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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]

Chronic respiratory failure and heart involvement may occur in Duchenne muscular dystrophy (DMD). We aimed to assess the prognostic value of the right ventricular (RV) systolic dysfunction in DMD. We studied 90 genetically proven DMD patients from 2010 to 2019, to obtain respiratory function and Doppler echocardiographic RV systolic function. Prognostic value was assessed in terms of cardiac events and mortality. The median age was 27.5 years and median forced vital capacity (FVC) was at 10% of the predicted value: 83 patients (92%) were on home mechanical ventilation. A RV systolic dysfunction was found in 46 patients (51%). RV systolic dysfunction was significantly associated with cardiac events, mainly acute heart failure (62%) and cardiogenic shock (23%). In a multivariable Cox model, the adjusted hazard-ratio (adj.HR) was 4.96 (95% confidence interval = 1.09–22.6, P = 0.04). In terms of mortality, we found a significant difference between patients with RV systolic dysfunction vs. patients without RV systolic dysfunction (log-rank P = 0.045). RV systolic dysfunction is frequently present in DMD patients and may be associated with long-term poor prognosis, irrespective of left ventricular dysfunction and mechanical ventilation. [ABSTRACT FROM AUTHOR]

Introduction 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. Hypertrophic cardiomyopathy is a classical complication in this disease. Objectives We performed a longitudinal study in order to describe the natural history of heart involvement, relationship with genotype and to determine long term follow up related to hypertrophic cardiomyopathy in patients with GSD III. Method We included all consecutive patients with GSD III followed in Pitié-Salpêtrière and Antoine Beclere centers and collected clinical, genetic, electrocardiogram and echocardiography data and cardiac events. Result 37 patients were included in this study (12 males/25 females). Mean age was 22.4 years [1–52]. All patients were in sinus rhythm expect one patient (atrial fibrillation). Electrical left ventricular hypertrophy was found in 16 (43%) patients. Symptomatic heart failure was found in 8 (22%) patients and 1 (3%) patient disclosed left ventricular dysfunction. Left ventricular hypertrophy (LVH) was found in 16 (43%) patients, mostly symmetric and 4 (11%) patients disclosed obstructive hypertrophic cardiomyopathy. Patients essentially developed heart failure with preserved LVEF (HFpEF) which prevalence increased with age. In univariate analysis, nonsense mutations were associated with more LVH than other type of mutations but not in multivariate analysis. Conclusion Hypertrophic cardiomyopathy is frequent in patients with GSD3 and is associated with cardiac clinical events, especially HFpEF. [ABSTRACT FROM AUTHOR]

Background The risk for venous thromboembolism (VTE) in inherited myopathies, which can lead to chronic immobilization, is unknown. Purpose To evaluate incidence of VTE in inherited myopathies, including for patients who lost ambulation, to compare it to incidence of VTE in general population and to identify predictors of VTE events in inherited myopathies. Methods We retrospectively enrolled 2810 adult patients with genetically proven myopathy, admitted to our institutions between January 2000 and November 2014. We collected any information relative to their demographic and genetic characteristics, their muscular functional status including ambulation and the occurrence of VTE. We determined the incidence of venous thromboembolism in this population by using Kaplan–Meier product-limit method, compared it to general population with log-rank test and assessed its predictors with multivariable Cox modeling. Results Over a median follow-up of 8.5 years, 102 patients developed venous thromboembolism, representing a cumulative incidence of 6.2%, higher than in general population matched on age and sex. We identified four independent predictors of VTE: age (hazard-ratio ( HR ) = 1.02, 95%CI = 1.01–1.04, P = 0.002), a personal history of VTE ( HR = 5.54, 95%CI = 2.91–10.5, P < 0.0001), a diagnosis of myotonic dystrophy (DM) ( HR = 4.63, 95%CI = 2.63–8.18, P < 0.0001) and permanent loss of ambulation inpatients with DM ( HR = 4.07, 95%CI = 1.14–14.5, P = 0.030). Loss of ambulation alone was not a significant independent predictor of VTE. Conclusions VTE in inherited myopathies is not a rare condition and is more frequent than in general population. We identified four independent predictors of VTE in these patients. Patients with DM represented the population with the highest risk of VTE. [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]