Skip to content


  • Letter to the Editor
  • Open Access

Potential causes of sudden cardiac death in nemaline myopathy

Italian Journal of Pediatrics201541:67

Received: 2 July 2015

Accepted: 21 September 2015

Published: 29 September 2015


Non-compactionCardiomyopathyMyopathyCardiac involvementSudden cardiac deathVentricular arrhyhtmias

Letter to the Editor

With interest we read the article by Marseglia et al. about a 6yo boy with nemaline myopathy (NM) but without evidence for previous cardiac disease who experienced non-triggered asystole, underwent prolonged resuscitation, and died 1 week later from secondary cerebral hypoxia [1]. We have the following comments and concerns.

Was the previous history positive for palpitations, collapse, syncope, exertional dyspnea, or leg edema? Cardiac involvement in NM has been previously reported and includes sino-atrial block [2], WPW-syndrome [2], atrial fibrillation [3], bundle branch block [4], left anterior hemiblock [4], hypertrophic cardiomyopathy [5], outflow tract obstruction [6], dilative cardiomyopathy [5], pulmonary hypertension [4], heart failure [7], and sudden cardiac death [5] (Table 1). Did the patient undergo long-term ECG recording with 24 h-ECG, telemetry, or a reveal recorder?
Table 1

Manifestations of cardiac involvement in nemaline myopathy

Cardiac abnormality



Age (y)












Atrial fibrillation





Incomplete BBB





Complete BBB





Left anterior hemiblock





Pulmonary hypertension







f, 4 m, nm

9, 26, 29, 47, 50, nm

[4, 5, 1113]



5 m/2 nm


[6, 7, 10, 1419]

Outflow tract obstruction




[6, 14]

Heart failure


f, 2 m, nm

0/9, 3, nm

[5, 7, 20]

Sudden cardiac death



47, 37


NOP Number of patients, SA Sino-atrial, WPW Wolff-Parkinson-White, BBB Bundle branch block, dCMP Dilated cardiomyopathy, hCMP Hypertrophic cardiomyopathy, nm Not mentioned

Did laboratory parameters on admission, such as serum potassium, creatine-kinase, troponine-T, or proBNP, indicate cardiac disease? Was there any indication for intoxication or metabolic defect on blood gas analysis? Was there any indication for infectious disease, such as increased C-reactive protein, increased procalcitonin, or leukocytosis? Did the patient receive cardiotoxic medication prior to the event?

Were there indications on ECG or echocardiography that sudden cardiac death resulted from stress cardiomyopathy, also known as Takotsubo cardiomyopathy, broken heart syndrome, or stunned myocardium? Takotsubo syndrome may occur even in the absence of systolic dysfunction [8]. Was there any possible trigger leviable shortly before the event that could have induced anxiety? Was the patient exposed to physical or psychological stress prior to the event?

Were previous echocardiographies reviewed for left ventricular hypertrabeculation, also known as noncompaction (LVHT)? LVHT is frequently associated with embolism, heart failure, ventricular arrhythmias, and sudden cardiac death. LVHT is frequently missed on transthoracic echocardiography if the apex is not well depicted. Was there any indication for LVHT on the last bed-side echocardiography before decease? Did the patient undergo cardiac MRI? Did the parents undergo echocardiography to look for subclinical cardiac involvement?

Did the pathologist look for fibrosis of the cardiac conduction system? Was there any indication for endocardial fibrosis on myocardial autopsy frequently found in patients with LVHT [9]. Was there histological evidence for myocarditis? Why did the heart and cerebrum not undergo autopsy? LVHT can be easily missed on echocardiography and cardiac MRI? Autopsy is the golden standard to confirm LVHT. Was cerebral imaging carried out prior to the event? Embolic stroke may secondarily cause arrhythmias, particularly if the temporal lobe is affected from ischemia.

The most frequent of the cardiac abnormalities in NM is hypertrophic cardiomyopathy, followed by dilated cardiomyopathy and heart failure (Table 1). Only in 2 patients with NM has been sudden cardiac death so far reported (Table 1). Various different ECG abnormalities have been reported only in single patients (Table 1).

Overall, this interesting case would have deserved more and thorough work-up for the cause of cardiac conduction disturbance. It is also essential to screen the whole family not only for NM but also for cardiac involvement, in particular ventricular arrhythmias and LVHT. Sudden cardiac death in the presented patient may not only be attributed to arrhythmias but also to embolic stroke, TTS or LVHT.


Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

Krankenanstalt Rudolfstiftung, Vienna, Austria
1st Medical Department, Krankenanstalt Rudolfstiftung, Vienna, Austria


  1. Marseglia L, D’Angelo G, Manti S, Salpietro V, Arrigo T, Cavallari V, et al. Sudden cardiac arrest in a child with nemaline myopathy. Ital J Pediatr. 2015;41(1):20. doi:10.1186/s13052-015-0124-8.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Otsuji Y, Osame M, Tei C, Minagoe S, Kisanuki A, Arikawa K, et al. Cardiac involvement in congenital myopathy. Int J Cardiol. 1985;9:311–22.View ArticlePubMedGoogle Scholar
  3. Jones JG, Factor SM. Familial congestive cardiomyopathy with nemaline rods in heart and skeletal muscle. Virchows Arch A Pathol Anat Histopathol. 1985;408:307–12.View ArticlePubMedGoogle Scholar
  4. Taglia A, D’Ambrosio P, Palladino A, Politano L. On a case of respiratory failure due to diaphragmatic paralysis and dilated cardiomyopathy in a patient with nemaline myopathy. Acta Myol. 2012;31:201–3.PubMed CentralPubMedGoogle Scholar
  5. Meier C, Voellmy W, Gertsch M, Zimmermann A, Geissbühler J. Nemaline myopathy appearing in adults as cardiomyopathy. A clinicopathologic study. Arch Neurol. 1984;41:443–5.View ArticlePubMedGoogle Scholar
  6. Mir A, Lemler M, Ramaciotti C, Blalock S, Ikemba C. Hypertrophic cardiomyopathy in a neonate associated with nemaline myopathy. Congenit Heart Dis. 2012;7:E37–41.View ArticlePubMedGoogle Scholar
  7. Nakajima M, Shima Y, Kumasaka S, Kuwabara K, Migita M, Fukunaga Y. An infant with congenital nemaline myopathy and hypertrophic cardiomyopathy. J Nippon Med Sch. 2008;75:350–3.View ArticlePubMedGoogle Scholar
  8. Zawaideh C, Aste M, Cutuli O, Budaj I, Bezante GP, Brunelli C, et al. Transient left ventricular and stomach apical ballooning syndromes: when the trigger is also a clinical emergency. Am J Emerg Med. 2014;32:108.e1–3.View ArticleGoogle Scholar
  9. Karner J, Keller H, Stöllberger C, Feichtinger H, Finsterer J. Deficiency of mannose-binding lectin, myopathy, calcified endomyocardial fibrosis, and left ventricular noncompaction. Heart Lung. 2008;37:476–8.View ArticlePubMedGoogle Scholar
  10. Nagata R, Kamimura D, Suzuki Y, Saito T, Toyama H, Dejima T, et al. A case of nemaline myopathy with associated dilated cardiomyopathy and respiratory failure. Int Heart J. 2011;52:401–5.View ArticlePubMedGoogle Scholar
  11. Gatayama R, Ueno K, Nakamura H, Yanagi S, Ueda H, Yamagishi H, et al. Nemaline myopathy with dilated cardiomyopathy in childhood. Pediatrics. 2013;131:e1986–90.View ArticlePubMedGoogle Scholar
  12. Take C, Asano H, Komatsu A, Miyaji M, Iikuni K, Kowa H. An autopsy case of dilated cardiomyopathy associated with congenital nemaline myopathy. Nihon Naika Gakkai Zasshi. 2008;97:413–6.View ArticlePubMedGoogle Scholar
  13. Müller-Höcker J, Schäfer S, Mendel B, Lochmüller H, Pongratz D. Nemaline cardiomyopathy in a young adult: an ultraimmunohistochemical study and review of the literature. Ultrastruct Pathol. 2000;24:407–16.View ArticlePubMedGoogle Scholar
  14. Kim SY, Park YE, Kim HS, Lee CH, Yang DH, Kim DS. Nemaline myopathy and non-fatal hypertrophic cardiomyopathy caused by a novel ACTA1 E239K mutation. J Neurol Sci. 2011;307:171–3.View ArticlePubMedGoogle Scholar
  15. D’Amico A, Graziano C, Pacileo G, Petrini S, Nowak KJ, Boldrini R, et al. Fatal hypertrophic cardiomyopathy and nemaline myopathy associated with ACTA1 K336E mutation. Neuromuscul Disord. 2006;16:548–52.View ArticlePubMedGoogle Scholar
  16. Marston SB, Ingwall JS, Glueck SB. Calcium, contractions, and tropomyosin Focus on “divergent abnormal muscle relaxation by hypertrophic cardiomyopathy and nemaline myopathy mutant tropomyosins”. Physiol Genomics. 2002;9:57–8.View ArticlePubMedGoogle Scholar
  17. Skyllouriotis ML, Marx M, Skyllouriotis P, Bittner R, Wimmer M. Nemaline myopathy and cardiomyopathy. Pediatr Neurol. 1999;20:319–21.View ArticlePubMedGoogle Scholar
  18. Van Antwerpen CL, Gospe Jr SM, Dentinger MP. Nemaline myopathy associated with hypertrophic cardiomyopathy. Pediatr Neurol. 1988;4:306–8.View ArticlePubMedGoogle Scholar
  19. Michele DE, Coutu P, Metzger JM. Divergent abnormal muscle relaxation by hypertrophic cardiomyopathy and nemaline myopathy mutant tropomyosins. Physiol Genomics. 2002;9:103–11.View ArticlePubMedGoogle Scholar
  20. Ishibashi-Ueda H, Imakita M, Yutani C, Takahashi S, Yazawa K, Kamiya T, et al. Congenital nemaline myopathy with dilated cardiomyopathy: an autopsy study. Hum Pathol. 1990;21:77–82.View ArticlePubMedGoogle Scholar


© Finsterer and Frank. 2015