Search

AIMS: To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS). METHODS AND RESULTS: A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when \textless50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age \textgreater10 years old, and receiving standard therapy. 303 patients, mean age 29.9 years old, were randomized. The two groups were similar at baseline, 86% receiving β-blocker therapy. The median follow-up was 3.5 years. The evolution of aortic diameter at the level of the sinuses of Valsalva was not modified by the adjunction of Losartan, with a mean increase in aortic diameter at the level of the sinuses of Valsalva of 0.44 mm/year (s.e. = 0.07) (-0.043 z/year, s.e. = 0.04) in patients receiving Losartan and 0.51 mm/year (s.e. = 0.06) (-0.01 z/year, s.e. = 0.03) in those receiving placebo (P = 0.36 for the comparison on slopes in millimeter per year and P = 0.69 for the comparison on slopes on z-scores). Patients receiving Losartan had a slight but significant decrease in systolic and diastolic blood pressure throughout the study (5 mmHg). During the study period, aortic surgery was performed in 28 patients (15 Losartan, 13 placebo), death occurred in 3 patients [0 Losartan, 3 placebo, sudden death (1) suicide (1) oesophagus cancer (1)]. CONCLUSION: Losartan was able to decrease blood pressure in patients with MFS but not to limit aortic dilatation during a 3-year period in patients \textgreater10 years old. β-Blocker therapy alone should therefore remain the standard first line therapy in these patients

Aim. Both aerobic training (AT) and electromyostimulation (EMS) of leg muscles improve exercise tolerance in patients suffering from chronic heart failure (CHF). It was speculated that combination of both methods might have an additive effect. This study was performed to evaluate the effects of a combination of AT and EMS in rehabilitation (RHB) of CHF patients. Patients and Methods. Patients (n=71; age 59±10.2 yrs, NYHA II/III, EF 32±7.1%) were randomized into 3 groups: a) group AT, b) group EMS, and c) group AT+EMS. AT protocol included standard activity on bicycle 3x a week at the level of individual anaerobic threshold. EMS (10Hz, mode 20s “on”/20s “off”) was applied to leg extensors for 2 h/day. Total time of given type of RHB was 12 weeks. Results. Data analysis revealed statistically significant improvements of patients in all experimental groups (averaged difference after 12 weeks of exercise as related to initial value: ∆VO 2peak : +12.9%, ∆VO 2AT : +9.3%, ∆W peak : +22.7%). No statistically significant difference among experimental groups was found. Quality of life (Minnesota Living with Heart Failure – MLHF) global score was significantly improved in all 3 groups: AT (∆MLHF: –27.9%; P=0.001), AT+EMS (∆MLHF: –29.1%; P=0.002), and EMS (∆MLHF: –16.6%; P=0.008). MLHF score in EMS group showed the smallest time–related improvement compared to AT and AT+EMS groups, and this difference in improvement between the groups was statistically significant (P=0.021). Conclusion. No significant difference was found between the two types of exercise training.and nor did, their combination have any significant additional improvement.

Aims In low-flow, low-gradient aortic stenosis (LF/LG AS), the assessment of contractile reserve (CR) by dobutamine stress echocardiography (DSE) is recommended for risk stratification and treatment strategy. However, DSE may show limitations in cases of left ventricular dyssynchrony (LVD). The impact of LVD in LF/LG AS, and the feasibility of CRT in this setting have never been evaluated. We aimed to assess: (i) the proportion of LF/LG AS patients with LVD; (ii) the influence of LVD on CR at DSE; and (iii) the effects of CRT in these patients. Methods and results Thirty consecutive patients with LF/LG AS underwent DSE with study of CR. The operative risk for aortic valve replacement (AVR) was assessed using the logistic EuroSCORE. Twenty-one of the 30 patients had LVD. They were significantly older, more symptomatic, had a higher EuroSCORE, and a lower prevalence of CR than those with a narrow QRS (47% vs. 100%, P = 0.009). A CRT pacemaker was implanted in 19 of the 21 patients with LVD. All 19 (except for one patient who died suddenly) experienced significant clinical and echocardiographic improvement. Fourteen CRT patients underwent subsequent AVR with a low event rate. Four CRT patients refused AVR; two of them worsened again 1–2 years post-CRT. Conclusion LVD is common in LF/LG AS patients and may be a major mechanism of afterload mismatch, as well as a cause of underdetection of CR. CRT in this population is feasible and may be proposed as a bridge to surgery.

Aims Our group has recently shown that in some patients, heart failure with preserved ejection fraction (HFPEF) may be explained by ‘atrial dyssynchrony syndrome’ (ADS) due to interatrial conduction delay (IACD), a short left atrioventricular interval (LAVI), and increased left atrial (LA) stiffness. Our primary objective was to evaluate LA pacing therapy as a new treatment to restore left ventricular active filling in patients with no other known causes for HF than ADS. Methods and results Six patients with severe HFPEF with IACD (P wave duration >120 ms in lead II), short LAVI during electrophysiological studies ( 15), and no standard indication for a pacemaker were implanted with a lead screwed inside the coronary sinus for active LA pacing. After 3 months of active pacing, a 2 week randomized double-blind crossover phase compared active vs. inactive LA pacing. After 3 months of pacing, the mean distance walked in 6 min (6MWD) was 21% greater (240 ± 25 m vs. 190 ± 15m, P < 0.05), mitral A wave duration was longer (104 ± 8 vs. 158 ± 25 ms, P = 0.002), and E/A and E/e' ratios were smaller (3.4 ± 1.3 vs. 1.8 ± 0.9, P = 0.009, and 22.6 ± 4.6 vs. 15.3 ± 4.3, P = 0.006, respectively). Inactivation of pacing for 1 week led to a significant reduction in the 6MWD, with an on/off response. Conclusion The beneficial effects of LA pacing observed in this pilot study will have to be confirmed by the randomized, controlled crossover ‘LEAD’ study.

Objectives Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with manifestations mainly involving the skeletal, ocular, and cardiovascular systems. The phenotypic variability observed in MFS makes genetic counselling difficult. Prenatal diagnosis (PND) and preimplantation genetic diagnosis are technically feasible when a causal mutation is identified, but both raise many ethical questions in this condition. Little is known about opinions and practices in such reproductive issues in MFS. The goal of this study was to report on patients' points of view and geneticists' standard practices. Methods Two different questionnaires were produced. Results Fifty geneticists filled in the questionnaire. Twenty-two per cent thought that PND was acceptable, 72% debatable and 6% not acceptable. Preimplantation genetic diagnosis was more often reported acceptable (34% of answers). Results varied according to the physician's experience with the disease. Fifty-four answers were collected for patients' questionnaires. Most of them (74%) were favourable to the development of prenatal testing, and believed that the choice should be given to parents. However, only a minority would opt for prenatal diagnosis for themselves. Conclusion This study showed that the majority of patients were in favour of PND and that opinions among practitioners varied widely, but that overall, practitioners favoured a systematic multidisciplinary evaluation of the couple's request. © 2012 John Wiley & Sons, Ltd.

OBJECTIVES: The aim of this study was to describe a new familial cardiac phenotype and to elucidate the electrophysiological mechanism responsible for the disease. BACKGROUND: Mutations in several genes encoding ion channels, especially SCN5A, have emerged as the basis for a variety of inherited cardiac arrhythmias. METHODS: Three unrelated families comprising 21 individuals affected by multifocal ectopic Purkinje-related premature contractions (MEPPC) characterized by narrow junctional and rare sinus beats competing with numerous premature ventricular contractions with right and/or left bundle branch block patterns were identified. RESULTS: Dilated cardiomyopathy was identified in 6 patients, atrial arrhythmias were detected in 9 patients, and sudden death was reported in 5 individuals. Invasive electrophysiological studies demonstrated that premature ventricular complexes originated from the Purkinje tissue. Hydroquinidine treatment dramatically decreased the number of premature ventricular complexes. It normalized the contractile function in 2 patients. All the affected subjects carried the c.665G>A transition in the SCN5A gene. Patch-clamp studies of resulting p.Arg222Gln (R222Q) Nav1.5 revealed a net gain of function of the sodium channel, leading, in silico, to incomplete repolarization in Purkinje cells responsible for premature ventricular action potentials. In vitro and in silico studies recapitulated the normalization of the ventricular action potentials in the presence of quinidine. CONCLUSIONS: A new SCN5A-related cardiac syndrome, MEPPC, was identified. The SCN5A mutation leads to a gain of function of the sodium channel responsible for hyperexcitability of the fascicular-Purkinje system. The MEPPC syndrome is responsive to hydroquinidine.

Aims The purpose of the present study was too explore the role of interatrial dyssynchrony in heart failure with preserved ejection fraction (HFPEF). Methods and results For the case study we selected seven patients with severe HFPEF, with interatrial block on electrocardiogram (ECG), and a delayed and interrupted A wave on mitral Doppler. Echocardiographic left atrial (LA) volumes/functions, mitral E/A and E/e‘ ratios, mitral A wave duration/deceleration time, and interatrial mechanical delays (IAMDs) at tissue Doppler, were studied. We performed right heart catheterization, and an electrophysiological study (EPS) for the measurement of interatrial conduction delay (IACD) and left atrioventricular interval (LAVI). Mean IAMD was 106 ms. All the patients exhibited a restrictive mitral Doppler pattern, high E/A and E/e' ratios, and short A wave duration/deceleration time. Left atrial volume was increased, with severely depressed functions. Right heart catheterization showed severe post-capillary pulmonary hypertension. The EPS showed an IACD of 170 ± 20 ms, with a short LAVI. Left atrial pacing through the coronary sinus reduced the IACD to 25 ± 15 ms. In the pilot study, 29 patients with HFPEF were compared with 27 age-matched control patients. HFPEF patients had longer P waves, shorter A waves, and a longer IAMD than the controls. Prevalence of severe IAMD >60 ms was 59% in HFPEF and 0% in controls. In the HFPEF group, patients with an IAMD >60 ms had significantly shorter A waves and higher E/e' ratio. Conclusion Some HFPEF patients present with IACD, delayed LA systole, shortened LA emptying, decreased LA compliance, and increased filling pressures. Whether the condition of these patients could be improved by atrial resynchronization deserves further investigation.

International audience; Interstitial deletions involving the 15q21.1 band are very rare. Only 4 of these cases have been studied using molecular cytogenetic techniques in order to confirm the deletion of the whole FBN1 gene. The presence of clinical features of the Marfan syndrome (MFS) spectrum associated with mental retardation has been described in only 2/4 patients. Here we report on a 16-year-old female referred for suspicion of MFS (positive thumb and wrist sign, scoliosis, joint hyperlaxity, high-arched palate with dental crowding, dysmorphism, mitral insufficiency with dystrophic valve, striae). She had therefore 3 minor criteria according to the Ghent nosology. She also had speech disabilities but could follow normal school training. Direct sequencing of the FBN1, TGFBR1 and TGFBR2 genes was negative. MLPA revealed a genomic deletion of the whole FBN1 gene, confirmed by loss of heterozygosity of maternal alleles for several microsatellite markers surrounding the FBN1 gene. The deletion was confirmed by FISH using a FBN1 probe and was not found in the parents. Array-CGH permitted to define a 2.97 Mb deletion, which was the smallest 15q microdeletion including FBN1. Contrary to the other published observations, our proband does not exhibit mental retardation, but neuropsychological evaluations revealed an attention deficit as well as a deficit in information-processing speed. Haploinsufficiency of FBN1 is likely to contribute to the presence of MFS features. However, attenuated features could be explained because disturbances of TGF-beta signalling associated with FBN1 mutations do not exert full phenotypic effect through simple haploinsufficiency. Phenotypic variability in other patients with interstitial deletions including 15q21.1 band may reflect differences in deletion size and/or cys/trans modifying factors.

Background Congenital defects of the pericardium are rare and poorly known cardiac malformations. Most of them are left-sided and asymptomatic and are usually incidentally diagnosed. Aims To describe the clinical, electrocardiographic, and imaging features of total absence of the left pericardium. Methods and Results We report the cases of 3 patients who have been seen in our institution with a diagnosis of total congenital absence of the pericardium. All of them complained of precordial pain; one of them experienced disabling symptoms that justified surgical intervention. All of them had previously been suspected to have an atrial septal defect because of the echocardiographic appearance of right ventricular volume overload. Electrocardiogram, chest x-ray, echocardiography, and magnetic resonance imaging of the heart consistently showed remarkably similar features including leftward displacement, increased mobility, and interposition of lung tissue between the heart and other intrathoracic structures. Conclusion Congenital absence of the left pericardium should be known by clinicians as a possible differential diagnosis of chest pain or pseudo-right heart overload. Copyright © 2010 Wiley Periodicals, Inc.

Resume Introduction Parmi les atteintes cardiaques survenant au cours des hypereosinophilies (HE), la fibrose endomyocardique avec comblement ventriculaire apical represente la forme la plus connue. Neanmoins, la cardiopathie eosinophilique peut prendre des aspects varies touchant les differentes tuniques du cœur avec une expression clinique et echocardiographique polymorphe. Methodes Etude retrospective descriptive de cinq observations illustrant la diversite de la cardiopathie eosinophilique. Resultats Les cinq observations rapportees d’atteinte cardiaque au cours d’une HE sont l’occasion de rappeler la physiopathologie de cette maladie potentiellement gravissime : la cytotoxicite des eosinophiles passe par la liberation de proteines granulaires qui agressent primitivement l’endocarde, faisant le lit de la thrombose et des accidents emboliques, puis de la fibrose et des complications valvulaires ; l’atteinte myocardique peut quant a elle conduire a la redoutable myocardite aigue a eosinophiles (MAE) ; enfin, la pericardite peut se compliquer de tamponnade. Conclusion Ces observations permettent de balayer le spectre des atteintes cardiaques et la diversite des etiologies possibles, de rappeler que le pronostic vital peut etre mis en jeu a la phase aigue et de souligner que le pronostic fonctionnel depend d’un depistage precoce et de la mise en route rapide d’un traitement qui permette de limiter le risque de complications thromboemboliques et fibrosantes.

International audience; Abstract: The aim of this study was to compare the prognostic significance of microvascular obstruction (MO) and persistent microvascular obstruction (PMO) as assessed by cardiac magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). CMR was performed in 184 patients within the week following successfully reperfused first AMI. First-pass images were performed to evaluate extent of MO and late gadolinium-enhanced images to assess PMO and infarct size (IS). Major adverse cardiac events (MACE) were collected at 1-year follow-up. MO and PMO were found in 127 (69%) and 87 (47%) patients, respectively. By using univariate logistic regression analysis, high Global Registry of Acute Coronary Events (GRACE) risk score (odds ratio [OR] 95% confidence interval [CI]: 3.6 [1.8-7.4], p < 0.001), IS greater than 10% (OR [95% CI]: 2.7 [1.1-6.9], p = 0.036), left ventricular ejection fraction less than 40% (OR [95% CI]: 2.4 [1.1-5.2], p = 0.027), presence of MO (OR [95% CI]: 3.1 [1.3-7.3], p = 0.004) and presence of PMO (OR [95% CI]:10 [4.1-23.9], p < 0.001) were shown to be significantly associated with the outcome. By using multivariate analysis, presence of MO (OR [95% CI]: 2.5 [1.0-6.2], p = 0.045) or of PMO (OR [95% CI]: 8.7 [3.6-21.1], p < 0.001), associated with GRACE score, were predictors of MACE. Presence of microvascular obstruction and persistent microvascular obstruction is very common in AMI patients even after successful reperfusion and is associated with a dramatically higher risk of subsequent cardiovascular events, beyond established prognostic markers. Moreover, our data suggest that the prognostic impact of PMO might be superior to MO.

Objective: To confirm that electrical myostimulation is a good alternative to conventional aerobic training in patients with chronic heart failure and to compare the effects of both training programmes in patients with different exercise capacities. Patients and methods: A total of 44 patients with stable chronic heart failure underwent 5 weeks of exercise training, with electrical myostimulation or conventional aerobic training programmes. At baseline and after the training period, patients performed a symptom-limited cardiopulmonary exercise test and a 6-min walk test. Results: Oxygen uptake at the end of exercise (V . O 2 peak) and at ventilatory threshold (V . O 2 VT) increased after electrical myostimulation (p< 0.001) and conventional aerobic training (p< 0.001) training programmes. The slope of the relationship between V . O 2 and workload was reduced after electrical myostimulation (p< 0.05), but not after conventional aerobic training. Recovery was improved after both training programmes (p< 0.05), and the distance walked in 6 min was increased (p< 0.001). These improvements were not statistically different between electrical myostimulation and conventional aerobic training. Moreover, electrical myostimulation induced greater improvements in patients with low exercise capacity, whereas conventional aerobic training induced improved performance in patients with average exercise capacity. Conclusion: Five weeks of electrical myostimulation and conventional aerobic training exercise training produced similar improvements in exercise capacity in patients with chronic heart failure. However, electrical myostimulation appears to be more effective in patients with low exercise capacity than in those with average exercise capacity.

The prognosis of patients with acute myocardial infarction (MI), according to the new criteria for impaired fasting glucose (IFG) (FG 100-126 mg/dl), has not been evaluated.A total of 2353 patients with acute MI and surviving at d 5 after admission were analyzed for short-term morbidity and mortality. FG was obtained at d 4 and 5. Patients were classified as diabetes mellitus (known diabetes or FGor = 126 mg/dl), high IFG (110or = FG126 mg/dl), low IFG (100or = FG110 mg/dl), and normal fasting glucose (NFG) (FG100 mg/dl).Among the 2353 patients, 968 (41%) had diabetes mellitus, 262 (11%) had high IFG, 332 (14%) had low IFG, and 791 (34%) had NFG. Compared with NFG patients, 30-d cardiovascular mortality was increased in high but not low IFG subjects. In-hospital heart failure was increased in high IFG subjects (42 vs. 20% for NFG, P0.0001) but not low IFG subjects (21 vs. 20%). High IFG, but not low IFG, was an independent factor associated with 30-d cardiovascular mortality [odds ratio 2.33 (1.55-3.47)] and in-hospital heart failure [odds ratio 1.70 (1.36-2.07)]. The optimal threshold levels of FG on the receiver-operating characteristic curves were 114 and 112 mg/dl to predict mortality and in-hospital heart failure, respectively.The present study, based on a nonselected cohort of MI patients, underscores the high prevalence of IFG (25%) and highlights the clinical relevance of 110 mg/dl, but not 100 mg/dl, as a cutoff value to define the risk for worse outcome.

Background We recently demonstrated that patients with platypnea-orthodeoxia syndrome and an enlarged aortic root had a smaller and hypermobile atrial septum (AS) compared with those with a normal aortic root. However, this was a partly retrospective study. Methods In all, 72 patients underwent transesophageal echocardiography and cardiac catheterization. The aortic root diameter, AS dimension, AS oscillation amplitude (ASo), and atrial pressure gradient were measured. Results Significant correlations were found: aortic root diameter and AS dimension ( r = −0.5, P r = +0.3, P = .014), AS dimension and ASo ( r = −0.28, P = .02), and ASo and atrial pressure gradient ( r = −0.36, P = .003). Nineteen patients presented with patent foramen ovale; those with grade 3 shunting had significantly higher mobility of the AS and larger aortic roots. Conclusion These results confirm that an increasing aortic size affects the AS by decreasing its apparent size and increasing its mobility. In case of a patent foramen ovale, increased AS mobility is associated with greater shunting.

Background: In patients with common atrial flutter (CAF), radiofrequency ablation (RFA) causes discomfort. Patients undergoing RFA often feel pain which is difficult to control as the mechanisms are unclear. Hypothesis: Inhaled nitrous oxide (N2O) is a potent sedative-analgesic-anxiolytic agent that may relieve anxiety and discomfort during CAF ablation. Methods and Results: In a prospective randomized study, the effect of Inhaled N2O was compared with that of intravenous sedation with Nalbuphine during CAF ablation in 76 patients (64 ± 13 years, 56 men). We used a 24 pole mapping catheter around the tricuspid annulus and a 8-mm tip ablation catheter for each patient. Forty-two patients (group 1) underwent radiofrequency (RF) application to the cavotricuspid isthmus 5 minutes after the beginning of inhalation of a (50% N2O/50% O2) mixture. Thirty-four patients (group 2), underwent the first RF application 15 minutes after the end of an infusion of Nalbuphine (20 mg delivered over 15 minutes). Ablation-related anxiety and discomfort were assessed using a visual analog scale (VAS) ranging from 0 to 100 mm, with 0 correlating to the statement “no pain at all” and 100 with “the worst possible pain.” The VAS score was determined at the end of each application.The number of RF applications (group 1; 10 ± 8 vs group 2; 11 ± 6, P = NS) and procedure duration (group 1; 75 ± 53 minutes vs group 2; 72 ± 45 minutes, P = NS), were similar for the two groups. N2O sedation compared with nalbuphine infusion reduced VAS for anxiety (10 mm ± 8 vs 58 mm ± 22, P < 0.05) and for discomfort (18 mm ± 9 vs 45 mm ± 34, P < 0.01), respectively. Although there was more frequent vomiting in group 1; 7 of 42 (17%) than in group 2; 3 of 34 (9%), P < 0.05, patients were less likely to have hypotension during the procedure 1 of 42 (2.5%) versus 4 of 34 (12%), P < 0.05, respectively. Conclusion: Inhalation of a (50% N2O/50% O2) mixture during RF ablation for atrial flutter is a safe and efficient way to reduce anxiety and discomfort caused by RF applications.

This study was designed to evaluate the effects of low-frequency electrical stimulation (LFES) on muscle strength and blood flow in patients with advanced chronic heart failure (CHF).Patients with CHF (n=15; age 56.5 +/- 5.2 years; New York Heart Association III - IV; ejection fraction 18.7 +/- 3.3%) were examined before and after 6 weeks of LFES (10 Hz) of the quadriceps and calf muscles of both legs (1 h/day, 7 days/week). Dynamometry was performed weekly to determine maximal muscle strength (F(max); N) and isokinetic peak torque (PT(max); Nm); blood flow velocity (BFV) was measured at baseline and after 6 weeks of LFES using pulsed-wave Doppler velocimetry of the right femoral artery. Six weeks of LFES significantly increased F(max) (from 224.5 +/- 96.8 N to 340.0 +/- 99.4 N; p0.001), and also PT(max) (from 94.5 +/- 41.5 Nm to 135.3 +/- 28.8 Nm; p0.01). BFV in the femoral artery increased after 6 weeks from 35.7 +/- 15.4 cm/s to 48.2 +/- 18.1 cm/s (p0.05); BFV values at rest before and after 6 weeks of LFES did not differ significantly.LFES may improve muscle strength and blood supply, and could be recommended for the treatment of patients with severe CHF.

The aim of this study was to investigate whether electrical stimulation of skeletal muscles could represent a rehabilitation alternative for patients with chronic heart failure (CHF). Thirty patients with CHF and NYHA class II-III were randomly assigned to a rehabilitation program using either electrical stimulation of skeletal muscles or bicycle training. Patients in the first group (n = 15) had 8 weeks of home-based low-frequency electrical stimulation (LFES) applied simultaneously to the quadriceps and calf muscles of both legs (1 h/day for 7 days/week); patients in the second group (n = 15) underwent 8 weeks of 40 minute aerobic exercise (3 times a week). After the 8-week period significant increases in several functional parameters were observed in both groups: maximal VO2 uptake (LFES group: from 17.5 +/- 4.4 mL/kg/min to 18.3 +/- 4.2 mL/kg/min, P < 0.05; bicycle group: from 18.1 +/- 3.9 mL/kg/min to 19.3 +/- 4.1 mL/kg/min, P < 0.01), maximal workload (LFES group: from 84.3 +/- 15.2 W to 95.9 +/- 9.8 W, P < 0.05; bicycle group: from 91.2 +/- 13.4 W to 112.9 +/- 10.8 W, P < 0.01), distance walked in 6 minutes (LFES group: from 398 +/- 105 m to 435 +/- 112 m, P < 0.05; bicycle group: from 425 +/- 118 m to 483 +/- 120 m, P < 0.03), and exercise duration (LFES group: from 488 +/- 45 seconds to 568 +/- 120 seconds, P < 0.05; bicycle group: from 510 +/- 90 seconds to 611 +/- 112 seconds, P < 0.03). These results demonstrate that an improvement of exercise capacities can be achieved either by classical exercise training or by home-based electrical stimulation. LFES should be considered as a valuable alternative to classical exercise training in patients with CHF.

A complete line of block (CLOB) in the cavotricuspid isthmus (CTI) is the endpoint of typical atrial flutter ablation. Before CTI block is obtained, a progressive CTI conduction delay due to an incomplete line of block (InLOB) can be difficult to distinguish from CLOB. The purpose of this study was to assess a new simple approach based on the changes in atrio-ventricular (AV) conduction delays during septal and lateral right atrial pacing, to distinguish a CLOB from an InLOB during typical atrial flutter (AFL) ablation.Forty patients who presented an InLOB before a CLOB, and a stable (AV) conduction delay at 600 ms cycle length pacing (when in sinus rhythm), during AFL ablation were included in this study. A 24-pole mapping catheter was positioned so that 2 adjacent dipoles bracketed the targeted CTI line of block (LOB), with proximal dipoles lateral to the LOB and distal dipoles in the coronary sinus. Two pacing sites were lateral (position L1 and L2) and one was septal (position S) to the LOB, with locations L1 and S closest to the LOB. During L1, L2 and S site pacing, the delay between the pacing artefact and the peak of the R wave in a surface ECG (lead II) was measured. We measured the following conduction delays (mean +/- SD in ms), during InLOB versus CLOB: (L1 to R) 320.5 +/- 68.0 versus 367.0 +/- 62.0, p = 0.001; (L2 to R) 333.0 +/- 59.0 versus 338.0 +/- 62.0, p = 0.663, (S to R) 259.4 +/- 51.5 versus 247.1 +/- 55.5, p = 0.987. We calculated the following data during an InLOB versus a CLOB: (L1R-L2R) -12.3 +/- 7 versus 20.2 +/- 12.7, p = 0.001; (L1R-SR) 51.1 +/- 21.5 versus 120.1 +/- 16.6, p0.05. The sensitivity, specificity, positive and negative predictive values for CLOB with (L1R-SR94 ms) and with (L1R-L2R0 ms) were respectively; 100%, 98%, 98% and 100%.This study establishes that lateral versus septal right atrial pacing sites combined with the measure of AV conduction delay on a surface ECG can be useful to distinguish a CLOB from an InLOB during AFL ablation.

The long-term outcome of repaired aortic coarctation may be complicated by dilatation of the ascending aorta notably in patients with bicuspid aortic valve. Magnetic resonance imaging was used to compare the size of the ascending aorta in patients with bicuspid or tricuspid aortic valve.In 50 patients with a repair of aortic coarctation, the size of the ascending aorta was measured in a bicuspid aortic valve group (n=11) and a tricuspid aortic valve group (n=39). The aortic diameter was measured at the level of the sinus of Valsalva and at the widest part of the ascending aorta using magnetic resonance imaging.The mean age of patients at surgical repair was respectively 2.2+/-3.3 years for the bicuspid aortic valve group and 2.5+/-3.5 years for the tricuspid aortic valve group (p=NS) and the mean age at the time of the magnetic resonance imaging was 10.2+/-4.7 years and 9.3+/-5.9 years (p=NS) respectively. A significant difference in the aortic diameter was found between the bicuspid aortic valve group and the tricuspid aortic group both at the level of sinus of Valsalva (34.8+/-8.2 mm, 19.5+/-4.4 mm, respectively, p0.01) and at the level of the ascending aorta (36.8+/-7.2 mm, 16.9+/-3.4 mm, respectively, p0.01).The occurrence of ascending aortic dilatation is significantly associated with the presence of a bicuspid aortic valve. This requires long-term follow-up, which can be effectively performed by magnetic resonance imaging.

Objective: To assess the mechanisms through which an enlarged aortic root may facilitate right to left shunting through a patent foramen ovale. Patients: 19 patients with the platypnoea-orthodeoxia syndrome (POS) were compared with 30 control patients without platypnoea. Interventions: Multiplane transoesophageal echocardiography. Main outcome measures: The aortic root diameter, atrial septal dimension behind the aortic root, and amplitude of the phasic oscillation of the septum were measured. Four groups of patients were compared: 12 platypnoeic patients with a dilated aortic root (POS-D), 7 platypnoeic patients with a normal aortic root (POS-N), 15 control patients with a dilated aortic root (CONT-D), and 15 control patients with a normal aortic root (CONT-N). Results: In POS-D and CONT-D patients, the apparent atrial septal dimension was 16.3 (2.7) mm and 17.4 (5.9) mm respectively, compared with 24.4 (5.2) mm in POS-N patients and 25 (4) mm in CONT-N (p < 0.005). Furthermore, the amplitude of septal oscillation was 14.7 (2.5) mm in the POS-D group versus 5.8 (2.4) mm in CONT-N (p < 0.001) compared with 23.3 (3) mm in seven patients with an atrial septal aneurysm (p

Background— Three loci have been shown to be responsible for nonsyndromic familial thoracic aortic aneurysms (TAAs) and aortic dissections (ADs). We recently described a large family in which TAA/AD associates with patent ductus arteriosus (PDA) and provided genetic arguments for a unique pathophysiological entity. Methods and Results— Genome-wide scan was performed in 40 subjects belonging to 3 generations in this large pedigree. Using the 7 TAA/AD cases as affected, we observed positive 2-point LOD scores on adjacent markers at chromosome 16p, with a maximum LOD score value of 2.73 at θ=0, a value that increased to 3.56 when 5 PDA cases were included. Multipoint linkage analysis yielded a maximum LOD score of 4.14 in the vicinity of marker D16S3103 . Fine mapping allowed the observation of recombinant haplotypes that delimited a critical 20-cM interval at 16p12.2-p13.13. Automatic determination of aortic compliance with cine MRI showed that all subjects bearing the disease haplotype, even asymptomatic, displayed a very low level of aortic compliance and distensibility. Aortic stiffness was strongly associated with disease haplotype with a marked effect of age, indicating subclinical and early manifestation of the disease. Conclusions— Genetic analysis of this family identified a unique locus responsible for both TAA/AD and PDA at chromosome 16p12.2-p13.13 with aortic stiffness as an early hallmark of the disease. TAA/AD with PDA is a new monogenic entity among the genetically heterogeneous group of TAA/AD disease.

Sudden cardiac death occurring in patients with end-stage renal disease (ESRD) may be related to poor autonomic function with a significant decreased heart-rate variability (HRV). In addition, coronary artery disease has a high prevalence in this population and accounts for 50% of deaths. In the present study, relationships between HRV and myocardial ischemic abnormalities revealed by myocardial scintigraphy (MS) were evaluated in 32 chronic hemodialysis patients.We prospectively studied 32 chronic hemodialysis patients. Each underwent MS and 24 h electrocardiography at baseline for analysis of time and frequency domain the day of dialysis. Three periods were analyzed: during dialysis session, the morning after (nondialytic period), and in a 24 h period. Patients were included in group 1 (seven women, 11 men; mean age: 62+/-19 years) when MS revealed no ischemia, whereas patients were included in group 2 (seven women, seven men; mean age: 63.1+/-20 years) when MS revealed ischemic lesions.A student+/-test revealed that during the nondialytic period, two important markers of HRV, percentage of delta RR50 ms (pNN50) (4.5+/-4.04 in group 1 versus 1.7+/-1.4 in group 2), and root mean square of delta RR (rMSSD) (27.7+/-13.4 versus 19.7+/-6.8) were significantly reduced in group 2 compared with values in group 1. No significant difference appears between the two groups for standard deviation of normal to normal intervals (SDNN), mean heart rate, and spectral analysis.Patients with ESRD and myocardial ischemia revealed by MS have reduced parasympathetic activity during the nondialytic period. Correlations between parameters of HRV and ischemic lesions revealed by MS have been shown for the first time.

International audience; Abstract: Aims: To evaluate the relationship between N-terminal Pro-Brain Natriuretic Peptide (N-BNP) level and contrast-enhanced MRI in patients after acute myocardial infarction (MI). Methods: Eighty-two patients were studied. Venous blood samples were obtained 3 days after MI and MRI was performed from 2 to 7 days after MI, with determination of left ventricular function and acquisition of perfusion data after injection of gadolinium-DTPA. First-pass images (FPI) and Delayed contrast-enhanced (CE) images were analyzed using a 17-segment model, and the extent of transmurality was determined by a visual score. Results: Univariate analysis showed that age (P < 0.001), sex (P < 0.02), Left Ventricular Ejection Fraction (LVEF)

Background. Despite the significant beneficial effects of antithrombotic therapy in primary prevention of stroke in patients with chronic nonvalvular atrial arrhythmia, this prevention therapy is underutilized. We conducted this population-based study to determine the rates and the trends of utilization of antithrombotic therapy for stroke patients with atrial fibrillation before stroke onset, and to evaluate indirectly the impact of medical recommendations on physician practice. Our aim was not to evaluate the efficacy of such prevention therapy. Methods. From 2,330 men and women of any age registered for a first-ever stroke from 1985 to 1997 in a community-based study, we selected 599 patients admitted for ischemic stroke or TIA, associated with prior atrial fibrillation. Previous antithrombotic treatment before stroke onset was recorded and we evaluated the ratio of stroke patients who had received antithrombotic treatment for atrial fibrillation, from 1985 through 1997. Results. Our study was performed to evaluate the practice of physicians in the prevention of stroke, and not to evaluate the efficacy of the anticoagulants in the prevention of stroke. Atrial fibrillation before stroke onset was identified in 599 patients. Of these, 222 (37%) received no antithrombotic therapy, 65 (10.8%) received an anticoagulant alone, 147 (24.5%) received an antiplatelet agent alone and 10 (1.7%) received both anticoagulation and antiplatelet treatment. From 1985 to 1988, the proportion of treated atrial fibrillation before stroke was small (14.6%). This increased to 21.5% within the period 1989–1991, to 40.3% within the period 1992–1994 and then to 47.6% within the period 1995–1997. It appears that the most significant change occurred within the period 1992–1994 (14.6% of treated atrial fibrillation within the period 1985–1987 constituted to 40.3% within the period 1992–1994) (P < 0.05), with a current rate of utilization of antithrombotic therapy close to 50%. The logistic regression analysis concerning anticoagulant therapy before stroke onset as a dependent variable, found that the factors independently associated with the use of anticoagulants before stroke were the lack of arterial hypertension and a history of smoking. The factors independently associated with the use of aspirin before stroke were arterial hypertension and lower limb peripheral vascular disease. Conclusion. For primary prevention of stroke onset in patients with atrial fibrillation, therapeutic trials have changed medical practices although not to ideal levels because close to 50% of patients with atrial fibrillation experiencing an acute stroke or TIA received antithrombotic treatment. Therefore, clinical practice is inconsistent with the guidelines resulting from therapeutic trials. It is necessary to know the reasons for this inconsistency and to improve medical information about the cerebrovascular risk of atrial fibrillation and the efficacy of anticoagulants in stroke prevention in this condition.

Preventing coronary in-stent restenosis is a major challenge for physicians and industry. To assess new stent technologies, a comparative paired iliac artery model in rabbits is proposed. One tubular stent was implanted in each external iliac artery in 12 rabbits (i.e., 24 stents). An artery overdilatation level of 20% was strictly observed. Restenosis was examined at 30 days by angiography, intravascular ultrasound (IVUS) examination, and histomorphometry. On quantitative angiography, the mean loss of angiographic diameter was 9.8 ± 4.4% in the right as compared to 9.3 ± 55% in the left artery (p = 0.75). On IVUS, the volume of intrastent neointimal proliferation was 26.6 ± 4.9 mm3 in the right and 25.8 ± 3.5 mm3 in the left artery (p = 0.58). In histomorphometry, the neointimal proliferation area was 0.78 ± 17 mm2 in the right and 0.76 ± 0.17 mm2 in the left artery (p = 0.87). Intrastent neointimal proliferation was comparable between the left and right arteries of all rabbits. The model has three main advantages: (1) arterial dilatation and thus arterial wall aggression are controlled, (2) pairing makes each animal its own control subject, and (3) the statistical power for comparative testing is maximized. The model enables the effect of a new drug-delivery device to be assessed. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 303–310, 2004

There is a growing concern about an increased risk for cardiovascular disease in HIV infected patients receiving antiretroviral therapy (ART). This risk could be related to metabolic abnormalities associated with long-term use of antiretroviral drugs. In fact, well recognized cardiovascular risk factors such as hypertension, dyslipidaemia, diabetes mellitus and central fat deposition are increasingly seen in HIV patients on ART. These factors can also be associated with non reversible risk factors, such as male sex, age greater than 40 years and family history of premature coronary artery disease. In addition, cigarette smoking and sedentary lifestyle may predispose these patients to significant cardiovascular disease. A direct atherogenic effect of HIV infection itself or antiretroviral drugs is unlikely. Epidemiological studies have suggested an increased risk for coronary artery disease in HIV infected persons; nevertheless, only long term follow-up could confirm this statement. Despite these uncertainties, it seems reasonable to identify and manage cardiovascular risk factors in HIV infected patients.

Mutation in blood coagulation factor V Leiden is the most frequently genetic polymorphism implied in venous thrombosis. A 57 year old man was hospitalised for acute myocardial infarction (MI). An emergency coronary angiography was performed, and no significant stenosis was observed. The haematologic check-up showed an heterozygous Leiden mutation of factor V. We report all publications about the relation between factor V Leiden and coronary thrombosis, and we performed a meta-analysis. We analysed the relation in general population and in subgroups, such as, younger and older, and patient with or without coronary stenosis. In global population, the meta-analysis did not found significant association between Factor V Leiden and myocardial infarction (OR = 1.25; IC = 0.97-1.58). In contrast, in patients less than < 55 years old after MI, Factor V Leiden prevalence was significantly higher than in control group (OR = 1.48; IC = 1.05-2.08). In addition, after MI without significant coronary stenosis Factor V Leiden prevalence was significantly higher than in normal patients (OR = 2.84; IC = 1.46-5.51). After MI, in patients without significant coronary stenosis, Factor V Leiden prevalence was significantly higher than in patients with significant coronary stenosis (OR = 3.26; IC = 1.67-6.36). Our study suggests that Factor V Leiden could be search after MI in young subjects and/or without significant stenosis.

Resume L'imagerie par resonance magnetique du cœur permet d'apprecier la fraction d'ejection et les volumes ventriculaires gauches. Elle permet en outre d'etudier la perfusion myocardique et de detecter la presence d'un rehaussement du signal tardivement apres l'injection de gadolinium. Ce travail propose une methode d'analyse de la perfusion et de la fonction myocardique selon le modele a 17 segments actuellement recommande pour les differentes methodes d'imagerie du myocarde. Soixante-neuf patients ont ete explores apres un infarctus du myocarde revascularise avec un succes angiographique et la restauration d'un flux anterograde Timi III. La fonction globale et segmentaire est appreciee en coupes petit-axe en cine-IRM. Apres injection de gadolinium, la perfusion myocardique est appreciee visuellement sur une echelle a 5 niveaux refletant l'etendue transmurale croissante des anomalies. Le rehaussement tardif lie a l'accumulation de gadolinium 10 min apres l'injection est apprecie selon la meme echelle. La fraction d'ejection moyenne est de 51 ± 13 %. Les parametres de contraction segmentaire (epaisseur systolique, epaississement absolu et epaississement relatif) sont tres fortement lies aux scores segmentaires d'hypoperfusion ou de rehaussement tardif (ainsi l'epaississement absolu varie de 4,8 ± 2,7 mm pour les segments sans rehaussement tardif a 2,4 ± 2,1 mm pour les segments ayant un rehaussement tardif transmural). Les parametres de perfusion sont aussi lies a la fonction ventriculaire gauche globale ( r = 0,65, p

Objective: We assessed the effects of glucose–insulin–potassium (GIK) by echocardiography in stable patients with ischemic dysfunction. Methods: Twelve male patients with stable coronary disease (SCD) and ejection fraction (EF)

The influence of direct calls to specialized Emergency Medical Services in case of suspected myocardial infarction has not been extensively studied. The RICO registry is an exhaustive registry implemented in all six institutions participating in primary care of patients with acute myocardial infarction in one French administrative department (Cote-d'Or). From January 2001 to October 2001, 322 patients were admitted for acute myocardial infarction, among whom only 57 (18%) had directly called emergency medical services after the onset of symptoms. The baseline characteristics of patients who had directly called the emergency services were not different from those of the patients who had not. However, the time from symptom onset to first medical intervention (48 versus 105 minutes, p = 0.02) and from first medical intervention to hospital admission (60 versus 103 minutes, p = 0.02) were markedly shorter in patients who had directly called the emergency medical services. This resulted in a significant increase in the use of reperfusion therapy (70% versus 38%, p = 0.003), including a higher proportion of primary angioplasty (33% versus 20%, p = 0.04). This study documents the beneficial effect of a direct call to the Emergency Medical Services by the patients themselves. Too few patients, however use this opportunity and actions should be taken for informing the lay public of the benefits of this medical service.

Background The prognostic value of 201Tl myocardial imaging has been demonstrated in several studies concerning patients with a known significant coronary artery disease. However, the evolution of a coronary stenosis after stenting is difficult to predict. This study was designed to assess the prognostic value of 201Tl single-photon emission computed tomography (thallium SPECT) perfusion imaging in patients after intracoronary stenting. Methods One hundred fifty-two patients were studied. They were followed up during 40 ± 13 (mean ± SD) months after thallium SPECT. Stent-related events were studied after thallium stress testing and included cardiovascular death, myocardial infarction, and revascularization. Stress thallium imaging was performed 5 ± 2 months after stenting, and ischemia was considered to be present if at least 2 contiguous segments were showing reversible defects. Results Only 3 (3%) among the 105 nonischemic patients had major cardiac events during the follow-up versus 13 (28%) of the 47 ischemic patients (P < .001) after thallium SPECT. The relative risk of major cardiac events for patients with significant ischemia was 10.5 compared with nonischemic patients (P < .001). Fourteen (30%) of the ischemic patients and 8 (8%) among the nonischemic patients underwent iterative revascularization (P < .001). Therefore, only 11 (10%) of the nonischemic patients had major cardiac events or revascularization compared with 24 (51%) of the ischemic patients (P < .001). Conclusions Absence of ischemia on thallium SPECT imaging at 5 months after coronary stenting indicates a low risk for cardiovascular events or interventional procedure. These results may have important clinical implications in patient treatment. (Am Heart J 2001;141:999-1006.)

Resume Le budget hospitalier repose sur l'evaluation de l'activite de l'etablissement, notamment a partir des donnees du PMSI (programme de medicalisation du systeme d'information). Ce travail a porte sur l'ensemble des hospitalisations dans l'unite de soins intensifs de cardiologie du CHU de Dijon pour un infarctus du myocarde (IDM) au cours du 1er semestre 1998 (59 patients). Les objectifs de cette etude ont ete : 1) l'estimation du cout reel de la prise en charge ; 2) la comparaison de ce cout au cout de reference, determine a partir des donnees de la base nationale de couts (BNC) ; 3) l'impact economique de differentes sources d'erreurs de codage. Le cout reel a ete en moyenne de 39 382±15 718 FF. L'analyse par poste de depenses montre que 68 % des couts de cette maladie sont directement lies aux frais fixes, par contre les actes medicaux et les therapeutiques ne representent que 32 % du cout reel estime. Une surestimation de 52 % du cout reel par rapport au cout de reference est mise en evidence (p

Overexpression of P-glycoprotein (P-gp) in cancer cells reduces intracellular accumulation of various anticancer drugs including anthracyclines and vinca alkaloids. This multidrug resistance (MDR) phenotype can be reversed in vitro by a number of non-cytotoxic drugs. We have identified the quinine's isomer cinchonine as a potent MDR reversing agent, both in vitro and in animal models. Here, we report an open phase I dose escalation trial in patients with refractory or relapsed malignant lymphoid diseases. Cinchonine dihydrochloride was administered by continuous i.v. infusion for 48 h and escalated over five dose levels ranging from 15 to 35 mg/kg/d. Cinchonine infusion started 24 h before i.v. doxorubicin (25 mg/m2), vinblastine (6 mg/m2), cyclophosphamide (600 mg/m2) and methylprednisolone (1 mg/kg/d) (CHVP regimen) and lasted for 24 h after chemotherapy infusion. Thirty-four patients received 87 cycles of CHVP/cinchonine. The MTD of cinchonine administered by continuous i.v. infusion was 30 mg/kg/d. Prolonged cardiac repolarization was the main dose-limiting toxicity. No ventricular arrhythmia including 'torsade de pointes' was observed. An MDR reversing activity was identified in the serum from every patient and correlated with cinchonine serum level. When infused at 30 mg/kg/d, cinchonine demonstrated a limited influence on doxorubicin pharmacokinetic. We conclude that i.v. infusion of cinchonine might be started 12 h before MDR-related chemotherapy infusion and requires continuous cardiac monitoring but no reduction of cytotoxic drug doses.

BACKGROUND We hypothesized that intramural delivery of nadroparin, a low molecular weight heparin, would prevent in-stent restenosis by inhibiting neointimal hyperplasia in an angioplasty model free of arterial remodelling. METHODS AND RESULTS In a prospective randomized multicentre trial, 250 patients submitted to balloon angioplasty followed by stent implantation were randomized into control group (no local drug delivery) or intramural delivery of nadroparin (2 ml of 2500 anti-Xa-units/ml with a microporous catheter). An ancillary intravascular ultrasound substudy was performed to supplement angiographic data with specific measurements of in-stent neointimal hyperplasia. The primary end-point was the late loss in minimal luminal diameter on the 6 month follow-up angiogram. Secondary end-points included feasibility and safety of local nadroparin delivery, and major adverse cardiac events at 8 weeks and 6 months follow-up. Local delivery of nadroparin was successful in 124 patients (99.2% success rate) and was not associated with an increase in stent thrombosis, coronary artery dissection, side branch occlusion, distal embolization or abrupt arterial closure. At angiographic follow-up, the late loss in lumen diameter was 0.84 +/- 0.62 mm in the control group compared to 0.88 +/- 0.63 mm in the nadroparin group (P=0.56). Angiographic restenosis rate (defined as a >50% diameter stenosis) did not differ in the control group (20%) compared to the nadroparin group (24%). The average area of neointimal tissue within the stent was 2.86 +/- 0.64 mm(2) vs 2.90 +/- 0.53 mm(2) (P=0.57), control vs nadroparin groups. There was no difference in major adverse cardiac events at any time (88.8% vs 89.6% event free survival at 6 months, control vs nadroparin). CONCLUSION Intramural delivery of nadroparin with a microporous catheter after stent deployment was feasible and safe but had no effect in reducing restenosis or the occurrence of major adverse clinical events over 6 months.

We studied the in-hospital outcome of 138 consecutive patients who received abciximab as a "rescue" intervention for complicated coronary angioplasty in a high-risk clinical setting. "Rescue" treatment with abciximab was associated with clinical and angiographic success rates of 83% and 84%, respectively, whereas the risk of bleeding was higher in patients of low body weight.

Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H2O2. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24-96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 +/- 0.80 (T0) to 4.57 +/- 1.24 (peak), and decreased to 2.96 +/- 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was observed at 9.7 +/- 7.5 hours. The iron increased significantly from 0.67 +/- 0.34 (T0) to 1.15 +/- 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 +/- 0.28 UI/L at T48 (TO vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was observed at 9.4 +/- 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in association with thrombolytic therapy might be useful.

Background Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty. Methods and Results In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10 250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37±0.66 mm, 51.9±21.0%) did not differ from the corresponding values in the control group (1.48±0.59 mm, 48.8±18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%). Conclusions Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.

In low-flow, low-gradient aortic stenosis (LF/LG AS), the assessment of contractile reserve (CR) by dobutamine stress echocardiography (DSE) is recommended for risk stratification and treatment strategy. However, DSE may show limitations in cases of left ventricular dyssynchrony (LVD). The impact of LVD in LF/LG AS, and the feasibility of CRT in this setting have never been evaluated. We aimed to assess: (i) the proportion of LF/LG AS patients with LVD; (ii) the influence of LVD on CR at DSE; and (iii) the effects of CRT in these patients.Thirty consecutive patients with LF/LG AS underwent DSE with study of CR. The operative risk for aortic valve replacement (AVR) was assessed using the logistic EuroSCORE. Twenty-one of the 30 patients had LVD. They were significantly older, more symptomatic, had a higher EuroSCORE, and a lower prevalence of CR than those with a narrow QRS (47% vs. 100%, P = 0.009). A CRT pacemaker was implanted in 19 of the 21 patients with LVD. All 19 (except for one patient who died suddenly) experienced significant clinical and echocardiographic improvement. Fourteen CRT patients underwent subsequent AVR with a low event rate. Four CRT patients refused AVR; two of them worsened again 1-2 years post-CRT.LVD is common in LF/LG AS patients and may be a major mechanism of afterload mismatch, as well as a cause of underdetection of CR. CRT in this population is feasible and may be proposed as a bridge to surgery.

Background The interpretation of exercise stress testing for coronary artery disease detection is affected by the many differences in chosen variables and mathematical methods. We conducted a prospective trial to evaluate a global muscle fatigue parameter—the blood lactate level achieved at maximal exercise—as a method of distinguishing between diseased and nondiseased coronary status. Methods and Results We evaluated 236 consecutive male patients without previous myocardial infarction who had been referred for the diagnosis of coronary artery disease. None of the patients had cardiomyopathy, severe cardiac heart failure, or valvular heart disease. Blood lactate concentration at maximal exercise was measured as well as other classic variables. Correlations between variables and coronary status as assessed by coronary arteriography were described using receiver operating characteristic (ROC) curves and logistic regression analysis. The first four most powerful variables (lactate level, maximal power output, exercise duration, and percentage of maximal predicted heart rate), which are directly representative of the global functional capacity, showed values of 0.777, 0.775, 0.760, and 0.740, respectively, by ROC curve analysis. Mean±SD blood lactate level at peak exercise reached 7.68±2.70 mmol/L in the 153 diseased and 10.56±2.75 mmol/L in the 83 nondiseased patients ( P Conclusions Global muscle fatigue as assessed by lactate levels in the blood at maximal exercise appears to be a powerful distinguisher of diseased and nondiseased coronary status.

Objectives. This study was designed to assess the prognostic value of thallium-201 single-photon emission computed tomographic (thallium SPECT) perfusion imaging in patients evaluated for stable angina pectoris and to examine the relation, if any, between the preface and extent of myocardial defect and future fatal or nonfatal cardiovascular events (revascularization, secondary myocardial infarction). Background. Compared with planar scintigraphy, thallium SPECT enables better evaluation of the extent of mayocardial perfusion defect. However, its prognostic value has not yet been studied in a large population of patients. Methods. Between 1987 and 1989 we studied 3,193 patients. After exclusion of patients with unstable angina, myocardial infarction during the previous month or earlier revascularization, 1,926 patients were followed up for 33 ± 10 (mean ± SD) months after stress thallium SPECT imaging (performed after exercise in 1,121 patients or during dipyridamole infusion in 805 patients). Thallium SPECT imaging of the left ventricle was divided into six segments. Results. After normal thallium SPECT imaging (715 patients), the annual total and cardiovascular mortality rates were, respectively, 0.42%/year and 0.10%/year and were significantly higher after abnormal thallium SPECT imaging (respectively, 2.1%, relative risk 5, p = 0.012; 1.5%, relative risk 15, p Conclusions. In patients with stable angina, normal thallium SPECT imaging indicates a low risk patient, and the extent of myocardial defect is an important prognostic predictive factor.

International audience; The diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up.

Primary cardiac tumors are rare with an estimated incidence of 0.27% in pediatric autopsies. The most common type of cardiac tumor identified in infancy and childhood is rhabdomyoma. We report a case of prenatal diagnosis of multiples cardiac rhabdomyoma at 29 weeks of gestation. Full-term delivery was straightforward without hydrops and dysrhythmia. In the immediate post-natal period, cyanosis appeared, and echocardiography showed multiple cardiac rhabdomyoma and severe right ventricular outflow tract obstruction (Image 1). Aprostadil perfusion was necessary. Aorto-pulmonary anastomisis was performed with success. The diagnosis of cardiac rhabdomyoma was confirmed histologically and tuberous sclerosis by molecular genetic analysis. Renal echocardiography was normal and cerebral MRI was not perfomed. Fourteen months later, neurodevelopment was normal. Echocardiography confirmed regression of the cardiac tumors with disappearance of the severe right ventricular outflow tract obstruction. ECG monitoring was normal. Conclusion The natural history of most cardiac rhabdomyoma is favorable with tumors regressing (completely or partially). Surgical resection of the tumors is required for severe ventricular outflow tract obstruction. Aorto-pulmonary anastomosis, as in our case with severe right ventricular outflow tract obstruction, is an alternative treatment because regression and even complete resolution of more than 80% of the tumors occurs during infancy and early childhood. Download : Download full-size image

International audience; OBJECTIVES: To compare 2 cardiac magnetic resonance (CMR) techniques for the evaluation of the prognostic significance of microvascular damage after non ST-segment elevation myocardial infarction (NSTEMI). MATERIALS AND METHODS: CMR was performed at 3T in 61 patients within the week following their first NSTEMI. A first-pass saturation-recovery gradient-echo perfusion sequence was started during the infusion of contrast material to evaluate the extent of microvascular obstruction (MO) during the first 2 minutes after injection (MO(

International audience; Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.

International audience; Mutations in the FBN1 gene cause Marfan syndrome (MFS) and a wide range of overlapping phenotypes. The severe end of the spectrum is represented by neonatal MFS, the vast majority of probands carrying a mutation within exons 24-32. We previously showed that a mutation in exons 24-32 is predictive of a severe cardiovascular phenotype even in non-neonatal cases, and that mutations leading to premature truncation codons are under-represented in this region. To describe patients carrying a mutation in this so-called 'neonatal' region, we studied the clinical and molecular characteristics of 198 probands with a mutation in exons 24-32 from a series of 1013 probands with a FBN1 mutation (20%). When comparing patients with mutations leading to a premature termination codon (PTC) within exons 24-32 to patients with an in-frame mutation within the same region, a significantly higher probability of developing ectopia lentis and mitral insufficiency were found in the second group. Patients with a PTC within exons 24-32 rarely displayed a neonatal or severe MFS presentation. We also found a higher probability of neonatal presentations associated with exon 25 mutations, as well as a higher probability of cardiovascular manifestations. A high phenotypic heterogeneity could be described for recurrent mutations, ranging from neonatal to classical MFS phenotype. In conclusion, even if the exons 24-32 location appears as a major cause of the severity of the phenotype in patients with a mutation in this region, other factors such as the type of mutation or modifier genes might also be relevant.

In recent acute myocardial infarction, early reperfusion of the infarct-related artery by intracoronary or intravenous thrombolytic therapy induces a significant limitation of infarct size, provided reperfusion occurs within a time frame that myocardial salvage can still be expected. Limitation of infarct size reduces scar tissue formation, aneurysm formation, infarct zone expansion, left ventricular volume enlargement, and eventually results in higher left ventricular ejection fraction. Infarct size limitation and left ventricular function preservation occur with all thrombolytic agents currently in clinical use: streptokinase, alteplase and, more recently, anistreplase. When anistreplase is compared with conventional heparin therapy, a 31% reduction in infarct size is found (estimated from single photon emission computed tomography, or SPECT). This translates into a significant preservation of left ventricular ejection fraction as observed in anistreplase-treated patients compared with heparin-treated patients (0.53 +/- 0.13 vs 0.47 +/- 0.12, p less than 0.002). In comparative trials of 2 thrombolytic agents, anistreplase was demonstrated to be as efficient as alteplase on left ventricular ejection fraction preservation and infarct size limitation.