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Introduction: Idiopathic ventricular fibrillation (IVF) is mainly associated with and triggered by short‐coupled (R‐on‐T) ventricular ectopics. However, little is known about the risk of VF associated with long‐coupled premature ventricular complexes (LCPVCs). Objective: To examine the prevalence and characteristics of IVF patients presenting with LCPVCs. Methods: Consecutive patients with IVF and PVCs from five arrhythmia referral centers were reviewed. We included patients presenting LCPVCs, defined as PVCs falling after the end of the T wave, with a normal QTc interval. We evaluated demographics, medical history, and clinical circumstances associated with PVCs and VF episodes. The origin of PVCs was determined by invasive mapping. Results: Seventy‐nine patients with IVF were reviewed. Among them, 12 (15.2%) met the inclusion criteria (8 women, age 36 ± 14 years). Eleven patients had documented LCPVCs initiating repetitive PVCs or sustained VF, whereas 1 had only documented isolated PVCs. In 10 of 12 patients, PVCs were recorded showing both long and short coupling intervals of 418 ± 46 and 304 ± 33 ms, respectively. Mapping showed that PVCs originated from the left Purkinje in 10 patients, from the right Purkinje in 1 patient, and both in 1 patient. Compared to other patients from the initial cohort, IVF with LCPVCs was associated with a left‐sided origin of PVCs (92% in long‐coupled IVF vs. 46% of left Purkinje PVCs in short‐coupled IVF, p =.004). Conclusion: Long‐coupled fascicular PVCs, traditionally recognized as benign, can be associated with IVF in a subset of patients. They can induce IVF by themselves or in association with short‐coupled PVCs. [ABSTRACT FROM AUTHOR]

Introduction: Oral targeted therapies (OTTs) are widely used for cancer management. However, there is no consensus on OTT dose adaptation in older patients with cancer. Methods: This noninterventional, retrospective study was a real‐life assessment of dose adaptation for six OTTs (afatinib, everolimus, palbociclib, pazopanib, sorafenib and sunitinib), at baseline and during treatment, and the reasons for the changes, in ≥70‐year‐old patients treated between February 2016 and August 2019. Data were compared with univariate models fitted with all variables. Results: Among the 986 patients treated with OTT, the group of ≥70‐year‐old patients (n = 122) received afatinib (15.6%), everolimus (14.8%), palbociclib (50.8%), pazopanib (9.8%), sorafenib (5.8%) or sunitinib (3.2%). At baseline, the prescribed OTT dose was adapted (reduction) in 29% of ≥70‐year‐old patients (35/122). These 35 patients were significantly older (mean age 80 vs 74 years, P <.001), and more frequently had a performance status score ≥2 (P <.01) than the other patients (n = 87). In the standard dose group, higher toxicity grades (P =.18) and subsequent dose reduction (41% of patients, 36/87) tended to be more frequent compared with the baseline adapted dose group (26%, 9/35, P =.1). At the study end, 53% of patients in the whole cohort (65/122) were taking a lower dose than the recommended one. Conclusion: At OTT initiation, dose was adapted in 29% of older adults with cancer, rarely after a formal oncogeriatric evaluation (6.5% of all patients). In the absence of recommendations, clinical studies are needed to evaluate the efficacy and safety of baseline OTT dose reduction in older adults with cancer. [ABSTRACT FROM AUTHOR]

Background: To evaluate FCH-PET/CT and parathyroid 4D-CT so as to guide surgery in patients with primary hyperparathyroidism (pHPT) and prior neck surgery. Methods: Medical records of all patients referred for a FCH-PET/CT in our institution were systematically reviewed. Only patients with pHPT, a history of neck surgery (for pHPT or another reason) and an indication of reoperation were included. All patients had parathyroid ultrasound (US) and Tc-99m-sestaMIBI scintigraphy, and furthermore, some patients had 4D-CT. Gold standard was defined by pathological findings and/or US-guided fine-needle aspiration with PTH level measurement in the washing liquid. Results: Twenty-nine patients were included in this retrospective study. FCH-PET/CT identified 34 abnormal foci including 19 ectopic localizations. 4D-CT, performed in 20 patients, detected 11 abnormal glands at first reading and 6 more under FCH-PET/CT guidance. US and Tc-99m-sestaMIBI found concordant foci in 8/29 patients. Gold standard was obtained for 32 abnormal FCH-PET/CT foci in 27 patients. On a per-lesion analysis, sensitivity, specificity, positive and negative predictive values were, respectively, 96%, 13%, 77% and 50% for FCH-PET/CT, 75%, 40%, 80% and 33% for 4D-CT. On a per-patient analysis, sensitivity was 85% for FCH-PET/CT and 63% for 4D-CT. FCH-PET/CT results made it possible to successfully remove an abnormal gland in 21 patients, including 12 with a negative or discordant US/Tc-99m-sestaMIBI scintigraphy result, with a global cure rate of 73%. Conclusion: FCH-PET/CT is a promising tool in the challenging population of reoperative patients with pHPT. Parathyroid 4D-CT appears as a confirmatory imaging modality. [ABSTRACT FROM AUTHOR]

Summary: Background: Thyroid cancers are threefold more frequent in women than in men. A role of reproductive or hormonal factors has been suggested but with contradictory results. We investigated potential associations between history of hysterectomy, with or without oophorectomy, and history of benign gynaecological disease (uterine fibroids, endometriosis) and the incidence of differentiated thyroid cancer, in a large French prospective cohort. Methods: A total of 89 340 women from the E3N cohort were followed up between 1990 and 2012. Gynaecological diseases treated by surgery were self‐reported. Thyroid cancers were validated by histological reports. Time‐dependent covariates included smoking status, BMI and history of benign thyroid disease. Cox proportional hazard models with age as timescale were used to estimate Hazard Ratios (HR) and 95% confidence intervals (CI). Results: A total of 412 cases of thyroid cancer were diagnosed during follow‐up. A history of hysterectomy was associated with an increased risk of differentiated thyroid cancer (adjusted HR=2.05; 95%CI: 1.65‐2.55). The association was not altered after further adjustment for reproductive factors. Endometriosis, uterine polyps, ovarian cysts and oophorectomy without hysterectomy were not associated with the risk of thyroid cancer. A history of fibroids was also significantly related to the risk of thyroid cancer over the follow‐up period (adjusted HR=1.91; 95%CI: 1.50‐2.44) and the increased risk persisted after adjustment for history of hysterectomy. Conclusions: Women who had either a history of fibroids or hysterectomy had an increased risk of differentiated thyroid cancer. These findings suggest shared biological mechanisms between fibroids and thyroid cancer, which deserve to be further dissected. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous laryngeal ultrasonography (TLUS) was recently developed to assess recurrent nerve palsy after thyroid/parathyroid surgery, with variable rates of efficiency. The aim of the current study was to evaluate this technique using subjective estimation and post-processing quantitative data. Methods: Fifty subjects presenting with a recurrent nerve palsy and 50 “controls” presenting with voice, swallowing, or breathing disorders following thyroid/parathyroid surgery were prospectively included. All of them underwent a flexible laryngoscopy, considered the gold standard, and a ten-second TLUS clip within the 10 days following surgery. In addition to the subjective interpretation of vocal fold motion, two quantitative criteria taking into account motion symmetry (symmetry index, SI) and amplitude (mobility index) of the two hemi-larynges were defined on TLUS acquisitions in adduction and abduction. Results: The subjective interpretation provided a sensitivity of 100% and a specificity of 96%, compared to the gold standard. The quantitative criteria provided a sensitivity and specificity of both 82%, when based on SI solely. When combining SI and mobility index, the sensitivity reached 94%, but the specificity fell to 66%.Conclusions: Visual assessment of recurrent nerve palsy using TLUS after thyroid/parathyroid surgery appeared a high sensitive and specific test compared to flexible laryngoscopy. Quantitative criteria are promising and need to be refined to better describe the whole TLUS video clip. [ABSTRACT FROM AUTHOR]

Vocal fold motion was analyzed during free breathing using two ‐ dimensional dynamic ultrasound imaging. Two cadavers were first analyzed to define easily identifiable landmarks. Motion of the laryngeal tract was then analyzed in an axial plane. Left and right arytenoids and thyroid cartilage were defined on images corresponding to abduction and adduction of the laryngeal tract. Associated area measurements were established for 50 healthy subjects. All area indices were significantly larger during abduction than adduction. Symmetry of motion was established by comparing each hemi ‐ larynx, and mobility fractions were defined. Normal values of laryngeal motion during free breathing were thus established. [ABSTRACT FROM AUTHOR]

Background: T-wave morphology parameters based on principal component analysis (PCA) are candidate to better understand the relation between QT prolongation and torsades de pointes. We aimed to assess the repeatability and to determine the influence of T-end position on PCA parameters.Methods: Digital ECGs recorded from 30 subjects were used to assess short term (5 minutes), circadian and long-term (28 days) repeatability of PCA parameters. The T-end cursor position was moved backward and forward (+/- 8 ms) from its optimal position. We calculated QRS-T angle, PCA ratio, and T-wave residuum (TWR).Results: At long-term evaluation, coefficients of variation were 11.3 +/- 9.9%, 11.7 +/- 7.1%, and 23.0 +/- 22.0% for the QRS-T angle, PCA ratio, TWR, respectively. After moving the T-end cursor, repeatability was 0.42 +/- 0.2%, 1.00 +/- 1.04%, 4.0 +/- 4.2% for the same PCA parameters.Conclusions: T-wave morphology parameters based on PCA are reproducible with the exception of TWR and QRS-T angle. In addition, PCA is robust, showing only little dependence on T-end cursor position. These data should be taken into account for safety pharmacology trials. [ABSTRACT FROM AUTHOR]

Background: Universal QT correction formulae have been shown to under or overcorrect the QT interval duration. Individual QT-R-R modeling has been proposed as a preferable solution for heart rate correction of QT intervals. However, the QT-R-R relationship stability over time needs to be evaluated.Methods: The present report is part of randomized, double-dummy, and placebo-controlled 4-way crossover phase 1 study (48 healthy volunteers). Each randomized period included a run-in placebo day followed the day after by drug administration, with moxifloxacin as a positive control for QT interval measurement. Digital Holter ECG data were analyzed using the "bin" approach. For each period, individual QT-R-R relationship were calculated using two different models (linear and parabolic log-log models).Results: The mean intrasubject variability for the alpha coefficient of the linear modeling (SDintra = 0.011 +/- 0.005) reached 28.6 +/- 10.2%. When the parabolic model was considered, the SDintra was 0.026 +/- 0.009 for the alpha coefficient. The QT-R-R relationship variability was in part related to long-term RR changes (R2 = 30%, P < 0.05). However, no significant time effect (ANOVA) was evidenced for QT-R-R coefficients. Moxifloxacin significantly increased the alpha coefficient of the QT-R-R relationship from 0.07 +/- 0.018 to 0.085 +/- 0.019, P < 0.05 (linear model).Conclusions: The individual QT-R-R relationship shows a residual variability in part related to long-term autonomic changes. In addition, the QT-R-R relationship might be modulated by the drug tested. As a consequence, pretherapy QT-R-R relationship obtained in a given patient cannot be used as a fingerprint throughout a drug trial. [ABSTRACT FROM AUTHOR]

Background: Although well established on the sinus node, the effects of beta-blockade on ventricular repolarization are still conflicting. The aim of the study was to investigate the effects of a chronic beta-blockade on sinus node and repolarization parameters and their relationship.Methods: Sixteen healthy volunteers (10 males, mean age: 40 +/- 6.7 years) were randomized to placebo or atenolol (100 mg). After 7 days, subjects were crossed over. Heart rate (HR) and HRV indices were calculated from long-term ECG recordings separately during the day and at night, together with ventricular repolarization parameters (QT interval duration and QT rate-dependence).Results: Mean R-R intervals were significantly and consistently increased after atenolol (Day: 916 +/- 103 ms vs. 712 +/- 89 ms, and Night: 1149 +/- 93 vs. 996 +/- 125 ms). HRV changes under atenolol were also consistent, with a significant decrease in sympathovagal ratio. In contrast, atenolol only lowered diurnal QT rate-dependence (0.123 +/- 0.032 vs. 0.190 +/- 0.065 on placebo, P < 0.001), but not the nocturnal pattern. After multivariate analysis QT rate-dependence changes induced by atenolol were correlated with pretreatment QT/RR relation (r = 0.65, P < 0.01) but not with any HR or HRV parameters.Conclusions: In healthy subjects, repolarization changes following chronic beta-blockade cannot be predicted by HR or HRV changes, but are dependent on pretreatment rate-dependence. [ABSTRACT FROM AUTHOR]

Background In the long QT syndrome (LQTS) the effects of beta-blocker treatment on prevention of cardiac events differs according to the genotype. We aimed to assess the effect of beta-blocker treatment on QT/QTc duration in Type 1 LQTS (LQT1) and Type 2 LQTS (LQT2) patients. Methods 24-hour digital Holter ECG were recorded before and after beta-blocking therapy initiation in LQT1 (n = 30) and LQT2 patients (n = 16). QT duration was measured on consecutive 1-minute averaged QRS-T complexes leading to up to 1440 edited QT-RR pairs for each recording. We computed subject- and treatment-specific log/log QT/RR relationships which were used to correct the QT intervals. The QT duration was also evaluated at predefined heart rates and after correction using Bazett and Fridericia coefficients. Results At baseline, individual QT/RR coefficients were higher in LQT2 than in LQT1 patients (0.53 ± 0.10 vs. 0.40 ± 0.11, P < 0.001) and QT1000 was longer in LQT2 than in LQT1 patients (521 ± 38 vs. 481 ± 39 ms, P < 0.01). Beta-blockers significantly prolonged the mean RR interval (from 827 ± 161 to 939 ± 197 ms, P < 0.0001). The individual QT/RR coefficients were not significantly modified by beta-blockers. Beta-blocker treatment was associated with a prolongation of the QT1000 interval (from 481 ± 39 to 498 ± 43 ms, P < 0.01) in LQT1 patients but with a shortening in LQT2 patients (from 521 ± 38 to 503 ± 32 ms, P < 0.01). Conclusions The effect of beta-adrenergic blockade on QTc duration is different in LQT1 and LQT2 patients. Our data suggest that, in LQT1 patients, the well-known positive effect of beta-blockade might be associated with a prolongation of QTc duration. The mechanisms of beta-blockade protection may be different in LQT1 and in LQT2 patients. [ABSTRACT FROM AUTHOR]

Background: Cervical lymph node (LN) metastases are common in patients with papillary thyroid carcinoma (PTC), and they have a negative impact on recurrence. The management of preoperatively node-negative (N0) PTC is still controversial. The aim of our study was to describe the results of a prophylactic bilateral lymph node dissection (LND) and to investigate its impact on recurrence. Methods: From 2003 to 2011, we analyzed 603 consecutive preoperatively N0 PTC patients. For each patient, we reviewed demographics data, tumor characteristics, pattern and risk factors of LN metastasis, and outcome. Results: Lymph node metastases were found in 23 % of patients: 19 % in the central compartment and 8 % in the lateral compartment, including 1 % in the lateral compartment on the opposite side from the tumor. Multivariate analysis showed that hyperthyroidism and extrathyroidal invasion of the tumor were significantly associated with LN metastasis. Further analysis showed that localization of the tumor in the upper third of the thyroid lobe and metastatic LN in the central compartment were independent risk factors for lateral LN metastasis. During the 4.3-year follow-up, 23 recurrences were observed (4 %), including 5 in the central compartment. Recurrence rates were 2 % in the N0 group, 5 % in N1a patients, and 22 % in N1b patients ( p < 0.001). Conclusions: In preoperatively N0 PTC patients, LN metastases are frequent in central and ipsilateral lateral compartments. Prophylactic LND in the central and ipsilateral lateral compartments should therefore be recommended in the presence of PTC to identify high-risk patients. [ABSTRACT FROM AUTHOR]

Background: T-wave alternans (TWA) is an accepted marker of risk for malignant ventricular arrhythmias, for which prognosis value has been established in different populations. Short QT syndrome (SQTS) is a very rare primary electrical disease carrying the risk of ventricular fibrillation. TWA in SQTS has not been evaluated yet. Methods: Thirteen patients with SQTS (QT = 308 ± 16 ms, QTc = 329 ± 10 ms, heart rate = 69 ± 8 beats/min) underwent microvolt TWA measurement using spectral analysis. TWA testing was performed using Heartwave II (Cambridge Heart™, Inc., Bedford, MA, USA) during bicycle exercice and classified as negative, positive, or indeterminate according to the published standards for clinical interpretation. Results: Twelve patients were male (mean age 23 ± 5 years). Five were asymptomatic, three presented with aborted sudden cardiac death, and five with unexplained syncope. Six patients belonged to two unrelated families, while familial cases of SQTS were present for two other patients. A familial history of sudden death (SD) was present for seven patients. Ventricular fibrillation was inducible in three patients. Four patients were implanted with an implantable cardioverter-defibrillator and one presented with polymorphic ventricular tachycardia during follow-up. TWA was negative in each but one patient (indeterminate). Maximal negative heart rate was 118 ± 12 beats/min. Patients with previous SD displayed significant shorter QT and higher resting heart rate compared to the remaining cases. Conclusions: TWA testing is negative in 12 of 13 SQTS patients, even in the symptomatic or inducible ones. Measurement of TWA using conventional protocol and criteria for risk stratification in SQTS seems therefore useless. (PACE 2012;35:1413-1419) [ABSTRACT FROM AUTHOR]

Backround: Centenarians have been proposed as a model of successful aging but recent studies suggest a high prevalence of cardiovascular diseases. Some findings on their electrocardiograms (ECGs) are simply age-related and others mirror underlying diseases. We aimed to identify ECG features truly associated with extreme age. Methods: Retrospective analysis of 55 centenarians hospitalized between January 2000 and June 2010. Each centenarian was matched with three octogenarians according to gender, presence of hypertension, aortic stenosis, heart failure, and ischemic heart disease. Results: A history of hypertension was present in 32 (58%) centenarians, aortic stenosis in 6 (11%), heart failure in 8 (15%), and ischemic heart disease in 6 (11%). Centenarians had a higher heart rate than octogenarians (81 ± 15 bpm vs. 72 ± 15 bpm, respectively, P < 0.001) but were less frequently on beta-blockers (7% vs. 36%, respectively, P < 0.001). Centenarians displayed more frequently atrial premature beats than octogenarians (18% vs. 3%, respectively, P < 0.001) but tended to have less atrial fibrillation (15% vs. 22% respectively, P = 0.21). Centenarians had more frequently left QRS axis deviation (48% vs. 28%, P = 0.009) and Q waves (14% vs. 1%, P = 0.02). QT interval was more prolonged in centenarians (446 ± 42 ms vs. 429 ± 39 ms, P = 0.008). Two centenarians (4%) and 24 (15%) octogenarians had a strictly normal ECG (P = 0.02). Conclusions: Abnormal ECG is a common finding in centenarians, with different characteristics than in younger elderly individuals. These differences are unrelated to the presence of cardiac diseases. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to assess the time course effect of IKr blockade on ECG biomarkers of ventricular repolarization and to evaluate the accuracy of a fully automatic approach for QT duration evaluation. Methods: Twelve-lead digital ECG Holter was recorded in 38 healthy subjects (27 males, mean age = 27.4 ± 8.0 years) on baseline conditions (day 0) and after administration of 160 mg (day 1) and 320 mg (day 2) of d-l sotalol. For each 24-hour period and each subject, ECGs were extracted every 10 minutes during the 4-hour period following drug dosage. Ventricular repolarization was characterized using three biomarker categories: conventional ECG time intervals, principal component analysis (PCA) analysis on the T wave, and fully automatic biomarkers computed from a mathematical model of the T wave. Results: QT interval was significantly prolonged starting 1 hour 20 minutes after drug dosing with 160 mg and 1 hour 10 minutes after drug dosing with 320 mg. PCA ventricular repolarization parameters sotalol-induced changes were delayed (>3 hours). After sotalol dosing, the early phase of the T wave changed earlier than the late phase prolongation. Globally, the modeled surrogate QT paralleled manual QT changes. The duration of manual QT and automatic surrogate QT were strongly correlated (R2= 0.92, P < 0.001). The Bland and Altman plot revealed a nonstationary systematic bias (bias = 26.5 ms ± 1.96*SD = 16 ms). Conclusions: Changes in different ECG biomarkers of ventricular repolarization display different kinetics after administration of a potent potassium channel blocker. These differences need to be taken into account when designing ventricular repolarization ECG studies. Ann Noninvasive Electrocardiol 2010;15(1):26–35 [ABSTRACT FROM AUTHOR]

WHAT IT IS ALREADY KNOW ABOUT THIS SUBJECT • Amiodarone is a highly effective antiarrhythmic drug, but is limited in practice by its adverse effects, which are frequent on long-term administration and can be severe. • Amiodarone is very lipophilic and attains high concentrations in many tissues. • Excessive accumulation in tissues is suspected as a possible cause of some of its adverse events, but sampling affected tissues (e.g. lung, thyroid, heart) in vivo is difficult. • Subcutaneous adipose tissue is more easily obtained, and studying concentrations of amiodarone and N-desethyl-amiodarone there could help to understand how amiodarone distributes and accumulates in tissues in general. WHAT THIS STUDY ADDS • No evidence of excessive or unexpected accumulation of amiodarone in fat tissue, with respect to dose, was found in patients treated for >3 months. • Concentrations in plasma and subcutaneous fat tissue were better related to maintenance daily dose than to cumulated dose or treatment duration. • Clinically relevant adverse effects of amiodarone, for the most part hypothyroidism, were significantly associated with longer duration of treatment and larger cumulated doses. • In contrast, adverse events were not correlated with higher amiodarone or N-desethyl-amiodarone concentrations, whether in plasma or in adipose subcutaneous tissue. • The measurement of these concentrations does not seem useful in predicting the risk of adverse effects. AIMS To determine if amiodarone, highly lipophilic, accumulates in excess with respect to dose in fat tissue during long-term administration, and study if plasma and fat tissue concentrations are correlated with adverse effects. METHODS Trough concentrations of amiodarone and N-desethyl-amiodarone were measured simultaneously in plasma and fat tissue, in 30 consecutive patients treated with amiodarone for 3 months to 12 years. Subcutaneous adipose tissue was obtained by needle aspiration from lumbar and abdominal areas. Concentrations were measured by liquid chromatography–tandem mass spectrometry. RESULTS Plasma levels of amiodarone and N-desethyl-amiodarone were significantly correlated with daily maintenance doses ( R= 0.52, P= 0.003). Amiodarone concentrations in fat tissue were four to 226 times (mean 55) higher than in plasma, and well correlated with plasma levels ( R= 0.68, P < 0.001). Concentrations of amiodarone and N-desethyl-amiodarone in adipose tissue did not significantly increase with higher total cumulated doses or longer treatment duration. Nine of 12 patients who had received amiodarone for ≥2 years developed clinically important adverse effects, predominantly hypothyroidism ( n= 6), compared with two of 18 patients treated for less time (relative risk 6.75; 95% confidence interval 1.8, 26). The incidence of those adverse effects was not significantly associated with amiodarone concentrations, whether in plasma or in adipose tissue. CONCLUSIONS We found no evidence of excessive or unexpected accumulation of amiodarone in fat tissue on long-term administration. Late amiodarone adverse effects, particularly hypothyroidism, are associated with longer exposure times, but do not seem to be explained by higher concentrations in plasma or in fat tissue. [ABSTRACT FROM AUTHOR]

Ventricular repolarization properties are dependent on cardiac cycle length. The aim of this article is to emphasize the importance of taking into account heart rate influences on QT duration but also on current and future T-wave morphology parameters. The relationship between QT interval duration and RR interval is a fundamental property of the myocardium that is impaired by the presence of channelopathies such as the LQTS or SQTS, but also by the presence of a cardiomyopathy. Assessing this property is also important when the individual QT/RR relationship is used for individual QT correction in the setting of evaluation of drugs' effect on QT duration. T-wave descriptors such as the relative weight of the terminal part of the T-wave, the amplitude of T-wave apex and Principal Component Analysis parameters are also dependent on heart rate. Assessing ventricular repolarisation ECG parameters at different heart rates avoids the need for difficult rate-correction and helps to better understand and characterize ventricular repolarisation properties. [ABSTRACT FROM AUTHOR]

Abstract: Background: Cardiac resynchronisation therapy (CRT) is a validated treatment for heart failure (HF) patients in NYHA class III–IV despite optimal medical therapy. We aimed to assess the beneficial effects of CRT in patients with catecholamine-dependent overt HF (CDOHF). Methods: We studied 20 CDOHF patients who had undergone CRT implantation. Patients had a mean baseline QRS duration of 174±25 ms and/or echocardiographic asynchrony, and LVEF of 18±3%. Mean follow-up was 18±12 months. Dependence on catecholamine agents was defined as the inability to stop or reduce drug infusion without re-occurrence of hypotension, low urine output and hypoxaemia. Results: After CRT implantation, catecholamine agents were mostly withdrawn within 2 days and blood pressure, urine output and BNP rapidly improved within 24 h. During follow-up, survival rates were 85% at 3 months, 80% at 6 months and 55% at 18 months. Among the 9 deaths, 5 were related to overt HF, 3 to sudden cardiac death and 1 to non-cardiac death. LVEF improved from 18±3% to 21±4% three months after CRT implantation. Conclusion: “Rescue” CRT implantation in CDOHF patients allowed a rapid and successful catecholamine weaning in all studied patients. Furthermore, this immediate beneficial effect is sustained for more than one year in surviving patients. [Copyright &y& Elsevier]

Background: T-wave morphology parameters based on principal component analysis (PCA) are candidate to better understand the relation between QT prolongation and torsades de pointes. We aimed to assess the repeatability and to determine the influence of T-end position on PCA parameters. Methods: Digital ECGs recorded from 30 subjects were used to assess short term (5 minutes), circadian and long-term (28 days) repeatability of PCA parameters. The T-end cursor position was moved backward and forward (± 8 ms) from its optimal position. We calculated QRS-T angle, PCA ratio, and T-wave residuum (TWR). Results: At long-term evaluation, coefficients of variation were 11.3 ± 9.9%, 11.7 ± 7.1%, and 23.0 ± 22.0% for the QRS-T angle, PCA ratio, TWR, respectively. After moving the T-end cursor, repeatability was 0.42 ± 0.2%, 1.00 ± 1.04%, 4.0 ± 4.2% for the same PCA parameters. Conclusions: T-wave morphology parameters based on PCA are reproducible with the exception of TWR and QRS-T angle. In addition, PCA is robust, showing only little dependence on T-end cursor position. These data should be taken into account for safety pharmacology trials. [ABSTRACT FROM AUTHOR]

The authors aim to highlight the pitfalls of different validated methods used for the assessment of drugs' effect on QT duration. Digital 12-lead Holter electrocardiograms were recorded at baseline and after a single dose of sotalol in 39 healthy subjects (age = 27.4 ± 8.0 years). Using both time- and rate-based approaches, the authors obtained averaged QRS-T complexes every minute ("time bins") and at different RR intervals ("rate bins"). Time bins were corrected for heart rate using a subject-specific approach. The individual a coefficients increased from placebo (0.309 ± 0.052) to sotalol (0.454 ± 0.136), P <.0001. When the placebo individual a coefficients were applied to correct the QT interval on sotalol, the changes were >5 ms smaller than those obtained using the ON drug a coefficients. The "rate "-averaging process leads to a complete loss of the time course of drug effect. In conclusion, the individual correction formula calculated from the placebo condition cannot always be used for QT correction on the drug. [ABSTRACT FROM AUTHOR]

Background: The formulas for heart rate (HR) correction of QT interval have been shown to overcorrect or undercorrect this interval with changes in HR. A Holter-monitoring method avoiding the need for any correction formulas is proposed as a means to assess drug-induced QT interval changes. Methods: A thorough QT study included 2 single doses of the α1-adrenergic receptor blocker alfuzosin, placebo, and a QT-positive control arm (moxifloxacin) in 48 healthy subjects. Bazett, Fridericia, populationspecific (QTcN), and subject-specific (QTcNi) correction formulas were applied to 12-lead electrocardiographic recording data. QT1000 (QT at RR = 1000 ms), QT largest bin (at the largest sample size bin), and QT average (average QT of all RR bins) were obtained from Holter recordings by use of custom software to perform rate-independent QT analysis. Results: The 3 Holter end points provided similar results, as follows: Moxifloxacin-induced QT prolongation was 7.0 ms (95% confidence interval [CI], 4.4-9.6 ms) for QT1000, 6.9 ms (95% CI, 4.8-9.1 ms) for QT largest bin, and 6.6 ms (95% CI, 4.6-8.6 ms) for QT average. At the therapeutic dose (10 mg), alfuzosin did not induce significant change in the QT. The 40-mg dose of alfuzosin increased HR by 3.7 beats/min and induced a small QT1000 increase of 2.9 ms (95% CI, 0.3-5.5 ms) (QTcN, +4.6 ms [95% CI, 2.1-7.0 ms]; QTcNi, +4.7 ms [95% CI, 2.2-7.1 ms]). Data corrected by ‘universal’ correction formulas still showed rate dependency and yielded larger QTc change estimations. The Holter method was able to show the druginduced changes in QT rate dependence. Conclusions: The direct Holter-based QT interval measurement method provides an alternative approach to measure rate-independent estimates of QT interval changes during treatment. (Clin Pharmacol Ther 2005; 77:247-58.) [ABSTRACT FROM AUTHOR]

Death Due to an ICD . Inappropriate therapy due to noise oversensing caused a true ventricular fibrillation (VF) and death of a patient. A 49-year-old patient with a history of dilated cardiomyopathy received a double-chamber implantable cardioverter defibrillator (ICD) in 1991 for a sustained inducible ventricular tachycardia (VT). One appropriate shock delivered in 1994 terminated an episode of VT. The generator was replaced in 1995 and in 2000, and was connected to the initial leads. Three months after the second replacement, the patient received six consecutive shocks related to detection of noise interpreted as VF. Unfortunately, the sixth shock triggered a true VF, which was not treated due to end of the therapeutic sequence, and the patient died. The causes of the dysfunction are discussed. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-4, August 2004) [ABSTRACT FROM AUTHOR]

Stroke Prevention During RF Ablation in Left Atrium. Introduction: Mechanisms for thromboembolic complications during complex ablation procedures in left atrium (LA) have not been defined. The aim of this study was to determine the effect of the perfusion rate of the transseptal sheath on the incidence of thromboembolic complications during catheter ablation for atrial fibrillation (AF) or LA macroreentrant tachycardia. Methods and Results: We analyzed clinical and procedural data from 86 consecutive patients (153 procedures) referred for catheter ablation of AF (74 patients) or LA macroreentrant tachycardia (12 patients). The transseptal sheath was continuously perfused at a low flow rate (3 mL/hour) for the first 32 patients and at a high flow rate (180 mL/hour) for the subsequent 54 patients. Ablation was mainly performed using map-guided isolation of pulmonary veins for AF and three-dimensional electroanatomic mapping for LA macroreentrant tachycardia. Five patients (6% of patients and 3.5% of procedures) developed a cerebral thromboembolic complication, all during procedures using low-flow perfusion. Sheath perfusion rate and total procedure duration were the two variables significantly associated with the occurrence of stroke (P = 0.013 and 0.001, respectively). After adjustment in a multivariable analysis, sheath perfusion rate remained the only risk factor for stroke. The risk was 17 times higher using low-flow than high-flow perfusion (odds ratio 17.26, 95% confidence interval 1.14–260.81, P = 0.04). No other clinical or procedural parameters had any significant effect. Conclusion: Sheath perfusion rate is an important determinant of the risk factor for stroke during complex LA ablation procedures. Continuous high-flow perfusion appears to be effective in preventing this complication. (J Cardiovasc Electrophysiol, Vol. 15, pp. 276-283, March 2004) [ABSTRACT FROM AUTHOR]

LEENHARDT, A., et al.: Study of Precursors of Ventricular Tachycardia from Data Stored in the Memory of a Dual Chamber Implantable Cardioverter Defibrillator. --> This study was performed to examine precursors of ventricular tachyarrhythmias in patients who experienced a sustained ventricular tachyarrhythmia and received appropriate therapy by ICD. From an overall consecutive population of 77 patients, 18 patients (1 woman,mean age 61.7 ± 10.8 years) were selected for having experienced a sustained ventricular tachyarrhythmia and received at least one appropriate ICD therapy preceded by 20 minutes of internal information. The number of premature ventricular complexes (PVCs)/min for each of the 20 minutes preceding the onset of ventricular tachyarrhythmia, the shortest coupling intervals between PVC and normal sinus beat, and the presence of short‐long‐short (SLS) interval sequences were examined. Data were stratified according to underlying disease, left ventricular ejection fraction, rate of ventricular tachyarrhythmia, and antiarrhythmic therapy. One hundred twenty‐eight episodes of spontaneous ventricular tachyarrhythmia were retrieved. Rapid ventricular tachyarrhythmia (>160 beats/min) were preceded by a significantly greater mean number(3.71 ± 6.36)of PVCs than slower ventricular tachyarrhythmia (≤160 beats/min)(0.63 ± 0.88, P = 0.0004). The mean shortest PVC coupling interval was significantly shorter in patients with(588 ± 99 ms)versus without(643 ± 111 ms, P = 0.03)ischemic heart disease, before episodes of rapid(527 ± 55 ms)versus slower(636 ± 105 ms, P = 0.0001)ventricular tachyarrhythmia, and in the absence(538 ± 80 ms)versus the presence(620 ± 105 ms, P = 0.006)of amiodarone. SLS sequences preceded 29% of rapid ventricular tachyarrhythmic episodes, versus 8% of the slower ventricular tachyarrhythmia(P < 0.01). Significant differences were found in the characteristics of PVCs preceding ventricular tachyarrhythmic episodes in accordance to their rate and the underlying cardiomyopathy. Though insufficient in isolation, these findings may be helpful when combined with other observations to develop preventive algorithms, or to refine the programming of implantable devices. (PACE 2003; 26[Pt. I]:1454–1460) [ABSTRACT FROM AUTHOR]

Summary Because of its high density of negatively charged phosphate groups, phytic acid (PA) forms very stable complexes with mineral ions rendering them unavailable for intestinal uptake. Indeed, the first step in mineral absorption requires that the mineral remains in the ionic state. As the PA content of the diet increases, the intestinal absorption of zinc, iron and calcium decreases. The inhibitory effects of PA on magnesium or copper are more controversial. Nevertheless, PA does not occur alone in foods and is often consumed with various compounds. Phytates are always present in vegetal matrix composed of fibres, minerals, trace elements and other phytomicronutrients. Thus, in order to evaluate mineral absorption from phytate-rich products, all components of diet and food interactions should be considered and it is hard to predict mineral bioavailability in such products by using only the phytate content. [ABSTRACT FROM AUTHOR]

Introduction: Despite technologic developments, accurate discrimination of ventricular tachyarrhythmia from rapid rhythms of nonventricular origin remains a challenge. We sought to examine the sensitivity and specificity of a dual-chamber arrhythmia detection algorithm, the PARAD algorithm, incorporated in a dual-chamber implantable cardioverter defibrillator, the Defender (ELA Medical). Methods and Results : All detailed tachycardia episodes (i.e., with stored atrial and ventricular channel markers and electrograms) retrieved from the Holter memory of the device were analyzed from 95 patients (86 men and 9 women; age 62 ± 12 years) implanted with the Defender with the algorithm programmed at nominal settings. Over a follow-up of 15 ± 8 months, 559 detailed sustained tachycardia episodes detected in the tachycardia zone were gathered in 62 patients. Of the 300 ventricular tachycardia (VT) episodes, 298 were appropriately classified as VT by the algorithm. Of the 259 supraventricular tachycardia (SVT) episodes, 231 were appropriately classified as SVT. In 8 patients, 28 episodes of SVT were misclassified as VT: 25 atrial fibrillation episodes (6 patients), 2 sinus tachycardia (1 patient), and X atrial tachycardia. Calculated sensitivity and specificity were 99.3% and 89.2% on a per episode basis and 99.8% (95% confidence interval: 97.8 to 100) and 91.6% (95% confidence interval: 86.0 to 97.3) on a per patient basis, respectively. Conclusion: In this selected population of patients, the PARAD algorithm was safe and reliable for detection of a wide spectrum of tachyarrhythmias. Its specificity was high, particularly with respect to sinus tachycardia detection, but it must be improved with respect to detection of atrial fibrillation. [ABSTRACT FROM AUTHOR]

Objectives: Short-term autonomic influences on the electrophysiological properties (EP) of the atrial myocardium are well known, but the role of long-term sympathovagal influences on EP is less clear. This study aimed at finding if a circadian pattern could be identified in atrial EP, using the fibrillatory wave (F wave) of surface ECG recordings as a surrogate of atrial refractoriness in patients with chronic permanent atrial fibrillation (AFib). Methods: 24-hour two-channel Holter ECG were obtained in 20 consecutive patients (mean age 70 ± 8 years) with nonvalvular, chronic and permanent AFib, free of antiarrhythmic agents except digoxin. Digitized ECG were analyzed by a custom software. After QRST substraction of detected complexes, the residual F waves (5-min duration) were computed by a Fourier algorithm. The dominant frequency peak of the power spectrum obtained has been shown to correspond to the dominant atrial cycle length (DACL). 24-hour recordings were analyzed separately during the day (8 active and awake consecutive hours) and at night (4 resting and asleep consecutive hours), and DACL was calculated hourly for each diurnal and nocturnal periods. Results: Spectra could be reliably studied in 17 patients (85%). The DACL showed a significant circadian pattern with a mean 3.3% increase, from 151 ms in the diurnal period to 156 ms at night (P < 0.001). A significant positive relation was found between circadian day-night changes of DACL and the baseline DACL value (P < 0.05). Mean ventricular heart rate decreased from 87 beats/min during the diurnal period to 71 beats/min at night (P < 0.001). Conclusion: Spectral analysis of the F wave can be successfully achieved from long-term Holter recordings. In chronic permanent AFib, the DACL still shows a circadian rhythmicity with an increase from day to night. In addition to atrial refractoriness, the amplitude of DACL circadian modulation could represent a new index of atrial electrical remodeling. [ABSTRACT FROM AUTHOR]

Introduction: QT dispersion assesses repolarization inhomogeneity on 12-lead standard ECG. However, the implications of the electrical cardiac vector during the repolarization phase (the T wave loop) with the genesis of this phenomenon are unknown. Methods and Results: The aim of this study was to explore conventional 12-lead resting ECG QT dispersion and the corresponding morphology of the spatial three-dimensional (3-D) T wave loop in 25 normals subjects, 30 postmyocardial infarction (Ml) patients, and in 17 individuals with congenital long QT syndrome (LQTS). Standard and XYZ ECG leads were simultaneously digitized (250 Hz) and automatically analyzed. Ventricular repolarization dispersion was estimated by the range (RAN12o) and standard deviation (SD12o) of the 12 rate corrected QTo intervals (between the Q wave onset and the T wave offset). Spatial T wave loops were extracted from XYZ data and analyzed with a 3-D algorithm which provides quantitative parameters related to the loop morphology. All scalar measurements of dispersion were significantly larger in the two pathological populations; however none of them could discriminate post-MI from LQTS groups (RAN12o = 33.3, 61.4, and 62.7 ms respectively, for the three populations). Conversely, a loss of planarity and an increased roundness of the T wave loop were observed in the two pathological groups, with the former effect more pronounced in the LQTS (P = 0.04 compared to post-MI) and the latter in the post-MI group (P = 0.02 compared to LQTS). Furthermore, multiple regression and principal component analyses showed that planarity and roundness are independently involved with QT dispersion. Conclusion: Changes in the morphology of the spatial T wave loop associated with QT dispersion were identified. These changes discriminate different substrates of repolarization inhomogeneity. The use of a 3-D technique to assess repolarization inhomogeneity may bring additional information on the intrinsic nature of this disorder. [ABSTRACT FROM AUTHOR]

The article focuses on the theoretical discourses regarding Lucien Goldmann's basic ideas of theory, wager and art. It states that Goldmann, a philosopher and sociologist of his time affirmed that ways of understanding, of seeing and of acting nonetheless organize themselves. It says that the wager of Goldman on the meaning of human action allows posing question concerning the meaning of culture to literature. Moreover, it explores the role of art in the human process called culture.

Complete atrioventricular block (AVB) following radiotherapy has been reported rarely, usually after high dose mediastinal irradiation for Hodgkin's disease or lung or breast carcinoma. We report six new cases of episodic complete infranodal AVB. requiring permanent pacemaker implantation. The mean age was 48-years old (ranging from 25-60) at the first Adams Stokes attack, mean delay was 12 years after irradiation (10-18), and mean radiation dose was 5,200 rads (4,000-6.500). All patients had abnormal interval electrocardiograms (right hundie branch block in two, left bundle branch block in three, alternating left and right bundle branch block in one). Electrocardiograms during the episode of AVB or Holter recordings were consistent with infranodal block in all patients; electrophysiological study performed in five patients confirmed infranodal AVB in four, and one was normal. Pericardial disease was constant, which included pericardial constriction in four patients. Two patients died after failure of pericardiectomy to improve congestive heart failure, due to epicardial, myocardial, and endocardial involvement. Noncardiac mediastinal lesions were present in four cases. Since this delayed complication may occur in patients of such age that the relation between the AVB and the chest irradiation is questionable, we propose the following etiologic criteria: high radiation dose (over 4,000 rads); delay of 10 years or more; abnormal interval tracings; pericardial involvement; and associated cardiac or mediastinal radiation-induced lesions. [ABSTRACT FROM AUTHOR]

A mere 25 years ago, the technique of external defibrillation became the starting point for the development of clinical electrophysiology by permitting routine use of endocavitary programmed electrical stimulation of the heart without undue risk. Major advances in knowledge of clinical arrhythmias and the understanding of their mechanisms were, thus, permitted. Mirowski's implanted defibrillator also constituted a major breakthrough therapeutically; unfortunately, however, some 10 years later, it has not yet induced similarly hoped for consequences in terms of progressing knowledge concerning lethal arrhythmias, largely due to the absence of Holter functions in the implanted devices. As a result of this, in our opinion, better established therapeutic indications are still needed. The reasons for the present situation, we believe, may be partly technical but are conceptual as well. The key point is that even the clear demonstration of the great practical efficacy of a therapeutic tool does not exempt us from the obligation of determining the mechanisms of this effect. [ABSTRACT FROM AUTHOR]

Torsades de pointes are typically characterized by an ECG pattern of polymorphous but organized electrical activity of ventricular origin that occurs in the setting of a long QT interval, long-coupled bigeminy, and has specific precipitating causes and therapeutic responses. Torsades de pointes can result from congenital (adrenergic dependent) and acquired (pause dependent) factors and may have similar cardiac substrates with different precipitating events. [ABSTRACT FROM AUTHOR]

The lack of specificity of VT detection is a significant shortcoming of current ICDs. In a French multicenter study, 18 patients underwent implantation of the Defender 9001 (ELA Medical), an ICD utilizing dual chamber pacing and arrhythmia detection. Over a mean follow-up period of 7.1 ± 4.5 months, 176 tachycardia episodes recorded in the device memory were analyzed, and physician diagnosis was compared with that by the device. All 122 VT/VF episodes were correctly diagnosed, as were 51 of 53 supraventricular tachyarrhythmias. Two episodes of AF with rapid regular ventricular rates were treated as VT, and a third episode, treated as VT, could not be diagnosed with certainty. A dual chamber pacemaker defibrillator offers improved diagnostic specificity without loss of sensitivity, in addition to the hemodynamic benefit of dual chamber pacing. [ABSTRACT FROM AUTHOR]

The technology of the implantable cardioverter defibrillator (ICD) offers the opportunity to overcome the present limits of the invasive and noninvasive approaches of clinical electrophysiology. The invasive approach enables us to reproduce severe arrhythmias if they are inducible, but does not give information concerning the way they spontaneously arise. The noninvasive approach (Holter) gives this information but it usually concerns only trivial arrhythmias with different therapeutic targets. One hopes in the future by means of an important extension to ICD technology, which is not technically possible for the time being, to have access to pertinent information and to a better understanding of the circumstances leading to severe spontaneous arrhythmias, potentially lethal. For the moment, we only have the diagnostic certainty leading to the therapeutic intervention. It is based on an ECC and on the sequence of cardiac cycles preceding the rhythmic controlled accident. These data allow verification of but not explanation of the events. To have a chance to be understood and explained, these "events" must be replaced in the context of the "nonevents." Ideally, one should have all the gross information concerning the last 24 hours and subsequently analyze them. It is already a big step, thanks to the defibrillators the right to therapeutic error has been gained, a unique and fatal accident has been transformed into a repeatable event and therefore, access is gained to the evolution of the responsible disease. [ABSTRACT FROM AUTHOR]

Explains that the prognostic implications of exercise induced arrhythmias depend on their mechanism, their significance, and their context. The exercise test may appear as arrhythmogenic as well as antiarrhythmic; Catecholergic ventricular tachyarrhythmias in children; Idiopathic repetitive ventricular tachycardias.

Sociology of literature covers two very different types of research, bearing respectively on literature as a consumer product and as an integral part of social reality. With the help of the sociological concepts of her own time and of Montesquieus time, author Madame de Staël undertook to show the original characteristics of the ancient and modern literatures of the north and the south. This article deals with the situation in the U.S., the Federal Republic of Germany and France. The American production of sociological works comprises of numerous notes on literature. Germany has a philosophical and sociological tradition which is directed to a much greater extent towards the sociology of literature. In the "Theory of the Novel," author G. Lukács abandons his Kantian attitude and adopts a Hegelian approach. He regards the novel as the characteristic literary form of a world in which man never feels entirely a part. The part of author Th. W. Adornos's work deals with the sociology of literature which comprises of numerous short essays.

BSTRACT [ABSTRACT FROM AUTHOR]

bstract [ABSTRACT FROM AUTHOR]

The article discusses the mechanism of tachycardia of a patient on the intracardiac electrograms at the time at the transition of QRS complexes of tachycardia from narrow to wide. The findings essentially proved an accessory pathway was the retrograde conduction pathway during this narrow QRS tachycardia. In the third, fifth, sixth, and seventh beats, the configuration of the QRS complex showed a left bundle branch block pattern.

Present a case study of a woman with a history of recurrent paroxymal supraventricular tachycardia using electrophysiology and radiofrequency ablation. Interpretation of the electrocardiography; Cycle length of the tachycardia.