. 2023 Apr 25;81(16):1569-1586.

doi: 10.1016/j.jacc.2023.02.039.

Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer

Alessia Lena¹, Ursula Wilkenshoff², Sara Hadzibegovic¹, Jan Porthun³, Lukas Rösnick⁴, Ann-Kathrin Fröhlich⁴, Tanja Zeller⁵, Mahir Karakas⁶, Ulrich Keller⁷, Johann Ahn⁸, Lars Bullinger⁹, Hanno Riess¹⁰, Stuart D Rosen¹¹, Alexander R Lyon¹², Thomas F Lüscher¹³, Matthias Totzeck¹⁴, Tienush Rassaf¹⁴, Daniel Burkhoff¹⁵, Mandeep R Mehra¹⁶, Jeroen J Bax¹⁷, Javed Butler¹⁸, Frank Edelmann¹⁹, Wilhelm Haverkamp²⁰, Stefan D Anker²⁰, Milton Packer²¹, Andrew J S Coats²², Stephan von Haehling²³, Ulf Landmesser²⁴, Markus S Anker²⁵

Affiliations

¹ Department of Cardiology, Angiology and Intensive Care Medicine Campus Benjamin Franklin, German Heart Center Charité, Berlin, Germany; Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany.
² Department of Cardiology, Angiology and Intensive Care Medicine Campus Benjamin Franklin, German Heart Center Charité, Berlin, Germany; Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; Berlin Institute of Health, Charité - University Medicine Berlin, Berlin, Germany.
³ Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; Department of Cardiology, Angiology and Intensive Care Medicine Campus Virchow Clinic, German Heart Center Charité, Berlin, Germany; Norwegian University of Science and Technology, Campus Gjøvik, Gjøvik, Norway.
⁴ Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany; Department of Cardiology, Angiology and Intensive Care Medicine Campus Virchow Clinic, German Heart Center Charité, Berlin, Germany.
⁵ University Center of Cardiovascular Science, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Clinic for Cardiology, University Heart and Vascular Centre Hamburg, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; German Centre for Cardiovascular Research, partner site HH/Kiel/HL, Hamburg, Germany.
⁶ German Centre for Cardiovascular Research, partner site HH/Kiel/HL, Hamburg, Germany; Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Hematology, Oncology and Cancer Immunology, Charité - University Medicine Berlin, Campus Benjamin-Franklin, Berlin, Germany; German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany; Max Delbrück Center, Berlin, Germany.
⁸ Department of Hematology, Oncology, and Tumor Immunology, Charité - University Medicine Berlin corporate member of Free University Berlin and Humboldt University Berlin, Berlin, Germany.
⁹ German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany; Department of Hematology, Oncology, and Tumor Immunology, Charité - University Medicine Berlin corporate member of Free University Berlin and Humboldt University Berlin, Berlin, Germany.
¹⁰ Department of Hematology, Oncology, and Tumor Immunology, Charité - University Medicine Berlin, Campus CCM, Berlin, Germany.
¹¹ Cardio-Oncology Service, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, United Kingdom; Heart Division, Royal Brompton & Harefield Hospitals, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
¹² Cardio-Oncology Service, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, United Kingdom.
¹³ Cardio-Oncology Service, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, United Kingdom; Heart Division, Royal Brompton & Harefield Hospitals, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland.
¹⁴ Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Essen, Germany.
¹⁵ Cardiovascular Research Foundation, New York, New York, USA.
¹⁶ Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts, USA.
¹⁷ Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Turku University, Turku, Finland.
¹⁸ Baylor Scott and White Research Institute, Dallas, Texas, USA; University of Mississippi, Jackson, Mississippi, USA.
¹⁹ Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health, Charité - University Medicine Berlin, Berlin, Germany; Department of Cardiology, Angiology and Intensive Care Medicine Campus Virchow Clinic, German Heart Center Charité, Berlin, Germany.
²⁰ German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany; Department of Cardiology Campus Virchow Clinic of German Heart Center Charité, Charité - University Medicine Berlin, Berlin, Germany.
²¹ Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas, USA.
²² Heart Research Institute, Sydney, New South Wales, Australia.
²³ Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany; German Centre for Cardiovascular Research, partner site Göttingen, Göttingen, Germany.
²⁴ Department of Cardiology, Angiology and Intensive Care Medicine Campus Benjamin Franklin, German Heart Center Charité, Berlin, Germany; Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health, Charité - University Medicine Berlin, Berlin, Germany.
²⁵ Department of Cardiology, Angiology and Intensive Care Medicine Campus Benjamin Franklin, German Heart Center Charité, Berlin, Germany; Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany. Electronic address: markus.anker@charite.de.

PMID: 37076211
DOI: 10.1016/j.jacc.2023.02.039

Free article

Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer

Alessia Lena et al. J Am Coll Cardiol. 2023.

Free article

. 2023 Apr 25;81(16):1569-1586.

doi: 10.1016/j.jacc.2023.02.039.

Authors

Affiliations

¹ Department of Cardiology, Angiology and Intensive Care Medicine Campus Benjamin Franklin, German Heart Center Charité, Berlin, Germany; Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany.
² Department of Cardiology, Angiology and Intensive Care Medicine Campus Benjamin Franklin, German Heart Center Charité, Berlin, Germany; Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; Berlin Institute of Health, Charité - University Medicine Berlin, Berlin, Germany.
³ Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; Department of Cardiology, Angiology and Intensive Care Medicine Campus Virchow Clinic, German Heart Center Charité, Berlin, Germany; Norwegian University of Science and Technology, Campus Gjøvik, Gjøvik, Norway.
⁴ Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany; Department of Cardiology, Angiology and Intensive Care Medicine Campus Virchow Clinic, German Heart Center Charité, Berlin, Germany.
⁵ University Center of Cardiovascular Science, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Clinic for Cardiology, University Heart and Vascular Centre Hamburg, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; German Centre for Cardiovascular Research, partner site HH/Kiel/HL, Hamburg, Germany.
⁶ German Centre for Cardiovascular Research, partner site HH/Kiel/HL, Hamburg, Germany; Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Hematology, Oncology and Cancer Immunology, Charité - University Medicine Berlin, Campus Benjamin-Franklin, Berlin, Germany; German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany; Max Delbrück Center, Berlin, Germany.
⁸ Department of Hematology, Oncology, and Tumor Immunology, Charité - University Medicine Berlin corporate member of Free University Berlin and Humboldt University Berlin, Berlin, Germany.
⁹ German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany; Department of Hematology, Oncology, and Tumor Immunology, Charité - University Medicine Berlin corporate member of Free University Berlin and Humboldt University Berlin, Berlin, Germany.
¹⁰ Department of Hematology, Oncology, and Tumor Immunology, Charité - University Medicine Berlin, Campus CCM, Berlin, Germany.
¹¹ Cardio-Oncology Service, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, United Kingdom; Heart Division, Royal Brompton & Harefield Hospitals, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
¹² Cardio-Oncology Service, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, United Kingdom.
¹³ Cardio-Oncology Service, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, United Kingdom; Heart Division, Royal Brompton & Harefield Hospitals, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom; Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland.
¹⁴ Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Essen, Germany.
¹⁵ Cardiovascular Research Foundation, New York, New York, USA.
¹⁶ Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts, USA.
¹⁷ Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Turku University, Turku, Finland.
¹⁸ Baylor Scott and White Research Institute, Dallas, Texas, USA; University of Mississippi, Jackson, Mississippi, USA.
¹⁹ Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health, Charité - University Medicine Berlin, Berlin, Germany; Department of Cardiology, Angiology and Intensive Care Medicine Campus Virchow Clinic, German Heart Center Charité, Berlin, Germany.
²⁰ German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany; Department of Cardiology Campus Virchow Clinic of German Heart Center Charité, Charité - University Medicine Berlin, Berlin, Germany.
²¹ Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas, USA.
²² Heart Research Institute, Sydney, New South Wales, Australia.
²³ Department of Cardiology and Pneumology, University of Göttingen Medical Center, Göttingen, Germany; German Centre for Cardiovascular Research, partner site Göttingen, Göttingen, Germany.
²⁴ Department of Cardiology, Angiology and Intensive Care Medicine Campus Benjamin Franklin, German Heart Center Charité, Berlin, Germany; Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health, Charité - University Medicine Berlin, Berlin, Germany.
²⁵ Department of Cardiology, Angiology and Intensive Care Medicine Campus Benjamin Franklin, German Heart Center Charité, Berlin, Germany; Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Centre for Cardiovascular Research, partner site Berlin, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany. Electronic address: markus.anker@charite.de.

PMID: 37076211
DOI: 10.1016/j.jacc.2023.02.039

Abstract

Background: Body wasting in patients with cancer can affect the heart.

Objectives: The frequency, extent, and clinical and prognostic importance of cardiac wasting in cancer patients is unknown.

Methods: This study prospectively enrolled 300 patients with mostly advanced, active cancer but without significant cardiovascular disease or infection. These patients were compared with 60 healthy control subjects and 60 patients with chronic heart failure (ejection fraction <40%) of similar age and sex distribution.

Results: Cancer patients presented with lower left ventricular (LV) mass than healthy control subjects or heart failure patients (assessed by transthoracic echocardiography: 177 ± 47 g vs 203 ± 64 g vs 300 ± 71 g, respectively; P < 0.001). LV mass was lowest in cancer patients with cachexia (153 ± 42 g; P < 0.001). Importantly, the presence of low LV mass was independent of previous cardiotoxic anticancer therapy. In 90 cancer patients with a second echocardiogram after 122 ± 71 days, LV mass had declined by 9.3% ± 1.4% (P < 0.001). In cancer patients with cardiac wasting during follow-up, stroke volume decreased (P < 0.001) and resting heart rate increased over time (P = 0.001). During follow-up of on average 16 months, 149 patients died (1-year all-cause mortality 43%; 95% CI: 37%-49%). LV mass and LV mass adjusted for height squared were independent prognostic markers (both P < 0.05). Adjustment of LV mass for body surface area masked the observed survival impact. LV mass below the prognostically relevant cutpoints in cancer was associated with reduced overall functional status and lower physical performance.

Conclusions: Low LV mass is associated with poor functional status and increased all-cause mortality in cancer. These findings provide clinical evidence of cardiac wasting-associated cardiomyopathy in cancer.

Keywords: cancer; cardiac wasting–associated cardiomyopathy; cardiology; echocardiography; left ventricular mass.

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Conflict of interest statement

Funding Support and Author Disclosures This study was partly funded by the German Centre for Cardiovascular Research through research support to Dr Hadzibegovic, Dr S. Anker, and Dr M. Anker. Dr Wilkenshoff is supported by a Clinical Fellowship Grant from the Berlin Institute of Health; and has received speaker fees and/or contributions to congresses from Abbott, AstraZeneca, Bayer, Berlin Chemie, Bristol Myers Squibb, GE Healthcare, Pfizer, Philips, and Servier, all outside the submitted work. Dr Zeller has received support from the German Centre for Cardiovascular Research (FKZ 81Z1710101 and FKZ 81Z0710102). Dr Karakas is supported by a Clinician Scientist Professorship Grant from the Else Kroener-Fresenius-Foundation; and has received personal fees and grant support from Daiichi-Sankyo, Adrenomed, Sphingotec, and Vifor Pharma, all outside the submitted work. Dr Keller has served on advisory boards for Roche, Janssen-Cilag, Celgene, Takeda, Bristol Myers Squibb, Gilead, Hexal, Pfizer, AstraZeneca, and Pentixapharm; has received clinical research support from Janssen-Cilag, Novartis, Takeda, Bristol Myers Squibb, Roche, and Pfizer; and has received travel support from Roche, Bristol Myers Squibb, Gilead, Takeda, Janssen-Cilag, and Celgene. Dr Bullinger has received honoraria from AbbVie, Amgen, Astellas, Bristol Myers Squibb, Celgene, Daiichi-Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Roche, Sanofi, and Seattle Genetics; and has received research support from Bayer and Jazz Pharmaceuticals. Dr Lyon has received support from the Fondation Leducq Transatlantic Network of Excellence in Cardio-Oncology; and has received speaker, advisory board, or consulting fees and/or research grants from Pfizer, Novartis, Servier, Amgen, Takeda, Roche, Janssens-Cilag, Clinigen, Eli Lilly, Eisai, Bristol Myers Squibb, Ferring Pharmaceuticals, Boehringer Ingelheim, Myocardial Solutions, iOWNA Health, and Heartfelt Technologies. Dr Lüscher has received educational and research grants from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Sanofi, Servier, and Vifor; and has received consulting honoraria from Amgen, COR2ED, Daiichi-Sankyo, and Pfizer, outside this work. Dr Totzeck has received honoraria, lecture fees, and grant support from Edwards Lifesciences, AstraZeneca, Bayer, Novartis, Berlin Chemie, and Daiicho-Sankyo, all unrelated to this work. Dr Rassaf has received honoraria, lecture fees, and grant support from Edwards Lifesciences, AstraZeneca, Bayer, Novartis, Berlin Chemie, Daiicho-Sankyo, Boehringer Ingelheim, Novo Nordisk, Cardiac Dimensions, and Pfizer, all unrelated to this work. Dr Burkhoff has received consulting fees from AquaPass, Axon Medical, BioMind, CardioDyme, Corvia Medical, IMPULSE Dynamics, Orchestra Biomedical, PVLoops, and Zoll, all unrelated to the present work. Dr Mehra has received payments from Abbott to his institution for consulting; has received consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and Baim Institute for Clinical Research; and serves on the advisory board of NuPulseCV, Leviticus, Transmedics, and FineHeart. Dr Bax has received unrestricted research grants to his institution from Edwards Lifesciences, Abbott, Medtronic, Biotronik, and Boston Scientific; and has received personal speaker fees from Abbott and Edwards Lifesciences. Dr Butler has received personal fees from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Roche, and Vifor. Dr S. Anker has received grants and personal fees from Vifor and Abbott Vascular; and has received personal fees for consulting, trial committee work, and/or lectures from Actimed, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bioventrix, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards Lifesciences, Faraday, Impulse Dynamics, Janssen, Novartis, Occlutech, Pfizer, Respicardia, Servier, Vectorious, and V-Wave, all outside the submitted work; and is named co-inventor of 2 patent applications regarding MR-proANP (DE 102007010834 & DE 102007022367), but does not benefit personally from the related issued patents. Dr Packer has served as a consultant for AbbVie, Actavis, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Eli Lilly, Moderna, Novartis, Reata, Relypsa, and Salamandra. Dr Coats has received honoraria and/or speaker fees from AstraZeneca, Boehringer Ingelheim, Menarini, Novartis, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, Respicardia, and Viatris. Dr von Haehling has received consulting fees and/or honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Brahms, Chugai, Grünenthal, Helsinn, Hexal, Novartis, Pharmacosmos, Respicardia, Roche, Servier, Sorin, and Vifor; and has received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Innovative Medicines Initiative, and the German Centre for Cardiovascular Research. Dr Landmesser has received institutional research grants from Amgen, Bayer, and Novartis; and has received speaker or consulting honoraria from AstraZeneca, Bayer, Boehringer, Amgen, Sanofi, Novartis, and Novo Nordisk. Dr M. Anker has received personal fees from Servier, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Comment in

New Insights Into Cardiac Wasting in Patients With Cancer.
Asnani A. Asnani A. J Am Coll Cardiol. 2023 Apr 25;81(16):1587-1589. doi: 10.1016/j.jacc.2023.02.035. J Am Coll Cardiol. 2023. PMID: 37076212 No abstract available.

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Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer

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Clinical and Prognostic Relevance of Cardiac Wasting in Patients With Advanced Cancer

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