June 08, 2015
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Treatment-related cardiac dysfunction common in adult survivors of childhood cancer

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Cardiac dysfunction, particularly abnormal global longitudinal strain and diastolic function, is common in adult survivors of childhood cancer, even in those with normal left ventricular ejection fraction, researchers reported in a new study.

Treatment-related cardiac death is the primary noncancer cause of mortality in adults treated for cancer in childhood, but optimal methods of early detection of cardiac dysfunction have not been determined. Researchers aimed to identify the prevalence of late-onset cardiac dysfunction in adult 10-year survivors of childhood malignancies from the St. Jude Lifetime Cohort Study, using echocardiographic evaluation of cardiac function, including 3-D LVEF, myocardial strain imaging and comprehensive diastolic assessment. The latter was graded based on American Society of Echocardiography guidelines.

The study population included 1,820 adults (median age, 31 years) who survived childhood cancer (median time from diagnosis, 23 years). All were exposed to anthracycline chemotherapy (n = 1,050), chest-directed radiotherapy (n = 306) or both (n = 464).

Gregory Armstrong, MD

Gregory T. Armstrong

Gregory T. Armstrong, MD, MSCE, and colleagues found that only 5.8% of survivors had abnormal 3-D LVEFs (≤ 50%).

Cardiac dysfunction evident

However, among survivors with normal 3-D LVEF, 32.1% had evidence of cardiac dysfunction, whether by global longitudinal strain (28%), diastolic assessment (8.7%) or both.

According to Armstrong and colleagues, abnormal global longitudinal strain was associated with chest-directed radiotherapy at 1 Gy to 19.9 Gy (RR = 1.38; 95% CI, 1.14-1.66), at 20 Gy to 29.9 Gy (RR = 1.65; 95% CI, 1.31-2.08) and at greater than 30 Gy (RR = 2.39; 95% CI, 1.79-3.18), as well as at anthracycline dose greater than 300 mg/m2 (RR = 1.72; 95% CI, 1.31-2.26).

Armstrong, a member of the HemOnc Today Editorial Board, and colleagues found that compared with those without metabolic syndrome, survivors with metabolic syndrome were more likely to have abnormal global longitudinal strain (RR = 1.94; 95% CI, 1.66-2.28) and abnormal diastolic function (RR = 1.68; 95% CI, 1.39-2.03), but not abnormal 3-D LVEF (RR = 1.07; 95% CI, 0.74-1.53).

“These findings suggest that traditional echocardiographic evaluation of cardiac function in adult survivors of childhood cancer that focuses on LVEF as the primary measure of function may be inadequate,” Armstrong, from the department of epidemiology and cancer control, St. Jude’s Children’s Research Hospital, Memphis, Tennessee, and colleagues wrote.

Implications for prevention

In a related editorial, Edward T.H. Yeh, MD, from the department of cardiology at The University of Texas MD Anderson Cancer Center, and Pimprapa Vejpongsa, MD, from the Texas Heart Institute, Houston, wrote that “the investigators have a unique opportunity to use the [St. Jude Lifetime Cohort Study] cohort to evaluate whether early intervention could prevent or slow the progression of subclinical LV dysfunction (assuming that subclinical LV dysfunction will progress to clinical HF with time). There is currently no proven treatment that will reverse cardiac injury that was already incurred after cancer treatment. It would be more desirable to prevent [CV] damage with primary prevention.” – by Erik Swain

Disclosure: One researcher reports receiving research grants from General Electric and equipment support from Siemens and Philips. Yeh and Vejpongsa report no relevant financial disclosures.