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Browsing by Author "Maack, Christoph (6701763468)"

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    Publication
    Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society
    (2020)
    Lyon, Alexander R. (57203046227)
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    Dent, Susan (8983699300)
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    Stanway, Susannah (12786793200)
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    Earl, Helena (7006036785)
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    Brezden-Masley, Christine (7801357890)
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    Cohen-Solal, Alain (57189610711)
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    Tocchetti, Carlo G. (6507913481)
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    Moslehi, Javid J. (6602839476)
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    Groarke, John D. (15022323600)
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    Bergler-Klein, Jutta (56019537300)
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    Khoo, Vincent (7003618620)
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    Tan, Li Ling (57191157868)
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    Anker, Markus S. (35763654100)
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    von Haehling, Stephan (6602981479)
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    Maack, Christoph (6701763468)
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    Pudil, Radek (57210201747)
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    Barac, Ana (16177111000)
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    Thavendiranathan, Paaladinesh (8530061100)
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    Ky, Bonnie (23393080500)
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    Neilan, Tomas G. (12141383200)
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    Belenkov, Yury (7006528098)
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    Rosen, Stuart D. (7401609522)
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    Iakobishvili, Zaza (6603020069)
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    Sverdlov, Aaron L. (24462692800)
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    Hajjar, Ludhmila A. (23987797600)
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    Macedo, Ariane V.S. (57216988850)
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    Manisty, Charlotte (6504025861)
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    Ciardiello, Fortunato (55410902800)
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    Farmakis, Dimitrios (55296706200)
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    de Boer, Rudolf A. (8572907800)
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    Skouri, Hadi (21934953600)
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    Suter, Thomas M. (7006001704)
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    Cardinale, Daniela (6602492476)
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    Witteles, Ronald M. (6506863794)
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    Fradley, Michael G. (55363426500)
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    Herrmann, Joerg (57203031339)
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    Cornell, Robert F. (54965749100)
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    Wechelaker, Ashutosh (57218399737)
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    Mauro, Michael J. (7103136425)
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    Milojkovic, Dragana (23019203700)
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    de Lavallade, Hugues (14821784500)
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    Ruschitzka, Frank (7003359126)
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    Coats, Andrew J.S. (35395386900)
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    Seferovic, Petar M. (6603594879)
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    Chioncel, Ovidiu (12769077100)
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    Thum, Thomas (57195743477)
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    Bauersachs, Johann (7004626054)
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    Andres, M. Sol (57220478892)
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    Wright, David J. (57214063391)
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    López-Fernández, Teresa (6507691686)
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    Plummer, Chris (35115498300)
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    Lenihan, Daniel (7003853556)
    This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies. © 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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    Cardiovascular toxicities of immune therapies for cancer – a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology
    (2024)
    Tocchetti, Carlo Gabriele (6507913481)
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    Farmakis, Dimitrios (55296706200)
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    Koop, Yvonne (57217019047)
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    Andres, Maria Sol (57220478892)
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    Couch, Liam S. (57201657451)
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    Formisano, Luigi (6508160049)
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    Ciardiello, Fortunato (55410902800)
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    Pane, Fabrizio (55949288100)
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    Au, Lewis (57201424996)
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    Emmerich, Max (58300578400)
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    Plummer, Chris (35115498300)
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    Gulati, Geeta (55506056700)
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    Ramalingam, Sivatharshini (57222656979)
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    Cardinale, Daniela (6602492476)
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    Brezden-Masley, Christine (7801357890)
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    Iakobishvili, Zaza (6603020069)
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    Thavendiranathan, Paaladinesh (8530061100)
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    Santoro, Ciro (54795845800)
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    Bergler-Klein, Jutta (56019537300)
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    Keramida, Kalliopi (57202300032)
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    de Boer, Rudolf A. (8572907800)
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    Maack, Christoph (6701763468)
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    Lutgens, Esther (6602189686)
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    Rassaf, Tienush (6603090893)
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    Fradley, Michael G. (55363426500)
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    Moslehi, Javid (57226668096)
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    Yang, Eric H. (36465820500)
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    De Keulenaer, Gilles (6603078918)
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    Ameri, Pietro (17342143000)
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    Bax, Jeroen (55429494700)
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    Neilan, Tomas G. (12141383200)
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    Herrmann, Joerg (57203031339)
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    Mbakwem, Amam C. (6506969430)
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    Mirabel, Mariana (19337718800)
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    Skouri, Hadi (21934953600)
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    Hirsch, Emilio (7201435266)
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    Cohen-Solal, Alain (57189610711)
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    Sverdlov, Aaron L. (24462692800)
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    van der Meer, Peter (7004669395)
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    Asteggiano, Riccardo (24761476900)
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    Barac, Ana (16177111000)
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    Ky, Bonnie (23393080500)
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    Lenihan, Daniel (7003853556)
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    Dent, Susan (8983699300)
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    Seferovic, Petar (55873742100)
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    Coats, Andrew J.S. (35395386900)
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    Metra, Marco (7006770735)
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    Rosano, Giuseppe (59142922200)
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    Suter, Thomas (7006001704)
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    Lopez-Fernandez, Teresa (6507691686)
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    Lyon, Alexander R. (57203046227)
    The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus. © 2024 European Society of Cardiology.
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    Publication
    Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)
    (2020)
    de Boer, Rudolf A. (8572907800)
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    Hulot, Jean-Sébastien (6603026259)
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    Tocchetti, Carlo Gabriele (6507913481)
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    Aboumsallem, Joseph Pierre (57195371732)
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    Ameri, Pietro (17342143000)
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    Anker, Stefan D. (56223993400)
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    Bauersachs, Johann (7004626054)
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    Bertero, Edoardo (57189520921)
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    Coats, Andrew J.S. (35395386900)
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    Čelutkienė, Jelena (6507133552)
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    Chioncel, Ovidiu (12769077100)
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    Dodion, Pierre (57205178617)
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    Eschenhagen, Thomas (7004716470)
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    Farmakis, Dimitrios (55296706200)
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    Bayes-Genis, Antoni (7004094140)
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    Jäger, Dirk (7005584966)
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    Jankowska, Ewa A. (21640520500)
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    Kitsis, Richard N. (7003793631)
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    Konety, Suma H. (8271066700)
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    Larkin, James (8762665400)
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    Lehmann, Lorenz (15760419100)
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    Lenihan, Daniel J. (7003853556)
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    Maack, Christoph (6701763468)
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    Moslehi, Javid J. (6602839476)
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    Müller, Oliver J. (57213328662)
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    Nowak-Sliwinska, Patrycja (6506106323)
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    Piepoli, Massimo Francesco (7005292730)
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    Ponikowski, Piotr (7005331011)
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    Pudil, Radek (57210201747)
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    Rainer, Peter P. (35590576100)
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    Ruschitzka, Frank (7003359126)
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    Sawyer, Douglas (7201550571)
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    Seferovic, Petar M. (6603594879)
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    Suter, Thomas (7006001704)
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    Thum, Thomas (57195743477)
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    van der Meer, Peter (7004669395)
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    Van Laake, Linda W. (9533995100)
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    von Haehling, Stephan (6602981479)
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    Heymans, Stephane (6603326423)
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    Lyon, Alexander R. (57203046227)
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    Backs, Johannes (6506659543)
    The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time. © 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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    Heart failure and diabetes: Metabolic alterations and therapeutic interventions: A state-of-The-Art review from the Translational Research Committee of the Heart Failure Association-European Society of Cardiology
    (2018)
    Maack, Christoph (6701763468)
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    Lehrke, Michael (57203333460)
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    Backs, Johannes (6506659543)
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    Heinzel, Frank R. (7005851989)
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    Hulot, Jean-Sebastien (6603026259)
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    Marx, Nikolaus (57203048581)
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    Paulus, Walter J. (7201614091)
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    Rossignol, Patrick (7006015976)
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    Taegtmeyer, Heinrich (7102044748)
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    Bauersachs, Johann (7004626054)
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    Bayes-Genis, Antoni (7004094140)
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    Brutsaert, Dirk (7006117073)
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    Bugger, Heiko (22233449600)
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    Clarke, Kieran (35476630000)
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    Cosentino, Francesco (7006332266)
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    De Keulenaer, Gilles (6603078918)
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    Cas, Alessandra Dei (18233496100)
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    González, Arantxa (57191823224)
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    Huelsmann, Martin (7006719269)
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    Iaccarino, Guido (57221543508)
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    Lunde, Ida Gjervold (17346352100)
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    Lyon, Alexander R (57203046227)
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    Pollesello, Piero (7004881964)
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    Rena, Graham (6603702420)
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    Riksen, Niels P (6603036752)
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    Rosano, Giuseppe (7007131876)
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    Staels, Bart (7102139355)
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    Van Laake, Linda W. (9533995100)
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    Wanner, Christoph (57212349814)
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    Farmakis, Dimitrios (55296706200)
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    Filippatos, Gerasimos (7003787662)
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    Ruschitzka, Frank (7003359126)
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    Seferovic, Petar (6603594879)
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    De Boer, Rudolf A. (8572907800)
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    Heymans, Stephane (6603326423)
    [No abstract available]
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    Heart failure and obesity: Translational approaches and therapeutic perspectives. A scientific statement of the Heart Failure Association of the ESC
    (2025)
    Savarese, Gianluigi (36189499900)
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    Schiattarella, Gabriele G. (16029615600)
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    Lindberg, Felix (57451813800)
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    Anker, Markus S. (35763654100)
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    Bayes-Genis, Antoni (7004094140)
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    Bäck, Magnus (7006363185)
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    Braunschweig, Frieder (6602194306)
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    Bucciarelli-Ducci, Chiara (18534251300)
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    Butler, Javed (57203521637)
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    Cannata, Antonio (56950331100)
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    Capone, Federico (57188624879)
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    Chioncel, Ovidiu (12769077100)
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    D'Elia, Emilia (40660899000)
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    González, Arantxa (57191823224)
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    Filippatos, Gerasimos (7003787662)
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    Girerd, Nicolas (23027379700)
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    Hulot, Jean-Sébastien (6603026259)
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    Lam, Carolyn S.P. (19934204100)
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    Lund, Lars H. (7102206508)
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    Maack, Christoph (6701763468)
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    Moura, Brenda (6602544591)
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    Petrie, Mark C. (7006426382)
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    Piepoli, Massimo (7005292730)
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    Shehab, Abdullah (6603838351)
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    Yilmaz, Mehmet B. (7202595585)
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    Seferovic, Peter (59774002200)
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    Tocchetti, Carlo G. (6507913481)
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    Rosano, Giuseppe M.C. (7007131876)
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    Metra, Marco (7006770735)
    Obesity and heart failure (HF) represent two growing pandemics. In the general population, obesity affects one in eight adults and is linked with an increased risk for HF. Obesity is even more common in patients with HF, where it complicates the diagnosis of HF and is linked with worse symptoms and impaired exercise capacity. Over the past few years, new evidence on the mechanisms linking obesity with HF has been reported, particularly in relation to HF with preserved ejection fraction. Novel therapies inducing weight loss appear to have favourable effects on health status and cardiovascular risk. Against the backdrop of this rapidly evolving evidence landscape, HF clinicians are increasingly required to tailor their preventive, diagnostic, and therapeutic approaches to HF in the presence of obesity. This scientific statement by the Heart Failure Association of the European Society of Cardiology provides an up-to-date summary on obesity in HF, covering key areas such as epidemiology, translational aspects, diagnostic challenges, therapeutic approaches, and trial design. © 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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    Recent advances in cardio-oncology: a report from the ‘Heart Failure Association 2019 and World Congress on Acute Heart Failure 2019’
    (2019)
    Anker, Markus S. (35763654100)
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    Hadzibegovic, Sara (57204551985)
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    Lena, Alessia (57204551352)
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    Belenkov, Yury (7006528098)
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    Bergler-Klein, Jutta (56019537300)
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    de Boer, Rudolf A. (8572907800)
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    Farmakis, Dimitrios (55296706200)
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    von Haehling, Stephan (6602981479)
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    Iakobishvili, Zaza (6603020069)
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    Maack, Christoph (6701763468)
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    Pudil, Radek (57210201747)
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    Skouri, Hadi (21934953600)
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    Cohen-Solal, Alain (57189610711)
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    Tocchetti, Carlo G. (6507913481)
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    Coats, Andrew J.S. (35395386900)
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    Seferović, Petar M. (6603594879)
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    Lyon, Alexander R. (57203046227)
    While anti-cancer therapies, including chemotherapy, immunotherapy, radiotherapy, and targeted therapy, are constantly advancing, cardiovascular toxicity has become a major challenge for cardiologists and oncologists. This has led to an increasing demand of cardio-oncology units in Europe and a growing interest of clinicians and researchers. The Heart Failure 2019 meeting of the Heart Failure Association of the European Society of Cardiology in Athens has therefore created a scientific programme that included four dedicated sessions on the topic along with several additional lectures. The major points that were discussed at the congress included the implementation and delivery of a cardio-oncology service, the collaboration among cardio-oncology experts, and the risk stratification, prevention, and early recognition of cardiotoxicity. Furthermore, sessions addressed the numerous different anti-cancer therapies associated with cardiotoxic effects and provided guidance on how to treat cancer patients who develop cardiovascular disease before, during, and after treatment. © 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology
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    Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology
    (2020)
    Pudil, Radek (57210201747)
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    Mueller, Christian (57638261900)
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    Čelutkienė, Jelena (6507133552)
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    Henriksen, Peter A. (12791695200)
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    Lenihan, Dan (7003853556)
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    Dent, Susan (8983699300)
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    Barac, Ana (16177111000)
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    Stanway, Susanna (12786793200)
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    Moslehi, Javid (6602839476)
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    Suter, Thomas M. (7006001704)
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    Ky, Bonnie (23393080500)
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    Štěrba, Martin (6602528504)
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    Cardinale, Daniela (6602492476)
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    Cohen-Solal, Alain (57189610711)
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    Tocchetti, Carlo Gabriele (6507913481)
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    Farmakis, Dimitrios (55296706200)
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    Bergler-Klein, Jutta (56019537300)
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    Anker, Markus S. (35763654100)
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    Von Haehling, Stephan (6602981479)
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    Belenkov, Yury (7006528098)
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    Iakobishvili, Zaza (6603020069)
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    Maack, Christoph (6701763468)
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    Ciardiello, Fortunato (55410902800)
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    Ruschitzka, Frank (7003359126)
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    Coats, Andrew J.S. (35395386900)
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    Seferovic, Petar (6603594879)
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    Lainscak, Mitja (9739432000)
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    Piepoli, Massimo F. (7005292730)
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    Chioncel, Ovidiu (12769077100)
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    Bax, Jereon (55429494700)
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    Hulot, Jean-Sebastien (6603026259)
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    Skouri, Hadi (21934953600)
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    Hägler-Laube, Eva Simona (57219470558)
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    Asteggiano, Riccardo (24761476900)
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    Fernandez, Teresa Lopez (57194588042)
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    de Boer, Rudolf A. (8572907800)
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    Lyon, Alexander R. (57203046227)
    Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed. © 2020 European Society of Cardiology
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    The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology
    (2017)
    van Bilsen, Marc (7004309395)
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    Patel, Hitesh C. (55911436600)
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    Bauersachs, Johann (7004626054)
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    Böhm, Michael (35392235500)
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    Borggrefe, Martin (35380094100)
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    Brutsaert, Dirk (7006117073)
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    Coats, Andrew J.S. (35395386900)
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    de Boer, Rudolf A. (8572907800)
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    de Keulenaer, Gilles W. (6603078918)
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    Filippatos, Gerasimos S. (7003787662)
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    Floras, John (7007043210)
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    Grassi, Guido (26643377500)
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    Jankowska, Ewa A. (21640520500)
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    Kornet, Lilian (56569437400)
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    Lunde, Ida G. (17346352100)
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    Maack, Christoph (6701763468)
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    Mahfoud, Felix (59837499200)
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    Pollesello, Piero (7004881964)
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    Ponikowski, Piotr (7005331011)
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    Ruschitzka, Frank (7003359126)
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    Sabbah, Hani N. (35500373600)
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    Schultz, Harold D. (7103187292)
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    Seferovic, Petar (6603594879)
    ;
    Slart, Riemer H.J.A. (6603818125)
    ;
    Taggart, Peter (7006677172)
    ;
    Tocchetti, Carlo G. (6507913481)
    ;
    Van Laake, Linda W. (9533995100)
    ;
    Zannad, Faiez (7102111367)
    ;
    Heymans, Stephane (6603326423)
    ;
    Lyon, Alexander R. (57203046227)
    Despite improvements in medical therapy and device-based treatment, heart failure (HF) continues to impose enormous burdens on patients and health care systems worldwide. Alterations in autonomic nervous system (ANS) activity contribute to cardiac disease progression, and the recent development of invasive techniques and electrical stimulation devices has opened new avenues for specific targeting of the sympathetic and parasympathetic branches of the ANS. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop which brought together clinicians, trialists and basic scientists to discuss the ANS as a therapeutic target in HF. The questions addressed were: (i) What are the abnormalities of ANS in HF patients? (ii) What methods are available to measure autonomic dysfunction? (iii) What therapeutic interventions are available to target the ANS in patients with HF, and what are their specific strengths and weaknesses? (iv) What have we learned from previous ANS trials? (v) How should we proceed in the future?. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology
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    The continuous heart failure spectrum: Moving beyond an ejection fraction classification
    (2019)
    Triposkiadis, Filippos (55399494500)
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    Butler, Javed (57203521637)
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    Abboud, Francois M. (7102796868)
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    Armstrong, Paul W. (35380325200)
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    Adamopoulos, Stamatis (55399885400)
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    Atherton, John J. (57202810067)
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    Backs, Johannes (6506659543)
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    Bauersachs, Johann (7004626054)
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    Burkhoff, Daniel (7006163840)
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    Bonow, Robert O. (7102250069)
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    Chopra, Vijay K. (57213319493)
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    De Boer, Rudolf A. (8572907800)
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    De Windt, Leon (7004313195)
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    Hamdani, Nazha (23094208600)
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    Hasenfuss, Gerd (26643367300)
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    Heymans, Stephane (6603326423)
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    Hulot, Jean-Sébastien (6603026259)
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    Konstam, Marvin (55628580428)
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    Lee, Richard T. (7408204096)
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    Linke, Wolfgang A. (7004812764)
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    Lunde, Ida G. (17346352100)
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    Lyon, Alexander R. (57203046227)
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    Maack, Christoph (6701763468)
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    Mann, Douglas L. (7402056905)
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    Mebazaa, Alexandre (57210091243)
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    Mentz, Robert J. (57001073900)
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    Nihoyannopoulos, Petros (55959198800)
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    Papp, Zoltan (29867593800)
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    Parissis, John (7004855782)
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    Pedrazzini, Thierry (57204343082)
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    Rosano, Giuseppe (7007131876)
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    Rouleau, Jean (7102610398)
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    Seferovic, Petar M. (6603594879)
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    Shah, Ajay M. (7403209323)
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    Starling, Randall C. (7005956570)
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    Tocchetti, Carlo G. (6507913481)
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    Trochu, Jean-Noel (18036119300)
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    Thum, Thomas (57195743477)
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    Zannad, Faiez (7102111367)
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    Brutsaert, Dirk L. (7006117073)
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    Segers, Vincent F. (16744903900)
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    De Keulenaer, Gilles W. (6603078918)
    Randomized clinical trials initially used heart failure (HF) patients with low left ventricular ejection fraction (LVEF) to select study populations with high risk to enhance statistical power. However, this use of LVEF in clinical trials has led to oversimplification of the scientific view of a complex syndrome. Descriptive terms such as ‘HFrEF’ (HF with reduced LVEF), ‘HFpEF’ (HF with preserved LVEF), and more recently ‘HFmrEF’ (HF with mid-range LVEF), assigned on arbitrary LVEF cut-off points, have gradually arisen as separate diseases, implying distinct pathophysiologies. In this article, based on pathophysiological reasoning, we challenge the paradigm of classifying HF according to LVEF. Instead, we propose that HF is a heterogeneous syndrome in which disease progression is associated with a dynamic evolution of functional and structural changes leading to unique disease trajectories creating a spectrum of phenotypes with overlapping and distinct characteristics. Moreover, we argue that by recognizing the spectral nature of the disease a novel stratification will arise from new technologies and scientific insights that will shape the design of future trials based on deeper understanding beyond the LVEF construct alone. © The Author(s) 2019.
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    Treatments targeting inotropy
    (2019)
    Maack, Christoph (6701763468)
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    Eschenhagen, Thomas (7004716470)
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    Hamdani, Nazha (23094208600)
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    Heinze, Frank R. (57212263844)
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    Lyon, Alexander R. (57203046227)
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    Manstein, Dietmar J. (7006283059)
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    Metzger, Joseph (7202074710)
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    Papp, Zoltan (29867593800)
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    Tocchetti, Carlo G. (6507913481)
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    Yilmaz, M. Birhan (7202595585)
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    Anker, Stefan D. (56223993400)
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    Balligand, Jean-Luc (7003921084)
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    Bauersachs, Johann (7004626054)
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    Brutsaert, Dirk (7006117073)
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    Carrier, Lucie (55199727100)
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    Chlopicki, Stefan (7003634171)
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    Cleland, John G. (7202164137)
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    De Boer, Rudolf A. (8572907800)
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    Dietl, Alexander (55324535700)
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    Fischmeister, Rodolphe (7006457996)
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    Harjola, Veli-Pekka (6602728533)
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    Heymans, Stephane (6603326423)
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    Hilfiker-Kleiner, Denise (6602676885)
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    Holzmeister, Johannes (6603169763)
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    De Keulenaer, Gilles (6603078918)
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    Limongelli, Giuseppe (6603359014)
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    Linke, Wolfgang A. (7004812764)
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    Lund, Lars H. (7102206508)
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    Masip, Josep (57221962429)
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    Metra, Marco (7006770735)
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    Mueller, Christian (57638261900)
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    Pieske, Burkert (35499467500)
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    Ponikowski, Piotr (7005331011)
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    Risti, Arsen (18936987100)
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    Ruschitzka, Frank (7003359126)
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    Seferovi, Petar M. (57212274303)
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    Skouri, Hadi (21934953600)
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    Zimmermann, Wolfram H. (7203058782)
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    Mebazaa, Alexandre (57210091243)
    Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesteraseinhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2þ. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term. © 2018 The Author(s).

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