{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:09:57Z","timestamp":1785802197828,"version":"3.56.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T00:00:00Z","timestamp":1590105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Increased chemosensitivity to carbon dioxide (CO\n                      <jats:sub>2<\/jats:sub>\n                      ) is an important trigger of central apnoeas (CA) in heart failure (HF), with negative impact on outcome. We hypothesized that buspirone, a 5HT\n                      <jats:sub>1A<\/jats:sub>\n                      receptor agonist that inhibits serotonergic chemoreceptor neuron firing in animals, can decrease CO\n                      <jats:sub>2<\/jats:sub>\n                      chemosensitivity and CA in \nHF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      The BREATH study was a randomized, double\u2010blind, placebo\u2010controlled, crossover study (EudraCT\u2010code 2015\u2010005383\u201042). Outpatients with systolic HF (left ventricular ejection fraction &lt;50%) and moderate\u2010severe CA [nocturnal apnoea\u2010hypopnoea index (AHI)\u2009\u226515\u2009events\/h] were randomly assigned to either oral buspirone (15\u2009mg thrice daily) or placebo for 1\u00a0week, with a crossover design (1\u00a0week of wash\u2010out). The primary effectiveness endpoint was a decrease in CO\n                      <jats:sub>2<\/jats:sub>\n                      chemosensitivity &gt;0.5\u00a0L\/min\/mmHg. The primary safety endpoint was freedom from serious adverse events. Sixteen patients (age 71.3\u2009\u00b1\u20095.8\u2009years, all males, left ventricular ejection fraction 29.8\u2009\u00b1\u20097.8%) were enrolled. In the intention\u2010to\u2010treat analysis, more patients treated with buspirone (8\/16, 50%) had a CO\n                      <jats:sub>2<\/jats:sub>\n                      chemosensitivity reduction &gt;0.5\u00a0L\/min\/mmHg from baseline than those treated with placebo (1\/16, 6.7%) (difference between groups 43%, 95% confidence interval 14\u201373%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.016). Buspirone compared to baseline led to a 41% reduction in CO\n                      <jats:sub>2<\/jats:sub>\n                      chemosensitivity (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001) and to a reduction in the AHI, central apnoea index and oxygen desaturation index of 42%, 79%, 77% at nighttime and 50%, 78%, 86% at daytime (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01); no difference was observed after placebo administration (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&gt;\u20090.05). No patient reported buspirone\u2010related serious adverse events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Buspirone reduces CO\n                      <jats:sub>2<\/jats:sub>\n                      chemosensitivity and improves CA and oxygen saturation across the 24\u2009h in patients with \nHF.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1854","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T06:58:30Z","timestamp":1590130710000},"page":"312-320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Benefit of buspirone on chemoreflex and central apnoeas in heart failure: a randomized controlled crossover trial"],"prefix":"10.1093","volume":"23","author":[{"given":"Alberto","family":"Giannoni","sequence":"first","affiliation":[{"name":"Fondazione Toscana G. 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