{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:40:26Z","timestamp":1789681226307,"version":"4.0.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2013,2,15]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) genes. Sinoatrial node dysfunction associated with CPVT may increase the risk for ventricular arrhythmia (VA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>To test the hypothesis that CPVT is suppressed by supraventricular overdrive stimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Using CPVT mouse models (Casq2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and RyR2\n                      <jats:sup>R4496C\/+<\/jats:sup>\n                      mice), the effect of increasing sinus heart rate was tested by pretreatment with atropine and by atrial overdrive pacing. Increasing intrinsic sinus rate with atropine before catecholamine challenge suppressed ventricular tachycardia in 86% of Casq2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice (6\/7) and significantly reduced the VA score (atropine: 0.6\u00b10.2 versus vehicle: 1.7\u00b10.3;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). Atrial overdrive pacing completely prevented VA in 16 of 19 (84%) Casq2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and in 7 of 8 (88%) RyR2\n                      <jats:sup>R4496C\/+<\/jats:sup>\n                      mice and significantly reduced ventricular premature beats in both CPVT models (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). Rapid pacing also prevented spontaneous calcium waves and triggered beats in isolated CPVT myocytes. In humans, heart rate dependence of CPVT was evaluated by screening a CPVT patient registry for antiarrhythmic drug-na\u00efve individuals that reached &gt;85% of their maximum-predicted heart rate during exercise testing. All 18 CPVT patients who fulfilled the inclusion criteria exhibited VA before reaching 87% of maximum heart rate. In 6 CPVT patients (33%), VA were paradoxically suppressed as sinus heart rates increased further with continued exercise.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Accelerated supraventricular rates suppress VAs in 2 CPVT mouse models and in a subset of CPVT patients. Hypothetically, atrial overdrive pacing may be a therapy for preventing exercise-induced ventricular tachycardia in treatment-refractory CPVT patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.111.300076","type":"journal-article","created":{"date-parts":[[2013,1,8]],"date-time":"2013-01-08T11:08:05Z","timestamp":1357643285000},"page":"689-697","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":56,"title":["Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients"],"prefix":"10.1161","volume":"112","author":[{"given":"Michela","family":"Faggioni","sequence":"first","affiliation":[{"name":"From the Division of Clinical Pharmacology, Department of Medicine (M.F., H.S.H., P.J.K., B.C.K.), Division of Cardiology, Department of Pediatrics (P.J.K.), Vanderbilt University Medical School, Nashville, TN; and Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands (C.v.d.W., I.N., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Seok","family":"Hwang","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Pharmacology, Department of Medicine (M.F., H.S.H., P.J.K., B.C.K.), Division of Cardiology, Department of Pediatrics (P.J.K.), Vanderbilt University Medical School, Nashville, TN; and Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands (C.v.d.W., I.N., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"van der Werf","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Pharmacology, Department of Medicine (M.F., H.S.H., P.J.K., B.C.K.), Division of Cardiology, Department of Pediatrics (P.J.K.), Vanderbilt University Medical School, Nashville, TN; and Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands (C.v.d.W., I.N., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ineke","family":"Nederend","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Pharmacology, Department of Medicine (M.F., H.S.H., P.J.K., B.C.K.), Division of Cardiology, Department of Pediatrics (P.J.K.), Vanderbilt University Medical School, Nashville, TN; and Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands (C.v.d.W., I.N., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prince J.","family":"Kannankeril","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Pharmacology, Department of Medicine (M.F., H.S.H., P.J.K., B.C.K.), Division of Cardiology, Department of Pediatrics (P.J.K.), Vanderbilt University Medical School, Nashville, TN; and Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands (C.v.d.W., I.N., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur A.M.","family":"Wilde","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Pharmacology, Department of Medicine (M.F., H.S.H., P.J.K., B.C.K.), Division of Cardiology, Department of Pediatrics (P.J.K.), Vanderbilt University Medical School, Nashville, TN; and Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands (C.v.d.W., I.N., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn C.","family":"Knollmann","sequence":"additional","affiliation":[{"name":"From the Division of Clinical Pharmacology, Department of Medicine (M.F., H.S.H., P.J.K., B.C.K.), Division of Cardiology, Department of Pediatrics (P.J.K.), Vanderbilt University Medical School, Nashville, TN; and Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, the Netherlands (C.v.d.W., I.N., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.5.1512"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028993"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00461-1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/324565"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000038886.18992.6b"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds104"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.110.221481"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000173375.26489.fe"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.171660"},{"key":"e_1_3_4_11_2","first-page":"2510","article-title":"Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia.","volume":"116","author":"Knollmann BC","year":"2006","unstructured":"Knollmann BC, Chopra N, Hlaing T, Akin B, Yang T, Ettensohn K, Knollmann BE, Horton KD, Weissman NJ, Holinstat I, Zhang W, Roden DM, Jones LR, Franzini-Armstrong C, Pfeifer K. 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