It is well documented that some anti-cancer drugs can damage the heart, but a long-term follow-up of children and young adults who had doxorubicin[1] treatment for bone tumours suggests that the damage gets progressively worse as the years go on.
In a study published on-line today in Annals of Oncology[2] researchers from the University Medical Centre at the University of Groningen in the Netherlands, say that all patients treated with drugs known as anthracyclines should have life-long cardiac monitoring.
Their study followed 22 patients, who had been treated with moderate or high doses of doxorubicin for osteogenic sarcomas or malignant fibrous histiocytomas, for a median time of 22 years (between 15 and 27.5 years). It is believed to be the longest prospective follow-up to evaluate heart function in children, adolescents and young adults treated with anthracylines.
The researchers found over a quarter had systolic dysfunction and nearly half had diastolic dysfunction and that this was a further deterioration in heart function compared to an earlier follow-up when fewer than one in ten had systolic dysfunction and less than a fifth had diastolic dysfunction.
Lead researcher Dr Inge Brouwer, from the subdivision of paediatric oncology at the centre, said: "We undertook this long-term study because – since it's known that overt heart failure has been found in up to 5% of cancer survivors treated with anthracyclines – it was possible that subclinical abnormalities might be even more frequent. The natural course of subclinical abnormalities was largely unknown and it was unclear whether we could expect progressive cardiac deterioration."
There were 31 long-term survivors in the original group of patients treated between 1977 and 1999. Most were children and adolescents but the age range was 10 to 38. All had cardiac assessment nine years after treatment. Twenty-nine were re-assessed 14 years after treatment, and 22 in the present round of assessment. Of the original group, one died from congestive heart failure; one from a second cancer; two – who were already known to have an abnormal heart function – were excluded because they had received thoracic radiotherapy for a second cancer; one had a terminal neurodegenerative disease and four refused to take part.
In addition to a physical examination and medical history the assessment involved blood tests and blood pressure measurements, Doppler echocardiography, a static ECG and 24-hour ECG monitoring during normal activities. Systolic and diastolic function tests showed how well the heart's left chamber was pumping (systolic function) and relaxing (diastolic function).
Dr Brouwer said: "We found progressive impairment of systolic and diastolic function. We also found a deterioration in heart rate variability (HRV) in the 19 of the 22 patients whose HRV we were able to evaluate. HRV is the alteration in the beat-to-beat rate of the heart and reduced HRV is a marker for potential heart problems.
"Forty-five per cent of the 22 long-term survivors, whose median age is now 39, had diastolic dysfunction compared with 18% in 1997 and 27% had systolic dysfunction compared with 9% in 1997. The six patients with impaired systolic function also had abnormalities in the motion of the heart wall with suggestions of ischaemic heart disease in two of them. In addition, we knew that three of the nine patients who did not take part in this latest assessment, have or had cardiac dysfunction."
She said that other studies involving moderate term follow-up of anthracyline-treated cancer survivors had produced conflicting results with some showing progressive abnormalities, while others showed no further deterioration. "We also found unchanged systolic function at our moderate term follow-up and now subsequently a further decrease, but our study, although small, has a 22-year median follow-up, which is considerably longer than most others, which have been about 13 years."