We aimed to evaluate the cardiac effects of the ADT and subsequent hypogonadism in patients with advanced prostate cancer by analyzing speckle-tracking derived parameters of left ventricular function in relation to repolarization and myocardial injury markers changes.
We conducted a longitudinal observational analytical study and included consecutive patients with the diagnosis of advanced prostate cancer treated with ADT, in accordance with the urological and oncological recommendations. The study protocol has been approved by the local ethics committee and was conducted according to the ethical principles stated in the Declaration of Helsinki. All patients were informed about the aim of the study and signed the written informed consent before inclusion.
The patients were screened 5-7 days before beginning ADT and included if they were in sinus rhythm, had optimal echocardiographic windows and no cardiac diseases or at most stable coronary disease, treated arterial hypertension, myocardial infarction more than 6 months prior to screening, NYHA class I-II heart failure, LVEF ≥45%, estimated glomerular filtration rate >30 mL/min/1.73 m2, diabetes mellitus with glycosylated hemoglobin ≤7.5%, normal serum potassium, magnesium and calcium levels.
Exclusion criteria were unstable angina, recent myocardial infarction, NYHA class III-IV heart failure, LVEF < 45%, sustained ventricular tachycardia, persistent or permanent atrial fibrillation, complete bundle branch block, diabetes mellitus with glycosylated hemoglobin > 7.5%, grade 4-5 chronic kidney disease, electrolyte disturbances, chronic use of drugs known to prolong QTc, life expectancy less than 6 months, poor echocardiographic window.
No patient received drugs that prolong QT interval during the 6 months follow-up period.
All patients had blood samples, clinical, echocardiographic and electrocardiogram examinations at screening (M0) and after 6 months of treatment (M1).
From the blood samples high sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-brain natriuretic peptide (NTproBNP) and testosterone were analysed.
Complete echocardiographic examinations were performed using a Philips iE33 system, respecting the guidelines for image acquisitions [12-14]. LVEF was measured by biplane method of disks. By tissue Doppler imaging, using the apical four-chamber view, septal and lateral early diastolic (e’) and late diastolic (a’) mitral annular velocities were measured, then averaged, and E/e’ ratio was calculated. Speckle tracking imaging with the Philips Q-Lab software was used for the assessment of global longitudinal left ventricular systolic strain (GLS) and global circumferential left ventricular systolic strain (GCS), after manually optimizing the adequacy of tracking. An acquisition was considered uninterpretable if the endocardial border was not clearly defined and the recordings needed to be rejected in more than two myocardial segments. This was an eligibility criterion, thus was checked before M0, and only patients with interpretable speckle-tracking acquisitions were included in the study. A GLS value under -16% and a fall by more than 15% from the baseline value were considered abnormal [10,15].
Mechanical dispersion was assessed using standard deviation of time intervals from the start of Q/R on ECG to peak myocardial longitudinal strain in the 16 segment left ventricular model (MDSD) and the difference between the longest and shortest time to peak strain intervals (MDdelta) (Fig. 1). Both MDSD and MDdelta values were corrected for heart rate using Fridericia formula [16-18].
All the measurements were performed by a single experienced member of the team, blinded to the patients’ data.
The following ECG parameters were measured: QT interval, between the onset of the QRS complex and the end of the T-wave measured in all leads; Tpeak-Tend wave interval (Tpe) between T wave peak and T wave end in the precordial leads; Tpe/QT ratio; Tpe dispersion (Tped) as the difference between the highest and lowest value of Tpe intervals. The end of the T wave was measured by the method of the tangent to the steepest slope of the descending portion of the T wave (Fig. 1). Maximum Tpe value (maxTpe) and mean Tpe value (meanTpe) were taken into account during the data analysis. QT, Tpe and Tped were corrected for heart rate using Fridericia formula (QTc = QT/RR1/3). Leads were considered uninterpretable if the T-wave amplitude was lower than 0.1 mV or if biphasic T-waves were present. The measurements were performed on a stable RR interval, with a heart rate between 50 and 90 beats/min [14,15].
For each patient, we compared the variations of laboratory, echocardiographic and ECG parameters between visits.
Data are presented as means ± standard deviation for numerical variables and as absolute numbers and percentages for categorical variables. Normality was checked using Shapiro-Wilk test. For numerical variables, parametric (two-tailed Student's t-test for dependent samples or for groups) or non-parametric (Mann-Withney) tests were used, according to the distribution of data. Linear regression and Pearson correlation coefficient or Spearman correlation coefficient were used to examine correlation between different numerical variables, according to their distribution. For comparison of categorical data proportions Chi-squared and Fischer’s exact tests were used. The statistical analysis and the graphic representations of data were performed using STATISTICA version 8. A p value <0.05 was considered statistically significant.