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MYOCARDIAL STRAIN IMAGING BY CARDIAC MRI FOR DETECTION OF SUBCLINICAL MYOCARDIAL DYSFUNCTION IN BREAST CANCER PATIENTS RECEIVING CHEMOTHERAPY
S298
Canadian Cardiovascular Society (CCS) ePoster IMAGING CARDIOTOXICITY Monday, October 24, 2016 406 EARLY DETECTION OF DOXORUBICIN INDUCED CARDIOTOXICITY USING MYOCARDIAL T1 AND T2 RELAXATION TIMES M Aissiou, F Cheriet, D Curnier, T Hafyane, M Friedrich, C Laverdiere, G Andelfinger, M Krajinovic, D Sinnett, D Perie
Canadian Journal of Cardiology Volume 32 2016
enhanced T1 relaxation time as an index for myocardial tissue damage in the onset of doxorubicin-induced cardiotoxicity. CIHR, Cole foundation
407 MYOCARDIAL STRAIN IMAGING BY CARDIAC MRI FOR DETECTION OF SUBCLINICAL MYOCARDIAL DYSFUNCTION IN BREAST CANCER PATIENTS RECEIVING CHEMOTHERAPY
Montréal, Québec
G Ong, C Brezden-Masley, R Haq, V Dhir, R Lee, R Nisenbaum, D Deva, KA Connelly, A Yan
BACKGROUND:
Toronto, Ontario
Doxorubicin-based chemotherapy is effective and widely used to treat leukemia. However, its effectiveness is hampered by a wide spectrum of dose-dependent cardiotoxicity, including both morphological and functional changes affecting the myocardium. Currently, very few techniques are available for estimating myocardial damage. Thus, we aim to assess the use of multiparametric MRI including T1 pre- and post-gadolinium enhancement and T2 relaxation times as indices of myocardial tissue changes following chemotherapy. METHODS: We prospectively assessed 26 cancer survivors that previously received doxorubicine-based chemotherapy with MRI acquisitions including pre- and post-gadolinium T1 and T2 sequences and 9 healthy volunteers (HV). Cancer survivors were divided into two groups: high risk (HR, n¼18) and standard risk (SR, n¼8) based on the cumulative doxorubicin dose received during treatment, age at the beginning of the treatment and other clinical factors. Images were acquired at apical, mid-ventricular and basal level. Myocardial contours were extracted using an interactive curve-based segmentation to create myocardial skeletons that were used to divide the myocardium into segments where relaxation times mean were estimated and compared between groups. RESULTS: Pre-gadolinium T1 was significantly different in 9 out of 19 segments between SR and HR groups. 9 and 6 out of 19 segments were significantly different when comparing SR group to healthy volunteers and HR group to healthy volunteers, respectively. Post-gadolinium T1 relaxation times were significantly higher in SR group compared to healthy volunteers in all segments (p<0.001). T2 relaxation times were significantly higher in the HR group compared to the SR group in all myocardial segments (p<0.001). Linear regressions between mean T1 and T2 relaxation times and volunteers’ age, gender, weight, received doxorubicin dose or time between end of treatment and MRI acquisition showed no significant correlations (R2<0.25). CONCLUSION: Local myocardial changes were found between standard risk and high risks cancer survivors using pre-gadolinium T1 relaxation times. These changes were further amplified with gadolinium enhancement, suggesting this MRI parameter as a candidate imaging marker of doxorubicin induced cardiomyopathy. Similarly, T2 relaxation times were slightly higher in the high risk group compared to the standard risk group and similar with reported T2 values. A larger cohort of cancer survivors may be required to assess the use of contrast
BACKGROUND:
Breast cancer is the second leading cause of cancer death among Canadian women. As life expectancy following breast cancer treatment has greatly improved, accurate techniques to detect early myocardial injury are essential to optimize cardiotoxicity management. Cardiac magnetic resonance imaging (CMR) has the unique ability to characterize myocardial tissue but its use to evaluate left ventricular (LV) strain has not been well studied in this setting. Our objectives were to evaluate the temporal changes in LV ejection fraction (LVEF) and strain parameters measured by CMR and examine their inter-relationship, in patients treated for breast cancer. METHODS: In this prospective observational study in 2 tertiary care hospitals, 40 patients with HER2+ breast cancer treated with chemotherapy (as per standard of care) underwent serial CMR using a standardized protocol, at baseline, 6, 12, and 18 months after initiation of trastuzumab (treatment duration 12 months). LVEF was measured by a single blinded reader; global longitudinal (GLS), radial (GRS) and circumferential (GCS) strain were independently measured by another blinded reader using a dedicated software (CVi42). All CMR were de-identified and interpreted in a random order. Linear mixed models were used to investigate temporal changes in LVEF and strain measurements over 18 months. RESULTS: Of the 40 patients (age 5211 years), 24% had treated hypertension, 10% had diabetes; 2% had coronary artery disease, and none had a history of heart failure. Anthracycline-based chemotherapy was administered to 51% and left-sided radiation therapy to 29% of patients; 92% had normal high-sensitivity troponin I levels and 95% had normal NT-BNP at baseline. Compared to baseline, there was a small but significant reduction in LVEF at 6 and 12 months, but not at 18 months (Table). Similarly, compared to baseline, all LV strain parameters decreased significantly at 6 and 12 months, but not at 18 months. There were significant correlations between the temporal (6 month-baseline) changes in LVEF, and GLS (Pearson r¼-0.44, p¼0.008), GRS (r¼0.43, p¼0.010), and GCS (r¼-0.48, p¼0.004). CONCLUSION: There was a significant reduction in LV strain, which correlated with a concurrent subtle decline in LVEF, during trastuzumab treatment. LV strain assessment by CMR may be a promising new method to monitor for early
Abstracts
myocardial dysfunction in breast cancer patients receiving chemotherapy, and future studies are needed to determine its prognostic and therapeutic implications.
408 COMBINED THREE-DIMENSIONAL MYOCARDIAL STRAIN AND NON-CONTRAST TISSUE MAPPING BY CARDIAC MAGNETIC RESONANCE IMAGING IDENTIFIES EARLY CARDIOTOXICITY IN PATIENTS RECEIVING ANTHRACYCLINE-BASED CHEMOTHERAPY
S299
with corresponding elevations in longitudinal, minimum principal and maximum principal TTP strain. SR was significantly reduced at 6 months for circumferential (p¼0.0002), longitudinal (p¼0.0003), radial (p¼0.021), minimal principal (p¼0.002) and maximal principal (p¼0.007) directions (Figure 1). Segmental analysis showed geographic reductions in strain measures, as shown in figure 1. Non-contrast T1 rose significantly at 6 months (5.58.9%, p¼0.03) without alteration in T2 values (1.35.9%, p¼0.41). CONCLUSION: Cardiac MRI revealed significant alterations in LV volumes, myocardial strain and myocardial T1 over the first 6 months of Anthracycline exposure despite no appreciable change in the LVEF. These findings suggest tissue injury and adverse remodelling occurs prior to an overt reduction in conventional parameters of global systolic function. The utility of cardiac MRI for cardiotoxicity surveillance in this population warrants further investigation.
A Satriano, Y Mikami, B Blume, NA Nixon, C Sheppard, J Chartrain, AG Howarth, CP Lydell, B Heydari, JD McMeekin, D Stewart, J Henning, NM Fine, B Clarke, JA White Calgary, Alberta BACKGROUND:
Up to 20% of cancer survivors may be affected by cardiotoxicity, a chronic disease associated with elevated mortality. While surveillance strategies are engaged during chemotherapy, current practice relies on significant drops in left ventricular ejection fraction (LVEF), a point where myocardial injury has already occurred. In this study we investigate the feasibility and preliminary findings of a non-contrast MRI protocol in patients receiving Anthracycline-based chemotherapy aimed at validating upstream markers of cardiotoxicity that are evident prior to significant reductions in LVEF. METHODS: Nineteen patients planned for Anthracycline-based chemotherapy (14 Breast cancer and 5 Lymphoma) were recruited. Cardiac magnetic resonance (CMR) imaging was performed at baseline, 3 and 6-months using a protocol inclusive of multi-planar cine imaging and short-axis T1 mapping. T1 maps, LV volumes, and LV mass were quantified using commercially available software (cvi42, Circle Cardiovascular Imaging Inc, Calgary Canada). Three-dimensional strain analysis was performed using custom in-house software (GIUSEPPE) using a 4D feature tracking algorithm. Global and segmental values for principal, circumferential, radial and longitudinal strain, strain rate (SR) and time to peak (TTP) strain were calculated. RESULTS: The mean age was 49.012.3 years with 16 (84%) being female. Cumulative Anthracycline dose exposure at 6 months was 534120 mg/m2. The mean baseline LVEF was 61.35.6% with no significant reduction at 6 months (-3.58.8%, p¼0.14). Both LVEDV and LVESV indexed to BSA showed significant elevations at 6 months (13.116.1%, p¼0.0015, and 12.823.1%, p¼0.0050, respectively). Significant reductions (p<0.05) were identified in global strain for circumferential and longitudinal directions at 6 months along
409 MYOCARDIAL 2D STRAIN AND STRESSES INDICES IN THE DETECTION OF CARDIOTOXICITY IN CANCER SURVIVORS M Aissiou, F Cheriet, D Curnier, M Friedrich, C Laverdiere, G Andelfinger, M Krajinovic, D Sinnett, D Perie Montréal, Québec BACKGROUND:
Doxorubicin-based chemotherapy is an effective treatment for cancer, however its successes are hindered by its alterations of myocardial physiology at multiple stages. From molecular scale up to morphological and functional scale, the induction of multiple cardiotoxicities is reported. Accurate estimation of myocardial strains and stresses requires accurate tracking of myocardial displacements. However, the heart is relatively complex to track since it has much fewer
Canadian Cardiovascular Society (CCS) ePoster IMAGING CARDIOTOXICITY Monday, October 24, 2016 406 EARLY DETECTION OF DOXORUBICIN INDUCED CARDIOTOXICITY USING MYOCARDIAL T1 AND T2 RELAXATION TIMES M Aissiou, F Cheriet, D Curnier, T Hafyane, M Friedrich, C Laverdiere, G Andelfinger, M Krajinovic, D Sinnett, D Perie
Canadian Journal of Cardiology Volume 32 2016
enhanced T1 relaxation time as an index for myocardial tissue damage in the onset of doxorubicin-induced cardiotoxicity. CIHR, Cole foundation
407 MYOCARDIAL STRAIN IMAGING BY CARDIAC MRI FOR DETECTION OF SUBCLINICAL MYOCARDIAL DYSFUNCTION IN BREAST CANCER PATIENTS RECEIVING CHEMOTHERAPY
Montréal, Québec
G Ong, C Brezden-Masley, R Haq, V Dhir, R Lee, R Nisenbaum, D Deva, KA Connelly, A Yan
BACKGROUND:
Toronto, Ontario
Doxorubicin-based chemotherapy is effective and widely used to treat leukemia. However, its effectiveness is hampered by a wide spectrum of dose-dependent cardiotoxicity, including both morphological and functional changes affecting the myocardium. Currently, very few techniques are available for estimating myocardial damage. Thus, we aim to assess the use of multiparametric MRI including T1 pre- and post-gadolinium enhancement and T2 relaxation times as indices of myocardial tissue changes following chemotherapy. METHODS: We prospectively assessed 26 cancer survivors that previously received doxorubicine-based chemotherapy with MRI acquisitions including pre- and post-gadolinium T1 and T2 sequences and 9 healthy volunteers (HV). Cancer survivors were divided into two groups: high risk (HR, n¼18) and standard risk (SR, n¼8) based on the cumulative doxorubicin dose received during treatment, age at the beginning of the treatment and other clinical factors. Images were acquired at apical, mid-ventricular and basal level. Myocardial contours were extracted using an interactive curve-based segmentation to create myocardial skeletons that were used to divide the myocardium into segments where relaxation times mean were estimated and compared between groups. RESULTS: Pre-gadolinium T1 was significantly different in 9 out of 19 segments between SR and HR groups. 9 and 6 out of 19 segments were significantly different when comparing SR group to healthy volunteers and HR group to healthy volunteers, respectively. Post-gadolinium T1 relaxation times were significantly higher in SR group compared to healthy volunteers in all segments (p<0.001). T2 relaxation times were significantly higher in the HR group compared to the SR group in all myocardial segments (p<0.001). Linear regressions between mean T1 and T2 relaxation times and volunteers’ age, gender, weight, received doxorubicin dose or time between end of treatment and MRI acquisition showed no significant correlations (R2<0.25). CONCLUSION: Local myocardial changes were found between standard risk and high risks cancer survivors using pre-gadolinium T1 relaxation times. These changes were further amplified with gadolinium enhancement, suggesting this MRI parameter as a candidate imaging marker of doxorubicin induced cardiomyopathy. Similarly, T2 relaxation times were slightly higher in the high risk group compared to the standard risk group and similar with reported T2 values. A larger cohort of cancer survivors may be required to assess the use of contrast
BACKGROUND:
Breast cancer is the second leading cause of cancer death among Canadian women. As life expectancy following breast cancer treatment has greatly improved, accurate techniques to detect early myocardial injury are essential to optimize cardiotoxicity management. Cardiac magnetic resonance imaging (CMR) has the unique ability to characterize myocardial tissue but its use to evaluate left ventricular (LV) strain has not been well studied in this setting. Our objectives were to evaluate the temporal changes in LV ejection fraction (LVEF) and strain parameters measured by CMR and examine their inter-relationship, in patients treated for breast cancer. METHODS: In this prospective observational study in 2 tertiary care hospitals, 40 patients with HER2+ breast cancer treated with chemotherapy (as per standard of care) underwent serial CMR using a standardized protocol, at baseline, 6, 12, and 18 months after initiation of trastuzumab (treatment duration 12 months). LVEF was measured by a single blinded reader; global longitudinal (GLS), radial (GRS) and circumferential (GCS) strain were independently measured by another blinded reader using a dedicated software (CVi42). All CMR were de-identified and interpreted in a random order. Linear mixed models were used to investigate temporal changes in LVEF and strain measurements over 18 months. RESULTS: Of the 40 patients (age 5211 years), 24% had treated hypertension, 10% had diabetes; 2% had coronary artery disease, and none had a history of heart failure. Anthracycline-based chemotherapy was administered to 51% and left-sided radiation therapy to 29% of patients; 92% had normal high-sensitivity troponin I levels and 95% had normal NT-BNP at baseline. Compared to baseline, there was a small but significant reduction in LVEF at 6 and 12 months, but not at 18 months (Table). Similarly, compared to baseline, all LV strain parameters decreased significantly at 6 and 12 months, but not at 18 months. There were significant correlations between the temporal (6 month-baseline) changes in LVEF, and GLS (Pearson r¼-0.44, p¼0.008), GRS (r¼0.43, p¼0.010), and GCS (r¼-0.48, p¼0.004). CONCLUSION: There was a significant reduction in LV strain, which correlated with a concurrent subtle decline in LVEF, during trastuzumab treatment. LV strain assessment by CMR may be a promising new method to monitor for early
Abstracts
myocardial dysfunction in breast cancer patients receiving chemotherapy, and future studies are needed to determine its prognostic and therapeutic implications.
408 COMBINED THREE-DIMENSIONAL MYOCARDIAL STRAIN AND NON-CONTRAST TISSUE MAPPING BY CARDIAC MAGNETIC RESONANCE IMAGING IDENTIFIES EARLY CARDIOTOXICITY IN PATIENTS RECEIVING ANTHRACYCLINE-BASED CHEMOTHERAPY
S299
with corresponding elevations in longitudinal, minimum principal and maximum principal TTP strain. SR was significantly reduced at 6 months for circumferential (p¼0.0002), longitudinal (p¼0.0003), radial (p¼0.021), minimal principal (p¼0.002) and maximal principal (p¼0.007) directions (Figure 1). Segmental analysis showed geographic reductions in strain measures, as shown in figure 1. Non-contrast T1 rose significantly at 6 months (5.58.9%, p¼0.03) without alteration in T2 values (1.35.9%, p¼0.41). CONCLUSION: Cardiac MRI revealed significant alterations in LV volumes, myocardial strain and myocardial T1 over the first 6 months of Anthracycline exposure despite no appreciable change in the LVEF. These findings suggest tissue injury and adverse remodelling occurs prior to an overt reduction in conventional parameters of global systolic function. The utility of cardiac MRI for cardiotoxicity surveillance in this population warrants further investigation.
A Satriano, Y Mikami, B Blume, NA Nixon, C Sheppard, J Chartrain, AG Howarth, CP Lydell, B Heydari, JD McMeekin, D Stewart, J Henning, NM Fine, B Clarke, JA White Calgary, Alberta BACKGROUND:
Up to 20% of cancer survivors may be affected by cardiotoxicity, a chronic disease associated with elevated mortality. While surveillance strategies are engaged during chemotherapy, current practice relies on significant drops in left ventricular ejection fraction (LVEF), a point where myocardial injury has already occurred. In this study we investigate the feasibility and preliminary findings of a non-contrast MRI protocol in patients receiving Anthracycline-based chemotherapy aimed at validating upstream markers of cardiotoxicity that are evident prior to significant reductions in LVEF. METHODS: Nineteen patients planned for Anthracycline-based chemotherapy (14 Breast cancer and 5 Lymphoma) were recruited. Cardiac magnetic resonance (CMR) imaging was performed at baseline, 3 and 6-months using a protocol inclusive of multi-planar cine imaging and short-axis T1 mapping. T1 maps, LV volumes, and LV mass were quantified using commercially available software (cvi42, Circle Cardiovascular Imaging Inc, Calgary Canada). Three-dimensional strain analysis was performed using custom in-house software (GIUSEPPE) using a 4D feature tracking algorithm. Global and segmental values for principal, circumferential, radial and longitudinal strain, strain rate (SR) and time to peak (TTP) strain were calculated. RESULTS: The mean age was 49.012.3 years with 16 (84%) being female. Cumulative Anthracycline dose exposure at 6 months was 534120 mg/m2. The mean baseline LVEF was 61.35.6% with no significant reduction at 6 months (-3.58.8%, p¼0.14). Both LVEDV and LVESV indexed to BSA showed significant elevations at 6 months (13.116.1%, p¼0.0015, and 12.823.1%, p¼0.0050, respectively). Significant reductions (p<0.05) were identified in global strain for circumferential and longitudinal directions at 6 months along
409 MYOCARDIAL 2D STRAIN AND STRESSES INDICES IN THE DETECTION OF CARDIOTOXICITY IN CANCER SURVIVORS M Aissiou, F Cheriet, D Curnier, M Friedrich, C Laverdiere, G Andelfinger, M Krajinovic, D Sinnett, D Perie Montréal, Québec BACKGROUND:
Doxorubicin-based chemotherapy is an effective treatment for cancer, however its successes are hindered by its alterations of myocardial physiology at multiple stages. From molecular scale up to morphological and functional scale, the induction of multiple cardiotoxicities is reported. Accurate estimation of myocardial strains and stresses requires accurate tracking of myocardial displacements. However, the heart is relatively complex to track since it has much fewer