Two-dimensional echocardiography is the most common modality for screening adult survivors of childhood cancer exposed to anthracyclines for possible heart failure. A study from St. Jude Children's Research Hospital, though, suggests that for some patients, 2D echo might not be enough.
The study, available online ahead of print in the Journal of Clinical Oncology (doi: 10.1200/JCO.2011.40.3584), showed that cardiac magnetic resonance (CMR) imaging identified a high prevalence of cardiomyopathy among adult survivors previously undiagnosed with cardiac disease.
The study, led by Gregory T. Armstrong, MD, a pediatric neuro-oncologist and Associate Member in the Department of Epidemiology and Cancer Control, described an evaluation of left ventricular structure and function in 114 adult survivors of childhood cancer, median age of 39. All had been exposed to anthracycline chemotherapy and/or chest-directed radiation therapy.
Cardiac MRI found that 14 percent of patients (16) had an ejection fraction of less than 50 percent. And 108 survivors previously undiagnosed with cardiotoxicity had a high prevalence of ejection fraction (32%) and cardiac mass (48%) that were more than two standard deviations below the mean.
Compared with CMR, 2D echocardiography had a sensitivity of 25 percent and a false-negative rate of 75 percent for detection of ejection fraction less than 50 percent, although 3D echocardiography had 53 and 47 percent, respectively.
Twelve survivors (11%) had an ejection fraction of less than 50 percent by CMR but were misclassified as 50 percent or more (range of 50% to 68%) by 2D echocardiography.
“In this high-risk population, survivors with an ejection fraction of 50 to 59 percent by 2D echocardiography should be considered for comprehensive cardiac assessment, which may include CMR,” the researchers concluded.
The data may be of most interest to primary care physicians and internists who follow adult survivors of childhood cancer, Armstrong said in a telephone interview. “They should have a low threshold for referring these patients on to a cardiologist. Cardiomyopathy after anthracyclines is a progressive disease, and the sooner we detect it the sooner we can begin to intervene.”
Although previous papers have compared MRI with echocardiography and MUGA scans, this is the first study done in cancer survivors, and the largest in any population, he said.
The study is part of the St. Jude Lifetime Cohort program, which is currently following approximately 4,000 adult survivors of childhood cancer.
The study's purpose was not to test MRI against 2D echo, Armstrong said, since cardiac MRI is known to be superior in detecting heart failure, but rather to identify the limitations of echo. “Not everyone with an ejection fraction of 50 percent or above [by 2D echo] is actually above 50 percent,” he said. “As a clinician, when I get an echo of 55 percent [in an adult survivor] I know it might be lower than that.
“When they're in the 50 to 60 percent range and I know this is a population that received cardiotoxic therapy, I have to consider that this patient could still be in early stage of cardiomyopathy and may merit seeing a cardiologist, and potentially undergoing MRI as part of the workup, along with treadmill testing and serum biomarkers.”
‘Clinical Management Not Likely Changed’
Still, a heart failure specialist asked to comment on the paper for this article called it interesting and provocative, but said it does not address whether this type of imaging approach would lead to a meaningful change in management.
“What you have is a more expensive technique that may or may not lead to changes in patient management and patient outcome,” said Douglas L. Mann, MD, Professor and Chief of the Cardiovascular Division of Washington University School of Medicine in St. Louis. “It may be more sensitive, but it may not help with patient care.”
He said the premise behind the research is sound—studying whether a more sensitive methodology can be used to detect mild clinical dysfunction in people who have been treated with chemotherapeutic agents known to be harmful. And the study was essentially positive, as it suggests that MRI is more sensitive. “But the question is, what does this mean for the primary care physician?”
He said that normally, if an ejection fraction goes down to lower than 35 to 40 percent—with 50 percent being normal—a variety of different medical regimens would be implemented to help stabilize the patient. “But although they show they were able to detect ejection fractions that were less than 50 percent better with MRI, a lot of the very minor abnormalities that MRI picked up would not be clinically actionable; it wouldn't have triggered a change in patient -management—Is the additional cost of screening going to change patient outcomes or is it just a more sensitive measure?”
Mann noted that the study cohort was relatively healthy, and that if the people had been sicker the MRI study might have changed management in more of them.
With this cohort, however, Mann estimated that therapy might have changed in only one or two of the 16 patients picked up by CMR with ejection fractions less than 50 percent.
An additional study might try to determine who best to follow with MRI as well as with chemical markers of cardiac injury, he said. “As opposed to just doing MR imaging on everybody, there might be people who have borderline ejection fraction who could be followed with a combination of biomarkers and intermittent MRI more effectively than an echo strategy.”
Still, Mann said, the study is important because it continues to focus the oncology community on the importance of serial followup of adult survivors of childhood cancers, “which for many years we ignored.”