Echocardiographic Phenotypic Differences between Light Chain and Transthyretin Cardiac Amyloid and Relation to Outcome.

Background and aims: Light chain cardiac amyloidosis (AL-CA), wild-type-transthyretin cardiac amyloidosis (ATTRwt-CA) and hereditary type-transthyretin cardiac amyloidosis (ATTRv-CA) have distinct presentations, clinical courses, and prognosis. To identify differentiating echocardiographic features and their prognostic significance, we investigated a large cohort of patients with CA.

Methods: In this multi-site cohort study, CA diagnosis was verified according to guidelines. Echocardiographic and clinical variables at the time of diagnosis were retrospectively compared. Previously validated staging for prognosis was applied and Cox regression was utilized to identify additional echocardiographic variables independently associated with mortality.

Results: Of 1968 CA patients, age 67.5 ± 11.4 years, 1456 (74%) male, 1128 (57.3%) had AL-CA, 624 (31.7%) had ATTRwt-CA, and 216 (11.0%) had ATTRv-CA. Patients with ATTRwt-CA were older, more often male, and had more comorbidities. Patients with ATTR-CA had greater left ventricular mass index and lower ejection fraction compared to AL-CA. Patients with ATTRwt-CA had larger left atrial volume index, and higher proportion of aortic stenosis compared to other types. During median follow up of 24 months, 953 patients died. During the first 3 years, patients with AL-CA had the highest mortality. Age and stroke volume index (SVi) were independently associated with mortality in both AL-CA and ATTR-CA; sex and right ventricular s' were also independently associated with mortality for AL-CA. Adding SVi to the staging prognostic model improved the C-statistic by 0.03 (95% confidence interval [CI]: 0.01- 0.04) and 0.04 (95% CI: 0.02-0.05) for ATTR-CA and AL-CA, respectively.

Conclusions: Among types of CA, distinct echocardiographic features were present at the time of diagnosis. SVi was independently associated with mortality and had incremental discriminatory power for mortality when added to staging.