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1. Safety, Tolerability, and Effects of a Single Subcutaneous Administration of SP16 – a SERPIN-like, Small Peptide Agonist of the Low-Density Lipoprotein–like Receptor 1– on the Acute Inflammatory Response in Patients With ST-Segment Elevation Myocardial Infarction

Author: Benjamin W, Van Tassell, George F, Wohlford, Marco Giuseppe, Del Buono, Juan Ignacio, Damonte, Roshanak, Markley, Jeremy, Turlington, Dinesh, Kadariya, Azita, Talasaz, Jane, Ho, Amr, Marawan, Georgia K, Thomas, Dana, Austin, Cyrille, Gineste, Cohava, Gelber, and Antonio, Abbate
Subjects: Lipoproteins, LDL, Inflammation, Pharmacology, Percutaneous Coronary Intervention, Treatment Outcome, Myocardial Infarction, Humans, ST Elevation Myocardial Infarction, Stroke Volume, Peptides, Cardiology and Cardiovascular Medicine, Serpins, Ventricular Function, Left
Abstract: Modulation of the inflammatory response is a promising therapeutic strategy in acute myocardial infarction. The novel approach is based on the anti-inflammatory and cytoprotective properties mediated by the engagement of the low-density lipoprotein‒related protein 1 (LRP1) receptor. SERPIN peptide 16 (SP16) is a synthetic, selective LRP1 agonist. We herein present the results of a study with a single subcutaneous administration of SP16 in 10 patients with STEMI, to appraise its safety and tolerability and explore the effects on the acute inflammatory response, infarct size, and cardiac function.Ten patients with ST-segment elevation myocardial infarction (STEMI) were enrolled within 12 hours of symptoms onset and 6 hours of percutaneous coronary intervention in a single-center, single-arm, open-label study of a single subcutaneous administration of SP16 (0.2 mg/kg). Serial clinical biomarkers and echocardiography data were collected up to 12 months. The data are presented separately for the treatment group and compared with historical controls from a placebo-treated arm in a recently completed clinical trial (N = 28) with similar enrollment criteria.All ten patients with STEMI received subcutaneous administration of SP16, 381 [272-478] minutes after percutaneous coronary intervention, without any treatment-related adverse events. The area under the curve for C-reactive protein was 133 [46-528] mg·d/L in the SP16-treated group versus 286 [141-581] mg·d/L in the historical placebo-treated group ( P = 0.161). The area under the curve for creatine kinase-myocardial band was 1432 [675-3089] ng·d/mL in the SP16-treated group versus 2367 [830-4750] ng·d/mL in the historical placebo-treated patients ( P = 0.428). Left ventricular ejection fraction was 46% [39-54] at baseline and 51% [46-58] at 1 year follow-up in SP16-treated patients (interval change 5% [-0.3% to +9%] P = 0.05) and 44% [38%-56%] at baseline and 53% [43%-59%] at 1 year follow-up in historical placebo-treated patients (interval change 3% [-5% to 10%], P = 0.305).A single subcutaneous administration of SP16, a synthetic targeted LRP1 agonist, was safe and well-tolerated in patients with STEMI. A trend toward reduction in the inflammatory response and infarct size with SP16 was noted; however, the sample size for this study was not based on formal statistical criteria. More extensive studies are planned to determine the clinical efficacy of SP16 in STEMI.NCT: NCT04225533.
Published: 2022
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2. Ischemic Cardiomyopathy and Heart Failure After Acute Myocardial Infarction

Author: Marco Giuseppe Del Buono, Francesco Moroni, Rocco Antonio Montone, Lorenzo Azzalini, Tommaso Sanna, and Antonio Abbate
Subjects: Heart Failure, Ventricular Dysfunction, Left, Myocardial Infarction, Myocardial Ischemia, Humans, Cardiomyopathies, Cardiology and Cardiovascular Medicine
Abstract: Purpose of Review Ischemic cardiomyopathy refers to systolic left ventricular dysfunction in the setting of obstructive coronary artery disease and represents the most common cause of heart failure worldwide. It is often the combination of an irreversible loss of viable mass following an acute myocardial infarction (AMI) with a dysfunctional, but still viable, myocardium in the context of a chronically reduced myocardial blood flow and reduced coronary reserve. Medical treatments aiming at modulating neurohumoral response and restoring blood flow to the ischemic cardiomyocytes were shown to dramatically abate the occurrence of ventricular dysfunction and adverse remodeling in ischemic cardiomyopathy. Recent Findings Novel therapeutic approaches, such as mechanical unloading and modulation of the inflammatory response, appear to be promising. Furthermore, the understanding of the mechanisms by which, despite optimal treatment, heart failure ensues after AMI, with or without adverse remodeling and systolic dysfunction, is a critical step in the search for novel ways to tackle heart failure risk beyond preservation of left ventricular volumes and systolic function. Summary In this review article, we explore the principal pathophysiological mechanisms and pathways of heart failure in ischemic cardiomyopathy, therapeutic opportunities, and knowledge gaps in this area.
Published: 2022
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3. In-Hospital Death Among Patients Undergoing Percutaneous Coronary Intervention: A Root-Cause Analysis

Author: Francesco Moroni, Hitinder S. Gurm, Zachary Gertz, Antonio Abbate, and Lorenzo Azzalini
Subjects: Percutaneous Coronary Intervention, Treatment Outcome, Shock, Cardiogenic, Humans, Hospital Mortality, General Medicine, Acute Coronary Syndrome, Cardiology and Cardiovascular Medicine, Retrospective Studies
Abstract: Mortality related to percutaneous coronary intervention (PCI) has gradually declined during the last decade. However, the causes and circumstances of death remain largely undescribed in contemporary practice.We retrospectively evaluated all patients undergoing PCI at our institution from July 2013 to March 2021. Three cardiologists independently determined the causes and circumstances of death, and evaluated the preventability of death using validated methods.During study period, 4334 patients underwent 5506 PCIs, of whom 166 patients suffered in-hospital death (3.0%). Ninety-three percent of deceased patients initially presented with acute coronary syndrome, and 45% with cardiogenic shock. Left ventricular failure was the most common cause of death (39.7%), followed by neurologic compromise after cardiac arrest (16.8%) and infections (13.8%). The circumstance of death was most commonly acute cardiac (51.8%), followed by non-cardiac (19.2%) and non-procedural complications (17.4%). Death was attributed to a procedural complication in only 12% of cases. Reviewers determined that 90% of cases as being unpreventable or slightly preventable. Inter-reviewer agreement was substantial (the three reviewers agreed in80% of cases for cause and preventability of death).Mortality after PCI is uncommon, largely unpreventable, and most often related to pre-existing, acute cardiovascular conditions. Procedural complications account for a minority of cases of death, and future effort should focus on the treatment of acute cardiovascular conditions, in particular cardiogenic shock, to decrease acute mortality after PCI.
Published: 2022
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4. Advances in pharmacotherapy for acute and recurrent pericarditis

Author: Alessandra Vecchié, Marco Giuseppe Del Buono, Adolfo Gabriele Mauro, Paul C. Cremer, Massimo Imazio, Allan L. Klein, Antonio Abbate, Francesco Dentali, and Aldo Bonaventura
Subjects: Inflammation, Pharmacology, IL-1 blockers, Acute pericarditis, anakinra, IL-1α, IL-1β, NLRP3 inflammasome, recurrent pericarditis, rilonacept, Inflammasomes, Anti-Inflammatory Agents, Non-Steroidal, General Medicine, Humans, Pericarditis, Pharmacology (medical), Colchicine
Abstract: Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are first-line treatments for acute and recurrent pericarditis. Drugs blocking the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome/interleukin-1β (IL-1β) axis are beneficial in patients with multiple recurrences.In this review, the role of the NLRP3 inflammasome/IL-1β axis in the pathophysiology of pericarditis is discussed. Updates about novel therapies targeting IL-1 for recurrent pericarditis (RP) and practical considerations for their use are provided.IL-1 inhibitors have been increasingly studied for RP in recent years. NLRP3 inflammasome is a key mediator in the pathophysiology of RP. IL-1β, its main product, can sustain its own production and feeds local and systemic inflammation. Randomized clinical trials testing anakinra (a recombinant form of the IL-1 receptor antagonist blocking IL-1α and IL-1β) and rilonacept (an IL-1α and IL-1β trap) have shown that IL-1 blockade reduces recurrences. These trials also helped in phenotyping patients with RP. Patients with multiple recurrences and signs of pericardial and/or systemic inflammation might benefit from IL-1 blockers in order to interrupt cyclic flares of auto-inflammation. Given this evidence, guidelines should consider incorporating IL-1 blockers.
Published: 2022
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5. Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation

Author: Aldo Bonaventura, Alessandra Vecchié, Lorenzo Dagna, Flavio Tangianu, Antonio Abbate, and Francesco Dentali
Subjects: Pharmacology, IL-6, SARS-CoV-2, Inflammasomes, Immunology, Anti-Inflammatory Agents, COVID-19, Review, NLRP3 inflammasome, COVID-19 Drug Treatment, IL-1β, NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Humans, Colchicine
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of inducing the activation of NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, a macromolecular structure sensing the danger and amplifying the inflammatory response. The main product processed by NLRP3 inflammasome is interleukin (IL)-1β, responsible for the downstream production of IL-6, which has been recognized as an important mediator in coronavirus disease 2019 (COVID-19). Since colchicine is an anti-inflammatory drug with the ability to block NLRP3 inflammasome oligomerization, this may prevent the release of active IL-1β and block the detrimental effects of downstream cytokines, i.e. IL-6. To date, few randomized clinical trials and many observational studies with colchicine have been conducted, showing interesting signals. As colchicine is a nonspecific inhibitor of the NLRP3 inflammasome, compounds specifically blocking this molecule might provide increased advantages in reducing the inflammatory burden and its related clinical manifestations. This may occur through a selective blockade of different steps preceding NLRP3 inflammasome oligomerization as well as through a reduced release of the main cytokines (IL-1β and IL-18). Since most evidence is based on observational studies, definitive conclusion cannot be drawn and additional studies are needed to confirm preliminary results and further dissect how colchicine and other NLRP3 inhibitors reduce the inflammatory burden and evaluate the timing and duration of treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s00011-022-01540-y.
Published: 2022

6. Pericarditis Recurrence After Initial Uncomplicated Clinical Course

Author: Alessandra Vecchié, Benjamin W. Van Tassell, Georgia K. Thomas, Daniel Berrocal, Aldo Bonaventura, Juan Guido Chiabrando, Marco Giuseppe Del Buono, Tamas S Gal, Megan Dell, Travis Oakes, Juan Ignacio Damonte, and Antonio Abbate
Subjects: Adult, Male, medicine.medical_specialty, Logistic regression, Severity of Illness Index, Pericardial effusion, Pericardial Effusion, Article, Pericarditis, Postoperative Complications, Acute pericarditis, Adrenal Cortex Hormones, Recurrence, Risk Factors, Interquartile range, Internal medicine, medicine, Humans, Retrospective Studies, First episode, business.industry, Incidence (epidemiology), Anti-Inflammatory Agents, Non-Steroidal, Age Factors, Middle Aged, medicine.disease, Tubulin Modulators, Surgery, Logistic Models, Acute Disease, Multivariate Analysis, Cardiology, Female, Tamponade, Colchicine, Cardiology and Cardiovascular Medicine, business
Abstract: Acute pericarditis is an inflammatory disease associated with a non-negligible risk of acute complications and future recurrence. However, the exact incidence of pericarditis recurrence in patients with a first uncomplicated clinical course is unknown. We sought to evaluate the incidence and clinical predictors of recurrence after a first episode of acute uncomplicated pericarditis in a large urban hospital in the United States. We conducted a retrospective review, through electronic health records, to complete a database that includes patients admitted with a first episode of acute pericarditis and selected only those with an uncomplicated course (without in-hospital death, large pericardial effusion [>20 mm] or tamponade, constriction, or incessant pericarditis) at the VCU Medical Center (Richmond, Virginia) from 2009 to 2018. A total of 240 patients met acute pericarditis criteria: of the 240 patients, 164 patients (68%) had an uncomplicated course (median age [interquartile range] in years: 50 [32 to 62], 43% females). The median follow-up time was 186 (19 to 467) days. Pericarditis was idiopathic in 84 patients (51%). Fifteen patients (9%) had at least 1 episode of recurrent pericarditis. Compared with those without recurrence, patients with recurrent pericarditis were younger (37 [25 to 59] vs 51 [34 to 62] years, p = 0.034), had a higher prevalence of subacute/delayed presentation (2 [13%] vs 1 [1%], p = 0.023), and less frequently received colchicine (6 [40%] vs 100 [67%], p = 0.036). At multivariate logistic regression analysis, subacute presentation and younger age remained predictors of recurrence at follow-up. In conclusion, 9% of patients with acute pericarditis experienced a recurrence over a 6-month median follow-up despite an initial uncomplicated course. Younger age and subacute presentation were associated with a significantly increased risk of recurrence.
Published: 2021
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7. Preservation of Cardiac Reserve and Cardiorespiratory Fitness in Patients With Acute De Novo Versus Acute on Chronic Heart Failure With Reduced Ejection Fraction

Author: Ross Arena, Juan Ignacio Damonte, Roshanak Markley, Hayley Billingsley, Azita Hajhossein Talasaz, Emily Federmann, Antonio Abbate, Benjamin W. Van Tassell, Salvatore Carbone, Justin M. Canada, Cory R. Trankle, Juan Lu, Ai-Chen Ho, Alessandra Vecchié, Virginia L. Mihalick, Jeremy Turlington, Marco Giuseppe Del Buono, George F. Wohlford, and Dinesh Kadayira
Subjects: Male, medicine.medical_specialty, Ventricular Function, Left, Article, Oxygen Consumption, Interquartile range, Internal medicine, Humans, Medicine, In patient, Retrospective Studies, Heart Failure, Ejection fraction, business.industry, Cardiac reserve, Stroke Volume, Cardiorespiratory fitness, Cardiopulmonary exercise testing, Middle Aged, medicine.disease, Pathophysiology, Cardiorespiratory Fitness, Heart failure, Acute Disease, Chronic Disease, Exercise Test, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: There is limited understanding on the potential differences in the pathophysiology between de novo heart failure with reduced ejection fraction (HFrEF) and acute on chronic HFrEF. The aim of this study was to assess differences in cardiorespiratory fitness (CRF) parameters between de novo heart failure and acute on chronic HFrEF using cardiopulmonary exercise testing (CPX). We retrospectively analyzed CPX data measured within 2 weeks of discharge following acute hospitalization for HFrEF. Data are reported as median and interquartile range or frequency and percentage (%). We included 102 patients: 32 (31%) women, 81 (79%) black, 57 [51–64] years of age, BMI of 34 [29–39] Kg/m(2). Of these, 26 (25%) had de novo HFrEF and 76 (75%) had acute on chronic HFrEF. When compared with acute on chronic, patients with de novo HFrEF had a significantly higher peak oxygen consumption (VO(2)) (16.5 [12.2–19.4] vs 12.8 [10.1 15.3] mL·kg(−1) min (−1), p
Published: 2021
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8. Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART)

Author: Frank Bogun, Kirsta Bray, Alpha Berry Fowler, Jennifer H. Jordan, Kenneth A. Ellenbogen, Amy Ladd, Melissa C. Smallfield, Sangeeta Lathkar-Pradhan, Shilpa Jasti, Lynda E. Rosenfeld, Huzaefah J. Syed, Todd M. Koelling, Emily Federmann, Kelly Polly, Jordana Kron, Virginia Mihalick, W. Gregory Hundley, Benjamin W. Van Tassell, Aamer Syed, David H. Birnie, Thomas Crawford, Antonio Abbate, Le Kang, and Thomas Iden
Subjects: medicine.medical_specialty, Myocarditis, Heart disease, Sarcoidosis, Pilot Projects, Heart failure, General Biochemistry, Genetics and Molecular Biology, law.invention, Cardiac sarcoidosis, Randomized controlled trial, law, Internal medicine, medicine, Protocol, Humans, Myocardial infarction, Translational Science, Biomedical, Inflammation, Anakinra, Granuloma, business.industry, General Medicine, medicine.disease, Clinical trial, Interleukin 1 Receptor Antagonist Protein, Treatment Outcome, Medicine, Female, business, medicine.drug, Interleukin-1
Abstract: BackgroundSarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis.MethodsBuilding on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis.DiscussionThe current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities.Trial RegistrationThe trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936.
Published: 2021

9. Interleukin-1 blockade with anakinra and heart failure following ST-segment elevation myocardial infarction: results from a pooled analysis of the VCUART clinical trials

Author: Dinesh Kadariya, Roshanak Markley, Michael J. Lipinski, Cory R. Trankle, Marco Giuseppe Del Buono, Antonio Abbate, Benjamin W. Van Tassell, George F. Wohlford, Giuseppe Biondi-Zoccai, Juan Guido Chiabrando, and Jeremy Turlington
Subjects: medicine.medical_specialty, Placebo, Internal medicine, Injection site reaction, medicine, Humans, ST segment, Pharmacology (medical), Myocardial infarction, Randomized Controlled Trials as Topic, Heart Failure, Anakinra, business.industry, Incidence (epidemiology), Area under the curve, medicine.disease, Interleukin 1 Receptor Antagonist Protein, C-Reactive Protein, Heart failure, Cardiology, ST Elevation Myocardial Infarction, Original Article, Cardiology and Cardiovascular Medicine, business, Interleukin-1, medicine.drug
Abstract: Aims ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). In this study, we sought to evaluate the effect of anakinra, a recombinant interleukin-1 receptor antagonist, on the incidence of HF. Methods and results We performed a pooled analysis of three early phase randomized clinical trials. The endpoints included the composite of all-cause death and new-onset HF, and the composite of all-cause death and hospitalization for HF at 1-year follow-up. Safety events, including injection site reaction and serious infections, were also recorded. We analysed 139 patients with STEMI from three separate trials: VCUART (N = 10), VCUART2 (N = 30), and VCUART3 (N = 99). Of these, 84 (60%) patients were randomized to anakinra and 55 (40%) to placebo. Treatment with anakinra significantly reduced the incidence of all-cause death or new-onset HF (7 [8.2%] vs. 16 [29.1%], log-rank P = 0.002) and of all-cause death or HF hospitalization (0 [0] vs. 5 [9.1%], log-rank P = 0.007). Patients treated with anakinra had significantly higher injection site reactions (19 [22.6%] vs. 3 [5.5%], P = 0.016) without a significant difference in the incidence of serious infections (11 [13.1%] vs. 7 [12.7%], P = 0.435). Treatment with anakinra significantly reduced the area under the curve for high-sensitivity C-reactive protein between baseline and 14 days (75.48 [41.7–147.47] vs. 222.82 [117.22–399.28] mg day/L, P Conclusion IL-1 blockade with anakinra for 14 days in patients with STEMI reduces the incidence of new-onset HF or hospitalization for HF at 1 year following STEMI.
Published: 2021
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10. Anti-interleukin-1 agents for pericarditis: a primer for cardiologists

Author: Martin M. LeWinter, Massimo Imazio, George Lazaros, Allan L. Klein, Antonio Abbate, Marco Gattorno, and Antonio Brucato
Subjects: Anakinra, business.industry, Interleukin, medicine.disease, Systemic inflammation, Proinflammatory cytokine, Rilonacept, Interleukin 1 Receptor Antagonist Protein, Canakinumab, Pericarditis, Cardiologists, Monoclonal, Immunology, medicine, Humans, medicine.symptom, Colchicine, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory and rheumatic conditions, where overproduction of IL-1 is an important pathophysiologic process. IL-1α and IL-1β are the most studied members of the IL-1 family of cytokines and have the strongest proinflammatory effects. A naturally occurring antagonist (IL-1Ra) mitigates their proinflammatory effects. Overproduction of both IL-1α (released by inflamed/damaged pericardial cells) and IL-1β (released by inflammatory cells) is now a well-recognized therapeutic target in patients with recurrent idiopathic pericarditis. Currently, there are three available anti-IL-1 agents: anakinra (recombinant human IL-1Ra), rilonacept (a soluble decoy receptor ‘trap’, binding both IL-1α and IL-1β), and canakinumab (human monoclonal anti-IL-1β antibody). For patients with corticosteroid-dependent and colchicine-resistant recurrent pericarditis with evidence of systemic inflammation, as evidenced by elevated C-reactive protein, the efficacy and safety of anakinra (2 mg/kg/day up to 100 mg/day subcutaneously usually for at least 6 months, then tapered) and rilonacept (320 mg subcutaneously for the first day followed by 160 mg subcutaneously weekly) have been clearly demonstrated in observational studies and randomized controlled clinical trials. Severe side effects are rare and discontinuation rates are very low (50% of patients). In this article, we describe the historical and pathophysiological background and provide a comprehensive review of these agents, which appear to be the most significant advance in medical therapy of recurrent pericarditis in the last 5 years.
Published: 2021
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11. Effect of Canagliflozin Compared With Sitagliptin on Serum Lipids in Patients with Type 2 Diabetes Mellitus and Heart Failure with Reduced Ejection Fraction: A Post-Hoc Analysis of the CANA-HF Study

Author: Dinesh Kadariya, Salvatore Carbone, Hayley Billingsley, Richard H. Cooke, Antonio Abbate, Benjamin W. Van Tassell, Cory R. Trankle, Dave L. Dixon, Justin M. Canada, and Linda Hart
Subjects: Male, medicine.medical_specialty, Time Factors, Urology, Blood lipids, Article, chemistry.chemical_compound, Double-Blind Method, Post-hoc analysis, medicine, Humans, Prospective Studies, Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Pharmacology, Dipeptidyl-Peptidase IV Inhibitors, Ejection fraction, Triglyceride, business.industry, Cholesterol, HDL, Sitagliptin Phosphate, Type 2 Diabetes Mellitus, Cholesterol, LDL, Middle Aged, medicine.disease, Cholesterol, Treatment Outcome, Diabetes Mellitus, Type 2, chemistry, Sitagliptin, Heart failure, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Heart Failure, Systolic, medicine.drug
Abstract: The sodium glucose co-transporter 2 inhibitors have demonstrated favorable effects on cardiovascular and renal disease; however, they may also increase low-density lipoprotein cholesterol (LDL-C). There are limited data directly comparing the effects of sodium glucose co-transporter 2inhibitors on serum lipids to other antihyperglycemic therapies. In this post-hoc analysis of the CANA-HF trial, we sought to compare the effects of canagliflozin to sitagliptin in patients with type 2 diabetes mellitus (T2DM) and heart failure and reduced ejection fraction (HFrEF). The CANA-HF trial was a prospective, randomized controlled study that compared the effects of canagliflozin 100 mg daily to sitagliptin 100 mg daily on cardiorespiratory fitness in patients with HFrEF and T2DM. Of the 36 patients enrolled in CANA-HF, 35 patients had both baseline and 12-weeks serum lipids obtained via venipuncture. The change in LDL-C from baseline to 12 weeks was 5 (-12.5 to 19.5) mg/dL versus -8 (-19 to -1) mg/dL (P = 0.82) and triglyceride levels was -4 (-26 to 9) mg/dL and -10.5 (-50 to 29.3) mg/dL (P = 0.52) for canagliflozin and sitagliptin, respectively. No significant differences were found between canagliflozin and sitagliptin for total cholesterol, high-density lipoprotein cholesterol or non-HDL-C (P > 0.5 for all). These data suggest that compared with sitagliptin, canagliflozin may not increase LDL-C in patients with T2DM and HFrEF.
Published: 2021
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12. Interleukin‐1 Trap Rilonacept Improved Health‐Related Quality of Life and Sleep in Patients With Recurrent Pericarditis: Results From the Phase 3 Clinical Trial RHAPSODY

Author: Antonio Brucato, Michelle Z. Lim‐Watson, Allan Klein, Massimo Imazio, David Cella, Paul Cremer, Martin M. LeWinter, Sushil Allen Luis, David Lin, Dor Lotan, Massimo Pancrazi, Lucia Trotta, Brittany Klooster, Leighann Litcher‐Kelly, Liangxing Zou, Matt Magestro, Alistair Wheeler, John F. Paolini, Antonio Abbate, Wael Abo‐Auda, Asif Akhtar, Michael Arad, Shaul Atar, Bipul Baibhav, Karan Bhalla, Sean Collins, David Colquhoun, David Cross, Girish Dwivedi, Alon Eisen, Nahum Freedberg, Shmuel Fuchs, Eliyazar Gaddam, Marco Gattorno, Eli Gelfand, Paul Grena, Majdi Halabi, David Harris, Antonella Insalaco, Amin Karim, Kirk Knowlton, Apostolos Kontzias, Robert Kornberg, Faisal Latif, David Leibowitz, and Martin LeWinter
Subjects: Treatment Outcome, Interleukin-1alpha, Quality of Life, Humans, Pain, Pericarditis, Sleep, Cardiology and Cardiovascular Medicine
Abstract: Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health‐related quality of life. RHAPSODY (rilonacept inhibition of interleukin‐1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL‐1α and ‐β cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient‐reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient‐reported outcome (PRO) questionnaires assessing pericarditis pain, health‐related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run‐in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run‐in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run‐in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health‐related quality of life. All PRO scores significantly improved ( P Conclusions These results demonstrate the burden of pericarditis recurrences and the improved physical and emotional health of patients with recurrent pericarditis while on rilonacept treatment. These findings extend prior rilonacept efficacy results, demonstrating improvements in patient‐reported health‐related quality of life, sleep, pain, and global symptom severity while on treatment. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03737110.
Published: 2022
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13. Sarcopenic Obesity Is Associated With Reduced Cardiorespiratory Fitness Compared With Nonsarcopenic Obesity in Patients With Heart Failure With Reduced Ejection Fraction

Author: Hayley E. Billingsley, Marco Giuseppe Del Buono, Justin M. Canada, Youngdeok Kim, Juan Ignacio Damonte, Cory R. Trankle, Geza Halasz, Virginia Mihalick, Alessandra Vecchié, Roshanak R. Markley, Dinesh Kadariya, Edoardo Bressi, Horacio Medina de Chazal, Juan Guido Chiabrando, James Mbualungu, Jeremy Turlington, Ross Arena, Benjamin W. Van Tassell, Antonio Abbate, and Salvatore Carbone
Subjects: Heart Failure, Oxygen, Sarcopenia, Oxygen Consumption, Cardiorespiratory Fitness, Exercise Test, Humans, Stroke Volume, Obesity, Cardiology and Cardiovascular Medicine
Abstract: Background: Sarcopenia impairs cardiorespiratory fitness (CRF) in patients with heart failure with reduced ejection fraction (HFrEF). Obesity has also been shown to impair CRF; however, the effects of sarcopenia on CRF in patients with obesity and HFrEF are unknown. The aim of this analysis was to examine differences in CRF between patients with sarcopenic obesity (SO) and non-SO (NSO) with HFrEF. We also assessed associations between skeletal muscle mass index (SMMI) and CRF. Methods: Forty patients with HFrEF and obesity underwent cardiopulmonary exercise testing to collect measures of CRF including peak oxygen consumption (VO 2 ), circulatory power, oxygen uptake efficiency slope, O 2 pulse, and exercise time. Body composition was performed in all patients using bioelectrical impedance analysis to quantify fat mass index and divide patients into SO and NSO based on SMMI cutoffs. Results are presented as mean (SD) or median [interquartile range] as appropriate. Results: Nearly half (43% [n=17]) of patients had SO. Patients with SO had a lower SMMI than those with NSO, and no differences in fat mass index were observed between groups. Those with SO achieved a lower absolute peak VO 2 (NSO, 1.62±0.53 L·min -1 versus SO, 1.27±0.44 L·min -1 , P =0.035), oxygen uptake efficiency slope (NSO, 1.92±0.59 versus SO, 1.54±0.48, P =0.036), and exercise time (NSO, 549±198 seconds versus SO, 413±140 seconds, P =0.021) compared to those with NSO. On multivariate analysis, SMMI remained a significant predictor of absolute peak VO 2 when adjusted for age, sex, adiposity, and HF severity. Conclusions: In patients with HFrEF and obesity, sarcopenia, defined as low SMMI, is associated with a clinically significant reduction in CRF, independent of adiposity.
Published: 2022
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14. The Conundrum of HFpEF Definition: Non-Invasive Assessment Uncertainties and Alternative Diagnostic Strategies

Author: Alberto Palazzuoli, Marco G.D. Buono, Gaetano Ruocco, Sergio Caravita, Antonio Abbate, and Carl J. Lavie
Subjects: Heart Failure, Clinical Trials, Phase III as Topic, Systole, Humans, Reproducibility of Results, Stroke Volume, General Medicine, Cardiology and Cardiovascular Medicine, Prognosis, Ventricular Function, Left
Abstract: Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome including several morphological phenotypes and varying pathophysiological mechanisms. The conventional classification of HF based on left ventricular ejection fraction (LVEF) has created an oversimplification in diagnostic criteria. Although LVEF is a standardized parameter easy to calculate and broadly applied in the large clinical trials, but it is erroneously considered an index of left ventricular (LV) systolic function. Indeed, it is affected by preload and afterload and it has limitations related to reproducibility, reduced sensitivity and scarce prognostic values especially when above 50%. Notably, additional diagnostic parameters have been recently proposed in order to improve diagnostic accuracy and to homogenize the different HFpEF populations. Unfortunately, these algorithms comprise sophisticated measurements that are difficult to apply in the daily clinical practice. Additionally, the scarce diffusion of these diagnostic criteria may have led to neutral or negative results in interventional phase 3 trials. We propose changes to the current HFpEF diagnostic approach mainly based on LVEF stratification measurement aiming towards a more inclusive model taking into consideration an integrative approach starting from the main diseases responsible for cardiac dysfunction through to cardiac structural and functional alterations. Accordingly, with recent universal HF definitions, a stepwise model could be helpful in recognizing patients with early vs. overt HFpEF by the appraisal of specific Doppler echocardiographic variables. Thus, we would encourage the application of new criteria in order to better identify the different phenotypes and to move towards more personalized medicine.
Published: 2022

15. Cardiopulmonary exercise testing during the COVID-19 pandemic

Author: Justin M. Canada, Virginia L. Mihalick, Ross Arena, Danielle L. Kirkman, and Antonio Abbate
Subjects: PA, Physical activity, medicine.medical_specialty, CP, Cardiopulmonary, Stress testing, medicine.medical_treatment, CRF, Cardiorespiratory fitness, Exercise intolerance, Disease, 030204 cardiovascular system & hematology, CPD, Cardiopulmonary disease, Article, 03 medical and health sciences, 0302 clinical medicine, Pandemic, Health care, Gas exchange, medicine, Humans, 030212 general & internal medicine, COVID-19, Corona virus infectious disease-19, CPET, Cardiopulmonary exercise testing, CV, Cardiovascular, Intensive care medicine, CDC, Centers for Disease Control and Prevention, HEPA, High efficiency particulate air, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, PPE, Personal and protective equipment, Rehabilitation, business.industry, Public health, COVID-19, Sterilization, Cardiorespiratory fitness, ERS, European Respiratory Society, Practice Guidelines as Topic, Exercise Test, PCR, Polymerase chain reaction, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has presented a global public health emergency. Although predominantly a pandemic of acute respiratory disease, corona virus infectious disease-19 (COVID-19) results in multi-organ damage that impairs cardiopulmonary (CP) function and reduces cardiorespiratory fitness. Superimposed on the CP consequences of COVID-19 is a marked reduction in physical activity that exacerbates CP disease (CPD) risk. CP exercise testing (CPET) is routinely used in clinical practice to diagnose CPD and assess prognosis; assess cardiovascular safety for rehabilitation; and delineate the physiological contributors to exercise intolerance and exertional fatigue. As such, CPET plays an important role in clinical assessments of convalescent COVID-19 patients as well as research aimed at understanding the long-term health effects of SARS-CoV-2 infection. However, due to the ventilatory expired gas analysis involved with CPET, the procedure is considered an aerosol generating procedure. Therefore, extra precautions should be taken by health care providers and exercise physiologists performing these tests. This paper provides recommendations for CPET testing during the COVID-19 pandemic. These recommendations include indications for CPET; pre-screening assessments; precautions required for testing; and suggested decontamination protocols. These safety recommendations are aimed at preventing SARS-CoV-2 transmission during CPET.
Published: 2021
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16. Usefulness of the Duke Activity Status Index to Select an Optimal Cardiovascular Exercise Stress Test Protocol

Author: Mary Ann Reynolds, W. Gregory Hundley, Justin M. Canada, Hem Bhardwaj, Josh West, Michael C. Kontos, Colton Powell, Antonio Abbate, Rachel Myers, Katey Sweat, Ross Arena, and Virginia McGhee
Subjects: Male, medicine.medical_specialty, Myocardial ischemia, 030204 cardiovascular system & hematology, Risk Assessment, Metabolic equivalent, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Stress test, Interquartile range, Internal medicine, Heart rate, medicine, Health Status Indicators, Humans, Aerobic exercise, Prospective Studies, Peak exercise, Exercise Tolerance, business.industry, Middle Aged, Activity Status, Cardiovascular Diseases, Exercise Test, Cardiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Exercise testing represents the preferred stress modality for individuals undergoing evaluation of suspected myocardial ischemia. Patients with limited functional status may be unable to achieve an adequate exercise stress, thus influencing the diagnostic sensitivity of the results. The Duke Activity Status Index (DASI) is a clinically applicable tool to estimate exercise capacity. The purpose of the current study was to assess the utility of the DASI to identify patients unable to achieve an adequate exercise stress result. Patients referred for exercise stress testing were administered the DASI pre-exercise. Baseline characteristics and exercise variables were evaluated including DASI-metabolic equivalents (DASI-METs), peak METs, exercise time (ET), and %-predicted maximal heart rate (%PMHR). Criteria for determining adequate exercise stress was defined as ≥85%PMHR or ≥ 5-METs at peak exercise. In 608 cardiovascular stress tests performed during the study period; 314 were exercise stress. The median DASI-METs (8.4 [interquartile range; 6.7 to 9.9]) was associated with estimated peak exercise METs (R=0.50, p0.001), ET (R=0.29, p0.001), and %PMHR (R=0.19, p = 0.003). DASI-METs were different between those withor ≥85%PMHR (7.9 [6.6-9.0] vs. 8.9 [7.1-9.9], P=0.025) and those withor ≥5-METs (5.8 [4.6 to 6.6] versus 8.9 [7.3-9.9], p0.001). Receiver operating characteristic curve analysis identified a DASI-MET threshold of ≤/7.4 to optimally predict adequate exercise stress (sensitivity=93%, specificity=71%). In conclusion, the DASI correlates with peak METs, ET, and %PMHR among patients referred for exercise testing and can be used to identify patients with an increased likelihood of an inadequate stress test result.
Published: 2021
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17. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

Author: Steffen Massberg, Marcel Levi, Francesco Dentali, Fabrizio Montecucco, Kimberly Martinod, Alessandra Vecchié, Lorenzo Dagna, Antonio Abbate, Benjamin W. Van Tassell, Dave L. Dixon, Aldo Bonaventura, and Vascular Medicine
Subjects: Blood Platelets, 0301 basic medicine, History, ARDS, Neutrophils, Critical Illness, Disease, Monocytes, Education, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, Fibrinolytic Agents, Immunity, Vascular, Antithrombotic, Humans, Innate, Medicine, Endothelium, Endothelial dysfunction, Blood Coagulation, Lung, Venous Thrombosis, Innate immunity, Innate immune system, SARS-CoV-2, business.industry, COVID-19, Cytokine Release Syndrome, Endothelium, Vascular, Immunity, Innate, Antimicrobial responses, medicine.disease, Coagulation system, Computer Science Applications, 030104 developmental biology, Viral infection, Perspective, Immunology, Cytokines, business, 030215 immunology
Abstract: Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease., Here, the authors propose that SARS-CoV-2 induces a prothrombotic state, with dysregulated immunothrombosis in lung microvessels and endothelial injury, which drive the clinical manifestations of severe COVID-19. They discuss potential antithrombotic and immunomodulating drugs that are being considered in the treatment of patients with COVID-19.
Published: 2021
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18. Interleukin-1 blockade with RPH-104 in patients with acute ST-elevation myocardial infarction: study design and rationale

Author: Antonio Abbate, M Samsonov, B.W. Van Tassell, and V Bogin
Subjects: Trial design, medicine.medical_specialty, Inflammation, 030204 cardiovascular system & hematology, Placebo, General Biochemistry, Genetics and Molecular Biology, STEMI, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Natriuretic Peptide, Brain, medicine, Clinical endpoint, Protocol, Humans, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Heart Failure, business.industry, IL-1, Interleukin, RPH-104, General Medicine, Brain natriuretic peptide, medicine.disease, Blockade, C-Reactive Protein, Cardiovascular diseases, Echocardiography, Heart failure, Cardiology, ST Elevation Myocardial Infarction, Medicine, medicine.symptom, business, Biomarkers, Interleukin-1
Abstract: Background Myocardial injury of ST-segment elevation myocardial infarction (STEMI) initiates an intense inflammatory response that contributes to further damage and is a predictor of increased risk of death or heart failure (HF). Interleukin-1 (IL-1) is a key mediator of local and systemic inflammatory response to myocardial damage. We postulate that the use of the drug RPH-104, which selectively binds and inactivates both α and β isoforms of IL-1 will lead to a decrease in the severity of the inflammatory response which will be reflected by decrease in the concentration of hsCRP, as well as the rate of fatal outcomes, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP) and changes in structural and functional echocardiographic parameters. Methods This is a double blind, randomized, placebo-controlled study in which 102 patients with STEMI will receive a single administration of RPH-104 80 mg, RPH-104 160 mg or placebo (1:1:1). The primary endpoint will be hsCRP area under curve (AUC) from day 1 until day 14. Secondary endpoints will include hsCRP AUC from day 1 until day 28, rate of fatal outcomes, hospitalizations due to HF and other cardiac and non-cardiac reasons during 12-month follow-up period, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP, NT-pro-BNP), changes in structural and functional echocardiographic parameters during 12-month follow-up period compared to baseline. The study started in October 2020 and is anticipated to end in 2Q 2022. Trial registration: ClinicalTrials.gov, NCT04463251. Registered on July 9, 2020
Published: 2021

19. Hypertension in Cancer Survivors: A Review of the Literature and Suggested Approach to Diagnosis and Treatment

Author: David, Chuquin, Antonio, Abbate, and Wendy, Bottinor
Subjects: Pharmacology, Adolescent, Antineoplastic Agents, Middle Aged, Young Adult, Cancer Survivors, Cardiovascular Diseases, Risk Factors, Neoplasms, Hypertension, Humans, Cardiomyopathies, Cardiology and Cardiovascular Medicine, Antihypertensive Agents
Abstract: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Hypertension, which is common among cancer survivors with a prevalence of greater than 70% by age 50, potentiates the risk for CVD in a more than additive fashion. For example, childhood cancer survivors who develop hypertension may have up to a 12 times higher risk for heart failure than survivors who remain normotensive. Studies have shown that mild valvular disease (28% incidence), cardiomyopathy (7.4%), arrhythmias (4.6%), and coronary artery disease (3.8%) are among the most common CVDs in childhood cancer survivors. Among adolescent and young adult cancer survivors, the most common reasons for cardiovascular-related hospital admission are venous/lymphatic disease (absolute excess risk 19%), cardiomyopathy and arrhythmia (15%), hypertension (13%), and ischemic heart disease (12%). In addition, cancer therapies can increase the risk for hypertension and CVD. Therefore, early detection and treatment of hypertension is essential to reducing cardiovascular morbidity and mortality among survivors.We present a literature review, which identified over 20 clinical trials, systemic reviews, and meta-analyses (13 clinical trials, 8 systemic reviews or meta-analyses) by searching PubMed, Google Scholar, and the Cochrane Library for relevant articles addressing hypertension in cancer survivors.Although our understanding of the complex relationship between cancer therapies and CVD has grown significantly over the past 2 decades, there remain several gaps in knowledge when specifically addressing CVD in the survivor population. This review provides an up-to-date survivor-centered approach to the screening and treatment of hypertension, which considers survivor-specific cardiovascular risk, applies guideline directed therapies when appropriate, screens for survivor-specific factors that may influence antihypertensive medication selection, and finally considers the prohypertensive mechanisms of antineoplastic agents as a potential target for antihypertensive medications.Screening for and treating hypertension among survivors can promote cardiovascular health in this vulnerable population.
Published: 2022
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20. Cardiovascular complications of anti-cancer therapy: a developing storm in medicine

Author: Alexander, Burashnikov, Antonio, Abbate, and George W, Booz
Subjects: Pharmacology, Heart Diseases, Humans, Cardiology and Cardiovascular Medicine
Published: 2022
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21. Prognostic Effect of Race on the Risk of Contrast-Associated Acute Kidney Injury Among Patients Who Undergo Percutaneous Coronary Intervention

Author: Francesco Moroni, Juan Ignacio Damonte, Devi Preetham R. Veeramgari, Krishna Ravindra, Sagar Sudhakar Prabhu, Mahreed Khan, Xin Wei, Luz Maria Vilca, Giuseppe Biondi-Zoccai, Rodrigo Bagur, Antonio Abbate, and Lorenzo Azzalini
Subjects: Percutaneous Coronary Intervention, Risk Factors, Creatinine, Humans, Contrast Media, Acute Kidney Injury, Cardiology and Cardiovascular Medicine, Prognosis
Published: 2022

22. Rationale and design of interleukin-1 blockade in recently decompensated heart failure (REDHART2): a randomized, double blind, placebo controlled, single center, phase 2 study

Author: Benjamin Van Tassell, Virginia Mihalick, Georgia Thomas, Amr Marawan, Azita H. Talasaz, Juan Lu, Le Kang, Amy Ladd, Juan Ignacio Damonte, Dave L. Dixon, Roshanak Markley, Jeremy Turlington, Emily Federmann, Marco Giuseppe Del Buono, Giuseppe Biondi-Zoccai, Justin M. Canada, Ross Arena, and Antonio Abbate
Subjects: Adult, Heart Failure, Interleukin 1 Receptor Antagonist Protein, Treatment Outcome, Double-Blind Method, Quality of Life, Humans, Stroke Volume, General Medicine, General Biochemistry, Genetics and Molecular Biology, Interleukin-1
Abstract: Background Heart failure (HF) is a global leading cause of mortality despite implementation of guideline directed therapy which warrants a need for novel treatment strategies. Proof-of-concept clinical trials of anakinra, a recombinant human Interleukin-1 (IL-1) receptor antagonist, have shown promising results in patients with HF. Method We designed a single center, randomized, placebo controlled, double-blind phase II randomized clinical trial. One hundred and two adult patients hospitalized within 2 weeks of discharge due to acute decompensated HF with reduced ejection fraction (HFrEF) and systemic inflammation (high sensitivity of C-reactive protein > 2 mg/L) will be randomized in 2:1 ratio to receive anakinra or placebo for 24 weeks. The primary objective is to determine the effect of anakinra on peak oxygen consumption (VO2) measured at cardiopulmonary exercise testing (CPX) after 24 weeks of treatment, with placebo-corrected changes in peak VO2 at CPX after 24 weeks (or longest available follow up). Secondary exploratory endpoints will assess the effects of anakinra on additional CPX parameters, structural and functional echocardiographic data, noninvasive hemodynamic, quality of life questionnaires, biomarkers, and HF outcomes. Discussion The current trial will assess the effects of IL-1 blockade with anakinra for 24 weeks on cardiorespiratory fitness in patients with recent hospitalization due to acute decompensated HFrEF. Trial registration: The trial was registered prospectively with ClinicalTrials.gov on Jan 8, 2019, identifier NCT03797001.
Published: 2022
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23. Sacubitril/Valsartan for the Prevention and Treatment of Postinfarction Heart Failure: Ready to Use?

Author: Hem Bhardwaj, Marco Giuseppe Del Buono, Antonio Abbate, Jeremy Turlington, Benjamin W. Van Tassell, Cory R. Trankle, Roshanak Markley, Fadi N Salloum, and Juan Ignacio Damonte
Subjects: medicine.medical_specialty, Clinical Decision-Making, Myocardial Infarction, Risk Assessment, medicine, Animals, Humans, Protease Inhibitors, Intensive care medicine, Heart Failure, Pharmacology, Evidence-Based Medicine, business.industry, Aminobutyrates, Biphenyl Compounds, Protective Factors, medicine.disease, Disease Models, Animal, Drug Combinations, Treatment Outcome, Heart Disease Risk Factors, Heart failure, Valsartan, Ready to use, Neprilysin, Cardiology and Cardiovascular Medicine, business, Angiotensin II Type 1 Receptor Blockers, Sacubitril, Valsartan
Published: 2021
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24. Exercise intolerance in kidney diseases: physiological contributors and therapeutic strategies

Author: Danielle L. Kirkman, Ryan S. Garten, Jason M. Kidd, Paula Rodriguez-Miguelez, Natalie J. Bohmke, Robert L. Franco, Salvatore Carbone, and Antonio Abbate
Subjects: medicine.medical_specialty, Kidney, Sympathetic Nervous System, Activities of daily living, Anemia, Iron-Deficiency, Physiology, business.industry, 030232 urology & nephrology, Review, Exercise intolerance, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Muscular Diseases, medicine, Humans, Kidney Failure, Chronic, Chronic renal insufficiency, medicine.symptom, Intensive care medicine, business, Exertional fatigue, Fatigue
Abstract: Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end-stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of exercise intolerance throughout the spectrum of the disease. The prevalence of exercise intolerance is clinically noteworthy, as it leads to increased frailty, worsened quality of life, and an increased risk of mortality. The physiological underpinnings of exercise intolerance are multifaceted and still not fully understood. This review aims to provide a comprehensive outline of the potential physiological contributors, both central and peripheral, to kidney disease-related exercise intolerance and highlight current and prospective interventions to target this symptom. In this review, the CKD-related metabolic derangements, cardiac and pulmonary dysfunction, altered physiological responses to oxygen consumption, vascular derangements, and sarcopenia are discussed in the context of exercise intolerance. Lifestyle interventions to improve exertional fatigue, such as aerobic and resistance exercise training, are discussed, and the lack of dietary interventions to improve exercise tolerance is highlighted. Current and prospective pharmaceutical and nutraceutical strategies to improve exertional fatigue are also broached. An extensive understanding of the pathophysiological mechanisms of exercise intolerance will allow for the development of more targeted therapeutic approached to improve exertional fatigue and health-related quality of life in CKD and ESRD.
Published: 2021
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25. Cardiopulmonary exercise testing – refining the clinical perspective by combining assessments

Author: Ross Arena, Antonio Abbate, Justin M. Canada, Marco Giuseppe Del Buono, Dejana Popovic, Alexander R. Lucas, and Cory R. Trankle
Subjects: endocrine system, medicine.medical_specialty, business.industry, Perspective (graphical), Cardiopulmonary exercise testing, Cardiorespiratory fitness, General Medicine, 030204 cardiovascular system & hematology, Prognosis, 03 medical and health sciences, Oxygen Consumption, 0302 clinical medicine, Physical medicine and rehabilitation, Echocardiography, Exercise Test, Internal Medicine, Humans, Medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Exercise, hormones, hormone substitutes, and hormone antagonists
Abstract: Cardiorespiratory fitness (CRF) is now established as a vital sign. Cardiopulmonary exercise testing (CPX) is the gold-standard approach to assessing CRF.A body of literature spanning several decades clearly supports the clinical utility of CPX in those who are apparently health and at risk for chronic disease as well as numerous patient populations. While CPX, in and of itself, is a valid and reliable clinical assessment, combining findings with other available assessments may provide a more comprehensive perspective that enhances clinical decision making and outcomes. The current review will accomplish the following: (1) define key CPX measures based upon current evidence; and (2) describe the current evidence addressing the relationships between CPX and echocardiography, serum biomarkers, and cardiovascular magnetic resonance.Cardiopulmonary exercise testing provides prognostic and diagnostic information in apparently healthy individuals, those at risk for one or more chronic conditions, as well as numerous patient populations. Moreover, if the goal of an intervention is to improve one or more systems integral to the physiologic response to exercise, CPX should be considered as a central assessment to gauge therapeutic efficacy. To further refine the information obtained from CPX, combining other assessments has demonstrated promise.
Published: 2020
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26. Cardiovascular Implications of the COVID-19 Pandemic: A Global Perspective

Author: Antonio Abbate, Marcelo Harada Ribeiro, Marouane Boukhris, Faouzi Addad, Luz Maria Vilca, Mohamed Salah Annabi, Luiz F. Ybarra, Lorenzo Azzalini, Francesco Moroni, Xiaohui Zhao, Ali Hillani, and Samer Mansour
Subjects: Male, medicine.medical_specialty, Myocarditis, Pneumonia, Viral, Comorbidity, 030204 cardiovascular system & hematology, Global Health, Severe Acute Respiratory Syndrome, Risk Assessment, Article, 03 medical and health sciences, 0302 clinical medicine, Cause of Death, Pandemic, Health care, Prevalence, Global health, Humans, Medicine, Hospital Mortality, 030212 general & internal medicine, Intensive care medicine, Pandemics, Stroke, business.industry, Cardiogenic shock, COVID-19, medicine.disease, Survival Analysis, Respiratory failure, Cardiovascular Diseases, Heart failure, Female, Coronavirus Infections, Cardiology and Cardiovascular Medicine, business
Abstract: The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased utilization of healthcare services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions., Although respiratory symptoms usually dominate the clinical presentation of COVID-19, cardiovascular manifestations have also been reported, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The pandemic might have an indirect impact on the delivery of cardiovascular care both among COVID-19 and non-COVID-19 patients. Innovative approaches that leverage modern technologies to tackle the pandemic have been used. This article provides an overview of the cardiovascular implications of COVID-19.
Published: 2020
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27. Clinical Presentation and Outcomes of Acute Pericarditis in a Large Urban Hospital in the United States of America

Author: Daniel Berrocal, Alessandra Vecchié, Benjamin W. Van Tassell, Megan Dell, Adolfo G Mauro, Aldo Bonaventura, Juan Guido Chiabrando, Fabrizio Montecucco, Tamas S Gal, Anna Beutler, George F. Wohlford, Antonio Abbate, and John F. Paolini
Subjects: Male, Pulmonary and Respiratory Medicine, Constrictive pericarditis, medicine.medical_specialty, recurrence, ICD, International Statistical Classification of Diseases and Related Health Problems, subacute presentation, Critical Care and Intensive Care Medicine, Risk Assessment, Pericardial Effusion, Pericarditis, Acute pericarditis, Hospitals, Urban, Internal medicine, Cardiac tamponade, medicine, troponin I, acute pericarditis, Humans, Myocardial infarction, First episode, biology, business.industry, Incidence, therapy failure, Patient Acuity, ESC, European Society of Cardiology, Middle Aged, Prognosis, medicine.disease, Troponin, United States, Cardiac Tamponade, AMI, acute myocardial infarction, Pulmonary and Cardiovascular: Original Research, Heart Injuries, Etiology, biology.protein, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Background Acute pericarditis is the most common presentation of pericardial diseases. Although generally benign, complications such as constrictive pericarditis, cardiac tamponade, and recurrence can occur. Research Question What are the clinical factors associated with adverse outcomes in acute pericarditis? Study Design and Methods We used an informatics-based search engine to search for International Classification of Diseases codes related to pericardial disease between January 1, 2009 and November 14, 2018 and then extracted clinical information, including only patients meeting the European Society of Cardiology criteria for acute pericarditis. We then evaluated the predictive value of clinical characteristics for adverse outcomes (cardiac tamponade, constrictive pericarditis, failure of therapy, recurrences, or death). Results We identified 240 patients with a first episode of pericarditis (51 [34-62] years, 56% males and 50% white). Pericarditis was determined to be idiopathic in 126 (53%) cases and related to cardiac injury in 79 (33%). During a median follow-up time of 179 (20-450) days, 82 (34%) patients experienced at least one adverse outcome. Subacute presentation was an independent predictor of adverse outcomes. Patients with postcardiac injury pericarditis had a lower incidence in the composite of failure of treatment and recurrence (13% vs 26%; P = .022) compared with patients with idiopathic pericarditis. Troponin I measurements were obtained in 167 patients (70%). Elevated troponin I levels were associated with lower incidence of recurrences (4% vs 17%; P = .024) and of the composite outcome (13% vs 36%; P = .004). Interpretation Acute pericarditis is associated with at least one adverse outcome in 34% of patients. Subacute presentation and idiopathic etiology are associated with higher incidence of adverse outcomes, whereas elevated troponin I levels identify a group with reduced risk of recurrences.
Published: 2020

28. Diabetes mellitus and heart failure: an update on pathophysiology and therapy

Author: Nicola, Potere, Marco G, Del Buono, Alessandra, Vecchié, Ettore, Porreca, Antonio, Abbate, Francesco, Dentali, and Aldo, Bonaventura
Subjects: Heart Failure, Glucose, Diabetes Mellitus, Type 2, Humans, Stroke Volume, Cardiology and Cardiovascular Medicine, Sodium-Glucose Transporter 2 Inhibitors
Abstract: Diabetes mellitus (DM) is frequent among heart failure (HF) patients with a further projected increase in prevalence in next years. DM promotes the development of both HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) through different mechanisms. As the general prevalence of both DM and HF is growing worldwide, it is important to define the pathophysiologic mechanisms driving the development of HF in DM patients. These include changes in the cardiac metabolism, mitochondrial dysfunction, impairment in insulin signaling, maladaptive inflammation, coronary microvascular dysfunction, endoplasmic reticulum stress, autophagy suppression, and structural changes, among the main ones. In recent years, novel glucose-lowering treatments, especially sodium-glucose cotransporter 2 inhibitors (SGLT-2is), have shown a strikingly positive impact on the natural history of HF. This has led to a progressive change in choosing SGLT-2is in DM patients at high risk for cardiovascular disease, supported by recent guidelines. The knowledge about novel pathophysiological mechanisms linking DM and HF may open the way to the development of new targeted therapies in the future. In this review, we will summarize general aspects dealing with incidence, prevalence, and pathophysiology of DM in HF patients. As well, we discuss the therapeutic targets to reduce the disease burden and the current evidence of glucose-lowering drugs in patients with DM and HF.
Published: 2022
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29. Patient Perceptions of Exertion and Dyspnea With Interleukin-1 Blockade in Patients With Recently Decompensated Systolic Heart Failure

Author: Virginia Mihalick, George Wohlford, Azita H. Talasaz, Ai-Chen (Jane) Ho, Francine Kim, Justin M. Canada, Salvatore Carbone, Dinesh Kadariya, Hayley Billingsley, Cory Trankle, Marco Giuseppe Del Buono, Francesco Moroni, Ross Arena, Antonio Abbate, and Benjamin Van Tassell
Subjects: Dyspnea, Exercise Tolerance, Oxygen Consumption, Physical Exertion, Exercise Test, Quality of Life, Humans, Cardiology and Cardiovascular Medicine, Article, Heart Failure, Systolic, Interleukin-1
Abstract: Interleukin-1 (IL-1) blockade is an anti-inflammatory treatment that may affect exercise capacity in heart failure (HF). We evaluated patient-reported perceptions of exertion and dyspnea at submaximal exercise during cardiopulmonary exercise testing (CPET) in a double-blind, placebo-controlled, randomized clinical trial of IL-1 blockade in patients with systolic HF (REDHART [Recently Decompensated Heart Failure Anakinra Response Trial]). Patients underwent maximal CPET at baseline, 2, 4, and 12 weeks and rated their perceived level of exertion (RPE, on a scale from 6 to 20) and dyspnea on exertion (DOE, on a scale from 0 to 10) every 3 minutes throughout exercise. Patients also answered 2 questionnaires to assess HF-related quality of life: the Duke Activity Status Index and the Minnesota Living with Heart Failure Questionnaire. From baseline to the 12-week follow-up, IL-1 blockade significantly reduced RPE and DOE at 3- and 6-minutes during CPET without changing values for heart rate, oxygen consumption, and cardiac workload at 3- and 6-minutes. Linear regression identified 6-minute RPE to be a strong independent predictor of both physical symptoms (Minnesota Living with Heart Failure Questionnaire; β = 0.474, p = 0.002) and perceived exercise capacity (Duke Activity Status Index; β = -0.443, p = 0.008). In conclusion, patient perceptions of exertion and dyspnea at submaximal exercise may be valuable surrogates for quality of life and markers of response to IL-1 blockade in patients with HF.
Published: 2022

30. Late breaking clinical trials at ACC 22

Author: Francesco Moroni and Antonio Abbate
Subjects: Clinical Trials as Topic, Cardiovascular Diseases, Humans, Pharmacology (medical), Cardiology and Cardiovascular Medicine
Published: 2022

31. The inflammasome as a therapeutic target for myopericardial diseases

Author: Massimo IMAZIO and Antonio ABBATE
Subjects: Inflammation, Inflammasomes, NLR Family, Pyrin Domain-Containing 3 Protein, Humans, Pericarditis, Cardiology and Cardiovascular Medicine, Colchicine
Abstract: Myopericardial diseases are relatively common in clinical practice although often neglected due to the limited availability of treatments and evidence to support management strategies. However in the past ten years, growing evidence has improved our knowledge of the pathophysiology of myopericardial diseases and first clinical trials have highlighted the importance of inflammation as therapeutic target developing first steps toward a personalized approach also in this field. The NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome is a protein complex that functions as a platform for rapid induction of the inflammatory response to infection or sterile injury through pro-inflammatory cytokines, now recognized as a new important therapeutic target for myopericardial diseases. Colchicine is an old drug that acts as non-specific inhibitor of the inflammasome and could be a useful and inexpensive option in clinical practice and it is currently registered for pericarditis in some European countries (e.g., Italy, Austria). Anti-interleukin-1 (IL-1) agents (anakinra and rilonacept) appear to be a major advance in medical therapy of recurrent pericarditis and could be a therapeutic option also for myocarditis if confirmed in additional studies. In this review, we provide an update on the inflammasome as therapeutic target for myopericardial diseases, a significant advance in medical therapy for these diseases in the last five years.
Published: 2022

32. Arrhythmic Recurrence and Outcomes in Patients Hospitalized With First Episode of Electrical Storm

Author: Juan Ignacio Damonte, Marco Giuseppe Del Buono, Georgia K. Thomas, James Mbualungu, Bennett Clark, Rocco Antonio Montone, Daniel H. Berrocal, Tamas S. Gal, Le Kang, Juan Lu, Benjamin Van Tassell, Jayanthi Koneru, Thomas C. Crawford, Kenneth A. Ellenbogen, Antonio Abbate, and Jordana Kron
Subjects: Treatment Outcome, Recurrence, Ventricular Fibrillation, Catheter Ablation, Tachycardia, Ventricular, Humans, Arrhythmias, Cardiac, Cardiology and Cardiovascular Medicine, Article, Defibrillators, Implantable, Retrospective Studies
Abstract: Electrical storm (ES) is a life-threatening condition that may lead to recurrent arrhythmias, need for ventricular mechanical support, and death. The study aimed to assess the burden of arrhythmia recurrence and in-hospital outcomes of patients admitted for ES in a large urban hospital. We performed a retrospective analysis of patients admitted with ventricular arrhythmias from January 2018 to June 2021 and identified 61 patients with ES, defined as 3 or more episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) within 24 hours. We reviewed the in-hospital outcomes and compared outcomes between patients who had no recurrence of VT/VF after the first 24 hours (34 [56%]), those with recurrence of 1 or 2 episodes of VT/VF within a 24-hour period (15 [24%]), and patients with 3 or more recurrent VT/VF events consistent with recurrent ES after the first 24 hours (12 [20%]). Patients with recurrent ES had significantly higher in-hospital mortality as compared with those with recurrent VT/VF not meeting criteria for ES or no recurrences of VT/VF (3 [25%] vs 0 [0%] vs 0 [0%]; p = 0.002). Moreover, patients with recurrent ES also had higher rates of the combined end points of ventricular mechanical support and death (7 [58%] vs 1 [6%] vs 1 [3%], p
Published: 2022

33. Midpoint of Energy Intake, Non-fasting Time and Cardiorespiratory Fitness in Heart Failure with Preserved Ejection Fraction and Obesity

Author: Hayley E. Billingsley, Justin M. Canada, Dave L. Dixon, Danielle L. Kirkman, Natalie Bohmke, Brando Rotelli, Dinesh Kadariya, Roshanak Markley, Benjamin W. Van Tassell, Francesco S. Celi, Antonio Abbate, and Salvatore Carbone
Subjects: Heart Failure, Exercise Tolerance, Oxygen Consumption, Cardiorespiratory Fitness, Exercise Test, Humans, Stroke Volume, Obesity, Cardiology and Cardiovascular Medicine, Energy Intake, Article
Abstract: BACKGROUND: Delayed time of evening meal is associated with favorable cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. It is unknown, however, if increasing daily non-fasting time or delaying the midpoint of energy intake may also be associated with CRF. OBJECTIVE: Our aim was to examine whether a longer non-fasting time, delayed midpoint of energy intake, or both, are associated with greater CRF in patients with HFpEF and obesity. METHODS: We measured peak oxygen consumption (VO(2)), a measure of CRF, in 32 patients with HFpEF and obesity with cardiopulmonary exercise testing, and dietary intake using a five-pass 24-h dietary recall. Participants were divided into groups by having lesser (
Published: 2022

34. Time of eating and cardiorespiratory fitness in patients with heart failure with preserved ejection fraction and obesity

Author: Francesco S. Celi, Brando Rotelli, Dinesh Kadariya, Justin M. Canada, Natalie J. Bohmke, Roshanak Markley, Danielle L. Kirkman, Salvatore Carbone, Hayley Billingsley, Benjamin W. Van Tassell, Dave L. Dixon, and Antonio Abbate
Subjects: Male, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, Group ii, Medicine (miscellaneous), 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Exercise time, Article, Ventricular Function, Left, 03 medical and health sciences, Oxygen Consumption, 0302 clinical medicine, Internal medicine, Natriuretic Peptide, Brain, medicine, Humans, In patient, Obesity, Prospective Studies, Meals, Aged, Heart Failure, Exercise Tolerance, Nutrition and Dietetics, business.industry, Stroke Volume, Cardiorespiratory fitness, Feeding Behavior, Middle Aged, medicine.disease, Peptide Fragments, Caloric intake, Cross-Sectional Studies, Cardiorespiratory Fitness, Concomitant, Cardiology, Female, Energy Intake, Cardiology and Cardiovascular Medicine, business, Heart failure with preserved ejection fraction, Biomarkers
Abstract: Background and aims Our objective was to examine the impact of caloric intake before or after the mean time of evening meal on cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Methods and results Twelve patients with HFpEF and obesity completed a cardiorespiratory exercise test to measure CRF, defined as peak oxygen consumption (VO2). Three five-pass 24-h dietary recalls were performed for each participant and mean evening meal time was determined for each participant individually as well as the group. Participants were divided into those who ate before (Group I) and after (Group II) the mean time of evening meal, 7:25 PM. Peak VO2 and exercise time were significantly greater in Group II compared to Group I, moreover, delaying time of evening meal was associated with greater peak VO2. Conclusion Caloric intake after the mean time of evening meal was associated with better CRF in patients with HFpEF and concomitant obesity. Later nutrient intake may help prevent fasting related stress associated with cardiac metabolic disturbances present in HFpEF. Based on these findings, prospective trials aimed at examining the effects of later evening meal times in patients with HFpEF and obesity are warranted.
Published: 2021
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35. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab

Author: Emil Hagström, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S Nieminen, Vakhtang Chumburidze, Pablo Carlos, Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J Dalby, José Tuñón, H. Asita de Silva, Ulf Landmesser, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B Schiavi, Marcelo Garrido, Andrés F Alvarisqueta, Sonia A Sassone, Anselmo P Bordonava, Alberto E Alves De Lima, Jorge M Schmidberg, Ernesto A Duronto, Orlando C Caruso, Leonardo P Novaretto, Miguel Angel Hominal, Oscar R Montaña, Alberto Caccavo, Oscar A Gomez Vilamajo, Alberto J Lorenzatti, Luis R Cartasegna, Gustavo A Paterlini, Ignacio J Mackinnon, Guillermo D Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R Codutti, Horacio O Jure, Julio OE Bono, Adrian D Hrabar, Julio A Vallejos, Rodolfo A Ahuad Guerrero, Federico Novoa, Cristian A Patocchi, Cesar J Zaidman, Maria E Giuliano, Ricardo D Dran, Marisa L Vico, Gabriela S Carnero, Pablo N Guzman, Juan C Medrano Allende, Daniela F Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S 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Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto F Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva- Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V 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Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Ph. 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Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, Georgios Hahalis, John Lekakis, Apostolos Hatzitolios, Sergio R Fausto Ovando, Pablo Carlos Montenegro Valdovinos, Juan L Arango Benecke, Edgar R Rodriguez De Leon, Bryan PY Yan, David CW Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D Abhyanakar, Prafulla Kerkar, Ravishankar A Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Dr. Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B De Cesare, Sergio Berti, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter AM Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J Wiersma, Dirk Basart, Ruud MA Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus JE Verdel, Bart RG Brueren, Roland PTh Troquay, Eric P Viergever, Nadea YY Al-Windy, Gerard L Bartels, Jan H Cornel, Walter RM Hermans, Johannes PR Herrman, Robert J Bos, Reginald GEJ Groutars, Coenraad C Van Der Zwaan, Refik Kaplan, Eelko Ronner, Bjorn E Groenemeijer, Patrick NA Bronzwaer, Anho AH Liem, Bernard JWM Rensing, Marcel JJA Bokern, Remco Nijmeijer, Ferry MRJ Hersbach, Frank F Willems, Antonius TM Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R Calderon Ticona, Julio R Durand Velasquez, Sandra A Negron Miguel, Enrique S Sanabria Perez, Jesus M Carrion Chambilla, Carlos A Chavez Ayala, Reynaldo P Castillo Leon, Rolando J Vargas GonzalesC, Jose D Hernandez Zuniga, Luis A Camacho Cosavalente, Jorge E Bravo Mannucci, Javier Heredia Landeo, Nassip C Llerena Navarro, Yudy M Roldan Concha, Víctor E Rodriguez Chavez, Henry A Anchante Hernandez, Carlos A Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H Pereira, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian GC Podoleanu, Mircea CA Constantinescu, Cristina M Bengus, Constantin Militaru, Doina Rosu, Irinel R Parepa, Adrian V Matei, Tom M Alexandru, Mihaela Malis, Ioan Coman, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I Voevoda, Tatyana V Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V Tyrenko, Igor G Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E Kapp, Matthys M de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J Van Zyl, Peter J Sebastian, Thayabran Pillay, Jan A Saaiman, Patrick J Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O Ebrahim, Mahomed Sarvan, Joseph H Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, Jose R Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J Alonso Martin, Jose Maria Serrano Antolin, José R De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei- Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey- Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K Aggarwal, Piers Clifford, Yuk- Ki Wong, Syed MR Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahma, Ayyaz Sultan, Timothy Reynolds, David Sharman, david Spriging, Rob Butler, Peter Wilkinson, Gregory YH Lip, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure II, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D’Urso, Fadi El- Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K Devarapalli, Michael Koren, Harish Chandna, George Dodds III, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl III, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun (Tom) Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O’Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Jean- Francois Tamby, Melanie Verrier, Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Roe, Matthew T., Blicharski, Tomasz, Bystryk, Leszek, Szpajer, Michal, Korol, Marek, Czerski, Tomasz, Gniot, Jacek, Lubinski, Andrzej, Gorny, Jerzy, Franek, Edward, Raczak, Grzegorz, Vogel, Robert, Szwed, Hanna, Monteiro, Pedro, Mesquita Bastos, Jose, Pereira, Helder H., Morais, Joao, Seixo, Filipe, Mendonça, Carlos, Botelho, Ana, Caetano, Francisca, Minescu, Bogdan, Chaitman, Bernard, Istratoaie, Octavian, Tesloianu, Dan N., Dorobantu, Maria, Cristian, Gabriel, Dumitrescu, Silviu, Podoleanu, Cristian Gc, Constantinescu, Mircea Ca, Bengus, Cristina M., Militaru, Constantin, Rosu, Doina, Kelsey, Sheryl F., Parepa, Irinel R., Matei, Adrian V., Alexandru, Tom M., Malis, Mihaela, Coman, Ioan, Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L., Markov, Valentin, Olsson, Anders G., Lyamina, Nadezhda, Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y., Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V., Bokarev, Igor, Khlevchuk, Tatiana, Shalaev, Sergey, Rouleau, Jean-Lucien, Khaisheva, Larisa, Chizhov, Petr, Viktorova, Inna, Osokina, Natalya, Shchekotov, Vladimir, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I., Tretyakova, Tatyana V., Simoons, Maarten L., Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Alexander, Karen, Baranova, Elena, Kosmachova, Elena, Karpov, Yuriy, Karpov, Yuri, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V., Ivanov, Igor G., Ilya, Masterov, Kanorsky, Sergey, Meloni, Chiara, Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Tosic, Biljana Putnikovic, Stankovic, Aleksandar, Rosenson, Robert, Arandjelovic, Aleksandra, Radovanovic, Slavica, Todic, Branislava, Ristic, Arsen D., Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Karadzic, Ana, Dodic, Slobodan, Dimkovic, Sinisa, Sijbrands, Eric J. G., Jakimov, Tamara, Poh, Kian-Keong, Yee Ong, Hean, Tang I-Shing, Justin, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Tricoci, Pierluigi, Mazur, Juraj, Majercák, Ivan, Dzupina, Andrej, Fazekas, František, Gonsorcik, Jozef, Bugan, Viliam, Murin, Jan, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Alexander, John H., Smik, Rudolf, Dukat, Andrej, Olexa, Peter, Žuran, Ivan, Poklukar, Janez, Šuligoj, Nataša Černič, Cevc, Matija, Fras, Zlatko, Cyster, Henry P., Ranjith, Naresh, Armaganijan, Luciana, Corbett, Clive, Bayat, Junaid, Makoali Makotoko, Ellen, du Toit Theron, Hendrik, Kapp, Ilse E., de V Basson, Matthys M., Lottering, Hanlie, Van Aswegen, Dina, Van Zyl, Louis J., Sebastian, Peter J., Bagai, Akshay, Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Riaz, Garda, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Dalby, Anthony J., Reuter, Helmuth, Bahit, Maria Cecilia, Moodley, Rajendran, Vida, Manuel, Fillat, Angel R. Cequier, Peris, Vicente Bodí, Jimenez, Francisco Fuentes, Marín, Francisco, Cruz Fernández, Jose M., Hidalgo Urbano, Rafael Jesus, Gil-Extremera, Blas, Toledo, Pablo, Brennan, J. Matthew, Worner Diz, Fernando, Garcia-Dorado, David, Iñiguez, Andres, Gonzalez-Juanatey, Jose R., Portales, Javier Fernandez, Murillo, Fernando Civeira, Pericas, Laia Matas, Zamorano, Jose Luis, De Mora Martin, Manuel, Cortada, Jordi Bruguera, Clifton, Shaun, Alonso Martin, Joaquin J., Serrano Antolin, Jose Maria, De Berrazueta Fernández, José R., Vázquez de Prada, José Antonio, Díaz Fernández, Jose Francisco, García Lledó, José Alberto, Cosín Sales, Juan, Rodriguez, Javier Botas, Tragant, Gabriel Gusi, Benedicto, Amparo, DeVore, Adam D., Gonzalez-Juanatey, Carlos, Camprubí Potau, Mercedes, Perez, Ignacio Plaza, De La Tassa, César Morís, Rincon, Pablo Loma-Osorio, Recena, Javier Balaguer, Escudier, Juan M., Payeras, Antonio Coca, Orcajo, Norberto Alonso, Constantine, Godwin, Deloatch, Shalonda, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Ponnamperuma, Chandrike, Fernando, Nimali, Fernando, Kaputella, Jayawardena, Jayanthimala, Wijeyasingam, Santharaj, Ranasinghe, Gotabhaya, Ekanayaka, Ruvan, Dickey, Sheila, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Rajapaksha, Ajantha, Sirisena, Thilak, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagström, Emil, Dombrowski, Keith, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Ducrocq, Grégory, Moccetti, Tiziano, Müller, Christian, Mach, Francois, Binde, Ronald, Landmesser, Ulf, Gämperli, Oliver, Chiang, Chern-En, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Eapen, Zubin, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I.-Chang, Hsieh, Ming-Jer, Hsiang Lin, Wei, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Endsley, Patricia, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Eppinger, Arleen, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Harrison, Robert W., Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Hess, Connie Ng, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Hlatky, Mark A., Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Jordan, Joseph Dedrick, Zheleznyy, Volodymyr, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-ki, Iqbal, Syed Mr, Subkovas, Eduardas, Knowles, Joshua W., Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Smith, Simon, Kurian, John, Levy, Terry, Barr, Craig, Kolls, Bradley J., Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Brodison, Adrian, Ayaz, Mohammad, Cheema, Muhammad, Oliver, Richard, Thackray, Simon, Mudawi, Telal, Kong, David F., Rahma, Gohar, Sultan, Ayyaz, Reynolds, Timothy, Sharman, David, Spriging, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Yh, Ossei-Gerning, Nicholas, Vardi, Gil, Leonardi, Sergio, Baldari, Duccio, Brabham, David, Treasure Ii, Charles, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Lillis, Linda, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Shoukfeh, Mohammad, Dagher, Georges, Lopes, Renato D., Cambier, Patrick, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, Hasan, Mian, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Maron, David J., Amidon, Thomas, Suh, David, Arif, Imran, Abdallah, Mouhamad, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, El-Ahdab, Fadi, Nelson, William, Moriarty, Katie, Mahaffey, Kenneth W., Harris, Barry, Cohen, Steven, Carter, Luther, Doty, Daniel, Sabatino, Kenneth, Haddad, Tariq, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Marcus, Jill, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds Iii, George, Goraya, Tauqir, Bengston, James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Mathews, Robin, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Fenton, Sarah, Singh, Narendra, Mehta, Rajendra H., Shah, Anil V., Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I., Mentz, Robert J., Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Kumar, Anil, Hattler, Brack, Do, Rose, Moreira, Humberto Graner, Link, Chad, Bortnick, Anna, Kinzfogl Iii, George, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Patel, Chetan B., Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Pereira, Sabrina Bernardez, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, Firas, Ponce, George, Jafar, Zubair, Perkins, Lynn, Mcgarvey, Joseph, Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Pederson, Robert, Herzog, William, Povsic, Thomas J., Friedman, Keith, Lindsey, Jason, Timothy, Eichenlaub, Leonard, Parilak, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, Alonso, Alvaro, May, Wade, Puymirat, Etienne, Christopher, Daniels, Galski, Thomas, Chu, Alan, Mody, Freny, Ramin, Ebrahimi, Hodes, Zachary, Rossi, Joseph, Rose, Gregory, Fairlamb, James, Lambert, Charles, Raisinghani, Ajit, Abbate, Antonio, Vetrovec, George, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun Tom, Vidovich, Mladen, Knutson, Thomas, Jones, William Schuyler, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Rozeman, Phillip, Kimmelstiel, Carey, Kuvin, Jeffrey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Espinoza, Andrey, Shah, Bimal R., Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Jong, Geert T., Massey, Clara, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Sherwood, Matthew W., Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Blonder, Ronald, Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Stringfellow, Kenya, Claxton, Edmund, Weiss, Robert, Kathryn, Rohr, Berk, Martin, Rossi, Peter, Joshi, Parag, Khera, Amit, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Sujjavanich, Darin, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Erenrich, Norman, Farrar, Michael, Toma, Mustafa, Pollock, Stewart, French, William J., Diamantis, Steve, Guy, Douglas, Gimple, Lawrence, Neustel, Mark, Schwartz, Steven, Pereira, Edward, Albert, Seals, Spriggs, Douglas, Trotter, Charlene, Strain, Janet, Mittal, Suneet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, van Diepen, Sean F. P., Nager, Paul, Vohra, Rakesh, Sharma, Mukesh, Bashir, Riyaz, Ahmed, Hinan, Berlowitz, Michael, Fishberg, Robert, Barrucco, Robert, Yang, Eric, Radin, Michael, Wilson, Matthew D., Sporn, Daniel, Stapleton, Dwight, Eisenberg, Steven, Landzberg, Joel, Mcgough, Martin, Turk, Samir, Schwartz, Michael, Sundram, P. Sandy, Jain, Diwakar, Zainea, Mark, Tze-Kay Yan, Andrew, Bayron, Carlos, Karlsberg, Ronald, Dohad, Suhail, Lui, Henry, Keen, William, Westerhausen, Donald, Khurana, Sandeep, Agarwal, Himanshu, Birchem, Jessica, Penny, William, Schiavi, Lilia B., Chang, Mark, Murphy, Sherrill, Henry, John, Schifferdecker, Branislav, Gilbert, John M., Chalavarya, Gopal, Eaton, Charles, Schmedtje, John F., Christenson, Stuart, Dotani, Imran, Garrido, Marcelo, Denham, Douglas, Macdonell, Alexander, Gibson, Paul, Rahman, Aref, Al Joundi, Tammam, Assi, Nizar, Conrad, Gary, Kotha, Purushotham, Love, Michael, Giesler, Gregory, Alvarisqueta, Andrés F., Rubenstein, Howard, Gamil, Dawood, Akright, Laura, Krawczyk, Justine, Cobler, Joanne, Wells, Terry, Welker, James, Foster, Robert, Gilmore, Richard, Anderson, Jay, Sassone, Sonia A., Jacoby, Douglas, Harris, Bill, Gardner, Geraldine, Dandillaya, Ramprasad, Vora, Kishor, Kostis, John, Hunter, John, Laxson, David, Ball, Eric, Bordonava, Anselmo P., Egydio, Flavia, Kawakami, Anelise, Oliveira, Janaina, Goodman, Shaun G., Wozniak, Julianna, Alves De Lima, Alberto E., Matthews, Alexander, Ratky, Caroline, Valiris, Janine, Berdan, Lisa, Hepditch, Anita, Quintero, Kirby, Rorick, Tyrus, Westbrook, Melissa, Danchin, Nicolas, Schmidberg, Jorge M., Bezault, Madeleine, Drouet, Elodie, Simon, Tabassome, White, Harvey D., Alsweiler, Caroline, Sinnaeve, Peter, Luyten, Anne, Aylward, Philip E., Butters, Julie, Griffith, Liddy, Duronto, Ernesto A., Shaw, Michelle, Grunberg, Lena, Szarek, Michael, Islam, Shahidul, Brégeault, Marie-France, Bougon, Nathalie, Faustino, Douglas, Fontecave, Sylvie, Murphy, Judith, Caruso, Orlando C., Tamby, Jean-Francois, Verrier, Melanie, Agnetti, Veronique, Andersen, Dorthe, Badreddine, Emmy, Bekkouche, Mhamed, Bouancheau, Cecile, Brigui, Imane, Brocklehurst, Maddy, Cianciarulo, Joseph, Novaretto, Leonardo P., Devaul, Dawn, Domokos, Szilvia, Gache, Cecile, Gobillot, Caroline, Guillou, Severine, Healy, Jan, Heath, Megan, Jaiwal, Gayatri, Javierre, Carine, Labeirie, Julien, Hominal, Miguel Angel, Monier, Myriam, Morales, Ulises, Mrabti, Asmaa, Mthombeni, Bicky, Okan, Betim, Smith, Lucile, Sheller, Jennifer, Sopena, Sebastien, Pellan, Valerie, Benbernou, Fadela, Montaña, Oscar R., Bengrait, Nafissa, Lamoureux, Maud, Kralova, Katarina, Scemama, Michel, Bejuit, Raphael, Coulange, Anthony, Berthou, Christelle, Repincay, Jérôme, Lorenzato, Christelle, Etienne, Alexis, Caccavo, Alberto, Gouet, Valerie, Lecorps, Guillaume, Loizeau, Virginie, Normand, Mickael, Ourliac, Anne, Rondel, Christelle, Adamo, Antony, Beltran, Pascale, Barraud, Pauline, Dubois-Gache, Helene, Gomez Vilamajo, Oscar A., Halle, Benjamin, Metwally, Lamia, Mourgues, Maxime, Sotty, Marc, Vincendet, Marion, Cotruta, Raluca, Chengyue, Zhu, Fournie-Lloret, Dominique, Morrello, Christine, Perthuis, Aurelie, Lorenzatti, Alberto J., Picault, Patrick, Zobouyan, Isabelle, Colhoun, Helen M., Dempsey, Michael A., McClanahan, Mark A., Cartasegna, Luis R., Paterlini, Gustavo A., Mackinnon, Ignacio J., Caime, Guillermo D., Amuchastegui, Marcos, Salomone, Oscar, Codutti, Oscar R., Jure, Horacio O., Bono, Julio Oe, Hrabar, Adrian D., Vallejos, Julio A., Ahuad Guerrero, Rodolfo A., Novoa, Federico, Patocchi, Cristian A., Zaidman, Cesar J., Giuliano, Maria E., Schwartz, Gregory G., Dran, Ricardo D., Vico, Marisa L., Carnero, Gabriela S., Guzman, Pablo N., Medrano Allende, Juan C., Garcia Brasca, Daniela F., Bustamante Labarta, Miguel H., Nani, Sebastian, Blumberg, Eduardo Ds, Colombo, Hugo R., Bhatt, Deepak L., Liberman, Alberto, Fuentealba, Victorino, Luciardi, Hector L., Waisman, Gabriel D., Berli, Mario A., Garcia Duran, Ruben O., Cestari, Horacio G., Luquez, Hugo A., Giordano, Jorge A., Saavedra, Silvia S., Bittner, Vera A., Zapata, Gerardo, Costamagna, Osvaldo, Llois, Susana, Waites, Jonathon H., Collins, Nicholas, Soward, Allan, Hii, Chris Ls, Shaw, James, Diaz, Rafael, Arstall, Margaret A., Horowitz, John, Ninio, Daniel, Rogers, James F., Colquhoun, David, Oqueli Flores, Romulo E., Roberts-Thomson, Philip, Raffel, Owen, Lehman, Sam J., Aroney, Constantine, Coverdale, Steven Gm, Garrahy, Paul J., Starmer, Gregory, Sader, Mark, Carroll, Patrick A., Dick, Ronald, Zweiker, Robert, Hoppe, Uta, Drexel, Heinz, Huber, Kurt, Harrington, Robert A., Berger, Rudolf, Delle-Karth, Georg, Frey, Bernhard, Weidinger, Franz, Faes, Dirk, Hermans, Kurt, Pirenne, Bruno, Leone, Attilio, Hoffer, Etienne, Jukema, J. Wouter, Vrolix, Mathias Cm, De Wolf, Luc, Wollaert, Bart, Castadot, Marc, Dujardin, Karl, Beauloye, Christophe, Vervoort, Geert, Striekwold, Harry, Convens, Carl, Roosen, John, Barbato, Emanuele, Claeys, Marc, Cools, Frank, Terzic, Ibrahim, Barakovic, Fahir, Midzic, Zlatko, Pojskic, Belma, Fazlibegovic, Emir, Dilic, Mirza, Durak-Nalbantic, Azra, Kulić, Mehmed, Vulic, Dusko, Muslibegovic, Adis, Goronja, Boris, Reis, Gilmar, Sousa, Luciano, Nicolau, Jose C., Giorgeto, Flavio E., Silva, Ricardo P., Maia, Lilia Nigro, Zeiher, Andreas M., Rech, Rafael, Rossi, Paulo Rf, Cerqueira, Maria José Ag, Duda, Norberto, Kalil, Renato, Kormann, Adrian, Abrantes, José Antonio M., Filho, Pedro Pimentel, Soggia, Ana Priscila, de Santos, Mayler On, Neuenschwander, Fernando, Bodanese, Luiz C., Michalaros, Yorghos L., Eliaschewitz, Freddy G., Vidotti, Maria H., Leaes, Paulo E., Botelho, Roberto V., Kaiser, Sergio, Manenti, Euler Roberto F. Fernandes, Precoma, Dalton B., Moura Jorge, Jose C., Silva, Pedro, Silveira, Jose A., Saporito, Wladmir, Neto, Jose A. Marin, Feitosa, Gilson S., Ritt, Luiz Eduardo F., de Souza, Juliana A., Costa, Fernando, Souza, Weimar Ksb, Reis, Helder Jl, Machado, Leandro, Aidar Ayoub, José Carlos, Todorov, Georgi V., Nikolov, Fedya P., Velcheva, Elena S., Tzekova, Maria L., Benov, Haralambi O., Petranov, Stanislav L., Edelberg, Jay M., Tumbev, Haralin S., Shehova-Yankova, Nina S., Markov, Dimitar T., Raev, Dimitar H., Mollov, Mihail N., Kichukov, Kostadin N., Ilieva-Pandeva, Katya A., Gotcheva, Nina N., Ivanova, Raya, Gospodinov, Maryana, Hanotin, Corinne, Mincheva, Valentina M., Lazov, Petar V., Dimov, Bojidar I., Senaratne, Manohara, Stone, James, Kornder, Jan, Pearce, Stephen, Dion, Danielle, Savard, Daniel, Pesant, Yves, Pandey, Amritanshu, Robinson, Simon, Gosselin, Gilbert, Vizel, Saul, Hoag, Gordon, Bourgeois, Ronald, Morisset, Anne, Sabbah, Eric, Sussex, Bruce, Kouz, Simon, Moryusef, Angèle, MacDonald, Paul, Diaz, Ariel, Michaud, Nicolas, Fell, David, Leung, Raymond, Vuurmans, Tycho, Lai, Christopher, Nigro, Frank, Davies, Richard, Nogareda, Gustavo, Pordy, Robert, Vijayaraghavan, Ram, Ducas, John, Lepage, Serge, Mehta, Shamir, Cha, James, Dupuis, Robert, Fong, Peter, Lutchmedial, Sohrab, Rodes-Cabau, Josep, Fadlallah, Hussein, Sasiela, William J., Cleveland, David, Huynh, Thao, Bata, Iqbal, Hameed, Adnan, Pincetti, Cristian, Potthoff, Sergio, Prieto, Juan C., Acevedo, Monica, Aguirre, Arnoldo, Vejar, Margarita, Tamby, Jean-François, Yañez, Mario, Araneda, Guillermo, Fernandez, Mauricio, Perez, Luis, Varleta, Paola, Florenzano, Fernando, Huidobro, Laura, Raffo, Carlos A., Olivares, Claudia, Nahuelpan, Leonardo, Montecinos, Humberto, Chen, Jiyan, Dong, Yugang, Huang, Weijian, Wang, Jianzhong, Huang, Shi'An, Yao, Zhuhua, Li, Xiang, Cui, Lan, Lin, Wenhua, Sun, Yuemin, Wang, Jingfeng, Li, Jianping, Zhang, Xuelian, Zhu, Hong, Chen, Dandan, Huang, Lan, Dong, Shaohong, Su, Guohai, Xu, Biao, Su, Xi, Cheng, Xiaoshu, Lin, Jinxiu, Zong, Wenxia, Li, Huanming, Feng, Yi, Xu, Dingli, Yang, Xinchun, Ke, Yuannan, Lin, Xuefeng, Zhang, Zheng, Zheng, Zeqi, Luo, Zhurong, Chen, Yundai, Ding, Chunhua, Zhong, Yi, Zheng, Yang, Li, Xiaodong, Peng, Daoquan, Zhao, Shuiping, Li, Ying, Liu, Xuebo, Wei, Meng, Liu, Shaowen, Yu, Yihua, Qu, Baiming, Jiang, Weihong, Zhou, Yujie, Zhao, Xingsheng, Yuan, Zuyi, Guo, Ying, Xu, Xiping, Shi, Xubo, Ge, Junbo, Fu, Guosheng, Bai, Feng, Fang, Weiyi, Shou, Xiling, Yang, Xiangjun, Wang, Jian'An, Xiang, Meixiang, Sun, Yingxian, Lu, Qinghua, Zhang, Ruiyan, Zhu, Jianhua, Xu, Yizhou, Fan, Zhongcai, Li, Tianchang, Wu, Chun, Jaramillo, Nicolas, Vallejo, Gregorio Sanchez, Luna Botia, Diana C., Lopez, Rodrigo Botero, De Salazar, Dora I. Molina, Bonfanti, Alberto J. Cadena, Aroca, Carlos Cotes, Higuera, Juan Diego, Blanquicett, Marco, Barrera Silva, Sandra I., Garcia Lozada, Henry J., Prieto, Juan-Carlos, Coronel Arroyo, Julian A., Accini Mendoza, Jose L., Fernandez Ruiz, Ricardo L., Quintero Ossa, Alvaro M., Manzur Jatin, Fernando G., Sotomayor Herazo, Aristides, Parada, Jeffrey Castellanos, Arambula, Rafael Suarez, Urina Triana, Miguel A., Trujillo, Angela M. 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Lomholdt, Jens D., Klausen, Ib C., Nielsen, Peter Kaiser, Davidsen, Flemming, Videbaek, Lars, Viigimaa, Margus, Soots, Mai, Vahula, Veiko, Hedman, Anu, Soopõld, Üllar, Märtsin, Kaja, Jurgenson, Tiina, Kristjan, Arved, Nieminen, Markku S., Vikman, Saila, Huikuri, Heikki, Airaksinen, Juhani, Coste, Pierre, Ferrari, Emile, Morel, Olivier, Montalescot, Gilles, Machecourt, Jacques, Barone-Rochette, Gilles, Mansourati, Jacques, Cottin, Yves, Steg, Ph Gabriel, Leclercq, Florence, Belhassane, Abdelkader, Delarche, Nicolas, Boccara, Franck, Paganelli, Franck, Clerc, Jérôme, Schiele, Francois, Aboyans, Victor, Probst, Vincent, Berland, Jacques, Chumburidze, Vakhtang, Lefèvre, Thierry, Khintibidze, Irakli, Shaburishvili, Tamaz, Pagava, Zurab, Ghlonti, Ramaz, Lominadze, Zaza, Khabeishvili, George, Hemetsberger, Rayyan, Edward, Kemala, Marx, Nikolaus, Rauch-Kröhnert, Ursula, Stratmann, Matthias, Appel, Karl-Friedrich, Schmidt, Ekkehard, Omran, Heyder, Stellbrink, Christoph, Dorsel, Thomas, Lianopoulos, Emmanouil, Vöhringer, Hans Friedrich, Marx, Roger, Liberopoulos, Evangelos, Zirlik, Andreas, Schellenberg, Detlev, Heitzer, Thomas, Laufs, Ulrich, Werner, Christian, Gielen, Stephan, Nuding, Sebastian, Winkelmann, Bernhard, Behrens, Steffen, Carlos, Pablo, Sydow, Karsten, Karakas, Mahir, Simonis, Gregor, Muenzel, Thomas, Werner, Nikos, Leggewie, Stefan, Böcker, Dirk, Braun-Dullaeus, Rüdiger, Toursarkissian, Nicole, Jeserich, Michael, Valdovinos, Montenegro, Weißbrodt, Matthias, Schaeufele, Tim, Weil, Joachim, Völler, Heinz, Waltenberger, Johannes, Natour, Mohammed, Schmitt, Susanne, Müller-Wieland, Dirk, Steiner, Stephan, Heidenreich, Lothar, Tse, Hung-Fat, Offers, Elmar, Gremmler, Uwe, Killat, Holger, Rieker, Werner, Patsilinakos, Sotiris, Kartalis, Athanasios, Manolis, Athanassios, Sionis, Dimitrios, Chachalis, Geargios, Kiss, Robert Gabor, Skoumas, Ioannis, Athyros, Vasilios, Vardas, Panagiotis, Parthenakis, Frangkiskos, Hahalis, Georgios, Lekakis, John, Hatzitolios, 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Gavish, Dov, Ramos López, Gabriel Arturo, Vered, Zvi, Caraco, Yoseph, Elias, Mazen, Tov, Naveh, Wolfovitz, Efrat, Lishner, Michael, Elias, Nizar, Piovaccari, Giancarlo, De Pellegrin, Annamaria, Garbelotto, Raffaella, Alings, Marco, Guardigli, Gabriele, Marco, Valgimigli, Licciardello, Giovanni, Auguadro, Carla, Scalise, Filippo, Cuccia, Claudio, Salvioni, Alessandro, Musumeci, Giuseppe, Senni, Michelle, Calabrò, Paolo, Novo, Salvatore, Faggiano, Pompilio, Metra, Marco, De Cesare, Nicoletta B., Berti, Sergio, Puccioni, Enrico, Galvani, Marcello, Tespili, Maurizio, Piatti, PierMarco, Palvarini, Michela, Halvorsen, Sigrun, De Luca, Giuseppe, Violini, Roberto, De Leo, Alessandro, Olivari, Zoran, Filardi, Pasquale Perrone, Ferratini, Maurizio, Racca, Vittorio, Dai, Kazuoki, Shimatani, Yuji, Kamiya, Haruo, Correa Flores, Roger M., Ando, Kenji, Takeda, Yoshihiro, Morino, Yoshihiro, Hata, Yoshiki, Kimura, Kazuo, Kishi, Koichi, Michishita, Ichiro, Uehara, Hiroki, Higashikata, Toshinori, Hirayama, Atsushi, Sy, Rody G., Hirooka, Keiji, Doi, Yasuji, Sakagami, Satoru, Taguchi, Shuichi, Koike, Akihiro, Fujinaga, Hiroyuki, Koba, Shinji, Kozuma, Ken, Kawasaki, Tomohiro, Ono, Yujiro, Budaj, Andrzej, Shimizu, Masatoshi, Katsuda, Yousuke, Wada, Atsuyuki, Shinke, Toshiro, Ako, Junya, Fujii, Kenshi, Takahashi, Toshiyuki, Nakao, Koichi, Furukawa, Yutaka, Sugino, Hiroshi, Tamura, Ritsu, Mano, Toshiaki, Uematsu, Masaaki, Utsu, Noriaki, Ito, Kashima, Haraguchi, Takuya, Sato, Katsuhiko, Ueda, Yasunori, Nishibe, Akira, Fujimoto, Kazuteru, Masutani, Motomaru, Yoon, Jung Han, Kim, Hack-Lyoung, Sik Park, Hun, Chae, In-Ho, Kim, Moo Hyun, Jeong, Myung Ho, Rha, Seungwoon, Kim, Chongjin, Kim, Hyo-Soo, Kim, Hae Young, Hong, Taekjong, Tahk, Seung-Jea, Kim, Youngkwon, Busmane, Arija, Pontaga, Natalija, Strelnieks, Aldis, Mintale, Iveta, Sime, Iveta, Petrulioniene, Zaneta, Kavaliauskiene, Roma, Jurgaitiene, Ruta, Sakalyte, Gintare, Slapikas, Rimvydas, Norkiene, Sigute, Misonis, Nerijus, Chua, 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Th, Viergever, Eric P., Al-Windy, Nadea Yy, Bartels, Gerard L., Cornel, Jan H., Hermans, Walter Rm, Herrman, Johannes Pr, Bos, Robert J., Groutars, Reginald Gej, Van Der Zwaan, Coenraad C., Kaplan, Refik, Ronner, Eelko, Groenemeijer, Bjorn E., Bronzwaer, Patrick Na, Liem, Anho Ah, Rensing, Bernard Jwm, Bokern, Marcel Jja, Nijmeijer, Remco, Hersbach, Ferry Mrj, Willems, Frank F., Gosselink, Antonius Tm, Rasoul, Saman, Elliott, John, Wilkins, Gerard, Fisher, Raewyn, Scott, Douglas, Hart, Hamish, Stewart, Ralph, Harding, Scott, Ternouth, Ian, Fisher, Nicholas, Wilson, Samuel, Aitken, Denise, Anscombe, Russell, Davidson, Laura, Tomala, Tadeusz, Nygård, Ottar, Sparby, Jon Arne, Andersen, Kjell, Gullestad, Lars, Jortveit, Jarle, Munk, Peter S., Singsaas, Erlend Gyllensten, Hurtig, Ulf, Calderon Ticona, Jorge R., Durand Velasquez, Julio R., Negron Miguel, Sandra A., Sanabria Perez, Enrique S., Carrion Chambilla, Jesus M., Chavez Ayala, Carlos A., Castillo Leon, Reynaldo P., Vargas GonzalesC, Rolando J., Hernandez Zuniga, Jose D., Camacho Cosavalente, Luis A., Bravo Mannucci, Jorge E., Landeo, Javier Heredia, Llerena Navarro, Nassip C., Roldan Concha, Yudy M., Rodriguez Chavez, Víctor E., Anchante Hernandez, Henry A., Zea Nunez, Carlos A., Ramos, Walter Mogrovejo, Ferrolino, Arthur, Sy, Rosa Allyn G., Tirador, Louie, Matiga, Generoso, Coching, Raul Martin, Bernan, Alisa, Rogelio, Gregorio, Morales, Dante D., Tan, Edgar, Sulit, Dennis Jose, Wlodarczak, Adrian, Skonieczny, Grzegorz, Ray, Kausik K., Pawlowicz, Lidia, Wojewoda, Pawel, Busz-Papiez, Benita, Bednarski, Janusz, Goch, Aleksander, Staneta, Pawel, Dulak, Elzbieta, Saminski, Krzysztof, Krasowski, Wlodzimierz, Sudnik, Wanda, Zurakowski, Aleksander, Skorski, Marcin, Lysek, Roman, Miklaszewicz, Beata, Lipko, Jan Andrzej, Kostarska-Srokosz, Edyta, Piepiorka, Marek, Drzewiecka, Anna, Stasiewski, Arkadiusz, Bhatt, Deepak L, Bittner, Vera A, Goodman, Shaun G, Harrington, Robert A, Jukema, J Wouter, White, Harvey D, Zeiher, Andreas M, Roe, Matthew T, Mahaffey, Kenneth W, Edelberg, Jay M, Sasiela, William J, Aylward, Philip E, Lopes, Renato D, Gotcheva, Nina N, Nieminen, Markku S, Laucevičius, Aleksandras, Correa Flores, Roger M, Sy, Rody G, Ristic, Arsen D, Dalby, Anthony J, de Silva, H Asita, Ray, Kausik K, Moriarty, Patrick M, Kelsey, Sheryl F, Olsson, Anders G, Simoons, Maarten L, Sijbrands, Eric J G, Alexander, John H, Brennan, J Matthew, DeVore, Adam D, Harrison, Robert W, Hlatky, Mark A, Knowles, Joshua W, Kolls, Bradley J, Kong, David F, Maron, David J, Mehta, Rajendra H, Mentz, Robert J, Patel, Chetan B, Povsic, Thomas J, Shah, Bimal R, Sherwood, Matthew W, van Diepen, Sean F P, Wilson, Matthew D, Schiavi, Lilia B, Alvarisqueta, Andrés F, Sassone, Sonia A, Bordonava, Anselmo P, Alves De Lima, Alberto E, Schmidberg, Jorge M, Duronto, Ernesto A, Caruso, Orlando C, Novaretto, Leonardo P, Montaña, Oscar R, Gomez Vilamajo, Oscar A, Lorenzatti, Alberto J, Cartasegna, Luis R, Paterlini, Gustavo A, Mackinnon, Ignacio J, Caime, Guillermo D, Codutti, Oscar R, Jure, Horacio O, Hrabar, Adrian D, Vallejos, Julio A, Ahuad Guerrero, Rodolfo A, Patocchi, Cristian A, Zaidman, Cesar J, Giuliano, Maria E, Dran, Ricardo D, Vico, Marisa L, Carnero, Gabriela S, Guzman, Pablo N, Medrano Allende, Juan C, Garcia Brasca, Daniela F, Bustamante Labarta, Miguel H, Colombo, Hugo R, Luciardi, Hector L, Waisman, Gabriel D, Berli, Mario A, Garcia Duran, Ruben O, Cestari, Horacio G, Luquez, Hugo A, Giordano, Jorge A, Saavedra, Silvia S, Waites, Jonathon H, Arstall, Margaret A, Rogers, James F, Oqueli Flores, Romulo E, Lehman, Sam J, Garrahy, Paul J, Carroll, Patrick A, Wolf, Luc De, Nicolau, Jose C, Giorgeto, Flavio E, Silva, Ricardo P, Abrantes, José Antonio M, Bodanese, Luiz C, Michalaros, Yorghos L, Eliaschewitz, Freddy G, Vidotti, Maria H, Leaes, Paulo E, Botelho, Roberto V, Manenti, Euler Roberto F Fernandes, Precoma, Dalton B, Moura Jorge, Jose C, Silveira, Jose A, Neto, Jose A Marin, Feitosa, Gilson S, Ritt, Luiz Eduardo F, de Souza, Juliana A, Todorov, Georgi V, Nikolov, Fedya P, Velcheva, Elena S, Tzekova, Maria L, Benov, Haralambi O, Petranov, Stanislav L, Tumbev, Haralin S, Shehova-Yankova, Nina S, Markov, Dimitar T, Raev, Dimitar H, Mollov, Mihail N, Kichukov, Kostadin N, Ilieva-Pandeva, Katya A, Mincheva, Valentina M, Lazov, Petar V, Dimov, Bojidar I, Prieto, Juan C, Raffo, Carlos A, Luna Botia, Diana C, De Salazar, Dora I Molina, Bonfanti, Alberto J Cadena, Barrera Silva, Sandra I, Garcia Lozada, Henry J, Coronel Arroyo, Julian A, Accini Mendoza, Jose L, Fernandez Ruiz, Ricardo L, Quintero Ossa, Alvaro M, Manzur Jatin, Fernando G, Urina Triana, Miguel A, Trujillo, Angela M Fernandez, Poulsen, Steen H, Bang, Lia E, Hove, Jens D, Kristensen, Kjeld S, Lomholdt, Jens D, Klausen, Ib C, Fausto Ovando, Sergio R, Arango Benecke, Juan L, Rodriguez De Leon, Edgar R, Premchand, Rajendra K, Abhyanakar, Atul D, Govinda, Ravishankar A, Patil, Sachin N, Joshi, Abhijeet B, Pothineni, Ramesh B, Monteiro, Minguel R, Iyengar, Shamanna S, Fulwani, Mahesh C, Chopra, Vijay K, Goyal, Naresh K, Manakshe, Gajendra V, Pellegrin, Annamaria De, De Cesare, Nicoletta B, Piatti, Piermarco, Luca, Giuseppe De, Leo, Alessandro De, Petrulionienė, Žaneta, Šakalytė, Gintarė, Šlapikas, Rimvydas, Liew, Houng B, Breedveld, Robert W, Wiersma, Jacobijne J, Troquay, Roland PTh, Viergever, Eric P, Bartels, Gerard L, Cornel, Jan H, Bos, Robert J, Van Der Zwaan, Coenraad C, Groenemeijer, Bjorn E, Willems, Frank F, Munk, Peter S, Calderon Ticona, Jorge R, Durand Velasquez, Julio R, Negron Miguel, Sandra A, Sanabria Perez, Enrique S, Carrion Chambilla, Jesus M, Chavez Ayala, Carlos A, Castillo Leon, Reynaldo P, Vargas GonzalesC, Rolando J, Hernandez Zuniga, Jose D, Camacho Cosavalente, Luis A, Bravo Mannucci, Jorge E, Llerena Navarro, Nassip C, Roldan Concha, Yudy M, Rodriguez Chavez, Víctor E, Anchante Hernandez, Henry A, Zea Nunez, Carlos A, Sy, Rosa Allyn G, Morales, Dante D, Pereira, Helder H, Tesloianu, Dan N, Bengus, Cristina M, Parepa, Irinel R, Matei, Adrian V, Alexandru, Tom M, Barbarash, Olga L, Vishnevsky, Alexander Y, Lomakin, Nikita V, Voevoda, Mikhail I, Tretyakova, Tatyana V, Tyrenko, Vadim V, Ivanov, Igor G, Asanin, Milika R, Apostolovic, Svetlana R, Dincic, Dragan V, Cyster, Henry P, Kapp, Ilse E, de V Basson, Matthys M, Aswegen, Dina Van, Van Zyl, Louis J, Sebastian, Peter J, Saaiman, Jan A, Commerford, Patrick J, Ebrahim, Iftikhar O, Mynhardt, Joseph H, Fillat, Angel R Cequier, Cruz Fernández, Jose M, Gonzalez-Juanatey, Jose R, Alonso Martin, Joaquin J, De Berrazueta Fernández, José R, Escudier, Juan M, Herath, Jagath I, Hsieh, I-Chang, Barna, Olga M, Aggarwal, Rajesh K, Wong, Yuk-Ki, Devarapalli, Sai K, Shah, Anil V, Kondo, Nicholas I, Azizad, Masoud M, Jong, Geert T, O'Donnell, Philip J, Marais, H John, Khaira, Ajit S, French, William J, Lester, F Martin, Sundram, P Sandy, Gilbert, John M, Schmedtje, John F, Colhoun, Helen M, Dempsey, Michael A, and McClanahan, Mark A
Subjects: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Anticholesteremic Agents/adverse effects, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], prevention & control, heart disease risk factors, diagnosis [Cardiovascular Diseases], Antibodies, Monoclonal, Humanized, PCSK9 inhibitors, acute coronary syndrome, apolipoproteins B, LDL cholesterol, Antibodies, acute coronary syndrome, LDL, drug therapy [Atherosclerosis], Risk Factors, Physiology (medical), therapeutic use [Hydroxymethylglutaryl-CoA Reductase Inhibitors], Monoclonal, Humans, Cardiac and Cardiovascular Systems, Humanized, Cardiovascular Diseases/diagnosis, Apolipoproteins B, Kardiologi, diagnosis [Acute Coronary Syndrome], Anticholesteremic Agents, PCSK9 inhibitors, apolipoproteins B, cholesterol, LDL, cholesterol, Atherosclerosis/drug therapy, Cholesterol, LDL, Atherosclerosis, Acute Coronary Syndrome/diagnosis, drug therapy, Cholesterol, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, epidemiology, adverse effects [Anticholesteremic Agents], Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine
Abstract: Circulation : an official journal of the American Heart Association / ed.-in-chief Ephraim Donosco 146(9), 657-672 (2022). doi:10.1161/CIRCULATIONAHA.121.057807, Published by Ovid, [Erscheinungsort nicht ermittelbar]
Published: 2022
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36. Association of Titin Variations with Late-Onset Dilated Cardiomyopathy

Author: Antonio Cannatà, Marco Merlo, Matteo Dal Ferro, Giulia Barbati, Paolo Manca, Alessia Paldino, Sharon Graw, Marta Gigli, Davide Stolfo, Renee Johnson, Darius Roy, Kevin Tharratt, Daniel I. Bromage, Jean Jirikowic, Antonio Abbate, Allison Goodwin, Krishnasree Rao, Amr Marawan, Gerry Carr-White, Leema Robert, Victoria Parikh, Euan Ashley, Theresa McDonagh, Neal K. Lakdawala, Diane Fatkin, Matthew R. G. Taylor, Luisa Mestroni, Gianfranco Sinagra, Cannata, A., Merlo, M., Dal Ferro, M., Barbati, G., Manca, P., Paldino, A., Graw, S., Gigli, M., Stolfo, D., Johnson, R., Roy, D., Tharratt, K., Bromage, D. I., Jirikowic, J., Abbate, A., Goodwin, A., Rao, K., Marawan, A., Carr-White, G., Robert, L., Parikh, V., Ashley, E., Mcdonagh, T., Lakdawala, N. K., Fatkin, D., Taylor, M. R. G., Mestroni, L., and Sinagra, G.
Subjects: Cardiomyopathy, Dilated, Male, Genotype, Stroke Volume, Ventricular Function, Left, dilated cardiomyopathy, cardiology, Humans, Connectin, Female, titin, Cardiology and Cardiovascular Medicine, Original Investigation, Aged
Abstract: IMPORTANCE: Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM). OBJECTIVE: To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM. DESIGN, SETTING, AND PARTICIPANTS: A population of patients with late-onset DCM who had undergone genetic testing in 7 international tertiary referral centers worldwide were enrolled from March 1990 to August 2020. A positive genotype was defined as the presence of pathogenic or likely pathogenic (P/LP) variants. MAIN OUTCOMES AND MEASURES: The study outcome was all-cause mortality. RESULTS: A total of 184 patients older than 60 years (103 female [56%]; mean [SD] age, 67 [6] years; mean [SD] left ventricular ejection fraction, 32% [10%]) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin-truncating variants were the most prevalent (present in 46 [25%] of the total population and accounting for 46 [69%] of all genotype-positive patients). During a median (interquartile range) follow-up of 42 (10-115) months, 23 patients (13%) died; 17 (25%) of these were carriers of P/LP variants, while 6 patients (5.1%) were genotype-negative. CONCLUSIONS AND RELEVANCE: Late-onset DCM might represent a distinct subgroup characterized by and a high genetic variation burden, largely due to titin-truncating variants. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in older patients.
Published: 2022

37. The Chronic Kidney Disease Phenotype of HFpEF: Unique Cardiac Characteristics

Author: Benjamin W. Van Tassell, Cory R. Trankle, Danielle L. Kirkman, Salvatore Carbone, Hailey Billingsley, Justin M. Canada, Dinesh Kadariya, Leo F. Buckley, Antonio Abbate, and Jason M. Kidd
Subjects: Male, medicine.medical_specialty, Galectin 3, MEDLINE, Article, Oxygen Consumption, Internal medicine, Natriuretic Peptide, Brain, Electric Impedance, medicine, Humans, Renal Insufficiency, Chronic, Aged, Heart Failure, Exercise Tolerance, business.industry, Stroke Volume, Middle Aged, medicine.disease, Phenotype, Echocardiography, Doppler, Peptide Fragments, Functional Status, Case-Control Studies, Body Composition, Exercise Test, Quality of Life, Cardiology, Mitral Valve, Female, Cardiology and Cardiovascular Medicine, business, Blood Flow Velocity, Glomerular Filtration Rate, Kidney disease
Published: 2021
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38. Myocarditis after RNA-based COVID-19 vaccines: Where do we stand?

Author: Francesco, Moroni, James, Mbualungu, and Antonio, Abbate
Subjects: Covid vaccine, Myocarditis, COVID-19 Vaccines, SARS-CoV-2, Short Communication, RNA vaccine, Vaccination, COVID-19, Humans, RNA, Cardiology and Cardiovascular Medicine
Abstract: Background The incidence of myocarditis after RNA-based vaccines for coronavirus has gained social and medical interest. Methods We performed an intention-to-treat meta-analysis, following the PRISMA statement. After a systematic search, without language restriction, 9 publications were selected. Two were excluded (one was only in subjects with age 12–17 and other might had included subjects from a larger publication). We followed the PRISMA guidelines for abstracting data and assessing data quality and validity. Data was verified by 2 investigators. Results We analyzed 17,704,413 subjects, from 7 studies, that included 627 cases of confirmed myocarditis). The incidence of myocarditis was 0.0035% (95% CI 0.0034–0.0035). Mean incidence rate was 10.69 per 100.000 persons-year. Cases reported from Israel represented 45.14% from total (283 out of the 627). Only 1 case of fatal myocarditis or death was reported. There was significant heterogeneity between results. The meta-regression analysis excluded mean age, region, number of cases or number of people included as sources of heterogeneity. No small-study effect was observed (p = 0.19). Conclusions and relevance Myocarditis incidence after RNA vaccines is very rare (0.0035%) and has a very favorable clinical course., Graphical abstract Unlabelled Image
Published: 2022
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39. Effect of interleukin-1 blockade with anakinra on leukocyte count in patients with ST-segment elevation acute myocardial infarction

Author: Benjamin W. Van Tassell, Roshanak Markley, Salvatore Carbone, Antonio Abbate, Juan Ignacio Damonte, Dinesh Kadariya, Marco Giuseppe Del Buono, G Biondi-Zoccai, Cory R. Trankle, Georgia K. Thomas, Justin M. Canada, Michael C. Kontos, and Jeremy Turlington
Subjects: Male, medicine.medical_specialty, Leukocytosis, Science, Article, Leukocyte Count, Double-Blind Method, Internal medicine, medicine, ST segment, Humans, In patient, Myocardial infarction, Aged, Anakinra, Multidisciplinary, Molecular medicine, business.industry, Interleukin, Middle Aged, medicine.disease, Cardiovascular biology, Blockade, Interleukin 1 Receptor Antagonist Protein, Antirheumatic Agents, Cardiology, Medicine, ST Elevation Myocardial Infarction, Female, Clinical pharmacology, business, medicine.drug
Abstract: Background. Leukocytosis is a common finding in patients with ST elevation myocardial infarction (STEMI) and portends a poor prognosis. Interleukin 1-b regulates leukopoiesis and pre-clinical studies suggest that anakinra (recombinant human interleukin-1 [IL-1] receptor antagonist) suppresses leukocytosis in myocardial infarction. However, the effect of IL-1 blockade with anakinra on leukocyte count in patients with STEMI is unknown. Methods. We reviewed the white blood cell (WBC) and differential count of 99 patients enrolled in a clinical trial of anakinra (n=64) versus placebo (n=35) for 14 days after STEMI. A complete blood cell count with differential count were obtained at admission, and after 72 hours, 14 days and 3 months.Results. After 72 hours from treatment, anakinra compared to placebo led to a statistically significant greater percent reduction in total WBC count (-35% [-48 to -24] vs -21% [-34 to -10], P=0.008), absolute neutrophil count (-48% [-60 to -22] vs -27% [-46 to -5], P=0.004) and to an increase in absolute eosinophil count (+50% [0 to +100] vs 0% [-50 to +62], P=0.022). These changes persisted while on treatment at 14 days and were no longer apparent at 3 months after treatment discontinuation. Conclusion. We found that in patients with STEMI IL-1 blockade with anakinra accelerates resolution of leukocytosis and neutrophilia. This modulation may represent one of the mechanisms by which IL-1 blockade improves clinical outcomes.
Published: 2021

40. Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Author: Marco Giuseppe Del Buono, Alessandra Vecchié, Antonio Abbate, Aldo Bonaventura, Francesco Dentali, and Guido Juan Chiabrando
Subjects: Heart Diseases, Acute pericarditis, Anakinra, IL-1, NLRP3 inflammasome, Recurrent pericarditis, Rilonacept, Animals, Cytokines, Humans, NLR Family, Pyrin Domain-Containing 3 Protein, Inflammasomes, Inflammation, NLR Family, Pyrin domain, Pericarditis, medicine, integumentary system, business.industry, Interleukin, Inflammasome, medicine.disease, Pyrin Domain-Containing 3 Protein, Pericardial Disease (L Klein and CL Jellis, Section Editors), Immunology, medicine.symptom, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: Purpose of Review Pericarditis is a generally benign disease, although complications and/or recurrences may occur in up to 30% of cases. New evidence on the pathophysiology of the disease has accumulated in recent years. Recent Findings Recently, it has been shown that the activation of the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome is central in the pathophysiology of pericarditis. These findings derive from clinical data, an experimental animal model of acute pericarditis supporting a role for the NLRP3 inflammasome in pericarditis, and from indirect evidence of inhibitors of NLRP3 inflammasome in clinical trials. Summary Pericarditis is regarded as a stereotypical response to an acute damage of the mesothelial cells of the pericardial layers. NLRP3 inflammasome, a macromolecular structure sensing damage and releasing pro-inflammatory cytokines, is centrally involved as it releases interleukin (IL)-1β, whose auto-induction feeds an autoinflammatory disease, mostly responsible for recurrences. Colchicine, an inhibitor of NLRP3 inflammasome formation, and IL-1-targeted therapies, such as anakinra and rilonacept, were found to effectively blunt the acute inflammation and reduce the risk for recurrences.
Published: 2021
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41. [Anti-interleukin-1 agents: a new class of drugs for recurrent pericarditis. A practical guide for cardiologists]

Author: Massimo, Imazio, George, Lazaros, Marco, Gattorno, Antonio, Abbate, and Antonio, Brucato
Subjects: Cardiologists, Pharmaceutical Preparations, Recurrence, Humans, Pericarditis, Colchicine, Interleukin-1
Abstract: Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory diseases characterized by overproduction of IL-1. Idiopathic recurrent pericarditis with inflammatory phenotype (fever, leukocytosis, and elevation of C-reactive protein) has similar features and responds well to this treatment. At present, in Italy, prescription of anakinra is possible for idiopathic recurrent pericarditis with corticosteroid dependence and colchicine resistance. Anakinra is a recombinant antagonist of IL-1 receptor and blocks either IL-1α (released from pericardial cells) or IL-1β (derived for inflammatory cells, during pericarditis). Anakinra is prescribed at the dose of 2 mg/kg/day subcutaneously up to 100 mg/day subcutaneously for at least 3 to 6 months with subsequent tapering. Anakinra allows a quick control of symptoms after 1-2 doses and a fast and safe tapering and withdrawal of corticosteroids. Colchicine can be used together with anakinra. The most common side effect is represented by local skin injection site reactions after 1-2 weeks of therapy. These reactions are usually transient and can be treated by anti-histamines and topical corticosteroids. Less common side effects include elevation of transaminases (4-5%), cutaneous or respiratory infections (2-3%), and leukopenia (1-3%). Side effects are rarely responsible for permanent discontinuation of therapy. The aim of the present review is to provide a practical guide on the use of these drugs for cardiologists, who are often not familial with this new therapy for pericarditis.
Published: 2021

42. The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial

Author: John A, Spertus, Mary C, Birmingham, Michael, Nassif, C V, Damaraju, Antonio, Abbate, Javed, Butler, David E, Lanfear, Ildiko, Lingvay, Mikhail N, Kosiborod, and James L, Januzzi
Subjects: Heart Failure, Ventricular Dysfunction, Left, Patient-Centered Care, Quality of Life, COVID-19, Humans, Stroke Volume, Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors
Abstract: Large traditional clinical trials suggest that sodium-glucose co-transporter 2 inhibitors improve symptoms in patients with heart failure and reduced ejection fraction (HFrEF) and in patients with heart failure and preserved ejection fraction (HFpEF). In the midst of the Coronavirus Disease 2019 pandemic, we sought to confirm these benefits in a new type of trial that was patient centered and conducted in a completely remote fashion. In the CHIEF-HF trial ( NCT04252287 ), 476 participants with HF, regardless of EF or diabetes status, were randomized to 100 mg of canagliflozin or placebo. Enrollment was stopped early due to shifting sponsor priorities, without unblinding. The primary outcome was change in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at 12 weeks. The 12-week change in KCCQ TSS was 4.3 points (95% confidence interval, 0.8-7.8; P = 0.016) higher with canagliflozin than with placebo, meeting the primary endpoint. Similar effects were observed in participants with HFpEF and in those with HFrEF and in participants with and without diabetes, demonstrating that canagliflozin significantly improves symptom burden in HF, regardless of EF or diabetes status. This randomized, double-blind trial, conducted without in-person interactions between doctor and patient, can serve as a model for future all-virtual clinical trials.
Published: 2021

43. Left ventricular concentric remodeling and impaired cardiorespiratory fitness in patients with heart failure and preserved ejection fraction

Author: Ross Arena, Hayley Billingsley, Salvatore Carbone, Antonio Abbate, Justin M. Canada, Benjamin W. Van Tassell, and Justin Heizer
Subjects: medicine.medical_specialty, Article, Myocardial perfusion imaging, Internal medicine, Heart rate, Medicine, Humans, Retrospective Studies, Heart Failure, Ejection fraction, medicine.diagnostic_test, Ventricular Remodeling, business.industry, Cardiorespiratory fitness, Stroke Volume, Stroke volume, Middle Aged, medicine.disease, Cardiorespiratory Fitness, Heart failure, Cardiology, Female, business, Heart failure with preserved ejection fraction, Cardiology and Cardiovascular Medicine, Anaerobic exercise
Abstract: BACKGROUND: Left ventricular (LV) concentric remodeling refers to a process by which increased LV relative wall thickness alters myocardial geometry, resulting in reduced LV end-diastolic volume (LVEDV) and stroke volume (SV). While the degree of concentric remodeling is a negative prognostic factor in heart failure with preserved ejection fraction (HFpEF), it is not known how it contributes to cardiorespiratory fitness (CRF). METHODS: We performed a retrospective analysis of patients with HFpEF who underwent treadmill single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) and cardiopulmonary exercise testing (CPX). From exercise SPECT-MPI, we recorded postexercise LVEDVi, LVESVi, SVi, LVEF, the presence and extent of perfusion defects, and perfusion reversibility. Peak oxygen consumption (VO(2)), the oxygen uptake efficiency slope (OUES), oxygen (O(2)) pulse, ventilatory efficiency (V(E)/VCO(2) slope), ventilatory anaerobic threshold, respiratory exchange ratio, exercise time, and maximum heart rate were obtained from CPX. Data are expressed as mean (±standard deviation). Univariate and multivariate linear regression was performed. RESULTS: We identified 23 subjects who had completed both an exercise SPECT-MPI and a CPX. Patients were more commonly women (83%), black (65%), middle age (50 [±7.3] years), and obese (Body Mass Index [BMI] 39.7 [±6.0] kg/m2). Greater LVEDVi and LVESVi correlated positively with peak VO(2) (R=+0.648, P=0.001; R=+0.601, P=0.002), O(2) pulse (R=+0.686, P
Published: 2021
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44. Weathering the Cytokine Storm in COVID-19: Therapeutic Implications

Author: Carl J. Lavie, Claudio Ronco, Giulia Iannaccone, Roberto Scacciavillani, Marco Giuseppe Del Buono, Antonio Abbate, Massimo Massetti, Nadia Aspromonte, Filippo Crea, and Massimiliano Camilli
Subjects: ARDS, medicine.medical_treatment, 030232 urology & nephrology, Review Article, Passive, HIV Antibodies, 030204 cardiovascular system & hematology, Cytokine storm, 0302 clinical medicine, Adrenal Cortex Hormones, Monoclonal, Receptors, Medicine, Viral, Enzyme Inhibitors, Humanized, Respiratory Distress Syndrome, Plasma Exchange, Immunoglobulins, Intravenous, Chloroquine, Lung Injury, Plasmapheresis, Cytokine release syndrome, Cytokine, CCR5 Receptor Antagonists, medicine.symptom, Intravenous, Coronavirus Infections, Cytokine Release Syndrome, Cardiology and Cardiovascular Medicine, Hydroxychloroquine, medicine.medical_specialty, Multiple Organ Failure, Urology, Pneumonia, Viral, Immunoglobulins, Antibodies, Monoclonal, Humanized, Mesenchymal Stem Cell Transplantation, Asymptomatic, Antibodies, Proinflammatory cytokine, Immunomodulation, Betacoronavirus, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, Humans, Immunologic Factors, Janus Kinase Inhibitors, Intensive care medicine, Pandemics, COVID-19 Serotherapy, Interleukin-6, SARS-CoV-2, business.industry, Mechanism (biology), Immunization, Passive, COVID-19, Pneumonia, medicine.disease, Receptors, Interleukin-6, COVID-19 Drug Treatment, Hemoperfusion, Interleukin 1 Receptor Antagonist Protein, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Immunization, Tumor Necrosis Factor Inhibitors, Therapy, business
Abstract: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. Summary: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients’ clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.
Published: 2020
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45. Determinants of Cardiorespiratory Fitness in Patients with Heart Failure Across a Wide Range of Ejection Fractions

Author: Ross Arena, Jessie van Wezenbeek, Dinesh Kadariya, Inna Tchoukina, Salvatore Carbone, Marco Giuseppe Del Buono, Justin M. Canada, Hayley Billingsley, Cory R. Trankle, Antonio Abbate, Leo F. Buckley, Keyur B. Shah, Krishna Ravindra, Michele Viscusi, George F. Wohlford, Benjamin W. Van Tassell, and Pulmonary medicine
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Heart Ventricles, 030204 cardiovascular system & hematology, Doppler echocardiography, Ventricular Function, Left, 03 medical and health sciences, Oxygen Consumption, 0302 clinical medicine, Internal medicine, Linear regression, medicine, Natriuretic peptide, Humans, 030212 general & internal medicine, Treadmill, Retrospective Studies, Heart Failure, Exercise Tolerance, Ejection fraction, medicine.diagnostic_test, business.industry, Stroke Volume, Cardiorespiratory fitness, Middle Aged, Stepwise regression, Prognosis, medicine.disease, Echocardiography, Doppler, Heart failure, Exercise Test, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, human activities, Follow-Up Studies
Abstract: Impaired cardiorespiratory fitness (CRF) in heart failure (HF) is influenced by a complex array of cardiac and extracardiac factors. The study aimed to identify clinical determinants of CRF measured as peak oxygen consumption (peak VO2) in HF patients, and to determine a peak VO2 prediction model using regression equations. Retrospective analysis of 200 HF patients who completed treadmill cardiopulmonary exercise testing and underwent Doppler echocardiography and/or biomarker analysis on the same day was performed. After univariate linear regression analysis, a multivariate peak VO2 prediction model was developed using significant variables in a stepwise linear regression analysis. In subjects with repeated testing, Pearson's correlation was used to assess correlations between measured and predicted change in peak VO2 (Δpeak VO2) over time. Mean age was 57 years, with 55% being male. Stepwise linear regression was used to generate a weighted model for peak VO2: 30.895 + (−0.112•age[years]) + (0.296•hemoglobin [g/dl]) + (−0.101•E/e'[unit change]) + (−0.202• body mass index [kg/m2]) + (−0.593• N-terminal pro-brain natriuretic peptide [logN pg/ml])) + (−1.349•CRP [log mg/L]). Predicted peak VO2 correlated strongly with measured peak VO2 in HF with reduced ejection fraction and HF with preserved ejection fraction patients (r = +0.63, p 2 correlated with measured Δpeak VO2 (r = +0.23, p 2 in HF patients and may be used to estimate peak VO2 changes over time.
Published: 2020
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46. Sleeve Gastrectomy Reduces BMI and Pill Count in Patients With LVAD

Author: Hayley Billingsley, Dave Dixon, Amin Yehya, Salvatore Carbone, and Antonio Abbate
Subjects: Heart Failure, Pharmacology, Treatment Outcome, Gastrectomy, Humans, Cardiology and Cardiovascular Medicine, Body Mass Index, Retrospective Studies
Published: 2022
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47. Alirocumab in Acute Myocardial Infarction

Author: Benjamin W. Van Tassell, Leo F. Buckley, Cory R. Trankle, Nicola Potere, Tae Shik Park, Dinesh Kadariya, George F. Wohlford, Krishna Ravindra, Roshanak Markley, and Antonio Abbate
Subjects: Adult, Male, 0301 basic medicine, Acute coronary syndrome, medicine.medical_specialty, Serine Proteinase Inhibitors, Time Factors, Down-Regulation, Pilot Projects, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Placebo, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Interquartile range, Internal medicine, Clinical endpoint, Humans, Medicine, Myocardial infarction, Non-ST Elevated Myocardial Infarction, Adverse effect, Aged, Dyslipidemias, Alirocumab, Pharmacology, business.industry, Anticholesteremic Agents, PCSK9 Inhibitors, Virginia, Cholesterol, LDL, Middle Aged, medicine.disease, Treatment Outcome, 030104 developmental biology, Feasibility Studies, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: Alirocumab improves outcomes in patients with a history of recent acute coronary syndrome, but treatment acutely at the time of myocardial infarction is untested. We present the results of a randomized, placebo-controlled, double-blinded pilot study of alirocumab treatment at the time of non-ST elevation MI (NSTEMI). Twenty patients with type 1 NSTEMI and low-density lipoprotein cholesterol (LDL-C) >70 mg/dL despite high intensity statin therapy were randomized 1:1 to one dose of alirocumab 150 mg subcutaneously or placebo within 24 hours of presentation. LDL-C and inflammatory biomarkers—including C-reactive protein—were obtained at baseline, 72 hours, and 14 days. Median (interquartile range) and number (%) were: age 59 (49, 65) years, 7 (35%) men, 16 (80%) black; baseline characteristics were similar between groups. Alirocumab significantly reduced LDL-C from baseline to 14 days by 64 mg/dL (−96, −47) compared with placebo [+1 mg/dL (−25, +16)] (primary endpoint). There were no significant between-group differences in C-reactive protein changes at any time point (all P > 0.2) or serious adverse events attributable to the study treatment. In conclusion, alirocumab administration at the time of NSTEMI significantly reduced LDL-C levels at 14 days, was safe, and had neutral effects on inflammatory biomarkers. Further studies are warranted to explore the effects on clinical outcomes.
Published: 2019
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48. Derivation and validation of a simple inflammation-based risk score system for predicting in-hospital mortality in acute coronary syndrome patients

Author: Armando Vazquez-Rangel, Jorge Carrillo-Vega, Alexandra Arias-Mendoza, Amada Álvarez-Sangabriel, José Luis Briseño-Cruz, Francisco Azar-Manzur, Luis M. Amezcua-Guerra, Carlos Martínez-Sánchez, Alfredo Altamirano-Castillo, Guering Eid-Lidt, Rafael Bojalil, Julio Sandoval, Héctor González-Pacheco, Antonio Abbate, and Jose Gomez-Arroyo
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Inflammation, 030204 cardiovascular system & hematology, Systemic inflammation, Cohort Studies, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, White blood cell, Odds Ratio, medicine, Humans, Hospital Mortality, 030212 general & internal medicine, Derivation, Acute Coronary Syndrome, Serum Albumin, Aged, Framingham Risk Score, In hospital mortality, business.industry, Reproducibility of Results, Middle Aged, medicine.disease, C-Reactive Protein, medicine.anatomical_structure, Cohort, Cardiology, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract: Accurate assessment of inflammatory status of patients during acute coronary syndrome (ACS) has become of great importance in their risk classification and in the research of new anti-inflammatory therapies.The study cohort included 7396 patients with ACS. We sought to derive and internally validate an inflammation-based score that included high-sensitivity C-reactive protein, white blood cell count, and serum albumin level at admission to evaluate the predictive role of systemic inflammation in the clinical outcome of these patients. We randomly assigned patients into derivation (66.6%) and validation (33.4%) cohorts. A total of four categories of systemic inflammation were defined.Assessed individually, the three biomarkers were associated with a higher rate of in-hospital mortality. When we combined them into an inflammation score, in-hospital mortality was significantly different across the four categories of inflammation in the derivation cohort (1.8%, 2.8%, 4.1%, and 13.8% for without, mild, moderate, and severe inflammation, respectively; p0.0001, C-statistic, 0.71). These results were similar in the validation cohort (1.1%, 2.9%, 5.2%, and 12.6%, respectively; p0.0001, C-statistic, 0.71). After multivariate adjustment, only the category of severe systemic inflammation was associated with a threefold increased risk of in-hospital mortality (odds ratios 3.02, p0.0001) and was the most powerful predictor of mortality. In the whole cohort, after subsetting patients based on GRACE risk score, the severe inflammation category was associated with a significant increase of in-hospital mortality across all sub-groups, mainly in patients with higher GRACE risk score. The inflammation-based risk score reclassified 25.3% of the population. The net reclassification index was 8.2% (p=0.001).A risk score system based on biomarkers of inflammation readily available at admission in patients with ACS, could better assess the inflammatory status and predict in-hospital mortality, as well as severe systemic inflammation that contributes to a worse outcome independently of clinical risk factors.
Published: 2019
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49. Near-infrared spectroscopic imaging of the whole hand: A new tool to assess tissue perfusion and peripheral microcirculation in scleroderma

Author: Tatiana Barskova, Martina Marinelli, Maria Giovanna Trivella, Marco Matucci-Cerinic, Valentina Hartwig, Antonio L'Abbate, Luna Gargani, and Cosimo Bruni
Subjects: Adult, Male, medicine.medical_specialty, Ischemia, 03 medical and health sciences, Oxygen Consumption, 0302 clinical medicine, Rheumatology, Forearm, Peripheral microcirculation, Internal medicine, medicine, Humans, 030212 general & internal medicine, Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, Spectroscopy, Near-Infrared, integumentary system, business.industry, Microcirculation, Middle Aged, Hand, medicine.disease, Peripheral, Functional imaging, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Case-Control Studies, Circulatory system, Cardiology, Female, business, Perfusion, Thenar eminence
Abstract: Objectives Systemic sclerosis (SSc) causes functional and structural microcirculatory dysfunction, affecting also distal extremities. Optical Near-InfraRed Spectroscopy (NIRS) of blood HbO2 saturation (stO2) is able to evaluate O2 delivery/consumption balance in the explored tissue. The NIRS-sensitive camera non-invasively detects stO2 values in superficial tissues, automatically generating 2D-imaging maps in real time. We aimed at testing whether NIRS hand imaging may evaluate peripheral microcirculatory dysfunction and its spatial heterogeneity in SSc patients compared to controls. Methods Forty SSc patients (aged 55.1 ± 15.6 years) and twenty-one healthy controls (aged 54.3 ± 14.5years, p = 0.89) were studied by palmar hand NIRS-2D imaging. A blood pressure cuff was applied to the forearm and 3 min ischemia was induced. Images were acquired at basal conditions and every 10 seconds during 3 minutes of ischemia and 5 minutes of reperfusion. Five regions of interest were positioned on each fingertip, from the second to the fifth finger and one on the thenar eminence. Results A significant difference was found between controls and SSc patients in basal stO2 (84.3 ± 7.5 vs. 75.4 ± 10.9%, p Conclusion NIRS-2D imaging is a simple, automated tool to non-invasively detect regional microcirculatory impairment in SSc, which seems to add significant functional information to the morphological picture of nailfold-videocapillaroscopy.
Published: 2019
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50. The relationship between coronary artery disease and cardiovascular events early after liver transplantation

Author: Taylor Pence, Mohammad S. Siddiqui, Antonio Abbate, Viviana Rodríguez, Chandra Bhati, Trevor Reichman, Fei-Pi Lin, Binu John, Samarth Patel, Adam Sima, and Mohammad Bilal Siddiqui
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Coronary Artery Disease, Liver transplantation, Coronary Angiography, Article, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, medicine, Humans, Prospective Studies, cardiovascular diseases, Stroke, Hepatology, medicine.diagnostic_test, business.industry, Disease mortality, Virginia, Cardiac stress test, Middle Aged, medicine.disease, Liver Transplantation, Logistic Models, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Heart failure, Cardiology, Female, 030211 gastroenterology & hepatology, business
Abstract: BACKGROUND & AIMS Cardiovascular complications are major contributors to mortality at liver transplantation (LT). However, the impact of coronary artery disease (CAD) on these complications is not well-understood as the literature is limited by non-invasive assessment of CAD, which is suboptimal in patients with cirrhosis. Thus, the current study evaluated cardiovascular events at LT stratified according to the presence and severity of CAD quantified on coronary angiography. METHODS All patients who had LT from January 2010 to January 2017 were evaluated (N = 348), but analysis was restricted to patients who had coronary angiography prior to LT (N = 283). Protocol coronary angiography was performed in all patients' ages >50 years, history of CAD, abnormal cardiac stress test or risk factors for CAD. The primary outcome was a cardiovascular composite outcome including myocardial infraction (MI), cardiac arrest, stroke, cardiac death, heart failure or arrhythmia occurring within 4 weeks after LT. RESULTS CAD was present in 92(32.5%) patients and 32(11.3%) had obstructive CAD. During the study period, 72(25.4%) patients met the primary cardiovascular outcome, the most common being arrhythmia (N = 59 or 20.8%). Non-ST elevation MI occurred in 11(3.9%) of patients. A total of 10 deaths (3.5%) occurred, of which 6(2.1%) were attributable to cardiac death. There was no evidence of a relationship between the presence and severity of CAD and composite cardiovascular events. In multiple regression modelling, only diabetes [OR 2.62, 95%CI (1.49, 4.64), P
Published: 2019
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