{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:44:29Z","timestamp":1790790269271,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease that often results in heart failure and death. Traditionally, biological staging systems are used to stratify disease severity. Reduced aerobic capacity has recently been described as useful in identifying higher risk of cardiovascular events and death. Assessment of lung volume via simple spirometry might also hold prognostic relevance. We aimed to assess the combined prognostic value of spirometry, cardiopulmonary exercise testing (CPET) and biomarker staging in ATTR-CA patients in a multi-parametric approach. We retrospectively reviewed patient records with pulmonary function and CPET testing. Patients were followed until study endpoint (MACE: composite of heart-failure-related hospitalization and all-cause death) or censure (1 April 2022). In total, 82 patients were enrolled. Median follow-up was 9 months with 31 (38%) MACE. Impaired peak VO2 and forced vital capacity (FVC) were independent predictors of MACE-free survival, with peak VO2 &lt; 50% and FVC &lt; 70% defining the highest risk group (HR 26, 95% CI: 5\u2013142, mean survival: 15 months) compared to patients with the lowest risk (peak VO2 \u2265 50% and FVC \u2265 70%). Combined peak VO2, FVC and ATTR biomarker staging significantly improved MACE prediction by 35% compared to ATTR staging alone, with 67% patients reassigned a higher risk category (p &lt; 0.01). In conclusion, combining functional and biological markers might synergistically improve risk stratification in ATTR-CA. Integrating simple, non-invasive and easily applicable CPET and spirometry in the routine management of ATTR-CA patients might prove useful for improved risk prediction, optimized monitoring and timely introduction of newer-generation therapies.<\/jats:p>","DOI":"10.3390\/jcm12113684","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T02:00:19Z","timestamp":1685066419000},"page":"3684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Risk Stratification in Transthyretin Cardiac Amyloidosis: The Added Value of Lung Spirometry"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8237-190X","authenticated-orcid":false,"given":"Rishika","family":"Banydeen","sequence":"first","affiliation":[{"name":"Department of Clinical Research, CHU Martinique (University Hospital of Martinique), 97200 Fort de France, France"},{"name":"Cardiovascular Research Team EA7525, Universit\u00e9 des Antilles (University of the French West Indies), 97200 Fort de France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6614-5021","authenticated-orcid":false,"given":"Reid","family":"Eggleston","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Deney","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rangueil Hospital, CHU Toulouse (University Hospital of Toulouse), 31400 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Monfort","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Team EA7525, Universit\u00e9 des Antilles (University of the French West Indies), 97200 Fort de France, France"},{"name":"Department of Cardiology, CHU Martinique (University Hospital of Martinique), 97200 Fort de France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9576-2272","authenticated-orcid":false,"given":"Jay H.","family":"Ryu","sequence":"additional","affiliation":[{"name":"Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Vergaro","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-2328","authenticated-orcid":false,"given":"Vincenzo","family":"Castiglione","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e di Sanita Pubblica, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-6582","authenticated-orcid":false,"given":"Olivier","family":"Lairez","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rangueil Hospital, CHU Toulouse (University Hospital of Toulouse), 31400 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Emdin","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, ScuolaSuperioreSant\u2019Anna, Pisa, Italy & Fondazione Toscana Gabriele Monasterio, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1057-9699","authenticated-orcid":false,"given":"Jocelyn","family":"Inamo","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Team EA7525, Universit\u00e9 des Antilles (University of the French West Indies), 97200 Fort de France, France"},{"name":"Department of Cardiology, CHU Martinique (University Hospital of Martinique), 97200 Fort de France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misbah","family":"Baqir","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7966-0110","authenticated-orcid":false,"given":"Remi","family":"Neviere","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Team EA7525, Universit\u00e9 des Antilles (University of the French West Indies), 97200 Fort de France, France"},{"name":"Department of Cardiology, CHU Martinique (University Hospital of Martinique), 97200 Fort de France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1001\/jama.2020.5493","article-title":"Systemic Amyloidosis Recognition, Prognosis, and Therapy: A Systematic Review","volume":"324","author":"Gertz","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/ejhf.2198","article-title":"Expert consensus on the monitoring of transthyretin amyloid cardiomyopathy","volume":"23","author":"Bengel","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/ejhf.2113","article-title":"Use of biomarkers to diagnose and manage cardiac amyloidosis","volume":"23","author":"Castiglione","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1002\/ejhf.2606","article-title":"Progression of echocardiographic parameters and prognosis in transthyretin cardiac amyloidosis","volume":"24","author":"Chacko","year":"2022","journal-title":"Eur. J. Heart Fail."},{"key":"ref_5","doi-asserted-by":"crossref","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":"ref_6","doi-asserted-by":"crossref","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":"ref_7","doi-asserted-by":"crossref","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":"ref_8","doi-asserted-by":"crossref","first-page":"106761","DOI":"10.1016\/j.rmed.2022.106761","article-title":"Clinical, radiologic, and pathologic features and outcomes of pulmonary transthyretin amyloidosis","volume":"194","author":"Eggleston","year":"2022","journal-title":"Respir. Med."},{"key":"ref_9","doi-asserted-by":"crossref","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":"ref_10","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s11739-022-03125-3","article-title":"Prognostic value of cardiopulmonary exercise testing in patients with transthyretin cardiac amyloidosis","volume":"18","author":"Silverii","year":"2023","journal-title":"Intern. Emerg. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1253\/circj.CJ-20-1069","article-title":"Prevalence and Prognostic Significance of Pulmonary Function Test Abnormalities in Hospitalized Patients with Acute Decompensated Heart Failure with Preserved and Reduced Ejection Fraction","volume":"85","author":"Kawakami","year":"2021","journal-title":"Circ. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.cardfail.2006.10.018","article-title":"Pulmonary function changes associated with cardiomegaly in chronic heart failure","volume":"13","author":"Olson","year":"2007","journal-title":"J. Card. Fail."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1002\/ehf2.13342","article-title":"All-cause mortality predicted by peak oxygen uptake differs depending on spirometry pattern in patients with heart failure and reduced ejection fraction","volume":"8","author":"Cho","year":"2021","journal-title":"ESC Heart Fail."},{"key":"ref_14","first-page":"e000030","article-title":"ASNC\/AHA\/ASE\/EANM\/HFSA\/ISA\/SCMR\/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 2 of 2-Diagnostic Criteria and Appropriate Utilization","volume":"14","author":"Dorbala","year":"2021","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1093\/eurheartj\/ehx589","article-title":"A new staging system for cardiac transthyretin amyloidosis","volume":"39","author":"Gillmore","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e70","DOI":"10.1164\/rccm.201908-1590ST","article-title":"Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement","volume":"200","author":"Graham","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1136\/thx.2009.126052","article-title":"Morbidity and mortality associated with the restrictive spirometric pattern: A longitudinal study","volume":"65","author":"Guerra","year":"2010","journal-title":"Thorax"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3\u201395-yr age range: The global lung function 2012 equations","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"American Thoracic Society, American College of Chest Physicians (2003). ATS\/ACCP Statement on cardiopulmonary exercise testing. Am. J. Respir. Crit. Care Med., 167, 211\u2013277.","DOI":"10.1164\/rccm.167.2.211"},{"key":"ref_20","unstructured":"Kennedy, K.F., and Pencina, M.J. (2022, August 31). A SAS\u00ae Macro to Compute Added Predictive Ability of New Markers Predicting a Dichotomous Outcome. Available online: https:\/\/analytics.ncsu.edu\/sesug\/2010\/SDA07.Kennedy.pdf."},{"key":"ref_21","unstructured":"Guo, C. (2022, August 31). Evaluating Predictive Accuracy of Survival Models with PROC PHREG. Available online: https:\/\/www.lexjansen.com\/phuse\/2021\/as\/PAP_AS04.pdf."},{"key":"ref_22","unstructured":"Roxane, D., and Lotte, J. (2022, August 31). Evaluating Predictive Accuracy of Survival Models with PROC PHREG. SAS. Available online: https:\/\/support.sas.com\/resources\/papers\/proceedings17\/SAS0462-2017.pdf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"247","DOI":"10.5858\/arpa.2016-0102-RA","article-title":"Amyloidosis of the lung","volume":"141","author":"Khoor","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"170046","DOI":"10.1183\/16000617.0046-2017","article-title":"The lung in amyloidosis","volume":"26","author":"Milani","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1602313","DOI":"10.1183\/13993003.02313-2016","article-title":"Clinical relevance of pulmonary amyloidosis: An analysis of 76 autopsy derived cases","volume":"49","author":"Ussavarungsi","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"874","DOI":"10.12659\/AJCR.900682","article-title":"Hereditary amyloidosis with recurrent lung infiltrates","volume":"17","author":"Revelo","year":"2016","journal-title":"Am. J. Case Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/pin.13041","article-title":"Distribution of amyloidosis subtypes based on tissue biopsy site\u2014Consecutive analysis of 729 patients at a single amyloidosis center in Japan","volume":"71","author":"Abe","year":"2021","journal-title":"Pathol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1183\/16000617.0048-2016","article-title":"Exertional dyspnoea in chronic heart failure: The role of the lung and respiratory mechanical factors","volume":"25","author":"Agostoni","year":"2016","journal-title":"Eur. Respir. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.cardfail.2016.06.001","article-title":"Restrictive lung function is related to sympathetic hyperactivity in patients with heart failure","volume":"23","author":"Joho","year":"2017","journal-title":"J. Card. Fail."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/eurheartj\/ehs123","article-title":"Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: An Italian perspective","volume":"34","author":"Rapezzi","year":"2013","journal-title":"Eur. Heart J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/11\/3684\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:42:30Z","timestamp":1760125350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/11\/3684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,26]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["jcm12113684"],"URL":"https:\/\/doi.org\/10.3390\/jcm12113684","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,26]]}}}