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Review: Advanced Imaging May Detect Earlier Signs of Cancer-related Cardiotoxicity

Key findings

  • The American Society of Clinical Oncology (ASCO) recommends measuring left ventricular ejection fraction by echocardiography before initiating a chemotoxic chemotherapeutic agent and again at 6-12 months after administration of a cardiotoxic chemotherapeutic agent in those at higher risk.
  • ASCO considers cardiac magnetic resonance (CMR) and multigated acquisition scans to be the alternative modalities of choice if needed after echocardiography, with preference given to CMR
  • New applications of CMR and positron emission tomography are being studied in research settings for cardiotoxicity screening
  • Substantial evidence suggests that echocardiographic myocardial strain imaging can detect very early damage

Because of recent advances in cancer treatment, more patients are surviving long enough to develop cardiotoxicity due to cancer, chemotherapy or radiation therapy. The standard method for detecting cardiotoxicity is the serial measurement of left ventricular ejection fraction (LVEF), but LVEF is generally a late manifestation of cardiovascular damage. According to a review in Current Problems in Cancer, Tomas G. Neilan, MD, MPH, director of the Cardio-Oncology Program, and colleagues say advanced imaging methods may be able to detect cardiotoxicity prior to the onset of LV dysfunction, thereby improving patient outcomes and reducing costs. They also discuss current and emerging imaging modalities for cardiotoxicity screening.

Current Standards

Cardiotoxicity is generally defined as:

  • A decrease in LVEF of ≥5% to < 55% and symptoms of heart failure
  • An asymptomatic decrease in LVEF of ≥10% to <55%

In 2016, the American Society of Clinical Oncology (ASCO) published a guideline on preventing cardiac dysfunction in adult cancer survivors. It recommends measuring LVEF by echocardiography before initiating a chemotherapeutic agent associated with a higher risk of cardiotoxicity. Subsequent surveillance depends on the drug and dose used and the patient's initial cardiovascular risk factors; however, given the typical profile of these patients, most end up being considered at elevated risk supporting a follow-up study.

Imaging Modalities

 

Cardiac magnetic resonance (CMR)

CMR is the gold standard for detecting cardiotoxicity because of its accuracy, reproducibility and ability to detect subtle changes in cardiac structure and function.

However, CMR has substantial disadvantages compared with echocardiography, including higher cost and less availability. ASCO suggests using CMR for detecting cardiotoxicity only if echocardiography is unavailable or not technically feasible.

There are additional potential strengths to CMR that may be applied to patients at risk of cardiotoxicity. These include tissue characterization, with measurement of native T1, the extracellular volume and T2 mapping. Beyond these tools, CMR also robustly measures cardiac mass and vascular function which can both be affected by cardiotoxic therapies.

Two-dimensional echocardiography

ASCO favors 2D echocardiography for cardiotoxicity screening because of its wide availability, reproducibility, versatility, lack of radiation exposure and safety in patients with renal disease. Its main limitation is variability in LVEF measurements over time (8–10%). That variability can be reduced by using contrast or 3D echocardiography, but the latter is not as widely available.

Echocardiography with strain imaging

Substantial evidence suggests, the authors say, that echocardiographic myocardial strain imaging can identify patients who are at risk of heart failure but do not yet have symptoms or structural changes.

In this technique, myocardial deformation is measured in three dimensions: longitudinal, radial and circumferential. Global longitudinal strain is a sensitive measure of systolic function and is reduced by cardiotoxic chemotherapies prior to change in EF. The American Society of Echocardiography recommends strain imaging for patients scheduled to receive cancer drugs that can cause type I cardiotoxicity (for example, anthracyclines) or type II cardiotoxicity (for example, trastuzumab). Patients who receive drugs with the potential for type I toxicity should also undergo strain imaging at the completion of therapy and six months later.

Multiple gated acquisition (MUGA)

ASCO recommends MUGA scans for LVEF assessment only if echocardiography and CMR are not feasible. MUGA correlates well with other 3D imaging such as CMR, but for serial monitoring of LVEF, it is best to choose a single modality.

Positron emission tomography (PET)

PET is the gold standard for assessing myocardial metabolism and perfusion. Several research groups suggest PET could monitor for anthracycline-induced and sunitinib-induced cardiotoxicity, but published data are so far limited.

Computed tomography (CT)

CT screening for cardiotoxicity is most useful after radiation therapy, which increases the risk of coronary artery disease. CT is a reliable, noninvasive method for imaging the coronary arteries.

Cardiac CT can also be used to assess the pericardial space for effusions and detect pericarditis. Alone or with CMR, it can also assess cardiac masses.

Towards the Future

All imaging methods have advantages and limitations, the authors note. They believe an algorithm for cardiotoxicity screening will be developed that has two parts:

  • Recommendations about risk stratification with one or more imaging modalities, to be conducted before and after commencing cancer therapy
  • Recommendations about subsequent surveillance, tailored to individual patients based on the risk stratification and type of cancer therapy

Whatever guidance is developed, the authors say, shifting away from reliance on LVEF measurement should allow for detection of cardiotoxicity prior to potentially irreversible damage.

Refer a patient to the Mass General Heart Center

Learn more about the Cardio-Oncology Program

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