Loading…
Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients
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...
Saved in:
| Published in: | Circulation research 2013-02, Vol.112 (4), p.689-697 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c5746-7d8919df85cd5bf5c103595186c08743bbc81ca48b8e6588ba0e8d6a1c8e03903 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c5746-7d8919df85cd5bf5c103595186c08743bbc81ca48b8e6588ba0e8d6a1c8e03903 |
| container_end_page | 697 |
| container_issue | 4 |
| container_start_page | 689 |
| container_title | Circulation research |
| container_volume | 112 |
| creator | Faggioni, Michela Hwang, Hyun Seok van der Werf, Christian Nederend, Ineke Kannankeril, Prince J Wilde, Arthur A.M Knollmann, Björn C |
| description | 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 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 (atropine0.6±0.2 versus vehicle1.7±0.3; P |
| doi_str_mv | 10.1161/CIRCRESAHA.111.300076 |
| format | article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3601570</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>23295832</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5746-7d8919df85cd5bf5c103595186c08743bbc81ca48b8e6588ba0e8d6a1c8e03903</originalsourceid><addsrcrecordid>eNpVUdtO3DAQtaqisqX9hCL_QOhMHCfOS6VVxE0CdbVAXy1n4iUuTrJysqD9exxtS-nT3M45M5rD2DeEM8Qcv1fX62p9fre8WsYazwQAFPkHtkCZZkkmC_zIFrFXJoUQcMw-j-NvAMxEWn5ix2kMUol0wYYlkfU2mMk2_M71u5Gv2_3UdnwV7LPtp5FXcUbt4E3nehseHfHV4PfdELZtzH9FTHC08ybwe0PtnkxonOGu57eOLDd9M-crM7lZ7Qs72hg_2q9_4gl7uDi_r66Sm5-X19XyJiFZZHlSNKrEstkoSY2sN5IQhCwlqpxAFZmoa1JIJlO1srlUqjZgVZMbJGVBlCBO2I-D7nZXd7ah-Urj9Ta4zoS9HozT_0961-rH4VmLHFAWs4A8CFAYxjHYzRsXQc8O6H8OxBr1wYHIO32_-I319-URkB0AL4OfbBif_O7FBt1a46dWRxEQgGmSAgpIUUISO5iLV_CYlTw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients</title><source>Freely Accessible Science Journals - check A-Z of ejournals</source><creator>Faggioni, Michela ; Hwang, Hyun Seok ; van der Werf, Christian ; Nederend, Ineke ; Kannankeril, Prince J ; Wilde, Arthur A.M ; Knollmann, Björn C</creator><creatorcontrib>Faggioni, Michela ; Hwang, Hyun Seok ; van der Werf, Christian ; Nederend, Ineke ; Kannankeril, Prince J ; Wilde, Arthur A.M ; Knollmann, Björn C</creatorcontrib><description>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 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 (atropine0.6±0.2 versus vehicle1.7±0.3; P<0.05). Atrial overdrive pacing completely prevented VA in 16 of 19 (84%) Casq2 and in 7 of 8 (88%) RyR2 mice and significantly reduced ventricular premature beats in both CPVT models (P<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-naïve individuals that reached >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.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/CIRCRESAHA.111.300076</identifier><identifier>PMID: 23295832</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Adult ; Animals ; Atropine - pharmacology ; Atropine - therapeutic use ; Bradycardia - genetics ; Bradycardia - physiopathology ; Caffeine - toxicity ; Calcium Signaling - physiology ; Calsequestrin - deficiency ; Calsequestrin - genetics ; Calsequestrin - physiology ; Cardiac Pacing, Artificial ; Exercise Test ; Heart Rate - drug effects ; Humans ; Isoproterenol - toxicity ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - physiology ; Random Allocation ; Ryanodine Receptor Calcium Release Channel - deficiency ; Ryanodine Receptor Calcium Release Channel - genetics ; Ryanodine Receptor Calcium Release Channel - physiology ; Sinoatrial Node - physiopathology ; Sympathectomy, Chemical ; Tachycardia, Ventricular ; Vagus Nerve - drug effects ; Vagus Nerve - physiopathology ; Ventricular Premature Complexes - etiology ; Ventricular Premature Complexes - prevention & control</subject><ispartof>Circulation research, 2013-02, Vol.112 (4), p.689-697</ispartof><rights>2013 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5746-7d8919df85cd5bf5c103595186c08743bbc81ca48b8e6588ba0e8d6a1c8e03903</citedby><cites>FETCH-LOGICAL-c5746-7d8919df85cd5bf5c103595186c08743bbc81ca48b8e6588ba0e8d6a1c8e03903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23295832$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Faggioni, Michela</creatorcontrib><creatorcontrib>Hwang, Hyun Seok</creatorcontrib><creatorcontrib>van der Werf, Christian</creatorcontrib><creatorcontrib>Nederend, Ineke</creatorcontrib><creatorcontrib>Kannankeril, Prince J</creatorcontrib><creatorcontrib>Wilde, Arthur A.M</creatorcontrib><creatorcontrib>Knollmann, Björn C</creatorcontrib><title>Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>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 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 (atropine0.6±0.2 versus vehicle1.7±0.3; P<0.05). Atrial overdrive pacing completely prevented VA in 16 of 19 (84%) Casq2 and in 7 of 8 (88%) RyR2 mice and significantly reduced ventricular premature beats in both CPVT models (P<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-naïve individuals that reached >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.</description><subject>Adult</subject><subject>Animals</subject><subject>Atropine - pharmacology</subject><subject>Atropine - therapeutic use</subject><subject>Bradycardia - genetics</subject><subject>Bradycardia - physiopathology</subject><subject>Caffeine - toxicity</subject><subject>Calcium Signaling - physiology</subject><subject>Calsequestrin - deficiency</subject><subject>Calsequestrin - genetics</subject><subject>Calsequestrin - physiology</subject><subject>Cardiac Pacing, Artificial</subject><subject>Exercise Test</subject><subject>Heart Rate - drug effects</subject><subject>Humans</subject><subject>Isoproterenol - toxicity</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Middle Aged</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - physiology</subject><subject>Random Allocation</subject><subject>Ryanodine Receptor Calcium Release Channel - deficiency</subject><subject>Ryanodine Receptor Calcium Release Channel - genetics</subject><subject>Ryanodine Receptor Calcium Release Channel - physiology</subject><subject>Sinoatrial Node - physiopathology</subject><subject>Sympathectomy, Chemical</subject><subject>Tachycardia, Ventricular</subject><subject>Vagus Nerve - drug effects</subject><subject>Vagus Nerve - physiopathology</subject><subject>Ventricular Premature Complexes - etiology</subject><subject>Ventricular Premature Complexes - prevention & control</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpVUdtO3DAQtaqisqX9hCL_QOhMHCfOS6VVxE0CdbVAXy1n4iUuTrJysqD9exxtS-nT3M45M5rD2DeEM8Qcv1fX62p9fre8WsYazwQAFPkHtkCZZkkmC_zIFrFXJoUQcMw-j-NvAMxEWn5ix2kMUol0wYYlkfU2mMk2_M71u5Gv2_3UdnwV7LPtp5FXcUbt4E3nehseHfHV4PfdELZtzH9FTHC08ybwe0PtnkxonOGu57eOLDd9M-crM7lZ7Qs72hg_2q9_4gl7uDi_r66Sm5-X19XyJiFZZHlSNKrEstkoSY2sN5IQhCwlqpxAFZmoa1JIJlO1srlUqjZgVZMbJGVBlCBO2I-D7nZXd7ah-Urj9Ta4zoS9HozT_0961-rH4VmLHFAWs4A8CFAYxjHYzRsXQc8O6H8OxBr1wYHIO32_-I319-URkB0AL4OfbBif_O7FBt1a46dWRxEQgGmSAgpIUUISO5iLV_CYlTw</recordid><startdate>20130215</startdate><enddate>20130215</enddate><creator>Faggioni, Michela</creator><creator>Hwang, Hyun Seok</creator><creator>van der Werf, Christian</creator><creator>Nederend, Ineke</creator><creator>Kannankeril, Prince J</creator><creator>Wilde, Arthur A.M</creator><creator>Knollmann, Björn C</creator><general>American Heart Association, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20130215</creationdate><title>Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients</title><author>Faggioni, Michela ; Hwang, Hyun Seok ; van der Werf, Christian ; Nederend, Ineke ; Kannankeril, Prince J ; Wilde, Arthur A.M ; Knollmann, Björn C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5746-7d8919df85cd5bf5c103595186c08743bbc81ca48b8e6588ba0e8d6a1c8e03903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Atropine - pharmacology</topic><topic>Atropine - therapeutic use</topic><topic>Bradycardia - genetics</topic><topic>Bradycardia - physiopathology</topic><topic>Caffeine - toxicity</topic><topic>Calcium Signaling - physiology</topic><topic>Calsequestrin - deficiency</topic><topic>Calsequestrin - genetics</topic><topic>Calsequestrin - physiology</topic><topic>Cardiac Pacing, Artificial</topic><topic>Exercise Test</topic><topic>Heart Rate - drug effects</topic><topic>Humans</topic><topic>Isoproterenol - toxicity</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Middle Aged</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - physiology</topic><topic>Random Allocation</topic><topic>Ryanodine Receptor Calcium Release Channel - deficiency</topic><topic>Ryanodine Receptor Calcium Release Channel - genetics</topic><topic>Ryanodine Receptor Calcium Release Channel - physiology</topic><topic>Sinoatrial Node - physiopathology</topic><topic>Sympathectomy, Chemical</topic><topic>Tachycardia, Ventricular</topic><topic>Vagus Nerve - drug effects</topic><topic>Vagus Nerve - physiopathology</topic><topic>Ventricular Premature Complexes - etiology</topic><topic>Ventricular Premature Complexes - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Faggioni, Michela</creatorcontrib><creatorcontrib>Hwang, Hyun Seok</creatorcontrib><creatorcontrib>van der Werf, Christian</creatorcontrib><creatorcontrib>Nederend, Ineke</creatorcontrib><creatorcontrib>Kannankeril, Prince J</creatorcontrib><creatorcontrib>Wilde, Arthur A.M</creatorcontrib><creatorcontrib>Knollmann, Björn C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Faggioni, Michela</au><au>Hwang, Hyun Seok</au><au>van der Werf, Christian</au><au>Nederend, Ineke</au><au>Kannankeril, Prince J</au><au>Wilde, Arthur A.M</au><au>Knollmann, Björn C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2013-02-15</date><risdate>2013</risdate><volume>112</volume><issue>4</issue><spage>689</spage><epage>697</epage><pages>689-697</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><abstract>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 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 (atropine0.6±0.2 versus vehicle1.7±0.3; P<0.05). Atrial overdrive pacing completely prevented VA in 16 of 19 (84%) Casq2 and in 7 of 8 (88%) RyR2 mice and significantly reduced ventricular premature beats in both CPVT models (P<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-naïve individuals that reached >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.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>23295832</pmid><doi>10.1161/CIRCRESAHA.111.300076</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7330 |
| ispartof | Circulation research, 2013-02, Vol.112 (4), p.689-697 |
| issn | 0009-7330 1524-4571 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3601570 |
| source | Freely Accessible Science Journals - check A-Z of ejournals |
| subjects | Adult Animals Atropine - pharmacology Atropine - therapeutic use Bradycardia - genetics Bradycardia - physiopathology Caffeine - toxicity Calcium Signaling - physiology Calsequestrin - deficiency Calsequestrin - genetics Calsequestrin - physiology Cardiac Pacing, Artificial Exercise Test Heart Rate - drug effects Humans Isoproterenol - toxicity Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Myocytes, Cardiac - drug effects Myocytes, Cardiac - physiology Random Allocation Ryanodine Receptor Calcium Release Channel - deficiency Ryanodine Receptor Calcium Release Channel - genetics Ryanodine Receptor Calcium Release Channel - physiology Sinoatrial Node - physiopathology Sympathectomy, Chemical Tachycardia, Ventricular Vagus Nerve - drug effects Vagus Nerve - physiopathology Ventricular Premature Complexes - etiology Ventricular Premature Complexes - prevention & control |
| title | Accelerated Sinus Rhythm Prevents Catecholaminergic Polymorphic Ventricular Tachycardia in Mice and in Patients |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T22%3A50%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Accelerated%20Sinus%20Rhythm%20Prevents%20Catecholaminergic%20Polymorphic%20Ventricular%20Tachycardia%20in%20Mice%20and%20in%20Patients&rft.jtitle=Circulation%20research&rft.au=Faggioni,%20Michela&rft.date=2013-02-15&rft.volume=112&rft.issue=4&rft.spage=689&rft.epage=697&rft.pages=689-697&rft.issn=0009-7330&rft.eissn=1524-4571&rft_id=info:doi/10.1161/CIRCRESAHA.111.300076&rft_dat=%3Cpubmed_cross%3E23295832%3C/pubmed_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c5746-7d8919df85cd5bf5c103595186c08743bbc81ca48b8e6588ba0e8d6a1c8e03903%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/23295832&rfr_iscdi=true |