Evaluation and Management of Arrhythmic Risk in Neuromuscular Disorders

Publication Date: April 28, 2022

Overview

Overview

Top 10 Take-Home Messages

  1. Shared decision-making among patients, their families, and clinicians is essential whenever diagnostic studies or therapies, particularly those that are invasive, are being utilized or contemplated. Counseling and education may result in patients’ refusal or withdrawal of such measures if inconsistent with their goals of care, and this should be respected.
  2. Cardiac testing is appropriate in most patients with neuromuscular disorders (NMDs) to evaluate for cardiac involvement. The type of cardiac test and the need for and frequency of repeat testing is governed by the underlying disorder, results of previous or new studies, and the patient’s symptomatic status. It should be noted that skeletal muscle impairment may mask or confound cardiovascular symptoms, requiring heightened vigilance to cardiac involvement and modification of testing.
  3. Previously published guideline-based indications for cardiovascular implantable electronic device (CIED) use, including cardiac resynchronization therapy (CRT), and for management of cardiomyopathy (CM) and heart failure may be applied in patients with NMDs. For some indications, the level of evidence (LOE) and/or class of recommendation (COR) in the current document have been modified from prior guidelines to reflect the under-representation of patients with NMDs in past studies.
  4. A patient’s overall prognosis may be affected by the impact of their underlying neuromuscular condition. Condition-specific technical challenges including body habitus (such as kyphoscoliosis), respiratory muscle weakness and sedation-related risks may influence clinical management. These effects may dominate a patient’s clinical picture and prognosis, possibly attenuating the benefit from arrhythmia therapy, particularly CIED implantation, when compared with other patient populations.
  5. Patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and recessive forms of limb-girdle muscular dystrophy (LGMD) rarely develop bradyarrhythmias, but CM, heart failure, and ventricular arrhythmias (VAs) may occur with increased frequency. When indicated, CIED therapy in these patients may pose technical challenges and limited benefit, particularly in those with advanced neuromuscular impairment.
  6. In addition to established indications, pacemaker implantation or, in selected individuals, pacing-capable implantable cardioverter-defibrillator (ICD) placement is indicated in patients with myotonic dystrophy type 1 (DM1) or type 2 (DM2) who have evidence of abnormal atrioventricular (AV) conduction, marked by PR interval ≥240 ms, QRS duration ≥120 ms, and/or HV interval ≥70 ms, even when asymptomatic.
  7. Patients with Emery-Dreifuss muscular dystrophy (EDMD) or limb-girdle muscular dystrophy type 1B (LGMD1B) with abnormal AV conduction, including PR interval ≥230 ms, or HV interval ≥70 ms, are at higher risk of arrhythmic events including sudden death, even when asymptomatic. Transvenous (or equivalent pacing-capable) ICD placement is indicated in such patients.
  8. Patients with mitochondrial myopathies, such as Kearns-Sayre syndrome, are susceptible to developing advanced, distal conduction disease. Pacemaker implantation is indicated in these patients who demonstrate AV conduction abnormalities, particularly if progressive, including fascicular block.
  9. Initiation of oral anticoagulation in patients with NMDs who develop atrial fibrillation (AF) should be based on established risk criteria (e.g., CHA2DS2-VASc, HAS-BLED in adults). Individuals with EDMD or LGMD1B and AF should be treated with oral anticoagulation regardless of CHA2DS2-VASc score because of the association with atrial standstill and suspected heightened risk of thromboembolism.
  10. Early but limited experience with gene modification in some heritable diseases has been promising and is now being employed in patients with NMDs. The hope for additional advances must be tempered by the complexity of these therapeutics and the small number of patients with NMDs who qualify for such treatment.

General Principles for Arrhythmic Risk in NMDs

...ples for Arrhythmic Risk in NMDs...

.... Genetics, cardiovascular complications...


Duchenne, Becker, and Recessive Limb-girdle Muscular Dystrophies

...chenne, Becker, and Recessive Limb-girdl...

...2. Recessive forms (type 2) of LGMDs ass...


...ostic testing and risk stratification i...

...rdinated care of patients with DMD, BMD, or L...

...ith DMD, BMD, or LGMD2, guideline-direc...

...s with DMD, BMD, or LGMD2, cardiac evaluation inc...

...re carriers of a pathogenic or likely...

...tients with DMD, BMD, or LGMD2 who have sy...


...as, conduction disorders, and use of p...

...s with DMD, BMD, or LGMD2, with documen...

...nts with DMD, BMD, or LGMD2 and third-deg...

...th DMD, BMD, or LGMD2 with an LVEF ≤35% desp...


Atrial arrhythmias in Duchenne, Becker, a...

...th DMD, BMD, or LGMD2, anticoagulation accordi...


...ardiac death, and use of ICDs in Duchenne, Becker...

...DMD, BMD, or LGMD2 with spontaneo...

...with DMD, BMD, or LGMD2 with an LVEF ≤35% de...


...Rhythm management and CIED in patients wit...


Table 3. Clinical scenarios for the management...

...Clinical scenario...

...scenario 2 A 31-year-old man with BMD is...

...Clini...


Myotonic Dystrophy Types 1 and 2

...onic Dystrophy Types 1...

...ting and risk stratification in DM1 a...

...care of patients with DM1 or DM2 sho...

...s with DM1 or DM2, cardiac evaluation in...

...patients with DM1 or DM2 and cardiac cond...

...th DM1 or DM2 with symptoms consis...

...patients with DM1 or DM2 with symptoms sugg...


...ycardias, conduction disorders, and use of pacing...

...atients with DM1 or DM2 with an LVEF ≤35...

...h DM1 or DM2 and documented symptomatic brady...

...ients with DM1 or DM2 and third-degree or...

...h DM1 or DM2 and marked first-degr...

...s with DM1 or DM2 with HV interval ≥7...


...arrhythmias in DM1 and DM2...

...patients with DM1 or DM2, anticoagula...


...sudden cardiac death, and use of ICDs in...

...ients with DM1 or DM2 in whom ICD therapy is...

...patients with DM1 or DM2, who are su...

...ents with DM1 or DM2 and an LVEF ≤35...

...nts with DM1 or DM2 in whom clinically relevant...

...nts with DM1 or DM2 in whom PPM im...


...management and CIED implantation...


...4. Clinical scenarios for the management of arr...

...rios cover different degrees of muscle impa...

DM...

Clinical scenario 1 A 63-year-old man with...

...cenario 2 A 52-year-old man with DM1...

...MD...

Clinical scenario 3 A 72-year-old woman...

...inical scenario 4 A 68-year-old woman wi...


Emery-Dreifuss and Limb-girdle Type 1B Muscular Dystrophy

...reifuss and Limb-girdle Type 1B Muscular Dystr...

...sting and risk stratification in EDMD and...

...ated care of patients with EDMD or LGMD1...

In patients with EDMD or LGMD1B, cardiac eva...

...-degree relatives of patients with gen...

...ts with EDMD or LGMD1B, who have sympto...

...ents with EDMD or LGMD1B with symptoms consist...


...cardias, conduction disorders, and use of pa...

...with EDMD or LGMD1B with an LVEF ≤35% de...

...n patients with EDMD or LGMD1B in whom pacing i...


...rhythmias in EDMD and LGMD...

...tients with EDMD or LGMD1B, anticoagulatio...

...tients with EDMD, anticoagulation is...


...cardiac death, and use of ICDs in EDM...

...nts with EDMD or LGMD1B in whom ICD thera...

...h EDMD or LGMD1B who are survivors...

...s with EDMD or LGMD1B with at least on...

...tients with EDMD or LGMD1B with an...

...n patients with EDMD or LGMD1B in whom clinica...

...s with EDMD or LGMD1B with L...

In patients with EDMD or LGMD1B with at least one...

...ients with EDMD or LGMD1B with sympto...


...re 3. Rhythm management and CIED i...


.... Clinical scenarios for the management of ar...

...DMD

...nical scenario 1 A 25-year-old man presents wi...

...al scenario 2 A 64-year-old man with E...

...Clinical scenario 3 A 12-year-old boy with EDM...

LGMD1...

...o 4 A 42-year-old woman is admit...

...ario 5 A 35-year-old man with LGMD1B prese...


Facioscapulohumeral Muscular Dystrophy

...scapulohumeral Muscular Dystrop...

...c testing and risk stratification in FSHD...

...ents with FSHD, cardiac evaluation inclu...


Mitochondrial Myopathies Including Friedreich Ataxia

...Myopathies Including Friedreich Ataxia...

...tic testing and risk stratification in mitochondri...

...nated care of patients with mitochondrial...

...tients with mitochondrial myopathies includ...


...nduction disorders, and use of pacing or CRT...

...th mitochondrial myopathies including FA and do...

...th mitochondrial myopathies includ...

...FA with an LVEF ≤35% despite GDMT, w...

...with mitochondrial myopathies including F...


...rrhythmias in mitochondrial myopathies including F...

...s with mitochondrial myopathies includ...


...ardiac death, and use of ICDs in m...

...mitochondrial myopathies including FA w...

...tients with mitochondrial myopathies...


...management and CIED implantation...


...6. Clinical scenarios for management of patients...

...scenario A 30-year-old man with FA is referre...


Shared Decision-making and End-of-life Care

Shared Decision-making and End-of-life Ca...

...le 7. NMDs, use of pacemakers and ICDs, sha...


...n-making and end-of-life decisions...

...patients with NMD who are conside...

...ith NMD in whom the presence of con...

...ith NMD who are considering ICD replacement and...

...n patients with NMD who have an ICD and ar...

...patients with NMD who have an ICD and are exp...

...n patients with NMD who have a pacem...


...linical scenarios for end-of-life manageme...

...io 1 A 62-year-old woman with D...

...inical scenario 2 A 39-year-ol...

...scenario 3 A 17-year-old adolescent...

...ario 4 A 46-year-old woman with DM1 and sev...