Succeeding with Cancer: Using Imaging to Avoid Treatment-induced Heart Failure

Treating today’s cancer patient no longer means simply targeting the cancer. Given the known cardiotoxicities of some established chemotherapies and the possibility that newer approaches may damage the heart, oncologists, cardiologists and imaging specialists now work together to detect and minimize the risk of treatment-induced heart failure.

Echocardiography can be used to help monitor cardiac toxicity using a baseline cardiac ultrasound and serial followup exams.

Anthracycline chemo agents can cause damage to the heart

Anthracyclines have long been oncologists’ first line of attack against a broad array of solid tumors and hematological malignancies because of their effectiveness. While anthracycline chemo agents destroy cancer cells, they also may induce cardiomyocyte death that leads to adverse left ventricular remodeling. Chemotherapy agents can cause cardiomyopathy and heart failure.

To prevent the risk of patients developing heart failure, oncologists now typically monitor left ventricular ejection fraction (LVEF) using either echocardiography or equilibrium radionuclide angiography/multigated acquisition (ERNA/MUGA) and discontinue or pause treatment if LVEF measures drop below a threshold.

Anthracyclines, probably the most commonly prescribed type of anticancer agent, are being joined by an expanding array of therapies, says Raymond R. Russell, MD, PhD, director of nuclear cardiology at the Cardiovascular Institute at Rhode Island Hospital in Providence and director of its cardio-oncology program. His research has helped elucidate the cellular pathways for anthracycline-induced heart failure.

Besides anthracyclines, oncologists may consider conventional therapies such as taxanes, an antimicrotubule agent, and radiation. Newer approaches include biological drugs such as trastuzumab, a monoclonal antibody; 5-fluorouracil, an antimetabolite; small molecule tyrosine kinase inhibitors; proteasome inhibitors; and immune therapy. Each is designed to exploit a potential vulnerability in cancer cells, widening physicians’ arsenal against the disease. And each carries its own potential, and sometimes as yet unknown drawbacks.

“There have been dramatic changes in what is being done for cancer, [but] there are some unique forms of cardiotoxicity with different agents,” says Russell, the lead author of an information statement from the American Society of Nuclear Cardiology (ASNC) on multimodality imaging and its role in the management of cardiac complications in patients under treatment for cancer (J Nucl Cardiol 2016;23[4]:856-84).

Cardiovascular risk factors and individual variability add other layers of complexity. Cumulative dose is the largest predictor of cardiotoxicity with anthracyclines, for instance, but some patients may develop LV dysfunction after one treatment and others may fare relatively well through a full cycle. The challenge with anthracyclines and other options is identifying who is at risk, or if complications develop, intervening early enough to reverse or minimize the development of heart failure.

“Part of [the risk of developing heart failure] is due to the cancer treatment, but there definitely is individual susceptibility,” says Ana Barac, MD, PhD, a cardiologist at MedStar Washington Hospital Center in Washington, D.C., who specializes in cardiac imaging. “There is also an increasing role of cardiovascular risk factors, in particular hypertension. While there are cancer treatments that are known to cause cardiomyopathy and lead to heart failure, there is this larger unknown yet to be discovered of individual susceptibility.”

Imaging’s role in assessing myocardial damage from chemotherapy agents

Cardio-oncology programs like the one Russell helped build at Smilow Cancer Hospital at Yale New Haven in Connecticut and later at the Cardiovascular Institute at Rhode Island emphasize a collaborative and integrated approach to care that includes imaging to promote cancer patients’ cardiovascular health. “Each test has its strengths and weaknesses,” Russell says. Cardio-oncology programs “understand the broad arsenal of imaging.”

The ASNC statement recommends multimodality imaging with nuclear cardiology techniques recognized as the gold standard of care for reducing the incidence and severity of heart failure. For instance, guidelines support the use of ERNA for monitoring patients on anthracyclines based on proven clinical effectiveness, but acknowledge radionuclide angiography exposes patients to diagnostic radiation. The American Society of Clinical Oncology’s guidelines, on which Barac is a co-author, recommend echocardiography during and after cancer treatment but, if echo is not available or feasible, then cardiac MRI or MUGA (J Clin Oncol online Dec. 5, 2016). But echo has its limitations, too, including technique-related variability.

It’s important to stick with one modality, the experts say, as long as it is reliable, reproducible and accurately measures changes over time. ASNC recognizes that numerous protocols exist with varying frequency for testing but, at least for anthracyclines and trastuzumab, all call for a baseline LVEF and serial monitoring. Some new, targeted therapies may not even require a baseline LVEF assessment, Barac says, and tipping points for intervening in time to avoid irreversible damage have yet to be established.

“We know that there are cardiac structure and function parameters that can be measured by echo or MRI or MUGA, and we know they all may start changing,” she says. “When is that key point of the change that will lead to clinical events? We don’t have a good answer.”

Russell also sees many fundamental questions outstanding. “Can we identify individuals who are at higher risk of cardiotoxicity?” In addition to noninvasive imaging, the answer may involve incorporating other tools such as biomarkers and genetic factors, he says. “With that information, what can we do to enhance cardioprotection? … The studies are a little messy here.”