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Aims: Dilated cardiomyopathy (DCM) associated with dystrophin gene (DMD) mutations in individuals with mild or absent skeletal myopathy is often indistinguishable from other DCM forms. We sought to describe the phenotype and prognosis of DMD associated DCM in DMD mutation carriers without severe skeletal myopathy. Methods and results: At 26 European centres, we retrospectively collected clinical characteristics and outcomes of 223 DMD mutation carriers (83% male, 33 ± 15 years). A total of 112 individuals (52%) had DCM at first evaluation [n = 85; left ventricular ejection fraction (LVEF) 34 ± 11.2%] or developed DCM (n = 27; LVEF 41.3 ± 7.5%) after a median follow-up of 96 months (interquartile range 5–311 months). DCM penetrance was 45% in carriers older than 40 years. DCM appeared earlier in males and was independent of the type of mutation, presence of skeletal myopathy, or elevated serum creatine kinase levels. Major adverse cardiac events (MACE) occurred in 22% individuals with DCM, 18% developed end-stage heart failure and 9% sudden cardiac death or equivalent. Skeletal myopathy was not associated with survival free of MACE in patients with DCM. Decreased LVEF and increased left ventricular end-diastolic diameter at baseline were associated with MACE. Individuals without DCM had favourable prognosis without MACE or death during follow-up. Conclusions: DMD-associated DCM without severe skeletal myopathy is characterized by incomplete penetrance but high risk of MACE, including progression to end-stage heart failure and ventricular arrhythmias. DCM onset is the major determinant of prognosis with similar survival regardless of the presence of skeletal myopathy.

Cardiac involvement is recorded in about 80% of patients affected by myotonic dystrophy type 1 (DM1). The prevalence of cardiac conduction abnormalities is well described. Data regarding the prevalence of atrial fibrillation (AF) are still conflicting. The primary objective of this review was to assess the prevalence of AF in DM1. The secondary aim was to examine the association of clinical features with AF, to detect predisposing and/or influencing prognosis factors. A systematic search was developed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials and Web of Science databases, to identify original reports between January 1, 2002 and January 30, 2020, assessing the prevalence of AF in DM1 population. Retrospective/prospective cohort studies and case series describing the prevalence of atrial fibrillation evaluated by periodic electrocardiogram (ECG) and/or ECG Holter 24 h, external loop recording (ELR) and implantable devices interrogation in DM1 patients were included. Case reports, simple reviews, commentaries and editorials were excluded. Thirteen reports fulfilled eligibility criteria and were included in our systematic review. According to the results from all the evaluated studies, the mean prevalence of AF in DM1 patients was 10.9% (n = 404) in 3677 DM1 patients. Male sex, conduction defects, echocardiographic findings of prolonged atrial electromechanical delay seem to be strongly associated with atrial fibrillation, representing factors favoring its onset. DM1 patients who develop AF seem to have a higher risk of cardiovascular and non-cardiovascular death. Further studies are needed to assess the prevalence of AF in DM1 patients and to investigate ECG abnormalities and other clinical features associated with this condition.

X-linked Emery&ndash, Dreifuss muscular dystrophy (EDMD1) affects approximately 1:100,000 male births. Female carriers are usually asymptomatic but, in some cases, they may present clinical symptoms after age 50 at cardiac level, especially in the form of conduction tissue anomalies. The aim of this study was to evaluate the relation between heart involvement in symptomatic EDMD1 carriers and the X-chromosome inactivation (XCI) pattern. The XCI pattern was determined on the lymphocytes of 30 symptomatic and asymptomatic EDMD1 female carriers&mdash, 25 familial and 5 sporadic cases&mdash, seeking genetic advice using the androgen receptor (AR) methylation-based assay. Carriers were subdivided according to whether they were above or below 50 years of age. A variance analysis was performed to compare the XCI pattern between symptomatic and asymptomatic carriers. The results show that 20% of EDMD1 carriers had cardiac symptoms, and that 50% of these were &ge, 50 years of age. The XCI pattern was similar in both symptomatic and asymptomatic carriers. Conclusions: Arrhythmias in EDMD1 carriers poorly correlate on lymphocytes to a skewed XCI, probably due to (a) the different embryological origin of cardiac conduction tissue compared to lymphocytes or (b) the preferential loss of atrial cells replaced by fibrous tissue.

Muscular dystrophy (MD) connotes a heterogeneous group of inherited disordersaffecting skeletal and cardiac muscle. Inseveral forms of MD, the cardiac disease may be the predominant manifestationof the underlying genetic myopathy. The cardiacinvolvement is due to progressive interstitial fibrosis and fatty replacement inboth the atria and ventricles, which may lead to cardiomyopathy, conductiondefects and tachyarrhythmias. Angiotensin-convertingenzyme inhibitors (ACE-Is) modulate the production of angiotensin II and limitthe amount of fibrosis in the myocardium, reducing mortality andhospitalization in cardiac patients. The aim of present review is to describethe antifibrotic proprieties of ACE inhibitor therapy and to summarize thecurrent body of scientific literature relating to the use of ACE-Is for theprevention and treatment of cardiomyopathy in patients with musculardystrophies.

Background Mutations in the LMNA (lamin A/C) gene have been associated with neuromuscular and cardiac manifestations, but the clinical implications of these signs are not well understood. Objective To learn more about the natural history of LMNA-related disease. Design Observational study. Setting 13 clinical centers in Italy from 2000 through 2018. Patients 164 carriers of an LMNA mutation. Measurements Detailed cardiologic and neurologic evaluation at study enrollment and for a median of 10 years of follow-up. Results The median age at enrollment was 38 years, and 51% of participants were female. Neuromuscular manifestations preceded cardiac signs by a median of 11 years, but by the end of follow-up, 90% of the patients had electrical heart disease followed by structural heart disease. Overall, 10 patients (6%) died, 14 (9%) received a heart transplant, and 32 (20%) had malignant ventricular arrhythmias. Fifteen patients had gait loss, and 6 had respiratory failure. Atrial fibrillation and second- and third-degree atrioventricular block were observed, respectively, in 56% and 51% of patients with combined cardiac and neuromuscular manifestations and 37% and 33% of those with heart disease only. Limitations Some of the data were collected retrospectively. Neuromuscular manifestations were more frequent in this analysis than in previous studies. Conclusion Many patients with an LMNA mutation have neurologic symptoms by their 30s and develop progressive cardiac manifestations during the next decade. A substantial proportion of these patients will have life-threatening neurologic or cardiologic conditions. Primary funding source None.

Background Paroxysmal episodes of atrial fibrillation frequently occur in Emery-Dreifuss muscular dystrophy (EDMD). Although previous studies have documented a variety of electrocardiographic abnormalities in EDMD, little is still known about P-wave dispersion (PD), an independent risk factor for the development of atrial fibrillation. The aim of our study was to evaluate the P-wave duration and PD in patients with EDMD with conserved systolic and diastolic cardiac function. Methods The study involved 36 patients with EDMD (age, 20 [SD, 12] years; 26 men) and 36 healthy subjects used as controls, matched for age and sex. P-wave dispersion was carefully measured using 12-lead electrocardiogram. Compared with the healthy control group, patients with EDMD presented increased maximum P-wave duration (108.2 [SD, 22.2] vs 97.8 [SD, 11] milliseconds, P = 0.04) and PD (51.4 [SD, 12.8] vs 39.3 [SD, 9.7] milliseconds, P = 0.004) values. No statistically significant differences in left atrium diameter (37.1 [SD, 2.9] vs 34.1 [SD, 4.2] mm, P = 0.3) and maximum left atrium volume (15.2 [SD, 3.8] vs 14.1 [SD, 4.2] mL/m2, P = 0.4) were found between the 2 groups. We divided our study population into 2 subgroups, according to the different genetic diagnosis, patients with laminopathy EDMD (n = 17) or with emerinopathy EDMD (n = 19). No statistically significant differences were found in PD between the 2 subgroups (54.6 [SD, 15.6] vs 50.2 [SD, 11.5] milliseconds, P = 0.4). Conclusions Our study showed a significant increase of maximum P-wave duration and PD in patients with EDMD with conserved systolic and diastolic cardiac function.

Aim: We performed a two-year follow-up comparative study of long-term electrical parameters between the right atrial appendage (RAA) and Bachmann’s Bundle (BB) stimulation in myotonic dystrophy type 1 (MD1) patients. Methods: Twenty-five MD1 patients (18 men; age: 54 ± 13 years) with no difference in the electrical parameters between the RAA site and the BB region at implantation were randomized into two groups: in group I (13 patients; age: 52 ± 14 years; four women) the atrial lead was placed in the RAA and in group II (12 patients, age: 56 ± 12 years, three women) the lead was placed in the BB region. Measurements of electrical parameters were recorded at follow-up intervals of 6 weeks and then 12 and 24 months postimplant. Results: There was no statistically significant different in P-wave amplitude, pacing threshold, and impedance values between the two groups at 6 weeks. At 24 months follow-up, the intrinsic P-wave amplitude was 2.05 ± 1.45 mV in the RAA group versus 3.28 ± 1.09 mV in the BB group (P < 0.05); the pacing threshold was 1.85 ± 1.8 V in the RAA group versus 0.50 ± 0.39 V in the BB group (P = 0.03); there were no differences in the atrial impedance between the two groups during the follow-up period. Conclusions: In a direct two-year follow-up comparison between the RAA and BB atrial pacing sites, we showed a statistically significant increased pacing threshold and decreased intrinsic P-wave amplitude during RAA stimulation in MD1 patients. (PACE 2009; 32:1191–1196) Bachmann’s bundle, myotonic dystrophy, pacemaker, arrhythmias, heart block, fibrosis, sensing,pacing, impedance, atrial lead

PURPOSE: To compare intraocular pressure (IOP) between patients with myotonic dystrophy (DM1) and normal subjects, taking into account corneal characteristics. To determine whether lower IOP measurements in patients with DM1 are due to thinner corneas. DESIGN: Comparative case series. PARTICIPANTS: Fifty-three eyes of patients with DM1 and 53 eyes of normal age- and sex-matched subjects. METHODS: Corneal biomechanical properties and corneal compensated intraocular pressure (IOPcc) measured with the Ocular Response Analyzer (Reichert Inc., Depew, NY), central corneal thickness measured with the Oculus Pentacam (Oculus, Wetzlar, Germany), and IOP were evaluated in patients with DM1 and compared with age- and sex-matched healthy subjects. MAIN OUTCOME MEASUREMENTS: Goldmann applanation tonometry, central corneal thickness, corneal hysteresis (CH), corneal resistance factor (CRF), and IOPcc. RESULTS: Compared with the healthy subjects, patients with DM1 showed lower IOP (12.4+/-3.6 mm Hg vs. 14.9+/-3.4 mmHg) (P

The development of malignant ventricular arrhythmias is a possible feature in Emery-Dreifuss muscular dystrophy (EDMD) patients with normal left ventricular systolic function. This event may be the cause of sudden cardiac death in EDMD patients. QTc dispersion (QTc-D), JTc dispersion (JTc-D) and Tpeak-end dispersion (TDR) could reflect the physiological variability of regional and transmural ventricular repolarisation and could provide a substrate for life-threatening ventricular arrhythmias.The current study was designed to evaluate the heterogeneity of ventricular repolarisation in EDMD patients.Echocardiograms and electrocardiograms from 40 EDMD patients (age 20 ± 13) were evaluated and compared to those of 40 healthy age-matched controls.The EDMD group, compared to the healthy control group, presented increased values of QTc-D (82.8 ± 44.1 vs. 53.3 ± 13.9, p = 0.003), JTc-D (73.6 ± 32.3 vs. 60.4 ± 11.1 ms, p = 0.001) and TDR (100.54 ± 19.06 vs. 92.15 ± 15.5 ms, p = 0.004). No correlation between QTc dispersion and ejection fraction (R = 0.2, p = 0.3) was found.EDMD is associated with significantly increased regional and transmural heterogeneity of ventricular repolarisation, in the absence of impaired systolic and diastolic cardiac function.

The spinal muscular atrophies (SMAs) include a group of disorders characterized by progressive weakness of the lower motor neurons. Several types of SMAs have been described based on age onset of clinical features: Acute infantile (SMA type I), chronic infantile (SMA type II), chronic juvenile (SMA type III), and adult onset (SMA type IV) forms. The incidence is about 1:6,000 live births with a carrier frequency of 1:40 for the severe form and 1:80 for the juvenile form. The mortality and/or morbidity rates of SMAs are inversely correlated with the age at onset. SMAs are believed to only affect skeletal muscles; however, new data on SMA mice models suggest they may also impact the heart. Aim of the study was to retrospectively examine the cardiological records of 37 type molecularly confirmed II/III SMA patients, aged 6 to 65 years, in order to evaluate the onset and evolution of the cardiac involvement in these disorders. All patients had a standard ECG and a routine echocardiography. The parameters analysed were the following: Heart rate (HR), PQ interval, PQ segment, Cardiomyopathic Index (ratio QT/PQs), ventricular and supraventricular ectopic beats, pausesor = 2,5 msec, ventricle diameters, wall and septum thickness, ejection fraction, fiber shortening. The results showed that HR and the other ECG parameters were within the normal limits except for the Cardiomyopathic Index that was higher than the normal values (2,6-4,2) in 2 patients. Left ventricular systolic function was within the normal limits in all patients. A dilation of the left ventricle without systolic dysfunction was observed in only 2 patients, aged respectively 65 and 63 years; however they were hypertensive and/or affected by coronary artery disease. Data here reported contribute to reassure patients and their clinicians that type II/III SMAs do not present heart dysfunction.

We report a clinic case of patient in whom angiosarcoma of the heart presents as bilateral pulmonary nodular infiltrates. The cardiac tumor was clinically silent, the electrocardiogram was normal and the cough was the only symptom. Chest CT scan (Fig. 1) showed bilateral diffuse nodular infiltrates ranging. Clinical clues, the results of laboratory tests and all of the cultures obtained excluded an infectious etiologies; the findings of CT-guided needle biopsy was inconclusive for a definitive diagnosis. Thus, the patient was scheduled for a thoracoscopic biopsy. Surprisingly, the pre-operatory echocardiogram showed a soft tissue mass fixed to the posterior wall of the right atrium. On retrospective reviewing of chest CT scan, a tumor was evident in the right atrium, but it was missed initially. In theory, the lung lesions attract the attention of the observer who had not taken into account anything else as to say: "the brain knows what the eyes want". The diagnosis ofpulmonary metastases was obtained by means ofpleural biopsy during right thoracoscopy. Immunoistochemical staining revealed a CK-, CK7-, EMA-, ESA-, CEA-, TTF1-, Vimentina+, CD31+, CD117+ lesion. Because at the time of diagnosis our patient already had lung metastases, he underwent chemotherapy.

OBJECTIVE: The aim of this study was to determine cardio-respiratory changes after endothoracic sympathetic denervation and their correlation with the extent of denervation. METHODS: A total of 45 patients with essential palmar hyperhidrosis were randomized into two groups: the conventional group (CG; 23 patients) and the simplified group (SG; 22 patients). In the CG, excision of T2 and T3 ganglia was performed, whereas in the SG only separation of the sympathetic chain was performed at the same level. Patients underwent respiratory and cardiovascular exercise tests before, at 2 weeks and again at 6 months after the procedure. The postoperative values were then compared with the preoperative values to assess the statistical difference. RESULTS: Twenty-one patients in each group completed the study. In the SG, forced expiratory volume in 1 s (FEV 1; P < 0.01) and forced vital capacity (FVC; P < 0.01) were significantly reduced at 2 weeks, but returned to similar baseline values 6 months after the procedure. No significant cardiac changes were observed. In the CG, both FEV 1 and FVC were significantly reduced at 2 weeks (P < 0.01) and at 6 months after operation (P < 0.05). A significant reduction in forced expiratory flow between 25 and 75% of vital capacity (P < 0.01) and a relevant increase in airway resistance (P < 0.05) during the entire postoperative course were also observed. Heart rates at rest and at peak exercise were significantly reduced at 2 weeks (P < 0.01) and significantly decreased 6 months after the procedure (P < 0.05). No other changes were registered. The cardio-respiratory alterations remained at a sub-clinical level; all patients completed the exercise test without symptoms. CONCLUSION: Sympathectomy may result in a disturbance of bronchomotor tone and cardiac function. Such changes remained at a sub-clinical level and seemed directly correlated with the extension of denervation.

PURPOSE: To investigate why myotonic dystrophy type 1 (DM1) patients have low intraocular pressure (IOP). DESIGN: Prospective, comparative case series. PARTICIPANTS: One hundred two eyes of 51 patients with DM1 (age range, 21-64 years) and 44 eyes of 22 healthy subjects of similar age (21-64 years). METHODS: All participants underwent IOP measurement with Goldmann applanation tonometry and an in vivo examination of the ciliary body with a 35-MHz high-resolution B-scan. The findings were compared between the 2 groups. In both groups, only patients with no history of ocular trauma or surgery were included. The differences were evaluated using the unpaired Student t test. MAIN OUTCOME MEASUREMENTS: Intraocular pressure, central corneal thickness (CCT), and echographic evidence of ciliary body detachment. RESULTS: The mean ± standard deviation (SD) IOP in patients with DM1 was 10.9 ± 3.1 mmHg and that in the control patients was 15.4 ± 2.2 mmHg, a difference that reached significance (P

Objective Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adults. DM1 is a multisystem disorder also affecting the heart with an increased incidence of sudden death, which has been explained with the common impairment of the conduction system often requiring pacemaker implantation; however, the occurrence of sudden death despite pacemaker implantation and the observation of major ventricular arrhythmias generated the hypothesis that ventricular arrhythmias may play a causal role as well. The aim of the study was to assess the 2-year cumulative incidence and the value of noninvasive and invasive findings as predictive factors for sudden death, resuscitated cardiac arrest, ventricular fibrillation, sustained ventricular tachycardia and severe sinus dysfunction or high-degree atrioventricular block. Methods/design More than 500 DM1 patients will be evaluated at baseline with a clinical interview, 12-lead ECG, 24-h ECG and echocardiogram. Conventional and nonconventional indications to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implantation have been developed. In the case of an indication to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implant at baseline or at follow-up, the patient will be referred for the procedure. At the end of 2-year follow-up, all candidate prognostic factors will be tested for their association with the endpoints. Trial registration ClinicalTrials.gov ID NCT00127582. Conclusion The available evidence supports the hypothesis that both bradyarrhythmias and tachyarrhythmias may cause sudden death in DM1, but the course of cardiac disease in DM1 is still unclear. We expect that this large, prospective, multicenter study will provide evidence to improve diagnostic and therapeutic strategies in DM1.

We report the case of 14-year-old boy with X-linked Emery-Dreifuss muscular dystrophy who developed sick sinus syndrome and required placement of an implantable intracardiac cardioverter-defibrillator (ICD) to prevent sudden death. He demonstrated no significant risk factors for sudden death such as depressed left ventricular ejection fraction, or spontaneous or inducible ventricular tachycardia. One month after implantation, the patient experienced one appropriate ICD discharge.