{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T22:53:40Z","timestamp":1783205620881,"version":"3.54.6"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":467,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"publisher","award":["22K08107"],"award-info":[{"award-number":["22K08107"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"publisher","award":["23K06870"],"award-info":[{"award-number":["23K06870"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K08107"],"award-info":[{"award-number":["22K08107"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K06870"],"award-info":[{"award-number":["23K06870"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The bicarbonate (HCO3\u2212) buffer system is crucial for maintaining acid\u2013base homeostasis and blood pH. Recent studies showed that elevated serum HCO3\u2212 levels serve as an indicator of the beneficial effects of acetazolamide in improving decongestion in acute heart failure. In this study, we sought to clarify the clinical relevance and prognostic impact of HCO3\u2212 in chronic heart failure (CHF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This cohort study enrolled 694 hospitalized patients with CHF (mean age 68.6 \u00b1 14.6, 62% male) who underwent arterial blood sampling and exhibited neutral pH ranging from 7.35 to 7.45. We characterized the patients based on HCO3\u2212 levels and followed them to register cardiac events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the patients, 17.3% (120 patients) had HCO3\u2212 levels exceeding 26 mmol\/L. Patients presenting HCO3\u2212 &amp;gt; 26 mmol\/L were more likely to use loop diuretics and had higher serum sodium and lower potassium levels, but left ventricular ejection fraction did not differ compared with those with HCO3\u2212 between 22 and 26 (379 patients) or those with HCO3\u2212 &amp;lt; 22 mmol\/L (195 patients). During a median follow-up period of 1950 days, Kaplan\u2013Meier analysis revealed that patients with HCO3\u2212 &amp;gt; 26 mmol\/L had the lowest event-free survival rate from either cardiac deaths or heart failure-related rehospitalization (P &amp;lt; 0.01 and 0.03, respectively). In the multivariable Cox model, the presence of HCO3\u2212 &amp;gt; 26 mmol\/L independently predicted increased risks of each cardiac event with a hazard ratio of 2.31 and 1.69 (P &amp;lt; 0.01 and 0.02, respectively), while HCO3\u2212 &amp;lt; 22 mmol\/L was not associated with these events (hazard ratios, 0.99 and 1.19; P = 0.98 and 0.43, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated blood HCO3\u2212 levels may signify enhanced proximal nephron activation and loop diuretic resistance, leading to long-term adverse outcomes in patients with CHF, even within a normal pH range.<\/jats:p>\n                  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