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Patisiran, an RNA interference therapeutic that inhibits hepatic synthesis of transthyretin, was approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy based on the phase 3 APOLLO study. We use left ventricular (LV) stroke volume (SV) to quantify LV function overtime and non-invasive pressure\u2013volume techniques to delineate the effects of patisiran on LV mechanics in the pre-specified cardiac subpopulation of the APOLLO study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Left ventricular SV was assessed by transthoracic echocardiography at baseline, and after 9 and 18\u2009months of therapy. To determine the mechanisms underlying changes in LV SV, non-invasive pressure\u2013volume parameters, including the end-systolic and end-diastolic pressure\u2013volume relationship, were derived using single beat techniques. At baseline, the mean SV was 51\u2009\u00b1\u200914 ml. At 9 months, the least-squares mean change in SV was \u22120.3\u2009\u00b1\u20091.2 ml for patisiran and\u2009\u22125.4\u2009\u00b1\u20091.9 ml for placebo (p =\u20090.021). At 18\u2009months, the least-squares mean change in SV was \u22121.7\u2009\u00b1\u20091.3 ml for patisiran and\u2009\u2212\u20098.1\u2009\u00b1\u20092.3 ml for placebo (p =\u20090.016). Decline in LV SV was driven by diminished LV capacitance in placebo relative to patisiran.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patisiran may delay progression of LV chamber dysfunction starting at 9 months of therapy. These data elucidate the mechanisms by which transthyretin-reducing therapies modulate progression of cardiac disease and need to be confirmed in ongoing phase 3 trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2783","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T22:18:05Z","timestamp":1674598685000},"page":"727-736","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effect of Patisiran on Stroke Volume in Hereditary Transthyretin-Mediated Amyloidosis: Insights from Pressure\u2013Volume Analysis of the APOLLO Study"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-4631","authenticated-orcid":false,"given":"Hannah R.","family":"Rosenblum","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center-NYP Hospital , New York, NY 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