Neuromuscular Disorders 13 (2003) 166–172 www.elsevier.com/locate/nmd Workshop report 107th ENMC International Workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th–9th June 2002, Naarden, the Netherlands K. Bushby*, F. Muntoni, J.P. Bourke Department of Neuromuscular Genetics, Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK Received 1 August 2002; accepted 16 August 2002 1. Introduction symptomatic presentation [13,14]. Although evidence in these rare conditions of the effect of treatment is lacking Sixteen participants from Austria, France, Germany, [15], extrapolation from other conditions causing heart fail- Italy, the Netherlands and the UK met to discuss the cardiac ure with dilated cardiomyopathy means that there is a strong implications of the diagnosis of muscular dystrophy and case for the use of ACE inhibitors and potentially also beta myotonic dystrophy. The group included both myologists blockers, certainly in the presence of detectable abnormal- and cardiologists from nine different European centers. The ities and possibly preventatively [16–25]. aims of the workshop were to agree and report minimum The recommendations of the group are as follows. recommendations for the investigation and treatment of cardiac involvement in muscular and myotonic dystrophies, 2.1. DMD and define areas where further research is needed. During the workshop, all participants contributed to a review and † Patients should have a cardiac investigation (echo and assessment of the published evidence in each area and electrocardiogram (ECG)) at diagnosis. current practice amongst the group. Consensus statements † DMD patients should have cardiac investigations before for the management of dystrophinopathy, myotonic dystro- any surgery, every 2 years to age 10 and annually after phy, limb-girdle muscular dystrophy, Emery Dreifuss age 10. muscular dystrophy, facio-scapulo-humeral muscular † Respiratory failure is also common in DMD and assess- dystrophy and congenital muscular dystrophy were ment and treatment of respiratory function should be produced. The need for further research to extend the performed in parallel with the cardiological investiga- evidence-base in certain key areas was also highlighted tions [26]. and outline proposals to resolve these deficiencies put † Patients should be treated with angiotensin-converting forward. A summary of the cardiac implications of the enzyme (ACE) inhibitors initially in the presence of disorders discussed is presented in Table 1. progressive abnormalities [15–19]. Subsequently the addition of beta blockers should be considered [20–23]. † There is no evidence that the currently used steroid treat- 2. Dystrophinopathy [Duchenne and Becker muscular ment regimes have a detrimental effect on cardiac invol- dystrophy (DMD and BMD) and carriers of DMD and vement or are a contraindication for the concurrent use of BMD] ACE inhibitors [27]. † The multiple other complications of DMD including There is strong evidence of frequent progressive cardiac scoliosis and respiratory failure mean that these patients involvement in these disorders, characterized ultimately by are rarely fit for cardiac transplantation. the development of dilated cardiomyopathy [1–12]. † There is an urgent need for multi-centre clinical trials to Abnormalities on investigation are more common than determine whether treatment of patients with cardiomyo- pathy, prior to the onset of symptoms, improves prog- * Corresponding author. Tel.: 144-191-241-8737; fax: 144-191-241- 8799. nosis and quality of life. There is also unpublished E-mail address: [email protected] (K. Bushby). evidence to suggest that treatment even before any 0960-8966/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. doi:10.1016/S0960-8966(02)00213-4 Table 1 Frequency, type and implications of cardiac involvement in different forms of muscular dystrophy and myotonic dystrophya Disease Cardiac involvement (in % of patients in whom Age range Morbidity/mortality References increasing order of severity) abnormality likely Duchenne muscular dystrophy ECG abnormalities: HCM Abnormal ECG .90%; ECG abnormalities Cardiac death in approx 10– de Kermadec et al. [2]; and DCM abnormal Echo .90% detectable from age 6, 20%, usually in teens Corrado et al. [3]; Farah et al. progressive thereafter [4]; Backman et al. [6] Becker muscular dystrophy ECG abnormalities: HCM ECG abnormal – 90%, Echo Variable, may be Cardiac death in up to 50% Melachini et al. [7]; Saito et and DCM abnormal – 65% disproportionate to al. [9]; Nigro et al. [8]; skeletal involvement Hoogerwaard et al. [10] Manifesting carriers of DMD/ ECG abnormalities: HCM Variable estimates 21–90% Variable, may be out of DCM in 7–11%. Several Politano et al. [33]; BMD and DCM proportion to skeletal reports of successful cardiac Hoogerwaard et al. [34]; muscle involvement transplantation Grain et al. [35] XL-EDMD AV block; atrial paralysis; . 95% by age 30 years 10–39 SCD common in non-paced Emery et al. [52]; Merlini et K. Bushby et al. / Neuromuscular Disorders 13 (2003) 166–172 atrial flutter and fibrillation individuals (mean age at al. [55]; Bione et al. [53]; pacing 24 years, range 14–35) Funakoshi et al. [54] Myotonic dystrophy AV-conduction disturbances; Approximately 65% of the Earliest age at which Approx 5% require pacemaker Hayashi et al. [38]; Olofsson atrial flutter and fibrillation, adult myotonic dystrophy abnormalities become insertion. Risk of SCD. et al. [36]; Hawley et al. [43]; ventricular tachy-arrhythmias population have abnormal clinically relevant is Antonini et al. [46]; Clarke et ECG unclear. Greatest risk is in al. [44] middle adulthood Sarcoglycanopathies ECG abnormalities; HCM 18.7% Not established Impact on overall prognosis Van der Kooi et al. [72]; (LGMD2C-2F) and DCM unclear Politano et al. [71]; Gnecchi- Ruscone et al. [76] LGMD2I ECG abnormalities, DCM 1/3 of adult onset cases Over whole spectrum of 1/3 of adult cases have Brockington et al. [74]; LGMD2I/MDC1C relates symptomatic cardiomyopathy. Poppe et al. [73] to severity of overall Further data needed on natural disease history MDC1C Dilated cardiomyopathy Invariable and clinically Present from early May be a major contributory Brockington et al. [74] significant childhood in most severe factor to early death cases Laminopathies (including AD- AV block; atrial paralysis; . 95% by age 30 years 15–52 Mean age at pacing 32 (range Bonne et al. [57]; van der EDMD, LGMD1B) atrial fibrillation/flutter 19–57) years; 50% of deaths Kooi [60]; Fatkin et al. [61]; are sudden despite pacing Becane et al. [62] Laminopathies (including AD- Dilated cardiomyopathy 35% of all cases 19–55 Death from heart failure Graham et al. [67]; Davies EDMD, LGMD1B) common if not transplanted [68]; Becane et al. [62]; Fatkin et al. [61] Facioscapulohumeral Conduction defects, atrial Minor ECG changes in up Further work needed to Few reports of clinically Stevenson et al. [83]; De muscular dystrophy arrhythmias to 30% establish prevalence of relevant cardiac involvement Visser et al. [77]; Laforet et cardiac involvement in al. [81] severe childhood onset disease MDC1A Reduced ejection fraction No reports to date of clinically significant cardiomyopathy a DCM ¼ dilated cardiomyopathy; HCM ¼ hypertrophic cardiomyopathy; and SCD ¼ sudden cardiac death. 167 168 K. Bushby et al. / Neuromuscular Disorders 13 (2003) 166–172 impairment of ventricular function is detectable on echo- When invasive electrophysiology testing is performed in cardiogram may delay the onset and progression of cardi- patients with abnormal ECGs, it typically detects more omyopathy [28]. Concerns about the possible impact of widespread conduction abnormalities that that suggested ACE-inhibition on left ventricular development in very by the surface recording [45,46]. Electrophysiological young children, means that treatment in the very young tests and MRI may help to predict those at particular risk should only be undertaken in the context of a formal of severe arrhythmia [45,47,48]. Ventricular arrhythmias clinical trial, at the present time. are likely to explain some cases of sudden death. However, † There is a case for continued evaluation of more sophis- in patients with pacemakers implanted, the best predictor of ticated tools (echo tissue Doppler imaging, cardiac death is deteriorating respiratory function. magnetic resonance imaging (MRI), etc.) for earlier Cardiac investigation in these patients should include. detection of abnormalities, but these are not required for routine management [29]. † Annual ECG from diagnosis. † Holter monitoring may also be valuable at diagnosis in 2.2. BMD adult patients. † Echocardiogram should be performed at diagnosis in Cardiac involvement in BMD is common and is congenital myotonic dystrophy. frequently out of proportion to the skeletal muscle involve- † Additional investigations should include Holter monitor- ment [7–10]. ing, if annual ECG shows increasing PR interval or other evidence of increased risk of bradycardia. Invasive † BMD patients should have cardiac evaluation (ECG and measurement of the HV interval (infra-nodal conduction echo) at diagnosis. delay: HV .70 ms) may help decide the need for pacing † BMD patients should be screened for the development of in borderline cases. cardiomyopathy at least every 5 years. † Atrial tachyarrhythmias (atrial flutter, fibrillation) are † They should be seen more regularly and treated