Arrhythmias in the Muscular Dystrophies

Rajdev, Archana; Groh, William J.

doi:10.1016/j.ccep.2015.03.011

Cited by 29 publications

(32 citation statements)

References 30 publications

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“…Contrary to DMD patients who usually manifest increased high heart rate, DMD iPSC‐CMs display low spontaneous firing rate compared to control. However, in DMD patients, increased heart rate is attributed to elevated sympathetic tone; hence, as this masking effect is absent in DMD iPSC‐CMs, the in vitro study exposes a fundamental pathophysiology of the pacemaker function—attenuated automaticity.…”

Section: Discussionmentioning

confidence: 74%

Electrophysiological abnormalities in induced pluripotent stem cell‐derived cardiomyocytes generated from Duchenne muscular dystrophy patients

Eisen

Jehuda

Cuttitta

et al. 2019

J Cellular Molecular Medi

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Duchenne muscular dystrophy (DMD) is an X‐linked progressive muscle degenerative disease, caused by mutations in the dystrophin gene and resulting in death because of respiratory or cardiac failure. To investigate the cardiac cellular manifestation of DMD, we generated induced pluripotent stem cells (iPSCs) and iPSC‐derived cardiomyocytes (iPSC‐CMs) from two DMD patients: a male and female manifesting heterozygous carrier. Dystrophin mRNA and protein expression were analysed by qRT‐PCR, RNAseq, Western blot and immunofluorescence staining. For comprehensive electrophysiological analysis, current and voltage clamp were used to record transmembrane action potentials and ion currents, respectively. Microelectrode array was used to record extracellular electrograms. X‐inactive specific transcript (XIST) and dystrophin expression analyses revealed that female iPSCs underwent X chromosome reactivation (XCR) or erosion of X chromosome inactivation, which was maintained in female iPSC‐CMs displaying mixed X chromosome expression of wild type (WT) and mutated alleles. Both DMD female and male iPSC‐CMs presented low spontaneous firing rate, arrhythmias and prolonged action potential duration. DMD female iPSC‐CMs displayed increased beat rate variability (BRV). DMD male iPSC‐CMs manifested decreased I f density, and DMD female and male iPSC‐CMs showed increased I Ca,L density. Our findings demonstrate cellular mechanisms underlying electrophysiological abnormalities and cardiac arrhythmias in DMD.

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Section: Discussionmentioning

confidence: 74%

Electrophysiological abnormalities in induced pluripotent stem cell‐derived cardiomyocytes generated from Duchenne muscular dystrophy patients

Eisen

Jehuda

Cuttitta

et al. 2019

J Cellular Molecular Medi

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“…Sudden cardiac death (SCD) can occur in patients with both DMD and BMD. It is difficult to discern whether SCD results primarily from ventricular arrhythmias or progressive skeletal and cardiac muscle failure …”

Section: Muscular Dystrophies With Prominent Cardiac Involvementmentioning

confidence: 99%

“…Emery‐Dreifuss muscular dystrophy (EDMD) is a rare disorder with X‐linked (EDMD1), autosomal dominant (AD; EDMD2) and, rarely, autosomal recessive (AR) inheritance. A major clinical hallmark is the presence of cardiac disease, typically AV conduction abnormalities and atrial arrhythmias . Although phenotypic expression and penetrance are highly variable, there is a high risk of SCD in all forms of EDMD, irrespective of the severity of neuromuscular involvement …”

Section: Muscular Dystrophies With Prominent Cardiac Involvementmentioning

confidence: 99%

“…Ventricular arrhythmias are common, and SCD is the leading cause of death in this disorder, often before age 50 . ECG abnormalities are usually present by 20 years of age with evidence of abnormal AV conduction including low P wave amplitude, atrial fibrillation, AV block, or even atrial standstill with a junctional escape rhythm (Table ) . Eventually, atrial paralysis occurs with total loss of electrical and mechanical activity.…”

Section: Muscular Dystrophies With Prominent Cardiac Involvementmentioning

confidence: 99%

“…Because of the risk of SCD, a pacing indication should prompt consideration of ICD implantation. Furthermore, if a severe DCM is present, an ICD may be warranted even in the absence of conduction disease because of the high risk of SCD …”

Section: Recommendations For Screening and Treatmentmentioning

confidence: 99%

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Cardiac involvement in the muscular dystrophies

et al. 2017

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Cardiac disease is a common clinical manifestation present in a variety of neuromuscular disorders, most notably the muscular dystrophies. Heart disease may produce the presenting or predominant symptoms in these disorders but more often not does not result in clinical features at the time of initial presentation. Cardiac involvement in the muscular dystrophies results from pathologic changes in the myocardium and the cardiac conduction system, leading to cardiomyopathy and/or rhythm disturbances including supraventricular arrhythmias, life-threatening ventricular arrhythmias, and sudden cardiac death. This Review covers the spectrum of cardiac dysfunction in these inherited muscle disorders and proposes practical recommendations for monitoring and management. Muscle Nerve 57: 707-715, 2018.

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Management of rhythm disorders in Duchenne muscular dystrophy: Is sudden death a cardiac or pulmonary problem?

Bennett

Kertesz

2021

Pediatric Pulmonology

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Dystrophin deficiency results in the cardiomyopathy of variable onset and deficiency. Myocardial scarring commonly results in cardiac dysfunction, with both atrial and ventricular dysrhythmias. Heart failure, rather than arrhythmia burden, remains the strongest cardiac predictor of mortality in this patient population. Current data suggest the overall rate of sudden cardiac death in pediatric dilated cardiomyopathy is significantly lower than in adults. Specifically, in the Duchenne cardiomyopathy population, sudden death from an arrhythmic cause appears to be rare, even in patients with previously diagnosed arrhythmias. Despite this, recommendations for implantable cardioverter‐defibrillator (ICD) placement in patients with Duchenne cardiomyopathy has traditionally been extrapolated from adult heart failure recommendations based on decreased left ventricular ejection fraction <35%. Early involvement of the cardiologist in the care for patients with dystrophin‐deficient cardiomyopathy is recommended for this reason. The indications for ICD placement to prevent sudden death in patients with Duchenne cardiomyopathy are not well defined. There is little evidence to suggest that placement meaningfully prolongs life in this population, and should be carefully considered in accordance with the care goals of the patient and his family.

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Arrhythmias in the Muscular Dystrophies

Cited by 29 publications

References 30 publications

Electrophysiological abnormalities in induced pluripotent stem cell‐derived cardiomyocytes generated from Duchenne muscular dystrophy patients

Electrophysiological abnormalities in induced pluripotent stem cell‐derived cardiomyocytes generated from Duchenne muscular dystrophy patients

Cardiac involvement in the muscular dystrophies

Management of rhythm disorders in Duchenne muscular dystrophy: Is sudden death a cardiac or pulmonary problem?

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