{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:44:09Z","timestamp":1790790249648,"version":"4.1.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Cardiac amyloidosis (CA) is a myocardial disease characterized by extracellular amyloid infiltration throughout the heart, resulting in increased myocardial stiffness, and restrictive heart wall chamber behavior. Its diagnosis among patients hospitalized for cardiovascular diseases is becoming increasingly frequent, suggesting improved disease awareness, and higher diagnostic capacities. One predominant functional manifestation of patients with CA is exercise intolerance, objectified by reduced peak oxygen uptake (VO<jats:sub>2<\/jats:sub> peak), and assessed by metabolic cart during cardiopulmonary exercise testing (CPET). Hemodynamic adaptation to exercise in patients with CA is characterized by low myocardial contractile reserve and impaired myocardial efficiency. Rapid shallow breathing and hyperventilation, in the absence of ventilatory limitation, are also typically observed in response to exercise. Ventilatory inefficiency is further suggested by an increased VE-VCO2 slope, which has been attributed to excessive sympathoexcitation and a high physiological dead space (VD\/VT) ratio during exercise. Growing evidence now suggests that, in addition to well-established biomarker risk models, a reduced VO<jats:sub>2<\/jats:sub> peak is potentially a strong and independent predictive factor of adverse patient outcomes, both for monoclonal immunoglobulin light chain (AL) or transthyretin (ATTR) CA. Besides generating prognostic information, CPET can be used for the evaluation of the impact of therapeutic interventions in patients with CA.<\/jats:p>","DOI":"10.3389\/fcvm.2022.898033","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T06:24:52Z","timestamp":1654496692000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Diagnostic and Prognostic Values of Cardiopulmonary Exercise Testing in Cardiac Amyloidosis"],"prefix":"10.3389","volume":"9","author":[{"given":"Rishika","family":"Banydeen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Monfort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn","family":"Inamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi","family":"Neviere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1016\/S0140-6736(15)01274-X","article-title":"Systemic amyloidosis.","volume":"387","author":"Wechalekar","year":"2016","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"crossref","first-page":"101106","DOI":"10.1016\/j.cpcardiol.2022.101106","article-title":"Diagnostic tools for cardiac amyloidosis: a pragmatic comparison of pathology, imaging and laboratories.","author":"Joury","year":"2022","journal-title":"Curr Probl Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1080\/13506129.2018.1496077","article-title":"Peak V\u2019O2 is an independent predictor of survival in patients with cardiac amyloidosis.","volume":"25","author":"Hein","year":"2018","journal-title":"Amyloid."},{"key":"B4","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/ejhf.2016","article-title":"Prognostic value of cardiopulmonary exercise testing in cardiac amyloidosis.","volume":"23","author":"Nicol","year":"2021","journal-title":"Eur J Heart Fail."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/j.cardfail.2021.06.022","article-title":"Prognostic role of cardiopulmonary exercise testing in wild-type transthyretin amyloid cardiomyopathy patients treated with tafamidis.","volume":"27","author":"Dalia","year":"2021","journal-title":"J Card Fail."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2102838","DOI":"10.1183\/13993003.02838-2021","article-title":"Restrictive spirometry pattern and abnormal cardiopulmonary response to exercise in transthyretin cardiac amyloidosis.","volume":"59","author":"Banydeen","year":"2022","journal-title":"Eur Respir J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1161\/CIRCRESAHA.121.318187","article-title":"Pathophysiology and therapeutic approaches to cardiac amyloidosis.","volume":"128","author":"Griffin","year":"2021","journal-title":"Circ Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e006075","DOI":"10.1161\/CIRCHEARTFAILURE.119.006075","article-title":"Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis.","volume":"12","author":"Maurer","year":"2019","journal-title":"Circ Heart Fail."},{"key":"B9","doi-asserted-by":"publisher","first-page":"751293","DOI":"10.3389\/fcvm.2021.751293","article-title":"Cardiac amyloidosis: a review of current imaging techniques.","volume":"8","author":"Razvi","year":"2021","journal-title":"Front Cardiovasc Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1002\/ejhf.899","article-title":"Inotropic myocardial reserve deficiency is the predominant feature of exercise haemodynamics in cardiac amyloidosis.","volume":"19","author":"Clemmensen","year":"2017","journal-title":"Eur J Heart Fail."},{"key":"B11","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.echo.2017.09.007","article-title":"Abnormal coronary flow velocity reserve and decreased myocardial contractile reserve are main factors in relation to physical exercise capacity in cardiac amyloidosis.","volume":"31","author":"Clemmensen","year":"2018","journal-title":"J Am Soc Echocardiogr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e009974","DOI":"10.1161\/JAHA.118.009974","article-title":"Myocardial oxygen consumption and efficiency in patients with cardiac amyloidosis.","volume":"7","author":"Clemmensen","year":"2018","journal-title":"J Am Heart Assoc."},{"key":"B13","doi-asserted-by":"publisher","first-page":"4611","DOI":"10.3390\/molecules26154611","article-title":"The ultrastructure of tissue damage by amyloid fibrils.","volume":"26","author":"Koike","year":"2021","journal-title":"Molecules."},{"key":"B14","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.ijcard.2018.05.018","article-title":"Therapies for cardiac light chain amyloidosis: an update.","volume":"271","author":"Aimo","year":"2018","journal-title":"Int J Cardiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3390\/ijms23010025","article-title":"Molecular mechanisms of cardiac amyloidosis.","volume":"23","author":"Saito","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12931-021-01895-6","article-title":"Practical guide to cardiopulmonary exercise testing in adults.","volume":"23","author":"Glaab","year":"2022","journal-title":"Respir Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1164\/rccm.167.2.211.1451-2","article-title":"ATS\/ACCP statement on cardiopulmonary exercise testing. Erratum in: Am J Respir Crit Care Med. (2003).","volume":"167","year":"2003","journal-title":"Am J Respir Crit Care Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/clc.4960140317","article-title":"A case of cardiac amyloidosis presenting with symptoms of exertional syncope.","volume":"14","author":"Fujii","year":"1991","journal-title":"Clin Cardiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/s0002-9149(99)00497-x","article-title":"Comparison of usefulness between exercise capacity and echocardiographic indexes of left ventricular function in cardiac amyloidosis.","volume":"84","author":"Trikas","year":"1999","journal-title":"Am J Cardiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.amjcard.2019.03.035","article-title":"Use of ventilatory efficiency slope as a marker for increased mortality in wild-type transthyretin cardiac amyloidosis.","volume":"124","author":"Yunis","year":"2019","journal-title":"Am J Cardiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/s11739-020-02474-1","article-title":"Poor right ventricular function is associated with impaired exercise capacity and ventilatory efficiency in transthyretin cardiac amyloid patients.","volume":"16","author":"Bartolini","year":"2021","journal-title":"Intern Emerg Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1080\/13506129.2020.1722098","article-title":"Restrictive cardiac phenotype as primary cause of impaired aerobic capacity in Afro-Caribbean patients with val122ile variant transthyretin amyloid cardiomyopathy.","volume":"27","author":"Monfort","year":"2020","journal-title":"Amyloid."},{"key":"B23","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.clml.2021.03.015","article-title":"Cardiopulmonary exercise testing in patients with cardiac amyloidosis.","volume":"21","author":"Bhutani","year":"2021","journal-title":"Clin Lymphoma Myeloma Leuk."},{"key":"B24","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1080\/13506129.2019.1582024","article-title":"Chronotropic incompetence and autonomic dysfunction as mechanisms of dyspnoea in patients with late stage cardiac amyloidosis.","volume":"26","author":"Nativi-Nicolau","year":"2019","journal-title":"Amyloid."},{"key":"B25","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1007\/s10741-013-9407-6","article-title":"Aerobic exercise effect on prognostic markers for systolic heart failure patients: a systematic review and meta-analysis.","volume":"19","author":"Cipriano","year":"2014","journal-title":"Heart Fail Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.jchf.2016.03.022","article-title":"Cardiopulmonary exercise testing in heart failure.","volume":"4","author":"Malhotra","year":"2016","journal-title":"JACC Heart Fail."},{"key":"B27","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.cpcardiol.2015.01.009","article-title":"Cardiopulmonary exercise testing in heart failure.","volume":"40","author":"Myers","year":"2015","journal-title":"Curr Probl Cardiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s10741-007-9067-5","article-title":"The clinical and research applications of aerobic capacity and ventilatory efficiency in heart failure: an evidence-based review.","volume":"13","author":"Arena","year":"2008","journal-title":"Heart Fail Rev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1007\/s11897-013-0183-3","article-title":"Abnormalities in cardiopulmonary exercise testing ventilatory parameters in heart failure: pathophysiology and clinical usefulness.","volume":"11","author":"Guazzi","year":"2014","journal-title":"Curr Heart Fail Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"659","DOI":"10.3389\/fphys.2020.00659","article-title":"Measurement and interpretation of exercise ventilatory efficiency.","volume":"11","author":"Phillips","year":"2020","journal-title":"Front Physiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1700860","DOI":"10.1183\/13993003.00860-2017","article-title":"Ventilatory response to exercise in cardiopulmonary disease: the role of chemosensitivity and dead space.","volume":"51","author":"Weatherald","year":"2018","journal-title":"Eur Respir J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.cardfail.2010.05.003","article-title":"Causes of breathing inefficiency during exercise in heart failure.","volume":"16","author":"Woods","year":"2010","journal-title":"J Card Fail."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1016\/j.jcmg.2016.07.008","article-title":"Cardiac dysautonomia predicts long-term survival in hereditary transthyretin amyloidosis after liver transplantation.","volume":"9","author":"Algalarrondo","year":"2016","journal-title":"JACC Cardiovasc Imaging."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/j.jcmg.2016.08.003","article-title":"Cardiac dysautonomia and survival in hereditary transthyretin amyloidosis.","volume":"9","author":"Goldstein","year":"2016","journal-title":"JACC Cardiovasc Imaging."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1553","DOI":"10.3390\/cells9061553","article-title":"Amyloid proteins and peripheral neuropathy.","volume":"9","author":"Asiri","year":"2020","journal-title":"Cells."},{"key":"B36","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1055\/s-0039-1688994","article-title":"Neuropathy associated with systemic amyloidosis.","volume":"39","author":"Kaku","year":"2019","journal-title":"Semin Neurol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s10286-018-0514-2","article-title":"Autonomic involvement in hereditary transthyretin amyloidosis (hATTR amyloidosis).","volume":"29","author":"Gonzalez-Duarte","year":"2019","journal-title":"Clin Auton Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1080\/13506129.2019.1582023","article-title":"Cardiac and peripheral vasomotor autonomic functions in hereditary transthyretin amyloidosis with non-Val30Met mutation.","volume":"26","author":"Koike","year":"2019","journal-title":"Amyloid."},{"key":"B39","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/eurheartj\/ehz173","article-title":"THAOS Investigators. Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS).","volume":"43","author":"Damy","year":"2019","journal-title":"Eur Heart J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"200355","DOI":"10.1183\/16000617.0355-2020","article-title":"Cardiopulmonary exercise testing in interstitial lung diseases and the value of ventilatory efficiency.","volume":"30","author":"Gille","year":"2021","journal-title":"Eur Respir Rev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"911","DOI":"10.3390\/jcm11040911","article-title":"Physiology, diagnosis and treatment of cardiac light chain amyloidosis.","volume":"11","author":"Stelmach-Go\u0142dy\u015b","year":"2022","journal-title":"J Clin Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41408-020-0306-5","article-title":"A validated composite organ and hematologic response model for early assessment of treatment outcomes in light chain amyloidosis.","volume":"10","author":"Sidana","year":"2020","journal-title":"Blood Cancer J."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00683-z","article-title":"RNA-targeting and gene editing therapies for transthyretin amyloidosis.","author":"Aimo","year":"2022","journal-title":"Nat Rev Cardiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1056\/NEJMoa1805689","article-title":"Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy.","volume":"379","author":"Maurer","year":"2018","journal-title":"N Engl J Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"jeab226","DOI":"10.1093\/ehjci\/jeab226","article-title":"Tafamidis treatment delays structural and functional changes of the left ventricle in patients with transthyretin amyloid cardiomyopathy.","author":"Rettl","year":"2021","journal-title":"Eur Heart J Cardiovasc Imaging."},{"key":"B46","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1080\/13506129.2019.1685487","article-title":"Inotersen therapy of transthyretin amyloid cardiomyopathy.","volume":"27","author":"Dasgupta","year":"2020","journal-title":"Amyloid."},{"key":"B47","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/S1474-4422(20)30368-9","article-title":"Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study.","volume":"20","author":"Adams","year":"2021","journal-title":"Lancet Neurol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1056\/NEJMoa1716793","article-title":"Inotersen treatment for patients with hereditary transthyretin amyloidosis.","volume":"379","author":"Benson","year":"2018","journal-title":"N Engl J Med."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.898033\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T06:24:55Z","timestamp":1654496695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.898033\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,6]]},"references-count":48,"alternative-id":["10.3389\/fcvm.2022.898033"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.898033","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,6]]},"article-number":"898033"}}