Novel association of polymorphic genetic variants with predictors of outcome of catheter ablation in atrial fibrillation: new directions from a prospective study (DECAF)

Sanghamitra Mohanty, Amelia W. Hall, Prasant Mohanty, Sameer Prakash, Chintan Trivedi, Luigi Di Biase, Pasquale Santangeli, Rong Bai, J. David Burkhardt, G. Joseph Gallinghouse, Rodney Horton, Javier E. Sanchez, Patrick M. Hranitzky, Amin Al-Ahmad, Vishwanath R. Iyer, Andrea Natale

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: Non-pulmonary vein (non-PV) triggers and left atrial (LA) scars perpetuate atrial fibrillation (AF) and limit the success rate of catheter ablation. In order to understand the genetic basis of these risk factors, we examined the association of selected single nucleotide polymorphisms (SNPs) with scar and non-PV triggers. Methods: Four hundred AF patients (67 % male, 62 ± 12 years, LA size 45.3 ± 7 mm, 64 % non-paroxysmal) undergoing catheter ablation were prospectively enrolled. DNA extractions for 16 AF-related SNPS from blood samples were performed of which 371 DNA samples were available for genotyping. Multivariate logistic regression analysis was used for assessing predictive role of individual SNP, and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers and LA scar. False discovery rate (FDR) was computed for all candidate SNPs to address multiple testing. Results: SNPs rs6599230 and rs6843082 were inversely associated (OR 0.68, p = 0.04, and 0.62, p = 0.01, respectively) whereas rs1448817 (OR 1.74, p = 0.04) and rs7193343 (OR 1.66, p = 0.02) predicted higher risk of non-PV triggers. Genotypes for rs6599230 and rs6843082 conferred 51 % reduction in the odds for non-PV triggers (combined OR 0.49, p = 0.019), while rs1448817 and rs7193343 demonstrated a combined OR of 1.93, p = 0.025. FDR was controlled at 16 % to adjust for multiple testing. For LA scar, inverse association was observed with rs1448817 (OR 0.29, p = 0.006), rs17042171 (OR 0.27, p = 0.032), rs3807989 (OR 0.54, p = 0.017), and rs6843082 (OR 0.56, p = 0.009). Two SNPs were associated with increased scar risk: rs17375901 (OR 3.68, p = 0.03) and rs7193343 (OR 1.74, p = 0.037). For global association of SNPs with left atrial scar FDR was controlled at ≤10 % to adjust for multiple testing. Conclusions: This study has a strong clinical significance as it provides important insights into the molecular basis of pertinent therapeutic targets. Our findings demonstrate that the presence of certain genetic polymorphisms increases the risk of scar and non-PV triggers in AF patients. Therefore, PVAI alone will not be enough to eliminate the arrhythmia and the operators may need to identify and isolate the non-PV foci to maximize procedural success in patients carrying these risk variants. Clinical trial registration: clinicaltrials.gov (NCT01751607)

Original languageEnglish (US)
Pages (from-to)7-17
Number of pages11
JournalJournal of Interventional Cardiac Electrophysiology
Volume45
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Catheter Ablation
Atrial Fibrillation
Cicatrix
Single Nucleotide Polymorphism
Veins
Prospective Studies
DNA
Genetic Polymorphisms
Direction compound
Cardiac Arrhythmias
Logistic Models
Genotype
Regression Analysis
Clinical Trials

Keywords

  • Atrial fibrillation
  • Left atrial scar
  • Non-PV triggers
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Novel association of polymorphic genetic variants with predictors of outcome of catheter ablation in atrial fibrillation : new directions from a prospective study (DECAF). / Mohanty, Sanghamitra; Hall, Amelia W.; Mohanty, Prasant; Prakash, Sameer; Trivedi, Chintan; Di Biase, Luigi; Santangeli, Pasquale; Bai, Rong; Burkhardt, J. David; Gallinghouse, G. Joseph; Horton, Rodney; Sanchez, Javier E.; Hranitzky, Patrick M.; Al-Ahmad, Amin; Iyer, Vishwanath R.; Natale, Andrea.

In: Journal of Interventional Cardiac Electrophysiology, Vol. 45, No. 1, 01.01.2016, p. 7-17.

Research output: Contribution to journalArticle

Mohanty, S, Hall, AW, Mohanty, P, Prakash, S, Trivedi, C, Di Biase, L, Santangeli, P, Bai, R, Burkhardt, JD, Gallinghouse, GJ, Horton, R, Sanchez, JE, Hranitzky, PM, Al-Ahmad, A, Iyer, VR & Natale, A 2016, 'Novel association of polymorphic genetic variants with predictors of outcome of catheter ablation in atrial fibrillation: new directions from a prospective study (DECAF)', Journal of Interventional Cardiac Electrophysiology, vol. 45, no. 1, pp. 7-17. https://doi.org/10.1007/s10840-015-0069-2
Mohanty, Sanghamitra ; Hall, Amelia W. ; Mohanty, Prasant ; Prakash, Sameer ; Trivedi, Chintan ; Di Biase, Luigi ; Santangeli, Pasquale ; Bai, Rong ; Burkhardt, J. David ; Gallinghouse, G. Joseph ; Horton, Rodney ; Sanchez, Javier E. ; Hranitzky, Patrick M. ; Al-Ahmad, Amin ; Iyer, Vishwanath R. ; Natale, Andrea. / Novel association of polymorphic genetic variants with predictors of outcome of catheter ablation in atrial fibrillation : new directions from a prospective study (DECAF). In: Journal of Interventional Cardiac Electrophysiology. 2016 ; Vol. 45, No. 1. pp. 7-17.
@article{b2f3a40f98b34eaca7241d2680734956,
title = "Novel association of polymorphic genetic variants with predictors of outcome of catheter ablation in atrial fibrillation: new directions from a prospective study (DECAF)",
abstract = "Purpose: Non-pulmonary vein (non-PV) triggers and left atrial (LA) scars perpetuate atrial fibrillation (AF) and limit the success rate of catheter ablation. In order to understand the genetic basis of these risk factors, we examined the association of selected single nucleotide polymorphisms (SNPs) with scar and non-PV triggers. Methods: Four hundred AF patients (67 {\%} male, 62 ± 12 years, LA size 45.3 ± 7 mm, 64 {\%} non-paroxysmal) undergoing catheter ablation were prospectively enrolled. DNA extractions for 16 AF-related SNPS from blood samples were performed of which 371 DNA samples were available for genotyping. Multivariate logistic regression analysis was used for assessing predictive role of individual SNP, and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers and LA scar. False discovery rate (FDR) was computed for all candidate SNPs to address multiple testing. Results: SNPs rs6599230 and rs6843082 were inversely associated (OR 0.68, p = 0.04, and 0.62, p = 0.01, respectively) whereas rs1448817 (OR 1.74, p = 0.04) and rs7193343 (OR 1.66, p = 0.02) predicted higher risk of non-PV triggers. Genotypes for rs6599230 and rs6843082 conferred 51 {\%} reduction in the odds for non-PV triggers (combined OR 0.49, p = 0.019), while rs1448817 and rs7193343 demonstrated a combined OR of 1.93, p = 0.025. FDR was controlled at 16 {\%} to adjust for multiple testing. For LA scar, inverse association was observed with rs1448817 (OR 0.29, p = 0.006), rs17042171 (OR 0.27, p = 0.032), rs3807989 (OR 0.54, p = 0.017), and rs6843082 (OR 0.56, p = 0.009). Two SNPs were associated with increased scar risk: rs17375901 (OR 3.68, p = 0.03) and rs7193343 (OR 1.74, p = 0.037). For global association of SNPs with left atrial scar FDR was controlled at ≤10 {\%} to adjust for multiple testing. Conclusions: This study has a strong clinical significance as it provides important insights into the molecular basis of pertinent therapeutic targets. Our findings demonstrate that the presence of certain genetic polymorphisms increases the risk of scar and non-PV triggers in AF patients. Therefore, PVAI alone will not be enough to eliminate the arrhythmia and the operators may need to identify and isolate the non-PV foci to maximize procedural success in patients carrying these risk variants. Clinical trial registration: clinicaltrials.gov (NCT01751607)",
keywords = "Atrial fibrillation, Left atrial scar, Non-PV triggers, Single nucleotide polymorphism",
author = "Sanghamitra Mohanty and Hall, {Amelia W.} and Prasant Mohanty and Sameer Prakash and Chintan Trivedi and {Di Biase}, Luigi and Pasquale Santangeli and Rong Bai and Burkhardt, {J. David} and Gallinghouse, {G. Joseph} and Rodney Horton and Sanchez, {Javier E.} and Hranitzky, {Patrick M.} and Amin Al-Ahmad and Iyer, {Vishwanath R.} and Andrea Natale",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/s10840-015-0069-2",
language = "English (US)",
volume = "45",
pages = "7--17",
journal = "Journal of Interventional Cardiac Electrophysiology",
issn = "1383-875X",
publisher = "Springer Netherlands",
number = "1",

}

TY - JOUR

T1 - Novel association of polymorphic genetic variants with predictors of outcome of catheter ablation in atrial fibrillation

T2 - new directions from a prospective study (DECAF)

AU - Mohanty, Sanghamitra

AU - Hall, Amelia W.

AU - Mohanty, Prasant

AU - Prakash, Sameer

AU - Trivedi, Chintan

AU - Di Biase, Luigi

AU - Santangeli, Pasquale

AU - Bai, Rong

AU - Burkhardt, J. David

AU - Gallinghouse, G. Joseph

AU - Horton, Rodney

AU - Sanchez, Javier E.

AU - Hranitzky, Patrick M.

AU - Al-Ahmad, Amin

AU - Iyer, Vishwanath R.

AU - Natale, Andrea

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Purpose: Non-pulmonary vein (non-PV) triggers and left atrial (LA) scars perpetuate atrial fibrillation (AF) and limit the success rate of catheter ablation. In order to understand the genetic basis of these risk factors, we examined the association of selected single nucleotide polymorphisms (SNPs) with scar and non-PV triggers. Methods: Four hundred AF patients (67 % male, 62 ± 12 years, LA size 45.3 ± 7 mm, 64 % non-paroxysmal) undergoing catheter ablation were prospectively enrolled. DNA extractions for 16 AF-related SNPS from blood samples were performed of which 371 DNA samples were available for genotyping. Multivariate logistic regression analysis was used for assessing predictive role of individual SNP, and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers and LA scar. False discovery rate (FDR) was computed for all candidate SNPs to address multiple testing. Results: SNPs rs6599230 and rs6843082 were inversely associated (OR 0.68, p = 0.04, and 0.62, p = 0.01, respectively) whereas rs1448817 (OR 1.74, p = 0.04) and rs7193343 (OR 1.66, p = 0.02) predicted higher risk of non-PV triggers. Genotypes for rs6599230 and rs6843082 conferred 51 % reduction in the odds for non-PV triggers (combined OR 0.49, p = 0.019), while rs1448817 and rs7193343 demonstrated a combined OR of 1.93, p = 0.025. FDR was controlled at 16 % to adjust for multiple testing. For LA scar, inverse association was observed with rs1448817 (OR 0.29, p = 0.006), rs17042171 (OR 0.27, p = 0.032), rs3807989 (OR 0.54, p = 0.017), and rs6843082 (OR 0.56, p = 0.009). Two SNPs were associated with increased scar risk: rs17375901 (OR 3.68, p = 0.03) and rs7193343 (OR 1.74, p = 0.037). For global association of SNPs with left atrial scar FDR was controlled at ≤10 % to adjust for multiple testing. Conclusions: This study has a strong clinical significance as it provides important insights into the molecular basis of pertinent therapeutic targets. Our findings demonstrate that the presence of certain genetic polymorphisms increases the risk of scar and non-PV triggers in AF patients. Therefore, PVAI alone will not be enough to eliminate the arrhythmia and the operators may need to identify and isolate the non-PV foci to maximize procedural success in patients carrying these risk variants. Clinical trial registration: clinicaltrials.gov (NCT01751607)

AB - Purpose: Non-pulmonary vein (non-PV) triggers and left atrial (LA) scars perpetuate atrial fibrillation (AF) and limit the success rate of catheter ablation. In order to understand the genetic basis of these risk factors, we examined the association of selected single nucleotide polymorphisms (SNPs) with scar and non-PV triggers. Methods: Four hundred AF patients (67 % male, 62 ± 12 years, LA size 45.3 ± 7 mm, 64 % non-paroxysmal) undergoing catheter ablation were prospectively enrolled. DNA extractions for 16 AF-related SNPS from blood samples were performed of which 371 DNA samples were available for genotyping. Multivariate logistic regression analysis was used for assessing predictive role of individual SNP, and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers and LA scar. False discovery rate (FDR) was computed for all candidate SNPs to address multiple testing. Results: SNPs rs6599230 and rs6843082 were inversely associated (OR 0.68, p = 0.04, and 0.62, p = 0.01, respectively) whereas rs1448817 (OR 1.74, p = 0.04) and rs7193343 (OR 1.66, p = 0.02) predicted higher risk of non-PV triggers. Genotypes for rs6599230 and rs6843082 conferred 51 % reduction in the odds for non-PV triggers (combined OR 0.49, p = 0.019), while rs1448817 and rs7193343 demonstrated a combined OR of 1.93, p = 0.025. FDR was controlled at 16 % to adjust for multiple testing. For LA scar, inverse association was observed with rs1448817 (OR 0.29, p = 0.006), rs17042171 (OR 0.27, p = 0.032), rs3807989 (OR 0.54, p = 0.017), and rs6843082 (OR 0.56, p = 0.009). Two SNPs were associated with increased scar risk: rs17375901 (OR 3.68, p = 0.03) and rs7193343 (OR 1.74, p = 0.037). For global association of SNPs with left atrial scar FDR was controlled at ≤10 % to adjust for multiple testing. Conclusions: This study has a strong clinical significance as it provides important insights into the molecular basis of pertinent therapeutic targets. Our findings demonstrate that the presence of certain genetic polymorphisms increases the risk of scar and non-PV triggers in AF patients. Therefore, PVAI alone will not be enough to eliminate the arrhythmia and the operators may need to identify and isolate the non-PV foci to maximize procedural success in patients carrying these risk variants. Clinical trial registration: clinicaltrials.gov (NCT01751607)

KW - Atrial fibrillation

KW - Left atrial scar

KW - Non-PV triggers

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=84957435191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957435191&partnerID=8YFLogxK

U2 - 10.1007/s10840-015-0069-2

DO - 10.1007/s10840-015-0069-2

M3 - Article

C2 - 26497660

AN - SCOPUS:84957435191

VL - 45

SP - 7

EP - 17

JO - Journal of Interventional Cardiac Electrophysiology

JF - Journal of Interventional Cardiac Electrophysiology

SN - 1383-875X

IS - 1

ER -