cardiac remodeling and failure. Future Directions. Pilot clinical trials have explored blockade of the inflammasome-derived IL-1β and have shown beneficial effects on cardiac function. Additional clinical studies testing this approach are warranted. Moreover, specific inflammasome inhibitors that are ready for clinical use are currently lacking.
    Antioxidants & redox signaling. 10/2014;
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    ABSTRACT: Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, and poor exercise capacity due to insufficient cardiac function. HF represents the leading cause of hospitalization among adult patients over 65 years of age. Neurohormonal blockade has improved clinical outcomes; however, HF incidence continues to rise, suggesting an urgent need to develop novel drugs that target a different pathophysiological paradigm. Inflammation plays a central role in many cardiovascular diseases. Interleukin-1 (IL-1), a prototypical proinflammatory cytokine, is upregulated in HF and associated with worse prognosis. Preclinical models suggest a beneficial effect of IL-1 blockade, and pilot clinical trials are currently underway to evaluate the role of IL-1 blockade to reduce inflammation, ameliorate ventricular remodeling, and improve exercise capacity in patients with HF.
    Current Heart Failure Reports 10/2014;
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    ABSTRACT: Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties in addition to inhibiting serine proteases. Administration of human plasma-derived AAT is protective in models of acute myocardial infarction in mice. The objective of this study was to determine the safety and tolerability of human plasma-derived AAT and its effects on the acute inflammatory response in non-AAT deficient patients with ST-segment elevation myocardial infarction (STEMI). Ten patients with acute STEMI were enrolled in an open-label, single-arm treatment study of AAT at 60 mg/kg infused intravenously within 12 hours of admission and following standard of care treatment. C-reactive protein (CRP) and plasma AAT levels were determined at admission, 72 hours, and 14 days, and patients were followed clinically for 12 weeks for the occurrence of new onset heart failure, recurrent myocardial infarction, or death. Twenty patients with STEMI enrolled in previous randomized trials with identical inclusion and/or exclusion criteria, but who received placebo, served as historical controls. Prolastin C was well tolerated and there were no in-hospital adverse events. Compared with historical controls, the area under the curve of CRP levels was significantly lower 14 days after admission in the Prolastin C group (75.9 [31.4 to 147.8] vs 205.6 [78.8 to 410.9] mg/l, p = 0.048), primarily due to a significant blunting of the increase occurring between admission and 72 hours (delta CRP +1.7 [0.2 to 9.4] vs +21.1 [3.1 to 38.0] mg/l, p = 0.007). Plasma AAT levels increased from admission (149 [116 to 189]) to 203 ([185 to 225] mg/dl) to 72 hours (p = 0.005). In conclusion, a single administration of Prolastin C in patients with STEMI is well tolerated and is associated with a blunted acute inflammatory response. Copyright © 2014 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 10/2014; · 3.43 Impact Factor
  • Stefano Toldo, Antonio Abbate
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    ABSTRACT: Impairment in the myocardial relaxation and/or of the ventricular compliance determines the presence of diastolic dysfunction. Diastolic dysfunction in the heart may occur as a result of normal aging, but it more often is caused by metabolic or structural abnormalities in the myocardium, which are the substrate for diastolic heart failure (or heart failure with preserved ejection fraction -HFpEF-) (Borlaug, 2014). The pathophysiology of diastolic dysfunction and heart failure is poorly understood. In particular, it is not clear how acute metabolic changes, such as ischemia, hypoxia, or inflammation, cause impairment in myocardial relaxation (Butler J et al., 2014). This article is protected by copyright. All rights reserved.
    Acta Physiologica 10/2014; · 4.25 Impact Factor
  • JACC. Heart failure. 10/2014; 2(5):538.
  • Journal of Endovascular Therapy 10/2014; 21(5):693-696. · 3.59 Impact Factor
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    ABSTRACT: Prostacyclin and its analogues improve cardiac output and functional capacity in patients with pulmonary arterial hypertension (PAH); however, the underlying mechanism is not fully understood. We hypothesised that prostanoids have load-independent beneficial effects on the right ventricle (RV). Angio-obliterative PAH and RV failure were induced in rats with a single injection of SU5416 followed by 4 weeks of exposure to hypoxia. Upon confirmation of RV dysfunction and PAH, rats were randomised to 0.1 μg·kg(-1) nebulised iloprost or drug-free vehicle, three times daily for 2 weeks. RV function and treadmill running time were evaluated pre- and post-iloprost/vehicle treatment. Pulmonary artery banded rats were treated 8 weeks after surgery to allow for significant RV hypertrophy. Inhaled iloprost significantly improved tricuspid annulus plane systolic excursion and increased exercise capacity, while mean pulmonary artery pressure and the percentage of occluded pulmonary vessels remained unchanged. Rats treated with iloprost had a striking reduction in RV collagen deposition, procollagen mRNA levels and connective tissue growth factor expression in both SU5416/hypoxia and pulmonary artery banded rats. In vitro, cardiac fibroblasts treated with iloprost showed a reduction in transforming growth factor (TGF)-β1-induced connective tissue growth factor expression, in a protein kinase A-dependent manner. Iloprost decreased TGF-β1-induced procollagen mRNA expression as well as cardiac fibroblast activation and migration. Iloprost significantly induced metalloproteinase-9 gene expression and activity and increased the expression of autophagy genes associated with collagen degradation. Inhaled iloprost improves RV function and reverses established RV fibrosis partially by preventing collagen synthesis and by increasing collagen turnover.
    European Respiratory Journal 09/2014; · 7.13 Impact Factor
  • Antonio Abbate, Charles A Dinarello
    European Heart Journal 09/2014; · 14.72 Impact Factor
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    ABSTRACT: Cardiovascular disease represents an important cause of morbidity and mortality in patients with a diagnosis of systemic lupus erythematosus (SLE), due to a complex interplay between traditional risk factors and disregulation of autoimmunity but uncertainty is still present about the most important predictors of cardiovascular events.
    European Journal of Preventive Cardiology 08/2014; · 2.68 Impact Factor
  • Circulation 08/2014; 130(7):e63. · 14.95 Impact Factor
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    ABSTRACT: Anakinra, the recombinant form of the human IL-1 receptor antagonist, blunts the acute systemic inflammatory response in patients with ST-segment elevation myocardial infarction (STEMI), by determining a fall in peripheral blood leukocyte and plasma C reactive protein (CRP) levels. The aim of the present study was to determine the effects of anakinra on the activity of leukocytes measured ex vivo.
    Molecular medicine (Cambridge, Mass.). 08/2014;
  • International Journal of Statistics in Medical Research. 08/2014; 3(3):231-247.

Publication Stats

4k Citations
1,698.06 Total Impact Points

Institutions

  • 2007–2014
    • Richmond VA Medical Center
      Richmond, Virginia, United States
    • Università degli Studi di Torino
      • Department of Medical Science
      Torino, Piedmont, Italy
  • 2005–2014
    • Virginia Commonwealth University
      • • School of Pharmacy
      • • Division of Cardiology
      • • Department of Internal Medicine
      • • School of Medicine
      Richmond, Virginia, United States
  • 2013
    • Sapienza University of Rome
      • Department of Medico-Surgical Sciences and Biotechnologies
      Roma, Latium, Italy
    • Julphar School of Pharmacy
      Richmond, Virginia, United States
  • 2003–2013
    • Università degli Studi di Trieste
      • Department of Life Sciences
      Trieste, Friuli Venezia Giulia, Italy
    • Australian Catholic University
      Melbourne, Victoria, Australia
  • 2012
    • VU University Medical Center
      • Department of Pulmonary Medicine
      Amsterdam, North Holland, Netherlands
  • 2003–2011
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 2002–2011
    • Catholic University of the Sacred Heart
      • • Institute of Cardiology
      • • School of Cardiovascular Diseases
      Roma, Latium, Italy
    • Universitá degli Studi Internazionali di Roma
      Roma, Latium, Italy
  • 2009
    • Mount Sinai School of Medicine
      • Department of Radiology
      Manhattan, New York, United States
  • 2007–2008
    • University of Virginia
      • Division of Maternal Fetal Medicine
      Charlottesville, Virginia, United States
  • 2006
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
  • 2000–2005
    • LIUCBM Libera Università Campus Bio-Medico di Roma
      • Unit of Medical Oncology
      Roma, Latium, Italy