Cardiac and Neuromuscular Features of Patients With LMNA-Related Cardiomyopathy.

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.

Atrial fibrillation burden in Myotonic Dystrophy type 1 patients implanted with dual chamber pacemaker: the efficacy of the overdrive atrial algorithm at 2 year follow-up.

The role that atrial pacing therapy plays on the atrial fibrillation (AF) burden is still unclear. Aim of the study was to evaluate the effect of the atrial preference pacing algorithm on AF burden in patients affected by Myotonic Dystrophy type 1 (DM1) followed for a long follow up period. Sixty DM1 patients were -implanted with a dual chamber pacemaker (PM) for first degree or symptomatic type 1/type 2 second degree atrio-ventricular blocks- were followed for 2-years after implantation, by periodical examination. After 1 month of stabilization, they were randomized into two groups: 1) Patients implanted with conventional dual-chamber pacing mode (DDDR group) and 2) Patients implanted with DDDR plus Atrial Preference Pacing (APP) algorithm (APP ON group). The results showed that atrial tachycardia (AT)/AF burden was significantly reduced at 1 year follow up in the APP ON group (2122 ± 428 minutes vs 4127 ± 388 minutes, P = 0.03), with a further reduction at the end of the 2 year follow up period (4652 ± 348 minutes vs 7564 ± 638 minutes, P = 0.005). The data here reported show that the APP is an efficient algorithm to reduce AT/AF burden in DM1 patients implanted with dual chamber pacemaker.

Echocardiographic Features of Cardiac Involvement in Myotonic Dystrophy 1: Prevalence and Prognostic Value.

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. Cardiac involvement is reported in 80% of cases and includes conduction disturbances, arrhythmias, subclinical diastolic and systolic dysfunction in the early stage of the disease; in contrast, severe ventricular systolic dysfunction occurs in the late stage of the disease. Echocardiography is recommended at the time of diagnosis with periodic revaluation in DM1 patients, regardless of the presence or absence of symptoms. Data regarding the echocardiographic findings in DM1 patients are few and conflicting. This narrative review aimed to describe the echocardiographic features of DM1 patients and their prognostic role as predictors of cardiac arrhythmias and sudden death.

Current Views on Infective Endocarditis: Changing Epidemiology, Improving Diagnostic Tools and Centering the Patient for Up-to-Date Management.

Infective endocarditis (IE) is a rare but potentially life-threatening disease, sometimes with longstanding sequels among surviving patients. The population at high risk of IE is represented by patients with underlying structural heart disease and/or intravascular prosthetic material. Taking into account the increasing number of intravascular and intracardiac procedures associated with device implantation, the number of patients at risk is growing too. If bacteremia develops, infected vegetation on the native/prosthetic valve or any intracardiac/intravascular device may occur as the final result of invading microorganisms/host immune system interaction. In the case of IE suspicion, all efforts must be focused on the diagnosis as IE can spread to almost any organ in the body. Unfortunately, the diagnosis of IE might be difficult and require a combination of clinical examination, microbiological assessment and echocardiographic evaluation. There is a need of novel microbiological and imaging techniques, especially in cases of blood culture-negative. In the last few years, the management of IE has changed. A multidisciplinary care team, including experts in infectious diseases, cardiology and cardiac surgery, namely, the Endocarditis Team, is highly recommended by the current guidelines.

Cardiovascular Effects of Weight Loss in Obese Patients with Diabetes: Is Bariatric Surgery the Additional Arrow in the Quiver?

Obesity is an increasingly widespread disease worldwide because of lifestyle changes. It is associated with an increased risk of cardiovascular disease, primarily type 2 diabetes mellitus, with an increase in major cardiovascular adverse events. Bariatric surgery has been shown to be able to reduce the incidence of obesity-related cardiovascular disease and thus overall mortality. This result has been shown to be the result of hormonal and metabolic effects induced by post-surgical anatomical changes, with important effects on multiple hormonal and molecular axes that make this treatment more effective than conservative therapy in determining a marked improvement in the patient's cardiovascular risk profile. This review, therefore, aimed to examine the surgical techniques currently available and how these might be responsible not only for weight loss but also for metabolic improvement and cardiovascular benefits in patients undergoing such procedures.

On a case of respiratory failure due to diaphragmatic paralysis and dilated cardiomyopathy in a patient with nemaline myopathy.

Nemaline myopathy is a rare congenital disease that generally occurs in childhood. We report a case of a 50-year-old man who presented with severe heart failure as the initial manifestation of nemaline myopathy. Soon after he developed acute restrictive respiratory failure due to the diaphragmatic paralysis. The diagnosis of "nemaline myopathy" was obtained on muscle biopsy performed one year later. After starting appropriate cardiological treatment and non-invasive ventilation, his cardiac and pulmonary functions improved substantially, remaining stable for over the 10 years since diagnosis. In the last two years the patient had a progressive deterioration of respiratory function, enabling him to attend daily activities. Few cases of respiratory failure in patients with adult-onset nemaline myopathy are reported, but the insidious onset in this case is even more unusual. This case highlights the wide spectrum of presenting features of adult-onset nemaline myopathy and the temporary efficacy of non invasive ventilation on respiratory function.

Right atrial preference pacing algorithm in the prevention of paroxysmal atrial fibrillation in myotonic dystrophy type 1 patients: a long term follow-up study.

Atrial Preference Pacing (APP) is a pacemaker (PM) algorithm that works by increasing the atrial pacing rate to achieve continuous suppression of a spontaneous atrial rhythm and prevent supraventricular tachyarrhythmias. We have previously shown that atrial preference pacing may significantly reduce the number and the duration of AF episodes in myotonic dystrophy type 1 (DM1) patients who are paced for standard indications.However, the role that APP therapies play in the prevention of AF in a long-term period remains still unclear. Aim of the present prospective study was to evaluate whether this beneficial effect is maintained for 24-months follow-up period.To this aim, 50 patients with Myotonic Dystrophy type 1 who underwent dual-chamber PM implantation for first- and second- degree atrioventricular block, were consecutively enrolled and followed for 2 years. One month later the stabilization period, after the implantation, they were randomized to APP algorithm programmed OFF or ON for 6 months each, using a cross-over design, and remained in the same program for the second year. The results showed that while the number of AF episodes during active treatment (APP ON phases) was lower than that registered during no treatment (APP OFF phases), no statistically significant difference was found in AF episodes duration between the two phases. Furthermore, during the APP OFF and APP ON phases, the percentage of atrial pacing was 0 and 99%, respectively, while the percentage of ventricular pacing did not show differences statistically significant (11 vs. 9%, P = 0.2). Atrial premature beats were significantly higher during APP OFF phases than during APP ON phases. Lead parameters remained stable over time and there were no lead-related complications. Based on these 24-months follow-up data, we can conclude that, in DM1 patients who underwent dual-chamber PM implantation, APP is an efficacy algorithm for preventing paroxysmal AF even in long term periods.

Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients.

Duchenne Muscular Dystrophy (DMD) is the most common muscle disease in children. Historically, DMD results in loss of ambulation between ages 7 and 13 years and death in the teens or 20s. In order to determine whether survival has improved over the decades and whether the impact of nocturnal ventilation combined with a better management of cardiac involvement has been able to modify the pattern of survival, we reviewed the notes of 835 DMD patients followed at the Naples Centre of Cardiomyology and Medical Genetics from 1961 to 2006. Patients were divided, by decade of birth, into 3 groups: 1) DMD born between 1961 and 1970; 2) DMD born between 1971 and 1980; 3) DMD born between 1981 and 1990; each group was in turn subdivided into 15 two-year classes, from 14 to 40 years of age. Age and causes of death, type of cardiac treatment and use of a mechanical ventilator were carefully analyzed.The percentage of survivors in the different decades was statistically compared by chi-square test and Kaplan-Meier survival curves analyses. A significant decade on decade improvement in survival rate was observed at both the age of 20, where it passed from 23.3% of patients in group 1 to 54% of patients in group 2 and to 59,8% in patients in group 3 (p < 0.001) and at the age of 25 where the survival rate passed from 13.5% of patients in group 1 to 31.6% of patients in group 2 and to 49.2% in patients in group 3 (p < 0.001).The causes of death were both cardiac and respiratory, with a prevalence of the respiratory ones till 1980s. The overall mean age for cardiac deaths was 19.6 years (range 13.4-27.5), with an increasing age in the last 15 years. The overall mean age for respiratory deaths was 17.7 years (range 11.6-27.5) in patients without a ventilator support while increased to 27.9 years (range 23-38.6) in patients who could benefit of mechanical ventilation.This report documents that DMD should be now considered an adulthood disease as well, and as a consequence more public health interventions are needed to support these patients and their families as they pass from childhood into adult age.

Bilateral lung lesions: when the eyes deceive the brain!

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.

The Role of TRPM4 Gene Mutations in Causing Familial Progressive Cardiac Conduction Disease: A Further Contribution.

Progressive cardiac conduction disease (PCCD) is a relatively common condition in young and elderly populations, related to rare mutations in several genes, including SCN5A, SCN1B, LMNA and GJA5, TRPM4. Familial cases have also been reported. We describe a family with a large number of individuals necessitating pacemaker implantation, likely due to varying degrees of PCCD. The proband is a 47-year-old-patient, whose younger brother died at 25 years of unexplained sudden cardiac death. Three paternal uncles needed a pacemaker (PM) implantation between 40 and 65 years for unspecified causes. At the age of 42, he was implanted with a PM for two episodes of syncope and the presence of complete atrioventricular block (AVB). NGS analysis revealed the missense variation c. 2351G>A, p.Gly844Asp in the exon 17 of the TRPM4 gene. This gene encodes the TRPM4 channel, a calcium-activated nonselective cation channel of the transient receptor potential melastatin (TRPM) ion channel family. Variations in TRPM4 have been shown to cause an increase in cell surface current density, which results in a gain of gene function. Our report broadens and supports the causative role of TRPM4 gene mutations in PCCD. Genetic screening and identification of the causal mutation are critical for risk stratification and family counselling.

Low intraocular pressure resulting from ciliary body detachment in patients with myotonic dystrophy.

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<0.01). The mean ± SD CCT (measured at the pupillary center) was 574.4 ± 37.9 µm in the patients with DM1 and 557.8 ± 39.2 µm in the controls (P = 0.02). Detachment of the ciliary body was identified in all DM1 subjects. Size was variable and the detachment involved 1 or more quadrants. The number of quadrants affected by the detachment was not correlated with the IOP (R(2) = 0.088) or the size of the CTG expansion. No detachments were found in the healthy controls. CONCLUSIONS: Detachment of the ciliary body may explain the low IOP values in patients with DM1. The finding of a ciliary body detachment in an individual who has not had recent eye surgery or trauma raises the possibility of a DM1 diagnosis.

Cardiac involvement in patients with spinal muscular atrophies.

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, pauses > or = 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.

Prevalence of atrial fibrillation in myotonic dystrophy type 1: A systematic review.

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.

Prevalence and clinical outcomes of dystrophin-associated dilated cardiomyopathy without severe skeletal myopathy.

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.

Beneficial effects of one-month sacubitril/valsartan treatment in a patient affected by end-stage dystrophinopathic cardiomyopathy.

Dystrophinopathic cardiomyopathy (DCM) is an almost constant manifestation in Becker muscular dystrophy (BMD) patients significantly contributing to morbidity and mortality. The nearly complete replacement of the myocardium by fibrous and fatty connective tissue results in an irreversible cardiac failure, characterized by progressive reduction of the ejection fraction. According to PARADIGM-HF trial results, the European Society of Cardiology (ESC) guidelines recommend the use of sacubitril/valsartan in ambulatory patients with heart failure and reduced ejection fraction, who remain symptomatic despite an optimal medical therapy. To date, little is still known about the use of sacubitril/valsartan in DCM. We report the case of a patient with dystrophinopathic end stage dilated cardiomyopathy with reduced ejection fraction who successfully responded to sacubitril/valsartan treatment.

Efficacy and safety of ropivacaine HCl in peribulbar anaesthesia for cataract surgery in patients with myotonic dystrophy type 1.

Myotonic dystrophy (DM1) is the most common muscle disease in adults, affecting approximately 1:8000 individuals, characterized by myotonia and muscular wasting and a multisystemic involvement that includes heart, brain, respiratory and endocrine system, and eye. Conduction system is selectively involved, often causing cardiac sudden death. Early onset posterior subcapsular cataract is a characteristic feature of myotonic dystrophy, requiring surgical treatment. However, DM1 is associated with many anesthetic hazards; sensitivity to anesthetic drugs, especially muscle relaxants and opioids, may complicate postoperative care. Local anesthesia also requires attention. We investigated the heart response to local anesthesia Ropivacaine Hcl administration in 16 DM1 patients (12M:4F) consecutively undergoing cataract surgery, by analyzing heart rate, ventricular and supraventricular ectopic beats, runs of tachycardia and pauses ≥ 2.5 sec., through a 24h-Holter monitoring, registered before and within 24 hours after surgery. The average age of patients was 47.4 years (range 30.2-55.9). At baseline, one patient had a pacemaker and 3 a defibrillator. Two patients presented a first-degree atrio-ventricular-block; three showed ectopic ventricular beats, on anti-arrhythmic drug treatment. No significant differences in heart rate values (73 ± 15b/m versus 76 ± 13b/m) were observed after cataract surgery, nor in the onset of ectopic beats. Only patients who presented ventricular ectopic beats at baseline, showed an increase in their number after surgery, likely related to an arbitrary interruption of the specific treatment. These data confirm the safety and efficacy of ropivacaine HCl used as a local anesthetic in patients with myotonic dystrophy.

Intraocular pressure and corneal biomechanical properties in patients with myotonic dystrophy.

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<0.01) and IOPcc (12.7+/-4.5 vs. 15.9+/-3.5) (P<0.01), and thicker cornea (575.9+/-35.02 mum vs. 556.3+/-33.2 microm) (P<0.01), but no significant changes in CH (P = 0.03) and CRF (P = 0.37). CONCLUSIONS: Lower IOP in patients with DM1 is not related to differences in central corneal thickness or corneal biomechanical properties. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Right atrial appendage versus Bachmann's bundle stimulation: a two-year comparative study of electrical parameters in myotonic dystrophy type-1 patients.

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.

Are there real benefits to implanting cardiac devices in patients with end-stage dilated dystrophinopathic cardiomyopathy? Review of literature and personal results.

Cardiomyopathy associated with dystrophinopathies - Duchenne muscular Dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XL-CM) and cardiomyopathy of Duchenne/Becker (DMD/BMD carriers - is an almost constant manifestation of these neuromuscular disorders and contribute significantly to their morbidity and mortality. Dystrophinopathic cardiomyopathy is the result of the dystrophin protein deficiency at the myocardium level, parallel to that occurring at the skeletal muscle level. Typically, cardiomyopathy begins as a "presymptomatic" stage in the first decade of life and evolves in a stepwise manner toward an end-stage dilated cardiomyopathy. Nearly complete replacement of the myocardium by fibrous and fatty connective tissue results in an irreversible cardiac failure, characterized by a further reduction of ejection fraction (EF < 30%) and frequent episodes of acute heart failure (HF). The picture of a severe dilated cardiomyopathy with intractable heart failure is typical of dystrophinopathies. Despite an appropriate pharmacological treatment, this condition is irreversible because of the extensive loss of myocites. Heart transplantation is the only curative therapy for patients with end-stage heart failure, who remain symptomatic despite an optimal medical therapy. However there is a reluctance to perform heart transplantation (HT) in these patients due to the scarcity of donors and the concerns that the accompanying myopathy will limit the benefits obtained through this therapeutic option. Therefore the only possibility to ameliorate clinical symptoms, prevent fatal arrhythmias and cardiac death in dystrophinopathic patients could be the implantation of intracardiac device (ICD) or resynchronizing devices with defibrillator (CRT-D). This overview reports the personal series of patients affected by DMD and BMD and DMD carriers who received ICD or CRT-D system, describe the clinical outcomes so far published and discuss pro and cons in the use of such devices.

Cardiac diseases as a predictor warning of hereditary muscle diseases. The case of laminopathies.

Mutations in the LMNA gene are associated with a wide spectrum of disease phenotypes, ranging from neuromuscular, cardiac and metabolic disorders to premature aging syndromes. Skeletal muscle involvement may present with different phenotypes: limb-girdle muscular dystrophy type 1B or LMNA-related dystrophy; autosomal dominant Emery-Dreifuss muscular dystrophy; and a congenital form of muscular dystrophy, frequently associated with early onset of arrhythmias. Heart involvement may occur as part of the muscle involvement or independently, regardless of the presence of the myopathy. Notably conduction defects and dilated cardiomyopathy may exist without a muscle disease. This paper will focus on cardiac diseases presenting as the first manifestation of skeletal muscle hereditary disorders such as laminopathies, inspired by two large families with cardiovascular problems long followed by conventional cardiologists who did not suspect a genetic muscle disorder underlying these events. Furthermore it underlines the need for a multidisciplinary approach in these disorders and how the figure of the cardio-myo-geneticist may play a key role in facilitating the diagnostic process, and addressing the adoption of appropriate prevention measures.