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Oral targeted therapies (OTTs) are widely used for cancer management. However, there is no consensus on OTT dose adaptation in older patients with cancer.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.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.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.

This international consensus statement is the collaborative effort of three medical societies representing electrophysiology in North America, Europe, and Asian-Pacific area: the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), and the Asia Pacific Heart Rhythm Society. The objective of the consensus document is to provide clinical guidance for diagnosis, risk stratification, and management of patients affected by inherited primary arrhythmia syndromes. It summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the clinical data on patients affected by channelopathies. This document does not address the indications of genetic testing in patients affected by inherited arrhythmias and their family members. Diagnostic, prognostic, and therapeutic implications of the results of genetic testing are also not included in this document because this topic has been covered by a recent publication1 coauthored by some of the contributors of this consensus document, and it remains the reference text on this topic. Guidance for the evaluation of patients with idiopathic ventricular fibrillation, sudden arrhythmic death …

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.

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)

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

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.

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 α 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 α 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 α 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.

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.

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)

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.

Arrhythmia Discrimination by ICD.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 1 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.

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.

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.

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 ECG 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. I PACE 1995; 18[Pt. II].560–568)

The Agricultural Catchments Research Unit model (ACRU) includes a decision support system (DSS) for estimating the water content of soil at field capacity (θ FC ) and wilting point (θ WP ) when these characteristics are not directly measurable. Three methods of estimation are proposed: (a) based on silt and clay content and bulk density, (b) based on clay content only, and (c) based on soil series. These three pedotransfer functions are compared with respect to both the estimation of θ FC and θ WP and the propagation of errors when the actual evapotranspiration of a wheat crop (E) is predicted over the growing season by the ACRU model. The standard error of estimation was between 0.066 and 0.082 m 3 /m 3 for θ FC , between 0.056 and 0.069 m 3 /m 3 for θ WP and between 29.9 and 34.8 mm of water for E. The method based on silt and clay contents and bulk density predicted θ FC and θ WP for non-swelling soils most precisely. The method based on soil series was better than other methods for swelling soils. It also performed better for estimating available water capacity and consequently for predicting E from a conceptual soil water model. The propagated error of estimating θ FC and θ WP using the DSS reached 15-18% of the simulated E. The error in the prediction of E can reach 26-30% when spatial variation in soil properties is also estimated

Summary Conventional soil survey stratifies a region into mapping classes and characterizes each by a representative soil profile within it. The efficacy of the procedure for predicting particle-size fractions, bulk density, water retention, and available water capacity (AWC) of the soil at previously unvisited sites on the Plain of Languedoc in southern France is evaluated for three scales of survey (1/10 000, 1/25 000 and 1/100 000) and is compared to that of prediction from stratified random and simple random samples. Data from 85 soil profiles on a random transect were used for evaluation. Classification partitioned the variation of the measured properties, except for AWC, well at the 1/10 000 and 1/25 000 scales, whereas classification at the 1/100 000 scale was less effective. At the 1/10 000 and 1/25 000 scales both classification and stratified random sampling were better for prediction than simple random sampling for the same total sample. On average the representative profiles proved substantially better predictors than the stratified random samples, but in most situations where soil stratification performed well efficiencies of the two predictors were similar. In essence, the more successful the classification was the more difficult it was to improve prediction by selecting representatives instead of sampling randomly within classes. These results confirmed statistically that the soil surveyor can exercise intuition and judgement to classify and select representatives.

Torsades de Pointes. 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. (J Cardiovasc Electrophysiol, Vol. 3, pp. 281–292, June 1992)

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. The authors 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 bundle 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, they propose the following etiologic criteria; high radiation dose (overmore » 4,000 rads); delay of 10 years or more; abnormal interval tracings; pericardial involvement; and associated cardiac or mediastinal radiation-induced lesions.« less

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.

Catecholaminergic polymorphic ventricular tachycardia Prof. Antoine Leenhardt Lariboisiere University Hospital, Paris, France Catecholaminergic polymorphic ventricular tachycardias (CPVT) represent a clearly defined but still insufficiently recognized entity. They have a poor spontaneous outcome. The consequence of misdiagnosis is sudden death in children with an otherwise normal heart. They are responsible for syncope and include the risk of sudden death in young patients with no structural heart disease and a normal QT. Ventricular tachyarrhythmias are reproducibly induced by any form of sympathetic stimulation. It is crucial to make the parents and the child aware of the necessity of faultless compliance to beta-blockers. The prevalence of CPVT in the general population has been estimated 1 in 10000. CPVT is mostly the result of mutations in genes encoding the cardiac ryanodine receptor Ca2+ release channel (RyR2) or cardiac calsequestrin (CASQ2), which cause spontaneous RyR2 channel openings and trigger delayed afterdepolarizations. Cardiac events are not rare in both probands and affected family members, even while taking beta-blockers, which are associated with a lower event rate. Implantation of an ICD is recommended as primary prevention when syncope or sustained VT persist despite maximal tolerable dose of beta-blockers. Nevertheless, an ICD is not fully protective, and can even be proarrhythmic. Shocks may trigger catecholamine release, subsequently resulting in arrhythmic storms, multiple shocks, and death. There is a need for further therapies that should improve the outcome of these patients.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is inherited arrhythmic disorder with highly malignant clinical course. Exercise-stress test is the first-line approach to diagnose suspected individuals. We sought to elucidate the sensitivity and specificity of exercise-stress test for identifying mutations in young CPVT-family relatives. Methods and Results: The present study included 35 asymptomatic CPVT-family relatives younger than 20 years old who underwent exercise-stress test and genetic examination. Exercise-stress test, which was considered positive if ventricular tachycardia or premature ventricular contractions consisting of bigeminy or couplets were recorded, was positive in 12 relatives (34%), and the following genetic analysis disclosed mutations in 20 (57%). Mutation was identified in all 12 relatives with positive and in 8 of 23 (35%) with negative exercise-stress test; the sensitivity and specificity for a positive genotype were 60% and 100%, respectively (P

The therapeutic approach of the Brugada syndrome is highly debated especially in asymptomatic patients. Although there is a consensus to implant symptomatic patients with ICDs, the choice of appropriate treatment for asymptomatic patients is very difficult, principally because of a limited ability to identify those individuals at high risk of sudden cardiac death. It may be either follow-up with no treatment or implantation of an implantable cardioverter-defibrillator (ICD). As a consequence of improved recognition of this condition and advances in ICD technology, implantation rates among the young increased. Although the successful prevention of sudden cardiac death by device implantation is often paramount in the mind of the cardiologists, some studies show that the morbidity burden associated with both the diagnosis and the treatment is high. The decision to implant an ICD is not straightforward. Patient selection, device implantation, and programming must be meticulous to minimize the morbidity of this therapy. The last recommendations are probably no more appropriate. A better risk stratification of arrhythmic events in Brugada syndrome is eagerly awaited.