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Neuromuscular disorders (NMD) are a group of hereditary and acquired neurological diseases with skeletal disability. Patients may be wheelchair bound, depending of clinical severity and mechanical ventilation support is needed in patients with significant respiratory insufficiency. Right ventricular (RV) dimensions may be affected by intrathoracic pressures and venous return, this last one depending on peripheral skeletal function. We aimed to assess the impact of loss of ambulation on right ventricular size in patients with neuromuscular disorders, using the RV end diastolic area (RVEDA). We reviewed from our database patients with neuromuscular disorders who underwent transthoracic echocardiography. We systematically assessed right ventricular size, skeletal muscle function and pulmonary function. We included 320 patients (female gender: 32%) with neuromuscular disorders (including 40% myotonic dystrophy type I, 20% Duchenne muscular dystrophy, 10% Becker muscular dystrophy). Median age was 37 years [28–48], median body mass index (BMI) at 22.6 kg/m2 [19.4–26], median forced pulmonary vital capacity (FVC) at 75% of predicted value [45–96.5], 28% of patients were wheelchair bound and 35% of patients were on nocturnal noninvasive ventilation (NIV). Median left ventricular ejection fraction (LVEF) was 60% [55–66], median RVEDA was 17 cm2 [13–20] and median right ventricular peak systolic tissue Doppler velocity (Sm RV) was 13 cm/s [11–15]. The RVEDA was reduced in patients with beta-blocker (BB) use (14 cm2 vs. 17 cm2, P < 0.001), ACE inhibitor use (14 cm2 vs. 17.8 cm2, P < 0.001), NIV use (14 cm2 vs. 18 cm2, P < 0.001), wheelchair use (12.5cm2 vs. 18.6 cm2, P < 0.001). The RVEDA was associated with age (r = 0.1, p 0.04), BMI (r = 0.27, P < 0.001), Walton score (r = −0.53, P < 0.001), FVC (r = 0.5, P < 0.001), minimal vena cava diameter (r = −0.3, P < 0.001), left atrial diameter (r = 0.3, P < 0.001), right ventricular end diastolic volume (r = 0.97, P < 0.001), left ventricular end diastolic volume (r = 0.37, P < 0.001) and systolic arterial pulmonary pressure (r = 0.15, P 0.025). Using multivariate analysis, at the risk of 5%, by adjusting for age, BB, ACE inhibitor, LVEF, NIV and history of pacemaker, wheelchair use remained significantly associated with RVEDA (P < 0.001). In patients with NMD, the loss of ambulation is associated with a reduction of the right ventricular size, irrespective of age, betablockers, ACE inhibitor, LVEF and ventilation [ABSTRACT FROM AUTHOR]

Background The long-term cardiac prognosis of adults with mitochondrial diseases is unknown. Methods and Results Between January 2000 and May 2014, we retrospectively included in this study 260 consecutive patients (60% women) ε18 years of age, [interquartile range (IQR) = 31 to 54], with genetically proven mitochondrial diseases, including 109 with 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 genes mutations. Cardiac involvement was present at baseline in 81 patients (30%). Single and multiple variable analyses were performed in search of predictors of major adverse cardiac event (MACE), and hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Over a median follow-up of 7 years (IQR = 3.6 to 11.7), 27 patients (10%) experienced a MACE, defined as sudden death, death due to heart failure (HF), resuscitated cardiac arrest, 3rd degree atrioventricular block, sinus node dysfunction, cardiac transplantation, or hospitalization for management of HF. Patients with single large-scale mtDNA deletions or m.3243A>G mutations had the highest incidence of MACE. By multiple variable analysis, intraventricular conduction block (HR = 16.9; 95% CI: 7.2 to 39.4), diabetes (HR = 7.0; 95% CI: 2.9 to 16.7), premature ventricular complexes (HR = 3.6; 95% CI: 1.4 to 9.2) and left ventricular hypertrophy (HR=2.5; 95% CI: 1.1 to 5.8) were independent predictors of MACE. In patients with 0, 1, and ε2 risk factors, the incidence of MACE was 1.7, 15 and 42% respectively. Conclusions Patients with mitochondrial diseases are at high risk of MACE, independently predicted by intraventricular conduction block, diabetes, ventricular prematurity and left ventricular hypertrophy. [ABSTRACT FROM AUTHOR]

Aims 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 of age, (interquartile range [IQR]; 31 to 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 genes mutations. Cardiac involvement was present at baseline in 81 patients (30%). Single and multiple variable analyses were performed in search of predictors of major adverse cardiac event (MACE), and hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Over a median follow-up of 7 years [3.6 to 11.7], 27 patients (10%) suffered a MACE, defined as sudden death, death due to heart failure (HF), resuscitated cardiac arrest, 3 rd degree atrioventricular block, sinus node dysfunction, cardiac transplantation, or hospitalization for management of HF. Patients with single large-scale mtDNA deletions or m.3243A>G mutations had the highest incidence of MACE. By multiple variable analysis, intraventricular conduction block (HR=16.9; 95% CI: 7.2 to 39.4), diabetes (HR=7.0; 95% CI: 2.9 to 16.7), premature ventricular complexes (HR=3.6; 95% CI: 1.4 to 9.2) and left ventricular (LV) hypertrophy (HR=2.5; 95% CI: 1.1 to 5.8) were independent predictors of MACE. In patients with 0, 1, and ≥2 risk factors, the incidence of MACE was 1.7, 15 and 42% respectively. Conclusions Patients with mitochondrial diseases are at high risk of MACE, independently predicted by intraventricular conduction block, diabetes, ventricular prematurity and LV hypertrophy. [ABSTRACT FROM AUTHOR]

Background The characteristics of DM1 patients with atrial flutter (AFL) and their clinical outcome are unknown. Methods We retrospectively included the patients ≥18 years of age with DM1 who were admitted in our institutions with AFL between January 2000 and September 2013 and analyzed their clinical outcome. We compared the incidence of AFL recurrences in patients who were treated with versus without radiofrequency (RF) ablation. Single and multiple variable analyses were performed to identify predictors of AFL recurrences. Results We included 60 consecutive patients (age=41±13 years, male=34), including 55 with persistent, 2 with paroxysmal, and 3 permanent AFL. Over a 53±28 months mean follow-up duration, AFL recurrence occurred in 12 patients (24%), atrial fibrillation in 13 (26%), ischemic stroke in 2 (3%), cerebral hemorrhage in 1 (2%) and sinus node dysfunction in 4 (7%). Patients treated by RF ablation were significantly more frequently free of AFL recurrences by Kaplan Meier analysis (95% vs. 61%, HR=0.17, 95% CI 0.08 to 0.97, p=0.04). By multivariate analyses, RF ablation was the only parameter significantly associated with absence of AFL recurrence (p=0.01). Conclusions Patients with DM1 presenting with AFL are exposed to stroke, severe sinus node dysfunction and cerebral hemorrhage. RF catheter ablation is associated with a lower risk for AFL recurrences and may limit iatrogenic complications associated with pharmacological treatments. [ABSTRACT FROM AUTHOR]

Glycogen storage disease type III (GSD III) is an autosomal recessive disease, due to deficiency of glycogen debranching enzyme (GDE), a key enzyme involved in glycogen degradation. Clinical presentation includes hepatomegaly, myopathy, hypoglycemia and cardiomyopathy. The cardiac natural history of patients with GSD III and its relationship with genetic abnormalities is not well known. We performed a longitudinal study in order to describe the natural history of heart involvement in patients with glycogen GSD III. 47 patients were included our study (16 male/31 female). Mean age was 25.7 years ±15.4. All patients were in sinus rhythm expect one patient (atrial fibrillation). 9 patients/ 47 disclosed abnormal repolarization. Electrical left ventricular hypertrophy was found in 22 patients /47. Heart failure was found in 10 patients/47 and 2 patients/47 disclosed a left ventricular dysfunction. Hypertrophic cardiomyopathy was found in 23 patients /47; and 4 patients/47 disclosed obstructive hypertrophic cardiomyopathy. Patients with hypertrophic cardiomyopathy depicted 2 codon-stops (p 0.03). In conclusion, hypertrophic cardiomyopathy is frequent in patients with GSD III. [ABSTRACT FROM AUTHOR]

Introduction Laminopathies are rare genetic diseases, with various clinical manifestations. Cardiac involvement may include conduction system disease, supraventricular and ventricular arrhythmias, and dilated cardiomyopathy. In other cardiac diseases, right ventricular dysfunction has been associated with an impaired prognosis. Objective To study the prevalence of right ventricular involvement in laminopathies and its influence on patient outcome. Methods and results We retrospectively included 138 patients (age=37 [25-49], female=58%) with LMNA gene mutations. At baseline, conduction system disease was present in 36% of patients, supraventricular arrhythmias in 25%, non-sustained and sustained ventricular tachyarrhythmias (VT) in 7 and 6%, left ventricular dysfunction in 42%. The association of right ventricular systolic dysfunction and clinical signs of right heart failure was observed in 18 patients (13%) including 9 who presented with isolated right ventricular without left ventricular systolic dysfunction. Over a 13.5 median follow-up duration, 47 patients (34%) developed major cardiac adverse events, including 23 with end-stage heart failure, 28 with sustained VT, and 26 with 2 nd degree Mobitz II or 3 rd degree AV blocks. Right ventricular involvement was significantly associated with truncating mutations (44% vs. 22%, p=0.04), higher global mortality (44% vs. 17%, p<0.001), end-stage heart failure (56% vs. 11%, p<0.001), sustained ventricular tachycardia (56% vs. 17%, p<0.001), supraventricular tachyarrhythmias (94% vs. 49%, p<0.001), and sinus node dysfunction (33% vs. 7%, p<0.001). Conclusion Patients with laminopathies are at risk for right ventricular dysfunction, which may be present without any left ventricular systolic dys-function and frequently leads to end-stage heart failure. [ABSTRACT FROM AUTHOR]

New treatments are being developed for myotonic dystrophy type 1 (DM1). To evaluate their efficacy, knowledge about the natural history of respiratory dysfunction and its relationship with the genotype will be crucial. Also needed is information on factors predicting the time-course of respiratory function in DM1. Using data from 283 patients, we built a segmented linear mixed-effects regression model to assess respiratory function changes over time. Respiratory variables associated with the CTG repeat number were identified by multivariate linear regression analysis. Cox proportional-hazards regression was used to estimate hazard ratios (HRs) for starting non-invasive ventilation (NIV). Higher CTG repeat number was associated with peak cough flow impairment ( p  = 0.007) and with lower values for maximal inspiratory pressure ( p  <   0.0001) and upright vital capacity. A vital capacity decline over time was associated with older age at first evaluation ( p  <   0.0001), higher CTG repeat number ( p  <   0.0001), and higher baseline body mass index ( p  = 0.0004). NIV initiation was associated with lower peak cough flow ( p  <   0.001) after age and PaCO 2 adjustment. Earlier and closer monitoring with routine peak cough flow determination in adults with congenital DM1, combined with weight control, may diminish the risk of respiratory complications and optimise other aspects of management. [ABSTRACT FROM AUTHOR]

Highlights • Trunk extensors isokinetic strength is correlated with D4Z4 contraction. • D4Z4 contraction and Clinical Severity Scoring were correlated in our study. • 65% of CSS variability can be explained by trunk extensors isokinetic strength. • Severe trunk impairment is observed in FSHD1 patients. • Isokinetic assessment of trunk muscles is easily done in FSHD1 patients. Abstract Facioscapulohumeral muscular dystrophy type 1 is the third most common inherited myopathy. Its severity is proportionate to the loss of microsatellite D4Z4 repetitions, which are below 10. Patients suffer from weakness in facial muscles, shoulder girdles and ankle dorsiflexors. Trunk impairment is reported in few studies. To assess correlation between D4Z4 number of repetitions in facioscapulohumeral muscular dystrophy type 1 patients and trunk extensors and flexors isokinetic peak torque, 48 patients with southern Blot confirmed facioscapulohumeral muscular dystrophy type 1 were enrolled to perform clinical evaluation (Ricci's Clinical Severity Scoring, Berg Balance Scale, Functional Reach Test, timed up-and-go test, six-minute walk test, functional independence measure) and trunk isokinetic assessment. Trunk extensors and flexors isokinetic peak torque at 60°/sec were significantly correlated with number of D4Z4 microsatellite repetitions, sex, weight and age-independent (r = 0.391 [0.121; 0.662] , p < 0.006 and r = 0.334 [0.028; 0.641] , p < 0.033 , respectively). Ricci's Clinical Severity Scoring was significantly correlated to trunk extensors isokinetic peak torque at 60°/sec, sex and weight-independent (r = -0.743 [−0.938; −0.548], p < 0.0001). This study demonstrates moderate correlation between pathologic compression of D4Z4 microsatellite array and trunk extensors isokinetic strength among facioscapulohumeral muscular dystrophy type I patients. [ABSTRACT FROM AUTHOR]