Is it time to move from LVEF to cardiac reserve in CTRD?

Cardiac reserve assessment may be a more appropriate measure of cancer treatment-related cardiac dysfunction (CTRD) than left ventricular ejection fraction (LVEF).

That’s according to Dr Daniel Chen, cardio-oncology fellow at the Bart’s Heart Centre, University College of London Hospital, and the Hatter Cardiovascular Institute.

CTRCD refers to systolic or diastolic dysfunction following exposure to cardiotoxic cancer treatments, he explained. This may affect people as the treatment is administered, or as a late effect. 

The absence of measurable cardiotoxicity at the completion of treatment, he pointed out, does not mean the risk of subsequent heart failure (HF) is low. Dr Chen also highlighted the fact that HF detected years after cancer treatment is associated with worse outcomes than other forms of the disease.


Non-invasive cardiac imaging, including cardiac MRI (CMRI), 2D and 3D echocardiography, and radionuclide angiography (RNA), are the mainstays of CTRCD diagnosis. 

But there remains a lack of clarity around what defines the condition. Most diagnostic criteria include an asymptomatic decrease LVEF by 10 to 15% below a threshold of 50 to 55%, or HF symptoms associated with a decrease in LVEF by 5%.

Other diagnostic limitations include 2D echo re-test variability, and that a reduction in LVEF is a relatively late outcome of HF. “Perhaps most important is that the key presenting symptoms of these patients is that of exertional breathlessness, rather than at rest when current diagnostic strategies provide assessment,” said Dr Chen.

Cardiac reserve

Dr Chen suggested that cardiac reserve, defined as the increase in cardiac function from rest to peak exercise, was a more appropriate diagnostic strategy. “In non-cancer HF patients, reduced cardiac reserve is demonstrated, even in the setting of normal resting cardiac function. The progression of HF is similarly associated with decreased cardiac reserve alongside worsening symptoms and exercise capacity.”

Echo, RNA, CMRI, and pharmacological stress tests can all be used to assess cardiac reserve during exercise. Across all these modalities, the challenge has always been to maintain accuracy during peak exercise, said Dr Chen.

Cardiopulmonary exercise testing (CPET) can provide important information on respiratory, cardiovascular, and muscle metabolic function – including oxygen consumption, carbon dioxide production, and lung ventilation – at rest and during effort. 

During a CPET, the patient is monitored by ECG and wears a facemask connected to a gas analyser. A pulse oximeter and sphygmomanometer are also used. Exercise can be carried out on a treadmill or bike. The parameters measured include VO2, VCO2, and lung ventilation. 

Said Dr Chen: “The concept of cardiac reserve is important because despite normal cardiac function at rest, many cancer survivors demonstrate a reduced exercise capacity. Their peak VO2 values are consistently below those for healthy individuals matched for age and gender, and this is increasingly suggested to be a predictor of mortality.”

Early intervention 

A reduction in exercise capacity is a common finding in breast and haematological cancer survivors who were exposed to cardiotoxic treatment, but have a preserved resting LVEF. There is a growing body of evidence to suggest that this is associated with mortality, Dr Chen said.

“Consequently, cardiac reserve assessment is an important adjunct in the complete assessment for CTRCD, but the studies which demonstrate the benefit in the current literature are small and heterogenous, and therefore larger and more robust trials are still required,” he concluded. 

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