Cardiovascular Journal of Africa: Vol 35 No 3 (SEPTEMBER/OCTOBER 2024)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 3, September – October 2024 188 AFRICA ATTRwt-CM may have an associated monoclonal gammopathy, with no evidence of immunoglobulin light chains on biopsy, highlighting the need for biopsy for appropriate amyloid protein subtyping.6 ATTRv-CM can be distinguished from ATTRwtCM by sequencing of the TTR gene.10 Multimodality cardiac imaging plays a significant role in diagnosis, as demonstrated in our case. Of key importance is the observation of reduced LV systolic function in the presence of normal cardiac chamber sizes, which is consistent with cardiac amyloidosis but inconsistent with end-stage hypertensive heart disease. This pattern was similarly observed by Grogan and colleagues.4 In the absence of a monoclonal gammopathy, nuclear scintigraphy with technetium-labelled bisphosphonate is highly sensitive (99%) and specific (86%) for ATTR cardiac amyloidosis.10 The patient’s untimely demise limited our ability to perform further evaluation to accurately subtype his cardiac amyloidosis. However, based on his clinical trajectory, we considered a diagnosis of ATTRwt-CM to be most likely. As he presented with advanced disease involving multiple systems, further diagnostic evaluation to subtype his disease would have been beneficial based on his preferences and values. Emerging therapeutic options for ATTRwt-CM include tafamidis, a tetramer stabiliser, which is most effective when given in the early stages of the disease.10,13 Otherwise, the prognosis of ATTRwt-CM remains dismal, especially when diagnosis is delayed.4 Conclusion ATTRwt-CM may initially present with LVH and HFpEF in the elderly. It should therefore be considered a plausible differential diagnosis in the appropriate clinical context, irrespective of a history of long-standing hypertension. Multimodality cardiac imaging plays a key role and should be utilised as appropriate to help establish the diagnosis. With increasing awareness and a high index of clinical suspicion, it may be possible to detect ATTRwt-CM in the early stages of the disease. The diagnostic pathway should include more sensitive and specific diagnostic tools such as cardiac scintigraphy, in the absence of a monoclonal gammopathy, and genetic testing, to aid in the early detection of ATTRwt-CM. Early diagnosis is crucial as current therapeutic options have value largely in the early stages of the disease. In low-resource settings however, lack of specialist expertise results in low recognition of ATTRwt-CM, and cost and limited availability of advanced diagnostic tools and pharmacotherapy make early diagnosis and management challenging. We can surmount these challenges by improving careprovider awareness of the disease to increase clinical suspicion of ATTRwt-CM in the early stages, improving early diagnostic capacity by making additional diagnostic tools such as cardiac scintigraphy and genetic testing more available and affordable, and working to make novel therapeutic options for cardiac amyloidosis affordable and available in low-resource settings. The authors acknowledge Dr Daniel Baddoo who performed the carpal tunnel release surgery. We are also grateful to the patient’s relatives for their support in the care of the patient and for giving consent to share this case. References 1. Aje A, Adebiyi AA, Falase AO. Hypertensive heart disease in Africa. SA Heart 2009; 6(1): 42–51. 2. Weidemann F, Niemann M, Ertl G, Störk S. The different faces of echocardiographic left ventricular hypertrophy: clues to the etiology. J Am Soc Echocardiogr 2010; 23(8): 793–801. 3. Kittleson MM, Ruberg FL, Ambardekar AV, Brannagan TH, Cheng RK, Clarke JO, et al. 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis. J Am Coll Cardiol 2023; 81(11): 1078–126. 4. Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, et al. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol 2016; 68(10): 1014–2100. 5. Kyriakou P, Mouselimis D, Tsarouchas A, Rigopoulos A, Bakogiannis C, Noutsias M, et al. Diagnosis of cardiac amyloidosis: A systematic review on the role of imaging and biomarkers. BMC Cardiovasc Disord 2018; 2018(18): 221. 6. Liu PP, Smyth D. Wild-type transthyretin amyloid cardiomyopathy: a missed cause of heart failure with preserved ejection fraction with evolving treatment implications. Circulation 2016; 133(3): 245–247. 7. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol 2019; 73(22): 2872–2891. 8. Cornwell GG, Murdoch WL, Kyle RA, Westermark P, Pitkänen P. Frequency and distribution of senile cardiovascular amyloid. A clinicopathologic correlation. Am J Med 1983; 75(4): 618–23. 9. Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study. Ann Med 2008; 40(3): 232–239. 10. Muchtar E, Dispenzieri A, Magen H, Grogan M, Mauermann M, McPhail ED, et al. Systemic amyloidosis from A (AA) to T (ATTR): a review. J Intern Med 2021; 289(3): 268–292. 11. Cyrille NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol 2014; 114(7): 1089–1093. 12. Sood RF, Kamenko S, McCreary E, Sather BK, Schmitt M, Peterson SL, et al. Diagnosing systemic amyloidosis presenting as carpal tunnel syndrome: a risk nomogram to guide biopsy at time of carpal tunnel release. J Bone Joint Surg Am 2021; 103(14): 1284–1294. 13. Macedo AVS, Schwartzmann PV, de Gusmão BM, Melo MDT de, Coelho-Filho OR. Advances in the treatment of cardiac amyloidosis. Curr Treat Options Oncol 2020; 2020(21): 36.

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