No absolute safe dose! The latest CSCO guidelines teach you how to combat cardiac toxicity with the ring drug.

How to treat and prevent anthracycline induced cardiotoxicity? What kind of tests should be done? The latest guidelines set standards.on July 3, Professor Ma Jun, director of Harbin Institute of Hematology and oncology, explained the key points of CSCO 2020 guidelines on prevention and treatment of anthracycline cardiotoxicity.anthracycline cardiac toxicity overview: tumor and treatment related cardiovascular diseases, in recent years, with the prolongation of tumor survival, the incidence rate and mortality of complications related to tumor markers have increased. Cardiovascular disease incidence rate and mortality rate in tumor survivors are the second place, only after tumor recurrence. Therefore, cardiovascular disease is a non tumor tumor patient. The main cause of death.after 15-25 years of tumor diagnosis, the risk of cardiac mortality in children with cancer was 8.2 times higher than that of normal people, the risk of congestive heart failure increased by 1.5 times, the risk of cardiovascular disease increased by 10 times, and the risk of stroke increased by 9 times.in addition, among the patients with colorectal cancer, bladder cancer, kidney cancer, endometrial cancer, breast cancer, prostate cancer and testicular cancer, non cancer causes of death are the highest, among which heart disease accounts for more than 40% of the death rate.anthracycline drugs include adriamycin, daunorubicin, adriamycin, etc., which are the cornerstone of chemotherapy for leukemia, lymphoma and some solid tumors. Because of their myocardial affinity, anthracyclines are more likely to stay in myocardial cells and cause cardiac toxicity.its main mechanism is the damage of cell membrane and organelles, the damage of myocardial mitochondria, the energy metabolism disorder of myocardial cells and the induction of myocardial apoptosis.▍ the pathophysiological characteristics of cardiotoxicity induced by anthracyclines have obvious dose-response linear relationship, and the cardiotoxicity caused by anthracyclines is also closely related to the cumulative dose.Table 1 cumulative dose of anthracyclines and incidence of heart failure. The dose of cardiotoxicity caused by commonly used anthracyclines can be converted, as shown in the table below.Table 2 anthracycline dose conversion tables are different in cancer patients' sensitivity to anthracycline induced cardiotoxicity. Some patients can have cardiotoxicity symptoms when they are first used, so there is no absolute "safe dose".clinical manifestations of anthracycline induced cardiotoxicity. According to the 2016 European Society of Cardiology (ESC) guidelines, cardiovascular complications related to cancer treatment are divided into: ① cardiac insufficiency and heart failure. Cardiac insufficiency definition: with one or more of the following manifestations, but excluding subclinical cardiovascular injury in the early stage of chemotherapy / targeted drug use.cardiomyopathy with reduced left ventricular ejection fraction (LVEF) is characterized by decreased global function or ventricular septal movement; symptoms associated with congestive heart failure (CHF); CHF related signs, such as the third heart sound galloping, tachycardia; LVEF reduced by at least 5% to absolute value < 55% from baseline, accompanied by symptoms or signs of CHF, or LVEF reduced by at least 10% to absolute value Less than 55%, without symptoms or signs.② coronary artery disease, valvular heart disease, arrhythmia, hypertension, thromboembolic disease, peripheral vascular disease and stroke, pulmonary hypertension, and other cardiovascular complications. Cardiotoxicity induced by anthracycline drugs is usually progressive and irreversible. According to the occurrence time, it can be divided into acute, chronic and delayed, and the specific occurrence time, clinical manifestations and The characteristics are shown in the table below.Table 3 The characteristics of acute, chronic and delayed cardiotoxicity 3. Monitoring and management of cardiotoxicity ▍ inspection methods: there are six methods for cardiac toxicity: ① electrocardiogram; ② ultrasonic electrocardiogram, LVEF, overall longitudinal strain (GLS); ③ radionuclide imaging; ④ cardiac magnetic resonance imaging (CMRI); ⑤ biochemical markers: troponin I, high-sensitivity troponin I, B-type natriuretic Methods: the patients were divided into two groups: peptide (BNP), N-terminal pro BNP (NT Pro BNP), endomyocardial biopsy (more traumatic, not recommended for routine use).the specific diagnostic criteria, advantages and disadvantages of each method are shown in the table below.Table 4 Four principles of cardiac toxicity monitoring methods ▍ four principles of inspection methods at present, there are no clear provisions on the inspection methods, which can be selected according to the specialty and convenience of the hospital, but the following basic principles should be observed: ① the same imaging or marker should be selected in the whole treatment process; do not change the inspection method or laboratory test kit in the midway; ② the inspection method may be available The results showed that there were good repeatability; ③ the examination method should provide as much clinical data as possible (such as right ventricular function, pulmonary artery pressure, valve function, pericardial evaluation); ④ the less radiation exposure, the better.▍ cardiotoxicity management during tumor treatment ① screening before tumor treatment: pay attention to the risk factors of cardiac insufficiency. before anti-cancer treatment, we should pay attention to the patient's therapeutic drug dose, radiation dose and past medical history, and pay attention to the risk factors of cardiac toxicity, as shown in the table below. Table 5 risk factors of cardiac insufficiency ② monitoring during tumor treatment; monitoring of central function during treatment; expert consultation of tumor cardiology. in the process of treatment, the monitoring of cardiac function should be combined with echocardiography, serum cardiac markers, imaging and other methods, as well as consultation with cardiac experts. The evidence level is level 1 and level 2, and the recommended level is grade I and II. risk factors of cardiac insufficiency should be routinely monitored by imaging (grade 2B evidence, recommended by grade II experts). there is no recommendation on whether to continue anti-tumor therapy in patients with cardiac insufficiency, so we should weigh the advantages and disadvantages before making a decision. patients with breast cancer who may receive trastuzumab treatment should be regularly monitored by echocardiography (Level 3 evidence, recommended by level II experts). Table 6 screening items during tumor treatment; ③ follow up after tumor treatment: cardiac function follow-up monitoring (see the table below for details). Table 7 In the long-term follow-up of tumor survivors, the mortality of cardiotoxic diseases was the first, anthracycline drugs and radiotherapy were found to be the first cause of childhood tumor The most common factor of cardiotoxicity in tumor patients. ② asymptomatic cardiotoxicity of anthracyclines is a serious problem in children with cancer. many children who receive anthracyclines at doses less than 300 mg / m2 have already shown cardiac dysfunction. . A retrospective study of 32308 children with long-term tumor survival revealed that the incidence rate of cardiovascular complications was about 8.1%. Compared with the control group, the incidence of cardiovascular diseases increased by 20 times among young survivors. ▍ pregnant women are diagnosed with leukemia or lymphoma during pregnancy. If pregnancy is not terminated, the plasma concentration of anthracyclines should be evaluated to avoid complications of pregnant women or fetuses caused by increased cardiac load. prevention and treatment of pentaanthracycline cardiotoxicity ▍ commonly used prevention strategies: ① limit or reduce the maximum cumulative dose of anthracycline drugs; ② change the mode of Administration (continuous pumping); ③ change the dosage form (liposome encapsulation); ④ use of cardioprotective drugs (dextrrazol is class 1A evidence, others have angiotensin II receptor antagonist / angiotensin converting enzyme inhibitor) (5) behavioral therapy (lack of evidence). the evidence level and recommendation level of each common strategy are shown in the table below. Table 8: common prevention strategies for cardiotoxicity ▍ evidence based medicine ① reducing the maximum cumulative dose to prevent cardiotoxicity. 49017 cancer patients were reported in 18 studies, of whom 22815 were treated with anthracyclines. after a median follow-up of 9 years, the incidence of clinically significant cardiotoxicity was 9%, while the incidence of subclinical cardiotoxicity was 18%. the independent risk factors of cardiotoxicity were evaluated, and the cumulative anthracycline dose was an accurate and powerful predictor of cardiotoxicity. however, the limited cumulative dose may affect the anti-tumor efficacy, and there is no absolute "safe dose" of anthracyclines due to individual genetic differences. ② to prevent cardiotoxicity by changing the administration mode, previous literatures reported that the peak serum concentration of anthracyclines could be controlled by changing the administration rate of anthracyclines. therefore, long-term infusion therapy is recommended to reduce the cardiotoxicity of anthracyclines. in a randomized, double-blind trial, children newly diagnosed with acute lymphoblastic leukemia (all) were compared, and there was no significant difference between the two groups in terms of heart injury in patients receiving continuous administration and rapid injection. The incidence rate of congestive heart failure was significantly reduced by anthracycline combined with rightorasone (39% vs 13%, P < 0.001), and the incidence of congestive heart failure (11% vs 1%, P < 0.05) was reduced by 3. Fig.1 evidence that dexrazoxane does not affect the efficacy of anthracycline drugs Table 9 In 2013, JAMA published a process study involving 114 patients receiving high-dose chemotherapy. It showed that patients with early elevation of troponin (within 72 hours after chemotherapy) received enalapril treatment (12 months) could significantly reduce adverse cardiac events (including heart failure and asymptomatic left ventricular dysfunction) 。 a 2010 retrospective study compared the efficacy of enalapril and carvedilol in patients receiving high-dose anthracycline chemotherapy with LVEF ≤ 45%. although there was no control group, 42% of these patients completely recovered LVEF. for patients with asymptomatic decreased GLS, there is currently no evidence that any treatment is effective. ② patients with heart failure in the treatment of clinical cardiac dysfunction should refer to the requirements of "Chinese guidelines for diagnosis and treatment of heart failure". if heart failure occurs during chemotherapy, oncologists and cardiologists should be consulted together to form a consultation mechanism between oncologists and cardiologists to discuss the necessity and duration of anti-tumor treatment (generally until the heart failure is stable). Figure 2: composition of oncocardiology specialty