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Echo targets cancer drug cardiotoxicity

Echocardiography has a central role to play in identifying patients at cardiac risk from cancer therapies, and evaluating potential cardioprotective treatments, according to two studies presented recently at the European Society of Echocardiography’s annual ‘EUROECHO and other Imaging Modalities’ 2011 Congress in Budapest, Hungary.

One study1 reports on an initiative using echocardiography to document early warning signs of adverse effects from trastuzumab (Herceptin ®), while the other uses echocardiography to evaluate the protective role of ACE inhibitors and statins on the hearts of cancer patients.2

“These studies open the way for the early identification of myocardial damage at the subclinical level, thereby allowing clinicians to identify patients who might benefit from either changes in cancer therapy or the delivery of protective treatments,” says European Association of Echocardiograpy (EAE) president Dr Luigi Badano (University of Padua, Italy).

tim bannerThe cardiotoxic effects of cancer treatments encompass a heterogeneous group of disorders, says Dr Helder Dores (Santa Cruz Hospital/São Francisco Xavier Hospital, Lisbon, Portugal): “They range from relatively benign arrhythmias, and hypertension, to potentially lethal conditions such as thromboembolism, myocardial infarction and cardiomyopathy with symptomatic heart failure”.

In October 2011 the EAE announced that it is working with the American Society of Echocardiography (ASE) and American Society of Clinical Oncology (ASCO) to issue joint recommendations on the usefulness of echocardiographic evaluations in cancer patients, expected to be published in 2012. “The document should lay down guidance for the frequency of assessment with different chemotherapy agents, and also identify when patients should stop treatment or be prescribed protective treatments,” says Dr Badano.

In the first study Dr Dores and colleagues set out to identify early warning signs of adverse cardiac effects in women treated with trastuzumab for breast cancer. In the study 51 consecutive women, enrolled for treatment between May and September 2010, were assessed at baseline with echocardiography and then again at three months.
The investigators found that within the first three months no patients presented with overt signs of heart failure or significant left ventricular systolic function deterioration, although almost one-fifth developed impaired ventricular relaxation.

“Patients with impaired ventricular relaxation are known to be at higher risk for progression to advanced stages of cardiac dysfunction (both systolic and diastolic), making it important for these patients to be subject to more frequent evaluations both during and after therapy,” says Dr Dores.

Further studies are now needed, he says, to assess whether impaired ventricular relaxation occurs in larger populations of patients prescribed trastuzumab.  “We need studies identifying the women who go on to develop overt cardiac dysfunction to see whether we can more accurately determine predictors of these adverse events at an earlier stage of treatment.”

In the second study Dr Radulescu and colleagues used echo-Doppler echocardiography to investigate whether the ACE inhibitor lisinopril and the statin rosuvastatin might confer a cardio protective effect on patients treated with anthracyclines for a range of malignancies.

“While the exact mechanism of anthracycline related cardiotoxicity is not fully understood, animal studies have pointed to oxidative stress and inflammation.   Both ACE inhibitors and statins are known to play an important role in reducing oxidative stress and inflammation at the level of the heart muscle cells,”says Dr Andreea Parv.

In the prospective study left ventricular ejection fractions and LV diastolic function were compared for the study group of 26 patients treated with the anthracycline epirubicin who were also given the cardio protective treatments Lisinopril 10 mg and Rosuvastatin 10 mg, and a control group of 31 gender and age-matched patients who received epirubicin but had no accompanying cardioprotective treatments.

Results show that in comparison with patients receiving cardio protection the patients who receive no protection showed further deterioration of LV diastolic function, calculated as the ratio of early diastolic filling velocity(E) to filling velocity after atria contraction E/A (p<0.02).
“This is the first human prospective study documenting the cardioprotective effect of lisinopril and rosuvastatin in anthracycline induced cardiotoxicity,” says Dr Radulescu.  Further studies, she adds, are now needed in larger numbers of patients, exploring a range of different types of malignancies.



References

1 Dores H, Gandara F, Correia MJ et al. Early Trastuzumab induced cardiotoxicity in breast cancer patients.  Abstract P315
(Available from: http://spo.escardio.org/AbstractDetails.aspx?id=101200&eevtid=49).

2 Radulescu L, Radulescu D, Andreea P et al. Cardioprotective role of lisinopril and rosuvastatin in the prevention of anthracycline induced cardiotoxicity.  Abstract P316 (Available from http://spo.escardio.org/AbstractDetails.aspx?id=101201&eevtid=49).

Full scientific programme available here: http://www.escardio.org/congresses/euroecho2011/Pages/welcome.aspx

Published on: January 10, 2012

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