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Page 8 of 11 Pica et al. Vessel Plus 2022;6:10 https://dx.doi.org/10.20517/2574-1209.2021.81

Similarly, in ATTR, ECV and native T1 predicted mortality at 2.5 years. However, ECV showed stronger
correlations with systolic and diastolic function and ECV ≥ 0.59 was associated with prognosis after
adjustment for known independent predictors, including DPD grade and LGE, whereas myocardial T1 was
[25]
not . Finally, ECV demonstrated higher hazard ratio for adverse events compared with LGE and native T1
in a metanalysis, suggesting this metric as a robust prognostic marker .
[33]
The higher prognostic ability of ECV compared with LGE likely springs from its better discriminatory
power, being able to measure the continuum of infiltration rather than a binary categorization.
Furthermore, as compared with native T1, ECV likely reflects a purer quantifier of amyloid burden, not
being influenced by intracellular content.

T2 mapping techniques were also demonstrated to be helpful in prognostication; myocardial T2 > 55 ms
emerged as an independent prognostic factor after adjustment for ECV and NT-pro-BNP in AL patients,
but not in ATTR patients . This is possibly because of the additional toxic effect of light chains, which
[37]
could contribute to cell death, inducing myocardial edema . Prospective follow-up studies assessing
[3]
changes during therapy are needed to verify the hypothesis. Table 1 shows the current role of CMR
parameters for diagnosis, prognosis, and pathophysiological assessment in cardiac amyloidosis.

Future perspectives
The evolving field of CMR techniques pointed out some new insights into pathophysiology of CA.
Myocardial perfusion defects have been observed in CA, with different factors potentially contributing to
hypoperfusion and cell damage (physical presence of amyloid deposits, infiltration of vessels and
perivascular regions, and myocyte hypertrophy) [49,50] . Preliminary data using adenosine stress with
myocardial blood flow (MBF) assessed by CMR perfusion mapping show severe reduction in stress MBF in
CA, similar to patients with three-vessel coronary artery disease. The reduction correlates with the degree of
amyloid infiltration and markers of adverse prognosis, being significant also in early disease . Myocardial
[50]
perfusion reserve impairment was also shown by stress N-13 ammonia positron emission tomography in
both AL and ATTR, with coronary microvascular function inversely correlating to increased LV mass,
diastolic filling pressures, and subclinical systolic dysfunction by longitudinal strain .Over the last decade,
[49]
chemotherapy regimens for AL have improved, and several patients can now achieve large reductions in
[51]
circulating light chains . Multiple agents have been approved or are in late-phase trials for ATTR
[52]
amyloidosis, as well . NT-pro-BNP and echocardiography (more recently speckle tracking strain) are
commonly used for assessing cardiac response to therapy, but they represent processes downstream of
amyloid deposition. In contrast, ECV measurement by CMR has the potential to track structural changes
(amyloid burden and cardiomyocyte response). Preliminary studies in AL showed that the decrease in ECV
(and, to a lesser extent, LV mass and LGE) was higher in patients with complete or very good partial
hematological response. Of note, a proportion of patients with good hematological response did not show
[53]
ECV reduction .
Remarkable recent therapeutic developments in treating ATTR amyloidosis have been associated with
improved outcome in patients with ATTR cardiomyopathy and polyneuropathy. Convincing evidence of
[54]
cardiac response by echocardiography has not been demonstrated in patients treated with tafamidis ,
whereas, with patisiran, only a marginal improvement was observed . Instead, data on serial CMR
[55]
examinations with ECV suggest that regression of amyloid burden can occur in a proportion of patients
treated with patisiran and diflunisal . Although there was an average reduction of 6% in ECV compared to
[56]
controls, individual responses varied substantially, highlighting the importance of an individual assessment
of myocardial changes.