## 3 Materials and Methods
### Experimental Dataset: cTnT Concentration Levels and Clinical Covariates  
The experimental dataset exploited in the present study consists of a retrospective historical collection of time-series measurements of cTnT levels in the plasma of STEMI patients, provided by the Interventional Cardiology Unit of the Magna Graecia University Hospital in Catanzaro, Italy. The dataset includes some clinical information and biomarker measurements of 27 consecutive patients aged between 18 and 85 years, presented with STEMI and treated with percutaneous coronary revascularization (PTCA). Each blood sample was analyzed using highly sensitive assays (hs-cTnT) with a cut-off value of 0.014 [ng/mL], calculated on a reference population. According to the general guidelines, the first acquisitions were performed every 6 hours from the time of admission for the first one/two days, and then every 24 h, [22]. As previously mentioned, the dataset shows a high temporal inhomogeneity, mainly due to the fact that the time of the onset of symptoms varies from patient to patient, causing a mismatch between the acquisitions [19].  
In addition, the experimental dataset contains several categories of clinical information, related to:  
1. Pre-hospital data: diabetes, dyslipidemia, smoke, obesity, familiarity with the disease (presence of cases of AMI in the family), and other cardiac pathologies;
2. Admission data: time from onset of symptoms, gender, age;
3. Post-hospitalization data: ejection fraction, thrombolysis, revascularization, biomarkers, anterior wall, and other information, along with data and time labels.  
These covariates can be continuous, e.g., age, ejection fraction, and hemoglobin, or categorical, e.g., gender, dysplasia, diabetes, and smoke. Since the goal of the work is to investigate the influence of the clinical covariates on the cTnT release, we chose to not include all those covariates which can be identified as consequences rather than possible causes of an AMI, such as ejection fraction, hemoglobin, and anterior wall. Given the limited number of patients, and based on the indication suggested in [37] for the evaluation of the thrombolysis in myocardial infarction (TIMI) risk score for STEMI (an important predictor of mortality after AMI), we proceeded with the reorganization of the patients into two main groups based on their age (years): younger than 65, and older than 65. Figure 3 shows the distribution of all the categorical and continuous covariates exploited in the study.  
Another crucial aspect to investigate is represented by the relationship between circadian rhythm and onset of AMI, which shows a peak of incidence of cases during the early morning, [38]. During this time interval, the oxygen demand increases with the vascular tone, while the coronary blood flow undergoes a decrease. This imbalance between supply and demand seems to have an impact on the onset of AMI symptoms, as reported in [39]. All the onset times can be grouped into four temporal bands over 24 h: (i) night (\(0\leq t_{i}<6\)), (ii) morning (\(6\leq t_{i}<12\)), (iii) afternoon (\(12\leq t_{i}<18\)), and (iv) evening (\(18\leq t_{i}<24\)). In our dataset, most patients present an indicative time of onset of symptoms at 00:00 (\(0\leq t_{AMI}<6\)), arbitrarily chosen by clinicians following the inability to provide an estimation of this time by the patients. Since considering the onset of symptoms would imply a further reduction in the dataset (patients with AMI time at 00:00 cannot be included in the analysis), it was not taken into account in the present study. Informed consent was obtained by all patients.