T2 mapping derived from weekly cardiac MRIs helped researchers identify cardiotoxicity at an early and reversible stage, a finding which may have implications for cancer patients at risk of chemotherapy-induced heart failure.
Carlos Galan-Arriola, DVM, with the National Center for Cardiovascular Research in Madrid, and colleagues published their results from a pig study online Feb. 18 in the Journal of the American College of Cardiology. The authors noted their study is the first to use serial cardiac magnetic resonance (CMR) evaluations to evaluate anthracycline-induced cardiotoxicity in pigs, which more closely approximate human anatomy than the animals used in previous studies (mice, rats and rabbits). They also said it’s the most comprehensive trial in terms of collecting CMR evaluations weekly for four months, enabling them to cover all stages of cardiotoxicity.
“Current algorithms to identify early stages of anthracycline-induced cardiotoxicity are far from optimal,” Galan-Arriola et al. wrote. “Diagnosis generally occurs once left ventricular (LV) functional deterioration becomes manifest, either as a decline in left ventricular ejection fraction (LVEF) or longitudinal LV strain abnormalities. By this stage, the damage to the myocardium is often irreversible. The lack of a validated early damage marker limits the development of preventive strategies.”
The researchers also pointed out treatment with anthracyclines, a popular class of chemotherapy drugs, contributes to overt systolic heart failure in up to 25 percent of patients, depending on the dose delivered. That essentially results in a “tradeoff” from cancer to chronic heart failure.
In an effort to detect early CMR markers of anthracycline-induced cardiotoxicity, Galan-Arriola and co-authors studied 15 pigs which were given either three or five biweekly intracoronary doxorubicin doses and followed for up to 16 weeks, with CMR exams performed every week. They were compared to a control group of five pigs which didn’t receive doxorubicin.
A key finding was that T2 relaxation time increased significantly beginning at six weeks in pigs given doxorubicin, before they began showing declines in LVEF (week 9). In five pigs whose anthracycline therapy was halted after these T2 changes were observed, the T2 relaxation times returned to normal before week 16 and LVEF never deteriorated.
T1 relaxation times and extracellular volumes didn’t change significantly until week 10, after LVEF had already started to decline and later than T2 relaxation times began increasing.
“Almost 90% of patients developing anthracycline-mediated LVEF deterioration never fully recover pre-treatment LVEF even with heart failure therapies,” the researchers wrote. “The identification of T2 relaxation-time prolongation as a very early marker of reversible intracardiomyocyte vacuolization thus has important clinical implications. Serial T2 mapping might allow tailored anthracycline dose management, with patients showing no T2 mapping abnormalities perhaps able to receive further doses, even beyond currently accepted high cardiotoxicity limits, without increasing the risk of future LV dysfunction.”
Galan-Arriola et al. said this could be particularly helpful for patients who might benefit from higher anthracycline doses to stop cancer progression. Alternatively, lower doses might be used for patients with other comorbidities that put them at greater risk for heart failure.
However, the authors acknowledged the three-week time window between T2 relaxation time prolongation and the worsening of LVEF is “narrow to be picked up in the clinical setting,” but it may be different in humans.
“We speculate that this time window might be significantly wider in patients due to the more concealed evolution of the disease but this is to be demonstrated in the clinics,” they wrote.
Galan-Arriola et al. also said the performance of weekly, comprehensive CMR imaging isn’t currently feasible due to its high cost and the lack of access to facilities with CMR. They believe the highest-risk patients could be offered more frequent screenings for anthracycline-induced cardiotoxicity for now, and said the development of “ultra-fast CMR protocols” to capture the minimum information necessary for T2 mapping might ultimately broaden the reach of this strategy.
“Although CMR has several advantages over echocardiography, specifically the ability to perform tissue characterization, as was nicely demonstrated in this issue of the Journal, there will remain both economic and logistical roadblocks such as cost and lack of widespread availability that will limit the integration of CMR into cardio-oncology practice,” Anthony F. Yu, MD, with Memorial Sloan Kettering Cancer Center in New York, and colleagues wrote in a related JACC editorial. “Nonetheless, findings from this study are certain to encourage future investigation into the potential application of T2 mapping techniques for the surveillance and prevention of cardiotoxicity in cancer patients.”