{
  "abstract": "Background Current guidelines recommend evaluating patients with ambulatory heart failure (HF) for heart transplantation if their peak oxygen consumption (peak VO 2) is <12 mL/kg/min. However, these recommendations are based on decades-old data.Methods We retrospectively analysed 8060 patients with ambulatory HF with cardiopulmonary exercise testing (CPET) data. The primary analysis focused on 1218 patients with left ventricular ejection fraction <40% and peak VO 2 <12 mL/kg/min, enrolled between 2010 and 2022. Survival outcomes (composite of death/left ventricular assist device/heart transplantation) were compared with those of heart transplantation recipients from the International Society for Heart and Lung Transplantation registry. Patients were stratified by ventilatory efficiency (ventilation versus CO2 production slope (VE/VCO2) >34 vs ≤34) and presence of exercise oscillatory ventilation. Survival analyses were performed using Kaplan-Meier curves compared with log-rank tests and Cox proportional hazards models, with heart transplantation survival curves reconstructed from aggregate data.Results Patients with peak VO 2 <12 mL/kg/min demonstrated better survival than heart transplantation recipients, with survival curves intersecting at approximately 2.7 years. Among those with VE/VCO2 ≤34, 10-year mortality risk was halved (p<0.01), with survival curves crossing those of heart transplantation recipients around year 4. Absence of exercise oscillatory ventilation was similarly associated with a 50% lower long-term mortality. Combining VE/VCO2 and exercise oscillatory ventilation identified four distinct risk groups with significantly different 10-year outcomes (p<0.01). Patients with peak VO2 <12 mL/kg/min, VE/VCO2 ≤34 and no exercise oscillatory ventilation exhibited survival comparable to heart transplantation recipients at year 5.Conclusions In contemporary practice, a peak VO 2 <12 mL/kg/min alone may not reliably identify patients with HF with sufficiently high short-term mortality to warrant heart transplantation referral. VE/VCO2 and exercise oscillatory ventilation provide important additional risk stratification, supporting re-evaluation of transplant referral criteria to reflect improved HF management and outcomes.",
  "authors": [
    {
      "affiliations": [
        "Division of Cardiology, Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"
      ],
      "name": "Maryam Azar"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy"
      ],
      "name": "Anna Apostolo"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy"
      ],
      "name": "Elisabetta Salvioni"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy"
      ],
      "name": "Arianna Galotta"
    },
    {
      "affiliations": [
        "Health Science Interdisciplinary Center, Scuola Superiore Sant’Anna, Pisa, Italy",
        "Cardio-Thoracic Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy"
      ],
      "name": "Michele Emdin"
    },
    {
      "affiliations": [
        "Clinical Cardiology, IRCCS Policlinico San Donato, Milan, Italy",
        "Department of Biomedical Sciences for Health, University of Milan, Milan, Italy"
      ],
      "name": "Massimo Piepoli"
    },
    {
      "affiliations": [
        "Cardiovascular Diseases Unit, Cardio Thoracic and Vascular Department, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy"
      ],
      "name": "Alberto Palazzuoli"
    },
    {
      "affiliations": [
        "Cardiovascular Department, “Azienda Sanitaria Universitaria Giuliano-Isontina”, Trieste, Italy"
      ],
      "name": "Gianfranco Sinagra"
    },
    {
      "affiliations": [
        "Department of Clinical and Molecular Medicine, Azienda Ospedaliera Sant’Andrea, “Sapienza” Università degli Studi di Roma, Roma, Italy"
      ],
      "name": "Damiano Magrì"
    },
    {
      "affiliations": [
        "Dipartimento di scienze biomediche avanzate, Federico II University, Naples, Italy"
      ],
      "name": "Stefania Paolillo"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy",
        "Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy"
      ],
      "name": "Massimo Mapelli"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy",
        "Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy"
      ],
      "name": "Jeness Campodonico"
    },
    {
      "affiliations": [
        "Cardiology Department, Istituti Clinici Scientifici Maugeri, IRCCS, Veruno Institute, Veruno, Italy"
      ],
      "name": "Ugo Corrà"
    },
    {
      "affiliations": [
        "U.O. Prevenzione e Riabilitazione cardiovascolare, I.R.C.C.S. Ospedale San Raffaele, Milano, Italy"
      ],
      "name": "Rosa Raimondo"
    },
    {
      "affiliations": [
        "Department of Translational Medical Sciences, Federico II University, Naples, Italy",
        "Interdepartmental centre for gender medicine research ‘GENESIS’, University of Naples Federico II, Naples, Italy"
      ],
      "name": "Antonio Cittadini"
    },
    {
      "affiliations": [
        "Cardiovascular Department, Cardiology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy"
      ],
      "name": "Annamaria Iorio"
    },
    {
      "affiliations": [
        "Department of Translational Medical Sciences, Federico II University, Naples, Italy",
        "Interdepartmental centre for gender medicine research ‘GENESIS’, University of Naples Federico II, Naples, Italy",
        "Cardiac Unit, AORN A Cardarelli, Naples, Italy"
      ],
      "name": "Andrea Salzano"
    },
    {
      "affiliations": [
        "Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari, “Sapienza”, Rome University, Rome, Italy"
      ],
      "name": "Roberto Badagliacca"
    },
    {
      "affiliations": [
        "Cardiovascular Department, Cardiology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy"
      ],
      "name": "Michele Senni"
    },
    {
      "affiliations": [
        "Department of Advanced Biomedical Sciences, Federico II University of Naples and Mediterranea CardioCentro, Naples, Italy"
      ],
      "name": "Pasquale Perrone-Filardi"
    },
    {
      "affiliations": [
        "Department of Cardiology, University of Foggia, Foggia, Italy"
      ],
      "name": "Michele Correale"
    },
    {
      "affiliations": [
        "Dipartimento cardio-toraco-vascolare, Ospedale Cà Granda- A.O. Niguarda, Milano, Italy"
      ],
      "name": "Enrico Perna"
    },
    {
      "affiliations": [
        "Cardiology, Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"
      ],
      "name": "Marco Metra"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy",
        "Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy"
      ],
      "name": "Carlo Vignati"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy"
      ],
      "name": "Mauro C Contini"
    },
    {
      "affiliations": [
        "Cardiovascular Department, “Azienda Sanitaria Universitaria Giuliano-Isontina”, Trieste, Italy"
      ],
      "name": "Nikita Baracchini"
    },
    {
      "affiliations": [
        "Unità Operativa Cardiologia Riabilitativa, IRCCS Multimedica, Milano, Italy"
      ],
      "name": "Gaia Cattadori"
    },
    {
      "affiliations": [
        "Department of Cardiology, San Paolo Hospital, University of Milano School of Medicine, Milano, Italy"
      ],
      "name": "Marco Guazzi"
    },
    {
      "affiliations": [
        "Cardiologia SUN, Ospedale Monaldi (Azienda dei Colli), Seconda Università di Napoli, Napoli, Italy"
      ],
      "name": "Giuseppe Limongelli"
    },
    {
      "affiliations": [
        "Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Istituto Auxologico Italiano, IRCCS, Milan, Italy",
        "Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy"
      ],
      "name": "Gianfranco Parati"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy"
      ],
      "name": "Beatrice Pezzuto"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy"
      ],
      "name": "Robin Willixhofer"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy"
      ],
      "name": "Pietro Palermo"
    },
    {
      "affiliations": [
        "Cardiac Intensive Care Unit-Cardiology Division, Cardiovascular Department, Ospedali Riuniti di Ancona, Ancona, Italy"
      ],
      "name": "Maria Vittoria Matassini"
    },
    {
      "affiliations": [
        "Department of Biomedical Sciences for Health, University of Milan, Milan, Italy",
        "Department of Cardiology, IRCCS Multimedica, Milano, Italy"
      ],
      "name": "Francesco Bandera"
    },
    {
      "affiliations": [
        "Cardiac Rehabilitation Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Scientific Institute of Milan, Milan, Italy"
      ],
      "name": "Maurizio Bussotti"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy",
        "Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy",
        "Doctoral School in Translational Medicine, University of Milan, Milan, Italy"
      ],
      "name": "Ermes Carulli"
    },
    {
      "affiliations": [
        "Cardiology Division, Cardiac Arrhythmia Center and Cardiomyopathies Unit, San Camillo-Forlanini Hospital, Roma, Italy"
      ],
      "name": "Federica Re"
    },
    {
      "affiliations": [
        "Cardiology Division, Santo Spirito Hospital, Roma, Italy"
      ],
      "name": "Angela Beatrice Scardovi"
    },
    {
      "affiliations": [
        "Department of Advanced Biomedical Sciences, Federico II University of Naples and Mediterranea CardioCentro, Naples, Italy"
      ],
      "name": "Susanna Sciomer"
    },
    {
      "affiliations": [
        "Division of Cardiology, Istituti Clinici Scientifici Maugeri, IRCCS, Institute of Bari, Bari, Italy"
      ],
      "name": "Andrea Passantino"
    },
    {
      "affiliations": [
        "Centro Medico Chiasso Mendrisio, Mendrisio, Switzerland"
      ],
      "name": "Davide Girola"
    },
    {
      "affiliations": [
        "Health Science Interdisciplinary Center, Scuola Superiore Sant’Anna, Pisa, Italy"
      ],
      "name": "Claudio Passino"
    },
    {
      "affiliations": [
        "Division of Cardiology, Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"
      ],
      "name": "Luigi Adamo"
    },
    {
      "affiliations": [
        "Centro Cardiologico Monzino, IRCCS, Milan, Italy",
        "Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy"
      ],
      "name": "Piergiuseppe Agostoni"
    },
    {
      "affiliations": [],
      "name": "on behalf of MECKI score research group"
    }
  ],
  "title": "Cardiopulmonary exercise test criteria for heart transplantation referral of patients with ambulatory heart failure in the current era",
  "uid": "b19ae8a2-8319-5256-9580-69aac46a871f"
}