Myocardial Toxicity in Cancer Patients: CARDIOTOX Registry

Study Questions:

How are various definitions and severity of cardiotoxicity associated with outcomes?

Methods:

The authors reported findings from the CARDIOTOX registry; a multicenter prospective cohort of adult patients receiving chemotherapy associated with a reported incidence of cardiotoxicity of >2%. The study examined the association between various definitions of cardiotoxicity and outcomes (mild: asymptomatic patients with left ventricular ejection fraction [LVEF] ≥50% with elevated biomarkers; moderate: asymptomatic patients with LVEF 40-50% with or without biomarker increases; severe: asymptomatic with LVEF <40% or clinical heart failure). Blood sampling and echocardiography were performed according to a predefined protocol: precancer therapy, then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years, and 2 years after initiation of treatment.

Results:

A total of 865 registry participants (mean age 55, 16% men, 66% with breast cancer, and 85% having received anthracyclines) were followed for a median of 2 years. Cardiotoxicity was identified in 38% of patients during follow-up: 32% with mild, 3% moderate, and 3% with severe cardiotoxicity. A total of 54 patients (6%) died of any cause; of those only four (0.2%) were cardiovascular. Only severe cardiotoxicity was associated with an increased risk of all-cause death (hazard ratio, 10.2; 95% confidence interval, 5.5-19.2), with a mortality rate of 22.9 deaths per 100 patient-years versus 2.3 deaths per 100 patient-years in the rest of the groups.

Conclusions:

While a significant number of patients exhibited evidence of myocardial injury or dysfunction related to cancer therapy, only patients with severe cardiotoxicity, defined here as an asymptomatic decrease in LVEF <40% or clinical heart failure, were at higher risk of all-cause death.

Perspective:

Understanding cardiotoxicity warrants the prospective and systematic cardiovascular evaluation of patients undergoing cancer therapy, which is the purpose of the CARDIOTOX registry. The early findings are insightful: In the span of 2 years, while 38% of patients had signs of myocardial injury or dysfunction, 3% were severely impacted and had a higher risk of all-cause death. These findings should not be interpreted as the lack of clinical significance for milder forms of myocardial injury. Cardiotoxicity can occur years after the initial injury, and the registry is so far limited in its follow-up time, sample size, and number of events. Moreover, patients enrolled were heterogeneous and managed within the setting of a cardio-oncology specialty clinic, potentially impacting their outcomes. We look forward to future findings from CARDIOTOX and similar registries to further define thresholds for clinical significance and intervention in the cardiovascular care of cancer patients.

Clinical Topics: Cardio-Oncology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Anthracyclines, Biological Markers, Breast Neoplasms, Cardiotoxicity, Myocardial Reperfusion Injury, Echocardiography, Heart Failure, Secondary Prevention, Stroke Volume, Ventricular Dysfunction, Left


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