Complete Heart Block in a Thick Heart - Should we search further?

​​​Authors

Georgia Vogiatzi, Rosemary A. Rusk

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​​Key message

Presentation with complete heart block in a young individual should prompt investigation into the underlying aetiology

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Content Background: The combination of complete heart block (CHB) and left ventricular hypertrophy (LVH) is a red flag for a possible hypertrophic cardiomyopathy (HCM) phenocopy. HCM mimickers with advanced conduction disease include cardiac amyloidosis, advanced Fabry disease, Danon disease, sarcoidosis, and PRKAG2-related cardiomyopathy1. Danon disease is a X-linked lysosomal storage disorder caused by deficiency of lysosome-associated membrane protein 2 (LAMP2), typically presenting at a young age and with a triad of HCM, skeletal myopathy, and cognitive impairment.

 

Case Presentation: A 40-year-old normotensive male with type 2 diabetes, asthma, and learning difficulties presented on an acute medical take with dizziness, dyspnoea, and muscle cramps. Electrocardiography revealed complete heart block with ventricular rate 39bpm, narrow QRS duration. (Figure 1). There was a family history of pacemaker implantation in his mother and maternal grandfather. He is a persistent smoker.

 

Investigations: Laboratory tests showed elevated ALT (149U/l), CK (441U/l), and high troponin levels (1,400ng/l). Renal function, ACE and alpha-galactosidase levels were normal. Echocardiography reported LVH, and moderately reduced left ventricular systolic function. MRI showed a non-dilated left ventricle with LVH (14mm inferolateral wall, 12mm septum), left ventricular ejection fraction 39%, and mid-wall late gadolinium enhancement in the basal to mid inferolateral wall (Figure 2). Coronary arteries were unobstructed.

 

Management: The patient received device therapy and pillars of heart failure therapy were commenced. An HCM gene panel identified a pathogenic LAMP2 variant, confirming Danon disease. Predictive genetic testing was offered to family members.

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Conclusion: This case underscores the importance of recognizing HCM mimics in patients with advanced conduction disturbances and LVH. It also demonstrates the importance of a comprehensive biochemical profile at initial presentation, as recommended in the ESC Cardiomyopathy guidelines1, which raised suspicion in this case of Danon’s disease, and helped to prompt genetic testing. Danon disease, although rare, should be included in the differential diagnosis of hypertrophic cardiomyopathy, especially when skeletal muscle involvement or cognitive impairment are present. Management strategies, prognosis, and familial screening differ significantly in phenocopies from sarcomeric HCM. Early referral for transplantation assessment should be considered in Danon disease, and newer therapies, including gene therapy, are in development.

 

Figure 1. 12 lead ECG revealing complete heart block.

Figure 2. Cardiac MRI showed a non-dilated left ventricle with hypertrophy (A), and mid-wall late gadolinium enhancement in the basal inferolateral wall (B).

 

1Reference: Arbelo E, et al. 2023 ESC Guidelines for the management of cardiomyopathies. European Heart Journal (2023) 44, 3503–3626.​