Cardiac findings in pediatric patients with spinal muscular atrophy types 2 and 3

Abstract

Background: It is unclear whether the heart is affected in pediatric patients with milder forms of spinal muscular atrophy (SMA). Therefore, we aimed to determine the presence of any cardiac abnormalities in these patients. Methods: We conducted a cross-sectional study of children and adolescents with SMA types 2 and 3 between July 2018 and July 2019. All patients underwent a comprehensive cardiac evaluation, including history-taking, physical examination, electrocardiography, echocardiography, measurement of cardiac biomarkers (cardiac troponin T [cTnT] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 24-hour Holter monitoring. Results: In total, 42 patients were enrolled (27 and 15 with SMA type 2 and 3, respectively). No patient had structural heart disease, except for one with mitral valve prolapse. None had signs of ventricular dysfunction on echocardiography. Both cTnT and NT-proBNP levels were normal in all patients. Electrocardiography showed sinus tachycardia in seven patients (16.7%), and prolonged P-R interval in one (2.4%). Holter monitoring detected benign ventricular arrhythmias in two patients (4.8%), and rare supraventricular premature beats in one. The mean 24-hour heart rate was elevated in six patients (14.3%), whereas both the minimum 24-hour heart rate and the maximum R-R interval were increased in 23 (54.8%).

Safety Monitoring of Gene Therapy for Spinal Muscular Atrophy with Onasemnogene Abeparvovec –A Single Centre Experience

“…In contrast to troponin I, troponin T measurements were less consistent and often elevated above ULN even before treatment. There are several pathophysiological and analytical differences between troponin I and T [18], but little is known about normal troponin values in healthy children [19,20] and in children with SMA [21,22]. Our data suggests that troponin I is more appropriate to monitor cardiotoxicity than troponin T. Whether troponin I values above a certain cut-off are indicative of cardiac tissue injury and should induce additional examinations or an escalation of immunosuppression remains unclear.…”

The alteration of left ventricular strain in later-onset spinal muscular atrophy children

“…Patients with type 2 and 3 SMA, however, are less likely to manifest with significant clinical, electrocardiographic, or echocardiographic signs of cardiomyopathy; thus, they do not often undergo regular cardiac monitoring. Nevertheless, cases have been reported in which serious complications such as myocardial infarction with cardiac hypertrophy may still occur with aging ( Sokolska et al, 2020 ; Djordjevic et al, 2021b ). Cardiac abnormalities and autonomic defects have also been reported in SMA mouse models ( Bevan et al, 2010 ; Shababi et al, 2010 ; Sheng et al, 2018 ).…”

“…The deficiency of functional SMN proteins may cause multi-system impairment, along with a progressive decline in motor function ( Hamilton and Gillingwater, 2013 ; Shababi et al, 2014 ; Faravelli et al, 2015 ; Simone et al, 2016 ; Finkel et al, 2018 ; Mercuri et al, 2018 ; Yeo and Darras, 2020 ). Furthermore, the presence of cardiac complications has been mentioned in the 2018 international consensus statement and clinical studies ( Rudnik-Schöneborn et al, 2008 ; Wijngaarde et al, 2017 ; Finkel et al, 2018 ; Sokolska et al, 2020 ; Djordjevic et al, 2021b ); cardiac structural abnormalities, mainly septal defects and abnormalities of the cardiac outflow tract, were predominantly reported in type 0 and 1 SMA, while cardiac rhythm disorders were most frequently observed in patients with type 2 and 3 SMA. However, long-term cardiac complications, such as myocardial infarction with cardiac hypertrophy, has been confirmed in later-onset SMA patients ( Sokolska et al, 2020 ; Djordjevic et al, 2021b ).…”

“…Furthermore, the presence of cardiac complications has been mentioned in the 2018 international consensus statement and clinical studies ( Rudnik-Schöneborn et al, 2008 ; Wijngaarde et al, 2017 ; Finkel et al, 2018 ; Sokolska et al, 2020 ; Djordjevic et al, 2021b ); cardiac structural abnormalities, mainly septal defects and abnormalities of the cardiac outflow tract, were predominantly reported in type 0 and 1 SMA, while cardiac rhythm disorders were most frequently observed in patients with type 2 and 3 SMA. However, long-term cardiac complications, such as myocardial infarction with cardiac hypertrophy, has been confirmed in later-onset SMA patients ( Sokolska et al, 2020 ; Djordjevic et al, 2021b ). To date, although no specific mechanism has been established to link cardiovascular injury with SMN protein deficiency, patients with SMA may be severely affected by these defects in the absence of effective cardiac monitoring.…”

Surgical correction of a ventricular septal defect in a child with spinal muscular atrophy type 2 treated with nusinersen sodium: a case report

“…Spinal muscular atrophy is estimated to affect 1 in 11,000 live births and is one of the leading causes of infantile mortality [ 1 , 2 ]. The lack of SMN-1 gene expression is the main cause of this disease [ 1 – 4 ]. Reports of cardiac pathology co-existence with SMA are more frequent among the severely affected patients [ 4 ].…”