Unusual association of diseases/symptoms


Takotsubo cardiomyopathy in myasthaenia gravis crisis confirmed by cardiac MRI I B Harries,1 H Levoir,1 C Bucciarelli-Ducci,2 S Ramcharitar1 1

Wiltshire Cardiac Centre, Swindon, UK 2 Bristol Heart Institute, Bristol, UK Correspondence to Dr S Ramcharitar, steve. [email protected] Accepted 3 September 2015

SUMMARY Myasthaenia gravis crisis and Takotsubo cardiomyopathy are rare conditions that can be precipitated by emotional or physical stress. Myasthaenia gravis has a variety of cardiac manifestations but Takotsubo cardiomyopathy, particularly in male patients, has rarely been reported. We describe a unique case of a 70-year-old man who developed Takotsubo cardiomyopathy during his first presentation with a myasthaenia gravis crisis. He had not received plasmapharesis or immunoglobulin therapy. Striking ECG traces and cardiac MRI helped to confirm the diagnosis. Cardiac manifestations of myasthaenia gravis and myasthaenia gravis itself have overlapping symptoms; the importance of cardiac monitoring and clinical vigilance in such cases is discussed. The utility of cardiac MRI in assessing cardiac manifestations of myasthaenia gravis is also highlighted.

BACKGROUND The simultaneous occurrence of Takotsubo cardiomyopathy and myasthaenia gravis crisis has seldom been reported, particularly in male patients. The symptoms of cardiac involvement in myasthaenia gravis, which can be life-threatening, overlap with the symptoms of myasthaenia gravis itself (fatigue, dyspnoea and reduced exercise tolerance). This may pose a diagnostic challenge to the physician and it is therefore of critical importance that patients with myasthaenia gravis crisis be monitored and promptly treated if cardiac complications

To cite: Harries IB, Levoir H, Bucciarelli-Ducci C, et al. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2015209631

Figure 1

arise. Cardiac MRI is a useful tool to assess cardiac manifestations of myasthaenia gravis.

CASE PRESENTATION A 70-year-old man presented with a 3-week history of gradually progressive dyspnoea and lethargy. He also reported difficulty in swallowing and articulation. He had a medical history of diabetes mellitus, hypertension, hypothyroidism and polymyalgia rheumatica. He had no relevant family history. He was a non-smoker, consumed alcohol in moderation and lived with his wife. Cardiovascular and respiratory examination was unremarkable. Neurological examination revealed normal tone, power and reflexes and flexor plantars. Subtle bilateral ptosis was observed and upward gaze could only be held for 15 s. The combination of clinical signs and symptoms with reduced forced vital capacity led to a working diagnosis of respiratory failure due to myasthaenia gravis crisis. Progressive respiratory failure developed, prompting transfer to the high dependency unit for monitoring. The patient subsequently developed chest tightness and an ECG demonstrated widespread ST-elevation. He was treated with dual antiplatelet therapy, glyceryl trinitrate and morphine, and was prepared for urgent coronary angiography. He required mechanical ventilation for respiratory failure and pulmonary oedema. The deterioration occurred prior to immunoglobulin therapy and he did not receive plasmapharesis.

Standard 12-lead surface ECG at presentation. Harries IB, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209631


Unusual association of diseases/symptoms

Figure 2 Standard 12-lead surface ECG showing widespread ST-elevation.



ECG’s showed acute widespread ST-elevation (figures 1 and 2). High-sensitivity troponin was >100 000 ng/L. Coronary angiography demonstrated unobstructed coronary arteries. Left ventriculography was not undertaken because of haemodynamic instability, pulmonary oedema and mild acute kidney injury. In addition, transthoracic echocardiography had demonstrated severe biplane apical hypokinesia and preserved basal function (videos 1 and 2). A cardiac MRI confirmed severe apical hypokinesia with marked associated myocardial oedema, and absence of late myocardial enhancement (indicating no myocardial infarction), in keeping with Takotsubo cardiomyopathy (figure 3). Acetylcholine receptor antibodies were positive, confirming the diagnosis of myasthaenia gravis. CT of the neck and thorax demonstrated a normal thymus gland.

The patient required a tracheostomy for a prolonged ventilatory wean and was discharged from hospital after a 19-day inpatient stay. Following the recommendation of a neurologist, he was discharged on pyridostigmine and a reducing course of prednisolone. Follow-up transthoracic echocardiography at 3 months confirmed normalisation of left ventricular systolic function, confirming the diagnosis of Takotsubo cardiomyopathy. He remains under cardiac and neurological follow-up.


Treatment included 1.25 mg intravenous neostigmine and intravenous immunoglobulin, followed by pyridostigmine 60 mg four times a day, a reducing course of prednisolone once daily (60 mg initial dose), ramipril 2.5 mg twice daily and aspirin 75 mg once daily.

Myasthaenia gravis is an acquired autoimmune disease characterised by autoantibodies that act against the acetylcholine nicotinic postsynaptic receptors at the neuromuscular junction, leading to defective neuromuscular transmission in skeletal muscles. Clinically, this manifests as muscle weakness that typically progresses with repetitive use (fatigability). Precipitating factors include intercurrent illness, medications and emotional and physical stress.1 It is a multisystem disorder with cardiac involvement estimated to occur in 16% of cases.2 Arrhythmia,3 pericarditis,4 myocarditis5 (including the life-threatening giant

Video 1 Transthoracic echocardiogram apical four-chamber view showing apical hypokinesia.

Video 2 Transthoracic echocardiogram apical two-chamber view showing apical hypokinesia.



Harries IB, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209631

Unusual association of diseases/symptoms Figure 3 Cine two-chamber view, still frame in end-diastole (A) and end-systole (B), demonstrating impaired apical contraction and thickening. This apical area of severe hypokinesia is also oedematous (C) on the corresponding T2-weighted STIR image. Late gadolinium enhancement image showed the absence of myocardial scar or fibrosis (D).

cell form) and Takotsubo cardiomyopathy6–9 have all been reported to occur in association with myasthaenia gravis. Takotsubo cardiomyopathy is a reversible cardiomyopathy with transient left ventricular systolic dysfunction in the absence of significant coronary stenosis or myocardial scarring. It is typically precipitated by the catecholamine surge that accompanies significant emotional or physical stress, resulting in suppressed myocardial function. Symptoms include chest pain and dyspnoea. Significant rises in troponin and widespread ST segment deviation on a standard 12-lead ECG may be observed. It is more common in women.10 Myasthaenia gravis crisis can precipitate severe stress. Therefore, the aetiology for the relationship between Takotsubo cardiomyopathy and Myasthaenia gravis crisis may be catecholamine related.11 However, the pathophysiology of cardiac involvement in Myasthaenia gravis is more complex and autoimmune mechanisms involving anti-RyR, anti-titin and anti-Kv 1.4 antibodies (collectively called antistriational antibodies) are thought to participate.3 The symptoms of cardiac involvement in myasthaenia gravis, which can be life-threatening, overlap with the symptoms of myasthaenia gravis itself (fatigue, dyspnoea and reduced exercise tolerance). Therefore, recognising cardiac involvement in cases of myasthaenia gravis can be challenging, and clinical vigilance for cardiac involvement is advised. In myasthaenia gravis crisis, cardiac monitoring should always be considered; particularly during plasmapharesis or administration of immunoglobulin. There are only two previous reports of male patients with Takotsubo cardiomyopathy in the context of myasthaenia gravis,6–9 confirmed by echocardiography and/or left ventriculography. There are at least six reports in female patients.7 8 12–15 To the best of our knowledge, this is the first case to confirm Takotsubo cardiomyopathy in the context of myasthaenia gravis crisis by cardiac MRI, although it has previously been employed to demonstrate myocarditis3 and to confirm Takotsubo cardiomyopathy due to immunoglobulin infusion.15 Superior soft tissue resolution and dynamic imaging capabilities have led to cardiac MRI becoming an increasingly important diagnostic tool in the evaluation of Takotsubo cardiomyopathy.16 Typically, myocardial oedema, reversible wall Harries IB, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209631

motion abnormality extending beyond a single epicardial arterial distribution and the absence of late gadolinium enhancement, suggesting an absence of myocardial scar or fibrosis, are observed.16 However, it should be noted that late gadolinium enhancement has been reported to occur in Takotsubo cardiomyopathy, which suggests subtle fibrosis, but with complete resolution at follow-up.17 We conclude that cardiac MRI noninvasive tissue characterisation is a valuable tool in assessing cardiac involvement, particularly cardiomyopathy, in cases of myasthaenia gravis.

Learning points ▸ The physician should be mindful of cardiac involvement, including Takotsubo cardiomyopathy, during myasthaenia gravis crisis, which may be challenging to detect because of overlapping symptomatology. ▸ Cardiac monitoring of patients with myasthaenia gravis crisis should always be considered. ▸ Cardiac MRI is a useful tool in assessing cardiac manifestations of myasthaenia gravis.

Contributors All the authors contributed to the production of this manuscript. IBH and HL collated clinical details, wrote and edited the final manuscript, and edited the images for submission. SR performed coronary angiography and helped to write and edit the final manuscript. CB-D obtained and edited the cardiac MRIs and edited the final manuscript. Competing interests None declared. Provenance and peer review Not commissioned; externally peer reviewed.


Drachman D. Myasthenia gravis. N Engl J Med 1994;330:1797–810. Hofstad H, Ohm OJ, Mork SJ, et al. Heart disease in myasthenia gravis. Acta Neurol Scand 1984;70:176–84. Sakamoto A, Yamamoto M, Takahashi M, et al. A case of myasthenia gravis with cardiac fibrosis and easily provoked sustained ventricular tachycardia. J Cardiol Cases 2010;2:e41–4.


Unusual association of diseases/symptoms 4 5 6 7

8 9 10 11

Vats HS, Richardson SK, Pulukurthy S, et al. Pericarditis in myasthenia gravis. Cardiol Rev 2004;12:134–7. HooKim K, deRoux S, Igbokwe A, et al. IgG anti-cardiomyocyte antibodies in giant cell myocarditis. Ann Clin Lab Sci 2008;38:83–7. Bansal V, Kansal MM, Rowin J. Broken heart syndrome in myasthenia gravis. Muscle Nerve 2011;44:990–3. Arai M, Ukigai H, Miyata H. A case of transient left ventricular ballooning (“Takotsubo”-shaped cardiomyopathy) developed during plasmapheresis for treatment of myasthenic, crisis. Rinsho Shinkeigaku 2004;44:207–10. Mayor-Gomez S, Lacruz F, Ezpeleta D. Myasthenic crisis and Takotsubo syndrome: a non-chance relationship. Rev Neurol 2012;55:725–8. Sousa JM, Knobel M, Buchelle G, et al. Transient ventricular dysfunction (Takotsubo cardiomyopathy). Arq Bras Cardiol 2005;84:340–2. Golabchi A, Sarrafzadegan N. Takotsubo cardiomyopathy or broken heart syndrome: a review article. J Res Med Sci 2011;16:340–5. Lyon AR, Rees PS, Prasad S, et al. Stress (Takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008;5:22–9.







Bijulal S, Harikrishnan S, Namboodiri N, Tako-tsubo cardiomyopathy in a patient with myasthenia gravis crisis: a rare clinical association. BMJ Case Rep 2009;2009: bcr06.2008.0182. Beydoun SR, Wang J, Levine RL, et al. Emotional stress as a trigger of myasthenic crisis and concomitant takotsubo cardiomyopathy: a case report. J Med Case Rep 2010;4:393. Nishinarita R, Kawamura Y, Yasuda T, et al. A case of takotsubo cardiomyopathy leading to the diagnosis of myasthenia gravis. J Cardiol Cases 2012;6:e141–4. Gautiera P, Ravana R, Najjarb M. Tako-Tsubo syndrome during normal human immunoglobolin perfusion. Annales de Cardiologie et d’Angéiologie 2011;60:290–5. Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P, et al. Clinical characteristics and cardiovascular magnetic resonance findings in stress (takotsubo) cardiomyopathy. JAMA 2011;306:277–86. Nakamori S, Matsuoka K, Onishi K, et al. Prevalence and signal characteristics of late gadolinium enhancement on contrast-enhanced magnetic resonance imaging in patients with takotsubo cardiomyopathy. Circ J 2012;76:914–21.

Copyright 2015 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow


Harries IB, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-209631

Takotsubo cardiomyopathy in myasthaenia gravis crisis confirmed by cardiac MRI.

Myasthaenia gravis crisis and Takotsubo cardiomyopathy are rare conditions that can be precipitated by emotional or physical stress. Myasthaenia gravi...
NAN Sizes 1 Downloads 11 Views