A recent study by Dr. Lopez-Sendon, published in European Heart Journal, showed that cardiotoxicity in the form of left ventricular dysfunction or myocardial injury affects a large portion of patients receiving high-risk anticancer therapy with only severe form strongly associated with all-cause mortality.
Cardiotoxicity has been known as one of the major side effects of anti-cancer therapy that may present with left ventricular dysfunction and heart failure. Given that the early recognition and treatment of these side effects have been associated with a higher recovery rate, a united diagnostic and management guideline seems necessary.
The CARDIOTOX (CARDIOvascular TOXicity induced by cancer-related therapies) registry has been established to determine the prevalence of cardiotoxicity markers as well as their association with guideline-based heart failure criteria and treatment in patients receiving chemotherapeutic agents. To achieve this purpose, a total of 865 patients receiving anticancer regimens associated with moderate to high cardiotoxicity were selected and followed for a median of 24 months. Clinical data, blood samples, and echocardiographic features were collected before the initiation of anticancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years afterward. Patients with past or current history of heart failure or reduced left ventricular ejection fraction (< 40%) and those with a history of previous cancer therapy including chemotherapy and radiation therapy were excluded from the study. Cardiotoxicity was defined as any new deterioration from the baseline of myocardial/ventricular function during follow-up periods. Cardiotoxicity was also sub-classified into four stages depending on the worst myocardial dysfunction/injury observed in the follow-up period. Myocardial dysfunction/injury stages include the following: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥ 50%; moderate, LVD with LVEF 40–49%; and severe, LVD with LVEF ≤ 40% or symptomatic heart failure.
The study indicated a high incidence (37.5%) of ventricular dysfunction among the patients, of whom only 3.1% were classified as having severe dysfunction and the majority have been classified as mild (31.6%). All-cause mortality was also observed to be higher among those with severe cardiotoxicity than other groups. According to the author, the relatively low prevalence of severe cardiotoxicity in the study population was due to the exclusion of patients with a previous history of cardiac dysfunction and the improvement in the follow-up of the cancer patients in the context of cardio-oncology service. Severe cardiotoxicity has also been associated with a 10-fold increase in total mortality compared to a less severe form of cardiotoxicity. A classification of cardiotoxicity using current heart failure guidelines is also proposed by the authors for future studies. This study acknowledged the critical role of comprehensive monitoring and follow-up for the development of cardiovascular symptoms and left ventricular dysfunction in patients receiving chemotherapeutic agents with potential cardiotoxicity.
Limitations that are worthy of mentioning include the inclusion of patients with some degree of abnormality in biomarkers and echocardiographic findings at baseline. Secondly, the prevalence of myocardial damage may be underestimated due to a number of missing visits or incomplete data collection during the follow-up period. Future research is warranted to approve the relationship of different stages of cardiotoxicity with clinical outcomes.