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Page 4 of 10                 Licordari et al. Vessel Plus 2022;6:12  https://dx.doi.org/10.20517/2574-1209.2021.86

               Readers evaluated the eventual presence of cardiac radiotracer accumulation as positive when a
               semiquantitative score of 2 or 3 was found.

               Follow-up
               Patient outcome was evaluated from the day of the first visit to the day of the last medical contact (periodic
               ambulatory work up in our institute or telephone contact). The major events considered were cardiac death
               and appropriate implantable cardiac defibrillator (ICD) shock. The cause of death was derived from medical
               records or death certificates. The definition of cardiac death required the documentation of significant
               arrhythmia or cardiac arrest or death attributable to congestive heart failure. In the case of out-of-hospital
               death not followed by autopsy, sudden unexpected death was classified as cardiac death. Implantable cardiac
               defibrillator shocks were designated appropriate if triggered by lethal arrhythmias: ventricular tachycardia
               above the programmed cut-off of the ICD (12 intervals at 180 b.p.m.) or ventricular fibrillation. A complete
               interrogation of the ICD was performed by the referring physician to confirm the appropriateness of the
                    [13]
               shock .
               All cardiovascular events were assessed by two independent cardiologists, who were blinded to clinical and
               echocardiographic patients’ data.


               Statistical analysis
               Continuous variables were expressed as mean + SD or median (25th; 75th percentiles). Categorical variables
               were expressed as a percentage. The comparison between continuous variables in patients with and without
               cardiac events was performed by Student’s independent t-test or the Wilcoxon test as appropriate. A Cox
               regression analysis was performed for the identification of predictors of cardiovascular mortality-free
               survival. Receiver operating characteristic (ROC) curves were performed to find the best cut-off by
               sensitivity and specificity for variables. The Kaplan-Meier curves were processed, with the log-rank test for
               the comparison of survival curves. P-value ≤ 0.05 was considered significant. Statistical analysis was
               performed using dedicated software (IBM SPSS Statistics, v 26.0, Chicago, Illinois).

               RESULTS
               In total, 119 patients were identified; 20 patients were excluded according to the presence of previous heart
               diseases (previous myocardial infarction in 1 patient and moderate-severe aortic stenoses in 5 patients) and
               NYHA ≥ III (14 patients). Therefore, our population consists of 99 patients with TTRv (45 Glu89Gln, 40
               Phe64Leu, and 14 Thr49Ala) in NYHA functional class I or II and had no clinical history of previous
               cardiac disease.

               In all 99 patients,  Tc-DPD whole-body scan was performed and radiotracer accumulation (Perugini
                               99m
               score) showing CA was found in 46 subjects (19 female) [Figure 1].


               Echocardiographic findings: LV dimensions and function
               The CA group showed higher values of interventricular septal (IVS) thickness, LV posterior wall thickness,
               and E/E’ than the control group. LVEF was significantly lower, but still within the normal range, in the CA
               group than the no-CA group [Table 1].


               GLS, MBLS, and RRSR of the LV were higher in the CA group than the control group, while ALS was
               similar in the CA group and the control [Table 1].
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