Cardiomyopathies due to neuromuscular disorders are forms of cardiac involvement that occur in the context of inherited or acquired diseases of skeletal muscle, the motor neuron, the neuromuscular junction, or the intracellular structures that ensure mechanical stability, electrical conduction, energy metabolism and nuclear integrity of the muscle cell. This group mainly includes muscular dystrophies, congenital myopathies, myotonic dystrophies, laminopathies, desminopathies, sarcoglycanopathies, dystrophinopathies, Friedreich ataxia and some mitochondrial or metabolic diseases with predominant neuromuscular expression. The heart may manifest dilated cardiomyopathy, hypertrophic cardiomyopathy, a restrictive phenotype, non-dilated left ventricular cardiomyopathy, conduction disorders, atrial arrhythmias, ventricular arrhythmias, sudden death and heart failure.
The most important clinical feature is the possible dissociation between neuromuscular severity and cardiac severity. A patient may have marked muscle weakness and a relatively preserved heart, or mildly symptomatic skeletal muscles and advanced cardiomyopathy. This occurs because the altered proteins do not always have the same role in skeletal muscle and in the myocardium, and because the heart is exposed to continuous mechanical load, high energy demand and incessant electrical activity. Consequently, normal muscle strength does not exclude heart disease, and neurological stability does not justify suspending cardiological surveillance.
From an epidemiological point of view, the frequency of cardiac involvement varies greatly according to the underlying disease and genotype. In Duchenne muscular dystrophy, myocardial involvement becomes very frequent with age and represents a major cause of morbidity and mortality; in Becker muscular dystrophy, cardiomyopathy may be dominant compared with muscle weakness; in myotonic dystrophy type 1, conduction disorders, arrhythmias and sudden death predominate; in laminopathies and Emery-Dreifuss muscular dystrophy, arrhythmic risk may precede systolic dysfunction; in Friedreich ataxia, hypertrophic cardiomyopathy and impaired myocardial energy metabolism are central components of the natural history. For this reason, the page should be read as a cross-sectional framework, not as a single disease.
Neuromuscular diseases with cardiac involvement constitute a heterogeneous group in which the same genetic or cellular alteration may affect skeletal muscle, myocardium, conduction system, respiratory muscles and, sometimes, the central or peripheral nervous system. The term “cardiomyopathies due to neuromuscular disorders” therefore does not indicate a single diagnosis, but a cardiac phenotype secondary or parallel to a neuromuscular disease. This approach is decisive: the cardiologist must not merely classify the form as dilated, hypertrophic or arrhythmic, but must search for the underlying disease, because genotype, natural history, familial risk and therapeutic indications depend on the cause.
Dystrophinopathies are among the most representative causes. Duchenne muscular dystrophy, due to variants of the DMD gene with absence or severe reduction of dystrophin, produces progressive degeneration of skeletal muscle and almost inevitable cardiomyopathy during life. The increase in survival achieved with non-invasive ventilation, corticosteroids, physiotherapy, improved orthopedic management and multidisciplinary care has made the heart an even more relevant determinant of prognosis. Becker muscular dystrophy, in which dystrophin is reduced or altered but not completely absent, often has a slower muscular course, but may manifest severe dilated cardiomyopathy even when the patient is still ambulant or has only moderate weakness.
Limb-girdle muscular dystrophies include numerous genetic subtypes. Cardiac involvement is particularly relevant in forms related to FKRP, the fukutin-related protein gene, sarcoglycans, LMNA, the lamin A/C gene, DES, the desmin gene, and other genes with cardiac expression. Some forms have predominantly dilated cardiomyopathy; others present conduction disorders, atrial or ventricular arrhythmias; still others have modest or rare cardiac involvement. Molecular distinction is therefore indispensable, because the clinical label “limb-girdle muscular dystrophy” is too broad to predict individual cardiac risk.
Myotonic dystrophies, especially myotonic dystrophy type 1, represent a different model. The cardiac problem may be dominated by fibrofatty degeneration of the conduction system, atrioventricular blocks, intraventricular blocks, atrial arrhythmias, ventricular tachycardias and sudden death. Systolic dysfunction may occur, but in many patients the main risk is electrical before it is contractile. This makes the electrocardiogram and rhythm monitoring as important as echocardiography. Myotonic dystrophy type 2 may involve the heart, but on average with a less severe profile than type 1, although surveillance is still required.
Emery-Dreifuss muscular dystrophy and laminopathies show a particularly dangerous pattern because electrical disease may precede ventricular dysfunction. The patient may present early contractures, scapulohumeral and peroneal weakness, spinal rigidity, conduction blocks, atrial paralysis, atrial fibrillation, atrial flutter, bradyarrhythmias, ventricular tachyarrhythmias and dilated cardiomyopathy. In LMNA variants, the risk of sudden death may be high even when ejection fraction is not severely reduced; for this reason, risk stratification must not mechanically copy the general criteria used for common heart failure.
Friedreich ataxia is an autosomal recessive neurodegenerative disease caused by GAA expansion in the FXN gene, leading to frataxin deficiency. The heart often develops ventricular hypertrophy, energy abnormalities, fibrosis and, in advanced stages, systolic dysfunction. Unlike dystrophinopathies, here the primary problem is not loss of the mechanical connection between sarcolemma and cytoskeleton, but mitochondrial dysfunction with altered iron metabolism, oxidative stress and reduced energy efficiency. Cardiomyopathy may be an important cause of death and may not follow neurological progression in a linear way.
Other neuromuscular diseases may involve the heart with variable frequency: desminopathies, filaminopathies, myofibrillar myopathies, BAG3-related diseases, selected congenital myopathies, glycogenoses, muscle channelopathies, motor neuron diseases with less common cardiac involvement and some inherited neuropathies. The general clinical rule is that every neuromuscular diagnosis must be translated into a specific cardiological profile. It is not enough to know that the patient has a myopathy; one must know which gene, which protein, which natural history, which arrhythmic risk, which mode of surveillance and which intervention threshold.
The etiological causes are diverse and depend on the primary neuromuscular disease. In dystrophinopathies, the cause is a variant of the DMD gene that reduces or abolishes dystrophin, an essential protein that connects the actin cytoskeleton of the cardiomyocyte to the dystrophin-glycoprotein complex of the membrane. Under normal conditions this system distributes the mechanical stress generated at each contraction and protects the sarcolemma. When dystrophin is absent or defective, the membrane becomes vulnerable to microlesions; calcium enters abnormally; proteases, oxidative stress, cell necrosis, inflammation and replacement fibrosis are activated. In the heart, this sequence translates into progressive loss of cardiomyocytes, early inferolateral fibrosis, ventricular dilation and systolic dysfunction.
In sarcoglycanopathies and in some limb-girdle muscular dystrophies the mechanism is conceptually similar but molecularly distinct. Sarcoglycans are part of the membrane complex associated with dystrophin; their alteration destabilizes force transmission and increases the fragility of the muscle membrane. FKRP variants impair the correct glycosylation of alpha-dystroglycan, reducing the interaction between muscle fiber and extracellular matrix. The result is a skeletal myopathy with possible dilated cardiomyopathy, myocardial fibrosis and arrhythmias. The difference between subtypes is not secondary, because some genes strongly affect the heart while others almost never do.
In laminopathies, the injury originates in the nucleus. Lamin A/C is a component of the nuclear lamina, a structure that supports the nuclear envelope and organizes chromatin, gene regulation and the response to mechanical stress. The cardiomyocyte, exposed to continuous cyclic forces, is particularly sensitive to nuclear fragility. LMNA variants may cause altered mechanotransduction, nuclear instability, cell death, fibrosis and electrical dysfunction. Clinically, this produces a highly recognizable combination: conduction blocks, atrial arrhythmias, ventricular tachycardias, dilated cardiomyopathy and a risk of sudden death disproportionate to the initial degree of ventricular dysfunction.
In Emery-Dreifuss muscular dystrophy linked to EMD, the emerin gene, or to LMNA, the problem involves the nuclear envelope and the connection between nucleus, cytoskeleton and matrix. The muscle disease manifests with early contractures, a characteristic distribution of weakness and joint stiffness; the heart develops an electrical disease in which the atria and the conduction system may be affected early. Atrial paralysis, flutter, atrial fibrillation and atrioventricular blocks derive from fibrofatty replacement and from the vulnerability of the specialized cells of the conduction system.
In myotonic dystrophies, the mechanism is linked to non-coding repeat expansions that alter the regulation of messenger ribonucleic acid. In myotonic dystrophy type 1, the CTG expansion in the DMPK gene generates accumulation of toxic transcripts, sequestration of splicing regulatory proteins and widespread splicing abnormalities in muscle, heart, nervous system and other tissues. In the heart, this process promotes degeneration of the conduction system, fibrosis, fatty infiltration, atrial and ventricular arrhythmias and possible ventricular dysfunction. The pathogenesis is therefore a disease of post-transcriptional regulation, not a simple mechanical muscular dystrophy.
In Friedreich ataxia, frataxin deficiency impairs iron-sulfur cluster biogenesis, mitochondrial function and iron homeostasis. The cardiomyocyte develops energy inefficiency, oxidative stress, abnormal mitochondrial iron accumulation, hypertrophy, cellular injury and fibrosis. Cardiomyopathy may begin as concentric hypertrophy with preserved systolic function, but may evolve toward systolic dysfunction, arrhythmias and heart failure. The heart is vulnerable because it consumes large amounts of energy and depends on efficient mitochondria; even a moderate bioenergetic defect may become clinically relevant over time.
Desminopathies and myofibrillar myopathies produce damage through disorganization of the intermediate cytoskeleton and accumulation of protein aggregates. Desmin connects myofibrils, Z-discs, sarcolemma, nucleus and mitochondria; when it is altered, the cell loses structural alignment and mechanical stability. The myocardium may develop dilated, restrictive or hypertrophic cardiomyopathy, conduction blocks, arrhythmias and heart failure. In these patients, the presence of skeletal myopathy, cataract, neuropathy, elevated creatine kinase or family history may help distinguish the disease from an isolated primary cardiomyopathy.
The final pathophysiology depends on the relationship between three components: mechanical cardiomyocyte injury, energy injury and electrical injury. If membrane fragility predominates, as in dystrophinopathies, the typical trajectory is necrosis, fibrosis and dilated cardiomyopathy. If nuclear disease or conduction system disease predominates, as in laminopathies and Emery-Dreifuss, the trajectory may begin with blocks and arrhythmias before heart failure. If ribonucleic acid toxicity or fibrofatty degeneration of conduction tissue predominates, as in myotonic dystrophy, the risk of sudden death may occur even without severe ventricular dilation. If bioenergetic deficiency predominates, as in Friedreich ataxia, hypertrophy may be the initial response to inefficient metabolism.
The respiratory system further modifies pathophysiology. Many neuromuscular diseases weaken the diaphragm, intercostal muscles and expiratory muscles, resulting in nocturnal hypoventilation, hypercapnia, respiratory infections, ineffective cough, hypoxia and right ventricular overload. Cardiomyopathy therefore cannot be interpreted separately from respiratory function. A patient with Duchenne muscular dystrophy may worsen not only because of left ventricular dysfunction, but also because of chronic hypoventilation, sleep disturbance, scoliosis, infections and increased cardiopulmonary load.
The most frequent cardiac phenotype in dystrophinopathies is dilated or hypokinetic cardiomyopathy, but the course does not always begin with a dilated cavity. In Duchenne muscular dystrophy, cardiac magnetic resonance may show inferolateral subepicardial or mid-wall fibrosis before a reduction in ejection fraction. This finding is fundamental because a normal echocardiogram does not exclude early myocardial injury. With progression, reduced longitudinal strain, left ventricular dilation, functional mitral regurgitation, arrhythmias and heart failure appear. In Becker muscular dystrophy, cardiac involvement may be very severe and sometimes dominant compared with the muscular picture.
Limb-girdle muscular dystrophies show different phenotypes. FKRP-related forms may present dilated cardiomyopathy, myocardial fibrosis and arrhythmias; sarcoglycanopathies, especially beta-sarcoglycan, gamma-sarcoglycan and delta-sarcoglycan, may be associated with ventricular dysfunction; LMNA-related forms may have conduction disorders and arrhythmias with significant risk; classic calpainopathies have, in many cases, less cardiac involvement. This variability imposes an approach based on the genotype. Two patients with limb-girdle weakness may have completely different cardiac risks.
In myotonic dystrophy type 1, the heart may appear morphologically only mildly compromised while the electrical system is already diseased. Warning signs include prolongation of the PR interval, widening of the QRS complex, fascicular blocks, atrioventricular block, atrial fibrillation, atrial flutter, non-sustained ventricular tachycardia and syncope. Echocardiography may document left or right ventricular dysfunction, but electrical monitoring remains central. The risk of sudden death derives mainly from bradyarrhythmias and blocks, but may also include ventricular tachyarrhythmias.
In Emery-Dreifuss muscular dystrophy, the cardiac phenotype is dominated by atrial and conduction disease. Dilated atria, atrial paralysis, absence of effective atrial activity, atrial fibrillation, flutter and atrioventricular blocks may precede ventricular dysfunction. Embolic risk is high because the atrium may be mechanically ineffective even when the rhythm is not classically fibrillatory. In patients with LMNA, dilated cardiomyopathy may appear later, but arrhythmic risk must be considered from the earliest electrical abnormalities.
In Friedreich ataxia, cardiomyopathy is often hypertrophic, predominantly concentric, with a small or normal ventricular cavity in the early phases. Systolic function may remain preserved while diastole becomes less efficient; over time, fibrosis, relative wall thinning, dilation, reduced ejection fraction and arrhythmias may appear. Electrocardiographic abnormalities are frequent, but do not always correspond to clinical severity. Friedreich ataxia cardiomyopathy must not be confused with sarcomeric hypertrophic cardiomyopathy: the neurological, genetic and bioenergetic context is different.
Myofibrillar myopathies and desminopathies may produce mixed phenotypes: dilated, restrictive or hypertrophic cardiomyopathy, conduction blocks and ventricular arrhythmias. The presence of distal or proximal weakness, neuropathy, cataract, protein aggregates on muscle biopsy or family history points toward this category. In some cases, the heart precedes the neuromuscular diagnosis, and the patient is initially investigated as having an unexplained genetic cardiomyopathy. Neuromuscular reassessment becomes essential when elevated creatine kinase, early conduction disorders or a family history of myopathy appear.
Motor neuron diseases and neuromuscular junction diseases have a different cardiac profile. In amyotrophic lateral sclerosis, primary structural cardiac involvement is not typical as it is in dystrophies, but dysautonomia, respiratory failure, hypoxia and systemic stress may influence the heart. In myasthenia gravis, myocarditis or cardiomyopathy are rare, but may occur in particular autoimmune contexts, thymoma or inflammatory overlaps. These conditions should not be forcibly included among genetic neuromuscular cardiomyopathies, but should be considered when the clinical picture suggests them.
The distinction between primary cardiomyopathy and cardiomyopathy due to a neuromuscular disorder may be difficult because the heart may be the first evident organ. A young person with dilated cardiomyopathy, atrioventricular block and elevated creatine kinase may have a laminopathy; an adult with dilated cardiomyopathy and calf hypertrophy may have Becker muscular dystrophy; a woman with ventricular dilation and affected male children may be a manifesting carrier of a dystrophinopathy; a patient with progressive blocks, cataract and myotonia may have myotonic dystrophy. Diagnosis begins by recognizing that the heart often tells the story of a systemic disease.
The history must start from the cardiac symptom but not stop at the heart. The patient may report exertional dyspnea, fatigability, reduced activity tolerance, palpitations, syncope, chest pain, orthopnea, edema, nocturnal awakenings with air hunger or worsening during respiratory infections. However, similar symptoms may derive from weakness of the respiratory muscles, scoliosis, nocturnal hypoventilation, anemia, deconditioning, corticosteroid therapy, obesity or reduced mobility. The assessment must therefore separate what is cardiac from what is respiratory, neuromuscular or metabolic, without assuming that dyspnea is always heart failure.
The neuromuscular history must reconstruct age at onset, motor milestones, difficulty running, falls, waddling gait, Gowers sign, proximal or distal weakness, cramps, myalgia, myotonia, stiffness, contractures, loss of ambulation, scoliosis, use of ventilation, dysphagia, weight loss and recurrent respiratory infections. Some patients come to the cardiologist with an already known neuromuscular diagnosis; others present with a cardiac picture that must reveal an undiagnosed muscle disease. In the latter case, apparently simple questions are useful: difficulty rising from a chair, climbing stairs, opening jars, running as a child, keeping the head raised or clearing secretions with cough.
The family history must include cardiomyopathies, sudden death, pacemaker, implantable cardioverter-defibrillator, heart transplantation, muscle weakness, early cataract, premature frontal balding, respiratory disorders, learning difficulties, male infertility, diabetes, ataxia, consanguinity, affected males in the maternal line and apparently carrier women with cardiac symptoms. The inheritance pattern may be X-linked, autosomal dominant, autosomal recessive or mitochondrial. Recognizing it changes the pathway for relatives and may prevent late diagnoses in still asymptomatic subjects.
The cardiological physical examination searches for signs of heart failure, low output, arrhythmia and functional valve disease. Tachycardia, irregular rhythm, bradycardia, jugular venous distension, pulmonary crackles, hepatomegaly, dependent edema, murmurs due to mitral or tricuspid regurgitation, third heart sound and hypotension may be present. In a non-ambulant patient, peripheral edema may also derive from immobility and venous insufficiency, but the presence of jugular venous distension, congestive hepatomegaly, increased natriuretic peptides and ventricular dysfunction points toward heart failure.
The neurological and muscular examination must observe the distribution of weakness, atrophy, calf pseudohypertrophy, winged scapulae, contractures of the Achilles tendon, elbows or neck, percussion or grip myotonia, ptosis, ophthalmoplegia, dysarthria, ataxia, reduced reflexes, skeletal deformities and respiratory function. Early contractures of elbows, Achilles tendons and spine point toward Emery-Dreifuss; myotonia with cataract, frontal balding and endocrine-metabolic disorders points toward myotonic dystrophy; ataxia with areflexia and scoliosis points toward Friedreich ataxia; calf pseudohypertrophy points toward dystrophinopathy or some limb-girdle muscular dystrophies.
Electrical symptoms deserve specific attention. Rapid palpitations, syncope, presyncope, episodes of loss of consciousness during exertion or at rest, nocturnal awakenings with palpitations and family history of sudden death must be treated as high-risk signals. In myotonic dystrophies and laminopathies, syncope may be the first sign of advanced atrioventricular block or ventricular tachyarrhythmia. In Emery-Dreifuss, atrial paralysis and flutter may cause embolism even before heart failure. The clinical question is not only whether the patient has symptoms, but whether their genotype makes those symptoms particularly dangerous.
In pediatric patients, presentation may be indirect. Reduced play, easy fatigability, poor growth, refusal of physical activity, learning difficulties, respiratory infections, scoliosis and motor delay may precede a cardiological diagnosis. In Duchenne muscular dystrophy, the child may be asymptomatic from a cardiac point of view even with initial fibrosis; for this reason, surveillance must not wait for dyspnea or edema. When the cardiac symptom appears, myocardial damage may already be advanced.
In female carriers of dystrophinopathies or variants linked to the X chromosome, cardiac involvement may be underestimated. A woman carrying a DMD variant may develop dilated cardiomyopathy, myocardial fibrosis or arrhythmias even without significant muscle weakness. A woman with an EMD variant or with other X-linked conditions may become symptomatic in adulthood. The definition of “carrier” must not generate false reassurance: from a cardiological point of view, many carriers are patients who require active surveillance.
The diagnostic pathway must proceed along two parallel tracks: characterizing the heart and defining the neuromuscular disease. There is no single scheme valid for all diseases, because dystrophinopathies, laminopathies, myotonic dystrophies and Friedreich ataxia have different risks. The common principle is that every patient with a known neuromuscular disease must receive a baseline cardiological evaluation, and every patient with unexplained cardiomyopathy or conduction disorders must be questioned and investigated for neuromuscular signs. The most frequent error is to work in separate compartments, with the neurologist following muscle strength and the cardiologist seeing only the ejection fraction.
First-level examinations include 12-lead electrocardiogram, transthoracic echocardiography, creatine kinase, transaminases, renal function, electrolytes, B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin when indicated, respiratory evaluation and review of ongoing treatments. The electrocardiogram must be read by looking not only for ischemia or hypertrophy, but also for PR interval, QRS complex duration, fascicular blocks, bundle branch blocks, pre-excitation, pathological Q waves, atrial arrhythmias and signs of conduction system disease.
The echocardiogram evaluates ventricular dimensions, ejection fraction, global longitudinal strain, right ventricular function, valves, pulmonary pressures, atria and signs of dilated, hypertrophic or restrictive cardiomyopathy. In patients with a poor acoustic window due to scoliosis, chest deformity or postural difficulty, echocardiography may underestimate damage. Strain is useful for recognizing subclinical dysfunction, but it must be interpreted with adequate technical quality. A normal echocardiogram does not exclude early myocardial fibrosis, especially in dystrophinopathies.
Cardiac magnetic resonance is particularly important in neuromuscular diseases because it identifies fibrosis and tissue injury before overt systolic dysfunction. In Duchenne and Becker muscular dystrophy, inferolateral or subepicardial late gadolinium enhancement may precede reduced ejection fraction. In laminopathies and desminopathies, it may document fibrosis with arrhythmic significance. In Friedreich ataxia, it quantifies hypertrophy, volumes and function. When magnetic resonance is not possible because of non-compatible devices, claustrophobia, respiratory difficulty or inability to maintain position, advanced echocardiography, selected computed tomography or alternative strategies compatible with patient safety should be used.
Rhythm monitoring is mandatory in diseases with high electrical risk. Holter monitoring for 24 or 48 hours, prolonged monitoring, implantable loop recorder and electrophysiological study may be indicated according to symptoms, genotype, electrocardiogram and family history. In myotonic dystrophy type 1, PR prolongation, QRS widening, blocks and tachyarrhythmias are particularly important. In laminopathies, the presence of non-sustained ventricular arrhythmias, systolic dysfunction, male sex, non-missense variants and conduction blocks modifies risk assessment. In Emery-Dreifuss, atrial and atrioventricular surveillance must be very careful.
Respiratory evaluation is part of functional cardiological diagnosis. Spirometry, forced vital capacity in seated and supine positions, cough assessment, nocturnal saturation, capnography, polysomnography or sleep study may be necessary. Nocturnal hypoventilation may increase cardiac load, promote arrhythmias, worsen pulmonary hypertension and simulate cardiac dyspnea. In patients with respiratory weakness, starting or optimizing non-invasive ventilation may improve symptoms and reduce cardiopulmonary stress.
Genetic testing has a central role when the neuromuscular diagnosis has not already been defined or when cardiac risk must be stratified. The choice may include panels for cardiomyopathies, neuromuscular panels, panels for muscular dystrophies, DMD analysis with search for deletions, duplications and point variants, testing for repeat expansions in DMPK or CNBP, analysis of LMNA, EMD, DES, FKRP, sarcoglycans, FXN and other genes according to phenotype. The result must be interpreted according to variant classification criteria, avoiding transforming a variant of uncertain significance into a definitive diagnosis.
According to the approach of cardiological guidelines and specialist statements, correctly formulating the diagnosis of cardiomyopathy associated with a neuromuscular disorder requires integration of multiple levels of clinical and instrumental evidence. The practical sequence can be summarized as follows:
Muscle biopsy is less central today than in the past when genetics is conclusive, but remains useful in selected cases. It may show absence or reduction of dystrophin, sarcoglycan abnormalities, myofibrillar accumulations, vacuoles, mitochondrial abnormalities or inflammatory patterns. Endomyocardial biopsy is rarely necessary in routine genetic neuromuscular diseases, but may be considered when myocarditis, infiltrative disease, undefined accumulation, cardiotoxicity or an alternative diagnosis that would change treatment is suspected. Invasive examination must not replace well-conducted genetics and imaging.
The differential diagnosis includes sarcomeric cardiomyopathies, idiopathic dilated cardiomyopathy, myocarditis, ischemic heart disease, hypertensive heart disease, valvular heart disease, storage diseases, Anderson-Fabry disease, Pompe disease, PRKAG2, Danon disease, amyloidosis, sarcoidosis and cardiopathies due to oncological treatment. Elevated creatine kinase, muscle weakness, neuromuscular family history, early conduction disorders, pre-excitation, contractures or myotonia are clues that shift the reasoning toward a neuromuscular cause. However, the absence of elevated creatine kinase does not exclude myotonic dystrophy, laminopathy or some forms with predominantly cardiac expression.
Treatment requires a multidisciplinary model including cardiology, neurology, medical genetics, pulmonology, physiatry, nutrition, electrophysiology, rehabilitation, pediatrics when necessary and an advanced heart failure center in progressive cases. The objective is not only to treat heart failure when it appears, but to prevent or delay cardiomyopathy, intercept arrhythmias before a major event, protect respiratory function and plan advanced interventions before the irreversible phase. In neuromuscular diseases, cardiological prevention is part of therapy.
In dystrophinopathies, especially Duchenne muscular dystrophy, cardiac management must begin early, even in the absence of symptoms. International recommendations provide for periodic surveillance with electrocardiogram, cardiac imaging and possible cardiac magnetic resonance when available and tolerated. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are often introduced in an early phase to slow ventricular remodeling; mineralocorticoid receptor antagonists, beta-blockers and other heart failure therapies are added according to ventricular function, fibrosis, symptoms and tolerance. The approach is proactive because waiting for dyspnea often means intervening when the damage is already advanced.
When heart failure with reduced ejection fraction appears, treatment follows the principles of heart failure therapy, adapted to the neuromuscular patient. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter type 2 inhibitors and diuretics may be used according to clinical indication. Titration must consider low blood pressure, reduced muscle mass, falsely low creatinine due to sarcopenia, respiratory function, risk of hyperkalemia, dysphagia and treatment adherence.
Arrhythmic therapy must be disease-specific. In myotonic dystrophies, surveillance of conduction disorders is a priority and may lead to electrophysiological study, pacemaker or implantable cardioverter-defibrillator according to risk profile. In laminopathies and Emery-Dreifuss, a defibrillator may be preferable to a pacemaker alone when ventricular risk exists, because correcting bradycardia does not prevent ventricular tachycardias or sudden death. In dystrophinopathies, the indication for a defibrillator follows ventricular function, documented arrhythmias and the overall picture, but must be discussed by considering functional expectation, ventilation, quality of life and informed preferences.
Anticoagulation is indicated in the presence of atrial fibrillation, atrial flutter, intracardiac thrombi or specific high-risk contexts. In Emery-Dreifuss and in diseases with atrial paralysis, embolic risk may be high even when the electrical presentation does not fit the common models of atrial fibrillation in older patients. The decision must consider mobility, fall risk, liver function, nutrition, interactions, devices, adherence and the possibility of monitoring. Stroke prevention is particularly important because an additional neurological event may devastate the autonomy of an already fragile patient.
Respiratory management is an indirect but essential cardiac treatment. Non-invasive ventilation, cough assistance, vaccinations, treatment of respiratory infections, monitoring of nocturnal hypoventilation and scoliosis management reduce cardiopulmonary stress, hypoxia, hypercapnia and hospitalizations. In Duchenne muscular dystrophy, increased survival is closely linked to the quality of respiratory care; however, this greater survival exposes the heart for longer to the risk of progressive cardiomyopathy. Cardiology and pulmonology must therefore proceed together.
Treatment of the neuromuscular disease may indirectly influence the heart. Corticosteroids in Duchenne muscular dystrophy improve strength and slow some components of progression, but require control of weight, blood pressure, glucose, bone health and infectious risk. Genetic or molecular therapies for specific DMD variants, such as exon skipping or strategies to restore dystrophin, have muscular objectives and potential cardiac implications still under study and surveillance. In Friedreich ataxia, antioxidant and mitochondrial metabolism-modulating therapies have produced variable results; indications must follow updated approvals and recommendations, without attributing unproven cardiac benefits.
Follow-up must be scheduled according to disease, genotype and age. A patient with Duchenne muscular dystrophy requires regular cardiological checks from childhood; a patient with myotonic dystrophy requires electrocardiogram and rhythm surveillance; a patient with LMNA requires arrhythmic stratification even with mild ventricular dysfunction; a DMD carrier requires periodic cardiological evaluation even if asymptomatic; a patient with Friedreich ataxia requires monitoring of hypertrophy, ventricular function and arrhythmias. Frequency must not be the same for everyone, but surveillance must not be episodic.
In patients with advanced heart failure, early evaluation should include a heart failure center, defibrillator, cardiac resynchronization therapy when indicated, ventilatory support, nutrition, integrated palliative care and, in selected cases, ventricular assist device or heart transplantation. Advanced options are more complex than in common cardiomyopathies because respiratory weakness, scoliosis, infections, reduced muscle mass, nutrition and rehabilitation capacity modify risk and benefit. This does not mean automatically excluding neuromuscular patients, but evaluating them realistically and early.
Prognosis varies markedly. In Duchenne muscular dystrophy, progressive cardiomyopathy is a major cause of mortality in young adulthood; in Becker muscular dystrophy, cardiomyopathy may be severe and sometimes the main manifestation; in laminopathies, the risk of sudden death and heart failure requires intensive surveillance; in myotonic dystrophy, mortality is often related to respiratory and arrhythmic disorders; in Friedreich ataxia, the heart contributes substantially to mortality. Unfavorable factors include extensive fibrosis on magnetic resonance, reduced ejection fraction, non-sustained ventricular tachycardia, conduction blocks, syncope, respiratory failure, nocturnal hypoventilation, malnutrition and diagnostic delay.
The most frequent complication in dystrophinopathies and many limb-girdle muscular dystrophies is heart failure due to dilated or hypokinetic cardiomyopathy. Progressive loss of cardiomyocytes and replacement fibrosis reduce contractility, increase ventricular volumes, worsen functional mitral regurgitation and lead to pulmonary congestion, edema, hepatomegaly, fatigability and reduced output. In non-ambulant patients, symptoms may be atypical because reduced physical activity masks exertional dyspnea. For this reason, instrumental signs and biomarkers may precede clinical manifestations.
Sudden death is a cross-cutting complication but with different mechanisms. In laminopathies and Emery-Dreifuss it may derive from ventricular tachycardia, ventricular fibrillation or advanced blocks; in myotonic dystrophy it may be caused by bradyarrhythmias, atrioventricular block or ventricular tachyarrhythmias; in dystrophinopathies it may occur in the phase of ventricular dysfunction, fibrosis and arrhythmias; in Friedreich ataxia it may be associated with arrhythmias and advanced cardiomyopathy. Prevention requires recognition of genotype and not only measurement of ejection fraction.
Conduction disorders may evolve slowly or unpredictably. PR prolongation, fascicular blocks, bundle branch blocks, second- or third-degree atrioventricular block and pauses may cause presyncope, syncope, falls, cerebral hypoperfusion or sudden death. In patients with muscle weakness, a fall due to syncope may be mistakenly interpreted as muscular collapse. Serial electrocardiogram is therefore a prevention tool, not a formal examination.
Atrial arrhythmias are frequent in myotonic dystrophies, Emery-Dreifuss, laminopathies and advanced dilated cardiomyopathies. Atrial fibrillation and atrial flutter may worsen heart failure, reduce output, cause palpitations and increase embolic risk. In diseases with mechanically compromised atria, such as some forms of Emery-Dreifuss, atrial stasis may be particularly dangerous. Stroke and systemic embolism have a devastating impact because they add to neuromuscular disability.
Myocardial fibrosis is both a lesion and a complication. In dystrophinopathies it may appear early in the inferolateral wall; in laminopathies and desminopathies it may be an arrhythmic substrate; in Friedreich ataxia it accompanies hypertrophy and energy injury; in myofibrillar myopathies it reflects structural disorganization. Fibrosis reduces elasticity, impairs conduction, worsens contractility and signals progression. Its identification by cardiac magnetic resonance may anticipate therapeutic decisions compared with ejection fraction alone.
Respiratory failure interacts with cardiomyopathy. Nocturnal hypoventilation, hypercapnia, hypoxia, respiratory infections, ineffective cough and scoliosis increase cardiac load, worsen arrhythmias and reduce functional reserve. An infectious episode may precipitate heart failure in a cardiologically compensated patient. Poorly adjusted or unused non-invasive ventilation may promote progressive worsening; conversely, good respiratory management reduces cardiopulmonary stress and hospitalizations.
Renal, hepatic and metabolic complications derive from heart failure, low output, congestion, treatments and reduced muscle mass. Creatinine may underestimate renal impairment in sarcopenic patients, making it more difficult to titrate inhibitors of the renin-angiotensin-aldosterone system, mineralocorticoid receptor antagonists and diuretics. Corticosteroids may promote weight gain, hypertension, insulin resistance and bone fragility, indirectly influencing the heart. Insufficient nutrition worsens tolerance to therapy and recovery after hospitalization.
Complications of implantable devices must be considered. Pacemaker, implantable cardioverter-defibrillator and cardiac resynchronization therapy may be life-saving, but in neuromuscular patients they may encounter problems related to venous access, chest deformity, scoliosis, infections, anesthesia, skin fragility, respiratory progression and the need for careful sedation. The choice of device must take into account the risk of bradyarrhythmia, tachyarrhythmia, heart failure progression and the possibility of harmful chronic pacing if not properly programmed.
Familial and reproductive complications are part of the disease. A missed genetic diagnosis prevents screening of brothers, sisters, children, carrier mothers and other relatives. Women carrying DMD may develop cardiomyopathy and transmit the variant; relatives of patients with LMNA may have arrhythmic risk even before symptoms; relatives of patients with myotonic dystrophy may present cataract, myotonia or unrecognized electrical disorders. Prevention of complications also depends on familial genetics.
Finally, a frequent complication is clinical underestimation. The neuromuscular patient may be considered fragile for motor reasons and not adequately investigated for the heart; or the cardiologist may treat the cardiomyopathy without searching for the neuromuscular cause. This produces delayed therapy, missed arrhythmic prevention, missed genetic counseling and loss of the window for advanced interventions. In these diseases, early diagnosis is not a specialist detail: it is a prognostic measure.