Risk of atrial fibrillation as a function of the electrocardiographic PR interval: Results from the Copenhagen ECG Study

Nielsen, Jonas B.; Pietersen, Adrian; Graff, Claus; Lind, Bent; Struijk, Johannes; Olesen, Morten S.; Haunsø, Stig; Gerds, Thomas Alexander; Ellinor, Patrick T.; Køber, Lars; Svendsen, Jesper Hastrup; Holst, Anders G.

doi:10.1016/j.hrthm.2013.04.012

Cited by 113 publications

(97 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5 Several studies have shown PR-interval prolongation on an ECG to be an independent risk factor for developing AF. [6][7][8] Five independent GWAS publications have shown that genetic variants in SCN10A influence the PR-interval duration. [9][10][11][12][13] Pfeufer et al showed that 5 out of 9 PR-associated loci from GWAS increased the risk of AF.…”

Section: Clinical Perspective P 73mentioning

confidence: 99%

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Jabbari

Olesen

Yuan

et al. 2015

Circ Cardiovasc Genet

Self Cite

View full text Add to dashboard Cite

2=0.933). We therefore sought to determine whether common and rare SCN10A variants are associated with early onset AF. Methods and Results-SCN10A was sequenced in 225 AF patients in whom there was no evidence of other cardiovascular disease or dysfunction (lone AF). In an association study of the rs6795970 single nucleotide polymorphism variant, we included 515 AF patients and 2 control cohorts of 730 individuals free of AF and 6161 randomly sampled individuals. Functional characterization of SCN10A variants was performed by whole-cell patch-clamping. In the lone AF cohort, 9 rare missense variants and 1 splice site donor variant were detected. Interestingly, AF patients were found to have higher G allele frequency of rs6795970, which encodes the alanine variant at position 1073 (described from here on as A1073, odds ratio =1 ). Both of the common variants, A1073 and P1092, induced a gain-of-channel function, whereas the rare missense variants, V94G and R1588Q, resulted in a loss-of-channel function. Conclusions-The common variant A1073 is associated with increased susceptibility to AF. Both rare and common variants have effect on the function of the channel, indicating that these variants influence susceptibility to AF. Hence, our study suggests that SCN10A variations are involved in the genesis of AF. (Circ Cardiovasc Genet. 2015;8:64-73.

show abstract

Section: Clinical Perspective P 73mentioning

confidence: 99%

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Jabbari

Olesen

Yuan

et al. 2015

Circ Cardiovasc Genet

Self Cite

View full text Add to dashboard Cite

show abstract

“…The age dependence in our study is in accordance with previous studies demonstrating the close correlation between AF incidence and increasing age. 20,21 In the Event Monitor Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) study, also analyzing CS/TIA patients, age and the number of atrial extrasystoles on Holter were significant predictors of AF as well. 20,22 Patients in EMBRACE were significantly older (73 vs 61 years), and this potentially explains the higher AF detection rate in that study.…”

mentioning

confidence: 99%

“…Prolonged PR interval has been found in several epidemiologic studies to be an early marker of AF. 21,23,24 In the Framingham Heart Study, each 20-millisecond increase in PR interval was associated with a 20% increase in the risk of developing subsequent AF. In CRYSTAL AF, every 10-millisecond increase led to a relative PR interval increase of approximately 30%, averaging across patients on and off PR interval prolonging medications.…”

mentioning

confidence: 99%

Predictors for atrial fibrillation detection after cryptogenic stroke

et al. 2016

View full text Add to dashboard Cite

Objective: We assessed predictors of atrial fibrillation (AF) in cryptogenic stroke (CS) or transient ischemic attack (TIA) patients who received an insertable cardiac monitor (ICM). Methods:We studied patients with CS/TIA who were randomized to ICM within the CRYSTAL AF study. We assessed whether age, sex, race, body mass index, type and severity of index ischemic event, CHADS 2 score, PR interval, and presence of diabetes, hypertension, congestive heart failure, or patent foramen ovale and premature atrial contractions predicted AF development within the initial 12 and 36 months of follow-up using Cox proportional hazards models.Results: Among 221 patients randomized to ICM (age 61.6 6 11.4 years, 64% male), AF episodes were detected in 29 patients within 12 months and 42 patients at 36 months. Significant univariate predictors of AF at 12 months included age (hazard ratio [ Conclusion:Increasing age and a prolonged PR interval at enrollment were independently associated with an increased AF incidence in CS patients. However, they offered only moderate predictive ability in determining which CS patients had AF detected by the ICM. The CRYSTAL AF trial showed that the rate of atrial fibrillation (AF) detection among patients with cryptogenic stroke (CS) or transient ischemic attack (TIA) was 30% within 3 years after insertion of an insertable cardiac monitor (ICM). 1Numerous genetic, clinical, electrocardiographic, and echocardiographic features have been proposed as risk markers for developing AF.2-12 Within the Framingham Heart Study, a risk score for development of AF within 10 years was created, which included age, sex, body mass index, systolic blood pressure, treatment for hypertension, PR interval, clinically significant cardiac murmur, and heart failure.13 Echocardiographic measures did not improve risk prediction substantially.AF episodes are frequently asymptomatic and intermittent. Most CS/TIA patients monitored by ICM for AF detection have already undergone short-term Holter monitoring or telemetry in addition to cardiac and vascular imaging before device insertion.

show abstract

“…As the HF þ AF mouse model displays episodic AF, PR interval was used as an additional marker of disease status. Prolonged PR intervals in disease settings have been associated with AF, HF and death in humans [28][29][30] . Consistent with this association, PR interval deteriorates in the HF þ AF model with age and disease progression ( Supplementary Fig.…”

mentioning

confidence: 99%

The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

et al. 2014

View full text Add to dashboard Cite

Heart failure (HF) and atrial fibrillation (AF) share common risk factors, frequently coexist and are associated with high mortality. Treatment of HF with AF represents a major unmet need. Here we show that a small molecule, BGP-15, improves cardiac function and reduces arrhythmic episodes in two independent mouse models, which progressively develop HF and AF. In these models, BGP-15 treatment is associated with increased phosphorylation of the insulin-like growth factor 1 receptor (IGF1R), which is depressed in atrial tissue samples from patients with AF. Cardiac-specific IGF1R transgenic overexpression in mice with HF and AF recapitulates the protection observed with BGP-15. We further demonstrate that BGP-15 and IGF1R can provide protection independent of phosphoinositide 3-kinase-Akt and heat-shock protein 70; signalling mediators often defective in the aged and diseased heart. As BGP-15 is safe and well tolerated in humans, this study uncovers a potential therapeutic approach for HF and AF.

show abstract

Risk of atrial fibrillation as a function of the electrocardiographic PR interval: Results from the Copenhagen ECG Study

Cited by 113 publications

References 31 publications

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation

Predictors for atrial fibrillation detection after cryptogenic stroke

The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

Contact Info

Product

Resources

About