Prince J Kannankeril1,2, M Benjamin Shoemaker2,3, Kathryn A Gayle3, Darlene Fountain1,2, Dan M Roden2,3,4, Bjorn C Knollmann2,4. 1. Thomas P. Graham Jr. Division of Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, 2220 Children's Way, Suite 5230, Nashville, TN 37232-9119, USA. 2. Vanderbilt Center for Arrhythmia Research and Therapeutics, Vanderbilt University Medical Center, Nashville, TN, USA. 3. Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. 4. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Abstract
AIMS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by exercise-induced ventricular arrhythmias, sudden death, and sinus bradycardia. Elevating supraventricular rates with pacing or atropine protects against catecholaminergic ventricular arrhythmias in a CPVT mouse model. We tested the hypothesis that increasing sinus heart rate (HR) with atropine prevents exercise-induced ventricular arrhythmias in CPVT patients. METHODS AND RESULTS: We performed a prospective open-label trial of atropine prior to exercise in CPVT patients (clinicaltrials.gov NCT02927223). Subjects performed a baseline standard Bruce treadmill test on their usual medical regimen. After a 2-h recovery period, subjects performed a second exercise test after parasympathetic block with atropine (0.04 mg/kg intravenous). The primary outcome measure was the total number of ventricular ectopic beats during exercise. All six subjects (5 men, 22-57 years old) completed the study with no adverse events. Atropine increased resting sinus rate from median 52 b.p.m. (range 52-64) to 98 b.p.m. (84-119), P = 0.02. Peak HRs (149 b.p.m., range 136-181 vs. 149 b.p.m., range 127-182, P = 0.46) and exercise duration (612 s, range 544-733 vs. 584 s, range 543-742, P = 0.22) were not statistically different. All subjects had ventricular ectopy during the baseline exercise test. Atropine pre-treatment significantly decreased the median number of ventricular ectopic beats from 46 (6-192) to 0 (0-29), P = 0.026; ventricular ectopy was completely eliminated in 4/6 subjects. CONCLUSION: Elevating sinus rates with atropine reduces or eliminates exercise-induced ventricular ectopy in patients with CPVT. Increasing supraventricular rates may represent a novel therapeutic strategy in CPVT. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by exercise-induced ventricular arrhythmias, sudden death, and sinus bradycardia. Elevating supraventricular rates with pacing or atropine protects against catecholaminergic ventricular arrhythmias in a CPVT mouse model. We tested the hypothesis that increasing sinus heart rate (HR) with atropine prevents exercise-induced ventricular arrhythmias in CPVT patients. METHODS AND RESULTS: We performed a prospective open-label trial of atropine prior to exercise in CPVT patients (clinicaltrials.gov NCT02927223). Subjects performed a baseline standard Bruce treadmill test on their usual medical regimen. After a 2-h recovery period, subjects performed a second exercise test after parasympathetic block with atropine (0.04 mg/kg intravenous). The primary outcome measure was the total number of ventricular ectopic beats during exercise. All six subjects (5 men, 22-57 years old) completed the study with no adverse events. Atropine increased resting sinus rate from median 52 b.p.m. (range 52-64) to 98 b.p.m. (84-119), P = 0.02. Peak HRs (149 b.p.m., range 136-181 vs. 149 b.p.m., range 127-182, P = 0.46) and exercise duration (612 s, range 544-733 vs. 584 s, range 543-742, P = 0.22) were not statistically different. All subjects had ventricular ectopy during the baseline exercise test. Atropine pre-treatment significantly decreased the median number of ventricular ectopic beats from 46 (6-192) to 0 (0-29), P = 0.026; ventricular ectopy was completely eliminated in 4/6 subjects. CONCLUSION: Elevating sinus rates with atropine reduces or eliminates exercise-induced ventricular ectopy in patients with CPVT. Increasing supraventricular rates may represent a novel therapeutic strategy in CPVT. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Fernando Wangüemert; Cristina Bosch Calero; Carmelo Pérez; Oscar Campuzano; Pedro Beltran-Alvarez; Fabiana S Scornik; Anna Iglesias; Paola Berne; Catarina Allegue; Pablo M Ruiz Hernandez; Josep Brugada; Guillermo J Pérez; Ramon Brugada Journal: Heart Rhythm Date: 2015-03-23 Impact factor: 6.343
Authors: Ida S Leren; Jørg Saberniak; Eman Majid; Trine F Haland; Thor Edvardsen; Kristina H Haugaa Journal: Heart Rhythm Date: 2015-09-30 Impact factor: 6.343
Authors: Prince J Kannankeril; Jeremy P Moore; Marina Cerrone; Silvia G Priori; Naomi J Kertesz; Pamela S Ro; Anjan S Batra; Elizabeth S Kaufman; David L Fairbrother; Elizabeth V Saarel; Susan P Etheridge; Ronald J Kanter; Michael P Carboni; Matthew V Dzurik; Darlene Fountain; Heidi Chen; E Wesley Ely; Dan M Roden; Bjorn C Knollmann Journal: JAMA Cardiol Date: 2017-07-01 Impact factor: 14.676
Authors: Mette Nyegaard; Michael T Overgaard; Mads T Søndergaard; Marta Vranas; Elijah R Behr; Lasse L Hildebrandt; Jacob Lund; Paula L Hedley; A John Camm; Göran Wettrell; Inger Fosdal; Michael Christiansen; Anders D Børglum Journal: Am J Hum Genet Date: 2012-10-05 Impact factor: 11.025
Authors: Małgorzata Stępień-Wojno; Joanna Ponińska; Elżbieta K Biernacka; Bogna Foss-Nieradko; Tomasz Chwyczko; Paweł Syska; Rafał Płoski; Zofia T Bilińska Journal: Diagnostics (Basel) Date: 2020-06-27
Authors: Daniel J Blackwell; Michela Faggioni; Matthew J Wleklinski; Nieves Gomez-Hurtado; Raghav Venkataraman; Chelsea E Gibbs; Franz J Baudenbacher; Shiaoching Gong; Glenn I Fishman; Patrick M Boyle; Karl Pfeifer; Bjorn C Knollmann Journal: JCI Insight Date: 2022-02-08