Abstract
Objective:To assess whether hereditary myopathy with early respiratory failure (HMERF) due to the c.951434T>C; (p.Cys31712Arg) TTN missense mutation also includes a cardiac phenotype.Method:Clinical cohort study of our HMERF cohort using ECG, 2D echocardiogram, and cross-sectional cardiac imaging with MRI or CT.Results:We studied 22 participants with the c.951434T>C; (p.Cys31712Arg) TTN missense mutation. Three were deceased. Cardiac conduction abnormalities were identified in 7/22 (32%): sustained atrioventricular tachycardia (n = 2), atrial fibrillation (n = 2), nonsustained atrial tachycardia (n = 1), premature supraventricular complexes (n = 1), and unexplained sinus bradycardia (n = 1). In addition, 4/22 (18%) had imaging evidence of otherwise unexplained cardiomyopathy. These findings are supported by histopathologic correlation suggestive of myocardial cytoskeletal remodeling.Conclusions:Coexisting cardiac and skeletal muscle involvement is not uncommon in patients with HMERF arising due to the c.951434T>C; (p.Cys31712Arg) TTN mutation. All patients with pathogenic or putative pathogenic TTN mutations should be offered periodic cardiac surveillance.
Highlights
Coexisting cardiac and skeletal muscle involvement is not uncommon in patients with hereditary myopathy with early respiratory failure (HMERF) arising due to the c.951434T.C; (p.Cys31712Arg) TTN mutation
HMERF is characterized by adult onset of distal or proximal muscle weakness in association with early respiratory muscle weakness, which may be the presenting feature and require noninvasive ventilation
All participants known to the John Walton Muscular Dystrophy Research Centre, Newcastle upon Tyne, United Kingdom, with the c.951434T.C; (p.Cys31712Arg) TTN missense mutation had a 12-lead ECG and echocardiogram requested as part of routine clinical care
Summary
All participants known to the John Walton Muscular Dystrophy Research Centre, Newcastle upon Tyne, United Kingdom, with the c.951434T.C; (p.Cys31712Arg) TTN missense mutation had a 12-lead ECG and echocardiogram requested as part of routine clinical care. All available cardiac test results were reviewed. Thereafter, all participants residing within the North East of England were invited to attend for a cardiac MRI, irrespective of cardiac symptomatology or initial findings. Where participants were unable to tolerate MRI, cardiac CT scan was offered. All cardiac MRIs were performed on a 1.5T Siemens MRI scanner using a standardized cardiomyopathy protocol, with black blood anatomical, multiplanar short tau inversion recovery, multiplanar cines—including short axis stack for ventricular function, multiplanar cines, and delayed enhancement sequences obtained with gadoterate meglumine (Dotarem; Guerbet, Villepinte, France). All cardiac CT imaging was performed on a Siemens dual source CT scanner retrospectively gated at low dose for functional information only with a Flash mode delayed enhancement series 7 minutes following iohexol (Omnipaque; GE Healthcare, Cleveland, OH) administration
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