Abstract
Background - Cardiac device implantation can be complicated by inability to adequately place leads because of significant lead capture issues. This study sought to determine whether there are genetic bases that underlie poor lead capture. Methods and Results - Retrospective review of all patients with structurally normal hearts who underwent new device implantation at Texas Children's Hospital between 2009 and 2014 was performed. Patients with inability to capture at 10 V or a final capture threshold ≥3 V at 0.4 ms during implant were analyzed. Among a total of 136 patients (median age, 13 years; range, 3 days to 46 years), 11 patients (8.1%) who underwent dual chamber device implantation had elevated thresholds in the atria (4), ventricle (3), or both chambers (4; atrial-lead threshold, 4.7±4.3 versus 0.7±0.3 V; ventricular-lead, 3.0±3.3 versus 0.7±0.3 V). All 11 patients presented with sinus node dysfunction and 10 had atrial arrhythmias. At implant, inability to find atrial capture was seen in 4 patients. Three demonstrated intermittent complete loss of ventricular capture after implantation: 1 has recurrent syncope, 2 eventually died. Genetic testing performed in 10 demonstrated 7 patients with 6 distinct SCN5A mutations, all predicted to be severe loss-of-function mutations by bioinformatic analyses. In the remaining patients, although putative pathogenic mutations were not found, multiple SCN5A polymorphisms were identified in 2 and a desmin mutation in 1. Conclusions - This study suggests that significant capture issues at implant may be because of loss-of-function SCN5A mutations, providing new insights into SCN5A function. Recognition of this association may be critical for planning device implantation strategies and patient follow-up.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1105-1112 |
| Number of pages | 8 |
| Journal | Circulation: Arrhythmia and Electrophysiology |
| Volume | 8 |
| Issue number | 5 |
| DOIs | |
| State | Published - Oct 1 2015 |
| Externally published | Yes |
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Keywords
- atrial tachyarrhythmia with short PR
- Brugada syndrome
- cardiac pacemaker, artificial
- implantable cardioverter-defibrillators
- NaV1.5 voltage-gated sodium channel
- SCN5A protein, human
- sick sinus syndrome
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Loss-of-Function SCN5A Mutations Associated with Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture. / Chiang, David Y.; Kim, Jeffrey J.; Valdes, Santiago O.; de la Uz, Caridad; Fan, Yuxin; Orcutt, Jeffrey; Domino, Melissa; Smith, Melissa; Wehrens, Xander H.T.; Miyake, Christina Y.
In: Circulation: Arrhythmia and Electrophysiology, Vol. 8, No. 5, 01.10.2015, p. 1105-1112.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Loss-of-Function SCN5A Mutations Associated with Sinus Node Dysfunction, Atrial Arrhythmias, and Poor Pacemaker Capture
AU - Chiang, David Y.
AU - Kim, Jeffrey J.
AU - Valdes, Santiago O.
AU - de la Uz, Caridad
AU - Fan, Yuxin
AU - Orcutt, Jeffrey
AU - Domino, Melissa
AU - Smith, Melissa
AU - Wehrens, Xander H.T.
AU - Miyake, Christina Y.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Background - Cardiac device implantation can be complicated by inability to adequately place leads because of significant lead capture issues. This study sought to determine whether there are genetic bases that underlie poor lead capture. Methods and Results - Retrospective review of all patients with structurally normal hearts who underwent new device implantation at Texas Children's Hospital between 2009 and 2014 was performed. Patients with inability to capture at 10 V or a final capture threshold ≥3 V at 0.4 ms during implant were analyzed. Among a total of 136 patients (median age, 13 years; range, 3 days to 46 years), 11 patients (8.1%) who underwent dual chamber device implantation had elevated thresholds in the atria (4), ventricle (3), or both chambers (4; atrial-lead threshold, 4.7±4.3 versus 0.7±0.3 V; ventricular-lead, 3.0±3.3 versus 0.7±0.3 V). All 11 patients presented with sinus node dysfunction and 10 had atrial arrhythmias. At implant, inability to find atrial capture was seen in 4 patients. Three demonstrated intermittent complete loss of ventricular capture after implantation: 1 has recurrent syncope, 2 eventually died. Genetic testing performed in 10 demonstrated 7 patients with 6 distinct SCN5A mutations, all predicted to be severe loss-of-function mutations by bioinformatic analyses. In the remaining patients, although putative pathogenic mutations were not found, multiple SCN5A polymorphisms were identified in 2 and a desmin mutation in 1. Conclusions - This study suggests that significant capture issues at implant may be because of loss-of-function SCN5A mutations, providing new insights into SCN5A function. Recognition of this association may be critical for planning device implantation strategies and patient follow-up.
AB - Background - Cardiac device implantation can be complicated by inability to adequately place leads because of significant lead capture issues. This study sought to determine whether there are genetic bases that underlie poor lead capture. Methods and Results - Retrospective review of all patients with structurally normal hearts who underwent new device implantation at Texas Children's Hospital between 2009 and 2014 was performed. Patients with inability to capture at 10 V or a final capture threshold ≥3 V at 0.4 ms during implant were analyzed. Among a total of 136 patients (median age, 13 years; range, 3 days to 46 years), 11 patients (8.1%) who underwent dual chamber device implantation had elevated thresholds in the atria (4), ventricle (3), or both chambers (4; atrial-lead threshold, 4.7±4.3 versus 0.7±0.3 V; ventricular-lead, 3.0±3.3 versus 0.7±0.3 V). All 11 patients presented with sinus node dysfunction and 10 had atrial arrhythmias. At implant, inability to find atrial capture was seen in 4 patients. Three demonstrated intermittent complete loss of ventricular capture after implantation: 1 has recurrent syncope, 2 eventually died. Genetic testing performed in 10 demonstrated 7 patients with 6 distinct SCN5A mutations, all predicted to be severe loss-of-function mutations by bioinformatic analyses. In the remaining patients, although putative pathogenic mutations were not found, multiple SCN5A polymorphisms were identified in 2 and a desmin mutation in 1. Conclusions - This study suggests that significant capture issues at implant may be because of loss-of-function SCN5A mutations, providing new insights into SCN5A function. Recognition of this association may be critical for planning device implantation strategies and patient follow-up.
KW - atrial tachyarrhythmia with short PR
KW - Brugada syndrome
KW - cardiac pacemaker, artificial
KW - implantable cardioverter-defibrillators
KW - NaV1.5 voltage-gated sodium channel
KW - SCN5A protein, human
KW - sick sinus syndrome
UR - http://www.scopus.com/inward/record.url?scp=84944687596&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84944687596&partnerID=8YFLogxK
U2 - 10.1161/CIRCEP.115.003098
DO - 10.1161/CIRCEP.115.003098
M3 - Article
C2 - 26111534
AN - SCOPUS:84944687596
VL - 8
SP - 1105
EP - 1112
JO - Circulation: Arrhythmia and Electrophysiology
JF - Circulation: Arrhythmia and Electrophysiology
SN - 1941-3149
IS - 5
ER -