Russian Society of Cardiology (RSC)With the participation: National Society of Myocardial Diseases and Heart Failure, Society of Heart Failure Specialists, Russian Scientific Medical Society of Internal MedicineEndorsed by the Research and Practical Council of the Ministry of Health of the Russian Federation (12.09.2024)

Russian Society of Cardiology, National Society of Preventive Cardiology

Russian Society of Cardiology (RSC) With the participation of the Eurasian Association of Therapists, the Russian Scientific Medical Society of Therapists (RNMOT), the Russian Society of Pathologists, the Russian Society of Radiologists and Radiologists (RSR) Approved by the Scientific and Practical Council of the Russian Ministry of Health (30.09.2022)

Aim To evaluate the effect of cardiac monitoring on overall survival of patients with chronic lymphoid leukosis (CLL) on targeted therapy with ibrutinib.Material and methods Survival of oncological patients depends not only on the efficacy of the antitumor therapy. Cardiovascular comorbidities and emerging cardiotoxicity of the antitumor treatment can considerably impair the quality and duration of patients’ life. The problem of the need for regular cardiological monitoring of oncological patients remains unsolved. A prospective 5-year study was performed that included cardiological monitoring of patients with CLL on chronic targeted therapy with ibrutinib, the side effects of which include atrial fibrillation (AF) and arterial hypertension (AH). The study included 217 patients aged 66.0 [32.0; 910.] years; 144 of them were men aged 66.0 [32.0; 91.0] years and 83 were women aged 65.0 [39.0; 83.0] years. Electrocardiography and echocardiography, evaluation of comorbidity with the Charlson’s index, and evaluation of frailty with the Geriatric 8 questionnaire and the Groningen Frailty Index were performed repeatedly for all patients. In the active cardiac monitoring group (n=89), besides the standard evaluation, active medical monitoring of symptoms and general well-being, blood pressure (BP) and pulse rate, monitoring of cardioprotective drug intake and correction, if necessary, and calling patients for examination and additional evaluation were performed every week. The remaining 128 patients were evaluated repeatedly but did not maintain the remote monitoring with messengers; they constituted a standard follow-up group.Results This was a study of overall survival of patients with CLL on targeted therapy with ibrutinib depending on the cardiac monitoring program. The age of patients did not differ in the active cardiac monitoring group and the standard follow-up group (66.0 [60.0; 70.0] and 66.0 [59.0; 74.0] years, respectively). The active cardiac monitoring group contained somewhat more men than the standard follow-up group (68.8 and 53.9 %, respectively; р=0.026). At baseline, the groups did not differ in the number of pretreatment lines, frailty test results (Geriatric 8 questionnaire, Groningen Frailty Index), comorbidity (Charlson’s index), and echocardiographic data. The active cardiac monitoring group contained more patients with AH (р<0.0001), with AF (р<0.0001), patients receiving anticoagulants (р<0.0001), and a comparable number of patients with ischemic heart disease. In the active cardiac monitoring group, 70 (90.9%) of 77 patients with CLL and AH achieved goal BP whereas in the standard follow-up group, 26 (39.9 %) of 66 (р<0.0001) patients achieved the BP goal, regardless of whether their elevated BP developed before or during the ibrutinib treatment. This group contained significantly more patients who required cardiac surgical intervention (coronary stenting, pacemaker implantation), 12 vs. 0 in the standard follow-up group (р=0.0004). The overall 5-year survival was significantly higher for patients of the active cardiac monitoring group, both for men (р<0.0001) and women (р<0.0001) with CLL, including patients older than 70 years (р=0.0004), CLL patients with a median pretreatment line number of 1 (р<0.0001), patients with a median chemotherapy line number of 4 (р<0.0001), and patients with genetic abnormalities (р=0.004) pretreated with fludarabine and/or anthracyclines (р<0.0001). The Cox regression analysis showed that the strongest predictor of survival was the achievement of stable goal BP in CLL patients with AH during the continuous cardiac monitoring. Despite more pronounced cardiac comorbidity, CLL patients on the active cardiac monitoring group showed a longer survival than patients on the standard follow-up. Thus, mean survival time of deceased CLL patients who had been on the cardiac monitoring was 36.1 months vs. 17.5 months (р<0.0001) for patients who had been on the standard follow-up.Conclusion The study has demonstrated the prognostic significance of continuous participation of a cardiologist in managing onco-hematological patients. CLL patients on the active cardiac monitoring, the regular pattern of which was provided by the remote control, had a significantly higher overall survival compared to patients who visited a cardiologist periodically. A significant predomination of patients with CLL and AH who achieved stable goal BP, continuous monitoring of anticoagulant dosing in patients with AF in that group, and early detection and correction of cardiovascular complications can explain the highly significant difference in the 5-year survival between CLL patients on chronic targeted ibrutinib treatment with different cardiac monitoring programs (р<0.0001). The active cardiac monitoring with remote control allows achievement of a higher 5-year overall survival of CLL patients receiving ibrutinib (p<0.0001).

Background: Survival of chronic lymphocytic leukemia (CLL) patients receiving ibrutinib (Ib) is influenced by many factors, among which cardiovascular disease, both in history and during treatment with Ib, is of great importance. Aims: To assess the impact on 5-year overall survival (5-OS) of patients CLL treated with Ib two options for dynamic monitoring by a cardiologist: standard cardiac monitoring (SC) and active cardiac monitoring with remote control (ACM). Methods: We observed in dynamics for 5 years’ period 217 patients with CLL, constantly receiving therapy with Ib 420 mg/day. In the ACM group (n=89), in addition to the standard examination, every week or more often using messengers, we did active medical monitoring of the patient’s symptoms and well-being, assessment of blood pressure and heart rate, control of cardioprotective medicines taken, correction of the therapy, calling patients for examination and additional examination. The remaining 128 patients were examined in dynamics, but did not support remote control, constituting the SC group. The age of patients in the ACM group and in the SC group did not differ and was 66.0 (60.0–70.0) years and 66.0 (59.0–74.0) years, respectively (p = 0,39). There were slightly more men in the SC group (68.8%) than in the active cardiac monitoring group (53.9%), p = 0.026. The proportion of patients with CLL with the number of pretreatment lines from 0 to 2 (median -1) in the ACM group was 52.7%, in the SC group it was 58.1%; with the number of lines from 3 to 12 (median - 4) in the AKM group - 47.3%, in the SC group - 41.9% (p = 0.53). The AKM and SC groups did not differ in the results of the Geriatric 8 scale, Charlson index, and echocardiography parameters at visit 1. In the ACM group, there were more patients with cardiac problems: with arterial hypertension (AH) (p < 0.0001) and atrial fibrillation (p < 0.0001), receiving anticoagulants (p < 0.0001), a comparable number of patients with coronary artery disease. Results: In the ACM group, 70 out of 77 (90.9%) patients with CLL and AH achieved a stable level of target blood pressure values, in contrast to the SC group - 26 out of 66 (39.9%), p < 0.0001. Significantly more events requiring cardiac surgery (stenting of the coronary arteries, installation of a pacemaker) were detected in the ACM group – 12, versus 0 in the SC group (p = 0.0004). In the ACM group, despite a more pronounced cardiac comorbidity, 5-OS was significantly better, than in the SC group in both men (p < 0.0001) and women (p < 0.0001) with CLL and in patients older than 70 years old (p = 0.0004). 5-OS was also better in the ACM group than in the SC group in patients with CLL with a median number of previous lines of therapy equal to 1 (p<0.0001) and in patients with a median number of chemotherapy lines equal to 4 (p<0.0001), in patients with genetic abnormalities (p=0.004) and pretreated with fludarabine and/or anthracyclines (p < 0.0001). Summary/Conclusion: Early detection and correction of cardiovascular complications/events, achievement of stable target blood pressure values, constant monitoring of cardioprotective treatment in the ACM group explain the statistically highly significant differences in 5-OS in patients with CLL who are on constant Ib therapy. Conducting active cardiomonitoring with remote control makes it possible to achieve higher rates of total 5-OS in patients with CLL receiving Ib.

Aim      To determine the effect of major electrocardiographic (ECG) parameters on the prognosis of patients with COVID-19.Material and methods  One of systemic manifestations of COVID-19 is heart injury. ECG is the most simple and available method for diagnosing the heart injury, which influences the therapeutic approach. This study included 174 hospitalized patients with COVID-19. Major ECG parameters recorded on admission and their changes before the discharge from the hospital or death of the patient, were analyzed, and the effect of each parameter on the in-hospital prognosis was determined. Results were compared with the left ventricular ejection fraction (LV EF), laboratory data, and results of multispiral computed tomography (MSCT) of the lungs.Results ECG data differed on admission and their changes differed for deceased and discharged patients. Of special interest was the effect of the QRS complex duration at baseline and at the end of treatment on the in-hospital survival and mortality rate. The Cox regression analysis showed that the QRS complex duration (relative risk (RR) 2.07, 95% confidence interval (CI): 1.17-3.66; р=0.01), MSCT data (RR, 1.54; 95 % CI: 1.14-2.092; р=0.005), and glomerular filtration rate (GFR) (RR, 0.98; 95 % CI: 0.96-0.99; р=0.001) had the highest predictive significance. In further comparison of these three indexes, the QRS duration and GFR retained their predictive significance, and a ROC analysis showed that the cut-off QRS complex duration was 125 ms (р=0.001). Patients who developed left bundle branch block (LBBB) in the course of disease also had an unfavorable prognosis compared to other intraventricular conduction disorders (р=0.038). The presence of LBBB was associated with reduced LV EF (р=0.0078). The presence of atrial fibrillation (AF) significantly predetermines a worse outcome both at the start (р=0.011) and at the end of observation (р=0.034). A higher mortality was observed for the group of deceased patients with ST segment deviations, ST elevation (р=0.0059) and ST depression (р=0.028).Conclusion      Thus, the QTc interval elongation, LBBB that developed during the treatment, AF, and increased QRS complex duration are the indicators that determine the in-hospital prognosis of patients with COVID-19. The strongest electrocardiographic predictor for an unfavorable prognosis was the QRS complex duration that allowed stratification of patients to groups of risk.

Abstract Background The overall survival of oncohematological patients (pts) depends not only on the severity of the cancer, the anticancer therapy used and the comorbidity of the pts. The most important role in the management of these pts is played by the supervision of a cardiologist. Purpose To assess the effect of active cardiac management on the overall survival of oncohematological pts on targeted therapy with ibrutinib. Methods We examined and observed in dynamics for 5 years 217 pts with chronic lymphocytic leukemia (CLL), constantly receiving ibrutinib, inducing arterial hypertension (AH) and atrial fibrillation (AF) in a part of the pts. All pts underwent echocardiography (Echo), 24-hour Holter ECG monitoring (HM), assessment of comorbidity using the Charlson index and screening of fragility using the G8 questionnaire. Everyday measurement of blood pressure, heart rate in the morning and in the evening with keeping a measurement diary was recommended for all pts, but 89 pts were performed, who constantly contacted us remotely using instant messengers and formed an active cardiac management (ACM) group. Results We studied the overall survival of pts with CLL receiving targeted therapy with ibrutinib, depending on cardiac monitoring, starting from the first visit. The age of pts in the ACM group (n=89) and in other pts (n=138) did not differ and amounted to 66.0 (60.0–70.0) years and 66.0 (59.0–74.0) years respectively. The number of men and women in the groups was comparable. In the ACM group, there were significantly more pts with AH - 86.5% and with AF - 42.7% compared to 50.4% with AH and 15.9% with AF in the rest of the pts (p<0.0001 in both cases) and a comparable number of pts with coronary artery disease. According to the screening HM, there were more pts with short AF episodes in the ACM group - 31.4% versus 8.0% in the rest of the pts (p<0.0001). Accordingly, the number of pts who received cardiological treatment in the ACM group was 87.6%, in the group of other pts - 53.6% (p<0.0001). Echo parameters did not differ in the groups. Indicators that significantly affect survival in the general group (Charlson index, scores of the G8 questionnaire) did not differ significantly in the ACM group and in other pts with CLL. The groups also did not differ in hematological status and the number of cases of second tumors. At the same time, despite a significantly more pronounced cardiac comorbidity, oncohematological pts under active cardiac monitoring, including continuous remote monitoring, demonstrated better survival compared to other pts (p<0.0001). Conclusions Conducting active cardiac management, including constant remote observation, allows achieving higher overall survival rates of hematological cancer patients, despite a more severe cardiac status compared to other pts under periodic supervision of a cardiologist. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): no founding sources

Russian Society of Cardiology (RSC)With the participation: Eurasian Association of Therapists (EUAT), Society of Specialists in Heart Failure (OSSN), Russian Scientific Medical Society of Therapists (RNMOT), Russian Society of Pathologists, Russian Society of Radiologists and Radiologists (RSR)Endorsed by: Research and Practical Council of the Ministry of Health of the Russian Federation

Introduction. Long-term use of anticoagulants (AC) for atrial fibrillation (AF) in patients (pts) with chronic lymphocytic leukemia (CLL) in the setting of ibrutinib-associated thrombocytopathy (Ib), thrombocytopenia and platelet variability is associated with a particular risk of hemorrhagic hemorrhage complications. Method. We have observed in dynamics for 5 years 217 pts with CLL constantly receiving Ib. AF occurred in 39 pts (19.9%) during treatment Ib, 21 pts had AF before Ib. 46 pts with CLL and AF received AC from 12 to 58 months, of which 19 women aged 70.0 (64.0-74.0) years and 27 men aged 67.5 (63.5-70.0) years. 20 pts receive apixaban (api), 20 rivaroxaban (riva), 6 dabigatran (dabi). We tracked all emerging hemorrhagic manifestations in pts with CLL, taking AC. During the period of use of AC, the influence of platelet level and variability on the occurrence of hemorrhages in these pts was evaluated. Results. In 65.9% of pts with CLL receiving Ib and AC hemorrhages persist throughout the observation period, represented by nosebleeds (34.5%), hemorrhage in the sclera of the eye (27.6%), gross hematuria (20.7%), gingival bleeding (13.8%), hematomas (75.9%), petechiae (10.3%), bleeding from a rectal tumor in 2 pts, hemorrhage in the anterior chamber of the eye in 1 pts. Macrohematuria required discontinuation of AC for up to 2–3 weeks and transfer to the minimum dose api. In one pts with recurrent macrohematuria AC was canceled. Hemorrhage in the sclera of the eye required outpatient ophthalmic treatment without withdrawal of AC. Nosebleeds were recurrent and led to the transfer of pts to the minimum dose api. Hematomas were permanent, with predominant localization on the arms and legs, in 1 pts they appeared on the face, neck, tongue. Several types of hemorrhages were observed in 47.7% of patients. Transfer to the minimum dose api 2.5 mg * 2 times a day was required in 38.6% of patients due to recurrent nosebleeds, gross hematuria, combined hemorrhages. Clinically significant hemorrhages occurred less frequently in patients treated with api compared with riva (p = 0.019). We did not observe the influence of the level and variability of platelets on the occurrence of hemorrhages in pts with CLL receiving AC. Hemorrhages did not lead to dose changes and withdrawal of Ib. Conclusions. With long-term use of AC in pts with CLL and AF, among clinically significant hemorrhages, recurrent nosebleeds, recurrent hemorrhages in the sclera of the eye and gross hematuria prevailed, which led to a change in the tactics of using AC. Due to hemorrhages 38.6% of pts with CLL required transfer to the minimum api dose. Short-term discontinuation of AC required pts with gross hematuria. The level of platelets and their variability in our study did not have a significant effect on the occurrence of hemorrhages. Hemorrhages did not lead to dose reduction and withdrawal of Ib. Keywords: Chronic Lymphocytic Leukemia (CLL) No conflicts of interests pertinent to the abstract.

Introduction: overall survival of patients (pts) with chronic lymphocytic leukemia (CLL) depends not only on the severity of the CLL, the anticancer therapy used and the comorbidity of pts. The most important role in the management of these pts is played by the supervision of a cardiologist. Methods: we examined and observed in dynamics for 5 years 217 pts with CLL, constantly receiving ibrutinib, which induces arterial hypertension (AH) and atrial fibrillation (AF) in a part of the pts. All pts underwent echocardiography (ECHO), 24-hour Holter ECG monitoring (HM), assessment of comorbidity using the Charlson index and screening of fragility using the G8 questionnaire. Daily measurement of blood pressure, heart rate in the morning and in the evening with keeping a diary of measurements, was recommended for all pts, but only 81 pts were performed, who constantly contacted us remotely using instant messengers and made up an active cardiac monitoring group. Correction of treatment was carried out in accordance with these data. Results: a study of the overall survival of patients with CLL receiving ibrutinib, depending on cardiac monitoring, was carried out, starting from the first visit. The age of pts in the active cardiac monitoring group (n = 81) and in the rest of pts (n = 136) did not differ and amounted to 66.0 (60.0-70.0) years and 66.0 (59.0-74.0) years respectively. The number of men and women in the groups was comparable. In the active cardiac monitoring group, there were significantly more pts with AH - 86.5% and with AF - 42.7% compared to 50.4% with AH and 15.9% with AF in the remaining pts (p < 0.0001 in both cases) and a comparable number of pts with coronary artery disease. According to screening HM, there were more pts with short episodes of AF in the active cardiac monitoring group - 31.4% versus 8.0% in the rest of the pts (p < 0.0001). Accordingly, the number of pts receiving cardiac treatment in the active cardiac monitoring group was 87.6%, the rest was 53.6% (p <0.0001). ECHO parameters did not differ in the groups. Indicators that significantly affect survival in the general group (Charlson index, scores of the G8 questionnaire) did not have significant differences in the active cardiac monitoring group and in other pts with CLL. The groups also did not differ in hematological status and the number of cases of second tumors. Despite a significantly more pronounced cardiac comorbidity, CLL pts under active cardiac monitoring, including continuous remote monitoring, demonstrated better survival compared to other patients (p <0.0001). Conclusions: carrying out active cardiac monitoring, including constant remote observation, allows achieving higher overall survival rates for CLL pts, despite the more severe cardiac status compared to other patients under the periodic supervision of a cardiologist. Keywords: Cancer Health Disparities No conflicts of interests pertinent to the abstract.

Successful chemotherapy in the treatment of hematological diseases is determined not only by the efficacy of antitumor drugs, but by the timely correction of adverse events, among which especially important are cardiac complications associated with both already existing cardiovascular diseases and cardiotoxicity of cytostatic drugs. Of particular importance is also a frequent lack of systemic cardiological examination of oncohematological patients. The urgency of this issue was the reason for creating cardio-oncological clinics focused on the closest co-operation of cardiologists with drug chemotherapy experts. Hematological patients are a particular group among chemotherapy recipients. Potential curability of an oncohematological disease and achieving durable MRD-negative remission raise the importance of irreversible or long-term cardiac complications directly affecting the quality of life and life expectancy. Besides, in some cases long-term or life-long administration of certain cardiotoxic antitumor drugs requires a particular cardiological follow-up. A broad variety of cardiotoxic effects of antitumor drugs and peculiarities of their clinical manifestations call for the exact algorithms of cardiological examination to be observed for the timely detection and treatment of cardiovascular complications. The now available st udies and interdisciplinary work of cardiologists and oncologists (oncohematologists) can yield such algorithms for examination and the approaches to prophylactic and treatment of cardiotoxicity as well as to rehabilitation of patients.

Cardiovascular toxicity of cancer therapies remains an urgent problem today. The creation of highly effect antitumor drugs also means the appearance of new adverse effects. Immune checkpoint inhibitors (ICI) is a new class of antitumor drugs that is different from traditional chemotherapeutic and targeted drugs. Immunotherapy with ICI (monoclonal antibodies targeting the cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1)) significantly improved the results of treatment of cancer therapy. These drugs regulate antitumor immunity and promote cancer regression and improve survival, but can also cause a wide range of immunity-related adverse events (AEs). Although cardiotoxicity associated with ICI is rare, it is important because of its high mortality rates. In recent years, cases of myocarditis and fatal heart failure have been recorded more often in patients receiving ICI. This review focuses on the mechanisms of cardiotoxicity, methods for the prevention and treatment of these adverse events. Severe cardiovascular consequences associated with the use of ICI are important issues for oncologists, cardiologists and immunologists.

The article discusses the most frequently used prognostic scales intended to assess the risk of cardiac complications in surgical patients. The choice of optimal point scales for patients with colorectal cancer is justified.

Background. The use of NOACs in patients with chronic lymphocytic leukemia (CLL) is a difficult task due to the tendency to hemorrhage in these patients associated with CLL. The use of targeted ibrutinib (Ib) therapy in the treatment of CLL patients increases the risk of bleeding due to thrombocytopathy. A feature of targeted Ib therapy is the need for daily and lifelong use. One of the cardiotoxic effects of Ib is the development of atrial fibrillation (AF). Some patients receiving Ib have a history of AF. Warfarin is contraindicated in patients taking Ib, so all patients received NOACs. Purpose. To evaluate the possibility of using NOACs in CLL patients receiving Ib, taking into account the frequency and severity of hemorrhagic manifestations, the need to cancel, reduce the dose and replace with another NOACs. Methods. We examined and observed the dynamics of 224 patients with CLL receiving Ib from 5 to 56 months at a dose of 420 mg per day as 1, 2, 3, and 4 lines of CLL therapy. Patients with CLL aged 32 to 91 years (66.0 (59.0-72.0) years) were Included, of whom 82 are women aged 39 to 83 years (64.0 (54.0-71.0 ) years) and 142 men aged 32 to 91 years (66.0 (60.0-72.0) years). All hemorrhagic manifestations in patients receiving Ib and NOACs were evaluated, taking into account the glomerular filtration rate and platelet count. Results. AF were revealed in 51 patients with CLL receiving Ib. AF was registered in 32 patients during the treatment with Ib, in 19 patients AF was before prescribing of Ib. The need for NOACs because of AF arose in 38 patients with CLL who were prescribed rivaroxaban (n = 11), dabigatran (n = 6), apixaban (n = 21). Hemorrhages were observed in 88.2% of patients receiving NOACs and Ib, represented by hematomas (n = 32), petechiae (n = 4), nosebleeds (n = 6), gingival bleeding (n = 7), hemorrhage in the anterior chamber of the eye (n = 1), hemorrhage in the sclera of the eye (n = 3) and macrohematuria (n = 4). A combination of several hemorrhagic manifestations (combined hemorrhages) was observed in 40.7% of CLL patients receiving NOACs. 10 patients were transferred to the minimum dose of apixaban 2.5 mg twice a day due to the development of recurring nosebleeds (n = 5), macrohematuria (n = 3), large, recurring hematomas with localization on the neck and face (n = 1 ), hemorrhages in the anterior chamber of the eye (n = 1). Cancellation of NOACs in 1 patient was associated with recurrent macrohematuria. Rivaroxaban 20 mg per day was canceled in 6 patients due to the development of persistent thrombocytopenia of less than 50 × 109/L. Conclusions. There were no life-threatening hemorrhages. The main reason for the withdrawal of NOACs was persistent thrombocytopenia. Due to hemorrhagic complication, NOACs was canceled only in 1 patient, 10 patients (26.3%) required a transfer to the minimum dose of apixaban. The arising hemorrhages did not require hospitalization of patients.

Cardiovascular toxicity of cancer therapies remains an urgent problem today. The creation of highly effect antitumor drugs also means the appearance of new adverse effects. Immune checkpoint inhibitors (ICI) is a new class of antitumor drugs that is different from traditional chemotherapeutic and targeted drugs. Immunotherapy with ICI (monoclonal antibodies targeting the cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) or its ligand (PD-L1)) significantly improved the results of treatment of cancer therapy. These drugs regulate antitumor immunity and promote cancer regression and improve survival, but can also cause a wide range of immunity-related adverse events (AEs). Although cardiotoxicity associated with ICI is rare, it is important because of its high mortality rates. In recent years, cases of myocarditis and fatal heart failure have been recorded more often in patients receiving ICI. This review focuses on the mechanisms of cardiotoxicity, methods for the prevention and treatment of these adverse events. Severe cardiovascular consequences associated with the use of ICI are important issues for oncologists, cardiologists and immunologists.