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Michel Desnos

Publications and source records attributed to Michel Desnos.

At least 19 recordsLinked to original sources
PubMed2006

Skeletal myoblast transplantation in ischemic heart failure: long-term follow-up of the first phase I cohort of patients.

BACKGROUND: Skeletal myoblast (SM) transplantation (Tx) in a post-myocardial infarction (MI) scar experimentally improves left ventricular (LV) ejection fraction (EF). Short-term follow-up (FU) studies have suggested that a similar benefit could clinically occur despite an increased risk of LV arrhythmias. METHODS AND RESULTS: We report the long-term FU of the first worldwide cohort of grafted patients (n = 9, 61.8+/-11.6 years, previous MI, EF < or = 35%) operated on (autologous SM Tx and bypass surgery) in 2000 to 2001 and evaluated before Tx, at 1 month (M1) and at a median FU of 52 (18 to 58) months after Tx (37 patient-years). NYHA class improved from 2.5+/-0.5 to 1.8+/-0.4 at M1 (P=0.004 versus baseline) and 1.7+/-0.5 at FU (P=not significant versus M1; P=0.0007 versus baseline). EF increased from 24.3+/-4% to 31+/-4.1% at M1 (+28%, P=0.001 versus baseline) and remained stable thereafter (28.7+/-8.1%, +18% versus baseline). There were 5 hospitalizations for heart failure in 3 patients at 28.6+/-9.9 months, allowing implant in 2 patients with a resynchronization pacemaker. An automatic cardiac defibrillator (ACD) was implanted in 5 patients for nonsustained (n =1) or sustained (n =4) ventricular tachycardia at 12.2+/-18.6 (1 to 45) months. Despite a beta-blocker/amiodarone combination therapy, there were 14 appropriate shocks for 3 arrhythmic storms in 3 patients at 6, 7, and 18 months after ACD implantation. CONCLUSIONS: In this cohort of severe heart failure patients both clinical status and EF stably improve over time with a strikingly low incidence of hospitalizations for heart failure (0.13/patient-years) and the arrhythmic risk can be controlled by medical therapy and/or on-request ACD implantation.

Adrenergic beta-Antagonists↗
PubMed2006

Chordal cutting does not adversely affect left ventricle contractile function.

BACKGROUND: Severing a limited number of second-order chordae to the anterior leaflet can improve ischemic mitral regurgitation (MR). Some concerns have been raised regarding possible influence on regional and global left ventricle (LV) function. We evaluated changes in cardiac function in 5 normal sheep with cutting of pre-instrumented chords in the beating heart to maintain constant load. METHODS AND RESULTS: Under cardiopulmonary bypass, wires were placed around the 2 central basal chordae and brought outside the heart, which was restarted. Hemodynamic and imaging data were collected before and after chordal cutting by radiofrequency ablation using those wires. Segmental contractility was assessed invasively using sonomicrometers and noninvasively using Doppler tissue velocity and strain rate (with strain rate viewed as less load-dependent than ejection fraction) at 6 sites: base, mid-ventricle, and apex along the anteroseptal and posterolateral walls. We found no changes from before to after chordal cutting in LV end-diastolic volume (47.2+/-3.3 after cutting versus 48.4+/-4.6 mL before cutting, P=0.66), end-systolic volume (21.5+/-1.2 versus 22.3+/-2.8 mL, P=0.68), ejection fraction (54.2+/-1.8 versus 54.2+/-2.7%, P=0.96), systolic ventricular elastance (7.28+/-1.68 versus 7.66+/-2.11 mm Hg/mL, P=0.64), preload-recruitable stroke work (46.6+/-7.7 versus 50.2+/-10.7 mm Hg, P=0.76), and LVdP/dt (1480+/-238 versus 1392+/-250 mm Hg/s, P=0.45). Doppler tissue velocities and longitudinal strain rates surrounding the papillary muscles were unchanged, as were sonomicrometer longitudinal and mediolateral absolute strains. No wall motion abnormalities were visible around the papillary muscles, and no MR developed. CONCLUSIONS: We find no evidence for acutely decreased global or segmental LV contractility with chordal cutting. This absence of adverse effects is consistent with long-term clinical experience with cutting these chords in valve repair.

Animals↗
PubMed2006

Autologous myoblast transplantation for chronic ischemic mitral regurgitation.

OBJECTIVES: This study was designed to assess whether post-myocardial infarction (MI) in-scar transplantation of skeletal myoblasts (SM) could reduce chronic ischemic mitral regurgitation (MR) by decreasing left ventricular (LV) remodeling. BACKGROUND: Extensive work has confirmed the relationship between ischemic MR and post-myocardial infarction (MI) remodeling of the LV. METHODS: An infero-posterior MI was created in 13 sheep, thereby resulting in increasing MR. Two months post-MI, the animals were randomized and in-scar injected with expanded autologous SM (n = 6, mean: 251 x 10(6) cells) or culture medium only (n = 7). Three-dimensional echocardiography was performed at baseline, before transplantation, and for two months thereafter (sacrifice), with measurements of LV end-diastolic and end-systolic volumes (ESV), ejection fraction (EF), MR stroke volume, and leaflet tethering distance; wall motion score index (WMSi) was assessed by two-dimensional echo. RESULTS: Measurements were similar between groups at baseline and before transplantation. At sacrifice, transplantation was found to have reduced MR progression (regurgitant volume change: -1.83 +/- 0.32 ml vs. 5.9 +/- 0.7 ml in control group, p < 0.0001) and tethering distance (-0.41 +/- 0.09 cm vs. 0.44 +/- 0.12 cm in control group, p < 0.001), with significant improvement of EF (2.01 +/- 0.94% vs. -4.86 +/- 2.23%, p = 0.02), WMSi (-0.25 +/- 0.11 vs. 0.13 +/- 0.03 in controls, p < 0.01) and a trend to a lesser increase in ESV (23.3 +/- 3.5 ml vs. 35.4 +/- 4.2 ml in control group, p = 0.055). CONCLUSIONS: Autologous skeletal myoblast transplantation attenuates mild-to-moderate chronic ischemic MR, which otherwise is progressive, by decreasing tethering distance and improving EF and wall motion score, thereby enhancing valve coaptation. These data shed additional light on the mechanism by which skeletal myoblast transplantation may be cardioprotective.

Animals↗
PubMed2006

Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: The EFICA study.

BACKGROUND: Little is known about the epidemiology of acute decompensated heart failure (ADHF) in patients admitted to intensive and coronary care units (ICU/CCU). Observational data may improve disease management and guide the design of clinical trials. AIMS: EFICA is an observational study of the clinical profile, management and survival of ADHF patients admitted to ICU/CCU. METHODS: The study included 599 patients admitted to 60 ICU/CCUs across France. Relevant data was recorded during hospitalisation. Survival was assessed at 4 weeks and 1 year. RESULTS: The main cause of ADHF was ischaemic heart disease (61%); 29% of patients had cardiogenic shock. Mortality was 27.4% at 4 weeks and 46.5% at 1 year, increasing to 43.2% and 62.5%, respectively, when including pre-admission deaths. Shock patients had the highest [57.8% vs. 15.2% without shock (p < 0.001)] and patients with hypertension and pulmonary oedema had the lowest 4-week mortality: (7%). Pre-admission NYHA class III-IV heart failure, not initial clinical presentation, influenced 1-year mortality. CONCLUSION: ADHF is a heterogeneous syndrome. Based on initial clinical presentation, three entities with distinct features and outcome may be described: cardiogenic shock, pulmonary oedema with hypertension, and 'decompensated' chronic heart failure. This should be taken into account in future observational studies, guidelines and clinical trials.

Aged↗
PubMed2006

Routine delivery of myoblasts during coronary artery bypass surgery: why not?

Skeletal myoblast transplantation has now entered the clinical arena as a potential means of restoring function to scarred myocardium. While the current experience derived from phase I trials suggests that cell implantation during coronary artery bypass operations is a straightforward and safe procedure, routine use of myoblast transplantation would certainly be premature. Two major issues have not yet been addressed: firstly, the risk-benefit ratio needs to be assessed, specifically whether the potential proarrhythmic risk associated with myoblast transplantation is supported by the results of an ongoing large, randomized study, and if so, whether this risk is offset by a benefit in terms of improvement of left ventricular function and patient outcome. Secondly, this putative benefit will then have to be weighed against the financial burden inherent to this type of procedure, to assess whether the cost-effectiveness ratio is favorably shifted and supports the expanded indication of myoblast transplantation during coronary artery revascularization in patients with severe ischemic heart failure.

Cardiac Output, Low↗
PubMed2005

Severe dilated cardiomyopathy and quadriceps myopathy due to lamin A/C gene mutation: a phenotypic study.

UNLABELLED: This study reports a family affected by a new phenotype associated with dilated cardiomyopathy and quadriceps myopathy. METHODS: 29 family members underwent a physical and neurological examination, including an electromyogram and biopsy of muscle abnormalities. A cardiac examination was performed in all subjects. RESULTS: The family pedigree (n=72) demonstrated that transmission was autosomal dominant. Eleven subjects had cardiac involvement, only four had quadriceps muscle involvement. Cardiac impairment preceded neurological involvement. The mean age for neurological involvement was 44+/-0.8 years (range 43-45) and cardiac involvement was 37+/-7.9 years (range: 24-45). Cardiac involvement consisted of: hypokinetic dilated cardiomyopathy (64%); atrial fibrillation (100%); ventricular arrhythmias (64%); impaired conduction with bundle branch or complete atrio ventricular block (73%). Four patients required pacemakers and anti arrhythmic therapies. Four patients died: two of refractory heart failure and two of sudden death; two patients were resuscitated following cardiac arrest. Three patients required a prophylactic implantable cardiac defibrillator (ICD). Muscle morphological abnormalities were characterized by a variable number of fibers with rimmed vacuoles. The quadriceps deteriorated progressively without impairment of other muscles. Genotypic study showed a lamin A/C gene mutation. CONCLUSIONS: This family was affected by a new phenotype composed of an autosomal dominant severe dilated cardiomyopathy with conduction defects or arrhythmias and quadriceps myopathy. Cardiac abnormalities preceded neuromuscular disorders and defined the prognosis of this disease.

Adult↗
PubMed2005

Heart-rate profile during exercise as a predictor of sudden death.

BACKGROUND: Changes in heart rate during exercise and recovery from exercise are mediated by the balance between sympathetic and vagal activity. Since alterations in the neural control of cardiac function contribute to the risk of sudden death, we tested the hypothesis that among apparently healthy persons, sudden death is more likely to occur in the presence of abnormal heart-rate profiles during exercise and recovery. METHODS: A total of 5713 asymptomatic working men (between the ages of 42 and 53 years), none of whom had clinically detectable cardiovascular disease, underwent standardized graded exercise testing between 1967 and 1972. We examined data on the subjects' resting heart rates, the increase in rate from the resting level to the peak exercise level, and the decrease in rate from the peak exercise level to the level one minute after the termination of exercise. RESULTS: During a 23-year follow-up period, 81 subjects died suddenly. The risk of sudden death from myocardial infarction was increased in subjects with a resting heart rate that was more than 75 beats per minute (relative risk, 3.92; 95 percent confidence interval, 1.91 to 8.00); in subjects with an increase in heart rate during exercise that was less than 89 beats per minute (relative risk, 6.18; 95 percent confidence interval, 2.37 to 16.11); and in subjects with a decrease in heart rate of less than 25 beats per minute after the termination of exercise (relative risk, 2.20; 95 percent confidence interval, 1.02 to 4.74). After adjustment for potential confounding variables, these three factors remained strongly associated with an increased risk of sudden death, with a moderate but significantly increased risk of death from any cause but not of nonsudden death from myocardial infarction. CONCLUSIONS: The heart-rate profile during exercise and recovery is a predictor of sudden death.

Adult↗
PubMed2005

Adenovirus-mediated gene transfer of superoxide dismutase and catalase decreases restenosis after balloon angioplasty.

BACKGROUND: Reactive oxygen species (ROS) production increases after injury and potentially contributes to restenosis after angioplasty. We therefore evaluated the effect of adenovirus-mediated gene transfer (Ad) of superoxide dismutase (SOD) and catalase (CAT) on ROS production and restenosis after balloon angioplasty. METHODS: O(2)(-) and H(2)O(2 )production was quantified in cultured cells after incubation with either LPS or CuSO(4). Angioplasty and gene transfer were performed in rabbit atherosclerotic iliac arteries. One artery was injected with AdSOD and AdCAT, while the contralateral artery was injected with an adenovirus carrying no transgene, and served as control. RESULTS: ROS production was significantly decreased after adenovirus-mediated gene transfer of SOD and CAT as compared with control. Treated arteries showed less restenosis (32 +/- 27 vs. 63 +/- 19%, p = 0.003) and less constrictive remodeling (1.2 +/- 0.3 vs. 0.9 +/- 0.2, p = 0.02) than control arteries. Arteries injected with AdSOD and AdCAT showed better vasoreactivity to acetylcholine (11 +/- 4 vs. -1 +/- 6%, p < 0.05), lower collagen density (43 +/- 16 vs. 53 +/- 23%, p = 0.03), and lower inflammatory cell infiltration (22 +/- 6 vs. 36 +/- 11%, p = 0.04) than control arteries. CONCLUSIONS: Our data suggest that adenovirus-mediated gene transfer of SOD and CAT reduced oxidative stress, restenosis, collagen accumulation, and inflammation and improved endothelial function after angioplasty.

Adenoviridae↗
PubMed2005

Diagnostic accuracy of a 2D left ventricle hypertrophy score for familial hypertrophic cardiomyopathy.

AIMS: To study the diagnostic value of a new 2D left ventricle hypertrophy (2D LVH) score in families with hypertrophic cardiomyopathy (HCM) in comparison with the conventional maximal wall thickness (MWT) measurement (>13 mm in adults), which is limited by a low sensitivity in relatives. METHODS AND RESULTS: The study was performed in 237 adults from genotyped families with HCM. Population A (derivation sample) comprised 109 adults and population B (validation sample) comprised 128 adults. MWT and 2D LVH scores (sum of thicknesses of four segments) were determined by echocardiography. Genotyping was the gold standard for diagnosis. In population A, a theoretical value for LVH score was determined in the healthy population by a multiple linear regression model including age, sex, and body surface area. An abnormal cut-off value was defined as an LVH score above a maximum theoretical value according to receiver operating characteristic analysis. Sensitivity and specificity were, respectively, 73 and 96% for 2D LVH score and 62.5 and 100% for MWT. Improvement of sensitivity was particularly important in adults <50 years of age (69 vs. 54%, respectively, P<0.04). These results were validated in population B: sensitivity and specificity of LVH score were, respectively, 75 and 96% in this sample and 67 and 97%, in the subgroup <50 years. In the latter, sensitivity of LVH score increased when compared with that of MWT (67 vs. 53%, P<0.03). CONCLUSIONS: The LVH score has a higher diagnostic value for HCM than the conventional criterion of MWT, particularly in young adults. This echographic parameter may be proposed as an alternative diagnostic criterion for familial screening.

Adult↗
PubMed2005

Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium.

AIMS: This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium. METHODS AND RESULTS: An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n=7) or culture medium (n=7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35-48) vs. 51% (38-55), respectively, P=0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47-56) vs. 39% (36-47), respectively, P=0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. CONCLUSION: These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.

Animals↗
PubMed2005

Obstructive sleep apnoea and patent foramen ovale: successful treatment of symptoms by percutaneous foramen ovale closure.

Obstructive sleep apnoea (OSA) is a common sleep disorder often associated with cardiovascular problems. The role of right to left shunt through a patent foramen ovale (PFO) in OSA is still debated. We report the case of a 42-year-old man with OSA, treated by nocturnal continuous airway pressure, who had a PFO and severe dispnoea and desaturation at exercise. Percutaneous closure of PFO leads to immediate and complete resolution of symptoms. Our report shows for the first time that patients with OSA, PFO, and desaturation at exercise should be considered candidates to PFO closure, even in the absence of cerebral events.

Adult↗
PubMed2004

Does the functional efficacy of skeletal myoblast transplantation extend to nonischemic cardiomyopathy?

BACKGROUND: The benefits of skeletal myoblast (SM) transplantation on infarcted myocardium have been investigated extensively; however, little is known about its effects in nonischemic cardiomyopathy models. To address this issue, we tested SM transplantation in CHF147 Syrian hamsters, a strain characterized by a delta-sarcoglycan deficiency that phenotypically features the human setting of primary dilated cardiomyopathy. METHODS AND RESULTS: Cell culture techniques were used to prepare approximately 5x10(6) muscle cells from autologous tibialis anterior muscle, of which 50% were SMs (desmin staining). The cells were injected in 6 sites across the left ventricular wall (n=14). Control animals (n=12) received equivalent volumes of culture medium. Left ventricular systolic function was assessed in a blinded fashion from 2D echocardiographic left ventricular fractional area change, before transplantation, and 4 weeks later. Explanted hearts were processed for the detection of myotubes and quantification of fibrosis. Baseline functional data did not differ between the 2 groups. Four weeks after transplantation, 6 of the 10 surviving grafted hamsters were improved compared with 0 of the 8 survivors of the control group. This translated into a 6% decrease in fractional area change in controls compared with a 24% increase in cell-transplanted hamsters (P=0.001). Engrafted myotubes were consistently detected in all SM transplanted hearts by immunohistochemistry, whereas fibrosis was not worsened by cell injections. CONCLUSIONS: These data suggest that the functional benefits of SM transplantation might extend to nonischemic cardiomyopathy.

Animals↗
PubMed2003

Efficacy of chordal cutting to relieve chronic persistent ischemic mitral regurgitation.

BACKGROUND: Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Leaflet closure is restricted by tethering to displaced papillary muscles, and is, therefore, incompletely treated by annular reduction. In an acute ischemic model, we reduced such MR by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. Whether this is effective without prolapse, recurrent MR, or left ventricular (LV) failure in chronic persistent ischemic MR, despite greater LV remodeling, remains to be established. Therefore, we studied 7 sheep with chronic inferobasal infarcts known to produce progressive MR over 2 months. In all of those sheep, after a mean of 4.1 months, the 2 central basal (intermediate) chordae were cut at the chronic ischemic MR stage. 3-Dimensional echo quantified MR, LV function, and valve geometry. Five other sheep were followed for a mean of 7.8+/-1.2 months after inferobasal infarction with chordal cutting. RESULTS: All 7 of the sheep with chronic ischemic MR (increased from 1.4+/-0.4 to 11.1+/-0.5 mL/beat, regurgitant fraction=39.0+/-4.2%, P<0.0001) showed anterior leaflet angulation at the basal chord insertion. Although end-systolic volume had doubled, cutting the 2 central basal chordae significantly decreased the MR to baseline (P<0.0001) without prolapse or decline in EF (41.1+/-1.5% to 42.6+/-1.6%, P=not significant [NS]). The five sheep with long-term follow-up showed no prolapse or MR, and no significant post-infarct decrease in LV ejection fraction (EF; 38.9+/-2.4% to 41.4+/-1.2%, P=NS). CONCLUSIONS: Cutting a minimum number of basal (intermediate) chordae can improve coaptation and reduce chronic persistent ischemic MR without impairing LVEF. No adverse effects were noted long-term after chordal cutting at the time of infarction.

Animals↗
PubMed2003

Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy.

BACKGROUND: Hypertrophic cardiomyopathy is an autosomal-dominant disorder in which 10 genes and numerous mutations have been reported. The aim of the present study was to perform a systematic screening of these genes in a large population, to evaluate the distribution of the disease genes, and to determine the best molecular strategy in clinical practice. METHODS AND RESULTS: The entire coding sequences of 9 genes (MYH7, MYBPC3, TNNI3, TNNT2, MYL2, MYL3, TPM1, ACTC, andTNNC1) were analyzed in 197 unrelated index cases with familial or sporadic hypertrophic cardiomyopathy. Disease-causing mutations were identified in 124 index patients ( approximately 63%), and 97 different mutations, including 60 novel ones, were identified. The cardiac myosin-binding protein C (MYBPC3) and beta-myosin heavy chain (MYH7) genes accounted for 82% of families with identified mutations (42% and 40%, respectively). Distribution of the genes varied according to the prognosis (P=0.036). Moreover, a mutation was found in 15 of 25 index cases with "sporadic" hypertrophic cardiomyopathy (60%). Finally, 6 families had patients with more than one mutation, and phenotype analyses suggested a gene dose effect in these compound-heterozygous, double-heterozygous, or homozygous patients. CONCLUSIONS: These results might have implications for genetic diagnosis strategy and, subsequently, for genetic counseling. First, on the basis of this experience, the screening of already known mutations is not helpful. The analysis should start by testing MYBPC3 and MYH7 and then focus on TNNI3, TNNT2, and MYL2. Second, in particularly severe phenotypes, several mutations should be searched. Finally, sporadic cases can be successfully screened.

Cardiomyopathy, Hypertrophic, Familial↗
PubMed2003

Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction.

OBJECTIVES: This phase I trial was designed to assess the feasibility and safety of autologous skeletal myoblast transplantation in patients with severe ischemic cardiomyopathy. BACKGROUND: Experimentally, myoblast grafting into postinfarction myocardial scars improves left ventricular function. METHODS: Ten patients were included on the basis of the following criteria: 1) severe left ventricular dysfunction (ejection fraction < or = 35%); 2) the presence of a postinfarction akinetic and nonviable scar, as assessed by dobutamine echocardiography and 18-fluorodeoxyglucose positron emission tomography; and 3) an indication of coronary bypass in remote areas. Skeletal myoblasts were grown from a biopsy taken at the thigh. RESULTS: An average of 871 x 10(6) cells (86% of myoblasts) were obtained after a mean period of 16 days and implanted uneventfully across the scar at the time of bypass. Except for one patient whose early death was unrelated to the cell transplantation, all patients had an uncomplicated postoperative course. Four patients showed delayed episodes of sustained ventricular tachycardia and were implanted with an internal defibrillator. At an average follow-up of 10.9 months, the mean New York Heart Association functional class improved from 2.7 +/- 0.2 preoperatively to 1.6 +/- 0.1 postoperatively (p < 0.0001), and the ejection fraction increased from 24 +/- 1% to 32 +/- 1% (p < 0.02). A blinded echocardiographic analysis showed that 63% of the cell-implanted scars (14 of 22) demonstrated improved systolic thickening. One noncardiac death occurred 17.5 months after transplantation. CONCLUSIONS: These preliminary data suggest the feasibility and safety of autologous skeletal myoblast transplantation in severe ischemic cardiomyopathy, with the caveat of an arrhythmogenic potential. New-onset contraction of akinetic and nonviable segments suggests a functional efficacy that requires confirmation by randomized studies.

Adult↗
PubMed2003

Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy.

Autologous skeletal myoblast transplantation might improve postinfarction ventricular function, but graft viability and differentiation (ie, proof of concept) has not been shown. A 72-year-old man had autologous cultured myoblasts from his vastus lateralis injected to an area of transmural inferior myocardial infarction in non-reperfused scar tissue. He showed improvement in symptoms and left-ventricular ejection fraction. When he died 17.5 months after the procedure, the grafted post-infarction scar showed well developed skeletal myotubes with a preserved contractile apparatus. 65% of myotubes expressed the slow myosin isoform and 33% coexpressed the slow and fast isoforms (vs 44% and 0.6%, respectively, in skeletal muscle). Myoblast grafts can survive and show a switch to slow-twitch fibres, which might allow sustained improvement in cardiac function.

Aged↗
PubMed2003

Functional consequences of an LMNA mutation associated with a new cardiac and non-cardiac phenotype.

Heritable dilated cardiomyopathy is a genetically highly heterogeneous disease. To date 17 different chromosomal loci have been described for autosomal dominant forms of dilated cardiomyopathy with or without additional clinical manifestations. Among the 10 mutated genes associated with dilated cardiomyopathy, the lamin A/C (LMNA) gene has been reported in forms associated with conduction-system disease with or without skeletal muscle myopathy. For the first time, we report here a French family affected with a new phenotype composed of an autosomal dominant severe dilated cardiomyopathy with conduction defects or atrial/ventricular arrhythmias, and a specific quadriceps muscle myopathy. In all previously reported cases with both cardiac and neuromuscular involvement, neuromuscular disorders preceded cardiac abnormalities. The screening of the coding sequence of the LMNA gene on all family members was performed and we identified a missense mutation (R377H) in the lamin A/C gene that cosegregated with the disease in the family. Cell transfection experiments showed that the R377H mutation leads to mislocalization of both lamin and emerin. These results were obtained in both muscular (C2C12) and non-muscular cells (COS-7). This new phenotype points out the wide spectrum of neuromuscular and cardiac manifestations associated with lamin A/C mutations, with the functional consequence of this mutation seemingly associated with a disorganization of the lamina.

Adult↗