Background Apical sparing by longitudinal strain imaging has reported utility for the diagnosis of cardiac amyloidosis. However, potential differences in the apical sparing pattern in light chain (AL) versus transthyretin (ATTR) amyloidosis in patients with high clinical suspicion for cardiac amyloidosis is not clear. Purpose Our objective was to test the hypothesis that echocardiographic strain imaging could determine differences in patients with clinically suspected AL and ATTR cardiac amyloidosis. Methods We studied 206 patients, aged 64±11, with clinically suspected cardiac amyloidosis. Routine longitudinal strain imaging analyses was performed (EchoPAC, GE Healthcare) with bulls-eye plots. After 27 exclusions (8 arrhythmia/frame rate, 19 missing/poor images), there were 179 patients. Included were 129 patients with cardiac amyloid: 42 by endomyocardial biopsy, 4 by technetium pyrophosphate scan, 65 by non-cardiac biopsy with suggestive cardiac imaging (interventricular septal thickness ≥1.2cm by echocardiography or characteristic cardiac MRI findings), 15 with multiple myeloma and suggestive cardiac imaging, and 3 by autopsy; 50 patients had a negative endomyocardial biopsy or autopsy for cardiac amyloid. The apical sparing ratio by strain imaging was calculated as the (average of apical segments) / (average of mid segments + average of basal segments). Results Cardiac amyloidosis patients were 79% with AL and 21% with ATTR. Applying the previously published apical sparing ratio cut-off of 1.0 for longitudinal strain imaging, sensitivity and specificity were 29% and 78%, respectively, for diagnosis of cardiac amyloidosis. Applying a ratio cut-off of 0.81 improved sensitivity to 72% with specificity of 64% and area under the curve (AUC) of 0.66. Positive and negative predictive values were 85% and 46%, respectively, at this ratio cut-off. The apical sparing ratio was significantly higher in AL and ATTR as compared to the biopsy negative group (p<0.001). Furthermore, the apical sparing ratio was significantly higher in ATTR as compared to AL (p<0.05). Apical sparing pattern and ratio Conclusions Among patients with high clinical suspicion for cardiac amyloidosis, the apical sparing ratio by echocardiographic strain imaging can demonstrate differences for AL and ATTR cardiac amyloidosis and has potential for clinical utility.

Background With the advent of multiple novel therapeutics for light chain (AL) and transthyretin (ATTR) amyloidosis, there is a critical need for validated prognostic markers in cardiac amyloidosis. A discriminatory serum biomarker may improve prognostic and staging systems in AL and ATTR cardiac amyloidosis. Purpose Our objective was to test the hypothesis that hepatocyte growth factor (HGF) is associated with clinical outcomes in patients with AL and ATTR cardiac amyloidosis. Methods 102 patients with AL or ATTR and suspected cardiac involvement were prospectively enrolled. HGF, NT-proBNP, troponin-T, and eGFR were measured upon study enrollment. Cardiac involvement was established by 1) endomyocardial biopsy, or 2) non-cardiac biopsy with concentric hypertrophy on echocardiography, low voltage or pseudo-infarction on ECG, elevated NT-proBNP or troponin-T, or characteristic delayed myocardial enhancement on cardiac MRI. Patients were followed for the occurrence of all-cause mortality, cardiac transplantation, and left-ventricular assist device implantation. Results Of the total amyloidosis cohort, 72 had cardiac involvement while 30 had non-cardiac disease. HGF, NT-proBNP, and troponin-T levels were significantly higher in patients with cardiac involvement than in patients with non-cardiac disease (p<0.05 for all comparisons). Over a median follow-up period of 1.9 years there were 20 deaths, 1 cardiac transplant, and 1 left-ventricular assist device implant, all in patients with cardiac involvement. Patient stratification by cut-off levels of NT-proBNP (332 pg/mL), troponin-T (35 ng/L), and eGFR (45 mL/min/1.73m2) used in published staging models for AL and ATTR cardiac amyloidosis showed no association between abnormal biomarker level and adverse clinical outcome (p>0.05). In contrast, stratification by HGF level of 310 pg/mL (identified by the Youden Index for cardiac involvement by AL and ATTR in our cohort) showed that elevated HGF was associated with worse clinical outcomes (p=0.0211). Furthermore, event-free survival was worse in patients with elevated HGF, with survival curves diverging soon after enrollment (p=0.0730). HGF is Prognostic in Cardiac Amyloidosis Conclusions Elevated HGF is associated with worse clinical outcomes in patients with AL and ATTR cardiac amyloidosis and has potential for clinical utility.

No abstract