Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial.

BACKGROUND: The MESAMI 1 trial was a bicentric pilot study designed to test the feasibility and safety of intramyocardially injected autologous bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of ischemic cardiomyopathy. METHODS AND RESULTS: The study included 10 patients with chronic myocardial ischemia, left ventricular (LV) ejection fractions (EFs) of ≤35%, and reversible perfusion defects who were on stable optimal medical therapy and were not candidates for revascularization. MSCs (mean: 61.5×10(6) cells per patient) were injected into 10-16 viable sites at the border of the LV scar via a NOGA-guided catheter. Both primary endpoints, feasibility (successful harvest, expansion, and injection of autologous MSCs) and safety (absence of severe adverse events [SAEs]) were met in all 10 patients at the 1-month follow-up time point, and none of the SAEs reported during the full 2-year follow-up period were attributable to the study intervention. The results of secondary efficacy endpoint analyses identified significant improvements from baseline to Month 12 in LVEF (29.4±2.0% versus 35.7±2.5%; p=0.003), LV end-systolic volume (167.8±18.8mL versus 156.1±28.6mL; p=0.04), 6-min walk test and NYHA functional class. CONCLUSIONS: Our results suggest that autologous MSCs can be safely administered to the hearts of patients with severe, chronic, reversible myocardial ischemia and impaired cardiac function and may be associated with improvements in cardiac performance, LV remodeling, and patient functional status. A randomized, double blind, multicenter, placebo-controlled clinical trial (MESAMI 2) will evaluate the efficacy of this treatment approach in a larger patient population. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT01076920.

[Antisynthetase syndrome with pulmonary hypertension: 4 original observations]. / Syndrome des antisynthétases compliqué d'une hypertension pulmonaire : 4 observations originales.

INTRODUCTION: Pulmonary hypertension (PH) may occur in patients with antisynthetase syndrome (ASS) but this association is poorly studied. In this article, we report 4 new cases of PH associated with ASS, and we discuss PH mechanisms in this specific disease. CASES: Four patients (3 females, 1 male) with confirmed ASS associated with anti-Jo1 (n=3), anti-PL7 (n=1), and anti-Ro52 (n=3) antibodies were analyzed. They presented with subacute dyspnea in average ten years after they were first diagnosed as ASS. Diagnosis of pre-capillary PH was made (mean of mPAP: 34mmHg): PAH (n=1), group 3 PH (n=2) and PH associated to hyperthyroidism (n=1). Among three patients who received specific PAH therapy, two had significant improvement in both clinical and hemodynamic parameters. CONCLUSION: During ASS, PH may occur in 5 to 10 % of cases, caused by various mechanisms. Unexplained dyspnea may be due to PH among ASS patients.

[Three recurrent episodes of Tako-Tsubo cardiomyopathy precipitated by an emotional stressful event: a case report]. / Trois épisodes récurrents de Tako-Tsubo secondaires à un choc émotionnel : à propos d'un cas clinique.

Tako-Tsubo cardiomyopathy, first described in 1990 by Sato in Japan, has recently gained increasing consideration when reported in non-Japanese patients, including the United States and Europe. Typical presentation mimics acute coronary syndrome, with acute chest pain and/or dyspnoea, associated to electrocardiographic changes and moderate cardiac biomarkers release, but in which coronary angiography reveals no coronary arteries lesions and echocardiography or left ventriculography shows a reversible left ventricle systolic dysfunction. Prognosis is good, in contrast to acute coronary syndrome, provided that the patients survive the possible life-threatening acute presentation, with correction of the left ventricle systolic dysfunction within several days or weeks. As noted in several reviews, 3.5% to 10% of the patients have a recurrence during the first few years after the initial presentation. Here, we described a case of a 60-year-old female who had three episodes of Tako-Tsubo always preceded by severe emotional stress suggesting a potential common etiopathogenesis.

[Myocarditis]. / Myocardites.

Myocarditis is an inflammatory disease of the myocardium associated with cardiac dysfunction. Etiologies of myocarditis are numerous - viral causes being the most frequent - as well as their clinical presentations which varies from isolated increase in cardiac enzymes during a viral pericarditis, fulminant myocarditis associated with cardiogenic shock to endomyocardial biopsy proven inflammation discovered during the etiologic diagnosis of a dilated cardiomyopathy. This article will discuss the importance of recognition of specific clinical scenarios of myocarditis and their echocardiographic presentations that are very useful for the etiologic diagnosis and to decide the medical strategy. Recent advances in the field of myocarditis concern improvement in understanding the pathophysiology, in the diagnostic approach with the use of noninvasive imaging (MRI) and molecular biology. However, specific treatment is still limited. Clinical trials with antiviral medications are not conclusive, and the medical strategies remain mainly based on the symptomatic treatment of heart failure.

Imaging and modern assessment of the right ventricle.

The right ventricular function is difficult to assess owing to its complex morphology, structure and function. The right ventricle (RV) comprises three compartments, the inlet, the apex, and the outlet contracting with a peristaltic motion from the inflow to the outflow chamber and is tightly linked to left ventricular (LV) function through the pulmonary circulation, the interventricular septum and the myocardium inside the pericardial envelop. The relation of RV function to symptom occurrence, exercise capacity and prognosis in a wide variety of cardiac diseases emphasizes the usefulness of its routine assessment. The evaluation of the RV is largely carried out by echocardiography in daily clinical practice despite important limitations inherent to two-dimensional imaging. Multiple views and numerous parameters allow clinicians to integrate the RV function in the clinical decision-making process. Recent modalities of echocardiography such as myocardial deformation and three-dimensional imaging or exercise echocardiography are promising tools for the assessment of the RV. Cardiac magnetic resonance imaging provides the unique opportunity to image the RV in motion and in three dimensions without the limitation of echogenicity. Therefore, cardiac magnetic resonance imaging is taking a growing place in the assessment of the RV in a wide variety of cardio-pulmonary diseases as pulmonary hypertension, ischemia, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, heart failure or congenital heart diseases. Integrating the complex interplay between both ventricles and the pulmonary circulation, this review will discuss the latest results of standard and novel techniques allowing the assessment of RV function by echocardiography and cardiac magnetic resonance imaging, and will provide to the clinicians, facing therapeutic challenges, a comprehensive overview of right heart function.

[Viral cardiomyopathy]. / Cardiomyopathies virales. A propos de 4 observations d'infection myocardique à parvovirus B-19 et revue de la littérature.

In too many cases, the cause of dilated cardiomyopathy (DCM) remains undetermined. Coronary or valvular heart diseases, connective tissue disorders, toxic causes and signs of infection are systematically investigated. With the exceptions of coronary and sometimes valvular heart disease, the treatment of cardiac failure remains symptomatic treating the consequences but not the cause of DCM, which is therefore diagnosed as "idiopathic". This artericle reports the clinical history of 4 patients followed up for apparently "idiopathic" DCM in whom the presence of chronic Parvovirus B-19 infection was demonstrated. Based on these 4 cases, the hypothesis of an infectious cause of DCM and the role of myocardial biopsy, given the progress in molecular biology, are reconsidered. Parvovirus B-19 infection has recently been recognised not only as a cause of myocarditis but also of chronic viral cardiomyopathy, as in adeno and enteroviral infection. The authors conclude that the progress in molecular biology, the recognition of a viral aetiology and the efficacy of immuno-modulator therapy such as beta-interferon, may lead to a new management strategy of patients with DCM in cardiological referral centres.