2.4. Study Procedures
Diastolic LV dysfunction, dyslipidaemia, abnormal: septal, cardiac dysfunction
ARTERIAL HYPERTENSION, WASTED, DYSLIPIDAEMIA
All study patients underwent an ECG, transthoracic echocardiogram (TTE), and routine laboratory analyses including cardiac-specific biomarkers (high-sensitivity cardiac Tn I and NT-proBNP) and a biochemistry panel [The following sequential ECG, TTE, Tn I, and NT-proBNP were performed after the second and the fourth cycle of anthracycline chemotherapy and at six months of follow-up.All TTEs were performed by a single experienced cardiologist using the same Vivid E95™ GE Healthcare system to estimate LVEF and volumes, LV diastolic function, GLS and global myocardial work (MW) parameters, valves’ assessment, and RV function. Simpson’s 2D and semi-automated 3D assessment of LVEF were performed. Diastolic LV dysfunction was identified when more than half of the variables listed below were abnormal: septal e’ < 7 cm/s, lateral e’ < 10 cm/s, average E/e’ ratio > 14, left atrium volume index (LAVI) > 34 mL/mMW parameters, which included global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were assessed by the 2D strain–pressure loop using software version 204 for offline data analysis in an Echo PAC GE Healthcare workstation. GWI < 1310 mmHg%, GCW < 1543 mmHg%, GWW > 287 mmHg%, and GWE < 90% were defined as abnormal [According to the laboratory parameters, Tn I > 99th percentile and NT-proBNP ≥ 125 pg/mL or a new significant (>20%) increase from the baseline were considered elevated. Troponin I concentrations were measured using Abbott Diagnostics (Germany) reagents on an Architect systems analyser: elevated Tn I concentration is >35 ng/L for men and >16 ng/L for women.Arterial hypertension was diagnosed in patients with high CV risk when blood pressure exceeded ≥ 130 mmHg systolic and/or ≥80 mmHg diastolic, and in other patients if blood pressure exceeded ≥ 140 mmHg systolic and/or ≥90 mmHg diastolic [Dyslipidaemia was diagnosed according to 2019 ESC guidelines for the management of dyslipidaemia [Mild asymptomatic cancer-therapy-related cardiac dysfunction (CTRCD) was defined according to the latest 2022 European Society of Cardiology (ESC) guidelines on cardio-oncology as LVEF > 50% and new relative decrease in GLS by >15% from the baseline and/or a new increase in cardiac biomarkers After randomization, ivabradine was initiated on the first day of chemotherapy.At each visit (except the screening visit), ivabradine consumption was monitored by counting the number of tablets consumed based on the patient’s returned packages. The independent research coordinator was responsible for recording the study drug intake. The recommended minimum amount of ivabradine consumed to ensure the reliability of the study data was more than 80% of the total dose, the maximum possible duration of ivabradine administration. 