Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT Syndrome

MOENNIG, G., et al. : Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT Syndrome. Rate corrected QT interval (QTc) and QT dispersion (QTd) have been suggested as markers of an increased propensity to arrhythmic events and efficacy of therapy in patients with long QT syndrome (LQTS). To evaluate whether QTc and QTd correlate to genetic status and clinical symptoms in LQTS patients and their relatives, ECGs of 116 genotyped individuals were analyzed. JTc and QTc were longest in symptomatic patients (  n = 28  ). Both QTd and JTd were significantly higher in symptomatic patients than in asymptomatic (  n = 29  ) or unaffected family members (  n = 59  ). The product of QTd/JTd and QTc/JTc was significantly different among all three groups. Both dispersion and product put additional and independent power on identification of mutation carriers when adjusted for sex and age in a logistic regression analysis. Thus, symptomatic patients with LQTS show marked inhomogenity of repolarization in the surface ECG. QT dispersion and QT product might be helpful in finding LQTS mutation carriers and might serve as additional ECG tools to identify asymptomatic LQTS patients.     

Predictors of Atrial Tachyarrhythmias in Subjects with Type 1 ECG Pattern of Brugada Syndrome

Background: Previous studies have demonstrated a high incidence of atrial tachyarrhythmias (ATs) in patients with Brugada syndrome (BS). The present study aimed to investigate whether various 12-lead electrocardiogram (ECG) and electrophysiological parameters may help to differentiate subjects with a high probability to develop ATs.
Methods and Results: The clinical records of 38 individuals (31 males, age 44.4 ± 13.9) with spontaneous (n = 15) or ajmaline-induced (n = 23) type 1 ECG pattern of BS were analyzed. During a mean follow-up period of 4.6 ± 2.2 years, nine subjects suffered ATs (24%). Six subjects displayed paroxysmal atrial fibrillation and three typical atrial flutter. Among the studied 12-lead ECG parameters, subjects with ATs exhibited increased values of P-wave duration in lead II, P-wave dispersion, PR interval in leads II, QRS duration in leads II and V₂, Tpeak-end interval in lead II, and Tpeak-end dispersion of the 12 leads in relation to those without ATs (P < 0.05). Among the assessed electrophysiological parameters, atrial-His (AH) and His-ventricular (HV) intervals were significantly prolonged in subjects with ATs (P < 0.05). Multiple Cox proportional hazards analysis revealed that P-wave duration in lead II, P-wave dispersion, Tpeak-end in lead II, Tpeak-end dispersion of the 12 leads, as well as AH and HV intervals are independent predictors of ATs in subjects with BS (P < 0.05). Cut-off point analysis showed that an HV interval ≥ 56 ms displayed the highest predictive ability (P < 0.01).
Conclusion: Our findings demonstrate that simple 12-lead ECG and electrophysiological parameters may easily be applied to identify high-risk subjects with BS ECG phenotype to develop ATs .     

Cryoablation at Growing Myocardium: No Evidence of Coronary Artery Obstruction or Intimal Plaque Formation Early and Late after Energy Application

Background: Animal studies and clinical observations have demonstrated that radiofrequency current application at growing myocardium may result in coronary artery obstruction. Recently, cryoenergy has emerged as an effective alternative to radiofrequency ablation of arrhythmogenic substrates in pediatric patients. Up to now, there has been a lack of experimental data concerning the effects of cryoenergy application at growing myocardium.
Methods: During general anesthesia, selective coronary angiography of the right and left coronary artery was performed in 10 piglets (age: 6 weeks, body weight: 14–18 kg). Subsequently, cryoenergy was delivered at −75°C for 4 minutes using a 7-F catheter with a 6-mm-tip electrode at the atrial aspect of the tricuspid valve annulus in a posterior and lateral position. Additional cryoenergy lesions were induced via a retrograde approach at the lateral and posterior atrial and ventricular aspect of the mitral valve annulus, respectively. Five animals were restudied after 48 hours by coronary angiography and intracoronary ultrasound and in the remaining five piglets after 3 and 6 months, respectively.
Results: Selective coronary angiography and intracoronary ultrasound studies did not demonstrate any evidence for coronary artery obstruction after 48 hours, 3 months, or 6 months after cryoenergy application. In addition, histological examinations of the cryolesions after 48 hours and after 6 months did not demonstrate any intimal proliferations of the coronary arteries, respectively.
Conclusions: By means of the present study, we did not observe any affection of the coronary arteries after cryoenergy application at growing myocardium in young piglets.     

Discrimination of Sinus Rhythm, Atrial Flutter, and Atrial Fibrillation Using Bipolar Endocardial Signals

Discrimination of NSR, AFL, and AF. Introduction : Analysis of endocardial signals obtained from an electrode located in the right atrium as realized in newly designed dual chamber, implantable cardioverter defibrillators might be used to provide additional therapeutic options, such as overdrive pacing or low-energy atrial cardioversion for the treatment of concomitant atrial flutter (AFL) or atrial fibrillation (AF). Therefore, we developed a computer algorithm for discrimination of normal sinus rhythm (NSR), AFL, and AF that may lead to adequate differential therapy of atrial tachyarrhythmias in an automated mode.
Methods and Results : During an electrophysiologic study, bipolar endocardial signals from the high right atrium were obtained in 28 patients during sustained AFL or AF and after restoration of NSR. A total of 286 data segments of 5-second duration were recorded (NSR: 96, AFL: 86, AF: 104). Mean atrial cycle length (MCL), standard deviation of mean atrial cycle length (SDCK), and index of irregularity (IR). defined as the ratio between MCL and SDCL, were calculated for each data segment. A cutoff of 315 msec for MCL allowed discrimination of NSR from atrial tachyarrhythmias with 100% sensitivity and specificity. For discrimination of AF from AFI- by using SDCL, a cutoff value of 11.5 msec led to a sensitivity of 99% and a specificity of 90%. Best discrimination of AF from AFL was found for the criterion IR ≥ 7.5%, resulting in a sensitivity of 100% with a specificity of 95% for AF detection.
Conclusion : The investigated algorithm provides discrimination of NSR, AFL, and AF with high sensitivity and specificity. Incorporation of this algorithm in an implantable automated antitachycardia device may lead to adequate differential therapy in patients suffering from spontaneous episodes of AF and AFL.     

Thickness of the subchondral mineralised tissue zone (SMZ) in normal male and female and pathological human patellae

The objective of this paper was to analyse sex differences of the thickness of the subchondral mineralised tissue zone (SMZ), and to find out whether systematic changes of SMZ thickness are associated with naturally occurring, non-full-thickness cartilage lesions of human patellae. In 32 methyl-methacrylate-embedded specimens (16 normal, 8 with focal medial, and 8 with lateral lesions) the SMZ thickness was determined, using a binocular macroscope and an image analysing system. In each case, the thickness distribution was reconstructed throughout the entire joint surface. The maximal and mean SMZ thicknesses were significantly higher in males than in females ( P <0.01). In normal patellae and those with lateral lesions, the thickness was significantly thicker laterally than medially ( P <0.05), but it was not in specimens with medial damage. Patellae with medial damage exhibited a significantly lower total mean and lateral mean ( P <0.05). A lower SMZ thickness was found directly beneath medial lesions than beneath lateral ones, but the local thickness was always in the range of that observed in normal specimens. We conclude that differences of patellar SMZ thickness exist between males and females. Naturally occurring cartilage lesions appear, however, not to be associated with local changes of SMZ thickness, but they may be associated with an altered regional distribution pattern within the joint surface.     

Assessment of Intersignal Variability for Discrimination of Atrial Fibrillation from Atrial Flutter

The analysis of endocardial signals obtained from an electrode located in the right atrium enabled by new dual chamber implantable cardioverter defibrillators may be helpful to provide additional therapies such as overdrive pacing or low energy atrial cardioversion for the treatment of concomitant atrial flutter (AFL) or atrial fibrillation (AF). Algorithms for discrimination of atrial tachyarrhythmias based on rate counting are of limited efficacy. The aim of this study was to assess the intersignal variability by using fast discrete wavelet transforms (FDWT) as a new method of discrimination of AF from AFL. Patients with spontaneous episodes of AF/AFL or patients who developed AF/AFL during an electrophysiological study were studied. The endocardial signals were recorded from the high right atrium using a transvenous 5 Fr bipolar electrode catheter (interelectrode spacing: 1 cm). The signals were digitized (2 kHz, 12-bit resolution) after amplification and filtering (40–500 Hz). Within data segments of 10-second duration, 25 consecutive signals were selected and normalized and FDWT was applied. Standard deviations of the wavelet coefficients (SD) from coarse scales (scale 4–8) were calculated. A total of 94 data segments (AF: 52, AFL: 42) from 28 patients were analyzed. SD at each considered scale was higher for AF than for AFL (P < 0.001). SD at scale 8 discriminated between AF from AFL with 100% sensitivity and specificity. We conclude that assessment of intersignal variability of bipolar endocardial recordings using FDWT is an effective method for the discrimination of AF from AFL. The implementation of this tool in a discrimination algorithm of an implantable device may help provide the appropriate differential therapy for atrial tachyarrhythmias.     

Metabolism and Disposition of Dipropylene Glycol Monomethyl Ether (DPGME) in Male Rats

Metabolism and Disposition of Dipropylene Glycol MonomethylEther (DPGME) in Male Rats. MILLER, R. R., HERMANN, E. A., CALHOUN,L. L., KASTL, P. E., AND ZAKETT, D. (1985). Fundam. Appl. Toxicol.5, 721–726. Male Fischer 344 rats were given a singleoral dose of approximately 1289 mg/kg (8.7 mmol/kg) of [¹⁴C]DPGME.After dosing, expired air, excreta, and tissues were analyzedfor ¹⁴C activity, and metabolites in urine were isolated andidentified. Approximately 60% of the administered ¹⁴C activitywas excreted in urine, while 27% was eliminated as ¹⁴CO₂ within48 hr after dosing. DPGME, PGME, dipropylene glycol, propyleneglycol, as well as sulfate and glucuronide conjugates of DPGMEwere identified in urine of animals given [¹⁴C]DPGME. Resultsof the study indicate that DPGME is metabolized via the sameroutes to the same general types of metabolites as previouslyidentified for propylene glycol monomethyl ether (PGME)