Corrected Sinus Node Recovery Time Research Articles

α1-Adrenergic Receptors Control the Activity of Sinoatrial Node by Modulating Transmembrane Transport of Chloride Anions

Norepinephrine (NE), which is released by sympathetic nerve endings, causes an increase in the frequency of spontaneous action potentials in the pacemaker cardiomyocytes of the sinoatrial node (SAN), also known as the “pacemaker” of the heart. This results in an increase in heart rate (HR). It is known that two types of postsynaptic adrenoreceptors (ARs), α1-AR and β-AR, can mediate the effects of NE. The role of α1-AR in the sympathetic control of heart rate and SAN automaticity, as well as the membrane mechanisms mediation the effects of α1-AR on the pacemaker, have not yet been elucidated. In this study, we utilized immunofluorescence confocal microscopy to examine the distribution of α1A-AR in the SAN of rats. Additionally, we assessed the expression of α1A-AR mRNA in the SAN tissue using RT-PCR. Furthermore, we investigated the impact of α1-AR stimulation on key functional parameters of the pacemaker, including the corrected sinus node recovery time (SNRT/cSNRT) and the SAN accommodation, using the Langendorff perfused heart technique. We also used optical mapping of the electrical activity of perfused, isolated tissue preparations to study the effect of α1-AR stimulation on the spatiotemporal characteristics of SAN excitation. We tested the effects of chloride transmembrane conductance blockade on alteration of functional parameters and pattern of SAN excitation caused by α1-AR. Fluorescent signals corresponding to α1A-AR have been identified in SAN cardiomyocytes, indicating the presence of α1A-AR at protein level. The expression of α1A-AR in SAN has been also confirmed at the mRNA level. The stimulation of α1-AR affects SAN functioning Phenylephrine (PHE) utilized as α1A-AR agonist causes a decrease in SNRT/cSNRT, as well as an acceleration of SAN accommodation. These effects were rate dependent and were observed at a high frequency of pacemaker tissue stimulation. PHE induces changes in the excitation pattern of the SAN. The effects of PHE on functional parameters and SAN excitation pattern are attenuated by Ca2+-dependent chloride channel blocker NPPB but remains unaffected by the protein kinase C inhibitor BIM. Our results suggest that cardiac α1-ARs are important for maintaining function of SAN pacemaker at high heart rates and that α1-AR signalling cascades in the SAN target Ca2+-dependent chloride channels are involved in the α1-adrenergic modulation of the electrophysiological properties of the heart pacemaker.

Corrected sinus node recovery time as a screening test in patients with typical atrial flutter post-ablation to predict pacemaker implantation

Corrected sinus node recovery time as a screening test in patients with typical atrial flutter post-ablation to predict pacemaker implantation

Corrected sinus node recovery time as a screening test in patients with typical atrial flutter post-ablation to predict pacemaker implantation.

The objective of the study was to establish the prognostic value of CSNRT regarding the necessity for pacemaker implantation in patients with atrial flutter (AFL) post-ablation. This prospective cohort study, conducted at the National Institute of Cardiology "Ignacio Chavez" in Mexico City, assessed patients who had undergone ablation procedures to correct AFL, posterior to which an autonomic blockade was performed, and CSNRT was measured. The sample for this investigation was 40 patients. These were subdivided into two study groups depending on their requirement of pacemaker implant post-ablation (Pacemaker P, No Pacemaker NP). Sinus node (SN) dysfunction was diagnosed in 13 (32.5%) of the 40 participants, 10 (71.43%) of which required a pacemaker implant, while only 4 participants (28.57%) with normal SN function required pacemakers. Ten out of the 14 patients (71.43%) who required a pacemaker had an elevated CSNRT > 500 ms (p ≤ 0.01). Post-ablation CSNRT mean was 383.54 ms ± 67.96 ms in the NP group versus 1972.57 ms ± 3423.56 ms in the P group. Furthermore, SN pause in the P group had a mean of 1.86 s ± 0.96 s versus the NP group with 1.196 s ± 0.52 s. CSNRT has the potential to be a quantitative prognostic tool for the assessment of future pacemaker implants in patients with AFL post-ablation. This could aid in the timely diagnosis of sinus node dysfunction, which could, in the long run, result in the reduction of cardiac functional capacity loss due to cardiac remodeling.

Natriuretic peptide receptor B maintains heart rate and sinoatrial node function via cyclic GMP-mediated signalling.

Heart rate (HR) is a critical indicator of cardiac performance that is determined by sinoatrial node (SAN) function and regulation. Natriuretic peptides, including C-type NP (CNP), have been shown to modulate ion channel function in the SAN when applied exogenously. CNP is the only NP that acts as a ligand for natriuretic peptide receptor-B (NPR-B). Despite these properties, the ability of CNP and NPR-B to regulate HR and intrinsic SAN automaticity in vivo, and the mechanisms by which it does so, are incompletely understood. Thus, the objective of this study was to determine the role of NPR-B signalling in regulating HR and SAN function. We have used NPR-B deficient mice (NPR-B+/-) to study HR regulation and SAN function using telemetry in conscious mice, intracardiac electrophysiology in anaesthetized mice, high-resolution optical mapping in isolated SAN preparations, patch-clamping in isolated SAN myocytes, and molecular biology in isolated SAN tissue. These studies demonstrate that NPR-B+/- mice exhibit slow HR, increased corrected SAN recovery time, and slowed SAN conduction. Spontaneous AP firing frequency in isolated SAN myocytes was impaired in NPR-B+/- mice due to reductions in the hyperpolarization activated current (If) and L-type Ca2+ current (ICa,L). If and ICa,L were reduced due to lower cGMP levels and increased hydrolysis of cAMP by phosphodiesterase 3 (PDE3) in the SAN. Inhibiting PDE3 or restoring cGMP signalling via application of 8-Br-cGMP abolished the reductions in cAMP, AP firing, If, and ICa,L, and normalized SAN conduction, in the SAN in NPR-B+/- mice. NPR-B+/- mice did not exhibit changes in SAN fibrosis and showed no evidence of cardiac hypertrophy or changes in ventricular function. NPR-B plays an essential physiological role in maintaining normal HR and SAN function by modulating ion channel function in SAN myocytes via a cGMP/PDE3/cAMP signalling mechanism.

Impact of corrected sinus node recovery time in predicting recurrence in patients with paroxysmal atrial fibrillation.

ObjectiveAtrial fibrillation (AF) and sinus node dysfunction (SND) have common underlying pathophysiological mechanisms. As an index of SND, corrected sinus node recovery time (CSNRT) may also reflect atrial function. The aim of the present study was to determine whether CSNRT predicts AF recurrence in patients undergoing AF ablation.MethodsConsecutive patients with paroxysmal atrial fibrillation (PAF) who underwent radiofrequency catheter ablation between January 2017 and December 2018 were enrolled. Clinical data, CSNRT, and other electrophysiology indices were collected and analysed between patients with or without AF recurrence.ResultsA total of 159 patients with PAF who underwent the same radiofrequency catheter ablation procedure were enrolled, including 25 patients with SND. During the one-year follow-up period, 22 patients experienced AF recurrence. Patients with recurrence had a significantly longer CSNRT and a larger left atrial volume index (LAVI) than patients without AF recurrence. SND (CSNRT > 550 ms) and a larger LAVI were independently associated with AF recurrence after ablation. A statistically significant CSNRT cut-off value of 550 ms predicted AF recurrence with 73% sensitivity and 85% specificity.ConclusionCSNRT and LAVI are independent predictors of PAF recurrence following ablation.

MicroRNA-1976 regulates degeneration of the sinoatrial node by targeting Cav1.2 and Cav1.3 ion channels

Sick sinus syndrome (SSS) is primarily a disease of the elderly, and age-dependent decrease in Cav1.2 and Cav1.3 Ca2+ channels within the sinus node has been shown to play an important role in sinoatrial node (SAN) degeneration; however, posttranscriptional mechanisms regulating decrease in Cav1.2 and Cav1.3 Ca2+ channels remain unclear. Some studies have reported that microRNAs (miRNAs) are involved in age-related cardiovascular diseases. Nevertheless, little is known about the roles of miRNAs in age-related SSS. This study investigated whether miR-1976 was involved in the regulation of SAN degeneration by targeting Cav1.2 and Cav1.3 Ca2+ channels. First, using microarray-based miRNA expression profiling and qRT-PCR, we confirmed that miR-1976 was upregulated in the plasma of patients with age-related SSS relative to healthy controls. By employing target gene prediction software, luciferase assay and western blotting, we further confirmed Cav1.2 and Cav1.3 as direct targets of miR-1976. Furthermore, miR-1976 levels in rabbit SAN tissues were negatively correlated with Cav1.2 and Cav1.3 expression and intrinsic heart rates but positively correlated with corrected sinus node recovery time (CSNRT). Additionally, miR-1976 transgenic mice displayed attenuated Cav1.2 and Cav1.3 protein expression, which led to sinus node dysfunction. These results suggest that miR-1976 plays an important role in the SAN aging process by targeting Cav1.2 and Cav1.3. Thus, miR-1976 could have great potential as a noninvasive diagnostic tool and therapeutic target for SSS. These findings may reveal important insights into the pathogenesis of SSS.

Electrophysiologic effects and outcomes of sympatholysis in patients with recurrent ventricular arrhythmia and structural heart disease.

Autonomic modulation has been used as a therapy to control recurrent ventricular arrhythmia (VA). This study was to explore stellate ganglion block (SGB) effect on cardiac electrophysiologic properties and evaluate the long-term outcome of cardiac sympathetic denervation (CSD) for patients with recurrent VA and structural heart disease (SHD). Patients who had recurrent VA due to SHD were enrolled prospectively. Electrophysiologic study and ventricular tachycardia (VT) induction were performed before and after left and right SGB. VA burden and long-term outcomes were assessed for a separate patient group who underwent left or bilateral CSD for drug-refractory VA due to SHD. Electrophysiologic study of nine patients showed that baseline mean (SD) corrected sinus node recovery time (cSNRT) increased from 320.4 (73.3) ms to 402.9 (114.2) ms after left and 482.4 (95.7) ms after bilateral SGB (P = .03). SGB did not significantly change P-R, QRS, and Q-T intervals and ventricular effective refractory period, nor did the inducibility of VA. Nineteen patients underwent left (n = 14) or bilateral (n = 5) CSD. CSD reduced VA burden and appropriate ICD therapies from a median (interquartile range) of 2.5 (0.4-11.6) episodes weekly to 0.1 (0.0-2.4) episodes weekly at 6-month follow-up (P = .002). Three-year freedom from orthotopic heart transplant (OHT) and death was 52.6%. New York Heart Association functional class III/IV and VT rate less than 160 beats per minute were predictors of recurrent VA, OHT, and death. SGB increased cSNRT without changing heart rate. CSD was more beneficial for patients with mild-to-moderate heart failure and faster VA.

Chromosome 4q25 Variant rs6817105 Bring Sinus Node Dysfunction and Left Atrial Enlargement

Genome-wide association studies have reported a strong association of the single nucleotide polymorphism (SNP) rs6817105 (T > C) on chromosome 4q25 with atrial fibrillation (AF), but phenotype alterations conferred by this SNP have not been described. We genotyped SNP rs6817105 and examined the relationships among rs6817105 genotype, clinical characteristics, echocardiographic parameters, and electrophysiological parameters in 574 AF patients and 1,554 non-AF controls. Further, multiple microRNAs (miRNAs) are reported to be involved in atrial remodeling and AF pathogenesis, so we investigated relationships between rs6817105 genotype and serum concentrations of 2555 miRNAs. The rs6817105 minor allele frequency was significantly higher in AF patients than non-AF controls (66% vs. 47%, odds ratio 2.12, p = 4.9 × 10−26). Corrected sinus node recovery time (CSRT) was longer and left atrial volume index (LAVI) was larger in AF patients with the rs6817105 minor allele than patient non-carriers (CSRT: CC 557 ± 315 ms, CT 486 ± 273 ms, TT 447 ± 234 ms, p = 0.001; LAVI: CC 43.6 ± 12.1, CT 42.4 ± 13.6, TT 39.8 ± 11.6, p = 0.030). There were no significant differences between rs6817105 genotype and the serum concentrations of miRNAs. These findings strongly implicate rs6817105 minor allele in sinus node dysfunction and left atrial enlargement.

127Can corrected sinus node recovery time be used to predict the need for atrial pacing in an ICD population

127Can corrected sinus node recovery time be used to predict the need for atrial pacing in an ICD population

Interleukin-10 treatment attenuates sinus node dysfunction caused by streptozotocin-induced hyperglycaemia in mice

Diabetes, characterized by hyperglycaemia, causes sinus node dysfunction (SND) in several rodent models. Interleukin (IL)-10, which is a potent anti-inflammatory cytokine, has been reported to decrease in obese and diabetic patients. We tested the hypothesis that administration of IL-10 inhibits the development of SND caused by hyperglycaemia in streptozotocin (STZ)-induced diabetic mice. Six-week old CL57/B6 (WT) mice were divided into the following groups: control, STZ injection, and STZ injection with systemic administration of IL-10. IL-10 knockout mice were similarly treated. STZ-induced hyperglycaemia for 8 weeks significantly depressed serum levels of IL-10, but increased several proinflammatory cytokines in WT mice. STZ-induced hyperglycaemia-reduced resting heart rate (HR), and attenuated HR response to isoproterenol in WT mice. In isolated perfused heart experiments, corrected-sinus node recovery time was prolonged in WT mice with STZ injection. Sinus node tissue isolated from the WT-STZ group showed fibrosis, abundant infiltration of macrophages, increased production of reactive oxygen species (ROS), and depressed hyperpolarization activated cyclic nucleotide-gated potassium channel 4 (HCN4). However, the changes observed in the WT-STZ group were significantly attenuated by IL-10 administration and were further exaggerated in IL-10 knockout mice. In cultured cells, preincubation of IL-10 suppressed hyperglycaemia-induced apoptotic and profibrotic signals, and overproduction of ROS. IL-10 markedly inhibited the high glucose-induced p38 activation, and activated signal transducer and activator of transcription (STAT) 3 phosphorylation. Our results suggest that IL-10 attenuates ROS production, inflammation and fibrosis, and plays an important role in the inhibition of hyperglycaemia-induced SND by suppression of HCN4 downregulation. In addition, IL-10-mediated inhibition of p38 is dependent on STAT3 phosphorylation.

Age-dependent down-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 4 causes deterioration of canine sinoatrial node function.

The activity of pacemaker cells in the sinoatrial node (SAN) is an indicator of normal sinus rhythm. Clinical studies have revealed that the dysfunction of the SAN progressively increases with aging. In this study, we determined the changes in hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) expression and the relationship between aging and canine SAN dysfunction. The results of cardiac electrophysiological determination revealed that the intrinsic heart rate decreased from 168 ± 11 beats min-1 in young canines to 120 ± 9 beats min-1 in adults and to 88 ± 9 beats min-1 in aged canines. The sinus node recovery time (SNRT) increased from 412 ± 32 ms in young canines to 620 ± 56 ms in adults and to 838 ± 120 ms in aged canines. Corrected SNRT (CSNRT) increased from 55 ± 12 ms in young canines to 117 ± 27 ms in adults and to 171 ± 37 ms in aged canines. These results indicated that SAN function deteriorated with aging in the canine heart. However, histological staining illustrated that fibrosis was not significantly increased with aging in canine SAN. Real-time polymerase chain reaction indicated that the expression of HCN4 mRNA was downregulated in the elderly canine SAN. Similarly, we also verified that HCN4 protein expression within the SAN declined with aging via immunofluorescence staining and western blot analysis. Taken together, our data show that electrical remodeling, related to the down-regulation of HCN4, is responsible for the gradually increased incidence of SAN dysfunction with aging. Our results provide further evidence for explaining the mechanisms of age-related deterioration in the SAN.

Prolonged Sinus Pauses upon Termination of Paroxysmal Atrial Fibrillation: Abnormal Right Atrial Electrophysiologic and Electroanatomic Findings.

The efficacy of pulmonary vein antral isolation for patients with prolonged sinus pauses (PSP) on termination of atrial fibrillation has been reported. We studied the right atrial (RA) electrophysiologic and electroanatomic characteristics in such patients. Forty patients underwent electroanatomic mapping of the RA: 13 had PSP (group A), 13 had no PSP (group B), and 14 had paroxysmal supraventricular tachycardia (control group C). Group A had longer P-wave durations in lead II than did groups B and C (115.5 ± 15.4 vs 99.5 ± 10.9 vs 96.5 ± 10.4 ms; P=0.001), and RA activation times (106.8 ± 13.8 vs 99 ± 8.7 vs 94.5 ± 9.1 s; P=0.02). Group A's PP intervals were longer during adenosine triphosphate testing before ablation (4.6 ± 2.3 vs 1.7 ± 0.6 vs 1.5 ± 1 s; P <0.001) and after ablation (4.7 ± 2.5 vs 2.2 ± 1.4 vs 1.6 ± 0.8 s; P <0.001), and group A had more complex electrograms (11.4% ± 5.4% vs 9.3% ± 1.6% vs 5.8% ± 1.6%; P <0.001). Compared with group C, group A had significantly longer corrected sinus node recovery times at a 400-ms pacing cycle length after ablation, larger RA volumes (100.1 ± 23.1 vs 83 ± 22.1 mL; P=0.04), and lower conduction velocities in the high posterior (0.87 ± 0.13 vs 1.02 ± 0.21 mm/ms; P=0.02) and high lateral RA (0.89 ± 0.2 vs 1.1 ± 0.35 mm/ms; P=0.04). We found that patients with PSP upon termination of atrial fibrillation have RA electrophysiologic and electroanatomic abnormalities that warrant post-ablation monitoring.

A Sexy Approach to Pacemaking

Introduction: The sinoatrial node (SAN) is the primary pacemaker of the heart. Clinical evidence shows that SAN function differs between sexes. Males have slower resting (extrinsic and intrinsic) heart rates, and longer corrected SAN recovery time compared with females. Hypothesis: Sex based differences may be due to SAN ion channel differences. Therefore, we investigated functional behaviour and molecular makeup of SANs in male and female rats. Methods: Intracellular action potential recordings were obtained using sharp microelectrode technique (n=5 each). Gene expression was measured with quantitative PCR (n=6 each). Results: The amplitude of the action potential was significantly higher in male SANs (45.3 ± 2.4) compared with female (31.7 ± 2.5). The upstroke velocity (dV/dtmax) was significantly faster in female SANs (16.4 ± 1.6) compared with male (9.1 ± 1.5). Out of 96 transcripts investigated, two were significantly different between the sexes. L-Type Ca2+ channel, Cav1.3, and acetylcholine activated K+ channel, Kir3.1, mRNA levels were significantly higher in female SANs (66.6% and 45.6% respectively) compared with male. Immunolabelling for Cav1.3 showed levels were significantly higher in female SANs compared with male (18.6%, n=6 each). Inhibition of Cav1.3 with nifedipine (5μM) showed greater effect on the beating rate of male SANs compared with female (43%). A non-coding RNA, miR-139-3p (predicted by Ingenuity IPA software to affect Cav1.3) showed greater effect on the beating rate of male SAN preparations compared with female. Mathematical modelling showed that a higher density of Cav1.3 (as in the case of females) has a protective role from sinoatrial node arrhythmias. Conclusion: This study identified functional and molecular differences in key pacemaker ion channels in SAN between sexes. These differences advance our understanding of gender differences in cardiac electrophysiology and may have implications for gender specific design of anti-arrhythmic drugs and biological pacemakers.

Permanent pacemaker implantation in octogenarians with unexplained syncope and positive electrophysiologic testing

Syncope is a common problem in the elderly, and a permanent pacemaker is a therapeutic option when a bradycardic etiology is revealed. However, the benefit of pacing when no association of symptoms to bradycardia has been shown is not clear, especially in the elderly. The aim of this study was to evaluate the effect of pacing on syncope-free mortality in patients aged 80 years or older with unexplained syncope and "positive" invasive electrophysiologic testing (EPT). This was an observational study. A positive EPT for the purposes of this study was defined by at least 1 of the following: a corrected sinus node recovery time of >525 ms, a basic HV interval of >55 ms, detection of infra-Hisian block, or appearance of second-degree atrioventricular block on atrial decremental pacing at a paced cycle length of >400 ms. Among the 2435 screened patients, 228 eligible patients were identified, 145 of whom were implanted with a pacemaker. Kaplan-Meier analysis determined that time to event (syncope or death) was 50.1 months (95% confidence interval 45.4-54.8 months) with a pacemaker vs 37.8 months (95% confidence interval 31.3-44.4 months) without a pacemaker (log-rank test, P = .001). The 4-year time-dependent estimate of the rate of syncope was 12% vs 44% (P < .001) and that of any-cause death was 41% vs 56% (P = .023), respectively. The multivariable odds ratio was 0.25 (95% confidence interval 0.15-0.40) after adjustment for potential confounders. In patients with unexplained syncope and signs of sinus node dysfunction or impaired atrioventricular conduction on invasive EPT, pacemaker implantation was independently associated with longer syncope-free survival. Significant differences were also shown in the individual components of the primary outcome measure (syncope and death from any cause).

Normal Values for Heart Electrophysiology Parameters of Healthy Swine Determined on Electrophysiology Study.

Swine are a well-recognized animal model for human cardiovascular diseases. Despite the widespread use of porcine model in experimental electrophysiology, still no reference values for intracardiac electrical activity and conduction parameters determined during an invasive electrophysiology study (EPS) have been developed in this species thus far. The aim of the study was to develop a set of normal values for intracardiac electrical activity and conduction parameters determined during an invasive EPS of swine. The study included 36 healthy domestic swine (24-40 kg body weight). EPS was performed under a general anesthesia with midazolam, propofol and isoflurane. The reference values for intracardiac electrical activity and conduction parameters were calculated as arithmetic means ± 2 standard deviations. The reference values were determined for AH, HV and PA intervals, interatrial conduction time at its own and imposed rhythm, sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), anterograde and retrograde Wenckebach points, atrial, atrioventricular node and ventricular refractory periods. No significant correlations were found between body weight and heart rate of the examined pigs and their electrophysiological parameters. The hereby presented reference values can be helpful in comparing the results of various studies, as well as in more accurately estimating the values of electrophysiological parameters that can be expected in a given experiment.

Dexmedetomidine Depresses Sinoatrial and Atrioventricular Nodal Function Without Any Change in Atrial Fibrillation Inducibility.

It has been reported that dexmedetomidine (dex) has an impact on the cardiac conduction system and even has potential antiarrhythmic actions. We examined the influence of dex on the cardiac electrophysiological properties and atrial fibrillation (AF) inducibility. Adult paroxysmal AF patients were randomly assigned to receive (N = 107) or not receive (N = 108) dex during cardiac electrophysiological studies. The corrected sinus node recovery time (558 ± 331 vs. 459 ± 260 milliseconds; P = 0.02), Wenckebach cycle length (P < 0.001), atrioventricular nodal effective refractory period (317 ± 76 vs. 252 ± 54 milliseconds; P < 0.001), and atrio-His interval (P < 0.001) were longer in patients with dex than in those without. We tested the induction of repetitive atrial firing (RFA) defined as the occurrence of ≥2 successive atrial activities induced by single premature atrial stimuli to determine the AF inducibility. RFA was seen with a similar proportion (41.1% vs. 44.4%), yet it was evoked at a longer stimulus coupling interval in the dex patients, which was potentially attributed to the longer atrial effective refractory period (237 ± 36 vs. 213 ± 27 milliseconds; P < 0.001) and more prolonged atrial conduction delay seen in the dex group. In conclusion, dex may depress the sinus and atrioventricular nodal function, however, it may not reduce the AF inducibility.

Abstract 13920: Common Variant in Pitx2 Contributes to the Pathogenesis of Paroxysmal Atrial Fibrillation by Impairing Sinus Node Function and Progression of Atrial Remodeling

Introduction: Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with atrial fibrillation (AF). The most notably PITX2 SNPs have been known to show the strong association with AF, but how these SNPs affect clinical phenotype of AF has not been clarified. Hypothesis: We assessed the hypothesis that PITX2 SNPs influence the cardiac structures and electrophysiological properties, and increase the susceptibility to AF. Methods: To investigate the association between the PITX2 SNP and paroxysmal atrial fibrillation (PAF), we genotyped PITX2 SNP (rs6817105) in 344 Japanese PAF patients hospitalized in Hiroshima University hospital and 1,507 healthy controls and compared the allele frequencies of the PITX2 SNP between the PAF patients and controls. The PITX2 SNP was significantly associated with PAF (minor allele (C) frequency: PAF 64.7% vs control 47.3%, P =3.7х10 − 16 , odds ratio (OR)=2.0). We investigated the relationships between the PITX2 C risk allele and clinical characteristics, ECG parameters, parameters of cardiac ultrasound, and electrophysiological study. Results: There were significant linear correlations between the PITX2 genotypes(CC, CT, and TT) and the max sinus node recovery time(SNRT) , corrected sinus node recovery time(CSNRT) and left atrial diameter (LAD) (max SNRT, CC: 1328ms, CT: 1235ms , TT: 1225ms , P =1.5х10 − 2 , CSNRT, CC: 482ms, CT: 418ms, TT: 409ms ,P =1.3х10 − 2 , LAD; CC:37.2±5.6mm, CT:34.4±5.3mm, TT:34.1±5mm, P=1.3х10 − 2 , respectively). Conclusions: To the best of our knowledge, this was the first report showing that PITX2 risk allele was related to the sinus node dysfunction and progression of atrial remodeling in humans. The result was meaningful for considering the mechanism of why PITX2 contributes to the pathogenesis of AF.

Prediction of Sinus Node Dysfunction in Patients with Paroxysmal Atrial Fibrillation and Sinus Pause

Background and Objectives: Sinus pause association of paroxysmal atrial fibrillation (PAP) is generally considered a sinus node dysfunction (SND) known as tachycardia-bradycardia syndrome (TBS). Cure of tachyarrhythmias in some patients with prolonged pauses on termination of tachyarrhythmia resulted in an improvement in sinus node function and/or a return to normal ranges thus avoiding the need for permanent pacing. The purpose of this study was to investigate the electrophysiological and clinical characteristics as well as their sinus node function in patients with prolonged pauses and PAP. Methods and Results: Of 1266 PAP patients undergoing radiofrequency catheter ablation (RFCA), 122 patients with pauses (>2 s) were studied. The mean maximum symptomatic prolonged pause on termination of tachycardias was 2.67 ± 1.4 s (2.0–12.6 s). SND developed in 32 patients. There was no difference between the patients with and without SND in terms of the age and sex. Patients were divided into two groups based on the intracardiac electrophysiology study after the RFCA procedure. Eleven patients (8 men, 3 women; age 30–72 years, mean 48.2 ± 9.3 years) were placed in a normal sinus node function (NSF) group, and 17 patients (12 men, 5 women; age 37–75 years, mean 62.2 ± 7.5 years) were in an SND group. There was no significant difference in gender, left atrial dimension, left ventricular ejection fraction, blood pressure, or the longest pause between the two groups. RFCA was successful in 28 patients. Electrophysiological data show that corrected sinus node recovery time (CSNRT) was 409 ± 152 ms in NSF group patients and 558 ± 178 ms in SND group before the ablation procedure (P 2 cycle lengths in 12 patients. In the multivariate analysis, prolonged pauses on termination of tachyarrhythmia, frequency of pauses, and mean heart rate after ablation were independent predictors of SND. Conclusions: (1) Catheter ablation of atrial fibrillation (AF) is effective in treating paroxysmal AF-related TBS; (2) in some patients, there is progressive improvement of sinus node function after elimination of AF, an indication that these sinus pauses may be a manifestation of tachycardia-mediated remodeling of the sinus node, and that permanent pacemaker implantation is unnecessary; (3) among the extrinsic and intrinsic causes of SND, intrinsic causes are seldom reversible and some causes of extrinsic SND may be reversible; and (4) prolonged pauses on termination of PAF, frequency of pauses (>2.0 s), and mean heart rate after ablation were independent predictive factors of SND.

Cardiac nodal and cardiac autonomic functions in children with vasovagal syncope.

In the present study, cardiac nodal (sinoatrial node and atrioventricular node) and cardiac autonomic functions have been investigated in children with vasovagal syncope (VVS). Thus, the effect of existing autonomic status on the characteristics of cardiac conduction system has been demonstrated in children with VVS. The study included 51 pediatric patients (the mean age was 14.01±2.79 years, range 7 to 18 years; 30 females), who were evaluated for syncope using ECG, Holter monitoring, and echocardiography, all of which showed normal findings. All patients underwent head-up tilt testing (HUTT), and the parameters of heart rate variability (HRV) (SDNN, SDANN, SDANNi, rMSSD, pNN50, HF, LF, VLF) were evaluated with the analysis of 24-hour Holter testing. Corrected sinus node recovery time (CNRT) and Wenckebach point (WP) were measured in all patients using transesophageal atrial stimulation. The patients were divided into groups according to HUTT results and evaluated accordingly. Cardiac nodal functions were normal in all patients. HRV parameters (HF, rMSSD, pNN50) indicating parasympathetic effect were higher in patients with positive HUTT results. CNRT did not differ significantly between patients with positive HUTT results and patients with negative HUTT results. However, WP was found to be higher in patients with positive HUTT results. The studies evaluating the parameters of HRV has demonstrated increased parasympathetic tonus in children with VVS. Impairment in cardiac nodal functions may not be expected in children with VVS. However, these patients may exhibit prolonged WP due to increased autonomic tonus in favor of parasympathetic activity.

Abstract 13992: The Impact of Dexmedetomidine on the Cardiac Electrophysiological Properties in Patients With Paroxysmal Atrial Fibrillation

Background: Dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, has increasingly been used as a sedative during ablation of atrial fibrillation. DEX is known to have some suppressive effects on the cardiac conduction system, however, that has not yet been extensively assessed in human adults. We aimed to perform a detailed analysis of the impact of DEX on the cardiac electrophysiological properties in patients with paroxysmal atrial fibrillation (AF). Methods and Results: We measured the cardiac electrophysiological properties in adult patients (65±11 years) undergoing ablation of paroxysmal AF who were assigned to receive DEX (10 minutes of a loading at a dose of 6μg/kg/min followed by a maintenance dose of 0.6μg/kg/min; N=120) or those who were assigned not to receive any sedative (N=120). The patients with DEX were more likely than those without to have a longer sinus cycle length (943±190 vs. 802±142ms; p&lt;0.001), greater corrected sinus node recovery time (547±334 vs. 441±239ms; p&lt;0.001), and more prolonged atrial effective refractory period (234±35 vs. 220±33ms; p&lt;0.001). The AH interval (103±24 vs. 91±20ms; p&lt;0.001), atrioventricular (AV) nodal effective refractory period (324±70 vs. 268±58ms; p&lt;0.001), and Wenckebach cycle length (446±76 vs. 377±55ms; p&lt;0.001) were greater in patients with DEX, while the HV interval was similar between the groups (42±11 vs. 41±8ms; p=0.63). AF was less often induced in the patients with DEX than in those without (8.3% vs. 20.8%; p=0.01), when a single extra stimulus was given within the atrial vulnerable period. Conclusions: DEX may have inhibitory effects on both the sinus node and AV node, and may even reduce the AF inducibility in adult AF patients.