Prognosis of Right Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy.

Background Chronic respiratory failure and heart involvement may occur in Duchenne muscular dystrophy. We aimed to assess the prognostic value of the right ventricular (RV) systolic dysfunction in patients with Duchenne muscular dystrophy. Methods and Results We studied 90 genetically proven patients with Duchenne muscular dystrophy from 2010 to 2019, to obtain respiratory function and Doppler echocardiographic RV systolic function.

Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy-analysis of registry data.

Aims: To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD).

Methods And Results: We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115).

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies.

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation.

Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA.

Development and Validation of a New Scoring System to Predict Survival in Patients With Myotonic Dystrophy Type 1.

Importance: Life expectancy is greatly shortened in patients presenting with myotonic dystrophy type 1 (DM1), the most common neuromuscular disease. A reliable prediction of survival in patients with DM1 is critically important to plan personalized health supervision.

Objective: To develop and validate a prognostic score to predict 10-year survival in patients with DM1.

Association Between Mutation Size and Cardiac Involvement in Myotonic Dystrophy Type 1: An Analysis of the DM1-Heart Registry.

Background: In myotonic dystrophy type 1, the association between mutation size (CTG expansion) and the severity of cardiac involvement is controversial.

Methods And Results: We selected 855 patients with myotonic dystrophy type 1 (women, 51%; median age, 37 years), with genetic testing performed at the moment of their initial cardiac evaluation, out of 1014 patients included in the Myotonic Dystrophy Type 1-Heart Registry between January 2000 and December 2015. We studied the association between CTG expansion size and other baseline characteristics and (1) cardiac involvement at baseline and (2) the incidence of death, sudden death, and other cardiac adverse events.

Risk for Complications after Pacemaker or Cardioverter Defibrillator Implantations in Patients with Myotonic Dystrophy Type 1.

Background: Pacemakers (PM) and implantable cardioverter defibrillators (ICD) may be indicated for sudden death prevention in myotonic dystrophy type 1 (DM1), however the risk of complications after the placement of these devices is unknown.

Objective: To compare the rate of device-related complications between PM and ICD implantations in patients with DM1.

Methods: Among 914 patients with DM1 included in the DM1 Heart Registry between January 2000 and January 2010, we retrospectively selected 23 patients who were implanted with an ICD and matched them to 46 controls with a PM on age, gender, and year of device placement.

Incidence and predictors of sudden death, major conduction defects and sustained ventricular tachyarrhythmias in 1388 patients with myotonic dystrophy type 1.

Aims: To describe the incidence and identify predictors of sudden death (SD), major conduction defects and sustained ventricular tachyarrhythmias (VTA) in myotonic dystrophy type 1 (DM1).

Methods And Results: We retrospectively enrolled 1388 adults with DM1 referred to six French medical centres between January 2000 and October 2013. We confirmed their vital status, classified all deaths, and determined the incidence of major conduction defects requiring permanent pacing and sustained VTA.

Prediction of long-term prognosis by heteroplasmy levels of the m.3243A>G mutation in patients with the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome.

Background And Purpose: Our aim was to determine the prognostic value of urine and blood heteroplasmy in patients with the m.3243A>G mutation.

Methods: Adults with the m.

Non Random Distribution of DMD Deletion Breakpoints and Implication of Double Strand Breaks Repair and Replication Error Repair Mechanisms.

Background: Dystrophinopathies are mostly caused by copy number variations, especially deletions, in the dystrophin gene (DMD). Despite the large size of the gene, deletions do not occur randomly but mainly in two hot spots, the main one involving exons 45 to 55. The underlying mechanisms are complex and implicate two main mechanisms: Non-homologous end joining (NHEJ) and micro-homology mediated replication-dependent recombination (MMRDR).

Cardiac arrhythmia and late-onset muscle weakness caused by a myofibrillar myopathy with unusual histopathological features due to a novel missense mutation in FLNC.

Myofibrillar myopathies (MFM) are mostly adult-onset diseases characterized by progressive morphological alterations of the muscle fibers beginning in the Z-disk and the presence of protein aggregates in the sarcoplasm. They are mostly caused by mutations in different genes that encode Z-disk proteins, including DES, CRYAB, LDB3, MYOT, FLNC and BAG3. A large family of French origin, presenting an autosomal dominant pattern, characterized by cardiac arrhythmia associated to late-onset muscle weakness, was evaluated to clarify clinical, morphological and genetic diagnosis.

Atrial flutter in myotonic dystrophy type 1: Patient characteristics and clinical outcome.

The prevalence and the incidence of atrial flutter in patients with myotonic dystrophy type 1 (DM1) and the most appropriate strategies for its management are unknown. We retrospectively included in the DM1 Heart Registry 929 adult patients with DM1 admitted to our Institutions between January 2000 and September 2013. We selected patients presenting with atrial flutter and analysed data relative to the occurrence of arterial thromboembolism, severe bradyarrhythmias and atrial flutter recurrences.

Myofibrillar myopathies: State of the art, present and future challenges.

Myofibrillar myopathies (MFM) have been described in the mid-1990s as a group of diseases sharing common histological features, including an abnormal accumulation of intrasarcoplasmic proteins, the presence of vacuoles and a disorganization of the intermyofibrillar network beginning at the Z-disk. The boundaries of this concept are still uncertain, and whereas six genes (DES, CRYAB, LDB3/ZASP, MYOT, FLNC and BAG3) are now classically considered as responsible for MFM, other entities such as FHL1 myopathy or Hereditary Myopathy with Early Respiratory Failure linked to mutations of titin can now as well be included in this group. The diagnosis of MFM is not always easy; as histological lesions can be focal, and muscle biopsy may be disappointing; this has led to a growing importance of muscle imaging, and the selectivity of muscle involvement has now been described in several disorders.

Laminin α2 Deficiency-Related Muscular Dystrophy Mimicking Emery-Dreifuss and Collagen VI related Diseases.

Background: Laminin α2 deficient congenital muscular dystrophy, caused by mutations in the LAMA2 gene, is characterized by early muscle weakness associated with abnormal white matter signal on cerebral MRI.

Objective: To report on 4 patients with LAMA2 gene mutations whose original clinical features complicated the diagnosis strategy.

Methods: Clinical, electrophysiological, muscle imaging and histopathological data were retrospectively collected from all patients.

Long-term cardiac prognosis and risk stratification in 260 adults presenting with mitochondrial diseases.

Aims: The aim of this study is to assess the long-term cardiac prognosis of adults with mitochondrial diseases.

Methods And Results: Between January 2000 and May 2014, we retrospectively included in this study 260 consecutive patients (60% women) ≥18 years (interquartile range 31-54), with genetically proven mitochondrial diseases, including 109 with mitochondrial DNA (mtDNA) single large-scale deletions, 64 with the m.3243A>G mutation in MT-TL1, 51 with other mtDNA point mutations, and 36 patients with nuclear gene mutations.

Brugada syndrome and abnormal splicing of SCN5A in myotonic dystrophy type 1.

Background: In patients with myotonic dystrophy type 1 (DM1), the mechanisms underlying sudden cardiac death, which occurs in up to 1/3 of patients, are unclear.

Aims: To study the potential role of Brugada syndrome in ventricular tachyarrhythmias and sudden death in DM1 patients.

Methods: We screened 914 adult patients included in the DM1 Heart Registry during 2000-2009 for the presence of type 1 Brugada pattern on electrocardiogram (ECG).

High risk of severe cardiac adverse events in patients with mitochondrial m.3243A>G mutation.

Objectives: To determine the long-term incidence of cardiac life-threatening complications and death in patients with the m.3243A>G mutation, and to identify cardiac prognostic factors.

Methods: We retrospectively included patients carrying the m.

Dilated cardiomyopathy in patients with mutations in anoctamin 5.

Background: Homozygous mutations in ANO5, a gene encoding anoctamin 5, a putative calcium-activated chloride channel, have recently been reported in patients with adult-onset myopathies or isolated high-CK levels. Cardiomyopathy has not previously been reported in these populations despite a proven expression of anoctamin 5 in the cardiac muscle.

Methods: Patients presenting for the management of high-CK levels or overt myopathy with proven ANO5 mutations were prospectively investigated between June 2010 and March 2012 in Pitié Salpêtrière Hospital, according to a standardised protocol.

Electrophysiological study with prophylactic pacing and survival in adults with myotonic dystrophy and conduction system disease.

Context: Up to one-third of patients with myotonic dystrophy type 1 die suddenly. Thus far, no intervention has effectively prevented sudden death.

Objective: To determine whether an invasive strategy based on systematic electrophysiological studies and prophylactic permanent pacing is associated with longer survival in patients presenting with myotonic dystrophy type 1 and major infranodal conduction delays than a noninvasive strategy.

High cardiovascular morbidity and mortality in myofibrillar myopathies due to DES gene mutations: a 10-year longitudinal study.

To determine incidence and type of major cardiac adverse events in patients with mutated desmin (DES) gene, we retrospectively reviewed baseline medical information, and examined the long-term outcomes of 28 DES patients (17 men, baseline mean age=37.7±14.4 years [min=9, max=71]) from 19 families.

Left ventricular dysfunction and cardiac arrhythmias are frequent in type 2 myotonic dystrophy: a case control study.

In contrast with Steinert's disease (DM1), type 2 muscular dystrophy (DM2) is not known to be associated with a high prevalence of cardiac involvement. Our objective was to compare the results of detailed cardiac investigations in populations of DM2 and DM1 patients, and in controls. Thirty-eight DM2 patients (17 males; age=57.

Clinical heterogeneity of duchenne muscular dystrophy (DMD): definition of sub-phenotypes and predictive criteria by long-term follow-up.

Background: To explore clinical heterogeneity of Duchenne muscular dystrophy (DMD), viewed as a major obstacle to the interpretation of therapeutic trials

Methodology/principal Findings: A retrospective single institution long-term follow-up study was carried out in DMD patients with both complete lack of muscle dystrophin and genotyping. An exploratory series (series 1) was used to assess phenotypic heterogeneity and to identify early criteria predicting future outcome; it included 75 consecutive steroid-free patients, longitudinally evaluated for motor, respiratory, cardiac and cognitive functions (median follow-up: 10.5 yrs).

Cardiac assessment of limb-girdle muscular dystrophy 2I patients: an echography, Holter ECG and magnetic resonance imaging study.

Mutations in the FKRP gene may be associated with cardiac involvement. The aim of our study was to assess myocardial involvement in patients with LGMD2I, using physical examination, echocardiography, resting and 24-h ambulatory electrocardiogram and cardiac magnetic resonance imaging, with particular attention to the detection of myocardial morphologic abnormalities. Patients were compared to matched controls.