Delayed contrast enhancement cardiac magnetic resonance imaging in trastuzumab induced cardiomyopathy

Journal of Cardiovascular Magnetic Resonance Delayed contrast enhancement cardiac magnetic resonance imaging in trastuzumab induced cardiomyopathy Nazanin Fallah-Rad 2 Matthew Lytwyn 2 Tielan Fang 2 Iain Kirkpatrick 0 Davinder S Jassal 0 1 2 0 Department of Radiology, University of Manitoba , Winnipeg, Manitoba , Canada 1 Section of Cardiology, Department of Cardiac Sciences, University of Manitoba , Winnipeg, Manitoba , Canada 2 Institute of Cardiovascular Sciences, St. Boniface Research Centre, University of Manitoba , Winnipeg, Manitoba , Canada Background: Trastuzumab (Herceptin), an antagonist to the human epidermal growth factor 2 (HER2) receptor significantly decreases the rates of breast cancer recurrence and mortality by 50%. Despite therapeutic benefits, the risk of cardiotoxicity with trastuzumab ranges from 10-15% when administered sequentially following anthraycline chemotherapy. Little is known about the utility of cardiac magnetic resonance (CMR) in the assessment of trastuzumab mediated cardiomyopathy. Methods and results: Between 2005-2006 inclusive, 160 breast cancer patients were identified at a single tertiary care oncology centre. Of the total population, 10 patients (mean age 40 8 years) were identified with trastuzumab induced cardiomyopathy, based on a LVEF less than 40% on serial MUGA or echocardiography. CMR was performed in all patients to determine LV volumes, systolic function and evidence of late gadolinium enhancement (LGE). At the time of diagnosis of trastuzumab induced cardiomyopathy, the mean LVEF was 29 4%. Subepicardial linear LGE was present in the lateral portion of the left ventricles in all 10 patients. Conclusion: LGE-CMR is a novel way of detecting early changes in the myocardium due to trastuzumab induced cardiotoxicity. - Introduction Breast cancer is a major public health concern that affects 1 in 7 women in their lifetime [1]. Anthracyclines are commonly used in the setting of adjuvant therapy in the treatment of breast cancer patients. While anthracyclines significantly improve clinical morbidity and mortality, there are notable cardiotoxic side effects [2]. Recent understanding of the biology of breast cancer has lead to the introduction of a new therapeutic agent, Trastuzumab (Herceptin), an antagonist to the human epidermal growth factor 2 (HER2) receptor, which is found in 25% of breast cancer patients [3]. When added to conventional anthracycline chemotherapy, trastuzumab significantly decreases the rates of recurrence and mortality by 50% in HER-2 positive breast cancer patients [4-6]. Despite therapeutic benefits however, the risk of cardiotoxicity with trastuzumab ranges from 1015% when administered in combination with anthracyline therapy [7,8]. Serial multiple gated acquisition scans (MUGA) are widely used to monitor cardiac dysfunction in breast cancer patients. However, with the improvement in both spatial and temporal resolution of cardiac magnetic resonance (CMR) over the past decade, it has now become the gold standard for the non-invasive assessment of left ventricular (LV) systolic dysfunction. Additionally, late gadolinium enhancement (LGE) can detect myocardial scarring. Although frequently used in the assessment of dilated cardiomyopathies secondary to ischemia or myocarditis [9], little is known about the utility of CMR in the assessment of trastuzumab induced cardiomyopathy. We report a case series of trastuzumab induced myocarditis characterized by left ventricular dysfunction and focal epicardial LGE using CMR imaging. Methodology Patient population Between 20052006 inclusive, 160 breast cancer patients who received trastuzamab in addition to anthracyline based adjuvant therapy were identified at a tertiary care oncology centre. All patients received FEC (5-fluorouracil, epirubicin and cyclophoshamide) for a total of 6 cycles. The mean duration between completion of chemotherapy and initiation of trastuzumab was 2 1 months. Of the total population, 10 patients were identified with trastuzumab induced cardiomyopathy based on LV ejection fraction less than 40% on either serial MUGA or echocardiography. The medical records of all 10 patients were extensively reviewed for baseline demographic data. The retrospective study was approved by the local institutional review board. Cardiac MRI CMR was performed on all 10 patients using a 1.5 T scanner (Avanto, Siemens, Erlangen, Germany). Morphologic images in the cardiac short axis, 4 chamber long axis and 2 chamber long axis planes were acquired using IR-prepared dark blood HASTE sequences (TR 600 ms, TE 26 ms, 6 mm slice thickness, 1.8 mm interslice gap). In the same planes, cine-CMR was performed using a breathhold balanced steady state free precession sequence (TrueFISP, TR 42 ms, TE 1.2 ms, FA 70, 6 mm slice thickness, matrix 192 174). The cine-CMR short-axis images encompassed the entire LV from the base to the apex (stack of 10 sequential short-axis slices; TR 64 ms, TE 1 ms, FA 80, 8 mm slice thickness, 1.6 mm interslice gap, matrix 192 132) to obtain a left ventricular ejection fraction (LVEF). Late gadolinium enhancement was performed after 10 minutes of 0.2 mmol/kg injection of Gadolinium (Gd-DTPA, Magnevist, Schering, Germany) using a T1-weighted IR-prepared multislice TrueFISP sequence with magnitude and phase sensitive reconstruction. Images were acquired sequentially in the short axis, followed by horizontal and vertical long axis images (TR 700 ms, TE 1.0 ms, FA 40, 8 mm slice thickness, 1.6 mm interslice gap, matrix 192 144). Results The total population included 10 patients (mean age 40 8 years, range 27 to 56 years) with normal LVEF at baseline and preserved systolic function following administration of anthracycline based chemotherapy using serial MUGA scans (Table 1). Cardiovascular risk factors, dose and frequency of chemotherapy, concomitant use of radiation therapy, and duration of trastuzumab therapy (35 months) were similar in the entire patient cohort (Table 1). At the time of diagnosis of trastuzumab induced cardiomyopathy, the left ventricular cavities were dilated with moderate to severe global LV systolic dysfunction on CMR (Table 2). The mean LVEF was for the total population was 29 4% (Table 2). Subepicardial linear LGE was present in the lateral portion of the left ventricles in all 10 patients suggesting the presence of trastuzumab induced myocarditis (Figure 1). Following the discontinuation of trastuzumab, 6 patients have recovered normal LV systolic function, while 4 Baseline LVEF (%) Post Chemothx LVEF (%) Trastuzumab Duration CV, cardiovascular; LVEF, left ventricular ejection fraction; chemothx, chemotherapy; HTN, hypertension. Delayed enhancement 6 month f/u LVEF (%) ACEI, beta blockers ACEI, beta blockers ACEI, beta blockers ACEI, beta blockers ACEI, beta blockers ACEI, beta blockers ACEI, beta blockers ACEI, beta blockers ACEI, beta blockers ACEI, beta blockers LVEF, left ventricular eje (...truncated)