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Porcari et al. Vessel Plus 2022;6:33 https://dx.doi.org/10.20517/2574-1209.2021.134 Page 9 of 14

[33]
devices may be considered , even though they have not been studied in CA yet.

Characterization and management of aortic valve stenosis
AS is a common finding in CA, ranging from 6% to 29% of patients, being particularly prevalent in men >
70-75 years old with ATTR-CA [13,54] . Currently, the clinical management and outcome of patients with CA
and AS relies on empirical experience rather than official indications [Table 1]. Data from small
retrospective studies [55-57] suggest that outcomes following AVR in CA patients are poorer than those in non-
CA patients, particularly in the presence of low flow low gradient (LF-LG) AS . In the absence of
[58]
[55]
peripheral artery disease, trans-femoral TAVI might be the strategy of choice at the cost of increased risk
of procedural complications (i.e., complete AV block) [59,60] .

A recent prospective study, part of ATTRact-AS (a study investigating the role of occult cardiac amyloid in
the elderly with aortic stenosis, NCT03029026), investigated the prevalence and outcome of ATTR-CA with
severe AS in patients ≥ 75 years old referred for TAVI. Compared to the others, patients with ATTR-CA
(13% of the study cohort) had similar incidence of periprocedural complications and overall mortality at a
median follow up of 19 months after TAVI. Furthermore, TAVI significantly improved the outcome of
ATTR-CA patients with AS compared to medical management. Notably, unlike previous studies, the
male:female ratio and the prevalence LF-LG AS were similar in patients with and without ATTR-CA.

Candidates to AVR should be carefully evaluated to define the severity of AS and the possibility of
consistent benefits as amyloid-induced myocardial dysfunction is expected to persist even after AVR. The
heart team should consider frailty, life expectancy, procedural risks, and comorbidities. Some factors are
associated with unfavorable prognosis and futility: LVEF < 50%, restrictive filling pattern, impaired global
longitudinal strain (> -10%), and LF-LG AS [55,56] . Recent results are promising and suggest that TAVI is not a
futile procedure in patients with CA, but further confirmation in larger cohorts is needed. Future research is
required to identify the best candidates.

Ventricular arrhythmias and usefulness of ICD therapy
Non-sustained ventricular tachycardia (VT) can be found in 27% of patients during routine monitoring ,
[61]
[62]
but this percentage increases up to 74% in patients with implanted devices and 100% of AL-CA patients
during stem cell transplant period . The clinical significance and prognostic implications of ventricular
[63]
arrhythmias in CA are yet to be determined, but recent studies suggest an association with increased
mortality [62,64,65] . Therefore, a history of non-sustained VT has been proposed as a useful finding when
[62]
considering CA patients for ICD implantation .
The latest European Society of Cardiology (ESC) and American Heart Association guidelines
[67]
[66]
acknowledge the absence of sufficient evidence for formal recommendation regarding ICD implantation in
primary prevention of SCD and support patient-tailored decision-making in CA. The 2015 ESC guidelines
recommend (Class IIa, level of evidence C) considering ICD implantation for secondary prevention in AL
or hereditary ATTR-CA with “ventricular arrhythmias causing hemodynamic instability who are expected
to survive > 1 year with good functional status” . Although secondary prevention is a strong indication for
[66]
ICD implantation in patients with HF , the role of prophylactic ICD in CA remains controversial.
[68]
Available data from retrospective small cohorts report a high incidence of appropriate ICD discharge,
predominantly in AL-CA patients implanted for secondary prevention [62,69,70] . Based on a retrospective
analysis of data from 31 patients with AL and ATTR-CA, Varr et al. from the Stanford Amyloid Center
[62]
proposed considering ICD implantation for primary prevention in patients with NYHA < IV, life
expectancy > 1 year, and history of exertional syncope or documentation of VT (either non-sustained or
sustained) on ambulatory Holter monitoring. However, studies to date failed to demonstrate a survival