{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:09:00Z","timestamp":1787191740553,"version":"build-2736575974"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Exposure to high altitude triggers hypoxic pulmonary vasoconstriction with a rise in pulmonary artery pressure (PAP). This may lead to symptomatic pulmonary hypertension with impaired right heart function and exercise capacity. We investigated whether preventive acetazolamide treatment would attenuate the altitude\u2010induced PAP\u2010increase and hereby improve hemodynamics in nonacclimatized middle\u2010aged healthy lowland residents ascending to 3100\u2009m.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">In this placebo\u2010controlled, double\u2010blind parallel trial, healthy lowland residents &gt;40\u2009years living &lt;800\u2009m, were randomized to acetazolamide (375\u2009mg\/day) or placebo during a 48\u2010hour stay at 3100\u2009m, starting 24\u2009hours before ascent. Echocardiography was performed at 760\u2009m before medication and repeated after the first night at 3100\u2009m. Systolic PAP, hemodynamics, and surrogates of right heart function were compared between the 2 groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The analysis included 171 healthy, 33% female subjects, age 53\u00b17\u2009years (mean\u00b1SD), randomized to placebo (n=82) or acetazolamide (n=89). The primary outcome, systolic PAP at 760\/3100\u2009m, was 22.0\u00b10.8\/26.6\u00b10.7\u2009mm\u2009Hg under placebo versus 21.6\u00b10.7\/24.1\u00b10.6\u2009mm\u2009Hg under acetazolamide with a mean altitude effect difference (acetazolamide\u2010placebo, treatment effect) of \u22122.5 (95% CI, \u22125.3 to 0.4)\u2009mm\u2009Hg (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.087). Significant treatment effects with acetazolamide were detected for saturation by pulse oxymetry 2 (1 to 2)%, heart rate \u22125 (95% CI, \u22129 to \u22121)\/minute, cardiac output \u22120.8 (95% CI, \u22121.3 to \u22120.4)\u2009L\/min, oxygen delivery \u2212123 (95% CI, \u2212211 to \u221234)\u2009mL\/min, and fractional area change of \u22124 (95% CI, \u22127 to \u22120)%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">In healthy, middle\u2010aged lowland residents traveling to 3100\u2009m, preventive acetazolamide tended to but did not significantly attenuate the altitude\u2010induced PAP\u2010increase. An alteration of hemodynamics and right heart function was observed resulting in a reduced overall oxygen delivery, which may counter the proven positive effects of acetazolamide on arterial oxygenation and acclimatization process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">https:\/\/clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique Identifier: NCT03540914.\n                    <\/jats:p>\n                  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