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Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients
| Content Provider | Scilit |
|---|---|
| Author | Faggioni, Michela Hwang, Hyun Seok van der Werf, Christian Nederend, Ineke Kannankeril, Prince J. Wilde, Arthur A. M. Knollmann, Björn C. |
| Copyright Year | 2013 |
| Description | Journal: Circulation Research Rationale:: 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). Objective:: To test the hypothesis that CPVT is suppressed by supraventricular overdrive stimulation. Methods and Results:: Using CPVT mouse models (Casq2$ ^{−/−}$ and RyR2$ ^{R4496C/+}$ 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$ ^{−/−}$ mice (6/7) and significantly reduced the VA score (atropine: 0.6±0.2 versus vehicle: 1.7±0.3; P <0.05). Atrial overdrive pacing completely prevented VA in 16 of 19 (84%) Casq2$ ^{−/−}$ and in 7 of 8 (88%) RyR2$ ^{R4496C/+}$ mice and significantly reduced ventricular premature beats in both CPVT models ( P 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. Conclusions:: 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601570/pdf https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.111.300076 |
| Ending Page | 697 |
| Page Count | 9 |
| Starting Page | 689 |
| ISSN | 00097330 |
| e-ISSN | 15244571 |
| DOI | 10.1161/circresaha.111.300076 |
| Journal | Circulation Research |
| Issue Number | 4 |
| Volume Number | 112 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2013-02-15 |
| Access Restriction | Open |
| Subject Keyword | Journal: Circulation Research Peripheral Vascular Disease Parasympathetic Tone Arrhythmia Suppression Catecholaminergic Polymorphic Ventricular Tachycardia |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Cardiology and Cardiovascular Medicine |
