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Background: The optimal right ventricular pacing site for patients requiring pacemaker implantation for permanent atrioventricular block is a matter of debate. Long-term right ventricular apical pacing has been associated with left ventricular ejection fraction impairment and heart failure. Right ventricular septal pacing has been proposed as an alternative., Aim: The aim of this randomized prospective multicentre trial was to compare left ventricular remodelling and outcomes between right ventricular apical and septal pacing after mid-term follow-up., Methods: Patients requiring pacemaker implantation for high-degree atrioventricular block were enrolled and randomized in a 1:1 fashion to receive a right ventricular apical or septal lead., Results: A total of 141 patients were included, 69 in the septal group and 72 in the apical group. Both groups exhibited similar left ventricular ejection fractions after 18 months of follow-up (septal 57.1±11.9% vs. apical 57.4±13.4%), and left ventricular ejection fraction variation was similar in the two groups at the end of follow-up (septal -1.5±13.2% vs. apical 0.3±13.3%). Additionally, left ventricular volume, quality of life and 6-minute walk distance were similar in the two groups. However, patients in the septal group were more likely to be asymptomatic, with a significantly lower concentration of N-terminal prohormone of brain natriuretic peptide. Lastly, lead position did not impact 18-month survival., Conclusion: Pacing from the right ventricular apex does not have any detrimental effect on left ventricular systolic function compared with septal pacing over an 18-month period., (Copyright © 2022. Published by Elsevier Masson SAS.)

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na V 1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na V 1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aims: Risk stratification of sudden cardiac arrest (SCA) in Brugada syndrome (Brs) remains the main challenge for physicians. Several scores have been suggested to improve risk stratification but never replicated. We aim to investigate the accuracy of the Brs risk scores., Methods and Results: A total of 1613 patients [mean age 45 ± 15 years, 69% male, 323 (20%) symptomatic] were prospectively enrolled from 1993 to 2016 in a multicentric database. All data described in the risk score were double reviewed for the study. Among them, all patients were evaluated with Shanghai score and 461 (29%) with Sieira score. After a mean follow-up of 6.5 ± 4.7 years, an arrhythmic event occurred in 75 (5%) patients including 16 SCA, 11 symptomatic ventricular arrhythmia, and 48 appropriate therapies. Predictive capacity of the Shanghai score (n = 1613) and the Sieira (n = 461) score was, respectively, estimated by an area under the curve of 0.73 (0.67-0.79) and 0.71 (0.61-0.81). Considering Sieira score, the event rate at 10 years was significantly higher with a score of 5 (26.4%) than with a score of 0 (0.9%) or 1 (1.1%) (P < 0.01). No statistical difference was found in intermediate-risk patients (score 2-4). The Shanghai score does not allow to better stratify the risk of SCA., Conclusions: In the largest cohort of Brs patient ever described, risk scores do not allow stratifying the risk of arrhythmic event in intermediate-risk patient., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: The evolution of atrioventricular conduction disorders after transcatheter aortic valve implantation (TAVI) remains poorly understood. We sought to identify factors associated with late (occurring ≥7 days after the procedure) high-grade atrioventricular blocks after TAVI, based on specific pacemaker memory data., Methods and Results: STIM-TAVI (NCT03338582) was a prospective, multicentre, observational study that enrolled all patients (from November 2015 to January 2017) implanted with a specific dual chamber pacemaker after TAVI, with the SafeR algorithm activated, allowing continuous monitoring of atrioventricular conduction. The primary endpoint was the occurrence of centrally adjudicated late high-grade atrioventricular blocks during the year after TAVI. Among 197 patients, 138 (70.1%) had ≥1 late high-grade atrioventricular block. Whereas oversizing (p = .005), high-grade atrioventricular block during TAVI (p < .001), and early (within 6 days) high-grade atrioventricular block (p < .001) were associated with occurrence of late high-grade atrioventricular block, self-expanding prothesis (p = .88), prior right bundle branch block (p = .45), low implantation (p = .06), and new or wider left bundle branch block and lengthening of PR interval (p = .24) were not. In multivariable analysis, only post-TAVI early high-grade atrioventricular block remained associated with late high-grade atrioventricular blocks (Days 0-1: odds ratio [OR], 3.25; 95% confidence interval [CI], 1.57-6.74; p = .001; Days 2-6: OR, 4.13; 95% CI, 2.06-8.31; p < .001), whereas other conventionally used predictors were not., Conclusion: One-third of pacemaker-implanted patients do not experience late high-grade atrioventricular block. Our findings suggest that post-TAVI early high-grade atrioventricular block is the main factor associated with occurrence of late high-grade atrioventricular blocks., (© 2021 Wiley Periodicals LLC.)

Background: Despite a strong genetic background, Brugada syndrome (BrS) mainly affects middle-age patients. Data are scarce in the youngest and oldest age groups., Objective: The purpose of this study was to describe the clinical characteristics and variations in rhythmic risk in BrS patients according to age., Methods: Consecutive BrS patients diagnosed in 15 French tertiary centers in France were enrolled from 1993 to 2016 and followed up prospectively. All of the clinical and ECG data were double reviewed., Results: Among the 1613 patients enrolled (age 45 ± 15 years; 69% male), 3 groups were defined according to age (52 patients <17 years; 1285 between 17 and 59 years; and 276 >60 years). In the youngest patients, we identified more female gender (42%), diagnosis by familial screening (63%), previous sudden cardiac death (15%), SCN5A mutation (62%) sinus dysfunction (8%) and aVR sign (37%) (P <.001). The oldest patients had the same clinical characteristics except for gender (40% women; P <.001). During median follow-up of 5.5 [2.1, 10.0] years, 91 patients experienced an arrhythmic event, including 7 (13%) in the youngest patients, 80 (6%) in middle-age patients, and 4 (1%) in the oldest patients. Annual event rates were 2.1%, 1%, and 0.3%, respectively (P <.01)., Conclusion: Age on diagnosis changes the clinical presentation of BrS. Although children are identified more during familial screening, they present the highest risk of sudden cardiac death, which is an argument for early and extensive familial screening. The oldest patients present the lowest risk of SCD., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The recently recommended single lead-based criterion for the diagnosis of Brugada syndrome may lead to overdiagnosis of this disorder and overestimation of the risk of sudden cardiac death., Aim: To investigate the value of a single-lead diagnosis in patients with Brugada syndrome and a spontaneous type 1 electrocardiogram., Methods: Consecutive patients with Brugada syndrome were included in a multicentre prospective registry; only those with a spontaneous type 1 electrocardiogram were enrolled. Clinical and electrocardiogram data were reviewed by two physicians blinded to the patients' clinical and genetic status., Results: Among 1613 patients, 505 (31%) were enrolled (79% male; mean age 46±15 years). A spontaneous type 1 electrocardiogram pattern was found in one lead in 250 patients (group 1), in two leads in 227 patients (group 2) and in three leads in 27 patients (group 3). Groups were similar except for individuals in group 3, who presented more frequently a fragmented QRS complex, an early repolarization pattern and a prolonged T peak -T end interval. After a mean follow-up of 6.4±4.7 years, ventricular arrhythmia, sudden cardiac death or implantable cardiac defibrillator shock occurred in 46 (9%) patients, without differences between groups., Conclusion: The prognosis of Brugada syndrome with a spontaneous type 1 electrocardiogram pattern does not appear to be affected by the number of leads required for the diagnosis., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Studies in Brugada syndrome (BrS) have mainly consisted of men., Objective: The purpose of this study was to describe the clinical characteristics and arrhythmic risk factors in BrS women., Methods: Consecutive BrS patients were enrolled from 1993 and followed prospectively., Results: Among 1613 patients, 494 were women (mean age 47 ± 16 years). Women were more frequently asymptomatic than men (423 [86%] vs 867 [77%], respectively; P = .001) and less frequently had a spontaneous ECG pattern (107 [22%] vs 398 [36%], respectively; P <.001). During median [25th, 75th percentile] follow-up of 57 [23, 118] vs 62 [22, 113] months (P = .65), arrhythmic events occurred in 12 women (2%) vs 79 men (7%) (P = .0005). Mean age at the first event was 48.6 ± 17.8 years for women vs 43 ± 14.2 years for men (P <.001). Gender was significantly related to cardiac events (hazard ratio [HR] 2.96; 95% confidence interval [CI] 1.6-5.4; P = .0005). In multivariate analysis, event predictors in women were index patient status (HR 10.15; 95% CI 1.7-61.4; P = .01), previous sudden cardiac death (HR 69.4; 95% CI 15-312.5; P <.0001), syncope (HR 6.8; 95% CI 1.4-34.5; P = .02), fragmented QRS (HR 20.2; 95% CI 1.8-228.9; P = .02), and QRS duration >120 ms (HR 4.7; 95% CI 1.2-19.5; P = .03)., Conclusion: Women represent a lower-risk group than men among individuals with BrS. In asymptomatic women, fragmented QRS and QRS >120 ms seem to be the only event predictors., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Stress-induced right bundle-branch block morphology ventricular ectopy (SI-RBVE) may be caused by left ventricular myocardial anomalies. While frequent ventricular ectopy (FVE) has been linked to poor outcomes, the prognostic value of SI-RBVE has not been established. The study aims to determine whether SI-RBVE is associated with increased mortality., Methods and Results: Three hundred forty-three patients with an intermediate to high probability of coronary artery disease were prospectively included. Patients were referred for a single-photon emission computed tomography and underwent a stress test according to standard protocols. Stress-induced right bundle-branch block morphology ventricular ectopy (VE) was defined as one or more induced premature beats with positive predominance in V1. Frequent VE was defined as the presence of seven or more ventricular premature beats per minute or any organized ventricular arrhythmia. During a mean follow-up of 4.5 ± 1.3 years, 59 deaths occurred. The death rate was higher in the SI-RBVE group (23.4% vs. 14.0%, P = 0.021). Age [odds ratio (OR) = 1.09 (95% CI: 1.06-1.13), P < 0.001] and peripheral artery disease [OR = 2.47 (95% CI: 1.35-4.50) P = 0.003] were independent factors of mortality, but single-photon emission computed tomography findings were not. There was an interaction between SI-RBVE and left ventricular ejection fraction (LVEF). In patients with LVEF > 50%, SI-RBVE was an incremental risk factor for mortality [OR = 2.83 (95% CI: 1.40-5.74), P = 0.004]. Stress-induced right bundle-branch block morphology VE patients also presented higher rates of known coronary artery disease, ischaemia, scar, and ST-segment changes. Frequent VE was not related to mortality., Conclusion: Stress-induced right bundle-branch block morphology VE is associated with an increased mortality in patients with preserved LVEF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Sodium-channel blocker challenge (SCBC) is frequently performed to unmask Brugada syndrome., Objective: We aim to identify predictors of positivity and complications of SCBC in the setting of familial screening of Brugada syndrome., Methods: All consecutive patients from 2000 to 2014 who benefit from a sodium-channel blocker and belong to a family with at least 2 subjects affected by the syndrome were enrolled and followed prospectively. Data were reviewed by 2 physicians blinded to the clinical and genetic status., Results: Of the 672 SCBCs performed in 137 families, 337 (50%) were positive. Multivariate analysis identified ajmaline (odds ratio [OR] 2.98; 95% CI 1.65-4.91) and a significant S wave in lead DII (OR 3.11; 95% CI 2.12-4.58), DIII (OR 2.75; 95% CI 1.78-4.25), or V 5 (OR 3.71; 95% CI 2.54-5.44) as predictors of a positive SCBC (P < .0001). Eleven patients (1.6%) presented complications (10 ventricular arrhythmias and 1 atrial flutter), but no deaths occurred. Familial history of complications (OR 41; lower quartile, upper quartile 10, 203; P < .0001), young age (P = .04), and decreased electrocardiographic conduction parameters at baseline (P = .04) were predictors of complications. QRS enlargement during SCBC was not associated with complications. During a median follow-up of 106 months (lower quartile, upper quartile 54, 143 months), 11 life-threatening arrhythmias occurred., Conclusion: SCBC in the screening of familial Brugada syndrome is safe. The risk of complication is considerably increased in the case of familial history of complicated SCBC, in young patients, and in the presence of decreased electrocardiographic conduction parameters. However, QRS enlargement during the test is not directly related to complications and should not be used to prematurely stop the test unless leading to false-negative results., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The emergency department (ED) can be an effective site for pediatric injury prevention initiatives, including child passenger safety. The objectives of this study were to evaluate the implementation of an ED child passenger safety program and to analyze the effectiveness of a computerized screening tool to identify car seat-related needs for children younger than 8 years., Methods: An ED-based group developed a child passenger safety program including (1) a computerized screening tool to assess the use of car seats in children younger than 8 years; (2) child passenger safety education, including state law; and (3) distribution of appropriate car seats for patients discharged from the ED. In July 2011, the screening tool was added to the initial nursing assessment. In January 2012, nursing education was performed to increase compliance with screening. In April 2012, the tool was made a mandatory field in the computerized initial nursing assessment., Results: From August 1 to December 31, 2011, 17 % (2270/13,637) of eligible children had computerized screenings performed; 18 car seats were distributed. From January 15 to March 15, 2012, 32% (2017/6270) of eligible children were screened; 9 car seats were distributed. From March 16 to May 19, 2012, 56% (3381/6063) were screened; 22 car seats were distributed. Screenings increased further from May 20 to July 25, 2012, with 87% (5077/5827) completed; 31 car seats were distributed., Conclusions: A child passenger safety program can be successfully implemented in the ED. A computerized nursing screening tool increases compliance with screening and providing needed car seats.

Background: Defibrillation testing (DT) is usually performed during implantable cardioverter defibrillator (ICD) implantation., Aims: We conducted a multicentre prospective study to determine the DT procedures used in everyday practice, to compare the characteristics of patients with or without DT, and to compare severe adverse events in these two populations during implantation and follow-up., Methods: The LEADER registry enrolled 904 patients included for primo-implantation of a single (n=261), dual (n=230) or triple (n=429) defibrillation system in 42 French centres., Results: Baseline characteristics of patients (62.0 ± 13.5 years; 88% men; primary indication 62%) who underwent ventricular fibrillation (VF) induction (VF induction group, n=810) and those who did not (untested group, n=94, representing 10.4% of the entire study population) revealed that the untested group were older (P<0.01), had a lower left ventricular ejection fraction, a wider QRS complex and a higher New York Heart Association class and were more often implanted for primary prevention (P<0.001 for all). The main reason given for not performing ICD testing was poor haemodynamic condition (59/94). At 1 year, the cumulative survival rate was 95% in tested patients and 85% in untested patients (P<0.001), mainly because of heart failure deaths. There was one sudden cardiac death in the VF induction group and none in the untested group (P=1.000)., Conclusions: In this study, more than 10% of ICD patients were implanted without VF induction. Untested patients appeared to be sicker than tested patients, with a more severe long-term outcome, but without any difference in mortality due to arrhythmic events., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: Progressive cardiac conduction defect (PCCD) is a frequent disease attributed to degeneration and fibrosis of the His bundle. Over the past years, gene defects have been identified demonstrating that PCCD could be a genetic disease. The aim of this study was to show a familial aggregation for PCCD using a genetic epidemiological approach to improve in fine genetic knowledge of the transmission of the disease., Methods and Results: Using the French social security number, the authors have been able to determine the city of birth of the 6667 patients implanted with a pacemaker (PM) for PCCD between 1995 and 2005 in the western part of France. The authors then mapped the frequency of PM implantations for PCCD. A large heterogeneity of the frequency of the disease has been observed, with a frequency of 0.21% in the major city (Nantes) ranging up to 2.28% in specific parishes. Familial studies performed in the parishes with the highest frequency of the disease allowed the authors to identify five large families with PCCD. Clinical investigations demonstrated phenotype heterogeneity between families. Three patterns have been differentiated., Conclusions: This study demonstrates a disparate geographical repartition of the frequency of PM implantation in the area of the authors at least in part related to a hereditary factor. The identification of five large families affected by PCCD using epidemiological approach underlines the existence of a major genetic background in PCCD.

Aims: SafeR performance versus DDD/automatic mode conversion (DDD/AMC) and DDD with a 250-ms atrioventricular (AV) delay (DDD/LD) modes was assessed toward ventricular pacing (Vp) reduction., Methods: After a 1-month run-in phase, recipients of dual-chamber pacemakers without persistent AV block and persistent atrial fibrillation (AF) were randomly assigned to SafeR, DDD/AMC, or DDD/LD in a 1:1:1 design. The main endpoint was the percentage of Vp (%Vp) at 2 months and 1 year after randomization, ascertained from device memories. Secondary endpoints include %Vp at 1 year according to pacing indication and 1-year AF incidence based on automatic mode switch device stored episodes., Results: Among 422 randomized patients (73.2±10.6 years, 50% men, sinus node dysfunction 47.4%, paroxysmal AV block 30.3%, bradycardia-tachycardia syndrome 21.8%), 141 were assigned to SafeR versus 146 to DDD/AMC and 135 to DDD/LD modes. Mean %Vp at 2 months was 3.4±12.6% in SafeR versus 33.6±34.7% and 14.0±26.0% in DDD/AMC and DDD/LD modes, respectively (P<0.0001 for both). At 1 year, mean %Vp in SafeR was 4.5±15.3% versus 37.9±34.4% and 16.7±28.0% in DDD/AMC and DDD/LD modes, respectively (P<0.0001 for both). The proportion of patients in whom Vp was completely eliminated was significantly higher in SafeR (69%) versus DDD/AMC (15%) and DDD/LD (45%) modes (P<0.0001 for both), regardless of pacing indication. The absolute risk of developing permanent AF or of remaining in AF for >30% of the time was 5.4% lower in SafeR than in the DDD pacing group (ns)., Conclusions: In this selected patient population, SafeR markedly suppressed unnecessary Vp compared with DDD modes., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

Objective: To study the correlation between heart sounds and peak endocardial acceleration (PEA) amplitudes and timings, by modulation of paced atrioventricular (AV) delay in recipients of dual chamber pacemakers., Methods: Ten recipients of dual chamber pacemakers implanted for high-degree AV block were studied. Endocardial acceleration (EA) and phonocardiographic and electrocardiographic signals were recorded during performance of an AV delay scan in VDD and DDD modes., Results: First PEA (PEA I) and first heart sound (S1) changed similarly with the AV delay. A close intrapatient correlation was observed between S1 and PEA I amplitudes in all patients (P < 0.0001). The interpatient normalized PEA I to S1 amplitudes correlation was r = 0.89 (P < 0.0001) in DDD mode, and r = 0.81 (P < 0.0001) in VDD mode. The mean cycle-by-cycle PEA I to S1 delay was -4.3 +/- 22 ms and second PEA (PEA II) to second heart sound (S2) delay was -7.7 +/- 15 ms., Conclusions: A close correlation was observed between PEA I and S1 amplitudes and timings, and between PEA II and S2 timings. These observations support the hypothesis that PEA and heart sounds are manifestations of the same phenomena. EA might be a useful tool to monitor cardiac function.

Implementation of colorectal cancer (CRC) mass screening is a public health priority. Obtaining the involvement of general practitioners (GPs) is crucial for ensuring participation by the general public. This study elicited GPs' reasons for promoting CRC screening. The method used was discrete choice modeling. Questionnaires with a set of pairs of hypothetical screening scenarios were sent to 700 GPs. Factors influencing GPs' screening practice were found to be: the effectiveness of the screening program, the proportion of false negatives and false positives, and their remuneration. Hence improving screening test sensitivity and setting up specific remuneration for conducting screening would help to increase GPs' participation in CRC screening in France.

The goal of the present study was to develop and evaluate new algorithms for the prediction of the outcome of a head-upright tilt test (HUTT). Using transthoracic impedance and its first derivative, we attempted to determine if indexes computed on these waveforms could detect a positive outcome to a 70 degrees -45min HUTT with reliable sensitivity and specificity. The methods were evaluated retrospectively in a group of 70 patients and validated prospectively in a group of 59 patients. The best detector obtained used a neural network. It compares very favorably with published results for other syncope detectors.

Unlabelled: There is only a few data on sudden unexpected death (SUD) in the pediatric population, as well as the role of sport., Materials and Methods: Between 1980 and 2003, 2220 autopsies were performed at the Lyon's forensic institute for SUD (all ages) as defined by world health organization., Results: Fifty-seven cases of SUD of cardiac origin concerned 6 to 18-year-old children. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy remained the main causes of SUD. Mitral valve prolapse were frequently observed and for the most part of the cases associated with other diseases. Twenty-four were observed during physical activity., Conclusion: Our study confirms the low incidence of SUD and its male predominance in the pediatric population (47 males, 10 females). It seems that physical activity is not the decisive factor for SUD. The authors emphasized the necessity to get a rapid access to cardiac resuscitation devices, as well as the formation of collaborators. Some preventive measures could be done.

Objective: Evaluation of physical capacity in kidney transplanted children for sport practice adequacy., Population and Methods: A retrospective study was carried out in 32 children transplanted at least one year before evaluation. We studied auxology, respiratory function testing, cardiovascular parameters at rest and after exercise, and aerobic capacity performed during a triangular effort test., Results: Kidney transplanted children were smaller and had a higher body mass index (IMC). Breathing parameters and cardiac ultrasound examinations were normal in all but one child. After exercise, four children had high systolic blood pressure requiring a treatment adaptation. Lower values of maximal aerobic power (Pmax) and oxygen maximal uptake (VO2max) were noticed, mainly in girls., Conclusion: Kidney transplanted children have a good physical exercise tolerance. Therefore they can be allowed to practise sports at school or in a club after a normal effort test (taking into account the risk of transplant trauma).

Background: Sublingual nitroglycerin is advocated to sensitize the passive 70 degrees head-upright tilt test (HUTT) of patients with unexplained syncope. We hypothesized that a detailed analysis of hemodynamic responses recorded during a negative HUTT could predict the outcome to a subsequent nitroglycerin sensitized HUTT (NTG-HUTT)., Methods: Thirty-two patients (46 +/- 3 years, 17 males) with recurrent unexplained syncope but a negative HUTT were included. Heart rate, arterial blood pressure, and central hemodynamics assessed by transthoracic impedance (preejection and rapid left ventricular ejection time, slow ejection time, peak amplitude of first derivative, and cardiac index) were recorded during supine rest and 45 minutes HUTT. Changes from supine rest of the variables were retrospectively compared between patients with a negative (n = 15, NTG-HUTT(-)) and positive (n = 17, NTG-HUTT(+)) outcome to 10 minutes subsequent NTG-HUTT., Result: Significant differences between groups were observed during the 15th-20th minutes (Italian protocol) and during the last 5 minutes of passive HUTT (Westminster protocol). The combination of cutoff values, determined by receiver operating curves, on hemodynamic variables changes during the last 5 minutes predicted the outcome to a NTG-HUTT with a sensitivity of 76% and a specificity of 87%. The cutoff values determined during 15th-20th minutes gave an attractive sensitivity (85%) but a too weak specificity (53%) to shorten the 45 minutes passive HUTT at 20 minutes., Conclusion: Outcome to a NTG-HUTT can be reliably predicted by selected criteria determined from multiple hemodynamic variables recorded during a passive 70 degrees HUTT.

Dilated cardiomyopathy (DCM) of genetic origin represents about 25% of all so-called primary DCM. Cases due to mutation of the gene which codes the lamins A and C (LMNA) carry a poor prognosis with a high risk of sudden death. The finding of primary DCM in a young person associated with conduction defects or arrhythmias should lead to investigation for mutation of the gene of lamins A and C, even in the absence of a suggestive family history. The authors report 5 cases of DCM, with and without associated skeletal muscular disease, due to laminopathies.

The implantable automatic defibrillator has completely changed the prognosis of potentially fatal ventricular arrhythmias by the delivery of an electric shock in the event of ventricular tachycardia or fibrillation. This vital device is sometimes poorly accepted from the psychological point of view by patients having been traumatised by experiences of sudden death from which they have been rescuscitated. Anxiety and depression are common and they have an important effect on the quality of life. The unpredictable occurrence of painful, multiple and uncontrollable electrical shocks may induce a state of acute stress with stunning, the resemblance of which to the model of learned helplessness described experimentally in the animal by Seligman, is discussed. The authors report the case of a 20 year old man whose automatic defibrillator was activated twenty times in one night. His state of stress and impotence was such that he lay prostate in his bed. Suicide seemed to be the only possible way of escaping from the electrical shocks of the device which was perceived as being dangerous. The management of this condition is not standardised but it requires the collaboration of the cardiac rhythmological and psychiatric teams. Medication with antidepressant drugs alone is not sufficient. The regulation of the sensitivity of the defibrillator gives the patient a feeling of mastering the situation: submission is not total! Research along this line should improve the patients' acceptation of the device and their quality of life.

In patients with recurrent unexplained syncope, exaggerated peripheral venous pooling and impaired circulatory adjustment is thought to contribute to the outcome of a head-up tilt (HUT) test. The present study investigated the role of leg volume changes during venous congestion in the haemodynamic response of patients with recurrent unexplained syncope and the ability to predict the outcome of a HUT test. Changes in calf volume (strain gauge plethysmography), heart rate and arterial blood pressure were recorded in 60 patients with history of unexplained syncope (without postural tachycardia symptom) during venous congestion provoked by pneumatic thigh cuffs while supine at rest and during the initial 10 min of a 45 min 70 degrees HUT test. Twenty-seven patients [age (mean+/-S.D.), 39+/-16 years] exhibited symptoms [HUT(+)] and 33 patients (45+/-14 years) were asymptomatic [HUT(-)]. During venous congestion, mean+/-S.E.M. calf volume increased in both groups [HUT(-), 4.5+/-0.2; HUT(+), 4.8+/-0.4 ml x 100 ml(-1), not significant), but significantly less during head-upright tilt [HUT(-), 3.3+/-0.2, P <0.01; HUT(+), 2.6+/-0.3 ml x 100 ml(-1), P <0.001] without differences between the groups. During venous congestion, arterial pressure increased significantly in asymptomatic HUT(-) patients, but not in the HUT(+) patients. Calf volume changes did not correlate with a symptomatic outcome to a 70 degrees HUT. The lack of exaggerated venous pooling during venous congestion and the inability of calf volume changes to predict a positive HUT suggest that excessive venous pooling does not contribute to the outcome of HUT. Attenuated changes in arterial pressure during venous congestion while supine suggest impaired adjustment of peripheral resistance to leg venous occlusion.

We determined whether early changes in central haemodynamics, as determined by transthoracic impedance, induced by a 70 degrees head-up tilt (HUT) test could predict syncope. Heart rate, arterial blood pressure and central haemodynamics [pre-ejection period and rapid left ventricular ejection time ( T (1)), slow ejection time ( T (2)) and d Z /d t (max) (where Z is thoracic impedance), assessed by the transthoracic impedance technique], were recorded during supine rest and during a 45 min 70 degrees HUT test in 68 patients (40+/-2 years) with a history of unexplained recurrent syncope. We found that 38 patients (42+/-3 years) had a symptomatic outcome to 70 degrees HUT (fainters) and 30 (39+/-2 years) had a negative outcome (non-fainters). When measured between 5 and 10 min of 70 degrees HUT, T (2) had increased significantly only in the fainters, and a change in T (2) of >40 ms from baseline predicted a positive outcome with a sensitivity of 68% and a specificity of 70%. During supine rest prior to 70 degrees HUT, the fainters exhibited a shorter T (2) than non-fainters (183+/-10 compared with 233+/-14 ms; P <0.01), and a T (2) of <199 ms predicted a positive outcome to 70 degrees HUT with a sensitivity of 68% and a specificity of 63%. Incorporation of the changes that occurred from rest to 70 degrees HUT in other haemodynamic variables (heart rate >11 beats/min, systolic pressure <2 mmHg, diastolic pressure <7 mmHg and pulse pressure <-3 mmHg) increased the specificity to 97% and the positive predictive value to 93%. Thus transthoracic impedance could detect differences in central haemodynamics between fainters and non-fainters during supine rest and during the initial period of 70 degrees HUT with a consistent sensitivity and specificity when combined with peripheral haemodynamic variables.

Optimization of programmed atrioventricular delay in dual chamber pacing is essential to the hemodynamic efficiency of the heart. Automatic AV delay optimization in an implanted pacemaker is highly desirable. Variations of peak endocardial acceleration (PEA) with AV delay at rest correlate well with echocardiography derived observations, particularly with end-diastolic filling and mitral valve closure timings. This suggests the possibility of devicing a procedure for the automatic determination of the optimal AV delay. The aim of this study was to compare a proposed algorithm for optimal AV delay determination with an accepted echocardiographic method. Fifteen patients with high degree AV block received BEST-Living pacing systems. Automatic AV delay scans were performed at rest (60-300 ms in 20-ms steps with 60 beats per step) in DDD at 90 ppm, while simultaneously recording cycle-by-cycle PEA values, which were averaged for each AV delay to obtain a PEA versus AV delay curve. Nonlinear regression analysis based on a Boltzmann sigmoid curve was performed, and the optimal AV delay (OAVD) was chosen as the sigmoid inflection point of the regression curve. The OAVD was also evaluated for each patient using the Ritter echocardiographic method. Good sigmoid fit was obtained in 13 of 15 patients. The mean OAVD obtained by the PEA sigmoid algorithm was 146.9 +/- 32.1 ms, and the corresponding result obtained by echocardiography was 156.4 +/- 34.3 ms (range 31.8-39.7 ms). Correlation analysis yielded r = 0.79, P = 0.0012. In conclusion, OAVD estimates obtained by PEA analysis during automatic AV delay scanning are consistent with those obtained by echocardiography. The proposed algorithm can be used for automatic OAVD determination in an implanted pacemaker pulse generator.

The aim of the study was to define criteria for left ventricular pacing in dilated cardiomyopathy (DCM) using an echocardiographic evaluation of interventricular electromechanical delay (IMD) and a correlation of IMD to QRS duration. Standard 12-lead ECG and echocardiography with pulsed Doppler tissue imaging (DTI) were recorded in 35 DCM patients (mean age 58 +/- 11 years) with QRS duration from narrow (80 ms) to broad (222 ms) patterns. The timefor left ventricular activation was evaluated from the onset of QRS to the onset of aortic flow (Q-Ao) by standard pulsed Doppler (SP) or to the onset of mitral annulus systolic wave (Q-Mit) (DTI). The time for right ventricular activation was determinedfrom the onset of QRS to the onset of pulmonary flow (Q-Pulm) (SP) or to the onset of tricuspid annulus systolic wave (Q-Tri) (DTI). (Q-Ao)-(Q-Pulm) and (Q-Mit)-(Q-Tri) determined IMD for each method, respectively. QRS width and IMD showed correlation coefficients of r = 0.86 ([Q-Ao]-[Q-Pulm]) and r = 0.82 ([Q-Mit]-[Q-Tri]) (P < or = 0.001 ). Mean IMD of 77 +/- 15 ms (SP) and 88 +/- 26 ms (DTI) were noted for QRS width above 150 ms. Left ventricle delayed activation was positively correlated to QRS widening with both methods, (r = 0.90, [Q-Ao]), (r = 0.83, [Q-Mit]) (P < or = 0.001). In conclusion, QRS duration is a good marker of an interventricular mechanical asynchrony. According to IMD correction, left ventricular pacing may be mainly proposed to symptomatic DCM patients with QRS duration > 150 ms.

Late responsive DDD pacemakers are the most technically advanced devices presently available. These pacemakers are particularly useful in patients with chronotropic insufficiency when the sinus node is incapable of accelerating during exercise. The latest pacemakers have two sensors to reproduce optimal physiological sinus acceleration. The aim of this study was to analyse the performances of a new rate responsive pacemaker with a double activity and respiratory sensor, the interaction of which is automatically controlled by a sophisticated algorithm, in 12 patients (8 men and 4 women) with a mean age of 75 +/- 7 years. Analysis was based on the performance of the sensors used singly or in association: during three exercise stress tests with measurement of the VO2 max; during everyday activities using the data archived by the pacemaker and the answers to a simplified questionnaire on quality of life. The results showed that during exercise stress testing with measurement of VO2 max, the best performances were obtained with the double sensor or the respiratory sensor compared with the activity sensor alone, suggesting that these two sensors are more effective in intense exercise. This tendency was also observed in the analysis of the memory bank of the pacemaker which showed that the total duration of the faster heart rates was greater with the two sensors. On the other hand, the quality of life was not significantly different, whichever sensor was studied. Longer scale trials are necessary to appreciate the real value of these new double sensor pacing devices and to identify the best indications for their usage.

The authors report a case of Löffler's fibroblastic endocarditis complicating a toxocarosis infection. Parasitic infestation with toxocara canis is usually asymptomatic, but this was a very rare observation of cerebral involvement associated with symptomatic Löffler's endocarditis. This is an unusual form of restrictive cardiac disease constantly accompanied by prolonged hypereosinophilia. In addition to the classical signs of cardiac failure, an acute febrile illness imitating a connective tissue disease may be observed. Echocardiography helps diagnosis by showing endomyocardial fibrosis and adherent thrombosis at one or both ventricular apices. The management of cardiac failure should include, whenever possible, radical treatment of the hypereosinophilia. At an advanced stage, surgical endocardial decortication is the only means of improving symptoms and the prognosis of these patients.

The aim of this retrospective study was to assess the incidence, timing and classical presentations of thyroid dysfunction in patients treated long-term with amiodarone. Ninety patients (sex ratio M/W 67/33, mean age 71 years) were followed up for 48 months. The daily dose of amiodarone was 200 mg after loading doses during the hospital stay for atrial fibrillation. The average treatment period was 33 +/- 19 months. Hypothyroidism, observed in 5.5% of cases, occurred at variable intervals with few clinical manifestations. Hyperthyroidism was more common (12.2%), occurred increasingly with time, and was clinically symptomatic with recurrent supraventricular arrhythmias in 36% of cases. Long-term amiodarone therapy causes undesirable thyroid side-effects for nearly 1 out of 5 patients. Hyperthyroidism is more common than hypothyroidism and may be explained by increased iodine intake. The increasing incidence of hyperthyroidism with time suggests a cumulated dose relationship, a situation which is not observed with hypothyroidism.

Psychotropic Drugs and ST Segment Elevation. Transient ST segment elevation in right precordial leads with use of psychotropic drugs is reported in two cases of overdose and one case of therapeutic administration. Flecainide did not reproduce ST segment elevation. The relationship of these abnormalities to the Brugada syndrome and the electrophysiologic hypothesis are discussed.

Objective: Estimation of both physical and psychological effects of an adapted physical training on children undergoing an obesity treatment., Material and Methods: The survey was carried out on 36 obese boys (ages = 12-16 years) who stayed in the medical center for at least four months. Eighteen of them were trained with the SELF method (the SELF-training is global, progressive, adapted to each boy, controlled and takes place within a ten-week period with five sessions a fortnight, each session lasting 30 to 40 minutes). The parameters that were studied concerned auxology, breathing function exploration, aerobic and anaerobic capacities, muscle strength and psychomotor qualities; the subjective effects of the training were estimated with a questionnaire about life quality, and the hand test. At inclusion the results were reported to a standard kind of population. At the end of the training the results of the 18 boys that were trained were compared to those of the 18 controls., Results: Compared to a standard population, the obese children' aerobic capacity is diminished for the maximum power but is identical in absolute value for the VO2 max; their anaerobic capacities, muscle strength and psychomotor capacities are lower and their psyche is affected by the disease. After a three-month training period and after comparison with the 'control' group, there can be noticed a significant improvement in the psychomotor capacities, a major tendency for the improvement of the aerobic capacities and very positive effects on the psyche., Conclusion: SELF-training in association with dietetics appears to be very useful in the therapeutic care of obese children. For the follow-up at home it would need to be registered within the domain of physiotherapy.

Carotid sinus syndrome (CSS) is a cause of syncope due to exaggerated baroreceptor-mediated cardioinhibitory/vasodepressive reflexes. We sought to determine if cerebral hemodynamics and regulation were specifically altered in these patients by comparison with pure asystole without vasodepression in patients with atrioventricular block (AVB). Mean blood flow velocity (transcranial Doppler sonography) and mean arterial blood pressure (Finapres) were recorded during cardioinhibition induced by carotid massage in patients with CSS (n = 14, 75 +/- SD 8 years) and asystole induced by temporary pacemaker inhibition in patients with complete AVB (n = 10, 69 +/- 11 years). Cerebrovascular resistance was estimated by the arterial pressure/cerebral flow velocity ratio, and dynamic cerebral autoregulatory responses were determined by the rate of regulation and autoregulatory index. Asystole and cardioinhibition each induced a decrease in arterial pressure (CSS 55 +/- 9% vs AVB 40 +/- 14%, p <0.05) and cerebral flow velocity (CSS 66 +/- 19% vs AVB 69 +/- 14%, p = NS), with an initial transient increase in cerebrovascular resistance (CSS 102 +/- 136% vs AVB 128 +/- 92%, p = NS) followed by a decrease (CSS 38 +/- 12%, AVB 29 +/- 13%, p = NS). The rate of regulation and autoregulatory index were higher with AVB (0.43 +/- 0.20 and 8.5 +/- 1.1 second(-1)) than CSS (0.20 +/- 0.12 and 4.8 +/- 1.3 second(-1), respectively, p <0.01 and p <0.001 vs AVB). During asystole and vasodepression, cerebral hypoperfusion in CSS is normally compensated for by cerebral autoregulation. The lower rate of regulation in CSS compared with AVB likely results from persistent peripheral vasodepression triggered by carotid massage.

We isolated five sunflower (Helianthus annuus) cDNAs belonging to the TIP (tonoplast intrinsic protein) family. SunRb7 and Sun gammaTIP (partial sequence) are homologous to tobacco TobRb7 and Arabidopsis gamma-TIP, respectively. SunTIP7, 18 and 20 (SunTIPs) are closely related and homologous to Arabidopsis delta-TIP (SunTIP7 and 20 have already been presented in Sarda et al., Plant J. 12 (1997) 1103-1111). As was previously shown for SunTIP7 and 20, expression of SunTIP18 and SunRb7 in Xenopus oocytes caused an increase in osmotic water permeability demonstrating that they are aquaporins. In roots, in situ hybridization revealed that SunTIP7 and 18 mRNAs accumulate in phloem tissues. The expression of TIP-like genes was studied in roots during 24 h water deprivation through exposure to air. During the course of the treatment, each SunTIP gene displayed an individual response: SunTIP7 transcript abundance increased, SunTIP18 decreased whereas that of SunTIP20 was transitorily enhanced. By contrast, SunRb7 and Sun gammaTIP mRNA levels did not fluctuate. Due to the changes in their transcript levels, it is proposed that SUNTIP aquaporins encoded by delta-TIP-like genes play a role in the sunflower response to drought.

The effect of dual-chamber detected atrioventricular pacing mode alone and combined with rate-drop response reduced vasodepression and cerebral hypoperfusion induced by carotid massage in patients with carotid sinus syndrome.

The effect of cardioinhibition and/or vasodepression on cerebral hemodynamics assessed by transcranial Doppler has been investigated during carotid massage in 11 patients (62-87 years, mean age 72) with carotid sinus syndrome. The patients were tested in the OOO mode (n = 11) with six tested in the DDD mode. Carotid massage in the OOO mode decreased mean arterial pressure by 44% (P < 0.01) and mean cerebral blood flow velocity by 50% (P < 0.01). Although not significant, cerebrovascular resistance increased transiently by 17% during massage, then decreased by 31% upon recovery. Carotid massage in the DDD mode decreased arterial pressure by 30% (P < 0.01), cerebral blood velocity by 23% (P < 0.01), and resistance by 15% (P < 0.05). The decreased cerebral perfusion induced by cardioinhibition and/or vasodepression results from the delayed onset of cerebral autoregulation. Pacing in the DDD mode temporarily assists the critical period preceding the onset of cerebral autoregulation that plays a key role in preventing the deleterious effects of vasodepression.

Plasma noradrenaline is little used in evaluating the prognosis of cardiac failure because of the theoretical necessity of interrupting treatment for a few days before blood sampling. The present study reevaluated the prognostic value of this parameter with blood sampling performed during treatment and then 48 hours after withdrawal of treatment in 192 patients with chronic stable cardiac failure at an advanced stage (64% of patients in Classes III or IV with an average ejection fraction of 28.5 +/- 13.5%). During follow-up (average 43 months) there were 51 deaths and 17 transplants. None of the patients were lost to follow-up. Univariate analysis of 52 variable observers during the initial phase of evaluation found in decreasing order of predictive value for death plasma noradrenaline levels before and after withdrawal of treatment for 48 hours. Serum sodium, age, systolic mean and diastolic pulmonary artery pressures. In multivariate analysis: noradrenaline with or without withdrawal of treatment, hyponatraemia and systolic pulmonary artery pressure. Actuarial survival curves distinguished the following parameters: noradrenaline levels became predictive at concentrations of over 210 pg/mL and there was a significant difference in survival with respect to 4 levels of serum noradrenaline (with or without treatment) > 300 pg/mL, 300 to 600 pg/mL and > 900 pg/mL. This serum noradrenaline measured without withdrawal of treatment (especially angiotensin converting enzyme inhibitors) is a powerful predictor of mortality, carrying a progressively poorer prognosis as the concentration increases.

The effect of head-upright tilting on the rate of cerebral autoregulation was studied in 12 healthy volunteers (nine men and three women; age range 20-36 years). The dynamics of cerebral autoregulation was determined from the rate of change in cerebral resistance (RoR) during a drop in arterial blood pressure induced by rapid deflation of a 3-min ischaemic thigh cuff and from the ratio of changes in cerebral blood flow and arterial blood pressure (CAI) during the recovery period after the drop in arterial blood pressure. The test was performed supine and with 40 degrees head-up tilt (40 degrees HUT). Middle cerebral artery mean blood flow velocity was measured by transcranial Doppler simultaneously with peripheral arterial blood pressure using Finapres. The thigh cuff deflation induced a larger drop in arterial pressure during 40 degrees HUT [median -28% (25 percentile -36, 75 percentile -19)] than in the supine position [-16% (-23, -15)] (P < 0.01) and in cerebral resistance [supine: -12% (-15, -6); 40 degrees HUT: -15% (-20, -12); P < 0.05]. There was no significant change in RoR [15% s-1 (12, 15)] and CAI [1.9 (1.5, 3.1)] measured supine and during 40 degrees HUT [RoR: 13% s-1 (12, 15); CAI: 1.3 (0.99, 1.9)]. During the drop in arterial pressure, the relationship between arterial blood pressure and systolic peak-to-peak interval exhibited an hysteresis loop, indicating a cardiopulmonary and/or baroreflex activation that was not observed with cerebral resistance. The rate of autoregulation is an intrinsic property of the cerebral vascular bed and is not affected by the vasodilator state in the range of arterial blood pressure changes induced by the tight cuff method.

SunTIP7 and SunTIP20 are closely related sunflower cDNAs showing a deduced amino acid sequence homologous to proteins of the tonoplast intrinsic protein (TIP) family. Their expression in Xenopus oocytes caused a marked increase in osmotic water permeability (demonstrating that they are water channels) which was sensitive to mercury. In leaves, in situ hybridization revealed that both SunTIP7 and SunTIP20 mRNA accumulated in the guard cells. The possible involvement of SunTIPs in stomatal movement was examined by comparing the time course of transcript accumulation and leaf conductance during the daily cycle and following a water limitation. SunTIP7 mRNA fluctuations fitted changes occurring in leaf conductance. The transcript levels were markedly and systematically increased during stomatal closure. It is suggested that aquaporin SunTIP7 facilitates water exit associated with a decrease in guard cell volume. In the same conditions, the transcript level of SunTIP20 remained constant indicating that SunTIP genes are differentially regulated within the same cell.

Results of radiofrequency ablation of the atrioventricular junction on functional capacity and left ventricular systolic function were assessed in 8 patients (aged 68 +/- 12 years) with refractory atrial fibrillation and severe left ventricular dysfunction, the mean ejection fraction being 31 +/- 11% (range: 20-48%). A clinical, echocardiographic and angioscintigraphic follow-up was performed 24 hours (basal), 3 and 6 months after the procedure. During follow-up, all patients reported the disappearance of palpitations and tiredness, a significant and early regression of effort dyspnoea from average NYHA Class 3.4 +/- 0.7 to 2.2 +/- 0.4 (M3), (p < 0.01), a decrease in end diastolic echocardiographic dimensions (from 57 +/- 10 to 52 +/- 9 mm (M3); p < 0.05) resulting in an increase in fractional shortening from 26 +/- 7% to 34 +/- 6%; p < 0.05. The isotopic EF increased from 31 +/- 11% to 42 +/- 12% (M3) (p < 0.01), and attained 48 +/- 12% (M6). This study shows that controlling the frequency and regularity of cardiac rhythm by ablation of the atrioventricular junction in patients with refractory AF and left ventricular dysfunction results in functional and haemodynamic improvement, especially when there is no apparent underlying cardiac disease. This suggests that this method should be proposed in all patients with refractory atrial fibrillation and left ventricular dysfunction.

Body composition using standard anthropometric methods and dual-energy X-ray absorptiometry (DEXA) was determined in a cross-sectional study among 26 pediatric renal transplant recipients. At the same time, spiroergometry exam, pulmonary function tests, dynamometry and tremometry exams were performed in all patients. Fat body mass obtained by DEXA correlated inversely with maximal physical load during spiroergometry exam (r2 = 0.51, p = 0.0001). The study demonstrates good tolerance of increased physical load in children after renal transplantation. An inverse relationship was found between fat body mass and physical performance. Exercise training programs for children after renal transplantation are therefore suggested.

The aim of this study was to assess "morphological" MRI data (spin-echo) compared with cine-MRI in 10 patients with documented right ventricular dysplasia and 10 normal controls. Data was acquired with a 0.5 Tesla superconductor magnet associating sequences of spin-echo and gradient echo (cine-MRI). An abnormal high intensity signal was observed in spin-echo in 9 out of the 10 patients. They were present on the anterior and sub-tricuspid walls of the right ventricle (8/10) and in the pulmonary infundibulum (8/10). A dyskinetic zone corresponding to the abnormal signals was detected in 8 patients. In the control group, only one subject had an abnormal high intensity signal and no dyskinesis could be detected. The association of high intensity signals and dyskinesis would seem to be very specific of right ventricular dysplasia. On the other hand, a high intensity signal alone may be observed in apparently normal subjects and would seem to be less specific.

We have studied two lines of sunflower (Helianthus annuus L.) selected in the field as drought-tolerant (R1 genotype) or drought-sensitive (S1 genotype). When subjected to drought conditions, the R1 line was able to maintain high leaf water potential longer and wilted later than the S1 line. Therefore, this indicates that R1 tolerance includes a leaf-adaptive response. By subtractive hybridization, we have isolated six different cDNAs (designated sdi for sunflower drought-induced) corresponding to transcripts accumulated in R1 and S1 leaves during adaptive response. Analysis of transcript accumulation in response to drought in both genotypes suggests a preferential expression of three sdi genes in the tolerant line. Abscisic acid-mediated induction, analysed in R1 leaves, was observed for only four sdi genes. Sequence analysis of six sdi clones revealed that five clones were related to known proteins including non specific lipid transfer proteins (nsLTP), early light-induced proteins (ELIP), l-aminocyclopropane-l-carboxylate oxidase (ACC oxidase) or dehydrins, predicted to be involved in a wide range of physiological processes.

Amiodarone-induced hyperthyroidism in a relatively rare complication of long-term treatment with this molecule. It usually carries a good prognosis with regression being the rule after withdrawal of the drug although lethal forms have been reported. Conventional medical therapy (synthetic antithyroid drugs, steroids, betablockers) used in severe forms, is not always effective. In addition, amiodarone may be essential for the treatment of life-threatening, poorly tolerated arrhythmias, refractory to other forms of treatment. The authors report the cases of three patients treated with amiodarone for malignant arrhythmias who developed severe hyperthyroidism resistant to medical therapy and who were treated by total thyroidectomy. Surgery was followed by rapid resolution of the thyrotoxicosis without significant complications and immediate represcription of amiodarone. Thyroidectomy therefore seems a simple solution for amiodarone-induced hyperthyroidism allowing very rapid resolution of the hyperthyroidism and the possibility of immediate represcription of amiodarone.

Based on the results of our study, > 95% of patients with a positive passive tilt test are also positive during 3 micrograms/min, and especially 5 micrograms/min, isoproterenol tilt test. A proposed time-saving protocol would be to initiate the test with an isoproterenol infusion and to perform a 45-minute passive tilt only in those patients with a positive 5 micrograms/min (an infusion rate reported to have an excessive low specificity) isoproterenol tilt test, and to consider only those with symptoms associated with objective changes during this latter test as "finally positive." An alternative option would be to perform a 45-minute passive tilt only in those patients with a negative 3 micrograms/min isoproterenol tilt test.