By Michael H. Crawford, MD

Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: Reductions in left ventricular ejection fraction in patients receiving potentially cardiotoxic chemotherapy may be because of significant decreases in left ventricular volume in up to 20% of these patients. In such patients, a trial of volume repletion may be appropriate before stopping chemotherapy or adding cardioprotective drugs.

SOURCE: Meléndez GC, Sukpraphrute B, D’Agostino RB Jr, et al. Frequency of left ventricular end-diastolic volume-mediated declines in ejection fraction in patients receiving potentially cardiotoxic cancer treatment. Am J Cardiol 2017;119:1637-1642.

Left ventricular ejection fraction (LVEF) is followed in patients receiving potentially cardiotoxic chemotherapy frequently. However, EF is preload-dependent, and little attention has been paid to changes in LV volume with chemotherapy. Investigators from Wake Forest University prospectively studied 112 patients receiving potentially cardiotoxic chemotherapy by cardiac magnetic resonance (CMR) imaging before and three months after chemotherapy. The patients received an admixture of agents: alkylating agents (74%), anthracyclines (72%), and tyrosine kinase inhibitors (51%). Exclusion criteria included contraindications to CMR and if they had an EF < 50% at baseline. Chemotherapy-induced LV dysfunction was defined as an EF decline of > 10% or to an absolute value of < 50%. Significant declines in LV end-diastolic volume (EDV) were defined as > 19mL (25th percentile) and increases in LV end-systolic volume (ESV) as > 10mL (75th percentile).

Chemotherapy-related decreases in LVEF were seen in 26 of the 112 patients (23%). Of these 26 patients, six exhibited significant drops in LVEDV, and only one of these had an increase in ESV. In 15 of the 26, ESV increased significantly without a change in EDV, which suggests a true decrease in contractility. Five of the 26 had minor changes in EDV and ESV. Thus, about 20% of the patients who experienced a significant decrease in EF had isolated reductions in EDV, suggesting that they moved downward on the Frank-Starling curve rather than experiencing a reduction in contractility. The authors concluded that nearly one-fifth of patients experiencing significant reductions in LVEF with chemotherapy have isolated reductions in EDV, which could be treated with volume repletion. They recommended paying more attention to LV volumes when assessing the imaging results of patients with large drops in EF associated with potentially cardiotoxic chemotherapy.

COMMENTARY

A reduced LVEF after chemotherapy is a common reason for an outpatient cardiology consultation, and many of these patients have their chemotherapy stopped, which might not be good for their long-term survival. Also, most end up on cardioprotective drug therapy, which no one knows how long to continue. This study suggests that nearly one-fifth of these patients may have a reduced EF solely due to reduced LVEDV, with the patient moving down the Frank-Starling curve. This is not surprising given that chemotherapy often causes emesis and nausea that could suppress oral intake. The tip-off is that the EDV is reduced, and the ESV is not increased. Usually with reduced contractility, the ESV increases. Of course, this requires accurate LV volume measurements, which you don’t get from a multiple gated acquisition scan, if your oncologists are still using that antiquated technology. Echocardiography should be more than adequate, and you can analyze diastolic function and LV strain rate, which will augment the assessment of LV performance. Not all echo labs provide a quantitative report, so you may have to make your own measurements or use another technique. This study used CMR, which is quite accurate but also expensive and not available everywhere.

The major weakness of this study is that the authors didn’t volume-replete the low EDV, low EF patients to see how many would recover their EF. However, it would seem worth trying in stable patients, before stopping chemotherapy or adding cardioprotective drugs that may lower blood pressure.