P Cosnay

University of Tours, Tours, Centre, France

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Publications (182)448.59 Total impact


  • No preview · Article · Dec 2014

  • No preview · Article · Dec 2014 · La Presse Médicale
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    ABSTRACT: Background Arrhythmogenic right ventricular Cardiomyopathy/Dysplasia (ARVC/D) is a genetic disease predominantly caused by desmosomal gene mutations that account for only ~50% of cases. RYR2 gene mutations usually cause Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) but have been associated with peculiar phenotype named ARVC2. Objectives We aim to determine the prevalence and phenotype associated with RYR2 mutations in a large ARVC/D population. Methods We analyzed the whole RYR2 coding sequence by Sanger sequencing in 64 ARVC/D probands without desmosomal gene mutations. Results We have identified six rare missense variants p.P1583S, p.A2213S, p.G2367R, p.Y2932H, p.V3219M and p.L4670V. It corresponds to a prevalence of 9% of rare RYR2 variants in ARVC/D population (6 probands/64) that is significantly higher than the estimated rate of rare RYR2 variants in control (Fisher test, p=0.03). Phenotypes associated with RYR2 variants were similar to desmosome-related ARVC/D, associating typical ECG abnormalities at rest, frequent monomorphic ventricular tachycardia, right ventricular dilatation, wall motion abnormalities and fibro-fatty replacement when histopathological examination was available. Conclusion In this first systematic screening of the whole coding region of the RYR2 gene in a large ARVC/D cohort without mutation in desmosomal genes, we show that putative RYR2 mutations are frequent (9% of ARVC/D probands) and are associated with a conventional phenotype of ARVC/D, in contrast with previous findings. The results support the role of RYR2 gene in conventional ARVC/D.
    Preview · Article · Nov 2014 · Heart Rhythm
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    ABSTRACT: Amyloidosis is a severe systemic disease. Cardiac involvement may occur in the three main types of amyloidosis (acquired monoclonal light-chain, hereditary transthyretin and senile amyloidosis) and has a major impact on prognosis. Imaging the heart to characterize and detect early cardiac involvement is one of the major aims in the assessment of this disease. Electrocardiography and transthoracic echocardiography are important diagnostic and prognostic tools in patients with cardiac involvement. Cardiac magnetic resonance imaging better characterizes myocardial involvement, functional abnormalities and amyloid deposition due to its high spatial resolution. Nuclear imaging has a role in the diagnosis of transthyretin amyloid cardiomyopathy. Cardiac biomarkers are now used for risk stratification and staging of patients with light-chain systemic amyloidosis. Different types of cardiac complications may occur, including diastolic followed by systolic heart failure, atrial and/or ventricular arrhythmias, conduction disturbances, embolic events and sometimes sudden death. Senile amyloid and hereditary transthyretin amyloid cardiomyopathy have better prognoses than light-chain amyloidosis. Cardiac treatment of heart failure is usually ineffective and is often poorly tolerated because of its hypotensive and bradycardiac effects. The three main types of amyloid disease, despite their similar cardiac appearance, have specific new aetiological treatments that may change the prognosis of this disease. Cardiologists should be aware of this disease to allow early treatment.
    Full-text · Article · Sep 2013 · Archives of cardiovascular diseases
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    ABSTRACT: Atrioventricular nodal radiofrequency ablation (AVNA) may be recommended for rate control in some patients with atrial fibrillation (AF). However, outcome after AVNA has not been assessed over the long term although it results in pacemaker dependency. Short-term follow-up may not capture the long-term risks of an irreversible procedure. This study investigated the outcome after AVNA, expected to achieve effective rate control and possibly to improve prognosis in AF. Methods: We examined the clinical course of 8,962 consecutive patients with AF seen in the cardiology department of a four-hospital institution between 2000 and 2010. The outcome in 218 patients with AVNA (group 1) was compared with those in other patients (group 2, n=8744). Results: Patients in the 2 groups had same age (71±11 vs 71±15, p=0.60). However, patients in group 1 were sicker than those in group 2 with more frequent heart failure (79% vs 54%, p<0.0001), renal failure (20% vs 9%, p<0.0001), permanent AF (57% vs 39%, p<0.0001), lower left ventricular ejection fraction (42±17 vs 47±16%, p=0.0009), more frequent cardiac resynchronisation therapy (23% vs 2%, p<0.0001) and higher CHA2DS2VASc score (3.5±1.6 vs 3.2±1.8, p=0.02). Death was recorded in 2,023/8,962 patients during follow-up of 934±1134 days. In univariate analysis, patients in group 1 did not have a higher risk of all-cause death than those in group 2 (hazard ratios [HR] = 0.82, 95% confidence interval [CI], 0.63-1.07; p=0.14). Using Cox proportional-hazards model and adjustment on 25 potential confounders, AVNA was associated with a lower risk of mortality (HR=0.59, 95% CI, 0.39-0.88; p=0.01) with younger age (HR=0.36 for age<65, p<0.0001), higher LVEF (HR=1.01 per 1% decrease, p<0.0001), non permanent AF (HR=0.64, p<0.0001), absence of diabetes (HR=0.76, p=0.02), use of beta blockers (HR=0.80, p=0.03), oral anticoagulation (HR=0.56, p<0.0001) and lack of diuretic use (HR=0.72, p=0.004). Conclusions: AVNA needed for rate control in AF (with or without cardiac resynchronisation therapy) was independently associated with a lower mortality in the systematic analysis of a large cohort of AF patients with one of the longest follow-up to date.
    Preview · Article · Aug 2013 · European Heart Journal
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    ABSTRACT: Stroke is a debilitating condition with an increased risk in patients with atrial fibrillation. Data from clinical trials suggest that both rate and rhythm control are acceptable approaches with comparable rates of mortality in the short term, but it is unclear whether stroke rates differ between patients who filled prescriptions for rhythm or rate control therapy. A recent observational analysis has found lower rates of stroke with rhythm control. Methods: We examined the clinical course of 6,068 consecutive patients with AF with a diagnosis of atrial fibrillation seen in a cardiology department during the period 2000 to 2010 with the use of linked administrative data from hospital discharge and drug prescription. We compared rates of stroke or thromboembolic events (TE) among patients using rhythm (class Ia, Ic, and III antiarrhythmic agents), versus rate control (Beta-blockers, calcium channel blockers, and digoxin) treatment strategies (either current or new users). The cohort consisted of 2,374/6,068 patients who filled a prescription for rhythm control therapy (with or without rate control therapy, n=2182) and/or had AF radiofrequency ablation (n=260), and 3,694/6,068 patients who filled a prescription for rate control therapy. Results: In patients on rhythm control therapy, CHA2DS2VASc score was higher than on rate control therapy (3.2±1.8 versus 3.1±1.8, p=0.03) and treatment with any antithrombotic drug was more frequent (90% in rhythm control versus 78% in rate control group, p<0.0001). Mean follow-up was 2.5 years (maximum 10.0 years) and 477 stroke/TE were recorded. Crude stroke/TE incidence rate was similar in patients treated with rhythm control in comparison with rate control therapy (2.97 versus 3.53, per 100 person-years, p=0.12). This finding was not different in patients in the moderate- and high-risk groups for stroke according to the CHA2DS2VASc risk score. In multivariable Cox regression analysis, rhythm control therapy was not associated with a significantly lower risk of stroke/TE after adjustment for age, CHA2DS2VASc and HAS BLED scores, use of cardiovascular medications and other confounders in comparison with rate control therapy (adjusted hazard ratio, 0.88; 95% confidence interval, 0.72-1.09). Conclusions: In comparison with rate control therapy, the use of rhythm control therapy was not associated with lower rates of stroke/TE among patients with atrial fibrillation. Antithrombotic strategy should not be influenced by rhythm strategy in atrial fibrillation.
    Preview · Article · Aug 2013 · European Heart Journal
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    ABSTRACT: Background Ventricular premature beats are common in patients with mitral valve prolapse (MVP). The purpose of this study was to determine whether symptomatic patients with MVP had certain functional characteristics and if ventricular arrhythmia (VA) could be explained by functional extravalvular abnormalities. Single photon emission computed tomography equilibrium radionuclide angiography with Fourier phase analysis was preferred to the planar radionuclide method. Only patients without significant mitral regurgitation were studied. Methods and Results A total of 23 symptomatic patients with MVP (13 men, 10 women, mean age, 47 ± 14 years) without mitral regurgitation underwent single photon emission computed tomography equilibrium radionuclide angiography. Symptoms were present in 20 patients, and VA was present in 14 patients. Ejection fraction, regional wall motion, and Fourier phase analysis were examined in both ventricles and compared with results for normal subjects. Ventricular abnormalities were observed in 20 (87%) patients: decreased left ventricular and right ventricular ejection fractions, increased standard deviations of the mean phase and focal wall motion, and/or delayed phase abnormalities. Abnormalities were less frequent but more marked in the right ventricular free wall, the infundibulum, or the septum compared with left ventricular delayed abnormalities, which were more frequent but limited. In 12 of 14 patients with VA, phase-delayed areas were observed in the ventricle where the origin of ventricular premature beats was suspected on the basis of their electrocardiographic morphologic features. A relation was found between late potentials and delayed-phase areas (right ventricle or septum) and left bundle branch block morphologic features of VA. Conclusions Symptomatic patients with MVP frequently have ventricular dysfunction in 1 or both ventricles, sometimes limited but more marked in the presence of severe VA even without significant mitral regurgitation, suggesting structural modification. The use of a sensitive, accurate, and 3-dimensional method such as single photon emission computed tomography equilibrium radionuclide angiography may be of interest for a noninvasive investigation, especially in young symptomatic patients with MVP and VA.
    No preview · Article · Apr 2012 · Journal of Nuclear Cardiology
  • Laurent Fauchier · Dominique Babuty · Pierre Cosnay

    No preview · Article · Apr 2012 · Journal of Neurology
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    ABSTRACT: Implantable cardioverter defibrillators (ICDs) are efficient in reducing mortality in patients with left ventricular systolic dysfunction. High-rate cut-off programming may be effective in reducing appropriate and inappropriate therapies, but as the long-term consequences on morbidity and mortality remain unclear, it is underutilized. We prospectively studied 365 consecutive patients (mean age 60 ± 10 years), with ischaemic (63%) or non-ischaemic cardiomyopathy and left ventricular dysfunction (mean ejection fraction 25 ± 7%), who were implanted with an ICD in primary prevention of sudden cardiac death (41% single chamber, 31% dual chamber, and 28% biventricular). All devices were programmed with a shock-only zone over 220 beats per minute (b.p.m.) and a monitoring zone between 170 and 220 b.p.m. During a median follow-up of 40 months, 41 patients received appropriate shocks (11.2%) and 24 inappropriate shocks (6.6%). Then, 306 patients never experienced any ICD shock (84%). Inappropriate discharges were related to supraventricular tachyarrhythmia in 10 patients, and noise/oversensing in 14 patients. Ventricular tachycardia episodes, sustained or not, were recorded in the monitoring zone in 43 patients (11.8%). Seven of these patients were symptomatic (1.9%), without lethal consequence. Sixty-two patients (17%) died: 35 from end-stage heart failure, 1 from unexplained sudden death, and 26 from a documented non-cardiac cause. High-rate cut-off (220 b.p.m.) shock-only ICD programming, in primary prevention patients with reduced left ventricular ejection fraction, appeared to be safe during a long-term follow-up. It also resulted in a very low rate of discharges, which are known to be deleterious in this population.
    Full-text · Article · Mar 2012 · Europace
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    Full-text · Article · Jan 2011 · Archives of Cardiovascular Diseases Supplements
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    L Fauchier · N Zannad · N Clementy · B Pierre · P Cosnay · D Babuty
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    ABSTRACT: In atrial fibrillation (AF), the absence of a clear benefit of a rhythm-control strategy over a rate-control strategy seen in recent trials may be due to the fact that many of the usual antiarrhythmic strategy have significant weaknesses. Besides research efforts to improve the efficacy and safety of conventional antiarrhythmic agents, therapies directed 'upstream'of the electrical aspects of AF, towards the underlying anatomical substrate and atrial remodelling, have been proposed as new pharmacological therapeutic approaches. Potential upstream therapies for AF comprise a variety of agents such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), statins, N-3 polyunsaturated fatty acids and steroids. On the basis of experimental data, clinical studies have provided information on the potential of upstream therapy for the prevention of AF across a broad spectrum of cardiovascular patient groups. In patients with heart failure or hypertension, data are sufficient to support the use of ACEI or ARB as treatment that may decrease the risk of AF beyond their other beneficial effects. Similarly, it is highly possible that the use of statin in patients with a recognized indication may be associated with a benefit against AF. However, in most clinical settings, the evidence appears to be insufficient to drive changes in therapy management per se, and large-scale, randomized controlled trials with adequately defined endpoints are still needed. The results from these trials may help to understand the complex mechanisms that lead to AF, and may clarify the benefit-to-risk ratio of these new therapeutic approaches.
    Full-text · Article · Dec 2010 · Annales de cardiologie et d'angeiologie
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    ABSTRACT: In atrial fibrillation (AF), the absence of a clear benefit of a rhythm-control strategy over a rate-control strategy seen in recent trials may be due to the fact that many of the usual antiarrhythmic strategy have significant weaknesses. Besides research efforts to improve the efficacy and safety of conventional antiarrhythmic agents, therapies directed ‘upstream’of the electrical aspects of AF, towards the underlying anatomical substrate and atrial remodelling, have been proposed as new pharmacological therapeutic approaches. Potential upstream therapies for AF comprise a variety of agents such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), statins, N-3 polyunsaturated fatty acids and steroids. On the basis of experimental data, clinical studies have provided information on the potential of upstream therapy for the prevention of AF across a broad spectrum of cardiovascular patient groups. In patients with heart failure or hypertension, data are sufficient to support the use of ACEI or ARB as treatment that may decrease the risk of AF beyond their other beneficial effects. Similarly, it is highly possible that the use of statin in patients with a recognized indication may be associated with a benefit against AF. However, in most clinical settings, the evidence appears to be insufficient to drive changes in therapy management per se, and large-scale, randomized controlled trials with adequately defined endpoints are still needed. The results from these trials may help to understand the complex mechanisms that lead to AF, and may clarify the benefit-to-risk ratio of these new therapeutic approaches.
    Full-text · Article · Dec 2010 · Annales de Cardiologie et d Angéiologie
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    ABSTRACT: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.
    Full-text · Article · Jun 2010 · Europace
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    ABSTRACT: We report the case of an 18-year-old man with Danon disease, a genetic disorder inclunding a severe hypertrophic cardiomyopathy with very broad QRS, who had an implantable cardioverter defibrillator for primary prevention. Nine months after implantation, he received two inappropriate shocks due to R-wave double counting during sinus tachycardia. We discuss how to avoid such inappropriate therapy.
    No preview · Article · Mar 2010 · Pacing and Clinical Electrophysiology
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    ABSTRACT: A 65-year-old patient presented with recurrent cardiac decompensation 12 years after aortic prosthesis replacement and expanded polytetrafluoroethylene (ePTFE) membrane pericardial substitution. Diagnosis of pericardial constriction was difficult. Only one cardiac imaging method, radionuclide ventriculography, was helpful. Upon re-operation, an epicardial fibrous strap which restricted right ventricle (RV) diastolic expansion was found between the anterior free wall and diaphragmatic portion of the RV. Clinical status dramatically improved after surgical removal of this bridle, as did ventricular filling curves in radionuclide imaging. This case shows that delayed cardiac constriction is possible after ePTFE pericardial substitution, especially if the membrane is applied to both anterior and diaphragmatic aspects of the heart.
    Full-text · Article · Feb 2010 · Interactive Cardiovascular and Thoracic Surgery
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    ABSTRACT: In patients with atrial fibrillation (AF) and an intermediate risk of stroke (CHADS2 score =1), available evidence from clinical trials is inconclusive and the present guidelines for the management of AF indicate that the choice between oral anticoagulant and aspirin in these patients is open. Our goal was to evaluate whether, in patients with AF and only one moderate risk factor for thromboembolism, treatment with an oral anticoagulant is appreciably more beneficial than treatment with an antiplatelet agent. Among 6,517 unselected patients with AF, 1,012 of them (15.5%) had a CHADS2 score of 1 and were liable to treatment with an antiplatelet agent or an anticoagulant. An oral anticoagulant was prescribed for 606 patients (59.9%) and an antiplatelet agent or no antithrombotic treatment for 406 (40.1%). During follow-up (median=793 days, interquartile range=1,332 days), 105 deaths (10.4%) and 19 strokes (1.9%) were recorded. The administration of an anticoagulant was associated with a lower rate of events (relative risk=0.42, 95% confidence interval 0.29-0.60, p<0.0001) than when no anticoagulant was prescribed. Results remained similar after adjustment for age and other confounding factors. In contrast, prescription of an antiplatelet agent was not associated with a lower risk of events. Factors independently associated with an increased risk of events were older age (p<0.0001), concomitant heart failure (p=0.0002), diabetes (p=0.0025), lack of prescription of an anticoagulant (p<0.0001) and permanent AF (p=0.04). Thus, prescription of an anticoagulant is independently associated with a decreased risk of death or stroke among patients with AF and a CHADS2 score =1.
    No preview · Article · Feb 2010 · Thrombosis and Haemostasis
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    ABSTRACT: Background Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiac disease, usually an autosomal dominant disorder, that may lead to sudden death, particularly in young people and athletes. Five desmosomal genes have been recently implicated in ARVD/C: JUP, DSP, PKP2, DSG2 and DSC2. We performed a systematic screening of these genes in a large population to address the potential clinical impact of genotyping. Methods and results Direct sequencing of the 5 predefined genes was performed in 135 unrelated patients with ARVD/C meeting the international Task Force criteria. We identified 66 disease-causing mutations in 61 patients (45%). Distribution of genes was 31% (41/135) for PKP2, 10% (14/135) for DSG2, 4% (6/135) for DSP, 1% (2/135) for DSC2 and 0% for JUP. The identification rate was not related to age of patients nor familial context. In 48% (32/66) a mutation was identified in a single family or individual (private mutation). In addition, a genetic variant of unknown significance was identified in additional 10 patients (7%). Finally, complex genetic status with double mutations was identified in 4% of patients and multiple mutations tend to be associated with a more severe phenotype (namely more frequent cardiac arrest). Conclusions We performed the most comprehensive screening of desmosomal genes in the largest population of ARVD/C patients reported until now. A molecular diagnosis strategy can be deduced, requiring however exhaustive genetic screening of four desmosomal genes, with the possible identification of genetic variants of unknown significance. The relatively high success rate of genotyping in ARVD/C suggests the possible use of genetic testing as a diagnostic tool, with potential important impact for early diagnosis in borderline patients and relatives.
    Full-text · Article · Jan 2010 · Archives of Cardiovascular Diseases Supplements
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    ABSTRACT: Ectopic activity in cardiac muscle within pulmonary veins (PVs) is associated with the onset and the maintenance of atrial fibrillation in humans. The mechanism underlying this ectopic activity is unknown. Here we investigate automatic activity generated by catecholaminergic stimulation in the rat PV. Intracellular microelectrodes were used to record electrical activity in isolated strips of rat PV and left atrium (LA). The resting cardiac muscle membrane potential was lower in PV [-70 +/- 1 (SE) mV, n = 8] than in LA (-85 +/- 1 mV, n = 8). No spontaneous activity was recorded in PV or LA under basal conditions. Norepinephrine (10(-5) M) induced first a hyperpolarization (-8 +/- 1 mV in PV, -3 +/- 1 mV in LA, n = 8 for both) then a slowly developing depolarization (+21 +/- 2 mV after 15 min in PV, +1 +/- 2 mV in LA) of the resting membrane potential. Automatic activity occurred only in PV; it was triggered at approximately -50 mV, and it occurred as repetitive bursts of slow action potentials. The diastolic membrane potential increased during a burst and slowly depolarized between bursts. Automatic activity in the PV was blocked by either atenolol or prazosine, and it could be generated with a mixture of cirazoline and isoprenaline. In both tissues, cirazoline (10(-6) M) induced a depolarization (+37 +/- 2 mV in PV, n = 5; +5 +/- 1 mV in LA, n = 5), and isoprenaline (10(-7) M) evoked a hyperpolarization (-11 +/- 3 mV in PV, n = 7; -3 +/- 1 mV in LA, n = 6). The differences in membrane potential and reaction to adrenergic stimulation lead to automatic electrical activity occurring specifically in cardiac muscle in the PV.
    Full-text · Article · Jun 2009 · AJP Heart and Circulatory Physiology

  • No preview · Article · Apr 2009 · La Presse Médicale
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    N. Doisne · N. Zannad · P. Cosnay · V. Maupoil · I. Findlay

    Full-text · Article · Mar 2009 · Archives of Cardiovascular Diseases

Publication Stats

2k Citations
448.59 Total Impact Points

Institutions

  • 1984-2014
    • University of Tours
      • Département des Microscopies
      Tours, Centre, France
  • 2012
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
  • 1998-2012
    • Centre Hospitalier Universitaire de Tours
      Tours, Centre, France
  • 1998-2008
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1999
    • Hôpital Ambroise Paré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Billancourt, Île-de-France, France