{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:07:50Z","timestamp":1792501670060,"version":"4.5.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2015,2,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>Characterization of myocardial structural changes in heart failure with preserved ejection fraction (HFpEF) has been hindered by the limited availability of human cardiac tissue. Cardiac hypertrophy, coronary artery disease (CAD), coronary microvascular rarefaction, and myocardial fibrosis may contribute to HFpEF pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      We identified HFpEF patients (n=124) and age-appropriate control subjects (noncardiac death, no heart failure diagnosis; n=104) who underwent autopsy. Heart weight and CAD severity were obtained from the autopsy reports. With the use of whole-field digital microscopy and automated analysis algorithms in full-thickness left ventricular sections, microvascular density (MVD), myocardial fibrosis, and their relationship were quantified. Subjects with HFpEF had heavier hearts (median, 538 g; 169% of age-, sex-, and body size\u2013expected heart weight versus 335 g; 112% in controls), more severe CAD (65% with \u22651 vessel with &gt;50% diameter stenosis in HFpEF versus 13% in controls), more left ventricular fibrosis (median % area fibrosis, 9.6 versus 7.1) and lower MVD (median 961 versus 1316 vessels\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ) than control (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001 for all). Myocardial fibrosis increased with decreasing MVD in controls (\n                      <jats:italic>r<\/jats:italic>\n                      =\u20130.28,\n                      <jats:italic>P<\/jats:italic>\n                      =0.004) and HFpEF (\n                      <jats:italic>r<\/jats:italic>\n                      =\u20130.26,\n                      <jats:italic>P<\/jats:italic>\n                      =0.004). Adjusting for MVD attenuated the group differences in fibrosis. Heart weight, fibrosis, and MVD were similar in HFpEF patients with CAD versus without CAD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>In this study, patients with HFpEF had more cardiac hypertrophy, epicardial CAD, coronary microvascular rarefaction, and myocardial fibrosis than controls. Each of these findings may contribute to the left ventricular diastolic dysfunction and cardiac reserve function impairment characteristic of HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.114.009625","type":"journal-article","created":{"date-parts":[[2014,12,31]],"date-time":"2014-12-31T22:45:56Z","timestamp":1420065956000},"page":"550-559","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":850,"title":["Coronary Microvascular Rarefaction and Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"131","author":[{"given":"Selma F.","family":"Mohammed","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Diseases (S.F.M., S.H., M.M.R.), Mayo Graduate School (S.F.M.), Mayo Medical School (S.A.M.), and Division of Anatomic Pathology (W.D.E., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad","family":"Hussain","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Diseases (S.F.M., S.H., M.M.R.), Mayo Graduate School (S.F.M.), Mayo Medical School (S.A.M.), and Division of Anatomic Pathology (W.D.E., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultan A.","family":"Mirzoyev","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Diseases (S.F.M., S.H., M.M.R.), Mayo Graduate School (S.F.M.), Mayo Medical School (S.A.M.), and Division of Anatomic Pathology (W.D.E., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Edwards","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Diseases (S.F.M., S.H., M.M.R.), Mayo Graduate School (S.F.M.), Mayo Medical School (S.A.M.), and Division of Anatomic Pathology (W.D.E., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J.","family":"Maleszewski","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Diseases (S.F.M., S.H., M.M.R.), Mayo Graduate School (S.F.M.), Mayo Medical School (S.A.M.), and Division of Anatomic Pathology (W.D.E., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Redfield","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Diseases (S.F.M., S.H., M.M.R.), Mayo Graduate School (S.F.M.), Mayo Medical School (S.A.M.), and Division of Anatomic Pathology (W.D.E., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052256"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.112.968594"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.02.092"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032566"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.659763"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000048123.22359.a0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.03.077"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.05.012"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000854"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00374-X"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.193326"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000155257.33485.6D"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.587519"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.728550"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.076075"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.109.931451"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.10.024"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.4161\/org.6.1.10427"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.71.5.889"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.2174\/157016108785909779"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(12)64946-5"},{"key":"e_1_3_4_23_2","first-page":"16","volume-title":"In: Acute Myocardial Infarction","author":"Edwards WE","year":"1997","unstructured":"Edwards WE. Pathology of myocardial infarction and reperfusion. , Gersh BJ, Rahimtoola SH, eds. In: Acute Myocardial Infarction. New York: Chapman & Hall; 1997:16\u201350."},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(20000401)39:4<275::AID-CYTO5>3.0.CO;2-8"},{"key":"e_1_3_4_25_2","first-page":"719","article-title":"Coronary and myocardial blood volumes: noninvasive tools to assess the coronary microcirculation?","volume":"96","author":"Kaul S","year":"1997","unstructured":"Kaul S, Jayaweera AR. Coronary and myocardial blood volumes: noninvasive tools to assess the coronary microcirculation? Circulation. 1997;96:719\u2013724.","journal-title":"Circulation"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.07.039"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.647149"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:MCBI.0000044373.61812.f7"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-11-0568"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(87)90618-7"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.86.1.38"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2009.10.022"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.011031"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(01)02345-1"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.03.034"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.05.064"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.04.019"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000249510.20326.72"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.680157"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.79.1.78"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.3.230"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-009-9142-5"},{"issue":"6","key":"e_1_3_4_43_2","first-page":"H2363","article-title":"Role of capillaries in determining CBF reserve: new insights using myocardial contrast echocardiography.","volume":"277","author":"Jayaweera AR","year":"1999","unstructured":"Jayaweera AR, Wei K, Coggins M, Bin JP, Goodman C, Kaul S. Role of capillaries in determining CBF reserve: new insights using myocardial contrast echocardiography. Am J Physiol. 1999;277(6 pt 2):H2363\u2013H2372.","journal-title":"Am J Physiol"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.834739"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.853127"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31824ea092"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3283468392"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.08.717"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2011.07.050"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.899336"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.114.009625","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T02:57:22Z","timestamp":1715569042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.114.009625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,10]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,2,10]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.114.009625"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.114.009625","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,10]]},"assertion":[{"value":"2014-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-11-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}