Background: Trastuzumab and trastuzumab emtansine are specific antibody and antibody–drug conjugates used in the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. The aim of this study was to test their effect on the QTc interval duration and left ventricular ejection fraction (LVEF) in our patients, two parameters used in evaluation of cardiotoxicity. From May 2015 to October 2017, 26 patients with preserved LVEF were included in the study. All of them were previously treated with standard paclitaxel and cisplatin-based chemotherapy regimens. Electrocardiogram (ECG) was recorded just before each trastuzumab dose application and six months after the last dose. Echocardiography with LVEF measurement was performed several days before the application of the initial dose, and six months after the last cycle. Later, 24 patients with metastatic disease received additional treatment with trastuzumab emtansine after six months and the same ECG and echocardiography protocol was performed again. Due to reduction in LVEF, two patients were discontinued from additional treatment. Results: A statistically significant QTc prolongation was found after each drug dose application, with an increase in mean QTc duration with every successive application, reaching the peak QTc values just before the fifth cycle of treatment. The QTc interval returned to its initial value six months after the last cycle (p < 0.001). These results were similar for both drugs. Mean LVEF before both treatment protocols was significantly higher compared to LVEF value after the treatment. LVEF before trastuzumab emtansine treatment was non-significantly higher than LVEF after trastuzumab treatment. Conclusion: Trastuzumab and trastuzumab emtansine cardiotoxicity manifested as a significant and progressive QTc prolongation after successive drug applications, reaching the peak value just before the fifth cycle of both drugs. Both medications also caused statistically significant but asymptomatic LVEF reduction. Complete reversibility of cardiotoxic effects of both drugs was confirmed by QTc interval and LVEF normalisation after the treatment discontinuation.

Background: Syncope, as the most frequent consciousness disorder, is very common in young individuals. The aim of this study was to analyze ECG parameters and clinical properties obtained during tilt-up testing in 12 to 30-year-old subjects. We enrolled a total of 142 patients from our outpatient clinic (39 males, 103 females) with a true positive tilt-up test and analyzed ECG records obtained during tilt-testing. Data were stratified according to the age, gender, and type of syncope. Results: PR interval shortening preceding syncope was found in all syncope types, irrespective of the gender. All types of syncope were more frequent in women (72.5%). Mixed syncope type was found to be the most common (47.18%). Male and female subjects differed in initial heart rate (71.56 vs 76.23/min, p=0.05), as well as heart rate dynamics during tilt-up testing. A gender difference was also found in systolic blood pressure (116.92 vs 110.44 mmHg, p<0.01), time to syncope onset (20.77 vs. 16.44 min, p=0.03), and the total number of syncopal episodes in patient history (2.79 vs. 4.62, p<0.05). Subjects with cardioinhibitory syncope had the longest PR interval (average 154.3 ms). PR interval prolongation and loss of variability during tilt-up testing positively correlated with aging (r=0.22, p<0.05). Nodal rhythm was found in 8 patients. Conclusion: PR interval shortening on ECG tracings during a tilt-up test can be found in all subtypes of vasovagal syncope, thereby contrasting previous reports that these changes are a hallmark of the cardioinhibitory type of syncope. PR shortening, if observed during ECG monitoring, could be a potential predictor of syncope.

Introduction: Cardiomyopathies (DCM, HCM, and ACM) and primary arrhythmogenic disorders (BrS, LQTS, and CPVT) represent the most common causes of sudden cardiac death (SCD) in young individuals. Systematic genome-wide single-nucleotide polymorphism (SNP) analyses and genome-wide association studies (GWASs) have enabled the identification of numerous genetic variants associated with cardiovascular diseases. Body: Genetic testing for cardiomyopathies and inherited channelopathies primarily involves panel testing of genes with definitive and strong evidence of disease association; genes supported by moderate evidence may also be considered. Cardiomyocytes express a variety of proteins implicated in the pathogenesis of genetic cardiomyopathies, including sarcomeric, cytoskeletal, desmosomal, and nuclear envelope proteins. Inherited cardiac channelopathies result from mutations in genes encoding cellular components that influence calcium ion availability or affect membrane ion channels, including sodium, potassium, and calcium channels. Common variants associated with SCD are found in genes encoding cardiac ion channels (e.g., SCN5A, KCNQ1, and KCNH2), calmodulin (CALM2), sarcomeric proteins (MYH7, MYBPC3, TTN, and TNNI3), and desmosomal proteins (RyR2 and DES). Conclusions: This review demonstrates that specific genetic variants are significantly associated with an increased risk of SCD. The evidence underscores the importance of genetic screening and early intervention in individuals with a family history of SCD or other risk factors for inherited cardiac disorders predisposing to SCD. Future research should focus on gene-specific management strategies for familial cardiomyopathies and inherited channelopathies, with the goal of improving targeted genetic therapies and reducing the burden of sudden cardiac death.

Introduction: Cardiomyopathies (DCM, HCM and ACM) and primary arrhythmogenic disorders (BrS, LQTS and CPVT) are the most common causes of sudden cardiac death (SCD) in young people. Systematic investigations of genome wide SNP, GWAS have enabled the identification of many genetic variants associated with cardiovascular diseases. Body: Genetic testing for cardiomyopathies and inherited channelopathies primarily includes panel testing for genes with definitive and strong evidence, and genes with moderate evidence can be considered. Cardiomyocyte exhibiting proteins, involved in the pathogenesis of the genetic cardiomyopathies, include sarcomeric, cytoskeletal, desmosomal and nuclear envelope proteins. Inherited cardiac channelopathies are caused by mutations in genes encoding cellular structures that affect calcium ion availability or membrane ion channels (sodium, potassium or calcium channels). Common variants associated with SCD included those in genes encoding cardiac ion channels (e.g., SCN5A, KCNQ1, KCNH2), calmodulin (CALM2), sarcomeric proteins (MYH7, MYBPC3, TNN, TNNI3), and desmosomal proteins (RyR2, DES).Conclusions: This review provides evidence that specific genetic variants are associated with an increased risk of SCD. The data emphasizes the importance of genetic screening and early intervention in individuals with a family history of SCD or risk factors for inherited cardiac conditions causing SCD. Gene-specific management of familial cardiomyopathies and inherited cardiac channelopathies causing SCD should be emphasized for further research with the improvement of targeted genetic disorders treatment.