p.51 抽出テキスト

......... 8.6.3 Dilated cardiomyopathy with lamin A/C mutation Mutations in the LMNA gene, which encodes lamin A and C intermediate filaments of the nuclear envelope, cause a variety of inherited diseases defined as ‘laminopathies’.605607 According to the type of mutation, they can lead to isolated cardiac disorders or additional systemic or musculoskeletal disorders such as the EmeryDreifuss autosomal dominant variant or limb-girdle dystrophy. Around 510% of dilated cardiomyopathies are induced by LMNA gene mutations, manifested as cardiac conduction disease, tachyarrhythmias, or impaired myocardial contractility.596,606620 SND and conduction disease are frequently the first manifestation, in many cases with preserved LV size and function.613,614 LMNA-related cardiomyopathy is more malignant than most other cardiomyopathies, carrying a higher risk of SCD in asymptomatic mutation carriers with preserved or only mildly decreased LV contractility.610615 Pacemaker implantation does not reduce the risk of SCD in these patients. A meta-analysis of mode of death in LMNA mutations demonstrated that 46% of patients who died suddenly had an implanted pacemaker. Sudden death rates were similar in those with isolated cardiomyopathy and those with an additional neuromuscular phenotype.611 Complex ventricular arrhythmias are common in patients with conduction disturbances.612,613,615 In two studies, patients with LMNA mutations and an indication for permanent pacing underwent ICD implantation, and appropriate ICD therapies occurred in 42% and 52% of patients within 3 and 5 years, respectively.612,613 These findings led to the clinical practice to consider ICD rather than pacemaker implantation in LMNA-related conduction disease.614,620 For additional clinical risk factors for ventricular tachyarrhythmias and sudden death found in patients with dilated cardiomyopathy due to LMNA gene mutations, see Supplementary Table 18. CRT(D) should be considered if the patient has AVB and LVEF <50%, and a high frequency of ventricular pacing is expected (section 6 and Supplementary Table 18). The risk score of life-threatening ventricular arrhythmia in laminopathies can be predicted by a recently developed and validated module (https://lmna-risk-vta.fr/).616

8.6.4 Mitochondrial cytopathies Mitochondrial cytopathies are a heterogeneous group of hereditary disorders, in which cardiomyopathies, conduction defects, and ventricular arrhythmias are the most common cardiac presentations.621,622 In KearnsSayre syndrome, the most common cardiac manifestation is conduction disease, which may progress to complete AVB and cause SCD.623625

8.6.5 Infiltrative and metabolic diseases Infiltrative cardiomyopathy is secondary to abnormal deposition and accumulation of pathological products in the myocardial interstitium, while storage diseases lead to their intracellular accumulation. The main cause of infiltrative cardiomyopathy is amyloidosis, while storage diseases include haemochromatosis, Fabry’s disease, and glycogen storage diseases. In patients with cardiac amyloid, conduction defects, tachyarrhythmias, and SCD are common. Based upon current knowledge, conventional indications should be used for pacing in this group of patients.

8.6.6 Inflammatory diseases Infections (viral, bacterial including Borreliosis, protozoa, fungal, parasites), autoimmune (e.g. giant cell myocarditis, sarcoidosis, rheumatic heart disease, connective tissue disease, eosinophilic myocarditis), toxic (alcohol, cocaine, cancer therapies, especially monoclonal antibodies), and physical reactions (radiation therapy) can cause inflammatory heart disease. Involvement of the AVN and the conduction system is more frequent than that of the sinus node. AVB may indicate involvement of the septum in the inflammatory process and is a predictor of adverse outcome. Ventricular arrhythmias may also occur because of myocardial pathology. When inflammatory heart disease is complicated by bradycardia, especially AVB, specific therapy should be applied if available, eventually backed-up by temporary pacing or intravenous administration of isoprenaline. Otherwise, immunosuppressive therapy or awaiting spontaneous resolution may be sufficient. If bradycardia does not resolve within a clinically reasonable period or cannot be expected to resolve (e.g. after radiation therapy), permanent pacing is indicated. Before choosing a device type, the indication for an ICD and/ or CRT rather than a single-chamber or DDD pacemaker should be

Recommendation for patients with LMNA gene mutations (for references, see Supplementary Table 18)

Recommendation Classa Levelb

In patients with LMNA gene mutations, including EmeryDreifuss and limb-girdle muscular dystrophies who fulfil conventional criteria for pacemaker implantation or who have prolonged PR interval with LBBB, ICD implantation with pacing capabilities should be considered if at least 1year survival is expected.616 IIa C

ICD = implantable cardioverter-defibrillator; LBBB, left bundle branch block. aClass of recommendation. bLevel of evidence. Recommendations for pacing in KearnsSayre syndrome

Recommendations Classa Levelb

In patients with KearnsSayre syndrome who have PR prolongation, any degree of AVB, BBB, or fascicular block, permanent pacing should be considered.c 621625 IIa C In patients with KearnsSayre syndrome without cardiac conduction disorder, permanent pacing may be considered prophylactically.c 621625 IIb C

AVB = atrioventricular block; BBB = bundle branch block; CRT = cardiac resynchronization therapy; ICD = implantable cardioverter-defibrillator; PR = PR interval. aClass of recommendation. bLevel of evidence. cWhenever pacing is indicated, CRT or an ICD should be considered according to the relevant guidelines.

ESC 2021 ESC 2021

.................................................................................................................................................................. Downloaded from academic.oup.com/eurheartj/article/42/35/3427/6358547 by guest on 07 October 2026