(See also Overview of Arrhythmogenic Cardiomyopathies Overview of Arrhythmogenic Cardiomyopathies Although any dilated or hypertrophic cardiomyopathy (see Overview of Cardiomyopathies) can produce cardiac and systemic factors that predispose to a number of different arrhythmias, including... read more and Overview of Arrhythmias Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more )
Lamin A and lamin C are structural filament proteins in the cell nucleus, encoded by the gene LMNA. Mutations in this gene produce a group of disorders called laminopathies. Many laminopathies cause a severe, usually dilated cardiomyopathy Dilated Cardiomyopathy Dilated cardiomyopathy is myocardial dysfunction causing heart failure in which ventricular dilation and systolic dysfunction predominate. Symptoms include dyspnea, fatigue, and peripheral edema... read more characterized by rapid progression, atrial tachyarrhythmias, atrioventricular (AV) blocks, ventricular tachyarrhythmias, and sudden death. Lamin A/C cardiomyopathies account for about 5 to 10% of idiopathic dilated cardiomyopathies.
Most cardiolaminopathies have autosomal dominant inheritance with high penetrance; thus, patients' family members are often affected.
Some LMNA mutations are associated with other disorders including certain muscular dystrophies (eg, Emery-Dreifuss dystrophy Emery-Dreifuss Dystrophy Emery-Dreifuss dystrophy is a muscular dystrophy with multiple modes of inheritance. In addition to weakness and muscle wasting, patients often have cardiac abnormalities that may cause sudden... read more ), neuropathies, premature ageing, and metabolic abnormalities, including insulin resistance, hypertriglyceridemia, and lipodystrophy.
Patients usually present first with symptoms of heart blocks and/or arrhythmias, including palpitations, syncope, or cardiac arrest. Age at presentation is typically < 40 years. Heart failure manifestations (eg, exertional dyspnea, fatigue, peripheral edema) typically develop later, but timing is variable. A significant number of patients also have skeletal muscle symptoms, eg, weakness, which may even precede cardiac manifestations.
Diagnosis of Lamin A/C Cardiomyopathy
Cardiac imaging (eg, echocardiography, cardiac MRI)
Screening of first-degree family members
Diagnosis is suspected in young patients with palpitations, syncope, or resuscitation from unexplained cardiac arrest, particularly if they also have skeletal muscle weakness and/or a family history of arrhythmias and/or heart failure.
Patients should have ECG, ambulatory cardiac rhythm monitoring, and cardiac imaging, typically echocardiography and/or cardiac MRI.
If conduction disturbances, tachyarrhythmias, and/or cardiomyopathy are detected, genetic testing is done. The yield of genetic testing rises from 5% to 10% in the general population of patients with idiopathic dilated cardiomyopathy to approximately one-third in patients with AV conduction disturbances and a family history of cardiomyopathy.
First-degree family members of patients have a significant risk of disease. They should have clinical evaluation (ie, to detect symptoms suggestive of arrhythmia, muscle weakness, and/or heart failure), ECG, ambulatory cardiac rhythm monitoring, and echocardiography initially and then every 1 to 3 years. Genetic testing is done if the index case has a mutation identified. Family members who are not carriers of that mutation do not require ongoing testing.
Treatment of Lamin A/C Cardiomyopathy
Moderation of physical activity
Usually an implantable cardioverter-defibrillator (ICD)
Sometimes antiarrhythmic drug therapy
Heart failure therapy (including transplantation) as required
Treatment focuses on prevention of sudden death and prevention of symptomatic ventricular tachyarrhythmias.
Patients should avoid athletic exertion because such activities may hasten the progression of the cardiomyopathy and may foster life-threatening arrhythmias.
Because of a high risk of sudden death, an ICD is typically implanted earlier in the course of illness in patients with lamin A/C cardiomyopathies than in others with dilated cardiomyopathy (see table Indications for Implantable Cardioverter-Defibrillators Indications for Implantable Cardioverter-Defibrillators in Ventricular Tachycardia and Ventricular Fibrillation ). In addition to the normal recommendations for ICD use in patients with dilated cardiomyopathy and left ventricular ejection fraction of < 35% and in patients with sustained VT/VF or resuscitated cardiac arrest, placement of an ICD may also be useful (class IIa recommendation) for patients with lamin A/C cardiomyopathy who have unexplained syncope, an independent indication for a permanent pacemaker Indications for pacemaker placement The need for treatment of arrhythmias depends on the symptoms and the seriousness of the arrhythmia. Treatment is directed at causes. If necessary, direct antiarrhythmic therapy, including antiarrhythmic... read more , or two or more other risk factors for sudden death (intermediate left ventricular ejection fraction in the range of 35% to 44%, male gender, non-sustained ventricular tachycardia, non-missence mutations).
A beta-blocker should be used in most patients but may increase the possibility of AV block.
Antiarrhythmic drug therapy with a class III drug, particularly sotalol or amiodarone, may reduce symptomatic ventricular tachyarrhythmias but is not a substitute for an ICD. However, these drugs may benefit patients who have frequent appropriate ICD discharges despite adequate beta-blocker therapy.
Lamin A/C cardiomyopathies are genetic disorders that cause tachyarrhythmias, heart blocks, and heart failure.
Some of the mutations also affect skeletal muscle.
Diagnosis is based on clinical and electrocardiographic factors, cardiac imaging, and genetic testing.
First-degree family members have a significant risk of disease and require screening.
Treatment requires usually requires an implantable cardioverter-defibrillator and a beta-blocker.
Drugs Mentioned In This Article
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|BETAPACE, BETAPACE AF, Sorine , SOTYLIZE|
|Cordarone, Nexterone, Pacerone|