Management of Cardiac Function in Cancer Patients
With the aggravation of population ageing, the global cancer burden will intensify annually. According to the global burden of cancer data released by the International Agency for Research on Cancer (IARC) in 2020, 19.3 million new cancer cases and 10.0 million cancer deaths worldwide (Sung et al., 2021). Classical chemotherapy is still the first-line treatment for most cancers, while targeted therapy and immunotherapy have become the focus of current cancer treatment.
However, these therapies are closely associated with cardiovascular and metabolic sequelae, and studies have demonstrated an increased risk of cardiovascular disease in patients with long-term survival of malignant tumours. The guideline issued by the European Society of Cardiology (ESC) in 2016 classified the cardiovascular complications caused during cancer treatment into nine categories. Including cardiac insufficiency and heart failure, coronary artery disease, valvular disease etc. (Zamorano et al., 2016), covering almost all types of cardiovascular diseases.
With the help of myocardial marker detection, improving the level of cardiovascular disease risk management in cancer patients has become a new interdisciplinary research focus of Cardio-Oncology.
Cardiotoxicity induced by anthracyclines is most common
A variety of chemotherapy drugs can cause cardiac toxicity in cancer treatment. Among which anthracycline drugs represented by doxorubicin and epirubicin are the most common, mainly due to the fact that anthracyclines can induce lipid peroxidation of the myocardial cell membrane and mitochondrial DNA damage, resulting in permanent myocardial cell damage and death. For example, in breast cancer treatment, a study has shown an adjusted heart failure hazard ratio of 1.26 in older breast cancer patients treated with anthracyclines and non-anthracene (Pinder et al., 2007).
Cardiotoxicity induced by anthracyclines can be classified as acute, chronic, and delayed types. Acute cardiotoxicity usually occurs within a few hours or days after administration. It is usually characterised by intracardiac conduction disorder and arrhythmia, rarely by pericarditis and acute left heart failure. Chronic cardiotoxicity generally occurs within one year of chemotherapy, manifested as left ventricular dysfunction, leading to heart failure. Delayed cardiotoxicity may occur several years after chemotherapy and may present as heart failure, cardiomyopathy, arrhythmia, etc.
Immune checkpoint inhibitors associated myocarditis tends to critical condition
Immune checkpoint inhibitors (ICI) are considered to be one of the most successful cancer therapies. Although the incidence of ICI-related cardiotoxicity is low, it is easy to progress to a particularly critical type(Moslehi et al., 2018). Which is characterised by relatively early onset and high mortality and is easily ignored at the early stage.
There have been case reports of myocarditis and fatal heart failure in ICI patients. A retrospective study reported that 6.2% of ICI-related adverse events were cardiotoxic, 35% of which were fatal, and up to half of patients with myocarditis died (Martins et al., 2019). The Lancet published a report on ICI-related myocarditis in 2018, which showed that among 101 severe myocarditis cases caused by ICI after treatment, the median onset time was 27 days, and the mortality caused by cardiovascular complications reached 46% (Moslehi et al., 2018b). It warned that patients treated with immune checkpoint inhibitors to be on high alert for the development of myocarditis.
Standardised management of cardiac function in cancer patients
The clinical manifestations of ICI-associated cardiotoxicity were atypical in the past review studies, and there were no universally accepted criteria for diagnosing ICI-associated myocarditis (Neilan et al., 2018). For example, the dominant histopathological feature of ICI-associated myocarditis is T-lymphocyte infiltration in necrotic areas and surrounding tissues, which is similar to the patients with cardiac transplant rejection (Läubli et al., 2015). Due to the lack of sensitivity and specificity for diagnosing ICI myocarditis, the criteria for assessing and diagnosing ICI-associated myocarditis should be comprehensive.
In clinical practice guidelines (Sinagra et al., 2016), clinicians can use several noninvasive diagnostic tests with varying diagnostic potential and accuracy to identify suspected myocarditis and grade the severity of the condition. The commonly used cardiac function monitoring methods are mainly the combination of biomarker, cardiac imaging and endomyocardial biopsy.
Cardiac imaging supports the assessment of heart function in patients with cancer
In the practice guideline (Zamorano et al., 2016), cardiac imaging, including echocardiography, nuclear imaging and cardiac magnetic resonance (CMR), is recommended as a means of evaluation for cardiac disease in cancer patients. Ultrasound echo-enhancers can display endocardium boundaries, accurately measure left ventricular ejection fraction (LVEF). Speckle tracking imaging assesses global left ventricular long-axis strain (GLS). Studies have shown that echocardiographic assessment of cardiotoxicity is reflected in GLS reduction from baseline at 1 year of chemotherapy. Meanwhile, LVEF is critical to the assessment of cardiotoxicity, and it requires accurate measurement. It is recommended that ultrasound enhancers be routinely used to assess LVEF when using chemotherapy or other new therapies. Patients with LVEF < 53% or GLS <-15% should be highly suspected of cardiotoxicity, and the best treatment should be discussed with the cardiologist (Ponikowski et al., 2016).
Detection of myocardial markers should be carried out throughout the whole course of tumour diagnosis and treatment
The American Society of Clinical Oncology (ASCO) guidelines for the Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers (Armenian et al., 2017) recommend routine serum myocardial marker (troponin and natriuretic peptide) monitoring in cancer patients. The consensus recommendations from the Society for Immunotherapy of Cancer also recommend baseline testing such as troponin, brain natriuretic peptide (BNP) and N terminal pro B type natriuretic peptide (NT-probNP) assessment for all patients before initiating ICI therapy (Puzanov et al., 2017).
Natriuretic peptide detection plays a vital role in the whole management of heart failure. Although symptoms and signs of heart failure patients have improved significantly after treatment, the incidence of cardiovascular events remains high after discharge.
In a study (Klimczak-Tomaniak et al., 2020) of 1,998 patients with chronic heart failure to investigate the association between all-cause mortality and repeated measurements of NT-probNP, the results showed that the variation trend of NT-probNP level was related to survival rate, and increased NT-probNP predicted poor survival rate, suggested that the continuous detection of NT-probNP can be used for dynamic risk stratification. Similarly, a study (Mishra et al., 2017) involving 635 patients with coronary heart disease showed that patients with relatively stable levels of NT-probNP had the lowest mortality risk. Changes in NT-probNP at 5 years predicted heart failure or cardiovascular death risk in patients with stable coronary heart disease, independent of other prognostic indicators, including baseline and follow-up levels of NT-probNP. Assessing natriuretic peptide changes during hospitalisation in patients with heart failure to establish a baseline for follow-up after discharge may help improve readmission rates and mortality.
Detection of myocardial markers with high sensitivity and accuracy should be widely used in cardiotoxicity monitoring, especially for patients with atypical clinical manifestations and electrocardiogram, which plays an early warning and identification role. It is one of the critical tools for cardiovascular risk management of cardiovascular disease in cancer patients throughout the life cycle.
Bibliography
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