High prevalence of arrhythmic and myocardial complications in patients with cardiac glycogenosis due to PRKAG2 mutations.

AIMS: Mutations in PRKAG2, the gene encoding for the γ2 subunit of 5'-AMP-activated protein kinase (AMPK), are responsible for an autosomal dominant glycogenosis with a cardiac presentation, associating hypertrophic cardiomyopathy (HCM), ventricular pre-excitation (VPE), and progressive heart block. The aim of this study was to perform a retrospective time-to-event study of the clinical manifestations associated with PRKAG2 mutations. METHODS AND RESULTS: A cohort of 34 patients from 9 families was recruited between 2001 and 2010. DNA were sequenced on all exons and flanking sequences of the PRKAG2 gene using Sanger sequencing. Overall, four families carried the recurrent p.Arg302Gln mutation, and the five others carried private mutations among which three had never been reported. In the total cohort, at 40 years of age, the risk of developing HCM was 61%, VPE 70%, conduction block 22%, and sudden cardiac death (SCD) 20%. The global survival at 60 years of age was 66%. Thirty-two per cent of patients (N = 10) required a device implantation (5 pacemakers and 5 defibrillators) at a median age of 66 years, and two patients required heart transplant. Only one patient presented with significant skeletal muscle symptoms. No significant differences regarding the occurrence of VPE, ablation complications, or death incidence were observed between different mutations. CONCLUSION: This study of patients with PRKAG2 mutations provides a more comprehensive view of the natural history of this disease and demonstrates a high risk of cardiac complications. Early recognition of this disease appears important to allow an appropriate management.

Population movement and sudden cardiac arrest location.

BACKGROUND: Although the benefits of automatic external defibrillators are undeniable, their effectiveness could be dramatically improved. One of the key issues is the disparity between the locations of automatic external defibrillators and sudden cardiac arrests (SCAs). METHODS AND RESULTS: From emergency medical services and other Parisian agencies, data on all SCAs occurring in public places in Paris, France, were prospectively collected between 2000 and 2010 and recorded using 2020 grid areas. For each area, population density, population movements, and landmarks were analyzed. Of the 4176 SCAs, 1255 (30%) occurred in public areas, with a highly clustered distribution of SCAs, especially in areas containing major train stations (12% of SCAs in 0.75% of the Paris area). The association with population density was poor, with a nonsignificant increase in SCAs with population density (P=0.4). Occurrence of public SCAs was, in contrast, highly associated with population movements (P<0.001). In multivariate analysis including other landmarks in each grid cell in the model and demographic characteristics, population movement remained significantly associated with the occurrence of SCA (odds ratio, 1.48; 95% confidence interval, 1.34-1.63; P<0.0001), as well as grid cells containing train stations (odds ratio, 3.80; 95% confidence interval, 2.66-5.36; P<0.0001). CONCLUSIONS: Using a systematic analysis of determinants of SCA in public places, we demonstrated the extent to which population movements influence SCA distribution. Our findings also suggested that beyond this key risk factor, some areas are dramatically associated with a higher risk of SCA.

First clinical use of a bioprosthetic total artificial heart: report of two cases.

BACKGROUND: The development of artificial hearts in patients with end-stage heart disease have been confronted with the major issues of thromboembolism or haemorrhage. Since valvular bioprostheses are associated with a low incidence of these complications, we decided to use bioprosthetic materials in the construction of a novel artificial heart (C-TAH). We report here the device characteristics and its first clinical applications in two patients with end-stage dilated cardiomyopathy. The aim of the study was to evaluate safety and feasibility of the CARMAT TAH for patients at imminent risk of death from biventricular heart failure and not eligible for transplant. METHODS: The C-TAH is an implantable electro-hydraulically actuated pulsatile biventricular pump. All components, batteries excepted, are embodied in a single device positioned in the pericardial sac after excision of the native ventricles. We selected patients admitted to hospital who were at imminent risk of death, having irreversible biventricular failure, and not eligible for heart transplantation, from three cardiac surgery centres in France. FINDINGS: The C-TAH was implanted in two male patients. Patient 1, aged 76 years, had the C-TAH implantation on Dec 18, 2013; patient 2, aged 68 years, had the implantation on Aug 5, 2014. The cardiopulmonary bypass times for C-TAH implantation were 170 min for patient 1 and 157 min for patient 2. Both patients were extubated within the first 12 postoperative hours and had a rapid recovery of their respiratory and circulatory functions as well as a normal mental status. Patient 1 presented with a tamponade on day 23 requiring re-intervention. Postoperative bleeding disorders prompted anticoagulant discontinuation. The C-TAH functioned well with a cardiac output of 4·8-5·8 L/min. On day 74, the patient died due to a device failure. Autopsy did not detect any relevant thrombus formation within the bioprosthesis nor the different organs, despite a 50-day anticoagulant-free period. Patient 2 experienced a transient period of renal failure and a pericardial effusion requiring drainage, but otherwise uneventful postoperative course. He was discharged from the hospital on day 150 after surgery with a wearable system without technical assistance. After 4 months at home, the patient suffered low cardiac output. A change of C-TAH was attempted but the patient died of multiorgan failure. INTERPRETATION: This preliminary experience could represent an important contribution to the development of total artificial hearts using bioprosthetic materials. FUNDING: CARMAT SA.

Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report.

AIMS: Comparative studies suggest that stem cells committed to a cardiac lineage are more effective for improving heart function than those featuring an extra-cardiac phenotype. We have therefore developed a population of human embryonic stem cell (ESC)-derived cardiac progenitor cells. METHODS AND RESULTS: Undifferentiated human ESCs (I6 line) were amplified and cardiac-committed by exposure to bone morphogenetic protein-2 and a fibroblast growth factor receptor inhibitor. Cells responding to these cardio-instructive cues express the cardiac transcription factor Isl-1 and the stage-specific embryonic antigen SSEA-1 which was then used to purify them by immunomagnetic sorting. The Isl-1(+) SSEA-1(+) cells were then embedded into a fibrin scaffold which was surgically delivered onto the infarct area in a 68-year-old patient suffering from severe heart failure [New York Heart Association [NYHA] functional Class III; left ventricular ejection fraction (LVEF): 26%]. A coronary artery bypass was performed concomitantly in a non-infarcted area. The implanted cells featured a high degree of purity (99% were SSEA-1(+)), had lost the expression of Sox-2 and Nanog, taken as markers for pluripotency, and strongly expressed Isl-1. The intraoperative delivery of the patch was expeditious. The post-operative course was uncomplicated either. After 3 months, the patient is symptomatically improved (NYHA functional Class I; LVEF: 36%) and a new-onset contractility is echocardiographically evident in the previously akinetic cell/patch-treated, non-revascularized area. There have been no complications such as arrhythmias, tumour formation, or immunosuppression-related adverse events. CONCLUSION: This observation demonstrates the feasibility of generating a clinical-grade population of human ESC-derived cardiac progenitors and combining it within a tissue-engineered construct. While any conclusion pertaining to efficacy would be meaningless, the patient's functional outcome yet provides an encouraging hint. Beyond this case, the platform that has been set could be useful for generating different ESC-derived lineage-specific progenies.

Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience.

AIM: There is now compelling evidence that cells committed to a cardiac lineage are most effective for improving the function of infarcted hearts. This has been confirmed by our pre-clinical studies entailing transplantation of human embryonic stem cell (hESC)-derived cardiac progenitors in rat and non-human primate models of myocardial infarction. These data have paved the way for a translational programme aimed at a phase I clinical trial. METHODS AND RESULTS: The main steps of this programme have included (i) the expansion of a clone of pluripotent hESC to generate a master cell bank under good manufacturing practice conditions (GMP); (ii) a growth factor-induced cardiac specification; (iii) the purification of committed cells by immunomagnetic sorting to yield a stage-specific embryonic antigen (SSEA)-1-positive cell population strongly expressing the early cardiac transcription factor Isl-1; (iv) the incorporation of these cells into a fibrin scaffold; (v) a safety assessment focused on the loss of teratoma-forming cells by in vitro (transcriptomics) and in vivo (cell injections in immunodeficient mice) measurements; (vi) an extensive cytogenetic and viral testing; and (vii) the characterization of the final cell product and its release criteria. The data collected throughout this process have led to approval by the French regulatory authorities for a first-in-man clinical trial of transplantation of these SSEA-1(+) progenitors in patients with severely impaired cardiac function. CONCLUSION: Although several facets of this manufacturing process still need to be improved, these data may yet provide a useful platform for the production of hESC-derived cardiac progenitor cells under safe and cost-effective GMP conditions.

Survival from sports-related sudden cardiac arrest: In sports facilities versus outside of sports facilities.

BACKGROUND: We sought to evaluate frequency, characteristics, and outcomes of sudden cardiac arrest (SCA) during sports activities according to the location of occurrence (in sports facilities vs those occurring outside of sports facilities). METHODS AND RESULTS: This is an observational 5-year prospective national French survey of subjects 10 to 75 years old presenting with SCA during sports (2005-2010), in 60 French administrative regions (covering a population of 35 million people). Of the 820 SCA during sports, 426 SCAs (52%) occurred in sports facilities. Overall, a substantially higher survival rate at hospital discharge was observed among SCA in sports facilities (22.8%, 95% CI 18.8-26.8) compared to those occurring outside (8.0%, 95% CI 5.3-10.7) (P < .0001). Patients with SCA in sports facilities were younger (42.1 vs 51.3 years, P < .0001) and less frequently had known cardiovascular diseases (P < .0001). The events were more often witnessed (99.8% vs 84.9%, 0.0001), and bystander cardiopulmonary resuscitation was more frequently initiated (35.4% vs 25.9%, P = .003). Delays of intervention were significantly shorter when SCA occurred in sports facilities (9.3 vs 13.6, P=0.03), and the proportion of initially shockable rhythm was higher (58.8% vs 33.1%, P < .0001). Better survival in sports facilities was mainly explained by concomitant circumstances of occurrence (adjusted odds ratio 1.48, 95% CI 0.88-2.49, P = .134). CONCLUSIONS: Sports-related SCA is not a homogeneous entity. The 3-fold higher survival rate reported among sports-related SCA is mainly due to cases that occur in sports facilities, whereas SCA during sports occurring outside of sports facilities has the usual very low rate of survival.

Major regional disparities in outcomes after sudden cardiac arrest during sports.

AIMS: Characteristics of sudden cardiac arrest (SCA) during sports offers a novel (and unexplored) setting to assess factors associated with disparities in outcomes across regions. METHODS AND RESULTS: From a prospective 5-year community-based French registry concerning SCA during sports in 10-75 year-olds, we evaluated whether outcomes differed significantly between geographic regions. We then determined the extent to which variations in community-related early interventions were associated with regional variations in survival. Among 820 SCA cases studied, overall survival at hospital discharge was 15.7% (95% confidence interval, 13.2-18.2%), with considerable regional disparities (from 3.4 to 42.6%, P < 0.001). Major differences were noted regarding bystander initiation of cardiopulmonary resuscitation (15.3-80.9%, P < 0.001) and presence of initial shockable rhythm (28.6-79.1%, P < 0.001), with higher values of these being associated with better survival rates. The proportion of survivors with favourable neurological outcome at discharge was fairly uniform among survival groups (CPC-1/2, varying from 77.4 to 90.0%, P = 0.83). No difference was observed regarding subjects' characteristics and circumstances of SCA occurrence, including delays in resuscitation (collapse-to-call period). With a comparable in-hospital mortality (P = 0.44), survival at hospital discharge was highly correlated with that at hospital admission (regional variations from 7.4 to 75.0%, P < 0.001). CONCLUSION: Major regional disparities exist in survival rates (up to 10-fold) after SCA during sports. SCA cases from regions with the highest levels of bystander resuscitation had the best survival rates to hospital admission and discharge.

[Stem cell therapy and heart failure: hopes and disappointments]. / Thérapie cellulaire et insuffisance cardiaque: ombres et lumières.

Despite therapeutic advances, heart failure remains a common and serious event characterized by initial and progressive loss of cardiac myocytes, a loss that is currently untreatable. Cell therapy has emerged as a promising new approach to the treatment of heart failure, with very encouraging experimental results. Since 2000, when human stem cell therapy was first attempted in France, clinical trials with adult stem cells (myoblasts, bone-marrow derived cells, mesenchymal stem cells) have given variable results. The inconsistent and modest therapeutic benefit observed in these studies is due more to paracrine effects than to the hoped-for cell replacement, as adult stem cells do not turn into cardiomyocytes and their survival rate after transplantation is very low. In order to be effective, cell therapy should use heart muscle cells derived from pluri- or multipotent cells (human embryonic stem cells, induced pluripotent stem cells, resident cardiac cells), which are likely to have a higher survival rate in a hostile biological environment and deteriorated tissue scaffold. Cardiac tissue engineering assisted by nanotechnologies may eventually help to meet this challenge.

Comprehensive annular and subvalvular repair of chronic ischemic mitral regurgitation improves long-term results with the least ventricular remodeling.

BACKGROUND: Undersized ring annuloplasty for ischemic mitral regurgitation (MR) is associated with variable results and >30% MR recurrence. We tested whether subvalvular repair by severing second-order mitral chordae can improve annuloplasty by reducing papillary muscle tethering. METHODS AND RESULTS: Posterolateral myocardial infarction known to produce chronic remodeling and MR was created in 28 sheep. At 3 months, sheep were randomized to sham surgery versus isolated undersized annuloplasty versus isolated bileaflet chordal cutting versus the combined therapy (n=7 each). At baseline, chronic myocardial infarction (3 months), and euthanasia (6.6 months), we measured left ventricular (LV) volumes and ejection fraction, wall motion score index, MR regurgitation fraction and vena contracta, mitral annulus area, and posterior leaflet restriction angle (posterior leaflet to mitral annulus area) by 2-dimensional and 3-dimensional echocardiography. All groups were comparable at baseline and chronic myocardial infarction, with mild to moderate MR (MR vena contracta, 4.6±0.1 mm; MR regurgitation fraction, 24.2±2.9%) and mitral annulus dilatation (P<0.01). At euthanasia, MR progressed to moderate to severe in controls but decreased to trace with ring plus chordal cutting versus trace to mild with chordal cutting alone versus mild to moderate with ring alone (MR vena contracta, 5.9±1.1 mm in controls, 0.5±0.08 with both, 1.0±0.3 with chordal cutting alone, 2.0±0.4 with ring alone; P<0.01). In addition, LV end-systolic volume increased by 108% in controls versus 28% with ring plus chordal cutting, less than with each intervention alone (P<0.01). In multivariate analysis, LV end-systolic volume and mitral annulus area most strongly predicted MR (r(2)=0.82, P<0.01). CONCLUSIONS: Comprehensive annular and subvalvular repair improves long-term reduction of both chronic ischemic MR and LV remodeling without decreasing global or segmental LV function at follow-up.

Immune response to human embryonic stem cell-derived cardiac progenitors and adipose-derived stromal cells.

Transplantation of allogeneic human embryonic stem cell-derived cardiac progenitors triggers an immune response. We assessed whether this response could be modulated by the concomitant use of adipose-derived stromal cells (ADSC). Peripheral blood mononuclear cells were collected from 40 patients with coronary artery disease (CAD) and nine healthy controls. Cardiac progenitors (CD15(+) Mesp1(+)) were generated as already reported from the I6 cell line treated with bone morphogenetic protein (BMP)-2. Adipose-derived stromal cells were obtained from abdominal dermolipectomies. We assessed the proliferative response of peripheral lymphocytes from patients and controls to cardiac progenitors cultured on a monolayer of ADSC, to allogeneic lymphocytes in mixed lymphocyte culture and to the T cell mitogen phytohemaglutin A in presence or absence of ADSC. Cardiac progenitors cultured on a monolayer of ADSC triggered a proliferation of lymphocytes from both patients and controls albeit lower than that induced by allogeneic lymphocytes. When cultured alone, ADSC did not induce any proliferation of allogeneic lymphocytes. When added to cultures of lymphocytes, ADSC significantly inhibited the alloantigen or mitogen-induced proliferative response. Compared to healthy controls, lymphocytes from patients presenting CAD expressed a decreased proliferative capacity, in particular to mitogen-induced stimulation. Adipose-derived stromal cells express an immunomodulatory effect that limits both alloantigen and mitogen-induced lymphocyte responses. Furthermore, lymphocytes from patients with CAD are low responders to conventional stimuli, possibly because of their age and disease-associated treatment regimens. We propose that, in combination, these factors may limit the in vivo immunogenicity of cardiac progenitors co-implanted with ADSC in patients with CAD.

Sports-related sudden death in the general population.

BACKGROUND: Although such data are available for young competitive athletes, the prevalence, characteristics, and outcome of sports-related sudden death have not been assessed previously in the general population. METHODS AND RESULTS: A prospective and comprehensive national survey was performed throughout France from 2005 to 2010, involving subjects 10 to 75 years of age. Case detection for sports-related sudden death, including resuscitated cardiac arrest, was undertaken via national ambulance service reporting and Web-based screening of media releases. The overall burden of sports-related sudden death was 4.6 cases per million population per year, with 6% of cases occurring in young competitive athletes. Sensitivity analyses used to address suspected underreporting demonstrated an incidence ranging from 5 to 17 new cases per million population per year. More than 90% of cases occurred in the context of recreational sports. The age of subjects was relatively young (mean ± SD 46 ± 15 years), with a predominance of men (95%). Although most cases were witnessed (93%), bystander cardiopulmonary resuscitation was only commenced in 30.7% of cases. Bystander cardiopulmonary resuscitation (odds ratio 3.73, 95% confidence interval 2.19 to 6.39, P<0.0001) and initial use of cardiac defibrillation (odds ratio 3.71, 95% confidence interval 2.07 to 6.64, P<0.0001) were the strongest independent predictors for survival to hospital discharge (15.7%, 95% confidence interval 13.2% to 18.2%). CONCLUSIONS: Sports-related sudden death in the general population is considerably more common than previously suspected. Most cases are witnessed, yet bystander cardiopulmonary resuscitation was only initiated in one third of cases. Given the often predictable setting of sports-related sudden death and that prompt interventions were significantly associated with improved survival, these data have implications for health services planning.

[Hypertrophic cardiomyopathy: current aspects and new developments]. / Cardiomyopathie hypertrophique: aspects actuels et nouveautés.

Hypertrophic cardiomyopathy (HCM) is a myocardial disorder characterized by left ventricular hypertrophy with no apparent cause (such as severe hypertension, aortic valve stenosis, etc.). The clinical diagnosis is based on cardiac imaging, commonly using 2D echocardiography and increasingly CMR. HCM is the leading cause of sudden death in young people, especially on the sports field. Many patients remain asymptomatic throughout life, while others develop heart failure, atrial fibrillation and stroke. HCM is the most common genetic (autosomal dominant) cardiovascular disease, with variable penetrance and expression. It is caused by mutations in genes coding for cardiac sarcomeric proteins. Genetic counseling and clinical risk stratification are crucial for all patients. Medical treatment with B-blockers or verapamil improves symptoms but has not been show to modify the clinical course. Patients with outflow obstruction and severe symptoms unresponsive to medical therapy are candidates for alcohol septal ablation or surgical myectomy. Current approaches focus on the prevention of sudden death by means of implantable defibrillators in high-risk patients.

Composite cell sheets: a further step toward safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells.

BACKGROUND: The safety and efficacy of myocardial regeneration using embryonic stem cells are limited by the risk of teratoma and the high rate of cell death. METHODS AND RESULTS: To address these issues, we developed a composite construct made of a sheet of adipose tissue-derived stroma cells and embryonic stem cell-derived cardiac progenitors. Ten Rhesus monkeys underwent a transient coronary artery occlusion followed, 2 weeks later, by the open-chest delivery of the composite cell sheet over the infarcted area or a sham operation. The sheet was made of adipose tissue-derived stroma cells grown from a biopsy of autologous adipose tissue and cultured onto temperature-responsive dishes. Allogeneic Rhesus embryonic stem cells were committed to a cardiac lineage and immunomagnetically sorted to yield SSEA-1(+) cardiac progenitors, which were then deposited onto the cell sheet. Cyclosporine was given for 2 months until the animals were euthanized. Preimplantation studies showed that the SSEA-1(+) progenitors expressed cardiac markers and had lost pluripotency. After 2 months, there was no teratoma in any of the 5 cell-treated monkeys. Analysis of >1500 histological sections showed that the SSEA-1(+) cardiac progenitors had differentiated into cardiomyocytes, as evidenced by immunofluorescence and real-time polymerase chain reaction. There were also a robust engraftment of autologous adipose tissue-derived stroma cells and increased angiogenesis compared with the sham animals. CONCLUSIONS: These data collected in a clinically relevant nonhuman primate model show that developmentally restricted SSEA-1(+) cardiac progenitors appear to be safe and highlight the benefit of the epicardial delivery of a construct harboring cells with a cardiomyogenic differentiation potential and cells providing them the necessary trophic support.

Can mesenchymal stem cells induce tolerance to cotransplanted human embryonic stem cells?

Mesenchymal stem cells (MSCs) are reported to be immune privileged. We assessed whether their transplantation (Tx) could create a suppressive microenvironment mitigating rejection of coinjected human embryonic stem cells (hESCs). Three weeks after ligation-induced myocardial infarction, 40 immunocompetent rats received 150 microl of cardiac-specified hESCs (5 x 10(6)), MSCs (5 x 10(6)), hESC + MSC (5 x 10(6) for each), or control medium. Two months after Tx, left ventricle (LV) function was assessed by echocardiography, and hearts were processed for the detection of human cells by immunostaining and quantitative RT-PCR, patterns of rejection, fibrosis, and angiogenesis. Two months after Tx, LV ejection fraction (LVEF) was significantly higher in the ESC and ESC + MSC groups compared with controls. There were few engrafted cells, which expressed markers of endothelial, smooth muscle, and ventricular cardiac cells, particularly in the MSC group. Hearts of all groups demonstrated a similar infiltration by CD4(+) and CD3(+) cells but MSC-Tx resulted in a greater infiltration of FoxP3 compared with the control and ESC-alone groups. No teratoma was observed. Thus, cotransplantation of ESCs and MSCs provided better functional preservation compared with single-cell treatment alone. However, there was only modest evidence for an immunosuppressive effect of coinjected MSCs and their beneficial effects seemed rather mediated by trophic effects on the host tissue.

Excessive heart rate increase during mild mental stress in preparation for exercise predicts sudden death in the general population.

AIMS: The aim of this study involves the early identification, among apparently healthy individuals, of those at high risk for sudden cardiac death. We tested the hypothesis that individuals who respond to mild mental stress in preparation for exercise test with the largest heart rate increases might be at highest risk. METHODS AND RESULTS: Data from 7746 civil servants participating in the Paris Prospective Study I, followed-up for 23 years, allowed to compare heart rate changes between rest and mild mental stress (preparation prior to an exercise test) between subjects who suffered sudden cardiac death (n = 81), non-sudden (n = 129) coronary death, or death from any cause (n = 1306). The mean heart rate increase during mild mental stress was 8.9 +/- 10.8 b.p.m. Risk of sudden cardiac death increased progressively with heart rate increase during mental stress and the relative risk of the third vs. the first tertile was 2.09 (95% confidence interval, 1.13-3.86) after adjustment for confounders. This relationship was not observed for non-sudden coronary death. CONCLUSION: An important heart rate increase produced by a mild mental stress predicts long-term risk for sudden cardiac death. Heart rate changes before an exercise test may provide a simple tool for risk stratification.

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation.

BACKGROUND: Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic. METHODS AND RESULTS: This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction < or = 35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). Myoblast transfer did not improve regional or global LV function beyond that seen in control patients. The absolute change in ejection fraction (median [interquartile range]) between 6 months and baseline was 4.4% (0.2; 7.3), 3.4% (-0.3; 12.4), and 5.2% (-4.4; 11.0) in the placebo, low-dose, and high-dose groups, respectively (P=0.95). However, the high-dose cell group demonstrated a significant decrease in LV volumes compared with the placebo group. Despite a higher number of arrhythmic events in the myoblast-treated patients, the 6-month rates of major cardiac adverse events and of ventricular arrhythmias did not differ significantly between the pooled treatment and placebo groups. CONCLUSIONS: Myoblast injections combined with coronary surgery in patients with depressed LV function failed to improve echocardiographic heart function. The increased number of early postoperative arrhythmic events after myoblast transplantation, as well as the capability of high-dose injections to revert LV remodeling, warrants further investigation.

Pericardial effusion causing echocardiographic mimicking of left intra-atrial thrombus.

A 71-year-old woman presented with dyspnoea and irregular tachycardia. Investigation revealed the presence of pericardial effusion and left intra-auricular mass. The patient was sent to the operation theatre and after pericardial drain, the intra-atrial mass disappeared with retroactive diagnosis of left atrial appendage invagination.

Influence of centre expertise on the diagnosis and management of hypertrophic cardiomyopathy: A study from the French register of hypertrophic cardiomyopathy (REMY).

BACKGROUND: Our knowledge of hypertrophic cardiomyopathy (HCM) mainly originates from quarternary centres. The objective is to assess the current management of HCM patients in a large multicentre French register according to the level of expertise. METHODS AND RESULTS: A total of 1431 HCM patients were recruited across 26 (11 expert and 15 non-expert) centres in REMY, a prospective hospital-based register of adult HCM patients. A sarcomeric origin was suspected in 1284 (89.7%) patients [261 (20.3%) with a reported gene mutation, 242 (18.8%) genotype-negative], while 107 (7.5%) had a diagnosis of non-sarcomeric HCM. Patients managed in non-expert centres were older (P < 0.01) and presented more often with NYHA III/IV class dyspnoea (P < 0.01), congestive heart failure (P < 0.01), low LEVF (P < 0.01), less often with a syncope history (P < 0.01) and lower LV obstruction (P < 0.01) than patients in expert centres. Genotype positive sarcomeric aetiologies were less frequent in non-expert centres (P < 0.01). The use of diagnostic and prognostic tests as cardiac MRI (P < 0.001), genetic (P < 0.001) and alpha-galactosidase A enzyme level testing (P < 0.001), Holter ECG (P < 0.001), and exercise test (P < 0.001), was lower in non-expert centres. Septal ablation procedures using alcohol (P < 0.001) or myectomy (P < 0.001) were more frequent in expert centres. CONCLUSION: In real life practice, only a minority of HCM patients are identified as sarcomere positive as per genetic testing. The management of HCM patients varies according to the centre's level of expertise, with less access to diagnostic and prognostic tests in non-expert centres. Non-sarcomeric HCM may therefore be overlooked despite specific treatment in some aetiologies.