Abstract
Accurate diagnosis of long QT syndrome is a key factor for reducing the risk of cardiac arrhythmias. Our goal is to investigate the potential use of dofetilide to unmask latent IKr mutation carriers. A modified version of the O'Hara et al. model was used to simulate the electrical activity of isolated cardiac cells. The original IKr formulation was replaced by the Fink et al. Markov model of the human IKr channels and our dynamic model of dofetilide was used to simulate drug administration. A sensitivity analysis was performed to study the effect of IKr transition rate alterations on AP duration (APD) prolongation in the absence and in the presence of dofetilide. Our results show that acceleration of the rate transition from open to the last closed state (ββ) produced the shortest prolongation of the APD in the absence of the drug. However, ββ acceleration provoked the highest additional APD prolongation under dofetilide exposure related to the APD prolongation observed before the drug application. In addition, this IKr alteration was the transition rate modification that most increased the rate of deactivation. In conclusion, our observations indicate that dofetilide could potentially be used to unmask I Kr mutations accelerating the deactivation process.
| Original language | English (US) |
|---|---|
| Title of host publication | Computing in Cardiology |
| Pages | 845-848 |
| Number of pages | 4 |
| Volume | 39 |
| State | Published - 2012 |
| Event | 39th Computing in Cardiology Conference, CinC 2012 - Krakow, Poland Duration: Sep 9 2012 → Sep 12 2012 |
Other
| Other | 39th Computing in Cardiology Conference, CinC 2012 |
|---|---|
| Country | Poland |
| City | Krakow |
| Period | 9/9/12 → 9/12/12 |
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ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Computer Science(all)
Cite this
Dofetilide unmasks occult congenital long QT syndrome type 2 : A simulation study. / Romero, Lucia; Trenor, Beatriz; Ferrero, Jose Maria; Saiz, Javier; Clancy, Colleen E.
Computing in Cardiology. Vol. 39 2012. p. 845-848 6420526.Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - Dofetilide unmasks occult congenital long QT syndrome type 2
T2 - A simulation study
AU - Romero, Lucia
AU - Trenor, Beatriz
AU - Ferrero, Jose Maria
AU - Saiz, Javier
AU - Clancy, Colleen E
PY - 2012
Y1 - 2012
N2 - Accurate diagnosis of long QT syndrome is a key factor for reducing the risk of cardiac arrhythmias. Our goal is to investigate the potential use of dofetilide to unmask latent IKr mutation carriers. A modified version of the O'Hara et al. model was used to simulate the electrical activity of isolated cardiac cells. The original IKr formulation was replaced by the Fink et al. Markov model of the human IKr channels and our dynamic model of dofetilide was used to simulate drug administration. A sensitivity analysis was performed to study the effect of IKr transition rate alterations on AP duration (APD) prolongation in the absence and in the presence of dofetilide. Our results show that acceleration of the rate transition from open to the last closed state (ββ) produced the shortest prolongation of the APD in the absence of the drug. However, ββ acceleration provoked the highest additional APD prolongation under dofetilide exposure related to the APD prolongation observed before the drug application. In addition, this IKr alteration was the transition rate modification that most increased the rate of deactivation. In conclusion, our observations indicate that dofetilide could potentially be used to unmask I Kr mutations accelerating the deactivation process.
AB - Accurate diagnosis of long QT syndrome is a key factor for reducing the risk of cardiac arrhythmias. Our goal is to investigate the potential use of dofetilide to unmask latent IKr mutation carriers. A modified version of the O'Hara et al. model was used to simulate the electrical activity of isolated cardiac cells. The original IKr formulation was replaced by the Fink et al. Markov model of the human IKr channels and our dynamic model of dofetilide was used to simulate drug administration. A sensitivity analysis was performed to study the effect of IKr transition rate alterations on AP duration (APD) prolongation in the absence and in the presence of dofetilide. Our results show that acceleration of the rate transition from open to the last closed state (ββ) produced the shortest prolongation of the APD in the absence of the drug. However, ββ acceleration provoked the highest additional APD prolongation under dofetilide exposure related to the APD prolongation observed before the drug application. In addition, this IKr alteration was the transition rate modification that most increased the rate of deactivation. In conclusion, our observations indicate that dofetilide could potentially be used to unmask I Kr mutations accelerating the deactivation process.
UR - http://www.scopus.com/inward/record.url?scp=84875650183&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875650183&partnerID=8YFLogxK
M3 - Conference contribution
AN - SCOPUS:84875650183
SN - 9781467320740
VL - 39
SP - 845
EP - 848
BT - Computing in Cardiology
ER -