Genome-wide association study and meta-analysis identify loci associated with ventricular and supraventricular ectopy.

The genetic basis of supraventricular and ventricular ectopy (SVE, VE) remains largely uncharacterized, despite established genetic mechanisms of arrhythmogenesis. To identify novel genetic variants associated with SVE/VE in ancestrally diverse human populations, we conducted a genome-wide association study of electrocardiographically identified SVE and VE in five cohorts including approximately 43,000 participants of African, European and Hispanic/Latino ancestry. In thirteen ancestry-stratified subgroups, we tested multivariable-adjusted associations of SVE and VE with single nucleotide polymorphism (SNP) dosage. We combined subgroup-specific association estimates in inverse variance-weighted, fixed-effects and Bayesian meta-analyses. We also combined fixed-effects meta-analytic t-test statistics for SVE and VE in multi-trait SNP association analyses. No loci reached genome-wide significance in trans-ethnic meta-analyses. However, we found genome-wide significant SNPs intronic to an apoptosis-enhancing gene previously associated with QRS interval duration (FAF1; lead SNP rs7545860; effect allele frequency = 0.02; P = 2.0 × 10-8) in multi-trait analysis among European ancestry participants and near a locus encoding calcium-dependent glycoproteins (DSC3; lead SNP rs8086068; effect allele frequency = 0.17) in meta-analysis of SVE (P = 4.0 × 10-8) and multi-trait analysis (P = 2.9 × 10-9) among African ancestry participants. The novel findings suggest several mechanisms by which genetic variation may predispose to ectopy in humans and highlight the potential value of leveraging pleiotropy in future studies of ectopy-related phenotypes.

Long-term Prognosis of Paroxysmal Atrial Fibrillation and Predictors for Progression to Persistnt or Chronic Atrial Fibrillation in the Korean Population.

Little is known about the long-term prognosis of or predictors for the different clinical types of atrial fibrillation (AF) in Korean populations. The aim of this study was to validate a risk stratification to assess the probability of AF progression from paroxysmal AF (PAF) to persistent AF (PeAF) or permanent AF. A total of 434 patients with PAF were consecutively enrolled (mean age; 71.7 ± 10.7 yr, 60.6% male). PeAF was defined as episodes that are sustained > 7 days and not self-terminating, while permanent AF was defined as an ongoing long-term episode. Atrial arrhythmia during follow-up was defined as atrial premature complex, atrial tachycardia, and atrial flutter. During a mean follow-up of 72.7 ± 58.3 months, 168 patients (38.7%) with PAF progressed to PeAF or permanent AF. The mean annual AF progression was 10.7% per year. In univariate analysis, age at diagnosis, body mass index, atrial arrhythmia during follow-up, left ventricular ejection fraction, concentric left ventricular hypertrophy, left atrial diameter (LAD), and severe mitral regurgitation (MR) were significantly associated with AF progression. In multivariate analysis, age at diagnosis (P = 0.009), atrial arrhythmia during follow-up (P = 0.015), LAD (P = 0.002) and MR grade (P = 0.026) were independent risk factors for AF progression. Patients with younger age at diagnosis, atrial arrhythmia during follow-up, larger left atrial chamber size, and severe MR grade are more likely to progress to PeAF or permanent AF, suggesting more intensive medical therapy with close clinical follow-up would be required in those patients.

The quantification of the QT-RR interaction in ECG signal using the detrended fluctuationanalysis and ARARX modelling.

In this paper, the detrended fluctuation analysis DFA is used to investigate and quantify the QT-RR interaction in different pathologic cases in order to distinguish between them. The study is carried out on the ECG signals of MIT-BIH universal database. Different ECG signals related to cardiac pathological cases are concerned with this study. These are: Premature Ventricular Contraction (PVC) (9 cases), Right Bundle Branch Block (RBBB) (4 cases), Left Bundle Branch Block (LBBB) (2 cases), Atrial Premature Beat (APB) (4 cases), Paced Beat (PB) (4 cases), and other pathologic cases with different severity (10 cases). All this cases are compared to the 15 normal cases. The obtained results show that the DFA can identify the healthy subject from the pathologic cases according to the values of the scaling exponent α. The results indicate that α varies between 0.5 and 1 in all cases which means that there is a long range correlation in RR and QT series. The QT and RR series are also modelled using the ARARX model. The parameters of the model are then extracted. The power spectral density (PSD) is estimated by using these parameters in order to provide further information about the causal interactions within the signals and also to determine the power scaling exponent ß. This scaling exponent confirms the relationship between RR and QT intervals in all the studied cases except in APB and PB cases where the behaviour is similar to that of the white noise. The QT variability degrees are calculated and the DFA is applied on it. The obtained results show a long range correlation between RR and QT intervals in all cases and an ambiguity in the APB case. The DFA is compared to the Poincaré method in order to evaluate the algorithm performance using the Fuzzy Sugeno classifier is used for this purpose.

Characteristics of ectopic triggers associated with paroxysmal and persistent atrial fibrillation: evidence for a changing role.

BACKGROUND: Atrial premature contractions (APCs) are well described to precede the initiation of paroxysmal atrial fibrillation (pAF). However, whether APC characteristics alter with progression of the arrhythmia is unknown. OBJECTIVE: To determine the APC characteristics in terms of burden and relative coupling interval with progression of the AF disease process. METHODS: Fifty consecutive patients with pAF, 50 consecutive patients with persistent AF (perAF), and 25 age-matched controls underwent clinical review, transthoracic echocardiography, and ambulatory electrocardiogram monitoring. After excluding 29 patients who had AF for the entire recording (n = 24) or unreliable recordings (n = 5), we analyzed data from 49 patients with pAF, 24 patients with perAF, and 23 healthy controls. All normal morphology R-R intervals with a >25% decrease in R-R coupling compared with the previous R-R interval (coupling interval index) were deemed APCs (n = 95,873). RESULTS: The median APC burden was higher in patients with pAF (2 [1-22] APCs/h; P = .004) and perAF (3 [1-6] APCs/h; P = .04) than in controls (1 [0-1] APCs/h) but was not different (P = .66) between the AF subgroups. Patients with pAF had a distinct increase in ectopy burden after 7 PM and elevation throughout the night (P = .002) in comparison with a blunted and complementary temporal response in the perAF cohort (P = .01). Patients with pAF demonstrated a greater proportion of shortly coupled APCs (29% [13-45]; P = .04) compared with persistent arrhythmia (17% [5-29]). CONCLUSIONS: "Real-life" atrial trigger statistics of APC burden, timing, and diurnal rhythms track the transition from a trigger-based, autonomically sensitive paroxysmal arrhythmia to a more substrate-based persistent disease.

Effect of obstructive sleep apnea syndrome on serum C-reactive protein level, left atrial size and premature atrial contraction.

OBJECTIVE: To assess the changes of serum C-reactive protein (CRP) level, left atrial size and atrial premature contraction (PAC) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: This study involved 277 patients with OSAS diagnosed after an overnight polysomnography, who underwent a 24-h Holter electrocardiography and ambulatory blood pressure monitoring for detection of PAC. According to the apnea-hypopnea index (AHI), 137 patients with PAC identified from these patients were classified into 3 groups, namely the mild (5≥AHI<15), moderate (15≥AHI<30) and severe (AHI≥30) groups. Serum CRP level was assessed by a high-sensitivity radio-immunoassay. The left atrial diameter and echocardiographic parameters were recorded by transthoracic Doppler echocardiography (TTE). RESULTS: We found a high prevalence of PAC in these OSAS patients (137/277, 49.4%). Serum CRP was significantly higher in severe OSAS group (5.01∓4.68 mg/L) than in the moderate (3.03∓1.94 mg/L) and mild OSAS (2.98∓1.82 mg/L) groups (P=0.040 and 0.033, respectively). The left atrial diameter was significantly increased in severe OSAS group (40.1∓7.9 mm) as compared to that in moderate (37.9∓5.5 mm) and mild (33.7 ∓ 3.8 mm) groups (P=0.025 and 0.002, respectively). The severity of OSAS was positively correlated to both CRP (r=0.304, P=0.034) and left atrial diameter (r=0.411, P=0.003). After adjusting for gender, age and body mass index (BMI), a strong correlation was found between the left atrial diameter and CRP (r=0.594, P=0.0005). CONCLUSION: There is a high prevalence of PAC in OSAS patients. The progression of OSAS is associated with increased serum CRP level and left atrial size in patients with premature atrial complexes. Our study suggests that inflammation associated with OSAS might contribute to atrial structural and electrical remodeling in OSAS patients with PAC.

Superior vena cava stenosis after radiofrequency catheter ablation for electrical isolation of the superior vena cava.

Ectopic beats originating from the superior vena cava (SVC) may initiate atrial fibrillation. This report describes a patient undergoing radiofrequency catheter ablation for electrical isolation of the SVC resulting in SVC stenosis. Noncircumferential lesion sets for SVC isolation to reduce ablation times may be preferred. (PACE 2010; e36-e38).

Pulmonary venous structural remodeling in a canine model of chronic atrial dilation due to mitral regurgitation.

OBJECTIVE: Structural remodelling plays an important role in the genesis and maintenance of atrial fibrillation (AF). Although some studies that associate structural remodelling with atrial dilation have been reported, structural pulmonary venous (PV) remodelling due to chronic atrial dilation remains unclear. METHODS: Six sham dogs and five mitral regurgitation (MR) dogs (three months after partial mitral valve avulsion) were studied. Separate cryosections from the PV and left atrium (LA) were immunolabelled with antibodies against connexin (Cx) 40 and Cx43 and analyzed by confocal laser scanning microscopy. Tissue samples from the PV and LA were stained with hematoxylin and eosin, and Masson's trichrome. RESULTS: In MR models, a decrease in Cx40 (0.57+/-0.2% versus 1.18+/-0.3%, P<0.05) and Cx43 (0.48+/-0.2% versus 1.56+/-0.5%, P<0.05) expression was observed compared with sham dogs. The distribution pattern of Cx40 and Cx43 changed from homogeneous to heterogeneous. Gap junction remodelling was not observed in the LA. In Masson's trichrome-stained sections from MR dogs, regions with increased interstitial fibrosis were present in the PV. Thickness in the PV and the PV-LA junction did not change in the MR group. CONCLUSION: The present study demonstrated a decrease in Cx40 and Cx43 expression and increased interstitial fibrosis in PV due to MR. These changes may potentially be a mechanism that renders the dilated atria more susceptible to AF.

[Chronostructure of ectopic heart activity in the acute phase of myocardial infarction]. / Khronostruktura éktopicheskoi aktivnosti serdtsa v ostroi faze infarkta miokarda.

7-day monitoring of cardiac rhythm has been conducted in 42 patients with myocardial infarction (MI) and 15 patients with chronic ischemic heart disease. Hour-by-hour analysis of extrasystole demonstrates that probability of ventricular arrhythmia is maximal in transmural MI, the first 3 days of acute MI are most arrhythmogenic. Follow-up of ventricular ectopic activity (VEA) showed the latter to significantly enhance early in the morning, afternoon and on the first 5 days after midnight. In unpenetrating MI, VEA intensifies in the morning, afternoon and postmidnight hoars. Atrial ectopic activity (AEA) in transmural MI enhances early in the morning, afternoon and at night (on the first 3 days). AEA in unpenetrating MI is more intensive late in the morning and afternoon.

Anatomic substrate of the experimentally-created atrioventricular node re-entrant tachycardia in the dog.

Despite major success in the treatment of atrioventricular (AV) node reentrant tachycardia using either catheter ablation or surgery, the morphologic basis underlying AV node reentry is not yet clear. A canine model of AV node reentrant tachycardia was used to examine the histologic features of the reentry circuit. AV node reentrant tachycardia was created in 4 of 8 dogs by a right atrial division which divided the right atrial free wall and the atrial septum into upper and lower portions on a plane between the mid-right atrial free wall and the fossa ovalis. The AV junctional area of all dogs were serially sectioned on a plane that was perpendicular to the AV annulus and the septum. The slices were stained with Masson's trichrome technique. The connections between atrial fibers and the compact AV node and the common AV bundle were examined, and comparison of the histologic features between dogs with and without AV nodal re-entry was made. The histologic examinations showed that, in all dogs, the operation scar was remote from the AV junctional area leaving the Koch's triangle intact. The compact node received its atrial inputs mainly from the anterosuperior and posterior aspects of the Koch's triangle. However, both atrial inputs gave off superficial (subendocardial) fibers that by-passed the compact node to terminate at the base of tricuspid valve. These superficial fibers might function as the proximal link between the dual AV nodal inputs by means of lateral connections. There was no bypass connection between atrial fibers and the common AV bundle. The histologic features of the AV junctional area was not different between dogs with and without AV nodal reentry. In conclusion, AV nodal reentry involves the anterior and posterior atrio-nodal inputs which function as dual AV nodal pathways, and the superficial bypass fibers form the proximal linkage between the two inputs. These structures, together with the compact node, complete the reentry circuit.