Advances in cancer therapy and supportive care during the last several decades have dramatically increased the number of patients surviving longer than ever before.¹ One major outcome of life-extending and life-saving medical improvements is the need to address chronic and long-term side effects, particularly those resulting in cardiac dysfunction.¹

For example, breast cancer patients treated with anthracycline or trastuzumab chemotherapy are linked to an elevated or even significantly higher risk of symptomatic heart failure.^1,2,3 This is also the case for patients who have below normal or even mildly reduced ejection fraction (EF) at the start of cancer therapy.^1,3

In these situations, clinicians are learning that surveillance using advanced imaging methods can play an important role in preventing and monitoring cardiotoxicity symptom development.^1,3 Currently, the definition of cardiotoxicity used by clinicians is a 5 to 10% decrease in left ventricular EF from its baseline, however, it has recently challenged as a potentially irreversible late stage.²

Growing Role of Cardio-Oncology Imaging

Cardio-oncology is the growing field of medicine based on new research showing that more advanced imaging modalities assist with the early detection of cardiotoxicity.² Early detection and diagnosis mean patients receive care that prevents cancer treatment-associated heart failure from developing.²

Heart failure is a progressive disorder that can manifest during or after completion of radiation treatment or chemotherapy.¹ It is a complication that impacts both survival and quality of life.¹ Onset of cardiotoxicity-induced heart failure can interrupt or cause the discontinuation of cancer treatment and impact a patient’s chance for survival.¹

Initial manifestation of asymptomatic cardiac dysfunction occurs before the development of obvious signs and symptoms in cancer patients receiving cardiotoxic cancer treatment.¹

Two-dimensional echocardiography in combination with Doppler flow studies has been a preferred imaging approach for diagnostic evaluation and monitoring of high-risk cancer patients without clinically significant symptoms.¹ It is a portable, non-invasive, safe, and readily available modality that’s able to provide critical information about right and left ventricular structure, systolic and diastolic function, valvular disease, and hemodynamics.¹

Left ventricular EF is a widely researched measure of cardiac function in cancer patients.¹ Hector and colleagues reported that two-dimensional speckle tracking echocardiography (2D-STE) derived strain and strain rate is able to identify changes in myocardial mechanics before changes in left ventricular EF occur.⁴ This means 2D-STE can assist in predicting a future decrease in ejection fraction to less than 50% or of greater than 10% indicative of cardiotoxicity.⁴

Recent advances in echocardiographic imaging have also allowed for the investigation of novel parameters that may offer crucial early information about cardiac function during and after cancer therapy.¹ Potential new data points include diastolic function, E/A ratio, tissue Doppler measures, prolonged isovolumetric relaxation time, and global longitudinal strain (GLS).¹

Longitudinal strain is a novel parameter for cardiac function recently identified as a potential predictor of cardiotoxicity.¹ GLS measurements in cancer patients may potentially change the field of cardio-oncology because strain allows clinicians to understand what is happening in a patient’s heart before a decline in left ventricular function.⁵ This can allow for pretreatment risk stratification, early dysfunction identification, recovery prediction, as well as surveillance and treatment of subclinical left ventricular damage.⁵

In one prospective study evaluating 81 patients with breast cancer, GLS was assessed at baseline after anthracycline treatment and every three months during trastuzumab therapy.¹ Researchers found that a strain value of greater than −19 percent after the completion of anthracyclines was predictive of cardiotoxicity.¹ This was defined by an asymptomatic decrease in left ventricular EF of greater than or equal to 10 percent to less than 55 percent, or a symptomatic decrease in left ventricular EF of greater than or equal to 5 percent to less than 55 percent. ¹

Other findings that support the use of GLS were corroborated by investigators in a separate study.¹ Researchers found an 11 percent reduction in longitudinal strain defined by a decrease in left ventricular EF of greater than or equal to 10 percent was predictive of cardiotoxicity.¹

Currently in progress, the Strain Surveillance During Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR] study intends to provide clarity on timing of screening and implementation of interventions based on change in GLS alone.^1,6 SUCCOUR is an international multi-center randomized controlled trial designed to evaluate the hypothesis that GLS guidance of cardioprotective therapy will improve cardiac function in at-risk patients undergoing potentially cardiotoxic chemotherapy compared with usual care.⁶

Other imaging modalities such as cardiac MRI or multigated acquisition scan (MUGA) may be considered if an echocardiogram is not available or technically feasible due to poor image quality, body habitus, chronic lung conditions, or history of mediastinal surgery.¹ In this setting, three-dimensional echocardiography may also be considered.¹

Use of serum cardiac biomarkers (troponins, natriuretic peptides) or echocardiography-derived strain imaging in conjunction with routine diagnostic imaging have demonstrated diagnostic and prognostic use in cancer patients undergoing cardiotoxic treatments.¹ One large study evaluated the use of serum monitoring in 703 patients with cancer using TnI measurements of myocardium damage at multiple time points, including immediately after treatment, then at 12, 24, 36, and 72 hours after each high-dose chemotherapy cycle.¹ This was then followed up again with a one-month evaluation after completion of chemotherapy.¹ The highest incidence of cardiotoxicity was observed among patients with TnI elevation within 72 hours of chemotherapy and it persisted at one month after treatment.¹

In a separate study by the same group of researchers but conducted with patients receiving trastuzumab, investigators demonstrated that an elevated TnI was associated with an increased risk of cardiotoxicity and a lack of left ventricular EF recovery.¹ It was also found to be indicative of a particularly high cardiovascular risk group with a poor prognosis.¹ While the use of biomarkers are common in the management of heart failure in non-oncology patients, their use in asymptomatic patients with cancer is still considered investigational.¹

Asymptomatic cancer patients assessed to be at increased risk of developing cardiac dysfunction should be offered routine surveillance with echocardiography at an individually determined frequency based on clinical evaluation and patient circumstances.¹

Some clinicians use routine echocardiographic surveillance in patients with metastatic breast cancer who continue receiving trastuzumab indefinitely with imaging frequency determined case by case.¹

Echocardiography has been the most widely used method for monitoring cardiac function after cancer treatment.1 Three-dimensional echocardiograms are preferred when available and feasible because two-dimensional imaging may not be sensitive enough to detect changes in left ventricular EF below 10 percent.¹ This can be significant since studies have shown even mild reductions of five percent have been indicative of disease onset.¹

For cancer survivors who received cardiotoxic treatments, the ideal timing for evaluation of clinical signs and symptoms of heart failure with echocardiography and serum biomarker techniques is between six and 12 months.¹ If no symptoms are identified during this evaluation, future surveillance frequency and duration can be determined individually.¹

Many oncologists have opted to conduct imaging studies using a variety of techniques to evaluate cardiac function at six to 12 months after therapy is completed in higher risk patients.¹ Onset of most cancer treatment-associated cardiac dysfunction is known to develop within the first year after treatment ends, whereas the greatest chance for improvement is when pharmacotherapy is started as close to cardiotoxicity-induced onset as possible.¹

In instances where echocardiography is not available or technically feasible due to poor image quality or other parameters, cardiac MRI can provide detailed information about cardiovascular anatomy, systolic and diastolic function, as well as the lack of additional radiation emission.¹ In a study that evaluated 91 patients with reduced left ventricular EF after anthracycline, cardiac MRI–derived left ventricular mass was found to be an independent predictor of cardiovascular death, implantable cardioverter-defibrillator placement, and admission for decompensated heart failure.¹

A separate study using cardiac MRI found the magnitude of early gadolinium relative enhancement following the initial dose of anthracycline was predictive of later decline in left ventricular EF by greater than 5 percent before, during, and after anthracycline-based chemotherapy for breast cancer.¹ Hector and colleagues found three-dimensional echocardiography derived left ventricular EF has an excellent correlation with cardiac MRI and can be used to monitor left ventricular EF.⁴

It’s important for clinicians to initiate a discussion and inform patients of the potential cardiovascular risks of cancer treatment and stress the need to report signs and symptoms as early as possible.^1,7 Prevention and screening strategies implemented during cancer treatment may be beneficial to certain at-risk populations of survivors.¹ Development of cardiac disease in patients is potentially preventable using echocardiograms, MRIs, and basic clinical checkups to screen for heart complications.⁸

REFERENCES:

Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. ASCO Journal of Clinical Oncology. http://ascopubs.org/doi/full/10.1200/JCO.2016.70.5400 Accessed 7/6/2018
Role of Imaging in Cardio-Oncology. Current Treatment Options in Cardiovascular Medicine. https://link.springer.com/article/10.1007percent2Fs11936-017-0546-2#citeas Accessed 7/6/2018
ASCO 2018: How cardiac imaging, biomarkers could improve cancer patient care. HealthImaging. https://www.healthimaging.com/topics/cardiovascular/asco-2018-how-cardiac-imaging-biomarkers-could-improve-cancer-patient-care Accessed 7/6/2018
Cardio-Oncology: Role of Echocardiography. Progress in Cardiovascular Diseases. https://www.sciencedirect.com/science/article/pii/S0033062014000668?viapercent3Dihub Accessed 7/6/2018
Imaging crucial to cardio-oncology strategy. Healio. https://www.healio.com/cardiology/imaging/news/online/percent7B6b62e7ee-d900-4a11-81fd-f2fe2f9b2487percent7D/imaging-crucial-to-cardio-oncology-strategy Accessed 7/6/2018
Rationale and Design of the Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes (SUCCOUR) Trial. Journal of the American College of Cardiology. http://imaging.onlinejacc.org/content/early/2018/06/08/j.jcmg.2018.03.019 Accessed 7/6/2018
ESC position paper addresses cardiotoxicity of cancer therapies. CardiologyToday. https://www.healio.com/cardiology/imaging/news/online/%7B65b3e32b-ec99-4e67-a337-01ed5610c280%7D/esc-position-paper-addresses-cardiotoxicity-of-cancer-therapies Accessed 7/6/2018
Five reasons imaging is a crucial component of cardio-oncology. Cardiovascular Business. https://www.cardiovascularbusiness.com/topics/imaging/5-reasons-imaging-crucial-component-cardio-oncology Accessed 7/6/2018