{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:45:31Z","timestamp":1790646331587,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>Chronotropic incompetence is defined as the inability to reach 80% of heart rate (HR) reserve or 80% of the maximally predicted HR during exercise. The presence of chronotropic incompetence is associated with reduced peak oxygen consumption, and rate\u2013responsive pacing therapy is under investigation to improve exercise capacity in heart failure (HF). However, uncertainty exists about whether chronotropic incompetence and reduced exercise tolerance in HF are attributable to \u03b2-blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Subjects with HF and receiving long-term \u03b2-blocker therapy underwent cardiopulmonary exercise tolerance testing under 2 conditions in random sequence: (1) after a 27-hour washout period (Off-BB) and (2) 3 hours after \u03b2-blocker ingestion (On-BB). Norepinephrine levels were drawn at rest and at peak exercise. \u03b21-response to norepinephrine was assessed using the chronotropic responsiveness index: \u0394HR\/\u0394log norepinephrine. Nineteen patients with systolic HF (left ventricular ejection fraction, 22.8\u00b17.7%) were enrolled. Mean age was 49.4\u00b112.3 years. Average carvedilol equivalent dose was 29.1\u00b117.0 mg daily. Peak HR off\/on \u03b2-blockers was 62.7\u00b118.7% and 51.4\u00b118.2% HR reserve (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01) and 79.1\u00b111.0% and 70.3\u00b112.3% maximally predicted HR (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01). For the Off-BB and On-BB conditions, the respiratory exchange ratios were 1.05\u00b10.06 and 1.05\u00b10.10 (\n                      <jats:italic>P<\/jats:italic>\n                      =0.77), respectively, confirming maximal and near identical effort in both conditions. The peak oxygen consumption was 16.6\u00b13.34 and 15.9\u00b13.31 mL\/kg\/min (\n                      <jats:italic>P<\/jats:italic>\n                      =0.03), and the chronotropic responsiveness index was 19.3\u00b17.2 and 16.2\u00b17.1 (\n                      <jats:italic>P<\/jats:italic>\n                      =0.18).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Acute \u03b2-blocker cessation does not normalize the chronotropic response to exercise in patients with advanced HF and chronotropic incompetence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.112.967695","type":"journal-article","created":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T21:00:42Z","timestamp":1343854842000},"page":"560-565","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Effect of \u03b2-Blocker Cessation on Chronotropic Incompetence and Exercise Tolerance in Patients With Advanced Heart Failure"],"prefix":"10.1161","volume":"5","author":[{"given":"Benjamin J.","family":"Hirsh","sequence":"first","affiliation":[{"name":"From the Cardiovascular Division, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mignatti","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Reshad","family":"Garan","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Uriel","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Colombo","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Sims","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich P.","family":"Jorde","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Division, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2007.11.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2004.058073"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5922.2010.00184.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.110.940577"},{"key":"e_1_3_3_6_2","first-page":"12","article-title":"Beta-adrenergic pathways in non-failing and failing human ventricular myocardium.","volume":"82","author":"Bristow MR","year":"1990","unstructured":"Bristow MR, Hershberger RE, Port JD. Beta-adrenergic pathways in non-failing and failing human ventricular myocardium. 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