Background and Objectives: Cancer therapy containing anthracyclines is associated with cancer-treatment-related cardiac dysfunction and heart failure (HF). Conventional cardioprotective medications can be frequently complicated by their blood-pressure-lowering effect. Recently, elevated resting heart rate was shown to independently predict mortality in patients with cancer. As a heart rate-lowering drug without affecting blood pressure, ivabradine could present an alternative management of anthracyclines-induced cardiotoxicity. Materials and Methods: This study aimed to investigate the probable protective effects of ivabradine in cancer patients with elevated heart rate (>75 beats per minute) undergoing anthracycline chemotherapy. Patients referred by oncologists for baseline cardiovascular risk stratification before anthracycline chemotherapy who met the inclusion criteria and had no exclusion criteria were randomly assigned to one of two strategies: ivabradine 5 mg twice a day (intervention group) or controls. Electrocardiogram, transthoracic echocardiogram with global longitudinal strain (GLS), troponin I (Tn I), and N-terminal natriuretic pro-peptide (NT-proBNP) were performed at baseline, after two and four cycles of chemotherapy and at six months of follow-up. The primary endpoint was the prevention of a >15% reduction in GLS. Secondary endpoints were effects of ivabradine on Tn I, NT-proBNP, left ventricular (LV) systolic and diastolic dysfunction, right ventricle dysfunction, and myocardial work indices. Results: A total of 48 patients were enrolled in the study; 21 were randomly assigned to the ivabradine group and 27 to the control group. Reduced GLS was detected 2.9 times less often in patients receiving ivabradine than in the control group, but this change was non-significant (OR [95% CI] = 2.9 [0.544, 16.274], p = 0.208). The incidence of troponin I elevation was four times higher in the control group (OR [95% CI] = 4.0 [1.136, 14.085], p = 0.031). There was no significant change in NT-proBNP between groups, but the increase in NT-proBNP was almost 12% higher in the control group (OR [95% CI] = 1.117 [0.347, 3.594], p = 0.853). LV diastolic dysfunction was found 2.7 times more frequently in the controls (OR [95% CI] = 2.71 [0.49, 15.10], p = 0.254). Patients in the ivabradine group were less likely to be diagnosed with mild asymptomatic CTRCD during the study (p = 0.045). No differences in right ventricle function were noted. A significant difference was found between the groups in global constructive work and global work index at six months in favour of the ivabradine group (p = 0.014 and p = 0.025). Ivabradine had no adverse effects on intracardiac conduction, ventricular repolarization, or blood pressure. However, visual side effects (phosphenes) were reported in 14.3% of patients. Conclusions: Ivabradine is a safe, well-tolerated drug that has shown possible cardioprotective properties reducing the incidence of mild asymptomatic cancer-therapy-induced cardiac dysfunction, characterised by a new rise in troponin concentrations and diminished myocardial performance in anthracycline-treated women with breast cancer and increased heart rate. However, more extensive multicentre trials are needed to provide more robust evidence.

Background: Iron deficiency (ID) and anemia are common in both heart failure (HF) and cancer patients and are associated with poor quality of life and survival. The aims of this study were (1) to evaluate the prevalence, types, and confounding factors of ID and anemia in patients referred to cardio-oncology clinic, and (2) identify the association between iron metabolism parameters and survival of cardio-oncology patients. Methods: We assessed iron, ferritin, hemoglobin concentrations, transferrin saturation (TSAT), cancer type, brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), kidney function, cardiovascular risk factors and survival in 599 patients who were referred to cardio-oncology clinic from 2011 to 2017. ID was defined by a TSAT < 20%, absolute iron deficiency (AID) with a serum ferritin level < 100 μg/L while serum ferritin level of ≥ 100 μg/L was considered as functional iron deficiency (FID) and TSAT ≥ 20% was considered as no ID. Results: The prevalence of ID, AID, and FID was 46, 31, and 15% of study patients, respectively. Anemia was present in approximately half (54%) of the patients with any ID. Multivariate Cox analyses showed that male gender (HR 1.704 [1.207–2.404] p = 0.002); previous cancer history (HR 1.879 [1.079–3.272] p = 0.026); elevated BNP (HR 2.126 [1.258–3.590] p = 0.005); TSAT< 20% (HR 1.721 [1.214–2.439] p = 0.002); ferritin ≥ 100 μg/L (HR 2.008 [1.088–3.706] p = 0.026); serum iron concentration < 12 μmol/L (HR 2.292 [1.614–3.255] p < 0.001); FID (HR 2.538 [1.1618–3.981] p < 0.001) and anemia (HR 2.462 [1.734–3.495] p < 0.001) were significantly associated with increased risk of all-cause death. Conclusions: About half of cardio-oncology patients had anemia and iron deficiency, with the absolute type being twice as prevalent as the functional one. Patients with breast, gastrointestinal, and genitourinary cancer were affected more often. Both anemia and iron deficiency independently predicted all-cause mortality. Future studies are required to confirm ID as a risk factor and evaluate the clinical benefits of iron replacement therapy.

Background. Iron deficiency (ID) and anemia are common in both heart failure (HF) and cancer patients and are associated with poor quality of life and survival. The aims of this study were (1) to evaluate the prevalence, types, and confounding factors of ID and anemia in patients referred to cardio-oncology clinic, and (2) identify the association between iron metabolism parameters and survival of cardio-oncology patients.Methods. We assessed iron, ferritin, hemoglobin concentrations, transferrin saturation (TSAT), cancer type, brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), kidney function, cardiovascular risk factors and survival in 599 patients who were referred to cardio-oncology clinic from 2011 to 2017.ID was defined by a TSAT < 20%, absolute iron deficiency (AID) with a serum ferritin level <100 μg/L while serum ferritin level of ≥100 µg/L was considered as functional iron deficiency (FID) and TSAT ≥20% was considered as no ID.Results. The prevalence of ID, AID, and FID was 46%, 31%, and 15% of study patients, respectively. Anemia was present in approximately half (54%) of the patients with any ID.Multivariate Cox analyses showed that male gender (HR 1.704 [1.207–2.404] p=0.002); previous cancer history (HR 1.879 [1.079–3.272] p=0.026); elevated BNP (HR 2.126 [1.258–3.590] p=0.005); TSAT<20% (HR 1.721 [1.214–2.439] p=0.002); ferritin c100 µg/L (HR 2.008 [1.088–3.706] p=0.026); serum iron concentration <12 µmol/L (HR 2.292 [1.614–3.255] p<0.001); FID (HR 2.538 [1.1618–3.981] p<0.001) and anemia (HR 2.462 [1.734–3.495] p<0.001) were significantly associated with increased risk of all-cause death.Conclusions. About half of cardio-oncology patients had anemia and iron deficiency, with the absolute type being twice as prevalent as the functional one. Patients with breast, gastrointestinal, and genitourinary cancer were affected more often. Both anemia and iron deficiency independently predicted all-cause mortality. Future studies are required to confirm ID as a risk factor and evaluate the clinical benefits of iron replacement therapy.

Study on implementing a cardio-oncology service, early diagnosis of cardiotoxicity, comorbidities and cardioprotective treatment