Progress in Prevention and Treatment of Myocardial Injury Induced by Cancer Therapy

Progress in Prevention and Treatment of Myocardial Injury Induced by Cancer Therapy

Introduction The rapid development of oncotherapy methods, including surgery, radiotherapy, chemotherapy, targeted therapy, endocrine therapy, and immune therapy, has significantly prolonged the life expectancy of cancer patients. However, these therapeutic methods can exert direct or indirect side effects on the cardiovascular system, leading to various types of cardiovascular complications. The establishment and development of cardio-oncology aim to reduce the mortality associated with cardiovascular disease caused by cancer therapy while maximizing the benefits of the cancer therapy itself. This article provides a comprehensive overview of the advances in the prevention and treatment of myocardial injury induced by cancer therapy, with a particular focus on breast cancer due to its unique relationship with cardiovascular disease.

Malignant Tumor and Cardiovascular Disease Malignant tumors and cardiovascular disease are the two leading causes of death worldwide. A retrospective study on the death spectrum among elderly inpatients over the past decade shows a rapid increase in the number of patients with malignant tumors and hypertension. Refractory hypertension can lead to cardiovascular and cerebrovascular diseases through mechanisms such as target-organ impairment and atherosclerosis promotion. The relationship between malignant tumors and cardiovascular disease is multifaceted and complex, with many common risk factors, including diabetes mellitus, obesity, hyperlipidemia, genetic mutations, chronic inflammation, oxidative stress, smoking, unhealthy diet, and lack of physical exercise.

Breast cancer, the most common malignant tumor among females, shares many risk factors with cardiovascular disease. The anatomical proximity between the breast and the heart further complicates the cardiovascular effects of breast cancer therapy. Cardiovascular diseases induced by cancer therapy include the aggravation of pre-existing heart-related diseases, the occurrence of potential heart-related diseases among high-risk patients, and heart diseases caused by direct damage to the structure and function of the heart.

Radiotherapy-Induced Cardiotoxicity Radiotherapy is a common therapeutic method for malignant tumors in the breast region, such as breast cancer and esophageal cancer. However, high doses of radiation can cause cardiotoxicity. The radiation dose to the heart depends on factors such as the radiologic technique, laterality, beam energy, and total dose used for radiotherapy. Radiation-induced heart disease includes a range of cardiovascular complications, from subclinical microscopic changes to symptomatic heart diseases such as conduction abnormalities, coronary heart disease, myocarditis, pericarditis, pericardial effusion, cardiac valve injury, and endocardial injury.

For patients with left-sided breast cancer, the average dose of radiation received by the heart is significantly higher than for those with right-sided breast cancer. Echocardiography results show significant differences in left ventricular ejection fraction (LVEF) before and after a year of radiotherapy only in patients with left breast cancer. Multi-field intensity-modulated radiotherapy (IMRT) is considered the most suitable approach for patients with left-sided breast cancer after mastectomy, while volumetric modulated arc therapy offers certain dosimetric advantages over fixed-field IMRT plans for patients receiving post-breast-conserving surgery irradiation.

Chemotherapy-Induced Cardiotoxicity Chemotherapy-induced cardiotoxicity is categorized into Type I and Type II. Type I cardiotoxicity, primarily caused by anthracyclines, leads to permanent and irreversible damage to the myocardium. This type of cardiotoxicity is dose-dependent and can result in progressive cardiac dysfunction over the long term. Type II cardiotoxicity, primarily induced by molecular-targeted therapeutic drugs, is reversible and non-dose-dependent. Common risk factors for chemotherapy-induced cardiotoxicity include the dose and administration frequency of chemotherapy drugs, patient age, female gender, hypertension or other complications, pre-existing cardiovascular disease, and radiation dose.

Anthracyclines, such as doxorubicin and epirubicin, remain one of the most commonly used anti-tumor drugs. The cardiotoxicity of anthracyclines can be classified as acute or chronic. Acute cardiotoxicity usually occurs during or shortly after the beginning of treatment and may manifest as self-limited and transient non-specific electrocardiogram changes, arrhythmias, elevated myocardial enzymes, or transient left ventricular dysfunction. Chronic cardiotoxicity often results in heart failure caused by a progressive decline in LV systolic function, which can develop into irreversible dilated cardiomyopathy.

Targeted therapy, particularly HER2 inhibitors like trastuzumab, has gained attention in breast cancer treatment. However, these drugs can also affect the normal protective pathways of myocardial cells, leading to myocardial injury or other cardiovascular diseases. The cardiotoxicity of targeted drugs is generally reversible, but factors such as gender, age, anthracycline use, pre-existing coronary artery disease, atrial fibrillation, renal failure, and cardiovascular risk factors can influence the development of heart failure.

Monitoring of Cardiotoxicity Monitoring cardiotoxicity during cancer therapy is crucial for early identification of cardiac abnormalities and timely intervention. The major cardiotoxicity monitoring methods include electrocardiogram, cardiac biomarkers, echocardiography, radioactive nuclide myocardial imaging, angiography, cardiac magnetic resonance imaging, and endomyocardial biopsy. The most common clinical manifestations of cardiotoxicity are cardiac dysfunction and heart failure, which can be identified by an increase in troponin or natriuretic peptide levels or a decrease in LVEF by more than 10%, falling below the lower limit of the normal value.

Echocardiography is the preferred mode of cardiac function monitoring due to its non-invasive nature, ease of operation, and accuracy. However, conventional ultrasound indexes, such as two-dimensional LVEF, LV shortening fraction, and tissue Doppler imaging, have low sensitivity in detecting early heart impairment in tumor patients. New technologies, such as speckle tracking imaging (STI), have been developed to address these limitations. STI can detect subclinical structural and functional changes in the heart related to anti-cancer therapy more sensitively and accurately in the early stages of therapy. STI is independent of angle and can provide quantitative evaluation of myocardial displacement, strain rate, rotation angle, and velocity, offering a comprehensive assessment of overall, systolic, and diastolic functions of each myocardial segment.

Medical Therapy and Prevention The prevention and treatment of tumor-related cardiovascular disease are still areas of active research. Currently, angiotensin-converting enzyme inhibitors (ACEIs) and beta-receptor blockers are recognized as effective therapies for preventing or treating cardiac dysfunction related to cancer therapy. Enalapril and carvedilol have shown significant benefits in reducing cardiac injury in patients with breast cancer after anthracycline chemotherapy, improving cardiac remodeling, and enhancing myocardial systolic and diastolic functions.

Carvedilol, in particular, has antioxidant effects in addition to its adrenergic receptor blocking activity, making it an ideal drug for preventing chemotherapy-induced myocardial dysfunction. Other drugs, such as trimetazidine, candesartan, acetylcysteine, vitamins, erythropoietin, endothelin-1 receptor antagonists, and lipid-lowering drugs, may also benefit the cardiovascular system in tumor patients. Statins and ACEIs have been shown to reduce myocardial injury in animal models of radioactive heart disease, while long-chain omega-3 polyunsaturated fatty acids can protect the heart by reducing triglycerides and exerting anti-inflammatory, anti-myocardial fibrosis, and anti-arrhythmia effects.

Conclusions The development of cardio-oncology faces several challenges, including the need for reasonable risk evaluation methods to enable early intervention in tumor patients at risk of developing acute or chronic heart diseases. Balancing the benefits of anti-cancer therapy with its cardiotoxicity is essential to maximize the overall benefits for cancer patients. The financial burden of tumor therapy on patients and their families necessitates the establishment of standards to screen high-risk patients who require long-term follow-up or early intervention, thereby reducing the mortality of heart-related diseases in tumor patients without imposing unnecessary economic burdens.

The multidisciplinary collaboration among cardiology, oncology, and nursing is crucial for the advancement of cardio-oncology. As our understanding of tumor development and drug-resistance mechanisms grows, the development of new drugs with stronger effects and lower toxicity will continue to improve the outcomes for cancer patients while minimizing cardiovascular complications.

doi.org/10.1097/CM9.0000000000000498

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