Giuseppe Sena

BACKGROUND: The tenet of cardiac amyloidosis (CA) as a paradigm of heart failure with restrictive ventricular physiology and preserved systolic function has come under scrutiny. We aimed to evaluate the prevalence and clinical significance of left ventricular (LV) systolic dysfunction versus restriction in a large real-world cohort with CA, assessed at the time of diagnosis. METHODS: We retrospectively analyzed 540 TTR (transthyretin)-CA and 280 AL (light chain)-CA. Patients were divided into 3 LV phenotypes: (1) preserved LV function: LV ejection fraction >40% associated with grade I diastolic dysfunction; (2) restriction: LV ejection fraction >40% associated with grade II/III diastolic dysfunction; (3) systolic dysfunction: LV ejection fraction ≤40% irrespective of diastolic function. We analyzed the progression from preserved LV function towards the other 2 LV phenotypes and survival free from the composite end point of all-cause mortality and heart transplantation. RESULTS: In TTR-CA, the prevalence of preserved LV function was 32.0%, restriction was 56.1%, and systolic dysfunction was 11.9%. Among patients with preserved LV function, at the last evaluation, the conversion rate to restriction was 16.3% and to systolic dysfunction was 1.8%. The 3-year freedom from the composite end point was 75%, 61%, and 44%, respectively. In AL-CA, the prevalence of preserved LV function was 32.9%, restriction was 58.6%, and systolic dysfunction was 8.5%. Among patients with preserved LV function, at the last evaluation, the conversion rate to restriction was 12.9%, and to systolic dysfunction was none. The 3-year freedom from the composite end point was 46%, 32%, and 21%, respectively. CONCLUSIONS: Restriction was the most common presenting phenotype, while preserved LV function represented approximately one-third. The rate of progression from preserved LV function towards restriction was high, whereas it was limited towards systolic dysfunction. Although patients with preserved LV function presented the best event-free survival, considering all-cause mortality and heart transplantation, compared with restriction or systolic dysfunction, these phenotypes are not independent predictors of this composite end point.

BACKGROUND: Thresholds to define prognosis with hs-cTnI (high-sensitivity cardiac troponin I) have not been systematically addressed in wild-type transthyretin amyloid cardiomyopathy, in part because of the multiplicity of hs-cTnI assays. The aims of this study were: first, to assess the prognostic performance of hs-cTnI measured with different assays in patients with wild-type transthyretin amyloid cardiomyopathy and, second, to identify assay-specific hs-cTnI thresholds for prognosis that could be integrated into staging systems for risk stratification. METHODS: Observational multicenter study of stable wild-type transthyretin amyloid cardiomyopathy patients from different cohorts using the Abbott Architect Stat hs-cTnI assay and the Beckman Coulter Access hs-cTnI assay (testing cohorts) and the Siemens Centaur XPT hs-cTnI assay (validation cohort). Outcome was all-cause mortality. RESULTS: In the Abbott cohort (n=136; median follow-up 22 [13–41] months; 31 [23%] deaths) and Beckman cohort (n=98; median follow-up 19 [12–28] months; 16 [16%] deaths), natural log-transformed hs-cTnI was an independent predictor of mortality (age- and sex-adjusted hazard ratio, 1.62 [95% CI, 1.11–2.35]; P =0.012 and 2.47 [95% CI, 1.48–4.14]; P 80 ng/L) and NPs (natriuretic peptides; NT-proBNP [N-terminal pro-B-type natriuretic peptide] >3000 ng/L or BNP [B-type natriuretic peptide] >250 ng/L) identified 3 groups with progressively worse prognosis. The staging system (using hs-cTnI >80 ng/L and NT-proBNP>3000 ng/L) was then applied to an independent cohort evaluated with the hs-cTnI Siemens assay (n=345, median follow-up 32 [24-42] months, 119 [34%] deaths). The significant differences between the groups were maintained. CONCLUSIONS: In patients with wild-type transthyretin amyloid cardiomyopathy, hs-cTnI is a strong and independent predictor of mortality. A threshold of hs-cTnI of 80 ng/L for these 3 assays provides effective risk stratification alone and in a staging system with NP.