Nine-month clinical outcomes in patients with diabetes treated with polymer-free sirolimus-eluting stents and 6­month vs. 12­month dual-antiplatelet therapy (DAPT).

BACKGROUND: Diabetes mellitus is known to be associated with worse clinical outcomes in patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI) with drug-eluting stents (DES). Defining the optimal duration of dual antiplatelet therapy (DAPT) after DES implantation is still under debate. The objective of this subgroup analysis of the all-comers ISAR 2000 registry was to assess the safety and efficacy of a short DAPT (<6 month) versus a longer DAPT (>6 month) in patients with diabetes electively treated with the polymer-free sirolimus-coated ultrathin strut drug-eluting stent (PF-SES). METHODS: Patients who received the PF-SES were investigated in a multicenter all-comers observational study. The primary endpoint was the 9­month target lesion revascularization (TLR) rate, whereas secondary endpoints included the 9­month major adverse cardiac event (MACE) and procedural success rates. RESULTS: In all, 167 patients were treated with DAPT for ≤6 months (S-DAPT group) and 350 patients underwent DAPT treatment for 12 months (L-DAPT group). There was no significant difference in the overall MACE rate (4.6% vs. 3.1%, p = 0.441), the 9­month accumulated stent thrombosis rates (0.8% vs. 0.3%, p = 0.51), or the accumulated rate of bleeding complications (5.3% vs. 3.4%, p = 0.341). CONCLUSION: PF-SES are safe and effective in daily clinical routine with low rates of TLR and MACE in patients with diabetes and stable disease. Our data suggest that extending the duration of DAPT beyond 6 months does not improve MACE or TLR at 9 months in patients with stable CAD (ClinicalTrials.gov Identifier NCT02629575).

No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2-3 on admission.

AIMS: Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning (PostC) reduces infarct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at admission. Whether PostC might also be protective in patients with a TIMI 2-3 flow grade on admission (corresponding to a delayed application of the post-conditioning algorithm) remains undetermined. METHODS AND RESULTS: In this multi-centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion, followed (PostC group) or not (control group) by four cycles of (1 min inflation/1 min deflation) of the angioplasty balloon to trigger post-conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day 5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety-nine patients were prospectively enrolled. Baseline characteristics were comparable between control and PostC groups. Despite comparable size of area at risk (AAR) (38 ± 12 vs. 38 ± 13% of the LV circumference, respectively, P = 0.89) and similar time from onset to intervention (249 ± 148 vs. 263 ± 209 min, respectively, P = 0.93) in the two groups, PostC did not significantly reduce cardiac magnetic resonance infarct size (23 ± 17 and 21 ± 18 g in the treated vs. control group, respectively, P = 0.64). Similar results were found when using creatine kinase and troponin I release, even after adjustment for the size of the AAR. CONCLUSION: This study shows that infarct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow grade at admission. This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients. CLINICAL TRIAL NUMBER: NCT01483755.

MR delayed enhancement imaging findings in suspected acute myocarditis.

The purpose of the study was to prospectively assess the clinical impact of routinely performed delayed enhancement imaging in suspected acute myocarditis. A two-centre prospective study was performed in patients with suspected acute myocarditis. The protocol included horizontal long axis, vertical long axis and short axis ciné MR and delayed enhancement imaging after Gd-DTPA infusion (0.2 mmol/kg). Sixty consecutive patients were enrolled (aged 49.4 +/- 17.8 years). MRI demonstrated delayed enhancement sparing the subendocardicardial layer in 51.6% of patients, concordant with the diagnosis of acute myocarditis; 16.7% of patients exhibited delayed enhancement involving the subendocardial layer with irregular margins, concordant with the diagnosis of acute myocardial infarction; 31.7% of patients had delayed enhancement imaging that was considered normal. Routine imaging to identify delayed enhancement provided crucial information in suspected acute myocarditis by reinforcing the diagnosis in 51.6% of patients and correcting a misdiagnosed acute myocardial infarction in 16.7% of patients.

Continuous glucose monitoring as a tool to identify hyperglycaemia in non-diabetic patients with acute coronary syndromes.

AIM: To explore the occurrence and the distribution of glucose excursions > 7.8 mmol/l by continuous glucose monitoring (CGM) in non-diabetic patients admitted with acute coronary syndrome (ACS). METHODS: Twenty-one non-diabetic patients without baseline hyperglycaemia admitted for ACS wore a continuous glucose monitoring system (CGMS) for a median period of 45.6 h. Occurrence and 24-h distribution of time spent with blood glucose > 7.8 mmol/l (TS > 7.8) were retrospectively investigated. RESULTS: CGMS data disclosed time spent > 7.8 in 17 patients, whereas only seven of them showed at least one capillary blood glucose test value above the threshold for the same time period. Glucose excursions were detectable earlier from CGMS data. Hyperglycaemia was detected most frequently in the morning, more than 2 h after breakfast. CONCLUSIONS: CGM discloses early and frequent hyperglycaemia in non-diabetic patients with ACS. Intensive glucose monitoring during the morning time period is the most efficient in screening for hyperglycaemia and could be a valuable guide to initiating insulin therapy and to further investigate outcomes in ACS.

Trophic position and individual feeding habits as drivers of differential PCB bioaccumulation in fish populations.

Despite PCBs being banned since the 1980's, some European peri-alpine lakes, and consequently their fish populations, are still contaminated by these xenobiotics. We investigated the relative contribution of physiological and trophic factors that could be implicated in fish PCB bioaccumulation in Lake Bourget (France), one of the most contaminated in Europe, by collecting Arctic char (n = 55) and European whitefish (n = 89) from 2013 to 2016. Concentrations of 7 indicator PCBs were 9-168 ng.g w.w-1 in whitefish and 90-701 ng.g w.w-1 in Arctic char. The fish trophic positions calculated from δ 15N values were positively correlated with PCB concentrations (r2 = 0.45; p < 0.001). A biomagnification model relying on TP and lipid content of fish was then designed, and it confirmed this result. A Bayesian mixing model based on δ 13C and δ 15N values was used to estimate the relative contribution of preys in the fish diet, which explained a significant proportion of the biomagnification model residuals (i.e., 17%). Zooplankton consumption was negatively correlated with PCB concentrations, whereas consumption of chironomids enhanced the PCB burden in fish. Correction of the biomagnification model for individual diets of fish increased the correlation between the predicted and measured fish PCB contents (R2 = 0.71; p < 0.001), highlighting the importance of fish feeding habits in the bioaccumulation process.

[C-reactive protein (CRP) after revascularized STEMI: is CRP a prognostic factor?]. / Intérêt de la C-reactive protein (CRP) dans l'évaluation pronostique de l'infarctus du myocarde revascularisé

PURPOSE: During myocardial infarction (MI), numerous biomarkers increase, such as troponin (necrosis), BNP, and high sensibility C-reactive protein (hsCRP) (inflammation). The objectives of the study were to study kinetics of hsCRP after a revascularized MI, and correlations between hsCRP and clinical outcomes or biological markers, and prognostic value of CRP. PATIENTS AND METHODS: Fifty-two patients were admitted for STEMI (ST segment Elevation MI). Primary coronarography interventions (PCI) were performed for urgent reperfusion. Patients were included only in case of success (TIMI 3). Clinical examination was completed by a biological follow-up of BNP, troponin-I (before and after PCI, days 1, 2, 3, 6) and hsCRP (days 0, 1, 2, 3, 6). Clinical outcomes follow-up was performed during hospitalization, on the first month, and the sixth month. RESULTS: hsCRP increases during the first days (peak on day 3: 46.1mg/L), and decreases between the third and the seventh day. Clinical outcomes were correlated with CRP: door-to-balloon time, age, creatinin level on admission. During follow-up, there were clinical events in 13/49 (26%) of the patients. Among them, hsCRP on day 2 was higher (p < 0.0001), compared to other patients. Compared to other biological markers, hsCRP was correlated with BNP on days 2 and 3 (p = 0.008). CONCLUSION: hsCRP increases after revascularized STEMI, in accordance to the infarct size, in the first days. hsCRP is correlated with cardiovascular pronostic biomarkers. hsCRP could play an active role, and could be used as a pronostic biomarker after revascularized STEMI, which are usually considered as a low-risk population.

[Daily management of acute pericarditis: clinical and paraclinical outcomes, etiological diagnosis]. / Prise en charge au quotidien des péricardites aiguës: présentation clinique, paraclinique, diagnostic étiologique.

INTRODUCTION: Acute pericarditis is a frequent hospitalization cause. A prospective, bicentric study aimed at different goals: population description, aetiologies screening, and evaluation of the interest of a coordinated and combined management between cardiologists and internists. PATIENTS AND METHODS: Between May 2005 and September 2007, all patients admitted for acute pericarditis were prospectively enrolled. Physical examination, ECG, echocardiography, biological screening were performed. Patients were asked to consult both cardiologist and internist, one month later. RESULTS: Hundred and three patients were enrolled (mean age 43 years). Clinical outcome was classical in 60% of cases. ECG was typical in 59%. Troponin elevation was noted in 30% of patients. CRP was normal at diagnosis in 27% of patients, and increased significantly at first day (P=0.002). Possible cause was identified in 44 patients. In 26 patients (24.3%), precise diagnosis was performed: six cancers, one hemopathy, three connectivities, one EBV and one parvovirus B19 seroconversions, two untreated HIV patients, four inflammatory diseases, three endocrinology troubles, one oesophagitis, one dental sepsis, one amyloidosis, one acute pancreatitis, one declined dialysis indication. Eighteen de novo diagnoses (16.5%) were performed, out of them at least 12 benefited from specific management. CONCLUSION: Population of patients admitted for acute pericarditis are very heterogeneous. Our co-management between internists and cardiologists aims to diagnose earlier and easier curable diseases. Long-term follow-up remains of great interest, in order to diagnose later other disorders, which remained hidden, and to follow evolution of the population.

[Surgery of ventricular tachycardia in post-infarction left ventricular aneurysm]. / Chirurgie des tachycardies ventriculaires sur anévrismes ventriculaires gauches post-infarctus.

The treatment of post-infarction ventricular tachycardias with antiarrhythmic drug therapy, implantable automatic defibrillators, radiofrequency ablation, also includes different surgical procedures such as endocardial resection of the infarct scar, encircling endocardial ventriculotomy and endocardial cryoablation or thermoexclusion by laser. These procedures may be extensive or limited, guided or not by preoperative mapping. The aim of this review of the literature is to update our knowledge of these different surgical techniques and to define their indications.

Treatment of drug-eluting stents in-stent restenosis with paclitaxel-coated balloon angioplasty: Insights from the French "real-world" prospective GARO Registry.

BACKGROUND: Data about paclitaxel-eluting balloon (PCB) angioplasty to treat drug-eluting stents (DES) in-stent restenosis (ISR) were mainly collected in selected patient populations in the setting of randomized trials. The main goal of this prospective registry was to confirm the positive findings of these studies in an unselected population in clinical practice. METHODS: Consecutive patients with DES-ISR treated by PCB angioplasty were recruited in this prospective real-world registry. The primary endpoint was clinically driven target-lesion revascularization (TLR) at 9 months. Secondary endpoints included acute technical success, in-hospital outcomes, 9-month major adverse cardiac events (MACE) a composite of death, myocardial infarction (MI) and TLR and the occurrence of target vessel revascularization. RESULTS: A total of 206 patients (67.7 ± 10.2 years, 80.6% male, 41.3% diabetics) with 210 lesions were recruited. Unstable coronary artery disease was present in 55.3% of patients. The time from DES implantation to DES-ISR was 3.0 ± 2.4 years. Quantitative analyses revealed that patterns of treated DES-ISR were focal in 55.7% and diffuse in 44.3%. The reference diameter was 2.76 ± 0.64 mm. The 9-month follow-up rate was 90.8% (187/206). At 9 months, the TLR rate was 7.0% (13/187) whereas the rates for MACE, MI and cardiac death were 10.7% (20/187), 4.8% (9/187) and 2.1% (4/187) respectively. Results were consistent in patients with paclitaxel and non-paclitaxel-eluting stents (PES) ISR. CONCLUSION: This large prospective registry demonstrated acceptable rates of TLR and MACE at 9 months after treatment of DES-ISR by PCB angioplasty. PCB angioplasty was equally effective in patients with PES-ISR and non PES-ISR.

The antiangiogenic factor 16K PRL induces programmed cell death in endothelial cells by caspase activation.

We asked whether the antiangiogenic action of 16K human PRL (hPRL), in addition to blocking mitogen-induced vascular endothelial cell proliferation, involved activation of programmed cell death. Treatment with recombinant 16K hPRL increased DNA fragmentation in cultured bovine brain capillary endothelial (BBE) and human umbilical vein endothelial (HUVE) cells in a time- and dose-dependent fashion, independent of the serum concentration. The activation of apoptosis by 16K hPRL was specific for endothelial cells, and the activity of the peptide could be inhibited by heat denaturation, trypsin digestion, and immunoneutralization, but not by treatment with the endotoxin blocker, polymyxin-B. 16K hPRL-induced apoptosis was correlated with the rapid activation of caspases 1 and 3 and was blocked by pharmacological inhibition of caspase activity. Caspase activation was followed by inactivation of two caspase substrates, poly(ADP-ribose) polymerase (PARP) and the inhibitor of caspase-activated deoxyribonuclease (DNase) (ICAD). Furthermore, 16K hPRL increased the conversion of Bcl-X to its proapoptotic form, suggesting that the Bcl-2 protein family may also be involved in 16K hPRL-induced apoptosis. These findings support the hypothesis that the antiangiogenic action of 16K hPRL includes the activation of programmed cell death of vascular endothelial cells.

Ca2+ currents in compensated hypertrophy and heart failure.

Transmembrane voltage-gated Ca2+ channels play a central role in the development and control of heart contractility which is modulated by the concentration of free cytosolic calcium ions (Ca2+). Ca2+ channels are closed at the normal membrane resting potential of cardiac cells. During the fast upstroke of the action potential (AP), they are gated into an open state by membrane depolarisation and thereby transduce the electrical signal into a chemical signal. In addition to its contribution to the AP plateau, Ca2+ influx through L-type Ca2+ channels induces a release of Ca2+ ions from the sarcoplasmic reticulum (SR) which initiates contraction. Because of their central role in excitation-contraction (E-C) coupling, L-type Ca2+ channels are a key target to regulate inotropy [1]. The role of T-type Ca2+ channels is more obscure. In addition to a putative part in the rhythmic activity of the heart, they may be implicated at early stages of development and during pathology of contractile tissues [2]. Despite therapeutic advances improving exercise tolerance and survival, congestive heart failure (HF) remains a major problem in cardiovascular medicine. It is a highly lethal disease; half of the mortality being related to ventricular failure whereas sudden death of the other patients is unexpected [3]. Although HF has diverse aetiologies, common abnormalities include hypertrophy, contractile dysfunction and alteration of electrophysiological properties contributing to low cardiac output and sudden death. A significant prolongation of the AP duration with delayed repolarisation has been observed both during compensated hypertrophy (CH) and in end-stage HF caused by dilated cardiomyopathy (Fig. 1A) [4-8]. This lengthening can result from either an increase in inward currents or a decrease in outward currents or both. A reduction of K+ currents has been demonstrated [6,9]. Prolonged Na+/Ca2+ exchange current may also be involved [9]. In contrast, there is a large variability in the results concerning Ca2+ currents (ICa). The purpose of this paper is to review results obtained in various animal models of CH and HF with special emphasis on recent studies in human cells. We focus on: (i) the pathophysiological role of T-type Ca2+ channels, present in some animal models of hypertrophy; (ii) the density and properties of L-type Ca2+ channels and alteration of major physiological regulations of these channels by heart rate and beta-adrenergic receptor stimulation; and (iii) recent advances in the molecular biology of the L-type Ca2+ channel and future directions.

Facilitation of L-type calcium currents by diastolic depolarization in cardiac cells: impairment in heart failure.

OBJECTIVE: Decay kinetics of the voltage-gated L-type Ca(2+) current (I(CaL)) control the magnitude of Ca(2+) influx during the cardiac action potential. We investigated the influence of changes in diastolic membrane potential on I(CaL) decay kinetics in cardiac cells. METHODS: Cells were isolated enzymatically from rat ventricles, human right atrial appendages obtained during corrective heart surgery and left ventricles from end-stage failing hearts of transplant recipients. The whole-cell patch-clamp technique was used to evoke I(CaL) by a 100-ms depolarizing test pulse to -10 mV. Conditioning potentials between -80 and 0 mV were applied for 5 s prior to the test pulse. RESULTS: Depolarizing the cells between -80 and -50 mV prior to the test pulse slowed the early inactivation of I(CaL) both in rat ventricular and human atrial cells. This slowing resulted in a significant increase of Ca(2+) influx. This type of facilitation was not observed when the sarcoplasmic reticulum (SR) Ca(2+) content was depleted using ryanodine which reduced the rate of inactivation of I(CaL), or when Ba(2+) replaced Ca(2+) as the permeating ion. Facilitation was favored by intracellular cAMP-promoting agents that, in addition to increasing current peak amplitude, enhanced the fast Ca(2+)-dependent inactivation of I(CaL). Facilitation was impaired in atrial and ventricular human failing hearts. CONCLUSION: Decay kinetics of I(CaL) are regulated by the diastolic membrane potential in rat and human cardiomyocytes. This regulation, which associates slowing of I(CaL) inactivation with reduced SR Ca(2+) release and underlies facilitation of Ca(2+) channels activity, may have profound physiological relevance for catecholamines enhancement of Ca(2+) influx. It is impaired in failing hearts, possibly due to lowered SR Ca(2+) release.

Ischemic preconditioning attenuates ischemia/reperfusion-induced activation of caspases and subsequent cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo.

Recently, we have demonstrated that ischemic preconditioning (IP) both limits infarct size and decreases internucleosomal DNA fragmentation in rat hearts in vivo, and that there was a direct correlation between myocardial infarct size and DNA fragmentation even after IP. In this study, we examined the ability of IP to attenuate processing and activation of caspase-1 and caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP), after prolonged ischemia and reperfusion using the same in vivo animal model. Rats that underwent IP and controls (Ctrl) were subjected to 30 min of left coronary artery occlusion followed by 180 min of reperfusion. IP was accomplished by five 5-min cycles of ischemia, each followed by 5 min of reperfusion. The amount of soluble nucleosomes was measured by enzyme-linked immunosorbent assay. Cleavage of caspases-1 and -3, and of one of their substrates PARP, was analyzed by Western blotting. Nucleosomal DNA fragmentation was significantly reduced in ischemic left ventricular (LV) tissue obtained from IP compared with Ctrl animals. The proforms of caspases-1 and -3, and the active form of PARP were not cleaved in the nonischemic LV region of both IP and Ctrl hearts. In contrast, the proform of caspase-3 and the active form of PARP were cleaved in the ischemic LV region of Ctrl hearts, while processing of caspase-1 was increased. Cleavages of caspases-1 and -3, and inactivation of PARP were prevented by IP. The results of this study indicate that IP attenuates both internucleosomal DNA fragmentation and caspases processing, and suggest that the prevention of caspases activation by IP may be important steps in protecting the heart against ischemia/reperfusion injury in vivo.

Dietary coconut oil affects more lipoprotein lipase activity than the mitochondria oxidative capacities in muscles of preruminant calves.

The presence of coconut oil in a milk replacer stimulates the growth rate of calves, suggesting a better oxidation of fatty acid in muscles. Because dietary fatty acid composition influences carnitine palmitoyltransferase I (CPT I) activity in rat muscles, this study was designed to examine the effects of a milk replacer containing either tallow (TA) or coconut oil (CO) on fatty acid utilization and oxidation and on the characteristics of intermyofibrillar (IM) and subsarcolemmal (SS) mitochondria in the heart and skeletal muscles of preruminant calves. Feeding CO did not affect palmitate oxidation rate by whole homogenates, but induced higher palmitate oxidation by IM mitochondria (+37%, P < 0.05). CPT I activity did not significantly differ between the two groups of calves. Heart and longissimus thoracis muscle of calves fed CO had higher lipoprotein lipase activity (+27% and 58%, respectively; P < 0.05) but showed no differences in fatty acid binding protein content or activity of oxidative enzymes. Whatever the muscle and the diet, IM mitochondria had higher respiration rates and enzyme activities than those of SS mitochondria (P < 0.05). Furthermore, CPT I activity of the heart was 28-fold less sensitive to malonyl-coenzyme A inhibition in IM mitochondria than in SS mitochondria. In conclusion, dietary CO marginally affected the activity of the two mitochondrial populations and the oxidative activity of muscles in the preruminant calf. In addition, this study showed that differences between IM and SS mitochondria in the heart and muscles were higher in calves than in other species studied so far.

[Metabolic considerations in the treatment of coronary disease in diabetic patients]. / Approche métabolique du traitement de la maladie coronaire chez le patient diabétique.

Coronary heart disease represents the first cause of death in diabetic patients. The poor outcome of this ischemic disease is multifactorial. The abnormalities in myocardial energy metabolism encountered by the diabetic heart explain both the ischemic severity and the worsening of reperfusion lesions. The metabolic abnormalities in diabetic heart consist in both an impairment of glucose metabolism (diminished glucose uptake, reduced glycolysis, decreased glucose oxidation...) and an increase in fatty acid oxidation. During ischemia, glucose oxidation is reduced and anaerobic glycolysis becomes the main ATP substrate. Lactate accumulate in myocardial cells, inducing both a metabolic acidosis and an intracellular calcium overload. During reperfusion, intracellular homeostasis is restored very slowly in diabetic heart. Several therapeutic approaches are used to correct these metabolic disturbances. Glucose--insulin--potassium infusion in acute myocardial infarction leads to a significant reduction in the mortality relative risk in diabetic patients (ECLA and DIGAMI studies). The benefit is greater in diabetic patients who where non-insulin-treated prior to ischemia followed by myocardial reperfusion therapy. Others more direct pharmacological approaches improve glucose oxidation during myocardial ischaemia and myocardial reperfusion. The reference drug remains trimetazidine for which one of the fundamental mechanism of action was discovered recently. This specific metabolic, non haemodynamic approach, complete the gold-standard treatment of coronary heart disease in diabetic patients (e.g. aspirin, beta-blockers, ACE inhibitors and statins).

Contribution of mitochondria and peroxisomes to palmitate oxidation in rat and bovine tissues.

Total and peroxisomal palmitate oxidation capacities and mitochondrial enzyme activities were compared in tissues from growing rats, preruminant calves and 15-month-old bulls. Total palmitate oxidation rates were 1.9-5.2-fold higher in rat than in bovine tissues and 1.7-fold higher in the heart and muscles from calves than from growing bulls. The peroxisomal contribution to palmitate oxidation was similar between rats and bovines (i.e. calves and bulls) in liver (35-51%), heart (26%) but not in muscles (14 +/- 3% in rats vs 33 +/- 4.5% in bovines, P < 0.05). Mitochondrial enzyme activities were 1.8-4.8-fold higher in rat than in bovine tissues but the citrate synthase to cytochrome-c oxidase ratio was the highest in the liver (17-38), intermediate in the heart and muscles from calves and rats (6-10) and the lowest in heart and muscles from bulls (2-3, P < 0.05). In all tissues and animal groups, palmitate oxidation rates were similar per unit cytochrome-c oxidase activity, but not always per unit citrate synthase activity. Therefore, differences in mitochondrial contents (as between rats and bovines) or in mitochondrial characteristics (as between liver and muscles) relate to the differences in palmitate oxidation capacity.

[Endoluminal occlusion, using a catheter, of patent ductus arteriosus in an adult]. / Occlusion par voie endoluminale d'un canal artériel chez l'adulte.

The risk of surgical closure of the ductus arteriosus in the adult is greater than in children. The ductus arteriosus can now be occluded by venous catheterisation using a Rashkind umbrella. This procedure vas performed in a 63 year old woman. The diagnosis was confirmed and the anatomy of the lesion defined by catheterisation with aortography. The patent ductus was then occluded with a balloon catheter to assess the reversibility of the pulmonary hypertension. A 17 mm Rashkind umbrella was then used to completely occlude the ductus. The advantages of the method over surgical closure are: absence of morbidity related to thoracotomy, to general anaesthesia, to blood transfusion and the reduction of hospital stay to 3 days.

[Electrophysiologic and anatomic atrial remodeling: an atrial rhythmic cardiomyopathy]. / Remodelage électrophysiologique et anatomique de l'oreillette: une cardiomyopathie rythmique auriculaire.

In 1995, Wijffels and Alessie, using a curious goat model of atrial fibrillation, introduced the concept of atrial remodelling. The classical atrial substrate (anatomopathological-dilatation and hypokinesis-, and electrophysiological-short refractory periods and decreased conduction-), appeared not only to be one of the causes of atrial fibrillation but also the consequence of atrial fibrillation itself, the mechanism being a vicious circle. In addition to ventricular rhythmic cardiomyopathy, responsible for cardiac failure, the concept of atrial rhythmic cardiomyopathy with the same mechanical and electrophysiological consequences, has developed. These changes, characterised mainly by calcium overload associated with cellular hibernation and differentiation, have not been totally elucidated but have already renewed the physiopathology of atrial fibrillation.

[Electrocardiographic alternans]. / Alternance en électrocardiographie.

A simple ECG curiosity or a precursor of serious arrhythmia, associated with pericardial effusion or a sign of inotropic alteration, the phenomenon of electrical alternans has intrigued clinicians and research workers in its multiple facets, mechanical and electrical, consequences on PR interval, QRS complex or ventricular repolarisation. As a consequence, the causal mechanisms are very different, but these last few years, a predominant role of calcium flux, especially intracellular, has been demonstrated. Recently, clinical interest in this phenomenon has been revived with the demonstration of micro-alternans of repolarisation, apparently a new marker for the risk of sudden death.

[Mechanisms of action of antiarrhythmics in cardioversion of atrial fibrillation and atrial flutter]. / Mécanismes d'action des antiarythmiques dans la cardioversion de la fibrillation et du flutter auriculaires.

The mechanisms of action of antiarrhythmic drugs at atrial level are multiple. Antiarrhythmics may act at three levels in the prevention of paroxysmal atrial fibrillation: on the arrhythmogenic atrial substrate, the initiating extrasystoles including those of the pulmonary veins, and in the modulation of the autonomic nervous system. However, there are many modes of initiation which are not well understood so that the preventive role of the antiarrhythmic drugs remains imprecise. Cardioversion of persistent atrial fibrillation has been better analysed in healthy hearts: Class I antiarrhythmics in particular, despite their depressive effects on the conduction which are potentially arrhythmogenic, are beneficial by decreasing the number of reentry circuits, prolonging the atrial refractory period on short cycles and, paradoxically, by increasing the period of excitability in AF. All have a preferential action on anisotropic conduction, especially at the pivotal point of reentry. On the other hand, their role in electrophysiological remodelling in the prevention of immediate recurrences and in pathological atria, remains poorly understood. As for atrial flutter, despite many clinical and experimental studies with antiarrhythmics, the current predominant role of radiofrequency ablation greatly limits the value of these pharmacological studies.