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POSTER PRESENTATION Open Access CMR shows that anthracycline cardiotoxicity is common in women treated for early breast cancer and associated with undiagnosed hypertension; but cannot be reliably detected using late-gadolinium enhancement imaging Paul Kotwinski 1,2* , Gillian Smith 1 , Julie Sanders 1 , Jackie Cooper 4 , David Kotwinski 1 , Albert Teis 2 , Michael (Monty) G Mythen 5 , Alison Jones 3 , Hugh E Montgomery 1 , Dudley J Pennell 2 From 16th Annual SCMR Scientific Sessions San Francisco, CA, USA. 31 January - 3 February 2013 Background A growing number of patients with cancer are at risk from chronic anthracycline cardiotoxicity (cAC) as a result of improving cancer prognosis. Although susceptibility is cumulative dose-related, it is also idiosyncratic. Further- more, at present there is no way to reliably identify those at risk. The common practice of serially measuring LV ejection fraction (LVEF) only identifies cardiotoxicity after significant damage has been incurred. We hypothesised that risk of cAC could be determined from patient and treatment factors, known at baseline, together with assess- ment of the cardiac response to the 1st dose of anthracy- cline. Here we report the prevalence of cAC detected using CMR, together with the associations with baseline BP and anthracycline dose. Methods Women due to receive anthracycline-based chemotherapy for early breast cancer were recruited. Those with known cardiovascular disease were excluded. CMR was per- formed on Siemens 1.5T scanners before chemotherapy and at follow-up (>1 year after the final anthracycline cycle, and >3 months after Trastuzumab). LVEF was mea- sured from cine images by a single operator (PK) blind to clinical and temporal data, using CMRtools. Chronic AC (cAC) was defined as a fall in absolute LVEF 5%. Results 164 subjects completed the study 18.5 [15.1-23.7] months after finishing treatment. 99% received epirubicin (400 [300-450] mg/m2). The mean fall in LVEF was 2.2% (p<0.001), compared with a projected increase of 0.2%. The cardiac response was heterogeneous: 20.7% (N=34) were in the subclinical cAC group. Mean LVEF also fell in the remainder of the cohort (by 0.8%, p=0.03), demon- strating this group were minimally affected, rather than unaffected. No subjects developed late gadolinium enhancement as a result of treatment (LGE images in N=119). There was a trend towards patients who received epirubicin 450mg/m2 being in the cAC group (odds ratio (OR) 2.12 [0.97-4.60], p=0.06). Patients with baseline BP 140/90mmg were more likely to be in the cAC group (OR 3.63 [1.31-10.09], p=0.01); of these 18, only 1 was diagnosed and treated for hypertension. Conclusions Falls in LVEF 5% were detected in >20% of patients. Declines in resting LVEF are relatively late in the patholo- gical process of cAC and therefore likely to reflect increased risk of heart failure as a late-effectof cancer treatment. Our data suggest that undiagnosed hyperten- sion was common; diagnosing and treating it may offer an opportunity to reduce cAC. A fall in LVEF 5% detected by CMR may be a better end-point for monitoring cardiotoxicity in oncology trials than those currently used. Although fibrosis is a hallmark of cAC based on biopsy 1 Institute of Human Health and Performance, UCL, London, UK Full list of author information is available at the end of the article Kotwinski et al. Journal of Cardiovascular Magnetic Resonance 2013, 15(Suppl 1):P276 http://www.jcmr-online.com/content/15/S1/P276 © 2013 Kotwinski et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

CMR shows that anthracycline cardiotoxicity is common in women treated for early breast cancer and associated with undiagnosed hypertension; but cannot be reliably detected using late-gadolinium

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POSTER PRESENTATION Open Access

CMR shows that anthracycline cardiotoxicityis common in women treated for early breastcancer and associated with undiagnosedhypertension; but cannot be reliably detectedusing late-gadolinium enhancement imagingPaul Kotwinski1,2*, Gillian Smith1, Julie Sanders1, Jackie Cooper4, David Kotwinski1, Albert Teis2,Michael (Monty) G Mythen5, Alison Jones3, Hugh E Montgomery1, Dudley J Pennell2

From 16th Annual SCMR Scientific SessionsSan Francisco, CA, USA. 31 January - 3 February 2013

BackgroundA growing number of patients with cancer are at risk fromchronic anthracycline cardiotoxicity (cAC) as a result ofimproving cancer prognosis. Although susceptibility iscumulative dose-related, it is also idiosyncratic. Further-more, at present there is no way to reliably identify thoseat risk. The common practice of serially measuring LVejection fraction (LVEF) only identifies cardiotoxicity aftersignificant damage has been incurred. We hypothesisedthat risk of cAC could be determined from patient andtreatment factors, known at baseline, together with assess-ment of the cardiac response to the 1st dose of anthracy-cline. Here we report the prevalence of cAC detectedusing CMR, together with the associations with baselineBP and anthracycline dose.

MethodsWomen due to receive anthracycline-based chemotherapyfor early breast cancer were recruited. Those with knowncardiovascular disease were excluded. CMR was per-formed on Siemens 1.5T scanners before chemotherapyand at follow-up (>1 year after the final anthracyclinecycle, and >3 months after Trastuzumab). LVEF was mea-sured from cine images by a single operator (PK) blind toclinical and temporal data, using CMRtools. Chronic AC(cAC) was defined as a fall in absolute LVEF ≥5%.

Results164 subjects completed the study 18.5 [15.1-23.7] monthsafter finishing treatment. 99% received epirubicin (400[300-450] mg/m2). The mean fall in LVEF was 2.2%(p<0.001), compared with a projected increase of 0.2%.The cardiac response was heterogeneous: 20.7% (N=34)were in the subclinical cAC group. Mean LVEF also fell inthe remainder of the cohort (by 0.8%, p=0.03), demon-strating this group were minimally affected, rather thanunaffected. No subjects developed late gadoliniumenhancement as a result of treatment (LGE images inN=119). There was a trend towards patients who receivedepirubicin ≥450mg/m2 being in the cAC group (odds ratio(OR) 2.12 [0.97-4.60], p=0.06). Patients with baseline BP≥140/90mmg were more likely to be in the cAC group(OR 3.63 [1.31-10.09], p=0.01); of these 18, only 1 wasdiagnosed and treated for hypertension.

ConclusionsFalls in LVEF ≥5% were detected in >20% of patients.Declines in resting LVEF are relatively late in the patholo-gical process of cAC and therefore likely to reflectincreased risk of heart failure as a ‘late-effect’ of cancertreatment. Our data suggest that undiagnosed hyperten-sion was common; diagnosing and treating it may offer anopportunity to reduce cAC. A fall in LVEF ≥5% detectedby CMR may be a better end-point for monitoringcardiotoxicity in oncology trials than those currently used.Although fibrosis is a hallmark of cAC based on biopsy1Institute of Human Health and Performance, UCL, London, UK

Full list of author information is available at the end of the article

Kotwinski et al. Journal of Cardiovascular MagneticResonance 2013, 15(Suppl 1):P276http://www.jcmr-online.com/content/15/S1/P276

© 2013 Kotwinski et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

and ex-vivo data, it cannot be reliably detected using LGE;T1-mapping may be of greater utility.

FundingThis abstract presents independent research funded bythe UK Department of Health under the Genetics HealthResearch programme. It was sponsored by UniversityCollege London (UCL), and supported by the cardiovas-cular Biomedical Research Unit of Royal Brompton Hos-pital and Imperial College. Patients were recruitedthrough the auspices of the National cancer researchNetwork (NCRN). The views expressed in this publica-tion are those of the author(s) and not necessarily thoseof the NHS, NCRN or the Department of Health.

Author details1Institute of Human Health and Performance, UCL, London, UK. 2CMR Unit,The Royal Brompton Hosptial, London, UK. 3Department of Oncology, UCLPartners, London, UK. 4Centre for Cardiovascular Genetics, UCL, London, UK.5Biomedical Research Unit, UCLH/UCL, London, UK.

Published: 30 January 2013

doi:10.1186/1532-429X-15-S1-P276Cite this article as: Kotwinski et al.: CMR shows that anthracyclinecardiotoxicity is common in women treated for early breast cancer andassociated with undiagnosed hypertension; but cannot be reliablydetected using late-gadolinium enhancement imaging. Journal ofCardiovascular Magnetic Resonance 2013 15(Suppl 1):P276.

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Kotwinski et al. Journal of Cardiovascular MagneticResonance 2013, 15(Suppl 1):P276http://www.jcmr-online.com/content/15/S1/P276

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