Immune checkpoint inhibitors (ICIs) represent a break-through treatment for a large number of cancer types. This treatment is increasingly being recommended. ICIs are prescribed for primary tumours and for metastases, adjuvant/neo-adjuvant therapy. Thus, there is an increased need for expertise in the field, including the ways of response and toxicities related to them. ICIs become toxic because of the removal of self-tolerance, which in turn induces autoimmune processes that affect every organ. However, when relating to the heart, it has been noticed to be leading to acute heart failure and even death caused by various mechanisms, such as: myocarditis, pericarditis, arrhythmia, and Takotsubo cardiomyopathy. This review aims to address the above issues by focusing on the latest findings on the topic, by adding some insights on the mechanism of action of ICIs with a special focus on the myocardial tissue, by providing information on clinical manifestations, diagnosis and (wherever possible) treatment of the cardiotoxic events related to this therapy. The information is expanding and in many cases, the articles we found refer mainly to case-presentations and studies conducted on small populations. However, we consider that it is worthwhile to raise awareness of this new treatment, especially since it is widely now and it provides a significant increase in the survival rate in patients who receive it.

Elevated cardiac troponin I (cTnI) levels are diagnostic for myocardial injury. Moreover, they are essential for risk stratification in patients with acute cardiac ischemia and heart failure. However, their usefulness is not limited to the previous clinical conditions. The aim of this study was to evaluate the clinical significance of cTnI levels in the emergency department.In 324 patients, out of the 4147 referred to the emergency department, serum levels of cTnI were evaluated and represented the study population. Subjects were divided into 2 groups: Group 1 (66 patients) with cTnI ≥ 0.04 ng/mL and Group 2 (258 patients) with cTnI level [ 0.04 ng/mL. The clinical characteristics, laboratory data, ECG findings, echocardiographic abnormalities and discharge diagnosis were compared between the two groups. Patients with cTnI ≥0.04 ng/mL had more often a history of ischemic heart disease, lower levels of oxygen saturation, higher levels of blood glucose, increased white blood cells count, higher heart rate and deeper ST-segment depressions on ECG. The most common discharge diagnosis was heart failure. Although an elevated level of cTnI is highly suggestive for myocardial injury, it should always be interpretated in the clinical context. Heart failure is an important diagnosis in patients with elevated cTnI levels.

Introduction Survival after chemotherapy in cancer patients can be affected by several factors, including cardiotoxicity. Identification of high-risk patients and early diagnosis of cardiotoxicity would allow preventive therapies that would mitigate its effect. Although troponin I (hsTnI) and NT-proBNP have shown their usefulness, there still is incomplete data regarding the time and frequency of their testing. Aims The goal of our study was to identify new diagnostic biomarkers for early diagnosis of cardiotoxicity and analyze their predictive value for outcome. Methods We included 68 female patients with breast cancer treated with trastuzumab, who underwent clinical, biological and echocardiographic evaluation and signed informed consent. We performed biomarker testing (NT-proBNP, hsTnI, Gal 3 and GDF-15) and echocardiography at inclusion and on the day of the first chemotherapy course (after trastuzumab was administered).The patients was follow for 1 years and cardiovascular events was noted. Results The study group included middle-aged women (34.5±8.4). Although changes in the biomarker levels after the first chemotherapy course were found, these were not statistically significant. The more interesting aspect is that we found some markers increased (NTproBNP 11.12±2.9 vs 16.25±3.17, p=0.12, hsTnI 147.75±32.88 vs 151.09±34.67, p=0.74,) while other decreased (Gal-3 2300.92±982.26 vs 2193.53±377.69, p=0.78, GDF-15- 1014.09±1689 vs 1006±1662, p=0.76). Echocardiography showed no significant differences in systolic performance parameters – ejection fraction (EF) and global longitudinal strain (GLS) – but a significant change in left ventricular end-diastolic filling pressure (LVEDP) estimated by the e/e' ratio (5.68±5.63 vs 10.05±4.42, p=0.000. The LVEDP increase was correlated to NTproBNp (r=0.712, p=0.000) and Gal3 (r=0.44, p=0.009) variability. Univariate analysis showed that only NTproBNP variability predicts 16.3% of the LVEDP variability between the two moments, but the NTproBNP and LVEDP could predict the cardiovascular events during the 1-year follow-up. Conclusion Changes in diastolic performance – e/e' ratio – occur early after chemotherapy and correlate with the variability of serum natriuretic peptides. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Partnership for the transfer of knowledge in biogenomics applications in oncology and related fields - BIOGENONCO, Project co-financed by FEDR through Competitiveness Operational Programme 2014–2020, contract no. 10/01.09.2016.

Background The association between endotelial dysfunction and progression of diastolic dysfunction suggests that endotelial and myocardial impairment might have similar pathogenic pathways. Moreover, in hypertensive diabetics the endotelial function is worse in those with impaired diastolic performance compared to normal diastolic performance. ST2 provides additional data to echocardiography in early detection of diastolic performance alteration in hypertension (HT) and is a prominent predictive marker of worse clinical outcome in hypertensive patients. There is scarce data on ST2 role in detection of early vascular involvement in hypertensive patients. Purpose The aim of the study is to evaluate whether ST2 levels correlate with impaired endotelial function in hypertensive patients. Methods Our prospective study included 84 hypertensive patients (mean age 52.9±14.4 yrs, 54.3% males and 45.7% females), after they signed an informed consent. All patients underwent clinical and laboratory (including ST2) evaluation. To investigate endothelial function, we performed ultrasound measurement of the brachial artery diameter both at rest and during reactive hyperemia in the muscle distal to the brachial artery (BA) which causes endothelium-dependent vasodilatation. The study methodology was approved by the Ethical Committee and statistical data processing was performed with SPSS. Results Patients were assigned to group A – those without left ventricular hypertrophy (LVH) and group B – those with LVH. There were no significant differences regarding gender, age and HT stage between groups A and B. Patients in group A had lower ST2 levels [18.83 (13.98 - 42.05) vs 55.63 (48.6 - 100.21) vs, p<0.001] and fewer risk factors (1.4 vs 2.6, p<0.01) compared to group B. We found significant differences regarding diastolic performance parameters between the groups. The relative increase in diameter (% FMD; DD = D 100) was significantly higher in group A than group B (6.67±0.43% vs 3.10±0.33%, p<0.01). ST2 levels were greater in group B and correlated with the degree of endotelial dysfunction evaluated by flow-mediated dilatation (FMD) (r=0.411, p<0.01). Multiple regression analysis showed that ST2 had a significant negative correlation with the relative increase in arterial diameter while multivariate Cox regression analysis showed ST2 was an independent predictor of endothelial dysfunction severity in hypertensive patients (hazard ratio: 4.012, 95% confidence interval: 1.207–31.24, P=0.031). Conclusions ST2 levels correlate with cardiovascular risk and are a significant predictive marker of endothelial dysfunction in hypertensive patients regardless of diastolic dysfunction.