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International audience; Aims: We documented the midterm prognosis of left ventricular thrombus (LVT) in heart failure (HF) patients with dilated cardiomyopathy (DCM) and ischaemic cardiomyopathy (ICM). We aimed to characterize patients with LVT in the context of HF with reduced (≤40%) left ventricular ejection fraction and evaluate their risk for death and/or embolic events, overall, and specifically in patients with ischaemic or non-ischaemic aetiology. We also intended to identify risk factors for LVT in patients with DCM.Methods and results: We included all HF patients (N = 105, age 56 ± 13) admitted from 2005 to 2018 in our institution for LVT without significant valve disease/prosthesis, heart transplant/left ventricular assist device, congenital heart disease, or acute myocardial infarction. Our primary endpoint was the 1 year risk of the composite of all-cause mortality (ACM) and symptomatic embolic events. Mean left ventricular ejection fraction was 23 ± 9%, and median BNP was 1795 pg/mL. Most (97%) patients were treated with vitamin K anticoagulants, and 64% had ICM. Symptomatic embolic events and/or ACM occurred in 20% of the population [embolic events (all within 30 days of LVT diagnosis) 15% and ACM 6%] and was similarly frequent in DCM or ICM (P > 0.05). Suspected/transient embolic events were more frequent in DCM (overall 13%; 29% in DCM vs. 5% in ICM, P < 0.01). Major bleeding occurred in 5% of patients. Left ventricular reverse remodelling occurred in 65% of patients, more frequently in DCM (86% in DCM vs. 65% in ICM, P = 0.02). In a case-control analysis matching DCM patients, BNP level was the only factor significantly associated with LVT (2447 pg/mL in LVT vs. 347 pg/mL, P < 0.001).Conclusions: Patients with LVT have markedly high natriuretic peptides and experience a 20% 1 year risk for embolic events and/or death following diagnosis despite anticoagulant treatment. Most patients have favourable remodelling/recovery. As all symptomatic embolic events occurred within 30 days of LVT diagnosis, a very careful initial management is warranted.

Summary Background Ventricular arrhythmia is common after left ventricular assist device (LVAD) implantation, especially in the early postoperative phase ( Aim To identify the incidence of and risk factors for electrical storm (ES) occurring within 30 days of HeartMate ® II implantation. Methods We reviewed data from all consecutive patients undergoing HeartMate ® II device implantation at our institution from January 2008 to December 2014. Patient demographic data, pharmacotherapies and outcomes were collected. The primary endpoint was occurrence of early ES (within 30 days of surgery), defined as three or more separate episodes of sustained ventricular arrhythmia within a 24-hour interval, requiring appropriate therapy. Results Forty-three patients (mean age 56.7 ± 11.2 years; 39 men) were included. At HeartMate ® II implantation, mean left ventricular ejection fraction was 20 ± 5%, 32 (74.4%) patients had ischaemic cardiomyopathy and 31 (72.1%) were implanted with an indication of bridge to cardiac transplantation. During follow-up, 12 (27.9%) patients experienced early ES after HeartMate ® II implantation (median delay 9.1 ± 7.8 days). Early ES was more frequent in larger patients (body surface area 1.99 vs 1.81 m 2 ; P P = 0.08), previous implantable cardioverter-defibrillator implantation (66.7% vs 38.7%; P = 0.09), discontinuation of long-term beta-blocker therapy (75.0% vs 45.2%; P = 0.08), weaning of adrenergic drugs after the third day (66.7% vs 35.5%; P = 0.06) and the use of extracorporeal life support (50% vs 22.6%; P = 0.079), but was not associated with the cardiomyopathy aetiology or the indication for assistance. Catheter ventricular tachycardia ablation was performed in six (14.0%) patients. Early ES was associated with a significantly higher all-cause mortality rate at the 30th day (33.3% vs 6.5%; P = 0.02). Conclusion ES is a common and pejorative feature in the early postoperative period.

BACKGROUND Transcatheter aortic valve replacement (TAVR) has revolutionized management of high-risk patients with severe aortic stenosis. However, survival and the incidence of severe complications have been assessed in relatively small populations and/or with limited follow-up. OBJECTIVES This report details late clinical outcome and its determinants in the FRANCE-2 (FRench Aortic National CoreValve and Edwards) registry. METHODS The FRANCE-2 registry prospectively included all TAVRs performed in France. Follow-up was scheduled at 30 days, at 6 months, and annually from 1 to 5 years. Standardized VARC (Valve Academic Research Consortium) outcome definitions were used. RESULTS A total of 4,201 patients were enrolled between January 2010 and January 2012 in 34 centers. Approaches were transarterial (transfemoral 73%, transapical 18%, subclavian 6%, and transaortic or transcarotid 3%) or, in 18% of patients, transapical. Median follow-up was 3.8 years. Vital status was available for 97.2% of patients at 3 years. The 3-year all-cause mortality was 42.0% and cardiovascular mortality was 17.5%. In a multivariate model, predictors of 3-year all-cause mortality were male sex (p = 2 of 4 (p < 0.001). Severe events according to VARC criteria occurred mainly during the first month and subsequently in < 2% of patients/year. Mean gradient, valve area, and residual aortic regurgitation were stable during follow-up. CONCLUSIONS The FRANCE-2 registry represents the largest database available on late results of TAVR. Late mortality is largely related to noncardiac causes. Incidence rates of severe events are low after the first month. Valve performance remains stable over time. (J Am Coll Cardiol 2016; 68: 1637-47) (C) 2016 by the American College of Cardiology Foundation.

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep ( n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/d tmin were significantly higher ( P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/d tmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, 31P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications.

The onset of right ventricular dysfunction in patients presenting with congenital heart disease is associated with a dismal long-term outcome and often represents a therapeutic dead end. Our study had several objectives: (1) to analyse the anatomical, functional, histological and cellular characteristics of an animal model of repaired tetralogy of Fallot with right ventricular dysfunction (2) to test the new electrical treatment known as cardiac contractility modulation in this animal model. Seven sheep underwent a first surgery at the age of three weeks aiming to mimic the characteristics of a repaired tetralogy of Fallot. Five controls were sham-operated. Experimental studies were performed 12 months after the initial operation. The hemodynamic, echocardiographic, and mitochondrial function studies were carried out before and after cardiac contractility modulation in closed- and open-chest conditions. In this animal model of right ventricular dysfunction, short-term cardiac contractility modulation was associated with a significant improvement in (a) right ventricular function, as evidenced by a significant increase in right ventricular dP/dt (p

Background: The FRANCE-2 registry (French Aortic National Corevalve and Edwards) previously reported good early- and medium-term clinical and echocardiographic efficacy for transcatheter aortic valve replacement. We here report 5-year follow-up results from the registry. Methods: The registry includes all consecutive patients undergoing transcatheter aortic valve replacement for severe aortic stenosis in France. Follow-up is scheduled at 30 days, 6 months, then annually from 1 to 5 years. Clinical events were defined according to the Valve Academic Research Consortium criteria, and hemodynamic structural valve deterioration (SVD) was defined according to the consensus statement by the European Association of Percutaneous Cardiovascular Interventions. Results: Between January 2010 and January 2012, 4201 patients were enrolled in 34 centers. Five-year vital status was available for 95.5% of patients; 88.1% had clinical evaluation or died. Overall, at 5 years, all-cause mortality was 60.8% (n=2478; 95% CI, 59.3% to 62.3%). The majority of cardiovascular events occurred in the first month after valve implantation, and incidence remained low thereafter, at P =0.1). Finally, in the population of patients with severe SVD, 1 patient (1.7%) experienced a stroke, and 8 patients presented ≥1 heart failure event (13.3%). Conclusions: The 5-year follow-up results of the FRANCE-2 registry represent the largest long-term data set available in a high-risk population. In surviving patients, the low rate of clinical events and the low level of SVD after 1 year support the long-term efficacy of transcatheter aortic valve replacement in both types of transcatheter prosthesis featuring in the registry.

Purpose Heart failure (HF) is a common, serious, and still poorly known illness, which might benefit from studies in claims databases. However, to provide reliable estimates, HF patients must be adequately identified. This validation study aimed to estimate the diagnostic accuracy of the International Classification of Diseases, Tenth Revision (ICD-10) codes I50.x, heart failure, in the French hospital discharge diagnoses database. Methods This study was performed in two university hospitals, comparing recorded discharge diagnoses and electronic health records (EHRs). Patients with discharge ICD-10 codes 150.x were randomly selected. Their EHRs were reviewed to classify HF diagnosis as definite, potential, or miscoded based on the European Society of Cardiology diagnostic criteria, from which the codes' positive predictive value (PPV) was computed. To estimate sensitivity, patients with an EHR HF diagnosis were identified, and the presence of the I50.x codes was sought for in the hospital discharge database. Results Two hundred possible cases of HF were selected from the hospital discharge database, and 229 patients with an HF diagnosis were identified from the EHR. The PPV of I50.x codes was 60.5% (95% CI, 53.7%-67.3%) for definite HF and 88.0% (95% CI, 83.5%-92.5%) for definite/potential HF. The sensitivity of I50.x codes was 64.2% (95% CI, 58.0%-70.4%). PPV results were similar in both hospitals; sensitivity depended on the source of EHR: Departments of cardiology had a higher sensitivity than had nonspecialized wards. Conclusions Diagnosis codes I50.x in discharge summary databases accurately identify patients with HF but fail to capture some of them.

Background Left ventricular (LV) afterload could be associated with reduced myocardial contractility. The aim of this study was to evaluate the relative impact of increased afterload on LV myocardial deformation indices in chronic aortic constriction, with regard to hypertrophy, myocardial fibrosis, and mitochondrial function, and to differentiate acute versus chronic afterload effect. Methods Young pigs underwent aortic banding ( n = 11) or sham ( n = 7) operations. Nineteen weeks later, LV morphology and systolic function, including myocardial deformation, were assessed by echocardiography before and after banding release or acute aortic constriction (in the sham group). After the animals were euthanized, mitochondrial function and LV interstitial fibrosis were assessed. Results The chronic banding group ( n = 8) presented with significant LV hypertrophy compared with the sham group ( n = 7), and longitudinal strain (LS) was significantly altered (16.9 ± 0.7% vs 20.3 ± 0.7%, P = .001) while circumferential, radial strain, and ejection fraction were not. LS abnormalities were situated mostly on the basal and mid segments and on the septal wall. There was also significantly more myocardial fibrosis in the chronic banding group compared with the sham group, while mitochondrial function was preserved. The relative contributions of hypertrophic and fibrotic remodeling and of afterload to alter global LS were 62%, and 38%, respectively. Acute aortic banding also significantly altered LS. The ratio of LS to septal wall thickness enabled differentiation between chronic and acute afterload increase (1.9 ± 0.2 in the chronic group vs 2.9 ± 0.3 in the acute group, P = .001). Conclusions LS is susceptible to both hypertrophic and fibrotic remodeling and afterload increase, particularly on the basal and mid LV segments of the septum. The ratio of LS to septal wall thickness enables differentiation of acute from chronic afterload LS alteration.

Severe anaphylactoid reaction after the use of iodinated contrast media are rare but can contraindicate the use of contrast agent. It was the case of a 53-year-old woman suffering from symptomatic severe aortic stenosis, recused for cardiac surgery because of deleterious effects of chest-wall irradiation, with porcelain aorta. We decided to implant a 23-mm Edwards® SAPIEN® transcatheter aortic valve via a femoral route without using any contrast media. The implantation was successful after surgical approach of the femoral artery, transesophageal echocardiography guiding, and localization of native leaflets and coronary trunk with catheters. Immediate and one month post-interventional follow-up was favorable and echocardiography showed a good functioning of the aortic bioprosthesis. Although conventional angiography is the best way to visualize the good positioning of the valve before deployment, our case suggests that, in special situations, transfemoral implantation of an Edwards® SAPIEN® aortic bioprosthesis is feasible without any contrast injection. © 2012 Wiley Periodicals, Inc.

Background— Contact force (CF) is an important determinant of lesion formation for atrial endocardial radiofrequency ablation. There are minimal published data on CF and ventricular lesion formation. We studied the impact of CF on lesion formation using an ovine model both endocardially and epicardially. Methods and Results— Twenty sheep received 160 epicardial and 160 endocardial ventricular radiofrequency applications using either a 3.5-mm irrigated-tip catheter (Thermocool, Biosense-Webster, n=160) or a 3.5 irrigated-tip catheter with CF assessment (Tacticath, Endosense, n=160), via percutaneous access. Power was delivered at 30 watts for 60 seconds, when either catheter/tissue contact was felt to be good or when CF>10 g with Tacticath. After completion of all lesions, acute dimensions were taken at pathology. Identifiable lesion formation from radiofrequency application was improved with the aid of CF information, from 78% to 98% on the endocardium ( P P =0.02). The mean total force was greater on the endocardium (39±18 g versus 21±14 g for the epicardium; P 3 versus 209±131 mm 3 ; P =0.02) probably because of the absence of the heat sink effect of the circulating blood and covered a greater area (41±27 mm 2 versus 29±17 mm 2 ; P =0.03) because of catheter orientation. Conclusions— In the absence of CF feedback, 22% of endocardial radiofrequency applications that are thought to have good contact did not result in lesion formation. Epicardial ablation is associated with larger lesions.

Introduction: Patients who have undergone repair of Tetralogy of Fallot (TOF) often present with right bundle branch block. Cardiac resynchronization therapy (CRT) with right ventricular (RV) or biventricular (BiV) stimulation has been proposed as a modality to correct electrical abnormalities and improve cardiac contractility in patients with repaired TOF. We aimed to 1) compare ventricular electrical activation in adults with repaired TOF during RV versus BiV stimulation, using a non-invasive epicardial mapping system, and 2) examine the clinical mid-term effects of BiV resynchronization. Methods: 9 adults with repaired TOF were implanted with a CRT system and underwent 1) a non-invasive epicardial mapping (n = 9) during sinus intrinsic rhythm, RV and BiV pacing 2) a clinical evaluation (n = 7) before and after 6 months CRT with assessment of NYHA class and exercise capacity. Results: During intrinsic rhythm, non-invasive mapping demonstrated delayed activation of the right compared with the left ventricle in all patients, with the greatest activation delay noted near the infundibulum. However, we observed important differences among patients, in the severity of activation delays. Global activation time and an index of dyssynchrony were improved (p < 0.05) during BiV pacing compared with RV pacing and spontaneous rhythm. BiV pacing increased (p < 0.05) exercise tolerance and lowered the mean NYHA functional class at 6 months of follow up. Conclusion: Patients with corrected TOF present with different patterns of ventricular activation. RV stimulation modestly improved RV activation sequence and was associated with a delayed LV activation. Biventricular stimulation significantly decreased right and left ventricular dyssynchrony. © 2011 Elsevier Ireland Ltd.

Rhythmic complications seem common after left ventricular (LV) assist device (LVAD), especially in the early phase of implantation (

Background In the past 5years a few number of studies and case reports have come out focusing on biventricular (BiV) stimulation for treatment of congenital heart disease related ventricular dysfunction. The few available studies include a diverse group of pathophysiological entities ranging from a previously repaired tetralogy of Fallot (TOF) to a functional single ventricle anatomy. Patient's status is too heterogeneous to build important prospective study. To well understand the implication of prolonged electromechanical dyssynchrony we performed a chronic animal model that mimics essential parameters of postoperative TOF. Methods Significant pulmonary regurgitation, mild stenosis, as well as right ventricular outflow tract (RVOT) scars were induced in 15 piglets to mimic repaired TOF. 4months after hemodynamics and dyssynchrony parameters were compared with a control group and with a population of symptomatic adult with repaired TOF. Results Comparing the animal model with the animal control group on echocardiography, RV dilatation, RV and LV dysfunction, broad QRS complex and dyssynchrony were observed on the animal model piglets. Moreover, epicardial electrical mapping showed activation consistent with a right bundle branch block. The animal models displayed the same pathophysiological parameters as the post TOF repair patients in terms of QRS duration, pulmonary regurgitation biventricular dysfunction and dyssynchrony. Conclusion This chronic swine model mimics electromechanical ventricular activation delay, RV and LV dysfunction, as in adult population of repair TOF. It does appear to be a very useful and interesting model to study the implication of dyssynchrony and the interest of resynchronization therapy in TOF failing ventricle.

Background. Metaboreflex overactivation has been proprosed to explain exaggerated hyperventilation in heart failure population. We investigated the metaboreflex activation after cardiac resynchronization therapy (CRT). Methods. 10 heart failure patients (mean left ventricular ejection fraction (LVEF) 2 7 ± 4 %) schedulded for CRT implantation were prospectively studied. At baseline and after 6 month follow up two maximal cardiopulmonary exercise tests with and without regional circulatory occlusion (RCO) during recovery were performed. RCO was achieved by inflation of bilateral upper thigh tourniquets 30 mmHg above peak systolic blood pressure during 3 minutes after peak exercise. Metaboreflex contribution to the ventilatory response was assessed as the difference in ventilatory data at the third minute during recovery between the two tests (Δ). Results. Patients had enhanced VE/VCO2 slope ( 4 0 ± 9 ) and an evident metaboreflex contribution to the high ventilatory response (ΔVE: 3 ± 4 L/min; 𝑃 = 0 . 0 5 , ΔRR: 4 . 5 ± 4 /min; 𝑃 = 0 . 0 0 3 and ΔVE/VCO2: 5 . 5 ± 4 ; 𝑃 = 0 . 0 0 7 ). 6 months after CRT implantation, NYHA class, LVEF, peak VO2 and VE/VCO2 were significantly improved ( 1 . 4 ± 0 . 5 ; 𝑃 < 0 . 0 0 1 , 4 2 ± 7 %; 𝑃 < 0 . 0 0 1 , 1 6 . 5 ± 3 mL/kg/min; 𝑃 = 0 . 0 0 3 ; 3 3 ± 1 0 ; 𝑃 = 0 . 0 1 ). Metaboreflex contribution to VE, RR, and VE/VCO2 was reduced compared with baseline ( 𝑃 = 0 . 0 8 , 𝑃 = 0 . 0 1 and 𝑃 = 0 . 4 resp.). Conclusion. 6 months after CRT metaboreflex contribution to the ventilatory response is reduced.

SummaryAdults with congenital heart lesions constitute a rapidly growing group of patients with cardiovascular disease. This nascent demographic phenomenon is creating major issues concerning the optimal management of these patients, in whom sudden death and progressive heart failure are predominant causes of death. Ventricular dyssynchrony appears to be very common in this population and can appear early in the history of the disease. Recently, cardiac resynchronization therapy (CRT) has emerged as a potential treatment option for patients with congenital heart disease (CHD). In this paper, we review the clinical evidence for the role of CRT in a number of different groups of patients with congenital heart lesions. In particular, we focus on whether there is a plausible mechanistic role for CRT and, if so, whether this results in acute and longer-term beneficial effects. We conclude that CRT shows promise as a potential treatment option for patients with CHD and ventricular impairment, but larger clinical outcome studies are required before definitive guidance can be issued.

Aims Ischaemic preconditioning (IPC) protects the heart against prolonged lethal ischaemia through a signalling cascade involving Akt, glycogen synthase kinase-3β (GSK-3β), and mitochondrial ATP-sensitive potassium channels (mitoKATP). We previously demonstrated the involvement of the Wnt pathway in IPC in vivo via GSK-3β. A downstream target might be mammalian target of rapamycin (mTOR) since Wnt can impair tuberous sclerosis complex-2 (TSC2) phosphorylation by inhibiting GSK-3β. Here, we investigate whether the mTOR pathway is involved in cardioprotection. Methods and results Isolated-perfused mouse hearts were subjected to IPC via four cycles of ischaemia/reperfusion or pharmacological preconditioning (PPC) by diazoxide, a selective mitoKATP activator. IPC, like PPC, induced an inhibition/phosphorylation of GSK-3β through Akt activation. Preconditioning also induced phosphorylation of mTOR, p70S6K, and 4E-BP1 that correlated with a significant reduction in infarct size after 40-min ischaemia and 120-min reperfusion when compared with non-preconditioned controls. Preconditioning was impaired in GSK3 knock-in mice. In transgenic mice hearts overexpressing secreted frizzled protein 1 (sFRP1, a Wnt/Frz antagonist), GSK-3β phosphorylation, mTOR activation, and cardioprotection were impaired. Cardioprotection and its signalling were also inhibited by rapamycin (an mTOR inhibitor), 5-HD (a mitoKATP blocker), and N -(2-mercaptopropionyl) glycine (MPG) as a reactive oxygen species (ROS) scavenger. Conclusions We propose that the preconditioning signalling pathway involving an amplification loop results in a downregulation of GSK-3β and a constant opening of mitoKATP with ROS generation to activate the mTOR pathway and induce cardioprotection. The disruption of the Wnt/Frz pathway by sFRP1 modulates this loop, inducing GSK-3β activation. This study provides evidence that cardioprotection involves both a pro-survival mTOR pathway and a developmental Wnt pathway targeting GSK-3β.

Conventionally, the evaluation of left ventricular (LV) systolic function is based on ejection fraction assessment, which may be supplemented by other echocardiographic techniques, such as tissue Doppler imaging, 3D evaluation, and speckle tracking strains. However, these imaging modalities have a high technicity and are time-consuming, while being associated with reproducibility limitations. In this context, the usefulness of simpler measurements such as sys- tolic time intervals (STI) by pulsed Doppler echocardiography must be emphasized. Methods and results In this multicentre study, left ventricular ejection fraction (LVEF), dP/dtmax, LV stroke volume, myocardial longitudinal deformation, aortic pre-ejectional period (PEP, ms), and left ventricular ejection time (LVET, ms) were prospectively investigated and compared in 134 consecutive heart failure (HF) patients and 43 control subjects. Feasibility of STI measurements was 100%. Intra-observer reproducibility was 98% for PEP, 96% for LVET, 87% for LVEF, and 93% for global longitudinal strain (GLS). By subgroup analyses, with increasingly altered LVEF or GLS, PEP significantly increased, whereas significantly LVET decreased, resulting in a significantly increased PEP/LVET ratio (P , 0.001). In the HF patients group, a correlation between LVEF and PEP/LVET was found, with r ¼ 0.55 (y ¼ 20.0083x + 0.75, P , 0.001). Based on receiver operating curve analyses, the area under the curve was 0.91 for PEP/LVET . 0.43, which allowed us to detect LVEF , 35% with a sensitivity of 87%, and a specificity of 84%. Conclusion STI can be easily and accurately measured in clinical practice, and may be used for detecting alterations in LV systolic function. Moreover, this method is likely to have potential applications in the management of HF patients.

Background The recent development of accurate methods to measure two-dimensional strain during dobutamine stress echocardiography has reactivated the debate as to the respective value of myocardial perfusion versus myocardial function assessment in detecting coronary stenoses. The aim of our study was to compare the effects of progressive coronary constrictions on two-dimensional strain and myocardial contrast echocardiography parameters during stress conditions. Methods Nine open-chest pigs were studied in the setting of various degrees of coronary constrictions. Two-dimensional strain and myocardial contrast echocardiography with Flash refilling sequence acquisitions were obtained at rest and during dobutamine infusion. Values of longitudinal strain (LS), circumferential strain (CS), radial strain (RS), and wall thickening, as well as myocardial perfusion parameter (A.b), were then calculated. Results At rest, accuracy for detecting coronary stenosis was higher for CS, LS, and A.b (74%, 67%, and 69%, respectively) than for RS or wall thickening (62% and 64%, respectively). Dobutamine stress echocardiography increased the accuracy of A.b and LS to 77% and to 73%, respectively. Sensitivity during stress was higher for CS (93%) and A.b (77%), whereas specificity was higher for LS (89%) than for other parameters. Combined evaluations (CS+A.b, CS+LS, and LS+A.b) during dobutamine stress echocardiography improved both sensitivity and accuracy for detecting coronary stenosis. Conclusion Quantitative evaluation of contraction by LS and CS analysis and perfusion (A.b) during stress echocardiography resulted in similar accuracy levels, whereas the radial component was less accurate. Maximal sensitivities and accuracies were obtained by combined evaluations during stress.

International audience; AIMS: We sought to develop and validate a multiparametric algorithm by applying previously validated criteria to predict cardiac resynchronization therapy (CRT) response in a multicentre study. Thirty per cent of patients treated by CRT fail to respond to the treatment. Although dyssynchrony by echocardiography has been used to improve the selection of patients, the complexity of myocardial contraction has generated a moderate improvement using any of several individual parameters. METHODS AND RESULTS: Two hundred end-stage heart failure patients [NYHA 3-4 and left ventricular ejection fraction (LVEF)120 ms were included. Echocardiography analysis focused on the following parameters: atrioventricular dyssynchrony, interventricular dyssynchrony, and intraventricular dyssynchrony that integrated radial (PSAX M-mode) and longitudinal [tissue Doppler imaging (TDI)] evaluations for spatial (wall to wall) and temporal (wall end-systole to mitral valve opening) dyssynchrony diagnosis. Following CRT implantation, patients were monitored for 6 months with functional and echo evaluations defining responders by a 15% reduction in end-systolic volume. Mean QRS duration and LVEF were 152 +/- 17 ms and 25 +/- 8%. There was a CRT response in 57% of patients, independent of QRS width. Mean prevalence of positive criteria was 34 +/- 8%. Feasibility and variability averages were 81 +/- 20% and 9 +/- 4%. In a single parametric approach, ranges of sensitivities and specificities were 18-65% and 45-84% with a mean of 41% and 66%. A multiparametric approach by focusing on criteria combination decreased the mean rate of false-positive results to 14 +/- 12%, 5 +/- 4%, 2 +/- 2%, and 1 +/- 2% from one to four parameters, respectively. More than three parameters were associated with a specificity above 90% and a positive predictive value above 65%. Reproducibility of this global strategy was 91%. CONCLUSION: A multiparametric echocardiographic strategy based on the association of conventional criteria is a better indicator of CRT response than the existing single parametric approaches.

To compare MRI findings of left ventricular apical ballooning syndrome (LVABS) with those of acute myocardial infarction (AMI). Fifteen patients with a LVABS (group 1) and 25 patients with an AMI (group 2) were explored by MRI within 24 h after admission. Comparison of both groups for the number and location of myocardial segments with abnormal wall motion and abnormal perfusion or delayed enhancement was performed. The number of involved segments was higher in group 1 than in group 2 (p

ObjectivesThe aim of this study was to assess and validate 2-dimensional (2D) strain for the detection of ischemia during dobutamine stress echocardiography (DSE).BackgroundEvaluation of abnormalities of left ventricular (LV) function from wall thickening during DSE is unsatisfactory and requires a high level of expertise.MethodsIn 10 open-chest anesthetized pigs, myocardial deformation was studied before and during dobutamine infusion, under control and ischemic conditions produced by various degrees of coronary artery constriction: 2 of nonflow-limiting stenoses (NFLS) of increasing severity reducing left anterior descending artery hyperemic flow by 40% and 70% and 2 flow-limiting stenoses (FLS) reducing resting coronary flow by 25% and 50%. Agreement between 2D strain echocardiography and sonomicrometry (reference method) was evaluated by linear regression and Bland-Altman analysis.ResultsGood correlation and agreement were observed between 2-dimensional strain and sonomicrometry at rest and during dobutamine infusion; longitudinal strain: r = 0.77, p < 0.001 and r = 0.80, p < 0.001; radial strain: r = 0.57, p < 0.05 and r = 0.63, p < 0.05; and circumferential strain: r = 0.74, p < 0.001 and r = 0.58, p < 0.001. Circumferential and longitudinal strains in the risk area were significantly decreased at rest in the presence of FLS and during dobutamine infusion in the presence of NFLS. By contrast, radial strain was significantly decreased in the presence of severe FLS only during dobutamine infusion.ConclusionsThe 2D strain provides accurate assessment of LV regional function. Evaluation of circumferential and longitudinal strains during DSE has real potential for quantitative evaluation of LV deformation in the routine assessment of ischemia.

Background: Cardiac resynchronization therapy (CRT) is recommended in patients with ejection fraction 120 ms, and New York Heart Association (NYHA) functional class III or IV despite optimal medical therapy. We aimed to define demographic, clinical, and electrocardiographic predictors of positive clinical response to CRT. Methods and Results: Hundred consecutive patients fulfilling the recommended criteria were implanted with a CRT device. Demographic, clinical, two-dimensional echocardiographic and electrographic parameters were measured at baseline and after 6 months of simultaneous biventricular pacing. A positive response to CRT included an improvement of at least one NYHA functional class associated with an absence of hospitalization for worsening heart failure. At the end of follow-up, 12 patients were dead and 71% of the patients were classified as responders. After 6 months of CRT, the ejection fraction was significantly higher (P = 0.035) in responders versus nonresponders. Multivariate analysis identified three independent predictors of positive response to CRT: an idiopathic origin of the cardiomyopathy (P = 0.043), a wider QRS before implantation (P = 0.017), and a narrowing of the QRS after implantation (P = 0.037). Conclusion: An idiopathic origin of the cardiomyopathy, a wider QRS before implantation, and a narrowing of the QRS width after implantation were identified as independent predictors of clinical positive response to CRT.

Deformation analysis using 2-dimensional strain echocardiography can detect early systolic function abnormalities in patients with left ventricular hypertrophy. This study was designed to characterize global and regional myocardial deformation using 2-dimensional strain in professional soccer players (PSPs) compared with control subjects and patients with hypertrophic cardiomyopathy (HC). Twenty nine PSPs, 26 patients with HC, and 17 controls were investigated at rest using transthoracic echocardiography with 2-dimensional strain analysis. Radial and transverse strains were significantly higher in PSPs compared with controls, whereas longitudinal strain was lower. Compared with patients with HC, athletes had higher values for transverse, radial, and circumferential strains. In pathologic hypertrophic segments, longitudinal strain was lower in patients with HC than in PSPs. In conclusion, 2-dimensional strain can identify specific patterns of myocardial deformation in PSPs, controls, and patients with HC. It has the potential to become a routinely used method for the differentiation of athlete's heart and HC.

We compared 16-slice computed tomography (CT) with intravascular ultrasound (IVUS) in their ability to identify the culprit lesion, and to assess plaque characterization and vascular remodelling in acute coronary syndrome (ACS). Twenty patients were prospectively studied. Coronary plaque identification and characterization were compared using 16-slice CT and 40-MHz catheter-based IVUS. Minimum lumen area (MLA), cross-sectional vessel area (CVA) and vessel remodelling were determined for each comparable lesion. One hundred and sixty-nine segments were compared and 84 plaques analysed. Sixteen-slice CT detected 95% of culprit lesions (19/20). No feature suggestive of plaque rupture was detected by 16-slice CT. Attenuation measurements within all lesions revealed different values for hypoechoic (38 +/- 33 HU), hyperechoic (94 +/- 44 HU), and calcified plaques (561 +/- 216 HU), (P0.001). Agreement between 16-slice CT and IVUS on measuring MLA and CVA was evaluated using Bland-Altman analysis. Pearson and intra-class coefficient (ICC) were 0.81 and 0.70 for MLA, and 0.81 and 0.36 for CVA, for 16-slice CT and IVUS, respectively. Agreement between both techniques for vessel positive remodelling was moderate (kappa = 0.54, P0.001). Sixteen-slice CT has shown moderate accuracy in quantifying and characterizing coronary plaques compared with IVUS. Spatial resolution of 16-slice CT remains a major limitation, however, to accurately assess the complex lesions involved in ACS.

We showed recently that mitochondrial ATP-dependent K+channel (mitoKATP) opening is required for the inotropic response to ouabain. Because mitoKATPopening is also required for most forms of cardioprotection, we investigated whether exposure to ouabain was cardioprotective. We also began to map the signaling pathways linking ouabain binding to Na+-K+-ATPase with the opening of mitoKATP. In Langendorff-perfused rat hearts, 10–80 μM ouabain given before the onset of ischemia resulted in cardioprotection against ischemia-reperfusion injury, as documented by an improved recovery of contractile function and a reduction of infarct size. In skinned cardiac fibers, a ouabain-induced protection of mitochondrial outer membrane integrity, adenine nucleotide compartmentation, and energy transfer efficiency was evidenced by a decreased release of cytochrome c and preserved half-saturation constant of respiration for ADP and adenine nucleotide translocase-mitochondrial creatine kinase coupling, respectively. Ouabain-induced positive inotropy was dose dependent over the range studied, whereas ouabain-induced cardioprotection was maximal at the lowest dose tested. Compared with bradykinin (BK)-induced preconditioning, ouabain was equally efficient. However, the two ligands clearly diverge in the intracellular steps leading to mitoKATPopening from their respective receptors. Thus BK-induced cardioprotection was blocked by inhibitors of cGMP-dependent protein kinase (PKG) or guanylyl cyclase (GC), whereas ouabain-induced protection was not blocked by either agent. Interestingly, however, ouabain-induced inotropy appears to require PKG and GC. Thus 5-hydroxydecanoate (a selective mitoKATPinhibitor), N-(2-mercaptopropionyl)glycine (MPG; a reactive oxygen species scavenger), ODQ (a GC inhibitor), PP2 (a src kinase inhibitor), and KT-5823 (a PKG inhibitor) abolished preconditioning by BK and blocked the inotropic response to ouabain. However, only PP2, 5-HD, and MPG blocked ouabain-induced cardioprotection.

Objective To investigate transcatheter aortic valve implantation (TAVI) feasibility, effectiveness and safety in radiation-induced aortic valve stenosis cases. Methods 198 consecutive patients referred for TAVI were prospectively enrolled. They were divided into two groups: patients with a history of chest radiation therapy with suspected radiation-induced valvular disease (RXT) and others with suspected degenerative aortic valve stenosis (NRXT). Procedural, early and mid-term clinical outcomes were compared. Results Of the 198 patients enrolled in our study, 9.6% qualified for inclusion in the RXT group. A comparison of baseline characteristics revealed that patients with RXT were younger than patients with NRXT (68.3 vs 82.5 years; p

Background The ability to assess myocardial perfusion in small animals is important, especially to investigate models of myocardial ischemia. Myocardial perfusion is usually assessed by postmortem techniques, eliminating the possibility of follow-up. We sought to evaluate whether contrast echocardiography was able to quantify myocardial perfusion in rats. Methods Twenty-four rats divided in 3 groups (sham-operated, and 8 and 21 days after left anterior descending coronary artery stenosis) underwent myocardial contrast echocardiography using intermittent triggered imaging. Peak plateau intensity and slope of refilling were compared with myocardial blood flow achieved with fluorescent microspheres. Results High-quality images were easily obtained for each experiment. Close correlation was found between myocardial contrast echocardiography and myocardial blood flow, especially for measurements of peak plateau intensity × slope of refilling relative to the control area (y = 1.15 × −0.14, r = 0.86). Conclusion Quantification of myocardial perfusion in rats is feasible by myocardial contrast echocardiography using intermittent triggered imaging.

Phosphorylation and subsequent inactivation of glycogen synthase kinase (GSK)-3beta via the Akt/PI3-Kinase pathway during ischemic preconditioning (PC) has been shown to be cardioprotective. As FrzA/sFRP-1, a secreted antagonist of the Wnt/Frizzled pathway, is expressed in the heart and is able to decrease the phosphorylation of GSK-3beta in vitro on vascular cells, we examined its effect during PC using transgenic mouse overexpressing FrzA in cardiomyocytes (alpha-MHC promoter) under a conditional transgene expression approach (tet-off system). Overexpression of FrzA inhibited the increase in GSK-3beta phosphorylation as well as protein kinase C (PKC) epsilon activation in transgenic mice after PC as compared with littermates. Phospho-Akt (P-Akt), phospho-JNK, or the cytoplasmic beta-catenin levels were not modified, phospho-p38 (P-p38) was slightly increased in transgenic mice after PC as compared with littermates. FrzA transgenic mice displayed a larger infarct size and a greater worsening of cardiac function compared with littermates. All these differences were reversed by the addition of doxycycline. This study demonstrates for the first time that disruption of a beta-catenin independent Wnt/Frizzled pathway induces the activation of GSK-3beta and reverses the benefit of preconditioning.

Background The hexosamine biosynthetic pathway (HBP) is heightened in cardiomyopathies. We aimed at understanding how over-activation of HBP impacts on cardiac electrophysiology, and acts as a trigger or a substrate of cardiac arrhythmias. Methods Overactivation of the HBP by injection of glucosamine (GlcN 270mg/kg) was assessed under basal conditions and during beta-adrenergic stress on the myocardial energetic status (phosphocreatine to ATP ratio) of rats by 31 P nuclear magnetic resonance spectroscopy. Rat hearts were perfused ex vivo to evaluate the effects of the HBP activation (physiologically: glutamine 0.5mM – gln; overactivated: GlcN 1mM) on: cardiac function, MVO 2 , and arrhythmia score (AS) under basal (spontaneous arrhythmias: sAS) and pacing (pAS) conditions. At the cellular level (HL1 cells), HBP overactivation (GlcN) was assessed on conduction velocity characterized by micro-electrode arrays recordings, and properties of voltage gated ionic channels involved in cellular excitability and conduction by patch clamp experiments. Results In vivo GlcN did not modify PCr/ATP of the left ventricle under basal conditions. This ratio was significantly decreased during beta-adrenergic stress, while a similar increased heart rate was reported. When hearts were isolated and perfused ex vivo , GlcN induced a decrease of the heart rate and MVO 2 temporarily, and an increase of the sAS and pAS. Physiological activation of HBP with gln did not impact the ex vivo cardiac function and the sAS, but further increased the probability of atrial arrhythmias during pacing. In HL1 cells, GlcN reduced the rate of spontaneous depolarization, modified the direction and the velocity of the impulse propagation, and altered activation and inactivation properties of the sodium channel. Conclusion Acute HBP activation is associated with an increased vulnerability for arrhythmias and alteration of impulse conduction, suggesting its potential role in the atrial and ventricular arrhythmias. The author hereby declares no conflict of interest

Pulmonary artery (PA) hypertension was studied in a chronic hypoxic-pulmonary hypertension model (7–21 days) in the rat. Increase in PA pressure (measured by catheterism), cardiac right ventricle hypertrophy (determined by echocardiography), and PA remodeling (evaluated by histology) were almost entirely prevented after oral dehydroepiandrosterone (DHEA) administration (30 mg/kg every alternate day). Furthermore, in hypertensive rats, oral administration, or intravascular injection (into the jugular vein) of DHEA rapidly decreased PA hypertension. In PA smooth muscle cells, DHEA reduced the level of intracellular calcium (measured by microspectrofluorimetry). The effect of DHEA appears to involve a large conductance Ca 2+ -activated potassium channel (BK Ca )-dependent stimulatory mechanism, at both function and expression levels (isometric contraction and Western blot), via a redox-dependent pathway. Voltage-gated potassium (Kv) channels also may be involved because the antagonist 4-amino-pyridine blocked part of the DHEA effect. The possible pathophysiological and therapeutic significance of the results is discussed.

To assess the effect of optimal directional coronary atherectomy (DCA) on restenosis and left ventricular (LV) function, 95 patients who underwent DCA and adjunctive balloon angioplasty for de novo lesions were prospectively followed for 6 months. Absolute and relative coronary lumen measurements were analyzed with online quantitative coronary angiography. LV volumes, ejection fraction, and segmental wall motion were measured off-line according to the radial method for LV cineangiograms acquired in a right anterior oblique projection. Target vessels were the left anterior descending artery in 63 patients and right coronary artery in 32. Mean (+/- SD) reference diameter was 3.58 +/- 0.65 mm. Mean lumen diameter improved significantly after DCA from 1.19 +/- 0.44 to 3.03 +/- 0.45 mm, yielding a 14 +/- 10% residual stenosis. Overall angiographic restenosis rate (50% stenosis in diameter) at control was 23%. In patients without restenosis, there were no significant changes in LV volumes or in LV pressures. In this subgroup, ejection fraction improved significantly in the left anterior descending group (mean difference 3 +/- 10%, p0.04). Moreover, there was an increase in fractional shortening of all anterior segments (mean difference 11 +/- 16%, p0.005). Improvement in fractional shortening was less marked in the right coronary artery group even without restenosis. We conclude that: (1) optimal DCA can achieve a low restenosis rate in selected large vessels, (2) long-term beneficial effects on regional LV function are possible, particularly in patients with left anterior descending disease and in the absence of coronary restenosis.

Background Calcium leak from the sarcoplasmic reticulum (SR) favors cardiac sudden death through a calcium overload mechanism. Here we investigate the crosstalk between the calcium overload SR-mediated and the mitochondrial permeability transition pore (mPTP) opening during a ventricular arrhythmic episode. Methods and results a burst pacing protocol was developed to induce ventricular arrhythmia in the perfused rat heart. Surface electrocardiogram, left ventricular pressure, and oxygen consumption were monitored. Epicardial fluorescence was recorded from either a mitochondrial membrane potential dye or an intracellular calcium dye. ECG signals were used to assess both arrhythmia complexity and duration. Hearts were perfused with tacrolimus (FK506) alone or in combination with cyclosporin A (CsA) to promote SR calcium leak or inhibit mPTP, respectively. Prior to arrhythmia induction, FK506 promoted mitochondrial depolarization and intracellular calcium overload in a CsA-sensitive manner. More than 90% of hearts developed complex ventricular arrhythmias in the FK506 group and this was accompanied by a strong mitochondrial membrane depolarization. In contrast, in the FK506 + CsA group, 100% of the hearts spontaneously defibrillate after a few seconds of arrhythmias. In this group, following arrhythmia induction, mitochondrial depolarization amplitude, intracellular calcium overload and heart efficiency depression was decreased in comparison to the FK506 group. Conclusions Here we suggest that the FK506-induced calcium overload promotes mitochondrial calcium accumulation and leads to mPTP opening. We propose that mPTP opening should be considered as an arrhythmogenic substrate. The author hereby declares no conflict of interest

BackgroundHeart failure is the leading cause of hospital admissions and economic burden. In accordance with guidelines, a dedicated heart failure unit has been created in Bordeaux (France) in May 2011.AimEvaluate the impact of a heart failure management unit with ambulatory sector on readmission rate and mortality; and identify prognosis parameters at diagnosis and 6 months after.MethodsDescriptive study of mortality and heart-failure-related readmission rates after a first admission for heart failure, from May 2011 to July 2014 (inclusion stopped in July 2013). Student’s test and Cox’s regression have been performed.ResultsSince the creation of this unit, its activity has been growing by 30% in the first year and 10%, in the second. 421 patients with less than 40% left ventricular ejection fraction (LVEF) have been included; 181 had been treated before May 2011 while 240 were news patients treated during the study. Average age was 57±14 years old and average LVEF was 28%±7%. Therapeutics drugs cover was good compared to previous studies: 98% of patients has been treated by beta blockers, 94% by an antagonist of reninangiotensin-aldosteron system and 82% by an antagonist of mineralocorticoid receptor. Survival after 3 years of treatment was 87.5%. Re-admission rate was less than one readmission per patient and per year. No diagnosis parameter was a prognosis factor. But after 6 months of treatment, univariate analysis found significant prognosis factors of survival: dyspnea I-II, 6minutes walking test>300m, BNP

Background To date, Doppler echocardiography is the most widespread and well-recognized technique for the noninvasive evaluation of systolic pulmonary artery pressure (sPAP). However, recent studies have reported reservations about the relevance of Doppler echocardiography or the tool's reliability in the diagnosis and follow-up of patients with pulmonary hypertension (PH). Thus, the aim of this dedicated retrospective study was to address the questions of Doppler echocardiography's relevance and accuracy for PH diagnosis in the routine activity of a conventional echocardiography department. Methods Institutional databases were used to extract and analyze the records of 310 patients who underwent both hemodynamic and echocardiographic investigations within a single hospitalization period. Results Despite an underestimation of absolute Doppler sPAP values compared with measurements on right heart catheterization, data analysis revealed a strong correlation ( r = 0.80, P n = 310). Targeting a mean pulmonary pressure on right heart catheterization of 25 mm Hg for the definition of PH, receiver operating characteristic curve analysis demonstrated a strong association between sPAP and PH diagnosis (area under the curve, 0.82; n = 155). The cutoff obtained for sPAP was 38 mm Hg, and when applied on a second-test subgroup population ( n = 155), sensitivity, specificity, and accuracy were 88%, 83%, and 86%, respectively. When patients with examination intervals of n = 115), sensitivity and specificity reached 89% and 89%, respectively. No combination of parameters produced an improvement on the initial results. Conclusions In the real-world practice of a conventional echocardiography department, Doppler echocardiography is associated with high accuracy, sensitivity, and specificity for PH evaluation, thus confirming its major position as a primary noninvasive tool.

Dehydroepiandrosterone (DHEA) prevents chronic hypoxia-induced pulmonary hypertension and associated right ventricle dysfunction in rats. In this animal model, reoxygenation following hypoxia reverses pulmonary hypertension but not right ventricle dysfunction. We thus studied the effect of DHEA on the right ventricle after reoxygenation, i.e. after a normoxic recovery phase secondary to chronic hypoxia in rats. Right ventricle function was assessed in vivo by Doppler echocardiography and in vitro by the isolated perfused heart technique in three groups of animals: control, recovery (21 days of hypoxia followed by 21 days of normoxia) and recovery DHEA (30 mg · kg(-1) every 2 days during the recovery phase). Right ventricle tissue was assessed by optical and electron microscopy. DHEA abolished right ventricle diastolic dysfunction, as the echographic E wave remained close to that of controls (mean ± SD 76.5 ± 2.4 and 79.7 ± 1.7 cm · s(-1), respectively), whereas it was diminished to 40.3 ± 3.7 in the recovery group. DHEA also abolished right ventricle systolic dysfunction, as shown by the inhibition of the increase in the slope of the pressure-volume curve in isolated heart. The DHEA effect was related to cardiac myocytes proliferation. In conclusion, DHEA prevents right ventricle dysfunction in this animal model by preventing cardiomyocyte alteration.

Depression and Cardiac Resynchronization Therapy. Background: The relationship between depression and heart failure is neither coincidental nor trivial, since depression is a powerful predictor of re-hospitalization and mortality. We prospectively studied the prevalence and impact of depression on the clinical outcomes of patients attending for cardiac resynchronization therapy (CRT). We specifically examined whether patients with depression have a different rate of response to CRT and whether CRT has an effect on depressive symptoms. Methods: Sixty-eight recipients of CRT systems were included. The depressive status was evaluated before implant and after 6 months by a structured diagnostic interview measuring Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria of major depression and by a self-report questionnaire (Center for Epidemiological Studies Depression Scale, CES-D). The CRT response was assessed at 6 months by a clinical composite score. Results: At inclusion, DSM-IV criteria of major depression were identified in 41% of the population, while using the self-report questionnaire 65% were observed to have mild to major depressive symptoms (CES-D ≥ 16). Only 4 patients were taking antidepressants. At 6 months, 75% were considered responders to CRT. Response to CRT did not differ between those with and without depression at baseline. The rate of patients with depression at 6 months was significantly lower in responders to CRT compared with nonresponders. Conclusions: We found a high prevalence of depressive symptoms in patients receiving CRT systems. Patients with depression should not be excluded from CRT, because they demonstrate a similar rate of response than the persons without depression and the responders are less likely to be depressed at 6 months. (J Cardiovasc Electrophysiol, Vol. 23, pp. 631–636, June 2012)

To evaluate the incremental diagnostic and prognostic value of cardiac magnetic resonance (CMR) in patients with chest pain, raised troponin and unobstructed coronary arteries, and to compare subsequent event rates between diagnostic groups. 130 patients (mean age: 54 ± 17) presenting with troponin-positive acute chest pain and unobstructed coronary arteries were included. All patients were managed according to European Society of Cardiology guidelines, including echocardiography, and had CMR within 6.2 ± 5.3 days of presentation. During follow-up, major adverse cardiovascular events (MACE) were recorded. CMR provided a diagnosis in 100 of 130 patients (76.9%), with the remaining 30 (23.1%) having a normal examination. CMR diagnosed 37 (28.5%) acute myocardial infarctions, 34 (26.1%) myocarditis, 28 (21.5%) apical ballooning syndromes and 1 (0.8%) hypertrophic cardiomyopathy. When a single diagnosis was suspected by the referring physician, CMR validated this diagnosis in 32 patients (76.2%). CMR provided a formal diagnosis in 61 patients (69.3%) in which the clinical diagnosis was uncertain between at least two possibilities. CMR corrected a wrong diagnosis in 10 patients (7.7%). CMR-suggested diagnosis led to a modification of therapy in 42 patients (32.3%). Median follow-up was 34 months (interquartile range 24–49) in 124 patients. Sixteen patients (12.9%) experienced MACE. MACE rate was not different between patients with a conclusive CMR and normal CMR. In patients with acute troponin-positive chest pain and unobstructed coronary arteries, early CMR has important diagnostic and therapeutic implications. However its association with occurrence of MACE during mid term follow-up was not obvious.

PEA Recorded in the Atrium. Introduction: Preliminary studies have revealed a high correlation between peak endocardial acceleration (PEA) measured with a sensor embedded in a ventricular lead and human cardiac contractility. In this study we assessed (1) the contributions made by measurements of PEA1, an index of ventricular systolic contraction, from the right atrium, and (2) the feasibility of recording a fourth component of PEA (PEA4), coincident with atrial contraction and corresponding to the phonocardiographic fourth heart sound. Methods: We placed a PEA sensor embedded at the tip of a right atrial lead in 9 pigs. A 7F Millar catheter tip micromanometer was introduced into the left ventricular (LV) cavity to measure dP/dtmax. Myocardial contractility was increased by infusion of dobutamine and depressed by the infusion of esmolol. We searched, during VDD pacing, for PEA4 following atrial systole, while gradually lengthening the atrioventricular delay. Ventricular fibrillation was then triggered by rapid stimulation. Results: The changes in PEA1 were correlated with the changes in LV dP/dtmax (r = 0.91; P < 0.001). A low-frequency component of the endocardial signal (PEA4) was visible approximately 50 milliseconds after the atrial electrogram in all experiments. Following the induction of ventricular fibrillation, PEA4 remained visible on the endocardial recording, simultaneous with the sensed atrial electrogram. Conclusions: This study confirms the merit of embedding a PEA sensor in an atrial lead. The exploitation of the information provided by the PEA1 signal remains pertinent and the possibility to record an additional PEA4 component offers the perspective of new clinical applications. (J Cardiovasc Electrophysiol, Vol. 22, pp. 579-583 May 2011)

We present and characterize an original experimental model to create a chronic ischemic heart failure in pig. Two ameroid constrictors were placed around the LAD and the circumflex artery. Two months after surgery, pigs presented a poor LV function associated with a severe mitral valve insufficiency. Echocardiography analysis showed substantial anomalies in radial and circumferential deformations, both on the anterior and lateral surface of the heart. These anomalies in function were coupled with anomalies of perfusion observed in echocardiography after injection of contrast medium. No demonstration of myocardial infarction was observed with histological analysis. Our findings suggest that we were able to create and to stabilize a chronic ischemic heart failure model in the pig. This model represents a useful tool for the development of new medical or surgical treatment in this field.

t a e t o v i o c Introduction Among congenital heart defects causing cyanosis, tetralogy of Fallot (TOF) is the most common. Major progress has been made since 1954, when Lillehei performed the first surgical repair, such that most children operated today reach adulthood. The follow-up of adults presenting with various conenital heart diseases and management of the specific compliations they have are challenging. While, in the case of TOF, he shortand intermediate-term surgical results are generally xcellent, the longer term clinical course may be complicated y right heart failure, life-threatening ventricular tachyarrhythias, major impulse propagation disorders, and sudden eath. Right heart failure is due to the combined effects of pressure and volume overloads and of the myocardial lesions inflicted during and after the operation. Right bundle branch block (BBB) almost invariably develops after surgical repair of TOF. Furthermore, a wide QRS is prognostically important, and QRS duration and risk of developing ventricular arrhythmias are closely correlated. The hemodynamic consequences of right BBB might play a predominant role in the long-term clinical outcomes of these patients, and a relationship probably exists between electrical and mechanical dysfunction, as well as links between myocardial remodeling, rhythm disturbances, and electromechanical dyssynchrony. Depressed contractility and remodeling may be promoted by mechanical dyssynchrony, which, therefore, may be a desirable therapeutic target. Emulating studies of left ventricular (LV) stimulation in patients with left heart failure and left BBB, a few cases of resynchronization in patients with congenital

Despite much progress in the medical management of myocardial ischemia, several problems remain and experimental models help to improve our understanding of the pathophysiology involved in this domain. The ameroid constrictor model is the most widely used to create ischemia but evaluation of patent ischemia is still under debate. In the present study, we describe the potential of a two-dimensional (2D) strain for experimentally evaluating myocardial ischemia in the pig. An ameroid constrictor was placed around the circumflex artery in 30 pigs. Angiography showed 90% stenosis at one and two months. Left ventricular function was moderately altered and associated with mitral valve insufficiency in 30% of cases. Longitudinal and circumference strains were dramatically modified in the ischemic inferior-lateral zone compared to the healthy anterior zone (P

Background— Inflammatory processes play a critical role in myocarditis, dilated cardiomyopathy, and heart failure. The expression of the inflammatory chemokine osteopontin (OPN) is dramatically increased in cardiomyocytes and inflammatory cells during myocarditis and heart failure in human and animals. However, its role in the development of heart diseases is not known. Methods and Results— To understand whether OPN is involved in cardiomyopathies, we generated a transgenic mouse (MHC-OPN) that specifically overexpresses OPN in cardiomyocytes with cardiac-specific promoter-directed OPN expression. Young MHC-OPN mice were phenotypically indistinguishable from their control littermates, but most of them died prematurely with a half-life of 12 weeks of age. Electrocardiography revealed conduction defects. Echocardiography showed left ventricular dilation and systolic dysfunction. Histological analysis revealed cardiomyocyte loss, severe fibrosis, and inflammatory cell infiltration. Most of these inflammatory cells were activated T cells with Th1 polarization and cytotoxic activity. Autoantibodies against OPN, cardiac myosin, or troponin I, were not found in the serum of MHC-OPN mice. Conclusions— These data show that OPN expression in the heart induces in vivo T-cell recruitment and activation leading to chronic myocarditis, the consequence of which is myocyte destruction and hence, dilated cardiomyopathy. Thus, OPN might therefore constitute a potential therapeutic target to limit heart failure.

Optimal treatment of right ventricular (RV) dysfunction observed in patients after tetralogy of Fallot (TOF) repair is unclear. Studies of biventricular (BiV) stimulation in patients with congenital heart disease have been retrospective or have included patients with heterogeneous disorders.The purpose of this study was to determine the effects on cardiac function of stimulating at various cardiac sites in an animal model of RV dysfunction and dyssynchrony and in eight symptomatic adults with repaired TOF.Pulmonary stenosis and regurgitation as well as RV scars were induced in 15 piglets to mimic repaired TOF. The hemodynamic effects of various configurations of RV and BiV stimulation were compared with sinus rhythm (SR) 4 months after surgery. In eight adults with repaired TOF, RV and left ventricular (LV) dP/dt(max) were measured invasively during SR, apical RV stimulation, and BiV stimulation.At 4 months, RV dilation, dysfunction, and dyssynchrony were present in all piglets. RV stimulation caused a decrease in LV function but no change in RV function. In contrast, BiV stimulation significantly improved LV and RV function (P.05). Echocardiography and epicardial electrical mapping showed activation consistent with right bundle branch block during SR and marked resynchronization during BiV stimulation. In patients with repaired TOF, BiV stimulation increased significantly RV and LV dP/dt(max) (P.05).In this swine model of RV dysfunction and in adults with repaired TOF, BiV stimulation significantly improved RV and LV function by alleviating electromechanical dyssynchrony.

The aim of this study was to examine the relative value and the influence of the association of 4 cardiac magnetic resonance (CMR) viability indexes for predicting segmental functional recovery after optimal pharmacologic therapies and early percutaneous coronary intervention in acute myocardial infarction (AMI). CMR has been shown to predict functional recovery after AMI. The relative predictive value of CMR viability indexes remains disputed and has not been described in AMI reperfused within the first 12 hours. Sixty-nine patients with a first reperfused (12 hours) Thrombolysis In Myocardial Infarction grade 3 AMI (61 men, 57.6 +/- 12.6 years) were studied on day 5 +/- 2. Low-dose (10 microg/kg/min) dobutamine response (DOB), microvascular obstruction (MVO), relative delayed enhancement extent (DE), and transmural DE pattern (TMDE) were assessed in each of the 17 left ventricular segments. Segmental functional outcome was assessed by CMR at 3 months. Logistic regression and Bayesian probabilities evaluated the association between viability indexes and functional segmental outcome. At rest, 27% of segments (314 of 1,173) were dysfunctional of which 53% (165 of 314) recovered at follow-up. Odd ratios for dobutamine response, MVO, DE, and TMDE were 15.8, 5.9, 2.6, and 2.5 respectively. The probability of segmental recovery was 0.84 when dobutamine response was positive and increased successively to 0.91 when adding MVO absence, 0.94 when adding TMDE absence, and 0.97 when adding DE absence. In conclusion, contractile response to low-dose dobutamine is the best predictive factor of segmental recovery after Thrombolysis In Myocardial Infarction grade 3 early reperfused AMI. Its value is further increased by other CMR viability indexes.