{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:30:26Z","timestamp":1786527026971,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Cardiovasc. Dev. Dis.","JCDD"],"abstract":"<jats:p>Background: Surgical correction of severe degenerative Mitral Regurgitation (DMR) is indicated in the presence of symptoms and signs of left ventricular (LV) dysfunction. However, conventional clinical and resting echocardiographic parameters may underestimate myocardial impairment. Cardiopulmonary exercise testing (CPET) and exercise stress echocardiography (ESE) may provide a more complete functional and haemodynamic assessment. Objectives: To characterize preoperative CPET and ESE findings in patients with severe DMR and to explore, in a hypothesis-generating analysis, their association with early functional and left ventricular outcomes after surgery. Methods: We included patients with severe DMR who underwent CPET and ESE before surgery. Functional improvement was defined as an improvement of at least one NYHA class from the preoperative baseline to early follow-up. LV function was evaluated as the continuous change in LVEF from discharge to early follow-up (Delta LVEF = follow-up LVEF \u2212 discharge LVEF). Baseline parameters were compared between patients who did and did not improve functionally. Random forest analyses were used only as an exploratory secondary analysis to assess whether baseline variables showed any non-linear signal of association with the outcomes and to document the instability of variable-importance rankings. Results and Conclusions: We included 60 patients, of whom 72% were in NYHA class II and all had preserved LV function. At CPET, rest and peak oxygen uptake were 6 +\/\u2212 1.5 and 17.2 +\/\u2212 5 mL\/kg\/min, respectively; the VE\/VCO2 slope was 33 +\/\u2212 8.9 and the Oxygen Uptake Efficiency Slope was 1.6 (1.3\u20131.9). At ESE, LVOT-VTI increased from 18.3 +\/\u2212 3.9 cm at rest to 24.5 +\/\u2212 4.9 cm at peak; stroke volume from 51.0 (43.0\u201360.0) mL to 72.5 +\/\u2212 21.6 mL; and cardiac output from 3.8 (3.2\u20135.1) L\/min to 9.0 +\/\u2212 3.2 L\/min. No baseline clinical, CPET or ESE parameter significantly distinguished patients who improved functionally from those who did not, and early Delta LVEF was negligible. Random forest analyses did not discriminate above chance and variable-importance rankings were unstable. Patients with severe DMR and preserved LVEF showed objectively abnormal exercise responses despite mild symptoms, supporting the use of CPET and ESE for preoperative functional and haemodynamic characterization; larger prospective studies are required before any predictive or decision-support use can be proposed.<\/jats:p>","DOI":"10.3390\/jcdd13080383","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiopulmonary Exercise Testing and Exercise Stress Echocardiography in Degenerative Mitral Regurgitation: An Exploratory Analysis of Functional and Left Ventricular Outcomes After Surgery"],"prefix":"10.3390","volume":"13","author":[{"given":"Laura","family":"Besola","sequence":"first","affiliation":[{"name":"Cardiac Surgery Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Bacci","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9396-5025","authenticated-orcid":false,"given":"Cinzia Anna Maria","family":"Papappicco","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7906-0580","authenticated-orcid":false,"given":"Dario","family":"Gregori","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giosu\u00e8 Salvatore","family":"Falcetta","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6154-9111","authenticated-orcid":false,"given":"Federico","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-227X","authenticated-orcid":false,"given":"Nicola Riccardo","family":"Pugliese","sequence":"additional","affiliation":[{"name":"Heart Failure Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-3961","authenticated-orcid":false,"given":"Andrea","family":"Colli","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Unit, Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1161\/CIRCULATIONAHA.119.041080","article-title":"EORP VHD II Investigators. Contemporary Presentation and Management of Valvular Heart Disease: The EURObservational Research Programme Valvular Heart Disease II Survey","volume":"140","author":"Iung","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1016\/j.jacc.2020.11.018","article-title":"2020 ACC\/AHA Guideline for the Management of Patients with Valvular Heart Disease: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"77","author":"Otto","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1093\/eurheartj\/ehaf194","article-title":"2025 ESC\/EACTS Guidelines for the management of valvular heart disease","volume":"46","author":"Praz","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1056\/NEJMoa041451","article-title":"Quantitative determinants of the outcome of asymptomatic mitral regurgitation","volume":"352","author":"Avierinos","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.echo.2020.01.016","article-title":"Mitral Valve Prolapse Patients with Less than Moderate Mitral Regurgitation Exhibit Early Cardiac Chamber Remodeling","volume":"37","author":"Yang","year":"2020","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.jcmg.2018.05.014","article-title":"Long-term outcome of active surveillance in severe but asymptomatic primary mitral regurgitation","volume":"11","author":"Zilberszac","year":"2018","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/S0140-6736(18)30473-2","article-title":"Outcome and undertreatment of mitral regurgitation: A community cohort study","volume":"391","author":"Dziadzko","year":"2018","journal-title":"Lancet"},{"key":"ref_8","first-page":"1007","article-title":"A new, simple and accurate method for determining ejection fraction by Doppler echocardiography","volume":"11","author":"Dumesnil","year":"1995","journal-title":"Can. J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e006309","DOI":"10.1161\/JAHA.117.006309","article-title":"Forward Left Ventricular Ejection Fraction: A Simple Risk Marker in Patients with Primary Mitral Regurgitation","volume":"6","author":"Dupuis","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.echo.2012.04.009","article-title":"Predictive value of global longitudinal strain in a surgical population of organic mitral regurgitation","volume":"25","author":"Mascle","year":"2012","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jcmg.2019.03.024","article-title":"Prognostic Value of Global Longitudinal Strain and Etiology After Surgery for Primary Mitral Regurgitation","volume":"13","author":"Hiemstra","year":"2020","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.echo.2017.01.007","article-title":"Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance","volume":"30","author":"Zoghbi","year":"2017","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/sim.7992","article-title":"Minimum Sample Size for Developing a Multivariable Prediction Model: PART II\u2014Binary and Time-to-Event Outcomes","volume":"38","author":"Riley","year":"2019","journal-title":"Stat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"m441","DOI":"10.1136\/bmj.m441","article-title":"Calculating the Sample Size Required for Developing a Clinical Prediction Model","volume":"368","author":"Riley","year":"2020","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e078378","DOI":"10.1136\/bmj-2023-078378","article-title":"TRIPOD+AI Statement: Updated Guidance for Reporting Clinical Prediction Models That Use Regression or Machine Learning Methods","volume":"385","author":"Collins","year":"2024","journal-title":"BMJ"},{"key":"ref_16","unstructured":"R Core Team (2022). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_17","doi-asserted-by":"crossref","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":"ref_18","first-page":"467","article-title":"Cardiopulmonary Exercise Test: Background, Applicability and Interpretation","volume":"107","author":"Herdy","year":"2016","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_19","first-page":"296","article-title":"Mitral regurgitation in heart failure: Insights from CPET combined with exercise echocardiography","volume":"18","author":"Bandera","year":"2017","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"bbad002","DOI":"10.1093\/bib\/bbad002","article-title":"A review on longitudinal data analysis with random forest","volume":"24","author":"Hu","year":"2023","journal-title":"Brief. Bioinform."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"qyad021","DOI":"10.1093\/ehjimp\/qyad021","article-title":"Combining cardiopulmonary exercise testing with echocardiography: A multiparametric approach to the cardiovascular and cardiopulmonary systems","volume":"1","author":"Armenia","year":"2023","journal-title":"Eur. Heart J. Imaging Methods Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1016\/j.jacc.2006.02.043","article-title":"Cardiopulmonary exercise testing determination of functional capacity in mitral regurgitation: Physiologic and outcome implications","volume":"47","author":"Johnson","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.amjcard.2023.06.033","article-title":"Oxygen Uptake Efficiency Slope and Prognosis in Heart Failure With Reduced Ejection Fraction","volume":"201","author":"Gordon","year":"2023","journal-title":"Am. J. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e32378","DOI":"10.1016\/j.heliyon.2024.e32378","article-title":"Association between echocardiographic velocity time integral ratio of mitral valve and left ventricular outflow tract and clinical outcomes post transcatheter edge-to-edge mitral valve repair","volume":"10","author":"Scalia","year":"2024","journal-title":"Heliyon"},{"key":"ref_25","first-page":"e876","article-title":"2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e14163","DOI":"10.1111\/eci.14163","article-title":"2023 focused update of the 2021 ESC heart failure guidelines: Key messages for clinical practice","volume":"54","author":"Tomasoni","year":"2024","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_27","first-page":"406","article-title":"Efectos cl\u00ednicos de la correcci\u00f3n del valor de la fracci\u00f3n de expulsi\u00f3n del ventr\u00edculo izquierdo en pacientes con insuficiencia valvular mitral [Clinical impact of the correction of the value of left ventricular ejection fraction in patients with mitral valve regurgitation]","volume":"90","author":"Garillo","year":"2020","journal-title":"Arch. Cardiol. 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