{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T18:47:32Z","timestamp":1772131652882,"version":"3.50.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T00:00:00Z","timestamp":1484006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T00:00:00Z","timestamp":1484006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Presence of exercise-induced pulmonary hypertension (EIPH) in asymptomatic degenerative mitral regurgitation (DMR) determines prognosis. This study aimed to elucidate the mechanism and predictors of EIPH in asymptomatic DMR. Ninety-one consecutive asymptomatic patients with DMR who underwent exercise stress echocardiography were prospectively included. We obtained various conventional echocardiographic parameters at rest and during peak exercise, as well as left atrial (LA) function at rest using 2-dimensional speckle-tracking analysis. The 25 patients (33.3%) with EIPH were significantly older and had a greater ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity during peak exercise than those without EIPH. LA strain (LAS)-s and LAS-e, indices of LA reservoir and conduit function, respectively, were significantly lower in those with EIPH than in those without EIPH. Multivariate analysis indicated that LAS-s was the only resting echocardiographic parameter that independently predicted EIPH, with a cut-off value of 26.9%. Furthermore, Kaplan-Meier curve analysis showed that symptom-free survival was markedly lower among those with reduced LAS-s. In conclusion, decreased LA reservoir function contributes to EIPH, and LAS-s at rest is a useful indicator for predicting EIPH in asymptomatic patients with DMR.<\/jats:p>","DOI":"10.1038\/srep40008","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T10:16:02Z","timestamp":1484043362000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Predictors of Exercise-Induced Pulmonary Hypertension in Patients with Asymptomatic Degenerative Mitral Regurgitation: Mechanistic Insights from 2D Speckle-Tracking Echocardiography"],"prefix":"10.1038","volume":"7","author":[{"given":"Ryo","family":"Kamijima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kengo","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Izumo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Kuwata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Mizukoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manabu","family":"Takai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seisyou","family":"Kou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akio","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Kida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoo","family":"Harada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro J.","family":"Akashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,1,10]]},"reference":[{"key":"BFsrep40008_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1056\/NEJM199907013410101","volume":"341","author":"LA Freed","year":"1999","unstructured":"Freed, L. A. et al. Prevalence and clinical outcome of mitral-valve prolapse. N. Engl. J. Med. 341, 1\u20137 (1999).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep40008_CR2","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/S0002-9343(01)00981-0","volume":"111","author":"RB Devereux","year":"2001","unstructured":"Devereux, R. B. et al. Prevalence and correlates of mitral valve prolapse in a population-based sample of American Indians: the Strong Heart Study. Am. J. Med. 111, 679\u2013685 (2001).","journal-title":"Am. J. Med."},{"key":"BFsrep40008_CR3","first-page":"e521","volume":"129","author":"RA Nishimura","year":"2014","unstructured":"Nishimura, R. A. et al. 2014 AHA\/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines. Circulation 129, e521\u2013e643 (2014).","journal-title":"Circulation"},{"key":"BFsrep40008_CR4","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1093\/eurheartj\/ehs109","volume":"33","author":"A Vahanian","year":"2012","unstructured":"Vahanian, A. et al. Guidelines on the management of valvular heart disease (version 2012). Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology, European Association for Cardio-Thoracic Surgery (EACTS). Eur. Heart J. 33, 2451\u20132496 (2012).","journal-title":"Eur. Heart J"},{"key":"BFsrep40008_CR5","doi-asserted-by":"publisher","first-page":"2496","DOI":"10.1161\/01.CIR.92.9.2496","volume":"92","author":"M Enriquez-Sarano","year":"1995","unstructured":"Enriquez-Sarano, M. et al. Congestive heart failure after surgical correction of mitral regurgitation. A long-term study. Circulation 92, 2496\u20132503 (1995).","journal-title":"Circulation"},{"key":"BFsrep40008_CR6","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1161\/01.CIR.99.3.400","volume":"99","author":"CM Tribouilloy","year":"1999","unstructured":"Tribouilloy, C. M. et al. Impact of preoperative symptoms on survival after surgical correction of organic mitral regurgitation: rationale for optimizing surgical indications. Circulation 99, 400\u2013405 (1999).","journal-title":"Circulation"},{"key":"BFsrep40008_CR7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1161\/CIRCULATIONAHA.110.938241","volume":"122","author":"J Magne","year":"2010","unstructured":"Magne, J. et al. Exercise pulmonary hypertension in asymptomatic degenerative mitral regurgitation. Circulation 122, 33\u201341 (2010).","journal-title":"Circulation"},{"key":"BFsrep40008_CR8","first-page":"1","volume":"3","author":"H Patel","year":"2014","unstructured":"Patel, H. et al. Pulmonary hypertension in mitral regurgitation. J. Am. Heart Assoc. 3, 1\u20139 (2014).","journal-title":"J. Am. Heart Assoc"},{"key":"BFsrep40008_CR9","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1093\/eurheartj\/ehs188","volume":"34","author":"S Gupta","year":"2013","unstructured":"Gupta, S. et al. Left atrial structure and function and clinical outcomes in the general population. Eur. Heart J. 34, 278\u2013285 (2013).","journal-title":"Eur. Heart J."},{"key":"BFsrep40008_CR10","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1093\/eurheartj\/ehq105","volume":"31","author":"ML Antoni","year":"2010","unstructured":"Antoni, M. L. et al. Prognostic importance of strain and strain rate after acute myocardial infarction. Eur. Heart J. 31, 1640\u20131647 (2010).","journal-title":"Eur. Heart J."},{"key":"BFsrep40008_CR11","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.jacc.2011.11.012","volume":"59","author":"CC Welles","year":"2012","unstructured":"Welles, C. C. et al. Left atrial function predicts heart failure hospitalization in subjects with preserved ejection fraction and coronary heart disease: longitudinal data from the Heart and Soul Study. J. Am. Coll. Cardiol. 59, 673\u2013680 (2012).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR12","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1093\/ejechocard\/jep058","volume":"10","author":"P Caso","year":"2009","unstructured":"Caso, P. et al. Atrial reservoir function by strain rate imaging in asymptomatic mitral stenosis: prognostic value at 3 year follow-up. Eur. J. Echocardiogr. 10, 753\u2013759 (2009).","journal-title":"Eur. J. Echocardiogr."},{"key":"BFsrep40008_CR13","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.echo.2012.11.016","volume":"26","author":"R Ancona","year":"2013","unstructured":"Ancona, R. et al. Two-dimensional atrial systolic strain imaging predicts atrial fibrillation at 4-year follow-up in asymptomatic rheumatic mitral stenosis. J. Am. Soc. Echocardiogr. 26, 270\u2013277 (2013).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR14","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.echo.2014.01.021","volume":"27","author":"MJ Vieira","year":"2014","unstructured":"Vieira, M. J. et al. Left atrial mechanics: echocardiographic assessment and clinical implications. J. Am. Soc. Echocardiogr. 27, 463\u2013478 (2014).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR15","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.jacc.2013.10.055","volume":"63","author":"BD Hoit","year":"2014","unstructured":"Hoit, B. D. Left atrial size and function: role in prognosis. J. Am. Coll. Cardiol. 63, 493\u2013505 (2014).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR16","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1016\/j.echo.2005.10.005","volume":"18","author":"RM Lang","year":"2005","unstructured":"Lang, R. M. et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography\u2019s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J. Am. Soc. Echocardiogr. 18, 1440\u20131463 (2005).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR17","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1016\/S0735-1097(97)00344-6","volume":"30","author":"SF Nagueh","year":"1997","unstructured":"Nagueh, S. F. et al. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J. Am. Coll. Cardiol. 30, 1527\u20131533 (1997).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR18","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/0735-1097(94)90432-4","volume":"23","author":"M Enriquez-Sarano","year":"1994","unstructured":"Enriquez-Sarano, M. et al. Effective regurgitant orifice area: a noninvasive Doppler development of an old hemodynamic concept. J. Am. Coll. Cardiol. 23, 443\u2013451 (1994).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR19","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/0735-1097(94)00434-R","volume":"25","author":"M Enriquez-Sarano","year":"1995","unstructured":"Enriquez-Sarano, M. et al. Effective mitral regurgitation orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. J. Am. Coll. Cardiol. 25, 703\u2013709 (1995).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR20","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1067\/mje.2002.120202","volume":"15","author":"MA Qui\u00f1ones","year":"2002","unstructured":"Qui\u00f1ones, M. A. et al. Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J. Am. Soc. Echocardiogr. 15, 167\u2013184 (2002).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR21","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.echo.2008.12.017","volume":"22","author":"R Vianna-Pinton","year":"2009","unstructured":"Vianna-Pinton, R. et al. Two-dimensional speckle-tracking echocardiography of the left atrium: feasibility and regional contraction and relaxation differences in normal subjects. J. Am. Soc. Echocardiogr. 22, 299\u2013305 (2009).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR22","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.echo.2009.11.003","volume":"23","author":"RM Saraiva","year":"2010","unstructured":"Saraiva, R. M. et al. Left atrial strain measured by two-dimensional speckle tracking represents a new tool to evaluate left atrial function. J. Am. Soc. Echocardiogr. 23, 172\u2013180 (2010).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR23","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/j.echo.2013.05.019","volume":"26","author":"P Debonnaire","year":"2013","unstructured":"Debonnaire, P. et al. Left atrial function by two-dimensional speckle-tracking echocardiography in patients with severe organic mitral regurgitation: association with guidelines-based surgical indication and postoperative (long-term) survival. J. Am. Soc. Echocardiogr. 26, 1053\u20131062 (2013).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR24","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1016\/j.jacc.2006.02.048","volume":"47","author":"WP Abhayaratna","year":"2006","unstructured":"Abhayaratna, W. P. et al. Left atrial size: physiologic determinants and clinical applications. J. Am. Coll. Cardiol. 47, 2357\u20132363 (2006).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR25","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.jacc.2005.10.061","volume":"47","author":"K Serri","year":"2006","unstructured":"Serri, K. et al. Global and regional myocardial function quantification by two-dimensional strain: application in hypertrophic cardiomyopathy. J. Am. Coll. Cardiol. 47, 1175\u20131181 (2006).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR26","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.jacc.2005.10.040","volume":"47","author":"BH Amundsen","year":"2006","unstructured":"Amundsen, B. H. et al. Noninvasive myocardial strain measurement by speckle tracking echocardiography: validation against sonomicrometry and tagged magnetic resonance imaging. J. Am. Coll. Cardiol. 47, 789\u2013793 (2006).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR27","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.echo.2006.08.023","volume":"20","author":"G Perk","year":"2007","unstructured":"Perk, G. et al. Non-Doppler two-dimensional strain imaging by echocardiography-from technical considerations to clinical applications. J. Am. Soc. Echocardiogr. 20, 234\u2013243 (2007).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR28","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.echo.2006.07.007","volume":"20","author":"HK Kim","year":"2007","unstructured":"Kim, H. K. et al. Assessment of left ventricular rotation and torsion with two-dimensional speckle tracking echocardiography. J. Am. Soc. Echocardiogr. 20, 45\u201353 (2007).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR29","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.echo.2008.11.006","volume":"22","author":"K Okamatsu","year":"2009","unstructured":"Okamatsu, K. et al. Effects of aging on left atrial function assessed by two-dimensional speckle tracking echocardiography. J. Am. Soc. Echocardiogr. 22, 70\u201375 (2009).","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"BFsrep40008_CR30","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1097\/00000542-200304000-00027","volume":"98","author":"PS Pagel","year":"2003","unstructured":"Pagel, P. S. et al. Mechanical function of the left atrium: new insights based on analysis of pressure-volume relations and Doppler echocardiography. Anesthesiology 98, 975\u2013994 (2003).","journal-title":"Anesthesiology"},{"key":"BFsrep40008_CR31","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1136\/heartjnl-2011-300069","volume":"97","author":"M Rosca","year":"2011","unstructured":"Rosca, M. et al. Left atrial function: pathophysiology, echocardiographic assessment, and clinical applications. Heart 97, 1982\u20131989 (2011).","journal-title":"Heart"},{"key":"BFsrep40008_CR32","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1161\/01.CIR.100.4.427","volume":"100","author":"P Barbier","year":"1999","unstructured":"Barbier, P. et al. Left atrial relaxation and left ventricular systolic function determine left atrial reservoir function. Circulation 100, 427\u2013436 (1999).","journal-title":"Circulation"},{"key":"BFsrep40008_CR33","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.cardiores.2005.04.016","volume":"67","author":"W Ann\u00e9","year":"2005","unstructured":"Ann\u00e9, W. et al. Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation. Cardiovasc. Res. 67, 655\u2013666 (2005).","journal-title":"Cardiovasc. Res."},{"key":"BFsrep40008_CR34","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/j.1540-8167.2011.02187.x","volume":"23","author":"D Corradi","year":"2012","unstructured":"Corradi, D. et al. Differential structural remodeling of the left-atrial posterior wall in patients affected by mitral regurgitation with or without persistent atrial fibrillation: a morphological and molecular study. J. Cardiovasc. Electrophysiol. 23, 271\u2013279 (2012).","journal-title":"J. Cardiovasc. Electrophysiol"},{"key":"BFsrep40008_CR35","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1161\/01.CIR.0000066915.15187.51","volume":"107","author":"S Verheule","year":"2003","unstructured":"Verheule, S. et al. Alterations in atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation. Circulation 107, 2615\u20132622 (2003).","journal-title":"Circulation"},{"key":"BFsrep40008_CR36","first-page":"H1471","volume":"261","author":"MR Zile","year":"1991","unstructured":"Zile, M. R. et al. Effects of left ventricular volume overload produced by mitral regurgitation on diastolic function. Am. J. Physiol. 261, H1471\u20131480 (1991).","journal-title":"Am. J. Physiol."},{"key":"BFsrep40008_CR37","first-page":"817","volume":"41","author":"JW Kennedy","year":"1970","unstructured":"Kennedy, J. W. et al. Quantitative angiography. IV. Relationships of left atrial and ventricular pressure and volume in mitral valve disease. Circulation 41, 817\u2013824 (1970).","journal-title":"Relationships of left atrial and ventricular pressure and volume in mitral valve disease. Circulation"},{"key":"BFsrep40008_CR38","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1161\/CIRCIMAGING.110.961011","volume":"4","author":"D Rusinaru","year":"2011","unstructured":"Rusinaru, D. et al. Left atrial size is a potent predictor of mortality in mitral regurgitation due to flail leaflets: results from a large international multicenter study. Circ. Cardiovasc. Imaging 4, 473\u2013481 (2011).","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"BFsrep40008_CR39","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.jacc.2010.02.059","volume":"56","author":"T Le Tourneau","year":"2010","unstructured":"Le Tourneau, T. et al. Impact of left atrial volume on clinical outcome in organic mitral regurgitation. J. Am. Coll. Cardiol. 56, 570\u2013578 (2010).","journal-title":"J. Am. Coll. Cardiol."},{"key":"BFsrep40008_CR40","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1540-8175.2010.01329.x","volume":"28","author":"M Cameli","year":"2011","unstructured":"Cameli, M. et al. Chronic mitral regurgitation: left atrial deformation analysis by two-dimensional speckle tracking echocardiography. Echocardiography 28, 327\u2013334 (2011).","journal-title":"Echocardiography"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep40008.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep40008","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep40008.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T22:32:40Z","timestamp":1671834760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep40008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,10]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,2,14]]}},"alternative-id":["BFsrep40008"],"URL":"https:\/\/doi.org\/10.1038\/srep40008","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,10]]},"assertion":[{"value":"7 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"40008"}}