300. Case Report: A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins – Cambridge University

CardioNerds (Drs. Amit Goyal and Dan Ambinder) join Dr. Mina Fares, Dr. Johannes Bergehr, and Dr. Christina Peter from Cambridge University Hospitals in the UK. They discuss a case involving a man man in his 40’s presented with progressive heart failure symptoms. He has extensive background cardiac history including prior episodes of myocarditis and complete heart block status post permanent pacemaker implantation. Ultimately a diagnosis of Danon disease is made. Dr. Sharon Wilson provides the E-CPR for this episode. Audio editing by CardioNerds Academy Intern, Hirsh Elhence.





CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases’, with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ).











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Case Summary - A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins - Cambridge University



A man in his 40s with a history of cardiac issues, including prior myocarditis and complete heart block, presented with progressive heart failure symptoms. Extensive cardiac investigations were conducted, revealing dilated left ventricle, mild to moderate left ventricular systolic dysfunction, normal coronaries, infero-lateral late gadolinium enhancement on cardiac MRI, and low-level uptake on PET-CT. Differential diagnosis included worsening underlying cardiomyopathy, recurrent myocarditis, tachycardia-related cardiomyopathy, pacemaker-induced LV dysfunction, and sarcoidosis. The patient's condition improved with heart failure medications, and cardiac MRI showed a mildly dilated left ventricle with moderate systolic dysfunction and active inflammation in the anterior wall. Further evaluation indicated a family history of hereditary cardiomyopathy, and the patient exhibited phenotypic features such as early-onset heart disease, arrhythmias, family history of cardiomyopathy, learning problems, intellectual disability, and mild proximal myopathy. Genetic testing confirmed a LAMP2 mutation, leading to the diagnosis of Danon disease.



Case Media - A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins - Cambridge University








































































Show Notes -A Presentation of Heart Failure and Heart Block with Elusive Genetic Origins - Cambridge University





































References -




Danon, M. J., Oh, S. J., DiMauro, S., Miranda, A., De Vivo, D. C., & Rowland, L. P. (1981). Lysosomal glycogen storage disease with normal acid maltase. Neurology, 31(1), 51-7.



Nishino, I., Fu, J., Tanji, K., Nonaka, I., & Ozawa, T. (2000). Mutations in the gene encoding LAMP2 cause Danon disease. Nature, 406(6798), 906-10.



Tanaka, K., Nishino, I., Nonaka, I., Fu, J., & Ozawa, T. (2000). Danon disease is caused by mutations in the gene encoding LAMP2, a lysosomal membrane protein. Nature, 406(6798), 902-6.



Maron, B. J., Haas, T. S., Ackerman, M. J., Ahluwalia, A., Spirito, P., Nishino, I., ... & Seidman, C. E. (2009). Hypertrophic cardiomyopathy and sudden death in a family with Danon disease. JAMA, 301(12), 1253-9.



Hashem, S., Zhang, J., Zhang, Y., Wang, H., Zhang, H., Liu, L., ... & Wang, J. (2015). AAV-mediated gene transfer of LAMP2 improves cardiac function in Danon disease mice. Stem cells, 33(11), 2343-2350.



Chi, L., Wang, H., Zhang, J., Zhang, Y., Liu, L., Wang, J., ... & Hashem, S. (2019). CRISPR/Cas9-mediated gene editing of LAMP2 in patient-derived iPSCs ameliorates Danon disease phenotypes.