Outcomes of Heart Transplantation for Cardiac Amyloidosis: Subanalysis of the Spanish Registry for Heart Transplantation

Abstract

To the Editor: We read with interest the series about heart transplantation for cardiac amyloidosis from the Spanish Registry for heart transplantation (1). We generally agree with their conclusion that, in light of donor shortages, cardiac transplantation should be reserved for those with limited extracardiac disease. Furthermore, we would support the principle that, in most amyloid types including AL and hereditary transthyretin (TTR) amyloidosis, there should be a treatment strategy to ensure reduction of the underlying amyloid fibril precursor to prevent amyloid progression and recurrence in the graft. We would like to highlight, however, the differing rates of amyloid turnover between different amyloid types such that transplanted organs may last as long as 25 years without the need for reduction of amyloid fibril precursor protein supply in certain types of hereditary amyloidosis (2). We also have some concerns regarding the characterization of amyloid type in this study. Hereditary TTR amyloidosis is possible on the background of an incidental plasma cell dyscrasia and conversely, AL amyloidosis is possible despite the presence of a known amyloidogenic TTR mutation due to variable penetrance (3). Since therapy of amyloidosis is type-specific, immunohistochemical analysis of amyloid deposits in biopsy samples is crucial in all cases of amyloidosis; however, its sensitivity and specificity are not 100%. One frequently requires a combination of clinical assessment, histology, genetic testing and detailed biochemistry including the serum free light chain assay to confirm the amyloid type. We would like to also question the diagnosis of AA amyloidosis in two cases in this study. In our series of 374 patients with AA amyloidosis there was only one case of cardiac failure attributable to amyloidosis despite histological presence of amyloid in a substantial proportion (4). The cases in the Spanish study may represent incidental cardiac amyloid deposits rather than functionally significant cardiac amyloidosis. The AA deposits on immunohistochemistry were confirmed ‘in the explanted heart’ without mention of any specific preoperative echocardiographic features suggestive of cardiac amyloidosis. Takayasu's arteritis and ischaemic heart disease could have caused congestive cardiac failure requiring cardiac transplantation in their own right without amyloidosis. Finally, we would like to mention hereditary amyloidosis secondary to variant apolipoprotein AI (AApoAI), which was not sought in this study and can cause congestive cardiac failure. AApoAI could account for the two patients with ‘unknown’ TTR mutations, especially if the immunohistochemistry was not diagnostic. This type of amyloidosis commonly causes renal failure, which is rare in hereditary TTR amyloidosis but was present in one of the two patients. It can also cause cardiac failure and peripheral neuropathy, which are recognized in hereditary TTR amyloidosis. Furthermore, heart transplantation has a definite role in AApoAI despite the lack of an effective way to suppress amyloid fibril precursor protein supply and the frequent presence of extensive visceral amyloid, as assessed by serum amyloid P component scintigraphy (2).