There is widespread appreciation of the burdens of cancer survivorship, although the cardiac complications of cancer therapy are not as widely recognized as might be expected. As cancer therapies and survival have improved, millions of patients treated with cardiotoxic therapy are now cancer survivors. Prolongation of survival resulting from cancer treatment allows patients to live long enough for cardiac toxicity to become the main determinant of quality of life, and in some cases premature mortality – in fact, for early stage breast cancer, a patient is more likely to die from heart disease than cancer. Incidence of heart failure has been highly variable, ranging from <5% to >40% at 5 years.
The most common culprits for causing LV dysfunction are anthracycline drugs and biologic agents – especially tyrosine kinase inhibitors. Their cardiotoxic responses have been classified as types 1 (dose-dependent, involved with structural changes, potentially irreversible) and 2 (idiosyncratic, functional rather than structural changes, usually reversible)
Anthracycline-induced cardiomyopathy has been associated with an especially poor prognosis, with a 2 year mortality of up to 60%.
As late-stage heart failure has such an adverse prognosis, attention has been directed towards recognition of Stage B heart failure - defined in patients with structural disease but without signs and symptoms of heart failure. This group of patients benefits from treatment with b-blockers and ACE inhibitors. While stage B heart failure is readily defined in a patient with a scar after myocardial infarction, its recognition in a patients with diffuse disease is more challenging.
Left ventricular ejection fraction (LVEF), most commonly assessed by echocardiography, is an important predictor of outcome, and is widely used to monitor cardiac systolic function after chemotherapy. Recent guidelines suggest that a reduction of LVEF >5% to <55% with symptoms of heart failure or an asymptomatic reduction of LVEF of >10% to <55% constitute cardiotoxicity. However, the measurement of LVEF presents a number of challenges related to image quality, assumption of left ventricular geometry and expertise. The 95% confidence intervals of measured LVEF are ±11%, so this method fails to detect subtle alterations in LV function. In addition, LVEF is dependent on hemodynamic conditions.
Two-dimensional strain is an automated and quantitative technique for the measurement of myocardial deformation - the most robust parameter being global longitudinal strain. 2D based strain may help the clinician recognize the chemotherapy patient that has evidence of structural abnormalities, as demonstrated by abnormal deformation, and that as a result needs to be classified and treated as Stage B heart failure. Recent work by our and other groups has shown that changes in tissue deformation, assessed by myocardial strain, identify LV dysfunction earlier than conventional echocardiographic measures in patients treated with chemotherapy.
Surveillance using imaging techniques presents a number of logistic headaches. Troponin has been proposed as a useful screening test for toxicity, but this literature is inconclusive and most studies with BNP have been disappointing. The most effective surveillance strategy remains to be defined.