scholarly journals Assessment of the causal relevance of ECG parameters for risk of atrial fibrillation: A mendelian randomisation study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (5) ◽  
pp. e1003572
Author(s):  
Parag Ravindra Gajendragadkar ◽  
Adam Von Ende ◽  
Maysson Ibrahim ◽  
Elsa Valdes-Marquez ◽  
Christian Fielder Camm ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Qt Interval ◽  
P Wave ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Causal Relevance ◽  
Wave Duration ◽  
P Wave Duration ◽  
Atrial Size ◽  
Pr Interval

Background Atrial electrical and structural remodelling in older individuals with cardiovascular risk factors has been associated with changes in surface electrocardiographic (ECG) parameters (e.g., prolongation of the PR interval) and higher risks of atrial fibrillation (AF). However, it has been difficult to establish whether altered ECG parameters are the cause or a consequence of the myocardial substrate leading to AF. This study aimed to examine the potential causal relevance of ECG parameters on risk of AF using mendelian randomisation (MR). Methods and findings Weighted genetic scores explaining lifelong differences in P-wave duration, PR interval, and QT interval were constructed, and associations between these ECG scores and risk of AF were estimated among 278,792 UK Biobank participants (mean age: 57 years at recruitment; 19,132 AF cases). The independent genetic variants contributing to each of the separate ECG scores, and their corresponding weights, were based on published genome-wide association studies. In UK Biobank, genetic scores representing a 5 ms longer P-wave duration or PR interval were significantly associated with lower risks of AF (odds ratio [OR] 0.91; 95% confidence interval [CI]: 0.87–0.96, P = 2 × 10−4 and OR 0.94; 95% CI: 0.93–0.96, P = 2 × 10−19, respectively), while longer QT interval was not significantly associated with AF. These effects were independently replicated among a further 17,931 AF cases from the AFGen Consortium. Investigation of potential mechanistic pathways showed that differences in ECG parameters associated with specific ion channel genes had effects on risk of AF consistent with the overall scores, while the overall scores were not associated with changes in left atrial size. Limitations of the study included the inherent assumptions of MR, restriction to individuals of European ancestry, and possible restriction of results to the normal ECG ranges represented in UK Biobank. Conclusions In UK Biobank, we observed evidence suggesting a causal relationship between lifelong differences in ECG parameters (particularly PR interval) that reflect longer atrial conduction times and a lower risk of AF. These findings, which appear to be independent of atrial size and concomitant cardiovascular comorbidity, support the relevance of varying mechanisms underpinning AF and indicate that more individualised treatment strategies warrant consideration.

1348Impact of genetically determined differences in ECG parameters on risk of AF in c. 300,000 UK Biobank participants

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P R Gajendragadkar ◽  
A K Von Ende ◽  
B Casadei ◽  
J C Hopewell
Keyword(s):  
Odds Ratio ◽  
Qt Interval ◽  
P Wave ◽  
Sensitivity Analyses ◽  
Uk Biobank ◽  
Wave Duration ◽  
P Wave Duration ◽  
Pr Interval ◽  
Genetically Determined ◽  
The Impact

Abstract Background An abnormal electrical substrate has been associated with atrial cardiomyopathy, atrial fibrillation (AF), and other supraventricular tachycardias (SVT). However, many risk factors for AF influence ECG parameters, potentially confounding the association. As ECG intervals are highly heritable, using genetic scores as proxies limits confounding and the effects of reverse causation. Purpose To establish the nature of any causal relationship between ECG parameters and risk of AF using Mendelian randomisation (MR) techniques. Methods Genetic scores for P-wave duration, PR interval and QT interval were constructed from published genome-wide association studies and logistic regression models used to estimate their associations with AF using individual participant data in UK Biobank (UKB) (15,311 AF cases and 262,320 controls). Validation was performed using summary data from the AFGEN consortium (15,979 AF cases and 102,776 controls). Sensitivity analyses exploring the impact of potential pleiotropy were performed using conventional MR techniques (e.g. weighted median, MR-Egger etc). Results As expected, the genetic scores were strongly associated with their specified ECG parameters. Longer genetically determined P-wave and PR interval durations were associated with lower risks of AF. By contrast, a longer genetically determined QT interval was not associated with AF risk (Figure). To investigate the role of changes in electrical pathways affecting the ECG and AF risk, scores for each parameter were generated limited to genetic proxies associated with genes for known ion channels. Ion channel limited scores lowered risks of AF per 5ms increases in P-wave duration (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 078–0.89, P=2×10–8) and PR interval (OR: 0.92; 95% CI: 0.90–0.95, P=4×10–10) with no change in AF risk with longer score for QT interval (OR: 0.99; 95% CI: 0.96–1.03, P=0.68). These effects were consistently replicated in the AFGEN dataset and multiple sensitivity analyses supported the conclusions. To test associations between the ECG genetic scores and a specific AF subtype, 3,843 participants with AF but without known coronary heart disease, heart failure, hypertension or diabetes and 273,788 controls were identified. Overall odds ratio estimates were similar to the primary outcomes for each of the ECG parameters investigated (Figure). To investigate the effects of altered electrical substrate on other related arrhythmias, 2,621 cases of SVT and 275,010 controls were identified. Longer genetic P-wave and PR intervals were associated with lower risks of SVT. The genetic QT interval was not associated with SVT risk (Figure). Figure 1 Conclusions Genetically determined ECG parameters associated with shorter atrial electrical conduction times increased risk of AF and SVT. These findings provide a novel mechanistic insight into understanding the underlying pathophysiology of AF and potential development of therapeutic strategies. Acknowledgement/Funding British Heart Foundation

scholarly journals The Dose-Dependent Effects of Spironolactone on TGF-β1 Expression and the Vulnerability to Atrial Fibrillation in Spontaneously Hypertensive Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Mirong Tang ◽  
Yan Chen ◽  
Fuqing Sun ◽  
Liangliang Yan
Keyword(s):  
Atrial Fibrillation ◽  
Cell Size ◽  
Saline Solution ◽  
Myocardial Cell ◽  
P Wave ◽  
Atrial Fibrosis ◽  
Wave Duration ◽  
P Wave Duration ◽  
Pr Interval ◽  
Tgf Β1

Objective. This study tends to assess the dose-dependent effects of spironolactone on TGF-β1 expression, atrial fibrosis, and the vulnerability to atrial fibrillation in spontaneously hypertensive rats (SHRs) and tries to clarify the association of atrial fibrosis with the vulnerability to atrial fibrillation. Methods. Forty 20-week-old male SHRs were randomly divided into 4 groups (10 rats per group): 3 spironolactone groups were lower-dose group (10 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SL), medium-dose group (40 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SM), higher-dose group (80 mg·kg−1·d−1, dissolved in 2 ml saline solution, group SH) and one hypertension group (2 ml saline solution for stomach gavage, group H). Ten matched homologous WKY rats were set as the control group (group C). After 7 weeks of gavage, a multiple electroconductive physiological recorder was used to detect atrial electrical parameters, including P-wave duration, PR interval, and atrial effective refractory period (AERP), the inducibility, and duration of atrial fibrillation. HE staining was used to determine myocardial cell size. Masson staining was used to detect the deposition of the interstitial collagen fibers in atrial muscle. The expression of TGF-β1 was detected by immunohistochemistry and western blot. Results. Compared with group C, the myocardial cell size, atrial fibrosis, TGF-β1 expression, P-wave duration, PR interval, AERP, inducibility, and duration of atrial fibrillation in group H were conspicuously increased ( p  < 0.05); compared with group H, there was no significant difference in the myocardial cell size, atrial fibrosis, TGF-β1 expression, and electrophysiological indexes in group SH upon spironolactone intervention ( p  > 0.05); compared with group H, the myocardial cell size, atrial fibrosis, the expression of TGF-β1, P-wave duration, PR interval, the inducibility, and duration of atrial fibrillation in the group SL and group SM were all decreased ( p  < 0.05); compared with group SM, the effect in the group SL was more prominent ( p  < 0.01). Conclusion. Hypertension can lead to cardiomyocyte hypertrophy, deposition of interstitial fibrosis in myocardial tissue, and an increase in the vulnerability to atrial fibrillation. Spironolactone showed a certain dose-dependent effect in SHRs. Lower-dose spironolactone was superior to higher-dose spironolactone in the aspect of reducing hypertensive atrial fibrosis and TGF-β1 expression, as well as preventing the occurrence of atrial fibrillation.

scholarly journals Effectiveness of P-wave ECG index and left atrial appendage volume in predicting atrial fibrillation recurrence after first radiofrequency catheter ablation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruibin Li ◽  
Xiaohong Yang ◽  
Min Jia ◽  
Dong Wang ◽  
Xiaoran Cui ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Radiofrequency Catheter Ablation ◽  
P Wave ◽  
Atrial Fibrillation Recurrence ◽  
Interval Prolongation ◽  
Wave Duration ◽  
P Wave Duration ◽  
Pr Interval ◽  
Recurrence Group

Abstract Background The primary aim was to observe the predictive value of P-wave ECG index and left atrial appendage volume (LLAV) for atrial fibrillation recurrence after first radiofrequency catheter ablation. Methods A total of 196 patients with paroxysmal atrial fibrillation were enrolled. The preoperative LLAV was measured by cardiac enhanced CT. The P-wave ECG index including minimum P-wave duration (P-min), maximum P-wave duration (P-max), mean P-wave duration (mPWD), P-wave dispersion (PWD), P-wave terminal force in lead V1 (PtfV1), PR interval prolongation, and interatrial block (IAB) were analyzed and recorded in 12-lead ECG of sinus rhythm. Results According to the follow-up results, the patients were divided into two groups: the non-recurrence group and the recurrence group. P-min, PWD, P-max, PtfV1 ≥ 0.04 mV·s, PR interval prolongation, and the ratio of first and third-degree IAB in the recurrence group were higher than those in the non-recurrence group, with significant statistical differences (P < 0.05). Kaplan–Meier curve analysis was performed on time to atrial fibrillation recurrence after catheter ablation when PtfV1 ≥ 0.04 mv s by comparison between groups (Log Rank test: 2 = 4.739, P < 0.001). Kaplan–Meier curve analysis showed that the survival rate without recurrence of atrial fibrillation after catheter ablation was lower when the LLAV exceeded 8.0 mL (log-rank test P < 0.001). Conclusion PWD, P-max, PtfV1, PR interval prolongation, first and third-degree IAB, and LLAV can effectively predict atrial fibrillation recurrence after radiofrequency catheter ablation. The combination might be a valid and alternative independent predictor of recurrence.

Advanced interatrial block precedes atrial fibrillation and stroke. The prospective interatrial Block And Yearly EventS (BAYES) registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Martinez-Selles ◽  
R Elosua ◽  
M Ibarrola ◽  
M De Andres ◽  
P Diez-Villanueva ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Sinus Rhythm ◽  
Structural Heart Disease ◽  
P Wave ◽  
Wave Duration ◽  
P Wave Duration ◽  
Previous Diagnosis ◽  
Surface Ecg ◽  
Interatrial Block

Abstract Background Advanced interatrial block (IAB), prolonged and bimodal P waves in surface ECG inferior leads, is an unrecognized surrogate of atrial dysfunction and a trigger of atrial dysrhythmias, mainly atrial fibrillation (AF). Our aim was to prospectively assess whether advanced IAB in sinus rhythm precedes AF and stroke in elderly outpatients with structural heart disease, a group not previously studied. Methods Prospective observational registry that included outpatients aged ≥70 years with structural heart disease and no previous diagnosis of AF. Patients were divided into three groups according to P-wave characteristics. Results Among 556 individuals, 223 had normal P-wave (40.1%), 196 partial IAB (35.3%), and 137 advanced IAB (24.6%). After a median follow-up of 694 days; 93 patients (16.7%) developed AF, 30 stroke (5.4%), and 34 died (6.1%). Advanced IAB was independently associated with AF (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.7–5.1, p&lt;0.001), stroke (HR 3.8, 95% CI 1.4–10.7, p=0.010), and AF/stroke (HR 2.6, 95% CI 1.5–4.4, p=0.001). P-wave duration (ms) was independently associated with AF (HR 1.05, 95% CI 1.03–1.07, p&lt;0.001), AF/stroke (HR 1.04, 95% CI 1.02–1.06, p&lt;0.001), and mortality (HR 1.04, 95% CI 1.00–1.08, p=0.021). Conclusions The presence of advanced IAB in sinus rhythm is a risk factor for AF and stroke in an elderly population with structural heart disease and no previous diagnosis of AF. P-wave duration was also associated with all-cause mortality. Figure. Age- and sex-adjusted linear and non-linear association between P-wave duration (msec) and atrial fibrillation (A), stroke (B), and atrial fibrillation or stroke (C) risk. Results of a generalized additive model with spline smoothing functions and 4 degrees of freedom. Figure 1. Kaplan-Meyer curves of survival free of atrial fibrillation (A), stroke (B) and atrial fibrillation or stroke (C) in patients with normal P-wave, partial interatrial block (IAB) and advanced IAB. Funding Acknowledgement Type of funding source: None

scholarly journals B-AB16-03 P WAVE PARADOX: CAN THE P WAVE DURATION ON 12 LEAD ELECTROCARDIOGRAPHY INFORM ATRIAL FIBRILLATION RECURRENCE AFTER CATHETER ABLATION

Heart Rhythm ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. S31-S32
Author(s):  
Michael Gardner ◽  
Shruti Bidani ◽  
Muzammil Khan ◽  
Jianhui Zhu ◽  
William W. Barrington ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
P Wave ◽  
Atrial Fibrillation Recurrence ◽  
Wave Duration ◽  
P Wave Duration

Signal-averaged P wave duration in patients with atrial fibrillation treated with radiofrequency catheter ablation

Heart Rhythm ◽  
2005 ◽  
Vol 2 (5) ◽  
pp. S182-S183
Author(s):  
Brian Nilsson ◽  
Ulrik Dixen ◽  
Xu Chen ◽  
Steen Pehrson ◽  
Jesper H. Svendsen
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Radiofrequency Catheter Ablation ◽  
P Wave ◽  
Wave Duration ◽  
P Wave Duration

scholarly journals The effect of diabetic autonomic neuropathy on P-wave duration, dispersion and atrial fibrillation

2011 ◽  
Vol 5 ◽  
pp. 806-812 ◽  
Author(s):  
Andrzej Bissinger ◽  
Tomasz Grycewicz ◽  
Wlodzimierz Grabowicz ◽  
Andrzej Lubinski
Keyword(s):  
Atrial Fibrillation ◽  
Autonomic Neuropathy ◽  
Diabetic Autonomic Neuropathy ◽  
P Wave ◽  
Wave Duration ◽  
P Wave Duration

scholarly journals Associations between Intrinsic Heart Rate, P Wave and QT Interval Durations and Pulse Wave Analysis in Patients with Hypertension and High Normal Blood Pressure

2020 ◽  
Vol 17 (12) ◽  
pp. 4350
Author(s):  
Ioana Mozos ◽  
Cristina Gug ◽  
Costin Mozos ◽  
Dana Stoian ◽  
Marius Pricop ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Qt Interval ◽  
Pulse Wave ◽  
Pulse Wave Analysis ◽  
P Wave ◽  
Normal Blood Pressure ◽  
Wave Analysis ◽  
Wave Duration ◽  
P Wave Duration

The present study aimed to explore the relationship between electrocardiographic (ECG) and pulse wave analysis variables in patients with hypertension (HT) and high normal blood pressure (HNBP). A total of 56 consecutive, middle-aged hypertensive and HNBP patients underwent pulse wave analysis and standard 12-lead ECG. Pulse wave velocity (PWV), heart rate, intrinsic heart rate (IHR), P wave and QT interval durations were as follows: 7.26 ± 0.69 m/s, 69 ± 11 beats/minute, 91 ± 3 beats/minute, 105 ± 22 mm and 409 ± 64 mm, respectively. Significant correlations were obtained between PWV and IHR and P wave duration, respectively, between early vascular aging (EVA) and P wave and QT interval durations, respectively. Linear regression analysis revealed significant associations between ECG and pulse wave analysis variables but multiple regression analysis revealed only IHR as an independent predictor of PWV, even after adjusting for blood pressure variables and therapy. Receiver-operating characteristic (ROC) curve analysis revealed P wave duration (area under curve (AUC) = 0.731; 95% CI: 0.569–0.893) as a predictor of pathological PWV, and P wave and QT interval durations were found as sensitive and specific predictors of EVA. ECG provides information about PWV and EVA in patients with HT and HNBP. IHR and P wave durations are independent predictors of PWV, and P wave and QT interval may predict EVA.

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