In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.
Did you know that your browser is out of date? To get the best experience using our website we recommend that you upgrade to a newer version. Learn more.

We use cookies to optimise the design of this website and make continuous improvement. By continuing your visit, you consent to the use of cookies. Learn more

Critical changes in cardiomyopathy during adolescence

A 13 -year -old male was referred for cardiac evaluation after presenting with two syncopal episodes. After rushing to get to class on time, the young boy sat on the chair, noted rapid and regular beats, slight dizziness and then lost consciousness and fell onto the floor. Regarding past medical history: the patient had a traumatic subdural haematoma when aged 1 year which needed a ventriculo-peritoneal shunting until second year of age when it was removed with no sequelae or symptoms.
Myocardial Disease


A first ECG demonstrated sinus rhythm, shortish PR, QRS duration of 98 ms, high voltage QRS, Q waves in anterolateral and inferior leads, prominent R wave in V1 and negative T waves from V1-V3 (figure 1).
 

Echocardiogram showed septal hypertrophy of a maximum of 16 mm, normal systolic and diastolic function and no obstruction at the left ventricular outflow tract (figure 2).



Fig. 2. Echocardiogram.


The patient was admitted on the ward and cardiac telemetry during 7 days showed sinus bradycardia (45-55 bpm) but no arrhythmia. In the exercise testing, he exercised for 13:21 min, achieving 15.8 Mets with no symptoms apart from fatigue at the end of the test. The heart rate went from 64 to 190 /min (92% of predicted) and blood pressure increased from 110/60 to 160/60 mmHg. After all these tests, the patient was discharged with the diagnosis of hypertrophic cardiomyopathy and 3 month review was recommended. He was not recommended any medication on discharge, but was advised to avoid physical exercise for the moment. There was no family history of cardiac disease or sudden death, and the clinical findings of the parents and younger sister were normal.
 
The patient remained asymptomatic from 13-15 years of age. During these 2 years, serial ECG and echocardiogram demonstrated progression of wall thickness with no other major changes on ECG. A 24 hour and 7 a days Holter monitoring demonstrated no arrhythmias. Magnetic resonance corroborated the echocardiographic findings, showing a septum of 22 mm at 14 years of age,  contrast study with gadolinium was refused. Finally, genetic study of MYH7, MYBPC3, TNNT2, TNNI3, TPM1 and alfaGAL activity were all normal.

However, when the patient was 15 years old the ECG changed dramatically (figure 3).





QUESTION

1- What is your clinical advice?
(patient enjoys skiing, cycling and doing taekondo)

2- Would you repeat exercise testing and Holter?

3 - Would you start any medication such as betablocker or amiodarone? Would you perform an electrophysiological study or implant an ICD?

4 - What about genetic testing?


Case resolution:
It was decided to perform an exercise test and an adenosine test in order to assess pre-excitation. PR interval and QRS morphology did not changed significantly during exercise and no AV block was evidenced after 18 mg of adenosine. Therefore, an electrophysiologic study was performed, and in it two accessory pathways were evidenced (midseptal pathway and intermittent left-side pathway). Partial ablation of the midseptal pathway was achieved.

Echocardiographic control performed 4 months later demonstrated severe left ventricular hypertrophy (maximum of 34 mm at the interventricular septum) with right ventricular free wall involvement (maximum of 6mm), no systolic anterior motion of mitral valve (SAM) and no dynamic subaortic obstruction at rest or with Valsalva maneuver were evidenced (Figure 1). Systolic function remained normal.

 

Figure 1. Echocardiography showed severe left ventricular hypertrophy (maximum of 34 mm at the interventricular septum) with right ventricular free wall involvement.











Despite patient remained asymptomatic and no arrhythmia was demonstrated to that day, exercise was strongly unadvisable. On the basis of the presence of 2 risk factors in a young patient, such as syncope and severe hypertrophy, together with the presence of accessory pathway, ICD and medication was recommended. The parents were reluctant to any type of treatment initially but finally accepted the ICD which was implanted when aged 16.

 

Patient remained without any medication and continued with his exercise despite medical recommendation. Recently, he has been admitted to hospital for a pre-syncopal episode after exercise followed by an ICD shock. Interrogation of the device showed an episode of atrial fibrillation with rapid conduction to ventricle at a rate of 260 bpm which was successfully treated by the defibrillator. At that time, a new ablation attempt and oral anticoagulation have been recommended.

Regarding genetic testing, a previously described mutation in PRKAG2 R302Q (heterozygous) was identified. LAMP2 gene was also screened and normal. Typical phenotype of carriers of PRKAG2 mutations includes severe hypertrophy, often with biventricular involvement, and conduction abnormalities (particularly AV block and accesory AV pathways). PRKAG2 gene encodes information for the regulatory ¡ subunit of AMP-activated protein kinase, being the pathology of PRKAG2-hypertrophic cardiomyopathy characterized by the presence of glycogen-filled vacuoles within the myocytes. In contrast to sarcomeric hypertrophic cardiomyopathy, interstitial fibrosis and disarray of the myofibres is not typical.

10 families (119 carriers) with the R302Q mutation have been reported to date. Compared to previous cases, our patient developed the disease earlier and expressed a more severe phenotype. Carriers of this mutation express hypertrophy, conduction disease or both conditions. Mutations in PRKAG2 are associated to a bad prognosis, particularly the R302Q, with high rate of systolic dysfunction, arrhythmias and sudden death. In our patient, the exercise may have triggered the atrial fibrillation since the size of the left atrium was normal in the last echocardiogram. In addition, according to previous studies, atrial fibrillation or other supraventricular tachycardias have been found in 75% of patients with the R302Q variant.

Conclusion:

This particular case illustrates: (1) the difficulties to manage an adolescence patient in whom dramatic changes can appear in a short period of time in the absence of symptoms, (2) the value of close monitoring to prevent complications and the role of genetic information to confirm the diagnosis and (3) to assess risk when there is available clinical data on patients with the same mutation.

References


  1. Murphy RT, Mogensen J, McGarry K, Bahl A, Evans A, Osman E, et al.. Adenosine-monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome. J Am Coll Cardiol 2005;45 (6):922-30.

  2. Gollob MH, Seger JJ, Gollob TN, et al. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 2001;104:3030-3.

  3. Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG, Seidman CE. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 2002;109(3):357-362.

  4. Arad M, Maron BJ, Gorham JM, Johnson WH, Saul JP, Perez-Atayde AR, Spirito P, Wright GB, Kanter RJ, Seidman CE, Seidman JG. Glycogen storage diseases presenting as Hypertrophic Cardiomyopathy. N Engl J Med 2005;352:362-72.

Notes to editor


Authors: Maria José Oliva, Carmen Muñoz, Juan Gimeno.
Cardiac Department. University Hospital Virgen Arrixaca. Murcia. Spain
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

Contact us

WORKING GROUP ON MYOCARDIAL AND PERICARDIAL DISEASES

European Society of Cardiology

Les Templiers
2035 Route des Colles
CS 80179 BIOT

06903Sophia Antipolis, FR