Internal Medicine Resident University of Alberta Edmonton, Alberta, Canada
Background: Limb-girdle muscular dystrophy (LGMD) describes a group of more than 30 diverse autosomal muscular dystrophies (MDs) affecting the proximal musculature. LGMDR9, formerly LGMD 2I, is due to abnormal glycosylation of α-dystroglycan due to mutations in the fukutin-related protein (FKRP) gene. Through our Neuromuscular Multidisciplinary (NMMD) clinic, we assessed for cardiac involvement, the role of cardiac magnetic resonance imaging (CMR) in detecting subclinical cardiac disease, and the early initiation of cardioprotective therapies in patients with LGMD R9.
METHODS AND RESULTS: Patients with genetically proven LGMD R9 (n=17) were recruited from our NMMD clinic in this prospective study. Screening cardiac investigations, including plasma biomarkers (BNP, cTnT, cTnI), electrocardiogram (ECG), transthoracic echocardiography (TTE), and CMR, were performed. All patients had genetic testing completed with the most common genotype in our cohort being the homozygous c.826C>A (p.L276I) mutation (14 patients, 82.4%) likely due to a founder effect, while the remainder had compound mutations. The median age of our cohort was 30 years old (26 – 47.5), most patients were females (58.8%), and there was a median of 8 years (6 – 10.5) follow-up. In our cohort, 7 patients had evidence of cardiac involvement following cardiac screening. 6 patients were asymptomatic (NYHA class I/AHA stage B) throughout their follow-up thus far, while 1 patient developed end-stage heart failure (NYHA class IV/AHA stage D) requiring a left ventricular assist device (LVAD) and ultimately, heart transplantation. CMR was the most sensitive in detecting early cardiac involvement in stage B patients, with 5 patients (83.3%) having abnormal CMR despite TTE showing normal biventricular function. The most common findings on CMR included moderate LV systolic impairment (median LVEF 52%, 5 patients) and non-ischemic distribution of late gadolinium enhancement (LGE) in three patients. Notably, three patients had only mild skeletal muscle weakness, and one patient had no skeletal muscle weakness despite evidence of cardiac involvement. Despite being asymptomatic, these patients were initiated on cardioprotective medications, specifically angiotensin-converting enzyme inhibitors and beta blockers. There was an improvement in LVEF from a median of 49.5% at baseline to 59% at follow-up for patients with follow-up CMR while on cardioprotective medications.
Conclusion: Cardiac magnetic resonance imaging can detect subclinical cardiac involvement in patients with LGMD R9, allowing for early initiation of cardioprotective therapies in this cohort, which may promote reverse biventricular remodelling in this cohort.
