Perlini, Stefano

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 <0.001, respectively). The best hs-cTnI threshold for 18-month mortality of the combined Abbott/Beckman cohorts (n=234) was 81 ng/L, rounded to 80 ng/L for simplicity of clinical use. A 2-variable staging system (based on the Mayo Clinic system) using hs-cTnI (>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.

Background: Heart involvement is the most important prognostic determinant in AL amyloidosis patients. Echocardiography is a cornerstone for the diagnosis and provides important prognostic information. Methods and Results: We studied 754 patients with AL amyloidosis who underwent echocardiographic assessment at the Mayo Clinic, including a Doppler-derived measurement of stroke volume (SV) within 30 days of their diagnosis to explore the prognostic role of echocardiographic variables in the context of a well-established soluble cardiac biomarker staging system. Reproducibility of SV, myocardial contraction fraction, and left ventricular strain was assessed in a separate, yet comparable, study cohort of 150 patients from the Pavia Amyloidosis Center. The echocardiographic measures most predictive for overall survival were SV index <33 mL/min, myocardial contraction fraction <34%, and cardiac index <2.4 L/min/m 2 with respective hazard ratios (95% confidence intervals) of 2.95 (2.37–3.66), 2.36 (1.96–2.85), and 2.32 (1.91–2.80). For the subset that had left ventricular strain performed, the prognostic cut point was −14% (hazard ratios, 2.70; 95% confidence intervals, 1.84–3.96). Each parameter was independent of systolic blood pressure, Mayo staging system (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and troponin), and ejection fraction on multivariable analysis. Simple predictive models for survival, including biomarker staging along with SV index or left ventricular strain, were generated. Conclusions: SV index prognostic performance was similar to left ventricular strain in predicting survival in AL amyloidosis, independently of biomarker staging. Because SV index is routinely calculated and widely available, it could serve as the preferred echocardiographic measure to predict outcomes in AL amyloidosis patients.