In the past 20 years or so, the survival of patients with malignant diseases has been prolonged due to the improved chemotherapy protocols, targeted biological treatment, enhanced surgery and radiotherapy and new interventional radiology methods (1). Nonetheless, certain metastatic diseases can be managed in the long term, making them practically chronic. However, improvement in survival is often at the expense of damage to other organs, including the cardiovascular (CV) system (2). CV diseases are the second leading cause of long-term morbidity and mortality in patients treated for cancer (3).
Initially, the occurrence of cardiotoxicity was almost exclusively associated with the anthracycline therapy induced irreversible left ventricular (LV) systolic dysfunction leading to symptomatic heart failure. With the development of biological anti-HER based therapy, it has been established that it can cause, for the most part, reversible damage of heart function. A decade and half ago, this triggered a division of cardiotoxicity into two basic types: irreversible (type I) and reversible (type II) (4). However, due to a substantial amount of overlapping in terms of both the clinical picture and the course of the disease, this division has not demonstrated to be indisputable and comprehensive. On the other hand, cardiotoxicity cannot be associated only with LV systolic dysfunction as oncology therapy may cause a number of CV diseases such as new or worsening hypertension, vasospastic and/or thrombotic ischemia in the myocardium, worsening of atherosclerosis, rhythm and conduction disorders, and myocarditis. It is also important to identify patients at high risk for developing cardiotoxicity; the predisposition is multifactorial and determined by an interaction of genetic and environmental factors. Some of the defined risk factors are a positive family history of CV disease, age, gender, arterial hypertension and dyslipidemia. It has also been established that there is an increased risk for the development of cardiotoxicity in patients with reduced LV systolic function and significant arrhythmias. (5) In addition, it was necessary to define the follow-up of patients currently receiving or who had previously received cardiotoxic chemotherapy. Cardiotoxicity can manifest itself symptomatically or completely asymptomatically during or immediately after treatment (in the following few days or weeks), but also long time after the end of antitumor therapy (e.g. after the use of anthracyclines). (6) Due to the complexity of the disease, it was necessary to form cardio-oncology teams.
All of the above demonstrates a need to develop guidelines in cardio-oncology. For that reason, after issuing Position Paper (7) in 2016, the European Society of Cardiology (ESC) started to develop comprehensive guidelines that were published in 2022 (8). The guidelines took into account all aspects of cardio-oncology, so instead of the old term cardiotoxicity, a new term cancer therapy-related cardiovascular toxicity (CTR-CVT) is used. The guidelines also introduce new standards for defining CV toxicity associated with oncology therapy, and protocols for monitoring patients during and after oncology treatment, diagnosis and treatment of CRT-CVT. In addition to the 6 basic pathophysiological mechanisms for the development of CRT-CVT, the exceptions of CV toxicity that can be caused by certain oncological drugs are listed as well. The emphasis is on prevention, i.e. risk assessment for the development of cardiovascular toxicity before the application of oncology therapy, which minimizes the unnecessary interruption of oncology treatment. It should always be kept in mind that any interruption or change in oncological treatment can significantly change the results of oncological treatment and the prognosis of the disease. The CRT-CVT approach needs to be multidisciplinary, and the development of cardio-oncology subspecialists who have broad knowledge of cardiology, oncology and hematology is recommended. The major weakness of the guidelines is that most of the recommendations are derived from expert opinions or registries (evidence level C). It is simply impossible to do enough randomized clinical trials.
In this issue of Cardiologia Croatica, the paper published by Czuriga et al. (9) explains the development of the definition of CV toxicity with special reference to the first ESC guidelines on cardio-oncology. The general goal is to provide patients with the best possible oncology therapy in a safe manner, and to reduce CTR-CVT to a minimum. This would reduce unwanted disturbance of therapy. The authors also briefly presented the key CARDIOTOX registry.
An increasing number of patients are treated with chemotherapy and biological drugs, so the incidence of CV toxicity is continuously increasing. (10) The extent of the problem is even greater because some patients have to take a combination of several cardiotoxic drugs (11). Oncology patients with an increased risk of CV toxicity require a multidisciplinary approach and regular cardiological monitoring in order to recognize and adequately treat side effects in a timely manner. In this way, the improvement of clinical outcomes and quality of life is achieved and, possibly, the optimal continuation of specific oncological treatment.