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Purpose-Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Two dimensional-speckle tracking echocardiography (2D-STE) has recently emerged as a non-invasive functional biomarker for early detection of DMD-related cardiomyopathy. This study aimed to determine, in DMD children, the existence of a left ventricle (LV) dyssynchrony using 2D-STE analysis.Methods-This prospective controlled study enrolled 25 boys with DMD (mean age 11.0±3.5 years) with normal LV ejection fraction and 50 age-matched controls. Three measures were performed to assess LV mechanical dyssynchrony: the opposing-wall delays (longitudinal and radial analyses), the modified Yu index, and the time-to-peak delays of each segment. Feasibility and reproducibility of 2D-STE dyssynchrony were evaluated. Results-All three mechanical dyssynchrony criteria were significantly higher in the DMD group than in healthy subjects: (1) opposing-wall delays in basal inferoseptal to basal anterolateral segments (61.4±45.3 msec vs. 18.3±50.4 msec, Prespectively) and in mid inferoseptal to mid anterolateral segments (58.6±35.3 msec vs. 42.4±36.4 msec, Prespectively), (2) modified Yu index (33.3±10.1 msec vs. 28.5±8.1 msec, P, respectively), and (3) most of time-to-peak values, especially in basal and mid anterolateral segments. Feasibility was excellent and reliability was moderate to excellent, with ICC values ranging from 0.49 to 0.97.Conclusion-Detection of LV mechanical dyssynchrony using 2D-STE analysis is an easily and reproducible method in pediatrics. The existence of an early LV mechanical dyssynchrony visualized using 2D-STE analysis in children with DMD before the onset of cardiomyopathy represents a perspective for future pediatric drug trials in the DMD-related cardiomyopathy prevention. Clinical Trial Registration-Clinicaltrials.gov NCT02418338. Post-hoc study, registered on April 16, 2015.

No abstract available.

Aims Pulmonary hypertension (PH) is a common complication of left heart disease (LHD, Group 2 PH) leading to right ventricular (RV) failure and death. Several loss-of-function (LOF) mutations in KCNK3 were identified in pulmonary arterial hypertension (PAH, Group 1 PH). Additionally, we found that KCNK3 dysfunction is a hallmark of PAH at pulmonary vascular and RV levels. However, the role of KCNK3 in the pathobiology of PH due to LHD is unknown. Methods and results We evaluated the role of KCNK3 on PH induced by ascending aortic constriction (AAC), in WT and Kcnk3-LOF-mutated rats, by echocardiography, RV catheterization, histology analyses, and molecular biology experiments. We found that Kcnk3-LOF-mutation had no consequence on the development of left ventricular (LV) compensated concentric hypertrophy in AAC, while left atrial emptying fraction was impaired in AAC-Kcnk3-mutated rats. AAC-animals (WT and Kcnk3-mutated rats) developed PH secondary to AAC and Kcnk3-mutated rats developed more severe PH than WT. AAC-Kcnk3-mutated rats developed RV and LV fibrosis in association with an increase of Col1a1 mRNA in right ventricle and left ventricle. AAC-Kcnk3-mutated rats developed severe pulmonary vascular (pulmonary artery as well as pulmonary veins) remodelling with intense peri-vascular and peri-bronchial inflammation, perivascular oedema, alveolar wall thickening, and exaggerated lung vascular cell proliferation compared to AAC-WT-rats. Finally, in lung, right ventricle, left ventricle, and left atrium of AAC-Kcnk3-mutated rats, we found a strong increased expression of Il-6 and periostin expression and a reduction of lung Ctnnd1 mRNA (coding for p120 catenin), contributing to the exaggerated pulmonary and heart remodelling and pulmonary vascular oedema in AAC-Kcnk3-mutated rats. Conclusions Our results indicate that Kcnk3-LOF is a key event in the pathobiology of PH due to AAC, suggesting that Kcnk3 channel dysfunction could play a potential key role in the development of PH due to LHD.

Aims EPHESUS was a multicentre, double-blind clinical trial in which 6632 patients with acute myocardial infarction (AMI) complicated by LV systolic dysfunction (LVSD) were randomized to receive eplerenone (n = 3319) or placebo (n = 3313). A total of 1580 EPHESUS patients were treated with PCI, which is now the standard treatment for AMI. This EPHESUS substudy examined the effects of eplerenone upon cardiovascular outcomes in PCI-treated patients. Methods and results EPHESUS patients were divided into PCI-treated and non-PCI-treated cohorts, and the effect of eplerenone upon mortality and other major adverse cardiovascular outcomes was assessed in each cohort. The PCI-treated patients (n = 1580) were younger, and had better renal function and fewer co-morbidities than non-PCI-treated patients (n = 5052). Cardiovascular mortality was significantly lower in PCI-treated patients as compared with non-PCI-treated patients (7% vs. 16%, P < 0.0001). However, the incidence of non-fatal events was similar in PCI-treated and non-PCI-treated cohorts. There was no statistical difference between the PCI-treated and non-PCI-treated cohorts in the primary or secondary outcomes of the trial. Eplerenone administration, compared with placebo, in the PCI-treated cohort did not affect PCI-related clinical outcomes, including recurrence of angina, the occurrence of acute coronary syndromes, or the need for further revascularization. Conclusions The beneficial effects of eplerenone in the EPHESUS trial exist for both PCI- and non-PCI-treated AMI patients with LVSD. Eplerenone has minimal, if any, effect upon reducing PCI-related adverse events in the PCI-treated cohort.

International audience; OBJECTIVE: To investigate the prevalence and significance of increased left ventricular (LV) trabeculation in highly trained athletes. DESIGN: Cross sectional echocardiographic study. SETTING: Sports cardiology institutions in the UK and France. SUBJECTS: 1146 athletes aged 14-35 years (63.3% male), participating in 27 sporting disciplines, and 415 healthy controls of similar age. The results of athletes fulfilling conventional criteria for LV non-compaction (LVNC) were compared with 75 patients with LVNC. MAIN OUTCOME MEASURE: Number of athletes with increased LV trabeculation and the number fulfilling criteria for LVNC. RESULTS: Athletes displayed a higher prevalence of increased LV trabeculation compared with controls (18.3% vs 7.0%; p ≤ 0.0001) and 8.1% athletes fulfilled conventional criteria for LVNC. Increased LV trabeculation were more common in athletes of African/Afro-Caribbean origin. A small proportion of athletes (n = 10; 0.9%) revealed reduced systolic function and marked repolarisation changes in association with echocardiographic criteria for LVNC raising the possibility of an underlying cardiomyopathy. Follow-up during the ensuing 48.6 ± 14.6 months did not reveal adverse events. CONCLUSIONS: A high proportion of young athletes exhibit conventional criteria for LVNC highlighting the non-specific nature of current diagnostic criteria if applied to elite athletic populations. Further assessment of such athletes should be confined to the small minority that demonstrate low indices of systolic function and marked repolarisation changes.

Mineralocorticoid receptor antagonists (MRAs) have been accorded a class 1 indication for patients with chronic heart failure and a reduced left ventricular ejection fraction (HFREF) in both European and American guidelines. Uptake, however, has been less than optimal largely due to concerns about their safety, in particular the risk of hyperkalemia and renal dysfunction.This review presents the current state of affairs regarding the safety of MRAs in heart failure with reduced ejection fraction.Careful patient selection and adherence to guideline-recommended inclusion and exclusion criteria, dosing, and serial monitoring of serum potassium and renal function, along with patient education regarding the potassium content of common foods, should minimize these risks and allow increased use of MRAs. Additionally, this may also result in a further reduction in cardiovascular mortality and hospitalizations for heart failure. The development of new non-steroidal MRAs, and especially new potassium binding molecules that are well tolerated and effective, hold the promise for increased safety and, therefore, increased and more prolonged use of MRAs in patients with heart failure, especially those with chronic kidney disease, diabetes mellitus, and the elderly.

International audience

International audience; AIMS:Serum uric acid (SUA) levels are associated with poorer outcomes in healthy cohorts and patients with stable and unstable coronary heart disease. We investigated the relationship between SUA and clinical outcomes in subjects with acute myocardial infarction (MI) complicated by reduced left ventricular (LV) function, heart failure (HF), or both.METHODS AND RESULTS:Univariable and multivariable Cox proportional hazards modelling was performed to study the association of baseline SUA and all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in an individual patient meta-analysis of four merged large randomized trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT). Three trials (excluding VALIANT) reported SUA, which was available in a total of 12 677 subjects. The ranges of SUA for quartiles I-IV were 45-280, 281-344, 345-420, and 420-1640 mmol/L, respectively. While almost 90% of patients in the lowest SUA quartile were alive after a mean follow-up of 23 ± 11 months

International audience; Prolonged strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Previous studies suggest that β-adrenergic pathway desensitization could be involved in this phenomenon, but it remains to be confirmed. Moreover, other underlying mechanisms involving oxidative stress have been recently proposed. The present study aimed to evaluate the involvement of both the β-adrenergic pathway and NADPH oxidase (Nox) enzyme-induced oxidative stress in myocardial dysfunction in rats following PSE. Rats were divided into 4 groups: controls (Ctrl), 4-h exercised on treadmill (PSE), and 2 groups in which Nox enzyme was inhibited with apocynin treatment (Ctrl APO and PSE APO, respectively). We evaluated cardiac function in vivo and ex vivo during basal conditions and isoproterenol stress. GSH/GSSG ratio, cardiac troponin I (cTnI) release, and lipid peroxidation (MDA) were evaluated. PSE induced a decrease in LV developed pressure, intrinsic myocardial contractility, and relaxation associated with an increase in plasma cTnI release. Our in vivo and ex vivo results demonstrated no differences in myocardial response to isoproterenol and of effective dose 50 between control and PSE rats. Interestingly, the LV dysfunction was reversed by apocynin treatment. Moreover, apocynin prevented cellular oxidation [GSH/GSSG ratio: PSE APO rats vs. PSE rats in arbitrary units (au): 1.98 ± 0.07 vs. 1.35 ± 0.10; P < 0.001]. However, no differences in MDA were observed between groups. These data suggest that myocardial dysfunction observed after PSE was not due to β-adrenergic receptor desensitization but could be due to a signaling oxidative stress from the Nox enzyme.

International audience; UNLABELLED: In aortic stenosis (AS), left ventricular (LV) adaptation to exercise has poorly been examined. Changes in LV ejection fraction may lack accuracy in identifying the presence of intrinsic myocardial impairment. AIMS: We sought to determine the impact of aortic stenosis (AS) on left ventricular (LV) longitudinal function at exercise in a series of asymptomatic patients with AS and preserved LV ejection fraction. METHODS AND RESULTS: Long-axis function was assessed at rest and at exercise by using 2D speckle tracking of myocardial deformation in 207 AS patients (aortic valve area 0.87 ± 0.19 cm²) and 43 aged-matched control subjects. When compared with control subjects, patients with AS have reduced longitudinal myocardial function at rest (-20.2 ± 2.7 vs. -15.4 ± 4.0%) and at peak exercise (-25.0 ± 3.7 vs. -16.5 ± 4.9%) (P < 0.0001 for both). Exercise changes in global longitudinal strain were correlated with changes in LV ejection in controls but not in patients with AS. Changes in LV global longitudinal strain during test were lower in AS patients with an abnormal response to exercise (-0.5 ± 2.7 vs. -1.5 ± 2.8%, P = 0.001). In multivariate analysis, a lower global longitudinal strain at rest (P = 0.04), a higher increase in mean trans-valvular pressure gradient (P < 0.001) at exercise, and smaller exercise-induced changes in global longitudinal strain (P < 0.001) were associated with an abnormal exercise test. CONCLUSION: In AS, subnormal LV function can be reliably identified by 2D strain imaging at rest and during a sub-maximal exercise. That sensitive measure of LV systolic function is depressed in AS and even more in patients having the most severe AS.

International audience; AIMS: To assess the cost-effectiveness of cardiac resynchronization therapy (CRT) compared with optimal medical therapy in patients with New York Heart Association (NYHA) II heart failure (HF) or NYHA I with previous HF symptoms. METHODS AND RESULTS: A proportion in state model with Monte Carlo simulation was developed to assess the costs, life years and quality-adjusted life year (QALYs) associated with CRT-ON and -OFF over a 10 year time period. Data from 262 patients in the European cohort of the REVERSE clinical trial (QRS ≥ 120 ms, left ventricular ejection fraction ≤ 40%, CRT-ON, n = 180, CRT-OFF, n = 82) were used to model all-cause mortality, change in NYHA class and resource use. EQ-5D preference weights were taken from a previous cost-effectiveness model of CRT and unit costs from national UK databases. Costs and benefits were discounted at 3.5% p.a. Extensive deterministic and probabilistic sensitivity analyses were performed. Compared with CRT-OFF, 0.94 life years or 0.80 QALYs were gained in the CRT ON group at an additional cost of €11 455, yielding an incremental cost-effectiveness ratio of €14.278 per quality-adjusted life year (QALY) gained. At a threshold of €33 000 (£30 000) per QALY gained, the probability that CRT is cost-effective is 79.6%. Cardiac resynchronization therapy becomes cost effective after ∼4.5 years. Cardiac resynchronization therapy needs only to demonstrate a modest impact on all cause mortality (hazard ratio = 0.82) in order to demonstrate cost-effectiveness. The results are robust to changes in all other parameters. CONCLUSION: Cardiac resynchronization therapy is a cost-effective intervention for patients with mildly symptomatic HF and for asymptomatic patients with left ventricular dysfunction and previous HF symptoms.

International audience; INTRODUCTION: Current guidelines recommend cardiac resynchronisation therapy (CRT) in patients with severe symptomatic heart failure, depressed left ventricular (LV) systolic function and a wide QRS complex (>or=120 ms). However, patients with heart failure having a narrow QRS complex might also benefit from CRT. DESIGN SETTING PATIENTS INTERVENTIONS: During the Predictors of Response to Cardiac Resynchronisation Therapy (PROSPECT) trial, 41 patients were enrolled in a 'narrow' QRS sub-study. These patients had a QRS complex

International audience; AIMS: A recent study suggested that no single echocardiographic index of cardiac dyssynchrony can reliably identify candidates for cardiac resynchronization therapy (CRT). We examined the value of three simple echocardiographic indices for predicting the 6-month clinical and echocardiographic responses to CRT. METHODS AND RESULTS: We analysed data from 75 CRT-D system recipients. Standard echocardiography was used to measure aortic pre-ejection delay (APED), interventricular mechanical delay (IVMD), and delayed activation of the left ventricular (LV) infero-lateral wall (OVERLAP). Clinical responders were defined as patients who had an improved status, based on rehospitalization for heart failure, NYHA class, and peak oxygen consumption. Echocardiographic responders had a > or =10% decrease in LV end-systolic volume. During the study, one patient died and five were lost to follow-up. Of the remaining 69 analysable patients, 50 (72.5%) were classed as clinical responders and 41 (59.4%) as echocardiographic responders to CRT. Before CRT implantation, APED, IVMD, and OVERLAP were similar in responders and non-responders. The value of these indices of dyssynchrony as single or combined predictors of the clinical or echocardiographic response to CRT was low, with sensitivities ranging between 4 and 63%, and specificities between 37 and 100%. CONCLUSION: Simple echocardiographic indices of dyssynchrony were poor predictors of response to CRT.

International audience; In aortic stenosis (AS), the increased afterload results in progressive structural and functional changes that precede the development of symptoms. We hypothesized that the detection of abnormalities in left ventricular long-axis function could identify patients with asymptomatic AS at increased risk of events. We prospectively examined the outcome of 126 patients with asymptomatic AS who underwent a comprehensive echocardiographic examination, including tissue Doppler imaging. B-type natriuretic peptide (BNP) was measured in all patients. During a median follow-up period of 20.3 + or - 17.8 months, 6 patients died, 8 developed symptoms but did not undergo surgery, and 48 underwent aortic valve replacement. On multivariate Cox regression analysis, the parameters associated with the predefined outcome were gender (p = 0.048), left atrial area index (p = 0.011), systolic annular velocity (p = 0.016), E/Ea ratio (p = 0.024), late diastolic annular velocity (p = 0.023), and BNP (p = 0.012). Using receiver operating characteristics curve analysis, a left atrial area index of > or = 12.4 cm(2)/m(2), systolic annular velocity of < or = 4.5 cm/s, E/Ea ratio >13.8, late diastolic annular velocity of < or = 9 cm/s, and BNP of > or = 61 pg/ml were identified as the best cutoff values to predict events. In conclusion, in asymptomatic AS, tissue Doppler imaging and BNP measurements provide prognostic information beyond that from clinical and conventional echocardiographic parameters.

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.

International audience; Cardiac resynchronization therapy is beneficial in heart failure patients with LVEF ≤35% and electrical dyssynchrony. However, its effects among patients with less severe LV dysfunction have not been established. Recent post-hoc analyses of landmark CRT trials suggest that CRT benefit may be present in patients with LVEF >35% and is associated with improvement in cardiac reverse remodelling, all-cause mortality, and need for heart failure hospitalizations. This review summarizes the currently available literature regarding the potential impact of CRT in patients with more modest reductions in LVEF.

Objective: Left-ventricular hypertrophy and interstitial fibrosis are the main pathophysiological factors of heart failure with preserved ejection fraction. Blockade of the serotonin 5-HT 2B receptor (5-HT 2B R) has been shown to reduce cardiac hypertrophy, oxidative stress, and extracellular cell matrix activation. In this study, we evaluated the effects of the 5-HT 2B R blockade, on hemodynamic and cardiac remodeling, in spontaneously hypertensive rats (SHRs) that display a diastolic dysfunction with preserved ejection fraction. Method: Thirty-seven-week-old SHRs were randomized in four groups receiving either saline, the selective 5-HT 2B R antagonist RS-127445 (1 mg/kg per day), a calcium channel blocker nicardipine (6 mg/kg per day), or RS-127445 R nicardipine. During the 14 weeks of treatment period, cardiac function and blood pressure were monitored by echocardiography and tail-cuff. Finally, electrocardiograms and invasive hemodynamics were obtained before blood collection. Heart was analyzed for morphology and mRNA expression. A complementary study evaluated the cardiac and vascular effects of serotonin on wild-type and mice knockout for the 5-HT 2B R (Htr 2B A/A) and/or the 5-HT 2A R (Htr 2A A/A). Results: Despite the left ventricular 5-HT 2B R overexpression, 5-HT 2B R blockade by RS-127445 did not affect left ventricular hypertrophy and fibrosis in SHRs. This antagonist did not improve diastolic dysfunction, neither alone nor in combination with nicardipine, although it induced plasma brain natriuretic peptide decrease. Moreover, RS-127445 amplified subendocardial fibrosis and favored left ventricular dilatation. Finally, a subendocardial left ventricular fibrosis was induced by chronic serotonin in wild-type mice, which was increased in Htr 2B A/A animals, but prevented in Htr 2A A/A and Htr 2A/2B A/A mice, and could be explained by a contribution of the endothelial 5-HT 2B Rs to coronary vasodilatation. Conclusion: This work is the first to identify a cardioprotective function of the 5-HT 2B R in an integrated model of diastolic dysfunction with preserved ejection fraction.

Aims Increased sympathetic activation and reduced parasympathetic tone are important pathophysiological contributors to the progression of heart failure, and are associated with poor outcome in patients. The aim of this study is to determine if vagal nerve stimulation (VNS) is a promising approach to modulate autonomic function and slow cardiac remodelling and the progression of heart failure. Methods The NECTAR-HF (NEural Cardiac TherApy foR Heart Failure) trial is designed to evaluate whether the Boston Scientific VNS device is safe and may attenuate cardiac remodelling, improve cardiac function and increase exercise capacity, in symptomatic heart failure patients (New York Heart Association Class II–III) with left ventricular systolic dysfunction (ejection fraction ≤35%) and receiving optimal medical therapy. Patients will be randomized in a 2:1 ratio to receive standard optimal medical treatment plus VNS system in an active mode vs. optimal medical treatment plus VNS system in an inactive mode, for a 6 month period. After the 6 month control period, inactive VNS systems will be activated and all patients will receive VNS. The study is powered to detect differences in the primary efficacy endpoint of change in left ventricular end systolic diameter. Secondary endpoints include ejection fraction, left ventricular volumes, quality of life scores, functional capacity, and changes in biomarkers. Conclusion This Phase II, randomized clinical trial conducted with vagal stimulation for heart failure will provide important new information on the potential of this novel and promising technique.

Duchenne muscular dystrophy is an X-linked neuromuscular disorder. The heart is traditionally involved, leading to heart failure. The mdx mouse is a natural animal model of the disease. We conducted a prospective study to analyze left ventricular (LV) function in mdx mice at different ages using high-resolution Doppler echocardiography.Echocardiography was performed with a 30-MHz cardiac probe. Wild-type and mdx mice were scanned at 10 and 12 months. We measured the interventricular septal wall thickness, posterior wall thickness, and LV diameter in systole and diastole. The LV shortening fraction, LV ejection fraction, and LV mass were then calculated.At 10 months, the shortening fractions in mdx and wild-type mice were relatively close (29% ± 5% versus 25% ± 4%). We found a significant difference in the posterior wall thickness change (40% ± 12% in mdx versus 28% ± 10% in wild-type; P = .048). The LV mass/body weight ratio was higher in mdx than wild-type mice (3.67 ± 0.25 versus 3.39 ± 0.26; P = .05). At 12 months, the LV mass was elevated in mdx mice compared to wild-type (152 ±16 versus 135 ± 3.7 mg; P = .04). The diastolic posterior wall thickness change was decreased in mdx mice at 12 months compared to wild-type (21% ± 7% versus 33% ± 4%; P = .01). The LV ejection fraction was not statistically different between mdx and wild-type mice (50% ± 6% versus 54% ± 2%).Ten-month-old mdx mice had a significantly higher posterior wall thickness than wild-type mice, but it was not significant at 12 months. In 12-month-old mdx mice, the posterior wall thickness change was significantly lower, and the LV mass was significantly higher. These findings indicate the role of LV function in the early stages of Duchenne muscular dystrophy.

Intrinsic QRS Narrowing with CRT. Background: Cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) in patients with congestive heart failure, LV systolic dysfunction, and a wide QRS complex. Previous reports suggest that CRT may also induce electrical remodeling but the impact on clinical outcome remains unknown. Objective: We sought to determine (1) if chronic CRT induces a relevant shortening of the intrinsic QRS (iQRS), (2) whether changes in the native conduction system correlate with clinical or echocardiographic response to CRT, and (3) to identify predictors of iQRS width shortening. Methods: We prospectively included 85 consecutive patients with left bundle-branch block who received a CRT device in 3 French centers. NYHA class, iQRS duration, LVEF, and left ventricular volumes were assessed before and 1 year after CRT implantation. Clinical and echocardiographic CRT responders were defined respectively as NYHA class improvement >1 class without heart failure hospitalization and an increase of LVEF by ≥10% and/or a decrease in LVESV by ≥15%. Electrocardiographic responders were defined as a decrease in iQRS duration by ≥20 ms. Results: Baseline and 1-year follow-up mean iQRS durations were, respectively, 168.0 ± 19.7 ms and 149.6 ± 31.6 ms (P

International audience; Cardiac resynchronization therapy (CRT) is one of the major advances in the treatment of patients with chronic heart failure due to impaired left ventricular ejection fraction. Current guidelines recommend with the highest levels of recommendation and evidence CRT in patients with low ejection fraction wide QRS, LBBB, and mild to severe heart failure (New York Heart Association class II to IV). However, other patients might benefit from CRT. This is the case for patients with permanent atrial fibrillation, patients conventional pacemaker indication, patients with mildly impaired left ventricular function (>35 %), or asymptomatic patients (NYHA I). We will discuss in this manuscript each new potential indication for CRT.

d i n a In this issue of HeartRhythm, Rickard et al provide some evidence that QRS widening after cardiac resynchronization therapy (CRT) may predict deterioration in left ventricular (LV) systolic function and thus an increased risk of echocardiographic nonresponse. They retrospectively studied a series of approximately 500 patients implanted with a CRT device for a guideline indication. Clinical, electrocardiographic, and echocardiographic data were collected preoperatively. QRS change after CRT was assessed postoperatively by measuring a QRS index equal to [(post-CRT biventricular-paced QRS duration – pre-CRT QRS duration)/(pre-CRT QRS duration)] 100. The echocardiographic response was assessed by the absolute change in the left ventricular ejection fraction. An LV function deterioration was defined by a decrease of 5% in left ventricular ejection fraction from baseline. Because of the retrospective design of the study, the time delay to follow-up echocardiogram varied greatly between patients, starting at 2 months. This is a clear limitation of the study as it is well known that reverse ventricular remodeling after CRT is a progressive process, starting rarely before 3 months and continuing to progress up to 9–12 months. However, the mean delay for follow-up echo was not statistically different between patients with (14.7 12.8 months) and without left ventricular ejection fraction deterioration (12.3 10.9 months). Within these limitations, the authors show that QRS widening indexed to the baseline QRS duration is an independent predictor of LV deterioration (odds ratio 1.14 (1.06–1.23); P .001). Is the change in QRS duration acutely after CRT predictive of midto long-term outcomes? The predictive value of QRS shortening or widening after CRT has been a matter of debate from the very first time of the therapy until now. As QRS change is based on 12-lead surface electrocardiogram analysis, it is important to know the accuracy and reproducibility of QRS duration measurement during both intrinsic conduction (before CRT) and biventricular pacing (after CRT). A core center analysis was done in the REsynchronization reVErses Remodeling in Systolic

Cardiac resynchronization therapy (CRT) is a proven treatment for heart failure but ∼30% of patients appear to not benefit from the therapy. Left ventricular (LV) endocardial and multisite epicardial [triventricular (TriV)] pacing have been proposed as alternatives to traditional LV transvenous epicardial pacing, but no study has directly compared the hemodynamic effects of these approaches. Left bundle branch block ablation and repeated microembolizations were performed in dogs to induce electrical dysynchrony and to reduce LV ejection fraction to max and other hemodynamic indexes were measured with a conductance catheter during LV epicardial, LV endocardial, biventricular (BiV) epicardial, BiV endocardial, and TriV pacing performed at three atrioventricular delays. LV endocardial pacing was obtained with a clinically available pacing system. The optimal site was defined as the site that increased dP/d tmax by the largest percentage. Implantation of the endocardial lead was feasible in all canines ( n = 8) without increased mitral regurgitation seen with transesophageal echocardiography and with full access to the different LV endocardial pacing sites. BiV endocardial pacing increased dP/d tmax more than BiV epicardial and TriV pacing on average ( P < 0.01) and at the optimal site ( P < 0.01). There were no significant differences between BiV epicardial and TriV pacing. BiV endocardial pacing was superior to BiV epicardial and to TriV pacing in terms of acute hemodynamic response. Further investigation is needed to confirm the chronic benefit of this approach in humans.

Background— Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. We aimed to assess the impact of baseline QRS duration and morphology and the change in QRS duration with pacing on CRT outcomes in mild heart failure. Methods and Results— Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) was a multicenter randomized trial of CRT among 610 patients with mild heart failure. Baseline and CRT-paced QRS durations and baseline QRS morphology were evaluated by blinded core laboratories. The mean baseline QRS duration was 151±23 milliseconds, and 60.5% of subjects had left bundle-branch block (LBBB). Patients with LBBB experienced a 25.3-mL/m 2 mean reduction in left ventricular end-systolic volume index ( P 2 ; P =0.18). Baseline QRS duration was also a strong predictor of change in left ventricular end-systolic volume index with monotonic increases as QRS duration prolonged. Similarly, the clinical composite score improved with CRT for LBBB subjects (odds ratio, 0.530; P =0.0034) but not for non-LBBB subjects (odds ratio, 0.724; P =0.21). The association between clinical composite score and QRS duration was highly significant (odds ratio, 0.831 for each 10-millisecond increase in QRS duration; P Conclusion— REVERSE demonstrated that LBBB and QRS prolongation are markers of reverse remodeling and clinical benefit with CRT in mild heart failure. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00271154.

International audience; BACKGROUND: Because of the lack of reliable echocardiographic parameters to predict recovery after surgery, the optimal timing of surgery for severe mitral regurgitation remains controversial. The aim of this study was to determine whether global longitudinal strain (GLS) recorded preoperatively could help in predicting left ventricular (LV) ejection fraction (LVEF) postoperatively. METHODS: A total of 88 patients (mean age, 63 ± 13 years; 59 men) with severe degenerative mitral regurgitation were included prospectively in this study. Rest echocardiography was performed before and 6 ± 1 months after mitral valve surgery. Patients were divided into two groups: group A (postoperative LVEF ≥ 50%) and group B (postoperative LVEF < 50%). RESULTS: In group B, patients had larger preoperative LV end-systolic diameters (21.6 ± 2.6 vs 19.2 ± 3.7 mm/m(2), P = .02) and impaired preoperative GLS (-17 ± 2.8% vs -19.6 ± 3.6%, P = .01), whereas there was no difference in preoperative LVEF. Preoperative LV end-systolic diameter ≥ 22 mm/m(2) and GLS < -18% were independent predictors of postoperative LV dysfunction. CONCLUSIONS: LV end-systolic diameter is a well-recognized prognostic marker. In addition, this study demonstrates the additive and independent predictive value of preoperative GLS for predicting postoperative LV dysfunction.

Background— Low-flow low-gradient (LFLG) is sometimes observed in severe aortic stenosis (AS) despite normal ejection fraction, but its frequency and mechanisms are still debated. We aimed to describe the characteristics of patients with LFLG AS and assess the presence of longitudinal left ventricular dysfunction in these patients. Methods and Results— In a multicenter prospective study, 340 consecutive patients with severe AS and normal ejection fraction were studied. Longitudinal left ventricular function was assessed by 2D-strain and global afterload by valvulo-arterial impedance. Patients were classified according to flow and gradient: low flow was defined as a stroke volume index ≤35 mL/m 2 , low gradient as a mean gradient ≤40 mm Hg. Most patients (n=258, 75.9%) presented with high-gradient AS, and 82 patients (24.1%) with low-gradient AS. Among the latter, 52 (15.3%) presented with normal flow and low gradient and 30 (8.8%) with LFLG. As compared with normal flow and low gradient, patients with LFLG had more severe AS (aortic valve area=0.7±0.12 cm 2 versus 0.86±0.14 cm 2 ), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m 2 ), and worse longitudinal left ventricular function (basal longitudinal strain=−11.6±3.4 versus −14.8±3%; P Conclusions— LFLG AS is observed in 9% of patients with severe AS and normal ejection fraction and is associated with high global afterload and reduced longitudinal systolic function. Patients with normal-flow low-gradient AS are more frequent and present with less severe AS, normal afterload, and less severe longitudinal dysfunction. Severe left ventricular longitudinal dysfunction is a new explanation to the concept of LFLG AS.

International audience; BACKGROUND: Primary systemic amyloidosis is a severe plasma cell disorder characterized by the extracellular deposition of amyloid fibrils in different organs. Echocardiography is usually performed to assess cardiac involvement. We hypothesized that in patients with systemic amyloidosis, simple echocardiographic measurement of the left atrial (LA) diameter indexed to the body surface area might provide an important risk marker for this disease. METHODS: Between 1997 and 2011, 134 patients were diagnosed with primary systemic amyloidosis and had echocardiography within 28 days; we collected their baseline characteristics and biological and echocardiographic data retrospectively. LA enlargement was defined as recommended as M-mode LA diameter greater or equal to 23 mm/m(2). RESULTS: One hundred and eleven patients (83%) had echocardiographic LA dimension data available (mean age 63±11 years; 61% men; 31% previously diagnosed with systemic hypertension). Mean left ventricular ejection fraction (LVEF) and interventricular septum thickness (IVST) were 62±12% and 14±4 mm, respectively. Mean follow-up was 2.8±2.9 years (maximum 12 years). Patients with LA enlargement had a slightly lower LVEF (P=0.08) and a significantly greater IVST (P

International audience; Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin.

International audience; Leptin is known to exert cardiodepressive effects and to induce left ventricular (LV) remodelling. Nevertheless, the autocrine and/or paracrine activities of this adipokine in the context of post-infarct dysfunction and remodelling have not yet been elucidated. Therefore, we have investigated the evolution of myocardial leptin expression following myocardial infarction (MI) and evaluated the consequences of specific cardiac leptin inhibition on subsequent LV dysfunction. Anaesthetized rats were subjected to temporary coronary occlusion. An antisense oligodesoxynucleotide (AS ODN) directed against leptin mRNA was injected intramyocardially along the border of the infarct 5 days after surgery. Cardiac morphometry and function were monitored by echocardiography over 11 weeks following MI. Production of myocardial leptin and pro-inflammatory cytokines interleukin (IL)-1β and IL-6 were assessed by ELISA. Our results show that (1) cardiac leptin level peaks 7 days after reperfused MI; (2) intramyocardial injection of leptin-AS ODN reduces early IL-1β and IL-6 overexpression and markedly protects contractile function. In conclusion, our findings demonstrate that cardiac leptin expression after MI could contribute to the evolution towards heart failure through autocrine and/or paracrine actions. The detrimental effect of leptin could be mediated by pro-inflammatory cytokines such as IL-1β and IL-6. Our data could constitute the basis of new therapeutic approaches aimed to improve post-MI outcome.

International audience; AIMS: Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability. METHODS AND RESULTS: One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed. CONCLUSION: Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. Clinical Trial Registration Information: URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707.

International audience; BACKGROUND: Cardiac resynchronization therapy (CRT) is an important therapeutic approach for patients with symptomatic heart failure. The assessment of mechanical dyssynchrony, however, remains an issue. Little data are available regarding the influence of the right ventricle (RV) on left ventricle (LV) mechanical dyssynchrony as assessed by echocardiography. AIMS: We sought to assess the impact of RV contractility on LV function and dyssynchrony. METHODS: A total of 40 patients with congestive heart failure were analyzed. Twenty had RV dysfunction, as defined by a tricuspid annular systolic peak of tissue Doppler (SaRV)11.5 cm/s. All patients underwent echocardiography in order to determine RV function, LV function, and dyssynchrony. RESULTS: The two populations were similar regarding diastolic function, atrio-ventricular conduction and interventricular dyssynchrony. Patients with RV dysfunction showed significantly more severe LV longitudinal dyssynchrony (130±103 ms vs. 62±59 ms; p=0.01). In addition, SaRV (systolic peak recorded at the tricuspid annulus) was correlated with LV longitudinal dyssynchrony (r=0.47; p=0.001). In contrast, LV radial contractility and dyssynchrony (103±110 ms vs. 100±78 ms; p=0.5) were not affected by RV function. CONCLUSION: Quantitative analysis of RV function is important when assessing LV function and dyssynchrony in patients with systolic heart failure. RV function is associated with intra-LV dyssynchrony, particularly when considering longitudinal function.

International audience; SCOPE: Post-infarct left ventricular dysfunction and cardiac remodeling are the primary causes of chronic heart failure in industrialized countries. In the present study, we examined the influence of dietary selenium intake on cardiac remodeling after reperfused myocardial infarction and explored one of the possible mechanisms. METHODS AND RESULTS: Rats were fed a diet containing either 0.05 mg/kg (Low-Se, group of rats receiving the low-selenium diet) or 1.50 mg/kg (group of rats receiving the high-selenium diet) selenium. At the end of the 5th week of the diet, rats were subjected to transient (1 h) coronary ligation followed by 8 days of reperfusion. Infarct size and cardiac passive compliance were increased in the Low-Se group compared with group of rats receiving the high-selenium diet. Similarly, indices of cardiac remodeling (thinning index and expansion index) were more altered in Low-Se hearts. These adverse effects of the Low-Se diet on cardiac remodeling were accompanied by an increase in cardiac TNF-α content, a decreased activity of antioxidant seleno-enzymes and an increase in connexin-43 dephosphorylation. CONCLUSION: Dietary selenium intake influences post-infarct cardiac remodeling even when provided within the range of physiological values. Our data suggest that the cardioprotective effect of selenium might be mediated by a reduced oxidative stress, a lower connexin-43 dephosphorylation, and a decreased TNF-α expression.

International audience; AIMS: The clinical features, prognosis, and even definition of left ventricular non-compaction (LVNC) are still the subject of much debate. The aim of this registry was to describe the clinical, echocardiographic, and prognostic features of LVNC in France. The main endpoint was to assess clinical and echocardiographic predictors of adverse outcome, defined as death or heart transplantation. METHODS AND RESULTS: Between 2004 and 2006, 154 suspected cases of LNVC were identified from a nationwide survey in France. The diagnosis of LVNC was confirmed in 105 cases by echocardiographic evaluation in a core laboratory. Clinical and echocardiographic data for the 105 cases of LVNC are presented. Left ventricular non-compaction was first detected from heart failure symptoms in 45 patients, rhythm disorders in 12, and familial screening in 8. Left ventricular ejection fraction (LVEF) was < 30% in 46% of patients, but ≥ 50% in 16%. The latter had less symptoms of severe heart failure (11 vs. 54%, P = 0.001), but similar extension of the NC zone. During 2.33 ± 1.47 years of follow-up, several complications occurred, including severe heart failure in 33 patients, transplantation in 9, ventricular arrhythmia in 7, embolic events in 9, and death in 12. Factors associated with death or heart transplantation were NYHA 3 or 4 (HR = 6.69; P = 0.0007), high LV filling pressures (HR = 7.59; P = 0.001), LVEF (HR = 0.93; P = 0.006), and hospitalization for heart failure (HR = 13.55; P < 0.0001). CONCLUSION: In this large reported series of LVNC, we observed that: (i) Left ventricular non-compaction was detected by familial screening in asymptomatic patients in 8% of cases. (ii) Left ventricular non-compaction was frequently over-diagnosed by echocardiography. (iii) Patients identified as LVNC presented with a high risk of severe complications, transplantation or death and needed close follow-up.

International audience; AIMS: left ventricular (LV) mechanical dyssynchrony (LVMD) has emerged as a therapeutic target using cardiac resynchronization therapy (CRT) in chronic heart failure patients. Current methods used to evaluate LVMD are technically challenging and do not assess all the components of LVMD simultaneously. We analysed real-time 3D speckle tracking (3DST) echocardiography as a novel method to assess LVMD. METHODS AND RESULTS: three-dimensional ST was performed in 60 unselected patients (71 ± 9 years old; 39% with ischaemic cardiomyopathy) who were referred to optimize and to control of a CRT device; implanted according to current guidelines (9 added to be excluded from the protocol). Two standardized conditions [right ventricular (RV) versus an optimized biventricular (BiV) pacing modality] were tested. These two pacing modalities lead to two distinct electrical activation patterns. We sought to test the capability of 3DST to distinguish these two patterns. The LV ejection fraction was 24 ± 9 in the RV mode and 29 ± 10% in BiV. By 3DST, we measured global end-systolic LV deformation and dyssynchrony (standard deviation of the time to peak/16 LV-segment). The 3D radial strain increased from 13.8 ± 5.7 in the RV to 15.9 ± 6.5% in theBiV mode, and the dyssynchrony index decreased from 15.1 ± 5.0 to 11.8 ± 4.1%. 3D longitudinal strain increased from -6.9 ± 2.8 in the RV to -7.8 ± 3.2% in the BiV mode, and the dyssynchrony index decreased from 14.2 ± 4.8 to 11.5 ± 5.0% (P < 0.01 for all). The 3D area strain (AS) increased from -15.4 ± 6 in the RV to -18.3 ± 7.0% in the BiV mode, and the dyssynchrony index decreased from 12.2 ± 5.1 to 9.5 ± 4.5% (P < 0.001 for all). CONCLUSION: When image quality is optimal, 3DST might offer a new rapid method to quantify global LVMD in CRT candidates. In a comparison of the utility of various 3D strain measurements, the 3D AS appears to be closed to the ideal parameter that we are looking for.

International audience; BACKGROUND: The risk stratification of patients with left ventricular (LV) dysfunction can be performed using echocardiographic parameters such as the ejection fraction (EF). Recently, new technologies based on deformation measurements have been shown to identify early myocardial dysfunction before EF decrease. Consequently, tools such as two-dimensional strain have been incorporated into echocardiographic systems, allowing for fast, reliable, and reproducible calculation of longitudinal components of LV systolic deformation. The hypothesis in this study was that as a more sensitive marker of LV dysfunction, longitudinal strain would allow for the risk stratification of patients with heart failure. METHODS: This multicenter study included 147 patients with heart failure with LV EFs ≤ 45% (mean age, 64 ± 14 years; 74% men; mean LV EF, 29.9 ± 8.9%). Conventional echocardiographic parameters as well as global and segmental longitudinal strain were measured and compared with these values in a control population. Patients were monitored for cardiac events, defined as a composite criterion, over 12 months. RESULTS: Clinical events were observed in 20% of patients during the 12-month follow-up period. On receiver operating characteristic curve analysis, global longitudinal strain had the highest prognostic value (area under the curve, 0.83) and the highest combination of sensitivity (73%) and specificity (83%), using a cutoff value of -7%. CONCLUSION: Strain assessment is highly feasible and reliable in patients with LV dysfunction and allows for cardiovascular risk stratification in patients with heart failure with greater accuracy than LV EF.

Adenylyl cyclase (AC) type 5 (AC5) and AC type 6 (AC6) are the two major AC isoforms in the heart. Cardiac overexpression of AC6 has been shown to be protective in response to several interventions. In this investigation, we examined the effects of chronic pressure overload in AC6 transgenic (TG) mice. In the absence of any stress, AC6 TG mice exhibited enhanced contractile function compared with their wild-type (WT) littermates, i.e., increased ( P < 0.05) left ventricular (LV) ejection fraction (EF) (75 ± 0.9 vs. 71 ± 0.5%) and LV dP/d t (7,850 ± 526 vs. 6,374 ± 315 mmHg/s). Forskolin (25 μg·kg−1·min−1for 5 min) increased LVEF more ( P < 0.05) in AC6 TG mice (14.8 ± 1.0%) than in WT mice (7.7 ± 1.0%). Also, isoproterenol (0.04 μg·kg−1·min−1for 5 min) increased LVEF more ( P < 0.05) in AC6 TG mice (18.0 ± 1.2%) than in WT mice (11.6 ± 2.1%). Pressure overload, induced by 4 wk of transverse aortic constriction (TAC), increased the LV weight-to-body weight ratio and myocyte cross-sectional area similarly in both groups, but reduced LVEF more in AC6 TG mice (22%) compared with WT mice (9%), despite the higher starting level of LVEF in AC6 TG mice. LV systolic wall stress increased more in AC6 TG mice than in WT mice, which could be responsible for the reduced LVEF in AC6 TG mice with chronic pressure overload. In addition, LV dP/d t was no longer elevated in AC6 TG mice after TAC compared with WT mice. LV end-diastolic diameter was also greater ( P < 0.05) in AC6 TG mice (3.8 ± 0.07 mm) than in WT mice (3.6 ± 0.05 mm) after TAC. Thus, in contrast to other interventions previously reported to be salutary with cardiac AC6 overpression, the response to chronic pressure overload was not; actually, AC6 TG mice fared worse than WT mice. The mechanism may be due to the increased LV systolic wall stress in AC6 TG mice with chronic pressure overload.

Background— Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics. Methods and Results— In dogs with left bundle branch block and pacing-induced heart failure (n=7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity. Conclusions— CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT.

International audience; Frequency domain analysis of heart rate variation has been suggested as an effective screening tool for sleep-disordered breathing (SDB) in the general population. The aim of this study was to assess this method in patients with chronic congestive heart failure (CHF). We included prospectively 84 patients with stable CHF, left ventricular ejection fraction (LVEF) or =15 h(-1) was diagnosed in 57.4% of patients. Percent VLFI was not correlated with AHI (r = 0.12). Receiver-operating characteristic curves constructed using various AHI cut-offs (5-30 h(-1)) failed to identify a %VLFI cut-off associated with SDB. The 2.4% VLFI cut-off recommended for the general population of patients with suspected SDB had low specificity (35%) and low positive and negative predictive values (35% and 54%, respectively). Heart rate increment analysis has several limitations in CHF patients and cannot be recommended as an SDB screening tool in the CHF population.

Background Early detection of diastolic dysfunction is crucial for patients with incipient heart failure. Although this evaluation could be performed from phase-contrast (PC) cardiovascular magnetic resonance (CMR) data, its usefulness in clinical routine is not yet established, mainly because the interpretation of such data remains mostly based on manual post-processing. Accordingly, our goal was to develop a robust process to automatically estimate velocity and flow rate-related diastolic parameters from PC-CMR data and to test the consistency of these parameters against echocardiography as well as their ability to characterize left ventricular (LV) diastolic dysfunction. Results We studied 35 controls and 18 patients with severe aortic valve stenosis and preserved LV ejection fraction who had PC-CMR and Doppler echocardiography exams on the same day. PC-CMR mitral flow and myocardial velocity data were analyzed using custom software for semi-automated extraction of diastolic parameters. Inter-operator reproducibility of flow pattern segmentation and functional parameters was assessed on a sub-group of 30 subjects. The mean percentage of overlap between the transmitral flow segmentations performed by two independent operators was 99.7 ± 1.6%, resulting in a small variability ( 0.71) and receiver operating characteristic (ROC) analysis revealed their ability to separate patients from controls, with sensitivity > 0.80, specificity > 0.80 and accuracy > 0.85. Slight superiority in terms of correlation with echocardiography (r = 0.81) and accuracy to detect LV abnormalities (sensitivity > 0.83, specificity > 0.91 and accuracy > 0.89) was found for the PC-CMR flow-rate related parameters. Conclusions A fast and reproducible technique for flow and myocardial PC-CMR data analysis was successfully used on controls and patients to extract consistent velocity-related diastolic parameters, as well as flow rate-related parameters. This technique provides a valuable addition to established CMR tools in the evaluation and the management of patients with diastolic dysfunction.

Objectives The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. Background Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. Methods We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS >= 120 ms and LV ejection fraction

International audience; Syncope is a common disorder which may recur and impair the survival and the quality of life of the patients. The objective of the investigation of syncope is to diagnose the cardiac etiology, as mortality rate is high. Implantable loop recorder or insertable cardiac monitor (ICM) is a useful tool to establish a correlation between syncope and heart rhythm. About half of implanted patients complain of a new syncope and about 50% of these patients had cardiac rhythm disturbances on ICM. The most frequent is a sinus bradycardia or sinus arrest, but these results depend on the age of patients, resting electrocardiography (ECG) abnormalities and structural cardiac disease. A classification of the mechanisms of recurrent syncopes has been defined with the results of the ISSUE study, separating the syncope due to primary cardiac arrhythmia from neurally-mediated syncope and from unknown syncope. The analysis of the presyncopal phase on the ICM restored ECG allows physicians to adapt the treatment (antiarrhytmic agents or pacemaker) and optimize the programming of the pacemaker when necessary. It is early recommended to implant the ICM in patients affected with syncope with normal physical examination, normal ECG and without structural heart disease and negative tilt testing. In the presence of cardiac disease, it is recommended to implant ICM after performing an electrophysiological study and tilt testing. In syncope patients with depressed left ventricular ejection fraction, the implantation of an automatic implantable cardiac defibrillator is preferable. The indications of the ICM tend to be extended to new syncope populations such as pediatric patients and epileptic population. Early application of ICM reduces the cost of the investigation of the patients suffering from syncope, especially when the electrophysiological study is avoided. In the future the implantation of the ICM should be early discussed in the Syncope Unit to shorten the duration and the cost of the hospitalizations of the patients with recurrent syncopes.

International audience; Post-myocardial infarction (MI) heart failure is a major public health problem in Western countries and results from ischemia/reperfusion (IR)-induced cell death, remodeling, and contractile dysfunction. Ex vivo studies have demonstrated the cardioprotective anti-inflammatory effect of the cannabinoid type 2 (CB2) receptor agonists within hours after IR. Herein, we evaluated the in vivo effect of CB2 receptors on IR-induced cell death, fibrosis, and cardiac dysfunction and investigated the target role of cardiac myocytes and fibroblasts. The infarct size was increased 24 h after IR in CB2(-/-) vs. wild-type (WT) hearts and decreased when WT hearts were injected with the CB2 agonist JWH133 (3 mg/kg) at reperfusion. Compared with WT hearts, CB2(-/-) hearts showed widespread injury 3 d after IR, with enhanced apoptosis and remodeling affecting the remote myocardium. Finally, CB2(-/-) hearts exhibited exacerbated fibrosis, associated with left ventricular dysfunction 4 wk after IR, whereas their WT counterparts recovered normal function. Cardiac myocytes and fibroblasts isolated from CB2(-/-) hearts displayed a higher H(2)O(2)-induced death than WT cells, whereas 1 microM JWH133 triggered survival effects. Furthermore, H(2)O(2)-induced myofibroblast activation was increased in CB2(-/-) fibroblasts but decreased in 1 microM JWH133-treated WT fibroblasts, compared with that in WT cells. Therefore, CB2 receptor activation may protect against post-IR heart failure through direct inhibition of cardiac myocyte and fibroblast death and prevention of myofibroblast activation.

International audience; Post-myocardial infarction (MI) heart failure is a major public health problem in Western countries and results from ischemia/reperfusion (IR)-induced cell death, remodeling, and contractile dysfunction. Ex vivo studies have demonstrated the cardioprotective anti-inflammatory effect of the cannabinoid type 2 (CB2) receptor agonists within hours after IR. Herein, we evaluated the in vivo effect of CB2 receptors on IR-induced cell death, fibrosis, and cardiac dysfunction and investigated the target role of cardiac myocytes and fibroblasts. The infarct size was increased 24 h after IR in CB2(-/-) vs. wild-type (WT) hearts and decreased when WT hearts were injected with the CB2 agonist JWH133 (3 mg/kg) at reperfusion. Compared with WT hearts, CB2(-/-) hearts showed widespread injury 3 d after IR, with enhanced apoptosis and remodeling affecting the remote myocardium. Finally, CB2(-/-) hearts exhibited exacerbated fibrosis, associated with left ventricular dysfunction 4 wk after IR, whereas their WT counterparts recovered normal function. Cardiac myocytes and fibroblasts isolated from CB2(-/-) hearts displayed a higher H(2)O(2)-induced death than WT cells, whereas 1 microM JWH133 triggered survival effects. Furthermore, H(2)O(2)-induced myofibroblast activation was increased in CB2(-/-) fibroblasts but decreased in 1 microM JWH133-treated WT fibroblasts, compared with that in WT cells. Therefore, CB2 receptor activation may protect against post-IR heart failure through direct inhibition of cardiac myocyte and fibroblast death and prevention of myofibroblast activation.

Background— Numerous studies have reported evidence of cardiac injury associated with transient left ventricular (LV) systolic and diastolic dysfunction after prolonged and strenuous exercise. We used 2D ultrasound speckle tracking imaging to evaluate the effect of an ultralong-duration exercise on LV regional strains and torsion. We speculated that systolic dysfunction after exercise is associated with depressed LV strains and torsion, and diastolic dysfunction results from decreased and delayed untwisting, a key factor of LV suction and early filling. Methods and Results— Twenty-three triathletes underwent conventional and speckle tracking imaging echocardiography at rest before and immediately after an ultralong distance triathlon. Measurements included LV longitudinal, circumferential and radial strains, LV rotations, and LV torsion. After the race, LV systolic dysfunction was characterized by a decrease in LV longitudinal, radial, and circumferential strains, especially for apical radial strains (44.6�15.1% versus 31.1�13.8%, P P =0.09) and significantly delayed (91�18% versus 128�31% of systolic duration, P Conclusions— This study documented major alterations in cardiac strains and torsion after an ultralong distance triathlon. LV systolic strains were depressed but not delayed, whereas twisting was decreased and delayed. This altered pattern hampered the rapid untwisting during isovolumic relaxation phase, reducing LV diastolic suction and early filling.

International audience; BACKGROUND: Since its first description in 1991, many cases of transient left ventricular apical ballooning syndrome (TLVABS) have been described, but the use of cardiac MRI in this condition is much more recent. METHODS AND RESULTS: We performed a systematic review of the present literature in the MEDLINE and EMBASE databases for relevant case series of TLVABS (>or=5 reported original cases, MRI analysis in the acute phase) and summarized the main results in a narrative synthesis. Only 8 studies met the eligible criteria, counting 176 patients (women: 95%; age: 68, stress trigger: 80%). MRI assessed an improvement of mean left ventricular ejection fraction from 39 (in the acute phase) to 64% (in the recovery phase). A right ventricular dysfunction was reported in 38%, a myocardial oedema in 81% and an apical thrombus in 5%. CONCLUSIONS: Although cardiac MRI is a very useful and inescapable tool in the management of TLVABS, there is no large published study concerning this topic. A systematic and multicentric register of TLVABS studied by cardiac MRI is necessary.

International audience; AIMS: Lack of response to cardiac resynchronization therapy (CRT) may be due to the presence of significant amount of scar or fibrotic tissue at myocardial level. This study sought to investigate the potential impact of myocardial contractile reserve as assessed during exercise echocardiography on left ventricular (LV) reverse remodelling (decrease in LV end-systolic volume > or =15% after 6 months of CRT). METHODS AND RESULTS: Fifty-one consecutive patients with heart failure underwent exercise Doppler echocardiography before CRT implantation to assess global contractile reserve and local contractile reserve (assessed by two-dimensional speckle tracking) in the region of the LV pacing lead. Responders (30 patients) showed a greater exercise-induced increase in left ventricular ejection fraction (LVEF) compared with non-responders (P < 0.001). Contractile reserve was directly related to the improvement in LVEF and to LV reverse remodelling after 6 months of CRT (P < 0.001). A 6.5% exercise-induced increase in LVEF yielded a sensitivity of 90% and a specificity of 85.7% to predict the response after 6 months of CRT. Baseline myocardial deformation as well as contractile reserve in the LV pacing lead region was greater in responders than in non-responders (P < 0.0001). CONCLUSION: Myocardial contractile reserve (global and regional) is a strong predictive factor of LV reverse remodelling after CRT.

Summary Background Meta-analyses have confirmed the high performance of multislice computed tomography (MSCT) in coronary stenosis detection. Recent reports have described the study of left ventricular anatomy and function and coronary venous anatomy with MSCT. Aims We sought to compare, in patients with cardiomyopathy of unknown origin, the performance of MSCT versus angiography for significant coronary artery disease detection and versus transthoracic echocardiography (TTE) for left ventricular anatomy and function evaluation, and to assess its ability to characterize coronary venous anatomy. Methods Fifty-nine patients with cardiomyopathy (left ventricular ejection fraction [LVEF] less than or equal to 40%) of unknown origin, in sinus rhythm, underwent MSCT, TTE and coronary angiography. Results Twenty-four (3%) of 724 analysable coronary segments (97%) and 12 (20%) patients had significant coronary artery disease. MSCT sensitivity, specificity, and positive and negative predictive values for coronary artery disease detection were 87.5%, 98.5%, 67.7% and 99.6% in the per-segment assessment and 100%, 91%, 75% and 100% in the per-patient evaluation, respectively. Statistical analyses showed good agreement between MSCT and TTE in LVEF measurement (33 ± 10% vs 32 ± 11%, p = 0.4, mean difference = 0.7%, limits of agreement ± 13.6%) and a small LVED diameter overestimation (65.0 ± 9.3 mm vs 63.6 ± 9.4 mm, p = 0.03). MSCT allowed detection of the posterolateral vein in 86% of cases. Conclusions In selected patients presenting with idiopathic cardiomyopathy, MSCT is accurate for coronary artery disease detection and is a useful coronary venous imaging tool. MSCT studies of left ventricular function and morphology were mostly concordant with TTE measurements.

International audience; AIM: To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS: A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION: CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.

International audience; BACKGROUND: Cardiac resynchronization therapy (CRT), which improves left ventricular (LV) function and reverses LV remodeling, is an established therapy for advanced heart failure with prolonged QRS duration. The aim of this study was to examine whether CRT improves atrial function and induces atrial reverse remodeling. METHODS: A total of 46 patients with heart failure (mean age, 66.7 +/- 10.4 years) who underwent CRT were evaluated with echocardiography before and after 6 months of optimized CRT. Atrial function and LV function were assessed with M-mode, two-dimensional echocardiography, Doppler, tissue Doppler velocity, and strain (epsilon) imaging. LV reverse remodeling was defined as a reduction in LV end-systolic volume of >15%. RESULTS: In responders (n = 23), significant improvements in left atrial (LA) functional, structural, and anatomic remodeling were observed. Maximum LA area and volume decreased, the LA emptying fraction increased, A' increased, and LA epsilon increased from 25.6 +/- 11.0% to 42.6 +/- 10.4% (P < .05 overall). LA reverse remodeling was correlated with baseline LA volume (R = 0.45). Although the correlation was not significant (r = 0.24), LA reverse remodeling was also more frequent in patients with LV reverse remodeling. CONCLUSIONS: In patients with LV remodeling, significant LA reverse remodeling after CRT could be observed and detailed on transthoracic echocardiography.

International audience; BACKGROUND: The tripeptide glutathione (L-gamma-glutamyl-cysteinyl-glycine) is essential to cell survival, and deficiency in cardiac and systemic glutathione relates to heart failure progression and cardiac remodelling in animal models. Accordingly, we investigated cardiac and blood glutathione levels in patients of different functional classes and with different structural heart diseases. METHODS: Glutathione was measured using standard enzymatic recycling method in venous blood samples obtained from 91 individuals, including 15 healthy volunteers and 76 patients of New York Heart Association (NYHA) functional class I to IV, undergoing cardiac surgery for coronary artery disease, aortic stenosis or terminal cardiomyopathy. Glutathione was also quantified in right atrial appendages obtained at the time of surgery. RESULTS: In atrial tissue, glutathione was severely depleted (-58%) in NYHA class IV patients compared to NYHA class I patients (P = 0.002). In patients with coronary artery disease, this depletion was related to the severity of left ventricular dysfunction (P = 0.006). Compared to healthy controls, blood glutathione was decreased by 21% in NYHA class I patients with structural cardiac disease (P