Increased P‐Wave Duration and P‐Wave Dispersion in Patients with Aortic Stenosis

Background: P‐wave dispersion (PWD), defined as the difference between the maximum and minimum P‐wave duration, has been proposed as being useful for the prediction of paroxysmal atrial fibrillation (AF). AF is the most common arrhythmia and an important prognostic indicator for clinical deterioration in patients with aortic stenosis (AS). The aim of the present study was to evaluate PWD in patients with AS. Methods: The study population consisted of two groups: Group I consisted of 98 patients with AS (76 men, 22 women; aged 63 ± 8 years) and group II consisted of 98 healthy subjects (same age and sex) without any cardiovascular disease. A 12‐lead electrocardiogram was recorded for each subject. The P‐wave duration was calculated in all leads of the surface electrocardiogram. The difference between the maximum and minimum P‐wave duration was calculated and was defined as the PWD. All patients and control subjects were also evaluated by echocardiography to measure the left atrial diameter, left ventricular ejection fraction, left ventricular wall thicknesses, and the maximum and mean aortic gradients. Patients were also evaluated for the presence of paroxysmal AF. Results: Maximum P‐wave duration and PWD of group I were found to be significantly higher than those of group II. In addition, patients with paroxysmal AF had significantly higher PWD than those without paroxysmal AF. There was no significant difference between the two groups regarding minimum P‐wave duration. In addition, there was no significant correlation between echocardiographic variables and PWD. Conclusion: PWD, indicating increased risk for paroxysmal AF, was found to be significantly higher in patients with AS than in those without it. Further assessment of the clinical utility of PWD for the prediction of paroxysmal AF in patients with severe AS will require longer prospective studies.     

Evolution of P‐Wave Morphology in Healthy Individuals: A 3‐Year Follow‐Up Study

Background: Orthogonal P‐wave morphology in healthy men and women has been described using unfiltered signal‐averaged technique and holds information on interatrial conduction. The stability of P‐wave morphology in healthy subjects over time is not fully known. Methods: Sixty‐seven healthy volunteers were investigated (29 males, aged 63 ± 14 years, 48 females, 60 ± 13 years). Orthogonal lead data (X, Y, and Z) were derived from standard 12‐lead ECGs (recording length 6 minutes, sampling rate 1kHz, resolution 0.625 μV) recorded at baseline (BL), and 3 years later at follow‐up (FU). P waves were then signal‐averaged and analyzed regarding P‐wave morphology, locations of maxima, minima, zero‐crossings, and P‐wave duration (PWD). Results: No differences of P‐wave variables were observed at FU compared to BL, including PWD (127 ± 12 vs 125 ± 14 ms at BL and FU, respectively, n.s.). In 59 of the 67 subjects (88%), the P‐wave morphology was unaltered at FU. However, in the remaining eight cases a distinctively different morphology was observed. The most common change (P = 0.030) was from negative polarity to biphasic (?/+) in Lead Z (n = 5). In one case the opposite change was observed and in two cases transition into advanced interatrial block morphology was evident at FU. Conclusions: In the majority of healthy subjects, P‐wave morphology is stable at 3‐year FU. Subtle morphological changes, observed principally in Lead Z, suggest variation of interatrial conduction. These changes could not be detected by measuring conventional PWD that remained unchanged in the total population.     

The parasitic helminth product ES‐62 suppresses pathogenesis in collagen‐induced arthritis by targeting the interleukin‐17–producing cellular network at multiple sites

Objective

Among many survival strategies, parasitic worms secrete molecules that modulate host immune responses. One such product, ES‐62, is protective against collagen‐induced arthritis (CIA), a model of rheumatoid arthritis (RA). Since interleukin‐17 (IL‐17) has been reported to play a pathogenic role in the development of RA, this study was undertaken to investigate whether targeting of IL‐17 may explain the protection against CIA afforded by ES‐62.

Methods

DBA/1 mice progressively display arthritis following immunization with type II collagen. The protective effects of ES‐62 were assessed by determination of cytokine levels, flow cytometric analysis of relevant cell populations, and in situ analysis of joint inflammation in mice with CIA.

Results

ES‐62 was found to down‐regulate IL‐17 responses in mice with CIA. First, it acted to inhibit priming and polarization of IL‐17 responses by targeting a complex IL‐17–producing network, involving signaling between dendritic cells and γ/δ or CD4+ T cells. In addition, ES‐62 directly targeted Th17 cells by down‐regulating myeloid differentiation factor 88 expression to suppress responses mediated by IL‐1 and Toll‐like receptor ligands. Moreover, ES‐62 modulated the migration of γ/δ T cells and this was reflected by direct suppression of CD44 up‐regulation and, as evidenced by in situ analysis, dramatically reduced levels of IL‐17–producing cells, including lymphocytes, infiltrating the joint. Finally, there was strong suppression of IL‐17 production by cells resident in the joint, such as osteoclasts within the bone areas.

Conclusion

Our findings indicate that ES‐62 treatment of mice with CIA leads to unique multisite manipulation of the initiation and effector phases of the IL‐17 inflammatory network. ES‐62 could be exploited in the development of novel therapeutics for RA.

     

Circadian Behavior of P‐Wave Duration,P‐Wave Area,and PR Interval in Healthy Subjects

Background: The prolongation of P‐wave duration has long been shown to indicate the presence of high risk for atrial fibrillation. The circadian variation of P‐wave characteristics and their dynamic adaptation to heart rate changes was not tested before. Methods: To evaluate the diurnal pattern of P‐wave duration, P area, and PR interval and of their linearly fitted relation with RR interval, 50 healthy volunteers (25 men, mean age 34 ± 10 years) underwent 24‐hour ambulatory electrocardiographic (ECG) recording with digital 12‐lead Holter recorders. The median P‐wave duration, P area, and PR interval were calculated from the average 12‐lead ECG constructed from each 10‐second ECC recording. Single harmonic regression analysis was performed to reveal the presence of circadian variation in the aforementioned ECG parameters. Results: The P area (P < 0.0001, R²= 0.78), the PR interval (P < 0.0001, R²= 0.92), the P area / RR slope (P < 0.0001, R²= 0.55), and the PR/RR slope (P < 0.0001, R²= 0.42) showed a highly significant circadian variation while the periodic nature of P‐wave duration (P = 0.016, R²= 0.32) and of the P duration / RR slope (P = 0.011, R²= 0.18) was only indicated by harmonic regression analysis. Conclusions: P‐wave duration, P area, and PR interval show a significant circadian variation in healthy subjects. The relations between P area/RR,PR/ RR, and P duration/RR also demonstrate a significant diurnal pattern. A.N.E. 2001;6(2):92–97     

Flow cytometry analysis of platelet P‐selectin expression in whole blood – methodological considerations

P‐selectin is an adhesion molecule found in the alpha granules of platelets. Activation occurs in response to a range of inflammatory and thrombotic agents resulting in rapid up‐regulation. Flow cytometry methods have recently been described for the analysis of platelet P‐selectin expression in whole blood. While introducing these methods into our laboratory it was noted that expression could be stimulated, in vitro, in a number of ways. This study shows that red cell lysis, the anticoagulant K₃ EDTA and the time elapse between blood collection and antibody labelling had statistically significant effects on P‐selectin expression. Post‐labelling fixation, with CellFIX, caused no significant effect. We conclude that blood for P‐selectin analysis should be collected in sodium citrate and that red cell lysis and centrifugation should be avoided. When comparing samples, the time between collection and labelling should be standardized. The relatively high CV for the assay indicates that all samples should be labelled and analysed in duplicate with the mean level reported.     

Symptom index P‐value and symptom sensitivity index P‐value to determine symptom association between apnea and reflux in premature infants at term

The current method to determine temporal association (TA) between reflux and symptoms is the symptom association probability (SAP), but this method has limitations due to the constraints of binning and the violation of statistical principles of the Fisher's exact test that lead to an invalid estimation of TA. The aim of this study is to develop improved methods of computing the TA between apneic and reflux events using simulation and permutation methods and to compare these to the SAP. TA was analyzed between polysomnographic obstructive apneas and multichannel intraluminal impedance (MII) reflux events. Three new numerical methods were compared to the SAP in four former premature infants with persistent apneas at term. The experimentally found association was compared to the association observed in simulated or permuted data consistent with the lack of association beyond what is expected by chance alone. Temporal association was computed based on symptom and symptom sensitivity indices, SI and SSI, with varying window of association (WA) times from 15 to 300 s. The three new methods estimated P‐values at varying WA that generally followed the same pattern of the SAP which had a more erratic pattern. The WA that gave the lowest P‐value was approximately 120 s. Each of the novel methods produced P‐value results consistent with each other and the SAP yet not subject to its limitations. The variation of WA gave a temporal profile of TA providing clues to its etiology. These new metrics are called Symptom Index (SIP) and Symptom Sensitivity Index (SSIP) P‐values.     

P‐Wave Rejection in a Transplanted Heart

Background: Heart block can occur at multiple levels in patients with prior cardiac transplant. This diagnosis is usually ascertained using the surface electrocardiogram. Results: A 24‐year‐old man with prior cardiac transplant presented with apparent complete atrioventricular nodal block and junctional escape on the surface ECG. During pacemaker implantation, we demonstrated sinus rhythm in the recipient atrium, block across the atrioatrial anastomosis, and sinus arrest with intact AV nodal conduction in the donor atrium. Conclusion: This case illustrates an unusual presentation of sinus arrest occurring 2 years after heart transplantation that appeared to be complete heart block. Ann Noninvasive Electrocardiol 2011;16(3):308–310     

Evaluation of the Relationship between Atrial Septal Aneurysm and Cardiac Arrhythmias via P‐Wave Dispersion and Signal‐Averaged P‐Wave Duration

Objective: The aim of the study was to investigate the relationship between atrial septal aneurysms (ASAs) and cardiac arrhythmias via signal‐averaged P‐wave duration (SAPWD) and P‐wave dispersion (Pd). Methods: Sixty‐six patients with ASA served as the study group (group 1; 28 men and 38 women; mean age, 34 ± 10 years) and 62 healthy volunteers served as the control group (group 2; 29 men and 33 women; mean age, 31 ± 8 years) in the current study. ASAs were diagnosed by transthoracic echocardiography based on the criteria of a minimal aneurysmal base of ≥15 mm; and an excursion of ≥10 mm. All subjects were evaluated by 24‐hour Holter monitoring, 12 lead body surface electrocardiogram for P‐wave analysis, and signal‐averaged electrocardiogram for P‐wave duration (PWD). Results: There was no significant difference between the study and control groups in terms of age, gender, left atrium diameter, and left ventricular ejection fraction. Supraventricular arrhythmias (SVAs) were detected in 29 patients with ASA (43.9%) and 5 controls (8.1%; P < 0.001). The mean Pd in patients with ASA was significantly longer compared to the control group (14.1 ± 8 ms vs 7.0 ± 2.9 ms; P < 0.001). Similarly, the mean SAPWD in group 1 was significantly longer compared to group 2 (127.4 ± 17.6 ms vs 99.8 ± 12.3 ms; P < 0.001). Conclusion: Prolonged SAPWD and Pd were determined to indicate electrical disturbances in the atrial myocardium, and predict the increase in the prevalence of SVA in patients with ASA. Ann Noninvasive Electrocardiol 2010;15(2):157–164