{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T22:25:53Z","timestamp":1794435953041,"version":"4.9.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,4,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory\/outpatient setting is unknown because previous studies lacked objective reference standards.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation. Derived cut points were tested in 3 additional validation cohorts (cohorts 4\u20136) in whom HFpEF was diagnosed by resting catheterization only (n=260), previous hospitalization for heart failure (n=447), or exercise echocardiography (n=517), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Current recommended rule-out NT-proBNP threshold &lt;125 pg\/mL had 82% sensitivity (95% CI, 77%\u201388%) with a body mass index (BMI) &lt;35 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , decreasing to 67% (95% CI, 58%\u201377%) with a BMI \u226535 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . A lower rule-out NT-proBNP threshold &lt;50 pg\/mL displayed good sensitivity with a BMI &lt;35 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (97% [95% CI, 95%\u201399%]), with a modest decline in sensitivity with a BMI \u226535 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (86% [95% CI, 79%\u201393%]); diagnostic thresholds were confirmed in validation cohorts 1 and 2 (91% [95% CI, 88%\u201395%] and 86% [95% CI, 80%\u201393%] with a BMI &lt;35 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ; 80% [95% CI, 74%\u201387%] and 84% [95% CI, 74%\u201393%] with a BMI \u226535 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). Current consensus age- and BMI-stratified rule-in thresholds demonstrated only 65% specificity (95% CI, 57%\u201372%). Rule-in NT-proBNP threshold \u2265500 pg\/mL had 85% specificity (95% CI, 78%\u201391%) with a BMI &lt;35 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (87% [95% CI, 80%\u201394%] and 90% [95% CI, 81%\u201399%] in validation cohorts), with 100% specificity at a BMI \u226535 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (93% [95% CI, 81%\u2013100%] and 100% in validation cohorts). With a BMI \u226535 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , lower rule-in thresholds (\u2265220 pg\/mL) provided good specificity (88% [95% CI, 73%\u2013100%]; 93% [95% CI, 81%\u2013100%] and 100% in validation cohorts). Findings were consistent in validation cohorts 3 through 6 (sensitivity of &lt;50 pg\/mL, 93%\u201398%; specificity of \u2265500 pg\/mL, 82%\u201389%). NT-proBNP provided no incremental discrimination among patients with history of AF; \u226598% of patients with AF and dyspnea were found to have HFpEF in our cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In patients with chronic unexplained dyspnea, current rule-in and rule-out NT-proBNP diagnostic thresholds lead to unacceptably high error rates, with important interactions by obesity and AF status. In our study, NT-proBNP provided little value in those with AF and dyspnea because the presence of AF is by itself a robust biomarker of HFpEF. Use of separate rule-in and rule-out diagnostic thresholds stratified by BMI reduces miscategorization and can guide more appropriate use of exercise testing for possible HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.124.072156","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T05:00:22Z","timestamp":1737522022000},"page":"976-989","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Evidence-Based Application of Natriuretic Peptides in the Evaluation of Chronic Heart Failure With Preserved Ejection Fraction in the Ambulatory Outpatient Setting"],"prefix":"10.1161","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5322-0902","authenticated-orcid":true,"given":"Yogesh N.V.","family":"Reddy","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., A.T., M.M.R., B.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., A.T., M.M.R., B.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-0688","authenticated-orcid":true,"given":"Masaru","family":"Obokata","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Gunma University Graduate School of Medicine, Maebashi, Japan (M.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0818-273X","authenticated-orcid":true,"given":"Rickey E.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL (R.E.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-0372","authenticated-orcid":true,"given":"David M.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia (D.M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-7865","authenticated-orcid":true,"given":"M. Louis","family":"Handoko","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Netherlands (M.L.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9320-8227","authenticated-orcid":true,"given":"Mads J.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital, Denmark (M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-1765","authenticated-orcid":true,"given":"Kavita","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD (K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9045-7722","authenticated-orcid":true,"given":"Ryan J.","family":"Tedford","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston (R.J.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0946-7518","authenticated-orcid":true,"given":"Margaret M.","family":"Redfield","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., A.T., M.M.R., B.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-0596","authenticated-orcid":true,"given":"Barry A.","family":"Borlaug","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.N.V.R., A.T., M.M.R., 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