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1. Congestion in heart failure: a circulating biomarker‐based perspective. A review from the Biomarkers Working Group of the Heart Failure Association, European Society of Cardiology

Author

Julio Núñez, Rafael de la Espriella, Patrick Rossignol, Adriaan A. Voors, Wilfried Mullens, Marco Metra, Ovidiu Chioncel, James L. Januzzi, Christian Mueller, A. Mark Richards, Rudolf A. de Boer, Thomas Thum, Henrike Arfsten, Arantxa González, Magdy Abdelhamid, Stamatis Adamopoulos, Stefan D. Anker, Tuvia Ben Gal, Jan Biegus, Alain Cohen‐Solal, Michael Böhm, Michele Emdin, Ewa A. Jankowska, Finn Gustafsson, Loreena Hill, Tiny Jaarsma, Pardeep S. Jhund, Yuri Lopatin, Lars H. Lund, Davor Milicic, Brenda Moura, Massimo F. Piepoli, Piotr Ponikowski, Amina Rakisheva, Arsen Ristic, Gianluigi Savarese, Carlo G. Tocchetti, Sophie Van Linthout, Maurizio Volterrani, Petar Seferovic, Giuseppe Rosano, Andrew J.S. Coats, Antoni Bayes‐Genis, Publica, Núñez, Julio, de la Espriella, Rafael, Rossignol, Patrick, Voors, Adriaan A, Mullens, Wilfried, Metra, Marco, Chioncel, Ovidiu, Januzzi, James L, Mueller, Christian, Richards, A Mark, de Boer, Rudolf A, Thum, Thoma, Arfsten, Henrike, González, Arantxa, Abdelhamid, Magdy, Adamopoulos, Stamati, Anker, Stefan D, Gal, Tuvia Ben, Biegus, Jan, Cohen-Solal, Alain, Böhm, Michael, Emdin, Michele, Jankowska, Ewa A, Gustafsson, Finn, Hill, Loreena, Jaarsma, Tiny, Jhund, Pardeep S, Lopatin, Yuri, Lund, Lars H, Milicic, Davor, Moura, Brenda, Piepoli, Massimo F, Ponikowski, Piotr, Rakisheva, Amina, Ristic, Arsen, Savarese, Gianluigi, Tocchetti, Carlo G, Van Linthout, Sophie, Volterrani, Maurizio, Seferovic, Petar, Rosano, Giuseppe, Coats, Andrew J S, and Bayes-Genis, Antoni

Subjects
Heart Failure, Adrenomedullin, Cardiology, Congestion, Humans, Acute heart failure, Biomarker, Prognosis, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract

Congestion is a cardinal sign of heart failure (HF). In the past, it was seen as a homogeneous epiphenomenon that identified patients with advanced HF. However, current evidence shows that congestion in HF varies in quantity and distribution. This updated view advocates for a congestive-driven classification of HF according to onset (acute vs. chronic), regional distribution (systemic vs. pulmonary), compartment of distribution (intravascular vs. extravascular), and clinical vs. subclinical. Thus, this review will focus on the utility of circulating biomarkers for assessing and managing the different fluid overload phenotypes. This discussion focused on the clinical utility of the natriuretic peptides, carbohydrate antigen 125 (also called mucin 16), bio-adrenomedullin and mid-regional pro-adrenomedullin, ST2 (also known as interleukin-1 receptor-like 1), cluster of differentiation 146, troponin, C-terminal pro-endothelin-1, and parameters of haemoconcentration. The utility of circulation biomarkers on top of clinical evaluation, haemodynamics, and imaging needs to be better determined by dedicated studies. Some multiparametric frameworks in which these tools contribute to management are proposed.

Published
2022

2. Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology

Author

Metra, Marco, Tomasoni, Daniela, Adamo, Marianna, Bayes-Genis, Antoni, Filippatos, Gerasimos, Abdelhamid, Magdy, Adamopoulos, Stamatis, Anker, Stefan D, Antohi, Laura, Böhm, Michael, Braunschweig, Frieder, Gal, Tuvia Ben, Butler, Javed, Cleland, John G F, Cohen-Solal, Alain, Damman, Kevin, Gustafsson, Finn, Hill, Loreena, Jankowska, Ewa A, Lainscak, Mitja, Lund, Lars H, McDonagh, Theresa, Mebazaa, Alexandre, Moura, Brenda, Mullens, Wilfried, Piepoli, Massimo, Ponikowski, Piotr, Rakisheva, Amina, Ristic, Arsen, Savarese, Gianluigi, Seferovic, Petar, Sharma, Rajan, Tocchetti, Carlo Gabriele, Yılmaz, Mehmet Birhan, Vitale, Cristiana, Volterrani, Maurizio, von Haehling, Stephan, Chioncel, Ovidiu, Coats, Andrew J S, Rosano, Giuseppe, Metra, Marco, Tomasoni, Daniela, Adamo, Marianna, Bayes-Genis, Antoni, Filippatos, Gerasimo, Abdelhamid, Magdy, Adamopoulos, Stamati, Anker, Stefan D, Antohi, Laura, Böhm, Michael, Braunschweig, Frieder, Gal, Tuvia Ben, Butler, Javed, Cleland, John G F, Cohen-Solal, Alain, Damman, Kevin, Gustafsson, Finn, Hill, Loreena, Jankowska, Ewa A, Lainscak, Mitja, Lund, Lars H, Mcdonagh, Theresa, Mebazaa, Alexandre, Moura, Brenda, Mullens, Wilfried, Piepoli, Massimo, Ponikowski, Piotr, Rakisheva, Amina, Ristic, Arsen, Savarese, Gianluigi, Seferovic, Petar, Sharma, Rajan, Tocchetti, Carlo Gabriele, Yılmaz, Mehmet Birhan, Vitale, Cristiana, Volterrani, Maurizio, von Haehling, Stephan, Chioncel, Ovidiu, Coats, Andrew J S, and Rosano, Giuseppe

Subjects
Hospitalization, Emergency department visits, Intensification of oral therapy, Outpatients, Prognosis, Worsening heart failure, Prognosi, Outpatient, Emergency department visit, Cardiology and Cardiovascular Medicine
Abstract

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice.

Published
2023

3. Impact analysis of heart failure across European countries: an ESC-HFA position paper

Author

Giuseppe M.C. Rosano, Petar Seferovic, Gianluigi Savarese, Ilaria Spoletini, Yuri Lopatin, Fin Gustafsson, Antoni Bayes‐Genis, Tiny Jaarsma, Magdy Abdelhamid, Arantxa Gonzalez Miqueo, Massimo Piepoli, Carlo G. Tocchetti, Arsen D. Ristić, Ewa Jankowska, Brenda Moura, Loreena Hill, Gerasimos Filippatos, Marco Metra, Davor Milicic, Thomas Thum, Ovidiu Chioncel, Tuvia Ben Gal, Lars H. Lund, Dimitrios Farmakis, Wilfried Mullens, Stamatis Adamopoulos, Michael Bohm, Anna Norhammar, Andreas Bollmann, Amitava Banerjee, Aldo P. Maggioni, Adriaan Voors, Alain Cohen Solal, Andrew J.S. Coats, Rosano, Giuseppe M C, Seferovic, Petar, Savarese, Gianluigi, Spoletini, Ilaria, Lopatin, Yuri, Gustafsson, Fin, Bayes-Genis, Antoni, Jaarsma, Tiny, Abdelhamid, Magdy, Miqueo, Arantxa Gonzalez, Piepoli, Massimo, Tocchetti, Carlo G, Ristić, Arsen D, Jankowska, Ewa, Moura, Brenda, Hill, Loreena, Filippatos, Gerasimo, Metra, Marco, Milicic, Davor, Thum, Thoma, Chioncel, Ovidiu, Gal, Tuvia Ben, Lund, Lars H, Farmakis, Dimitrio, Mullens, Wilfried, Adamopoulos, Stamati, Bohm, Michael, Norhammar, Anna, Bollmann, Andrea, Banerjee, Amitava, Maggioni, Aldo P, Voors, Adriaan, Solal, Alain Cohen, and Coats, Andrew J S

Subjects
Quality of life, Hälso- och sjukvårdsorganisation, hälsopolitik och hälsoekonomi, Epidemiology, Prognosi, Heart failure, EJECTION FRACTION, Impact, Prognosis, Mortality, Morbidity, SDG 3 - Good Health and Well-being, QUALITY-OF-LIFE, ECONOMIC BURDEN, CO-MORBIDITIES, Humans, Heart Failure / therapy, Heart Failure, OUTCOMES, Incidence, Heart Failure / epidemiology, Health Care Service and Management, Health Policy and Services and Health Economy, Health Care Costs, PREVALENCE, IRON-DEFICIENCY, Europe, Quality of Life, HEALTH, Europe / epidemiology, Cardiology and Cardiovascular Medicine, RC
Abstract

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs—in terms of quality of life—in European countries.

Published
2022

4. Cardiac remodelling part 2: clinical, imaging and laboratory findings: a review from the Biomarkers Working Group of the Heart Failure Association of the ESC

Author

Aimo, Alberto, Vergaro, Giuseppe, González, Arantxa, Barison, Andrea, Lupón, Josep, Delgado, Victoria, Richards, A Mark, de Boer, Rudolf A, Thum, Thomas, Arfsten, Henrike, Hülsmann, Martin, Falcao‐Pires, Inês, Díez, Javier, Foo, Roger SY, Chan, Mark Yan Yee, Anene‐Nzelu, George C, Abdelhamid, Magdy, Adamopoulos, Stamatis, Anker, Stefan D, Belenkov, Yuri, Gal, Tuvia B, Cohen‐Solal, Alain, Böhm, Michael, Chioncel, Ovidiu, Jankowska, Ewa A, Gustafsson, Finn, Hill, Loreena, Jaarsma, Tiny, Januzzi, James L, Jhund, Pardeep, Lopatin, Yuri, Lund, Lars H, Metra, Marco, Milicic, Davor, Moura, Brenda, Mueller, Christian, Mullens, Wilfried, Núñez, Julio, Piepoli, Massimo F, Rakisheva, Amina, Ristic, Arsen, Rossignol, Patrick, Savarese, Gianluigi, Tocchetti, Carlo G, van Linthout, Sophie, Volterrani, Maurizio, Seferovic, Petar, Rosano, Giuseppe, Coats, Andrew JS, Emdin, Michele, Bayes‐Genis, Antoni, Aimo, Alberto, Vergaro, Giuseppe, González, Arantxa, Barison, Andrea, Lupón, Josep, Delgado, Victoria, Richards, A Mark, de Boer, Rudolf A, Thum, Thoma, Arfsten, Henrike, Hülsmann, Martin, Falcao-Pires, Inê, Díez, Javier, Foo, Roger Sy, Chan, Mark Yan Yee, Anene-Nzelu, George C, Abdelhamid, Magdy, Adamopoulos, Stamati, Anker, Stefan D, Belenkov, Yuri, Gal, Tuvia B, Cohen-Solal, Alain, Böhm, Michael, Chioncel, Ovidiu, Jankowska, Ewa A, Gustafsson, Finn, Hill, Loreena, Jaarsma, Tiny, Januzzi, James L, Jhund, Pardeep, Lopatin, Yuri, Lund, Lars H, Metra, Marco, Milicic, Davor, Moura, Brenda, Mueller, Christian, Mullens, Wilfried, Núñez, Julio, Piepoli, Massimo F, Rakisheva, Amina, Ristic, Arsen, Rossignol, Patrick, Savarese, Gianluigi, Tocchetti, Carlo G, van Linthout, Sophie, Volterrani, Maurizio, Seferovic, Petar, Rosano, Giuseppe, Coats, Andrew J, Emdin, Michele, and Bayes-Genis, Antoni

Subjects
therapies, biomarker, heart failure, imaging, predictor, remodelling, ejection fraction, clinical
Abstract

In patients with heart failure (HF), the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Biomarker Study Group of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with HFrEF because most studies on cardiac remodelling focused on this setting.

Published
2022

5. Education and certification on heart failure of the Heart Failure Association of the European Society of Cardiology

Author

Mullens, Wilfried, Coats, Andrew J.S., Seferović, Petar M., Metra, Marco I., Mebazaa, Alexandre, Ruschitzka, Frank T., Filippatos, Gerasimos S., Volterrani, Maurizio, Ponikowski, Piotr P., Jankowska, Ewa Anita, Chioncel, Ovidiu, McDonagh, Theresa A., Piepoli, Massimo F., Milicic, Davor, Thum, Thomas, Hill, Loreena Michelle, Abdelhamid, Magdy, Adamopoulos, Stamatis, Belenkov, Yuri, Ben-Gal, Tuvia, Böhm, Michael, Cohen-Solal, Alain, Gustafsson, Finn, Jaarsma, Tiny, Moura, Brenda, Rakisheva, Amina, Ristic, Arsen D., Bayes-Genis, Antonio, Van Linthout, Sophia, Anker, Stefan D., Tocchetti, Carlo Gabriele, Lopatin, Yuri, Lund, Lars, Savarese, Gianluigi, Čelutkienė, Jelena, Cowie, Martin, Lambrinou, Ekaterini, Ray, Robin, Lainscak, Mitja, Skouri, Hadi, Wallner, Markus, Rosano, Giuseppe M C, Mullens, Wilfried, Coats, Andrew, Seferovic, Petar, Metra, Marco, Mebazaa, Alexandre, Ruschitzka, Frank, Filippatos, Gerasimo, Volterrani, Maurizio, Ponikowski, Piotr, Jankowska, Ewa A, Chioncel, Ovidiu, Mcdonagh, Theresa A, Piepoli, Massimo F, Milicic, Davor, Thum, Thoma, Hill, Loreena, Abdelhamid, Magdy, Adamopoulos, Stamati, Belenkov, Yuri, Gal, Tuvia Ben, Böhm, Michael, Cohen-Solal, Alain, Gustafsson, Finn, Jaarsma, Tiny, Moura, Brenda, Rakisheva, Amina, Ristic, Arsen, Bayes-Genis, Antonio, Van Linthout, Sophia, Anker, Stefan D, Tocchetti, Carlo Gabriele, Lopatin, Yury, Lund, Lar, Savarese, Gianluigi, Čelutkienė, Jelena, Cowie, Martin, Lambrinou, Ekaterini, Ray, Robin, Lainscak, Mitja, Skouri, Hadi, Wallner, Marku, and Rosano, Giuseppe M C

Subjects
Heart Failure, Certification, Europe, Humans, Societies, Medical, Cardiology, Quality of patient-centred, Heart failure, Medical and Health Sciences, Comprehensive educational programme, Medical, Quality of care centres, Clinical Medicine, Societies
Abstract

Heart failure (HF) is a devastating chronic and disabling disease with a wide variety of pharmaceutical and device treatment options which are becoming increasingly complex to implement. According to the Heart Failure Association (HFA) Atlas, a subspeciality resource aimed at sourcing contemporary data concerning the epidemiology and healthcare resources for HF, HF is prevalent in17.20 patients per1000 persons, accounting for 2671HFhospitalizations per million inhabitants annually in Europe.1HFpatients also suffer from a high prevalence of non-cardiac comorbidities, which adds complexity to their HF treatment and can negatively impact prognosis.2As a result, HF-related healthcare expenditure continues to rise, and healthcare organizations are becoming faced with the impossible challenge to provide the necessary financial and logistical support to this growing number of patients. In order to address these challenges, the HFA recently outlined the development of quality of care centres (QCC), in order to encourage multidisciplinary management of HF that will improve quality of care and survival.3However, there remains a significant unmet need to train sufficient multidisciplinary teams lead by HF specialists to take care of this expanding group of HF patients. In order to ensure that the next generation of medically-qualified HF specialists will receive high-quality training, this consensus statement of the HFA outlines the requirements for a European training and certification programme for such specialists. The primary goal of this comprehensive educational programme is to increase the quality of patient-centred care related to HF.

Published
2022

6. Cardiac Remodelling Part 1: From Cells and Tissues to Circulating Biomarkers

Author

Gonzalez A, Richards A, de Boer R, Thum T, Arfsten H, Hulsmann M, Falcao-Pires I, Diez J, Foo R, Chan M, Aimo A, Anene-Nzelu G, Abdelhamid M, Adamopoulos S, Anker S, Belenkov Y, Gal T, Cohen-Solal A, Bohm M, Chioncel O, Delgado V, Emdin M, Jankowska E, Gustafsson F, Hill L, Jaarsma T, Januzzi J, Jhund P, Lopatin Y, Lund L, Metra M, Milicic D, Moura B, Mueller C, Mullens W, Nunez J, Piepoli M, Rakisheva A, Ristic A, Rossignol P, Savarese G, Tocchetti C, Van Linthout S, Volterrani M, Seferovic P, Rosano G, Coats A, Bayes-Genis A, González, Arantxa, Richards, A Mark, de Boer, Rudolf A, Thum, Thoma, Arfsten, Henrike, Hülsmann, Martin, Falcao-Pires, Inê, Díez, Javier, Foo, Roger Sy, Chan, Mark Yan Yee, Aimo, Alberto, Anene-Nzelu, George C, Abdelhamid, Magdy, Adamopoulos, Stamati, Anker, Stefan D, Belenkov, Yuri, Gal, Tuvia B, Cohen-Solal, Alain, Böhm, Michael, Chioncel, Ovidiu, Delgado, Victoria, Emdin, Michele, Jankowska, Ewa A, Gustafsson, Finn, Hill, Loreena, Jaarsma, Tiny, Januzzi, James L, Jhund, Pardeep S, Lopatin, Yuri, Lund, Lars H, Metra, Marco, Milicic, Davor, Moura, Brenda, Mueller, Christian, Mullens, Wilfried, Núñez, Julio, Piepoli, Massimo F, Rakisheva, Amina, Ristic, Arsen, Rossignol, Patrick, Savarese, Gianluigi, Tocchetti, Carlo G, Van Linthout, Sophie, Volterrani, Maurizio, Seferovic, Petar, Rosano, Giuseppe, Coats, Andrew J, and Bayes-Genis, Antoni

Abstract

Cardiac remodelling refers to changes in left ventricular (LV) structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leukocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g., proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and many biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of review paper on biomarkers of cardiac remodelling. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Published
2022

7. The continuous heart failure spectrum: moving beyond an ejection fraction classification

Author

Gilles W. De Keulenaer, Robert O. Bonow, Nazha Hamdani, Filippos Triposkiadis, Johann Bauersachs, Richard T. Lee, Vincent F.M. Segers, Ida G. Lunde, Douglas L. Mann, John Parissis, Petros Nihoyannopoulos, Johannes Backs, Alexandre Mebazaa, Vijay K. Chopra, Stephane Heymans, Randall C. Starling, Javed Butler, Ajay M. Shah, Giuseppe M.C. Rosano, Christoph Maack, Alexander R. Lyon, Jean L. Rouleau, Jean Noel Trochu, Wolfgang A. Linke, Zoltán Papp, Rudolf A. de Boer, Marvin A. Konstam, Robert J. Mentz, Thomas Thum, Francois M. Abboud, Petar M. Seferović, Jean-Sébastien Hulot, Carlo G. Tocchetti, Stamatis Adamopoulos, Dirk L. Brutsaert, Faiez Zannad, Gerd Hasenfuss, John Atherton, Leon J. De Windt, Daniel Burkhoff, Paul W. Armstrong, Thierry Pedrazzini, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Triposkiadis, Filippo, Butler, Javed, Abboud, Francois M, Armstrong, Paul W, Adamopoulos, Stamati, Atherton, John J, Backs, Johanne, Bauersachs, Johann, Burkhoff, Daniel, Bonow, Robert O, Chopra, Vijay K, de Boer, Rudolf A, de Windt, Leon, Hamdani, Nazha, Hasenfuss, Gerd, Heymans, Stephane, Hulot, Jean-Sébastien, Konstam, Marvin, Lee, Richard T, Linke, Wolfgang A, Lunde, Ida G, Lyon, Alexander R, Maack, Christoph, Mann, Douglas L, Mebazaa, Alexandre, Mentz, Robert J, Nihoyannopoulos, Petro, Papp, Zoltan, Parissis, John, Pedrazzini, Thierry, Rosano, Giuseppe, Rouleau, Jean, Seferovic, Petar M, Shah, Ajay M, Starling, Randall C, Tocchetti, Carlo G, Trochu, Jean-Noel, Thum, Thoma, Zannad, Faiez, Brutsaert, Dirk L, Segers, Vincent F, and De Keulenaer, Gilles W

Subjects
Clinical Review, Ejection fraction, Cardiac & Cardiovascular Systems, [SDV]Life Sciences [q-bio], Disease, Comorbidity, 030204 cardiovascular system & hematology, EXERCISE CAPACITY, law.invention, Ventricular Dysfunction, Left, 0302 clinical medicine, Randomized controlled trial, law, Reference Values, Medicine, Myocytes, Cardiac, 030212 general & internal medicine, 1102 Cardiorespiratory Medicine and Haematology, OUTCOMES, Ventricular Remodeling, Stroke volume, ASSOCIATION, 3. Good health, PREVALENCE, VENTRICULAR-FUNCTION, Cardiology, Disease Progression, cardiovascular system, Cardiology and Cardiovascular Medicine, ECHOCARDIOGRAPHY, Life Sciences & Biomedicine, circulatory and respiratory physiology, medicine.medical_specialty, Heart failure, Pathophysiology, GLOBAL LONGITUDINAL STRAIN, 03 medical and health sciences, Internal medicine, CO-MORBIDITIES, Humans, cardiovascular diseases, Endothelium, Ventricular remodeling, Science & Technology, business.industry, Stroke Volume, medicine.disease, DYSFUNCTION, COMORBIDITIES, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, Human medicine, Endothelium, Vascular, business, Heart failure with preserved ejection fraction
Abstract

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.

Published
2021

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