Jean-René Lusson

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open‐label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long‐term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet‐only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet‐only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet‐only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289.)

Trend towards increased arterial stiffness or intima–media thickness in ankylosing spondylitis patients without clinically evident cardiovascular disease

OBJECTIVES Increased incidence of cardiovascular disease (CVD) has been observed in AS. The reasons of this increase are not fully understood (greater prevalence of traditional cardiovascular risks, consequences of treatment (NSAID) or biological inflammation). The objectives of this study are to assess intima-media thickness (IMT) and arterial stiffness (i.e augmentation index AIx), markers of sub-clinical atherosclerosis in AS patients and to examine the effects of TNF-alpha inhibitors on arterial stiffness in active AS patients. METHODS Sixty AS patients were enrolled with 60 healthy controls. Their BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) scores, ESR and CRP levels were recorded. Subclinical atherosclerosis was assessed by measurement of AIx by pulse wave analysis and IMT by carotid echography. RESULTS We found significantly increased IMT in the AS group compared with healthy controls. After adjustment for confounding factors, an underlying trend towards increased IMT was still present (P = 0.06). No difference was found in arterial stiffness between the two groups. AS patients, treated or not with anti-TNF-alpha at baseline, had significantly increased IMT and AIx or a trend towards increase. IMT was positively correlated with tobacco use, WHR and blood pressure but not correlated with CRP level. Despite improvement in markers of disease activity, arterial stiffness was unchanged after 14 weeks of treatment with TNF antagonists. CONCLUSION This study shows a trend towards increased subclinical atherosclerosis in AS patients. TNF-alpha blockade does not seem to improve arterial stiffness in AS patients, but our results lack statistical power.

Management of Spontaneous Coronary Artery Dissection: Review of the Literature and Discussion Based on a Series of 12 Young Women with Acute Coronary Syndrome

Spontaneous coronary artery dissection (SCAD) is a rare pathology, principally affecting young women free of atheroma risk factors. Its physiopathology remains little understood, and the prognosis for such acute coronary syndromes is poor, as they occur suddenly. Management is often difficult, and no guidelines exist. The present single-center retrospective study concerns 12 cases of SCAD occurring between 2001 and 2008 in female patients under the age of 60. Eleven patients survived, with a favorable long-term evolution. Only 2 had conservative medical therapy, the other 10 undergoing percutaneous coronary intervention (2 procedures involving a coronary artery bypass graft). On the basis of this series and data from the literature, we suggest a strategy to improve the often dire prognosis of SCAD. Emergency angiography to confirm diagnosis is essential. Treatment should be guided by the extent of the lesions, the myocardial ischemia and the hemodynamic status. Conservative medical therapy is a reasonable approach in the case of distal dissection or conserved coronary flow. Percutaneous coronary intervention is feasible in the acute phase to restore coronary perfusion and hemodynamic stability. Surgery – emergency bypass or assisted circulation – should be restricted to cases where percutaneous coronary intervention has failed or is impossible.

Characteristics and long-term outcome of non-immune isolated atrioventricular block diagnosed in utero or early childhood: a multicentre study

AIMS The natural history of congenital or childhood non-immune, isolated atrioventricular (AV) block is poorly defined. METHODS AND RESULTS We retrospectively studied 141 children with isolated, non-immune AV block diagnosed in utero, or up to 15 years of age, at 13 French medical centres, between 1980 and 2009. Patients with structural heart disease or maternal antibodies were excluded. Atrioventricular block was asymptomatic in 119 (84.4%) and complete in 100 (70.9%) patients. There was progression to complete AV block in 29/41 (70.7%) patients with incomplete AV block over 2.8 ± 3.4 years (1-155 months), but all patients with incomplete AV block may not have been included in the study. Narrow QRS complex was present in 18 of 26 patients (69.2%) with congenital, and 106 of 115 (92.2%) with childhood AV block. Pacemakers were implanted in 112 children (79.4%), during the first year of life in 18 (16.1%) and before 10 years of age in 90 (80.4%). The mean interval between diagnosis of AV block and pacemaker implants was 2.6 ± 3.9 years (0-300 months). The pacing indication was prophylactic in 70 children (62.5%). During a mean follow-up of 11.6 ± 6.7 years (1-32 years), no patient died or developed dilated cardiomyopathy (DCM). The long-term follow-up was uncomplicated in 127 children (90.1%). CONCLUSION In this large multicentre study, the long-term outcome of congenital or childhood non-immune, isolated AV block was favourable, regardless of the patients age at the time of diagnosis. No patient died or developed DCM, and pacemaker-related complications were few.

Comparison of INR stability between self-monitoring and standard laboratory method: Preliminary results of a prospective study in 67 mechanical heart valve patients

INTRODUCTION Thromboembolic accidents and haemorrhage are the main complications observed during long-term follow-up of mechanical heart valve patients. Several suggestions for improving anticoagulation quality have been made, including international normalised ratio (INR) self-monitoring. OBJECTIVES We report the preliminary results of a single-centre, open, randomised study (scheduled population of 200 patients), which compares monthly laboratory monitoring (group A) versus weekly self-monitoring of INR (group B). The primary aim is INR stability improvement within the target range, and the secondary aim is adverse events reduction. PATIENTS AND METHODS Between May 2004 and June 2005, 67 patients with an average age of 56.6 years (+/-9.6), were enrolled in the study (group A: 34 patients, group B: 33 patients). The mean follow-up was 47 weeks (+/-11.5). The two groups differed only in the sex ratio (44.1 and 21.2% of women in groups A and B respectively, p=0.0459). Mechanical heart valves were aortic in 73% of patients, mitral in 13.5%, and multiple in 13.5%. Sixty-five patients (97%) were treated with fluindione, the others with acenocoumarol. The intraclass correlation coefficient between the self- and laboratory-monitored INR was 0.75. RESULTS The time spent in the INR target range (group A: 53+/-19%, group B: 57+/--19%, p=0.45) and the time spent in the INR therapeutic range, between 2 and 4.5, (group A: 86+/-14%, group B: 91+/-7%, p=0.07) are longer in group B, but not significantly so. For patients outside the range, the absolute mean deviation of INR from the target or therapeutic range (range standardized between 0 and 100) is lower for the self-monitoring group (41.1+/-39.3 and 11.27+/-11.2) than for the control group (62.4+/-72.6 and 39.2+/-52.8). This difference is significant (p=0.0004 and p=0.0005). Eighteen adverse events were reported: 17 haemorrhages, 13 in group A (9 mild, 4 serious) and four in group B (all mild), and one sudden death in group B, two days after the patients discharge. No thromboembolic events were reported. Six patients (8.8 %), 3 in each group, dropped out of the study. CONCLUSION This first study evaluating INR self-monitoring in France shows that this method leads to better stability of the INR within the target range. On the basis of these preliminary data, this appears to be related to a decrease in serious haemorrhages (11.8% serious haemorrhage cases in group A versus 0% in group B, p=0.06, NS).

Significant persistent ductus arteriosus in infants less or equal to 6 kg: percutaneous closure or surgery?

BACKGROUND Percutaneous closure of large persistent ductus arteriosus using the Amplatzer duct occluder is an alternative to surgery. However, this device is not recommended in infants weighing less than 6 kg. AIM To evaluate the safety and effectiveness of this procedure in low-body-weight infants. METHODS We reviewed retrospectively data for infants weighing less or equal to 6 kg who underwent percutaneous closure of significant persistent ductus arteriosus using the Amplatzer duct occluder in France between 1998 and 2007. RESULTS Data for 58 patients (mean weight: 5 kg, range: 3.4-6; mean age: 5.5 months, range: 2.1-15.3) were reviewed. Mean angiographic persistent ductus arteriosus minimal diameter was 3.7 mm (range: 1-7.5). Implantation of the Amplatzer duct occluder was successful in 89.7% of cases. In six (10.3%) patients, the device was not implanted because it would have led to significant aortic obstruction. One procedure-related death occurred in a 4 kg infant (1.7%). Major and minor complications occurred in 6.9 and 31.0% of patients, respectively. Persistent ductus arteriosus diameter greater than 3.7 mm, type C (tubular shape) and diameter/patient weight ratio greater than 0.91 were significantly associated with an unsuccessful procedure and/or major complications. During a median 10-month follow-up, no late device embolization occurred. CONCLUSIONS Although percutaneous closure of significant persistent ductus arteriosus with the Amplatzer duct occluder is effective in low-body-weight infants, the level and severity of complications indicate surgery as first-line treatment, at least until further studies are done to assess the safety and effectiveness of the new Amplatzer duct occluder II in low-body-weight infants.

No significant change in arterial stiffness in RA after 6 months and 1 year of rituximab treatment

OBJECTIVE The excess cardiac risk, found in RA has been attributed to biological inflammation. Effective control of inflammation may be of benefit in reducing cardiovascular risk in RA patients. The aim of this study is to investigate the effects of 24 and 52 weeks of rituximab treatment on arterial stiffness and cardiovascular risk factors. METHODS Arterial stiffness was measured by augmentation index (AIx) and pulse wave velocity (PWV), and other cardiovascular risk factors (lipid profile, blood pressure) were collected in active RA patients. RESULTS Thirty-three patients, of whom 29 were females, with a mean age of 60.9 (12.0) years were included. Thirty patients had positive RFs, 27 had positive anti-CCP antibody and 93.9% (n = 31) were erosive. Nineteen patients were non-responders to anti-TNF-α treatments. After rituximab treatment, no change was observed in arterial stiffness, neither after 6 nor after 12 months [PWV 8.1 (3.1) m/s at baseline, 8.1 (2.8) at 6 months, 8.0 (2.7) at 1 year, P = 0.924; and AIx 30.4 (8.2)% at baseline, 28.6 (7.6) at 6 months, 29.4 (6.7) at 1 year, P = 0.216]. Total and low-density lipoprotein cholesterol levels increased significantly but high-density lipoprotein (HDL) and triglyceride levels were unchanged. The atherogenic index (total cholesterol/HDL cholesterol) was increased, but not to a level of significance. No change was found in other cardiovascular risk factors. DAS-28 according to levels of ESR and CRP and biologic inflammation were significantly improved. CONCLUSION Arterial stiffness did not improve after 6 and 12 months of rituximab therapy. The treatment had a beneficial effect on biologic inflammation and disease activity, but caused a pro-atherogenic lipid profile.

Parental Electrocardiographic Screening Identifies a High Degree of Inheritance for Congenital and Childhood Nonimmune Isolated Atrioventricular Block

Background— The origin of congenital or childhood nonimmune isolated atrioventricular (AV) block remains unknown. We hypothesized that this conduction abnormality in the young may be a heritable disease. Methods and Results— A multicenter retrospective study (13 French referral centers, from 1980–2009) included 141 children with AV block diagnosed in utero, at birth, or before 15 years of age without structural heart abnormalities and without maternal antibodies. Parents and matched control subjects were investigated for family history and for ECG screening. In parents, a family history of sudden death or progressive cardiac conduction defect was found in 1.4% and 11.1%, respectively. Screening ECGs from 130 parents (mean age 42.0±6.8 years, 57 couples) were compared with those of 130 matched healthy control subjects. All parents were asymptomatic and in sinus rhythm, except for 1 with undetected complete AV block. Conduction abnormalities were more frequent in parents than in control subjects, found in 50.8% versus 4.6%, respectively (P<0.001). A long PR interval was found in 18.5% of the parents but never in control subjects (P<0.0001). Complete or incomplete right bundle-branch block was observed in 39.2% of the parents and 1.5% of the control subjects (P<0.0001). Complete or incomplete left bundle-branch block was found in 15.4% of the parents and 3.1% of the control subjects (P<0.0006). Estimated heritability for isolated conduction disturbances was 91% (95% confidence interval, 80%–100%). SCN5A mutation screening identified 2 mutations in 2 patients among 97 children. Conclusions— ECG screening in parents of children affected by idiopathic AV block revealed a high prevalence of conduction abnormalities. These results support the hypothesis of an inheritable trait in congenital and childhood nonimmune isolated AV block.

A single pathophysiological pathway in Takotsubo cardiomyopathy: Catecholaminergic stress

BACKGROUND Takotsubo cardiomyopathy (TTC) continues to be under-diagnosed, due to its varying presentation, with potentially serious consequences if treatment is delayed. AIMS To demonstrate the consistent involvement of catecholaminergic stress in TTC, regardless of the trigger. METHODS Between 01 July 2009 and 31 August 2013, patients managed in our centre for thoracic pain syndrome, with or without troponin release, were followed up prospectively. TTC was diagnosed from the apical ballooning seen on left ventricular imaging (angiography or transthoracic echocardiography) in the absence of a significant coronary artery lesion. Triggers (emotional trauma, surgical stress and β2-mimetic intoxication) were recorded; catecholamine-secreting tumours were screened for with a urinary methoxylate-derivative assay. RESULTS TTC was diagnosed in 40 out of 2754 (1.5%) patients with thoracic pain syndrome, with or without troponin release. Triggers were emotional trauma (n=29, 72.5%), surgical stress (n=5, 12.5%), adrenergic intoxication (n=3, 7.5%) and catecholaminergic tumour (n=3, 7.5%). Mean left ventricular ejection fraction at admission was 38.0 ± 15.7%. Eight (20%) patients initially showed cardiogenic shock. In-hospital mortality was 7.5%, with no deaths from cardiogenic causes. Thirty-five (94.6%) of the survivors had recovered a normal left ventricular ejection fraction (> 55%) by discharge. CONCLUSION Whatever the trigger, the common denominator in TTC is catecholaminergic stress. Classically suggested after emotional trauma, TTC may also be induced by surgical stress or endogenous or iatrogenic β2-mimetic intoxication. The various contexts all have a similarly excellent cardiovascular prognosis if treated early.

Acute and Chronic Pheochromocytoma-Induced Cardiomyopathies: Different Prognoses?: A Systematic Analytical Review.

AbstractPheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe cardiomyopathies.We performed a computer-assisted systematic search of the electronic Medline databases using the MESH terms “myocarditis,” “myocardial infarction,” “Takotsubo,” “stress cardiomyopathy,” “cardiogenic shock”, or “dilated cardiomyopathy,” and “pheochromocytoma” or “paraganglioma” from 1961 to August 2012. All detailed case reports of cardiomyopathy due to a PPG, without coronary stenosis, and revealed by acute symptoms were included and analyzed.A total of 145 cases reports were collected (49 Takotsubo Cardiomyopathies [TTC] and 96 other Catecholamine Cardiomyopathies [CC]). At initial presentation, prevalence of high blood pressure (87.7%), chest pain (49.0%), headaches (47.6%), palpitations (46.9%), sweating (39.3%), and shock (51.0%) were comparable between CC and TTC. Acute pulmonary edema (58.3% vs 38.8%, P = 0.03) was more frequent in CC. There was no difference in proportion of patients with severe left ventricular systolic dysfunction (LV Ejection Fraction [LVEF] < 30%) at initial presentation between both groups (P = 0.15). LVEF recovery before (64.9% vs 40.8%, P = 0.005) and after surgical resection (97.7% vs73.3%, P = 0.001) was higher in the TTC group. Death occurred in 11 cases (7.6%). In multivariate analysis, only TTC was associated with a better LV recovery (0.15 [0.03–0.67], P = 0.03).Pheochromocytoma and paraganglioma can lead to different cardiomyopathies with the same brutal and life-threatening initial clinical presentation but with a different recovery rate. Diagnosis of unexplained dilated cardiomyopathy or TTC should lead clinicians to a specific search for PPG.