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Page 2 of 7 Di Nora et al. Vessel Plus 2022;6:46 https://dx.doi.org/10.20517/2574-1209.2021.126

Cardiac amyloidosis (CA) is a systemic disease due to the aggregation of amyloid fibrils that commonly
[1]
deposit in the renal, cardiac, and hepatic tissues, as well as the peripheral and autonomic nervous systems .
Restrictive cardiomyopathy is the worst manifestation of CA, and it is present in 20% of symptomatic
[2]
patients at diagnosis . There are different variants that involve the heart: primary (AL) amyloidosis and
familial (TTR) amyloidosis are the most common forms .
[3-5]
AL amyloidosis is due to the clonal production and deposition of immunoglobulin light chains, and this
phenomenon leads to an underlying plasma cell dyscrasia. For this reason, the most effective cyto-reduction
[6-7]
therapy is high-dose chemotherapy, followed by autologous stem cell transplantation (ASCT) . However,
when patients show severe heart impairment, they are not candidates for ASCT due to the high risk of
[8]
mortality, thus having a median survival not longer than nine months . Recent studies have revealed that,
in more than 40% of cases, CA is diagnosed with a long delay [9-10] . This point could justify the high number
(~30%) of patients with severe and advanced organ involvement and the relatively early death after
[11]
diagnosis .

ATTR amyloidosis usually has a slower progression than AL amyloidosis. Transthyretin is a hepatic protein
with carrier function. In ATTR, the protein deposits in the heart and/or the nerves and other organs and
tissues. There are two forms of ATTR amyloidosis: hereditary ATTR amyloidosis, where there is an
[12]
inherited mutation in the DNA, and wild-type ATTR amyloidosis, which usually affects the elderly .
Recent studies have reported satisfying results for the treatment of wild-type ATTR amyloidosis using new
molecules, such as tafamidis. Effectively, patients initially treated with tafamidis had better survival than
[13]
placebo, leading to the approbation of this drug in several countries .
BACKGROUND
Patients’ survival in amyloidosis is extremely heterogeneous: patients without heart involvement can survive
some years; conversely, most patients with advanced cardiac damage die early . Historically, cardiac
[13]
transplantation was a contraindication in AL-CA. Only recently has it been described in AL amyloidosis
patients . At that time, few case reports showed that outcomes at short and medium-term were similar to
[14]
those in other diseases [14-17] ; conversely, larger case series showed worst results compared to the patients
transplanted for other cardiomyopathies . Thus, patients affected by AL-CA were excluded for HTx for all
[18]
these reasons.

The real revolution in this approach came when it was standardized that AL-CA patients needed to be
treated with high-dose melphalan followed by ASCT after HTx to suppress the production of monoclonal
light chains . Of note, this strategy of treating patients after HTx allowed reaching a complete hematologic
[19]
response one year after treatment in 40% of patients with primary AL amyloidosis . Since cardiac
[20]
transplantation for amyloidosis is not common, the studies available are generally small and based on
single-center experience [Table 1]. Moreover, other difficulties in comparing studies are related to the
[21]
variability of follow-up lengths, the patient selection criteria, and the different concurrent treatments.

Concerning the ATTR CA patients, the first proposed option was liver transplant (LT); subsequently, HTx
has been combined with LT to avoid the potential development of the cardiomyopathy after LT alone [22-23] .
Conversely, isolated HTx has been done in those patients without extracardiac deposits and end-stage HF,
showing very encouraging results . Considering all these premises, the International Society of Heart and
[24]
Lung Transplantation has recently assigned a class IIA recommendation for HTx in CA patients .
[25]