The relationship between body composition and left ventricular performance in women with breast, lymphoma, or sarcoma cancer.

BACKGROUND: To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma. METHODS: Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change. RESULTS: Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047). CONCLUSIONS: These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet. TRIAL REGISTRATION: DETECTIV_NCT01719562, WF99112, & WF97415-NCT02791581.

Hypertension Severity and Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (WF-97415 UPBEAT).

BACKGROUND: Hypertension is a risk factor for experiencing left ventricular ejection fraction (LVEF) declines during receipt of potentially cardiotoxic breast cancer (BC) treatment. We sought to determine whether the hypertension stage is associated with LVEF decline during BC treatment. METHODS: Across 24 centers, cardiac magnetic resonance measures of LVEF and brachial arterial blood pressure (BP) measurements were performed in women with stages I to III BC before and 3 months after initiating potentially cardiotoxic chemotherapy. Using multivariable analysis, we assessed in a blinded fashion the association between 3-month ΔLVEF and precancer treatment American Heart Association/American College of Cardiology stages of hypertension. RESULTS: Among 204 women, age averaged 56±1 years with 75% being White and 20% of Black race. Participants received anthracycline (45.6%), trastuzumab (22.5%), cyclophosphamide (52.9%), or paclitaxel (50%). After accounting for pretreatment LVEF, diabetes status, tobacco use, age, the number of antihypertensive medications, and body mass index, those with stage II hypertension experienced an LVEF decline of -2.89% ([95% CI, -0.69% to -5.19%]; P=0.01) relative to individuals with normal BP. Other stages saw nonsignificant declines relative to normal BP to elevated BP (-1.63% [95% CI, -0.62% to 3.88%]; P=0.16) and stage I hypertension (-0.94% [95% CI, -0.90% to 2.78%]; P=0.32). CONCLUSIONS: Compared with women receiving treatment for BC with normal BP, there is a stronger association of decline in LVEF in women with stage II hypertension relative to women with other hypertension stages. This raises the possibility that stage along with hypertension presence may be associated with an increased risk for the LVEF decline among women receiving potentially cardiotoxic chemotherapy for BC. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02791581 and NCT01719562.

Impact of Anti-Estrogen Therapy on Early Cardiovascular Referrals, Tests and Medications in Premenopausal Women with Operable Breast Cancer.

INTRODUCTION: Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) and anti-estrogen therapy which induces near complete estrogen deprivation (NCED). This treatment improves recurrence-free survival but may increase cardiovascular risk. We sought to identify patterns of cardiovascular care and outcomes in premenopausal women with operable breast cancer. METHODS: Premenopausal women ≤ 50 years of age with stage I-III HR-positive or triple negative breast cancer (TNBC) were identified by retrospective review. We categorized women into 3 groups based on anti-estrogen therapy approach: NCED (HR + OFS), anti-estrogen therapy without OFS (HRnoOFS), and no anti-estrogen therapy (TNBC). Baseline characteristics, post-diagnosis cardiovascular events and cardiovascular actions (tests, referrals and medications) were recorded. Categorical variables were compared among the groups using chi-square and Fisher's exact tests; continuous outcomes were compared using ANOVA. RESULTS: 82, 83, and 52 women were identified in the HR + OFS, HRnoOFS, and TNBC groups respectively; mean follow-up was 5.0 years. Mean number of cardiovascular actions per year were highest in the HR + OFS group compared with HRnoOFS and TNBC groups (0.35 vs. 0.20 and 0.27, respectively; P = .036). The HR + OFS group had significantly more referrals and tests per year than the other groups. Cardiovascular medication initiation did not differ among groups. CONCLUSIONS: In this early follow-up period, there were meaningful numbers of cardiovascular actions, with women on NCED experiencing the most per year. Future work should seek to further understand the impact of anti-estrogen therapy on the cardiovascular health of premenopausal women and test strategies to mitigate cardiotoxicity.

Institutional experience report on the target contouring workflow in the radiotherapy department for stereotactic arrhythmia radioablation delivered on conventional linear accelerators.

PURPOSE: In stereotactic arrhythmia radioablation (STAR), the target is defined using multiple imaging studies and a multidisciplinary team consisting of electrophysiologist, cardiologist, cardiac radiologist, and radiation oncologist collaborate to identify the target and delineate it on the imaging studies of interest. This report describes the workflow employed in our radiotherapy department to transfer the target identified based on electrophysiology and cardiology imaging to the treatment planning image set. METHODS: The radiotherapy team was presented with an initial target in cardiac axes orientation, contoured on a wideband late gadolinium-enhanced (WB-LGE) cardiac magnetic resonance (CMR) study, which was subsequently transferred to the computed tomography (CT) scan used for treatment planning-i.e., the average intensity projection (AIP) image set derived from a 4D CT-via an axial CMR image set, using rigid image registration focused on the target area. The cardiac and the respiratory motion of the target were resolved using ciné-CMR and 4D CT imaging studies, respectively. RESULTS: The workflow was carried out for 6 patients and resulted in an internal target defined in standard anatomical orientation that encompassed the cardiac and the respiratory motion of the initial target. CONCLUSION: An image registration-based workflow was implemented to render the STAR target on the planning image set in a consistent manner, using commercial software traditionally available for radiation therapy.

Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study.

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

Physical Activity During Breast Cancer Therapy Associates With Preserved Exercise Capacity and Cardiac Function (WF97415).

Background: Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease. Objectives: This study examined whether greater PA was associated with better submaximal exercise capacity and cardiac function during cancer therapy. Methods: Participants included 223 women with stage I to III breast cancer (BC) before and 3 months after undergoing treatment and 126 control participants. Leisure-time PA (LTPA) was reported using the Godin-Shephard LTPA questionnaire. Cardiac function was assessed by cardiac magnetic resonance. Submaximal exercise capacity was determined by 6-minute walk distance. Results: BC participants reported similar baseline LTPA scores (24.7; 95% CI: 21.7-28.0) as control participants (29.4; 95% CI: 25.0-34.2). The BC group declined to 16.9 (95% CI: 14.4-19.6) at 3 months relative to 30.8 (95% CI: 26.2-35.8) in control participants. Among BC participants, more LTPA was related to better exercise capacity (ß ± SE: 7.1 ± 1.6; 95% CI: 4.0-10.1) and left ventricular (LV) circumferential strain (-0.16 ± 0.07; 95% CI: -0.29 to -0.02). Increased LTPA over the 3 months was associated with decreased likelihood of treatment-induced cardiac dysfunction according to LV circumferential strain classifications (OR: 0.98; 95% CI: 0.97-0.998). BC participants reporting insufficient LTPA according to PA guidelines exhibited deteriorations in exercise capacity (adjusted mean difference ± SE: -29 ± 10 m; P = 0.029), LV end-systolic volume (5.8 ± 1.3 mL; P < 0.001), LV ejection fraction (-3.2% ± 0.8%; P = 0.002), and LV circumferential strain (2.5% ± 0.5%; P < 0.001), but BC participants meeting LTPA guidelines did not exhibit these adverse changes. Conclusions: PA declined during BC therapy; however, PA participation was associated with attenuated declines in exercise capacity and cardiac function that are often observed in this population. (Understanding and Predicting Breast Cancer Events After Treatment [WF97415 UPBEAT]; NCT02791581).

Higher diet quality relates to better cardiac function in cancer survivors: The multi-ethnic study of atherosclerosis.

BACKGROUND: Cancer therapies induce cardiac injury and increase cardiovascular disease (CVD) risk. In non-cancer populations, higher diet quality is associated with protection against CVD, but the relationship between diet and cardiac function in cancer survivors is unknown. METHODS: This cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort included 113 cancer survivors (55 breast, 53 prostate, three lung, and three blood) and 4233 non-cancer controls. Dietary intake was reported via validated food frequency questionnaire. Alternate healthy eating index (AHEI) was calculated as a measure of quality. Cardiac function, determined as left ventricular ejection fraction (LVEF), was assessed by cardiac magnetic resonance. RESULTS: Cancer survivors had a lower LVEF compared to controls (61.3 ± 6.5% v 62.4 ± 6.1%, p = 0.04). In all participants, total fat (ß ± SE: -0.04 ± 0.01, p = 0.004), saturated fat (-0.11 ± 0.03, p < 0.001), and trans-fat (-0.36 ± 0.12, p = 0.002) intake were inversely associated with LVEF while AHEI (0.03 ± 0.01, p < 0.001) was positively associated with LVEF. Among cancer survivors only, sucrose intake was negatively related to LVEF (-0.15 ± 0.06, p = 0.02), and the ratio of unsaturated fat to saturated fat (2.7 ± 1.1, p = 0.01) and fiber intake (0.42 ± 0.14, p = 0.003) were positively related to LVEF. DISCUSSION: In cancer survivors, improved dietary fat and carbohydrate quality (i.e., greater consumption of unsaturated fatty acids and fiber) was associated with favorable cardiac function, while higher sucrose was associated with worse cardiac function. Further research is needed to confirm these findings and test whether changes in the identified dietary factors will modulate cardiac function in cancer survivors.

Myocardial Elasticity Imaging Correlates with Histopathology in a Model of Anthracycline-Induced Cardiotoxicity.

Background: There is considerable focus on developing strategies for identifying subclinical cardiac decline prior to cardiac failure. Myocardial tissue elasticity changes may precede irreversible cardiac damage, providing promise for an early biomarker for cardiac decline. Biomarker strategies are of particular interest in cardio-oncology due to cardiotoxic effects of anti-neoplastic therapies, particularly anthracycline-based chemotherapeutics. Current clinical methods for diagnosing cardiotoxicity are too coarse to identify cardiac decline early enough for meaningful therapeutic intervention, or too cumbersome for clinical implementation. Methods: Utilizing changes in myocardial elasticity as a biomarker for subclinical cardiac decline, we developed a biomechanical model-based elasticity imaging methodology (BEIM) to estimate spatial maps of left ventricle (LV) myocardial elasticity. In this study, we employ this methodology to assess changes in LV elasticity in a non-human primate model of doxorubicin-induced cardiotoxicity. Cardiac magnetic resonance imaging of five African Green monkeys was acquired at baseline prior to doxorubicin administration, 6-weeks, and 15-weeks after final doxorubicin dose and histopathological samples of the LV were taken at 15-weeks after final doxorubicin dose. Spatial elasticity maps of the mid-short axis plane of the LV were estimated at each image acquisition. Global and regional LV elasticity were calculated and changes between imaging time points was assessed. LV elasticity at baseline and final time point were compared to cardiomyocyte size and collagen volume fraction measurements calculated from histopathological staining of archived tissue bank samples and study endpoint tissue samples utilizing Pearson's correlation coefficients. Results: We identify significant changes in LV elasticity between each imaging time point both globally and regionally. We also demonstrate strong correlation between LV elasticity and cardiomyocyte size and collagen volume fraction measurements. Results indicate that LV elasticity estimates calculated using BEIM correlate with histopathological changes that occur due to doxorubicin administration, validating LV elasticity solutions and providing significant promise for use of BEIM to non-invasively elucidate cardiac injury. Conclusions: This methodology can show progressive changes in LV elasticity and has potential to be a more sensitive indicator of elasticity changes than current clinical measures of cardiotoxicity. LV elasticity may provide a valuable biomarker for cardiotoxic effects of anthracycline-based chemotherapeutics and cardiac disease detection.

Patients' and carers' priorities for cancer research in Aotearoa/New Zealand.

BACKGROUND: Discrepancies have been reported between what is being researched, and what patients/families deem important to be investigated. Our aim was to understand research priorities for those who live with cancer in Aotearoa/New Zealand, with emphasis on Maori. METHODS: Adult outpatients with cancer and their whanau/family completed a survey (demographics, selecting keywords, free-text comments) at Christchurch hospital. Quantitative and qualitative data were evaluated using standard statistical and thematic analyses, respectively. RESULTS: We recruited 205 participants, including both turoro/patients (n = 129) and their whanau/family/carer (n = 76). Partnership with Maori health workers enabled greater recruitment of Maori participants (19%), compared to the proportion of Maori in Canterbury (9%). Cancer research was seen as a priority by 96% of participants. Priorities were similar between Maori and non-Maori participants, with the keywords 'Cancer screening', 'Quality of Life' and 'Development of new drugs' chosen most often. Free-text analysis identified three themes; 'Genetics and Prevention', 'Early Detection and Treatment', and 'Service Delivery', with some differences by ethnicity. CONCLUSIONS: Cancer research is a high priority for those living with cancer. In addition, participants want researchers to listen to their immediate and practical needs. These findings may inform future cancer research in Aotearoa. MaORI TERMS AND TRANSLATION: Aotearoa (New Zealand) he aha o whakaaro (what are your thoughts) hui (gathering) mate pukupuku (cancer) mokopuna (descendent) Otautahi (Christchurch) rongoa (traditional healing) tane (male) te reo (Maori language) Te Whatu Ora (weaving of wellness, Health New Zealand) tikanga (methods, customary practices) turoro (patients) (alternative terms used: whanau affected by cancer or tangata whaiora (person seeking health)) wahine (female) Waitaha (Canterbury) whakapapa (genealogy) whanau ((extended) family, based on whakapapa, here also carer).

Simultaneous exercise stress cardiac magnetic resonance and cardiopulmonary exercise testing to elucidate the Fick components of aerobic exercise capacity: a feasibility and reproducibility study and pilot study in hematologic cancer survivors.

BACKGROUND: Patients treated for hematologic malignancy often experience reduced exercise capacity and increased fatigue; however whether this reduction is related to cardiac dysfunction or impairment of skeletal muscle oxygen extraction during activity is unknown. Cardiopulmonary exercise testing (CPET) coupled with stress cardiac magnetic resonance (ExeCMR), may provide a noninvasive method to identify the abnormalities of cardiac function or skeletal muscle oxygen extraction. This study was performed to determine the feasibility and reproducibility of a ExeCMR + CPET technique to measure the Fick components of peak oxygen consumption (VO2) and pilot its discriminatory potential in hematologic cancer patients experiencing fatigue. METHODS: We studied 16 individuals undergoing ExeCMR to determine exercise cardiac reserve with simultaneous measures of VO2. The arteriovenous oxygen content difference (a-vO2diff) was calculated as the quotient of VO2/cardiac index (CI). Repeatability in measurements of peak VO2, CI, and a-vO2diff was assessed in seven healthy controls. Finally, we measured the Fick determinants of peak VO2 in hematologic cancer survivors with fatigue (n = 6) and compared them to age/gender-matched healthy controls (n = 6). RESULTS: Study procedures were successfully completed without any adverse events in all subjects (N = 16, 100%). The protocol demonstrated good-excellent test-retest reproducibility for peak VO2 (intraclass correlation coefficient [ICC] = 0.992 [95%CI:0.955-0.999]; P < 0.001), peak CI (ICC = 0.970 [95%CI:0.838-0.995]; P < 0.001), and a-vO2diff (ICC = 0.953 [95%CI:0.744-0.992]; P < 0.001). Hematologic cancer survivors with fatigue demonstrated a significantly lower peak VO2 (17.1 [13.5-23.5] vs. 26.0 [19.7-29.5] mL·kg-1·min-1, P = 0.026) and lower peak CI (5.0 [4.7-6.3] vs. 7.4 [7.0-8.8] L·min-1/m2, P = 0.004) without a significant difference in a-vO2diff (14.4 [11.8-16.9] vs. 13.6 [10.9-15.4] mLO2/dL, P = 0.589). CONCLUSIONS: Noninvasive measurement of peak VO2 Fick determinants is feasible and reliable with an ExeCMR + CPET protocol in those treated for a hematologic malignancy and may offer insight into the mechanisms of exercise intolerance in those experiencing fatigue.

A Randomized Controlled Trial of Mindfulness in Recovery from Colorectal Cancer.

OBJECTIVE: This study examined whether a 4-week group-based mindfulness intervention would be superior in reducing psychological distress in colorectal cancer (CRC) patients compared to a psychoeducation and cognitive behavioural skills learning support active control group. METHODS: Patients with CRC were randomized via Computerised Permuted Block Randomisation to mindfulness or active control groups (2-h weekly sessions over 4 weeks). Outcomes were measured pre-intervention, and 8 weeks and 6 months post-baseline. The primary outcome was psychological distress measured by the Hospital Anxiety and Depression Scale. Secondary outcomes were generic quality of life (QoL), disease specific QoL, mindfulness, and intervention credibility and acceptability. RESULTS: Sixty-eight participants were randomized to mindfulness (n=35) or active control group (n=33). Uptake of potentially eligible patients consenting was low (28.0%) and the dropout rate was 33.8%. Depression scores were reduced in both groups at week 8 (P=0.020). Control participants had greater improvement in generic mental QoL scores at week 8 than mindfulness (P=0.023). In disease specific QoL, there was reduction in impotence symptom in the mindfulness group (P=0.022) and reduction in faecal incontinence in the control group (P=0.019). The embarrassment symptom had a significantly lower increase in the mindfulness group at week 8 compared to the control group (P=0.009). Both groups rated the treatments as credible and acceptable. CONCLUSIONS: Mindfulness was not superior to the active control group in terms of alleviating psychological distress but both treatments were associated with some improvements in depression. There was low uptake of both interventions. (Trial registration number: ACTRN12616001033437).

Reimagining eating disorder spaces: a qualitative study exploring Maori experiences of accessing treatment for eating disorders in Aotearoa New Zealand.

BACKGROUND: Health, illness, and the body are conceptualized within the cultural context of a society. The values and belief systems of a society, including media portrayals, shape how health and illness present. Traditionally, Western portrayals of eating disorders have been prioritized over and above Indigenous realities. This paper explores the lived experiences of Maori with eating disorders and their whanau (family/support system) to identify the enablers and barriers to accessing specialist services for eating disorders in New Zealand. METHOD: Kaupapa Maori research methodology was used to ensure the research supported Maori health advancement. Fifteen semi-structured interviews were completed with Maori participants including; those with an eating disorder diagnosis (anorexia nervosa, bulimia nervosa, and binge eating disorder), and/or their whanau. Structural, descriptive, and pattern coding was undertaken within the thematic analysis. Low's spatializing culture framework was used to interpret the findings. RESULTS: Two overarching themes identified systemic and social barriers to accessing treatment for Maori with eating disorders. The first theme, was space, that described the material culture within eating disorder settings. This theme critiqued eating disorder services, including idiosyncratic use of assessment methods, inaccessible service locations, and the limited number of beds available in specialist mental health services. The second theme, place, referred to the meaning given to social interactions created within space. Participants critiqued the privileging of non-Maori experiences, and how this makes a place and space of exclusion for Maori and their whanau in eating disorder services in New Zealand. Other barriers included shame and stigma, while enablers included family support and self-advocacy. CONCLUSION: More education is needed for those working in the space of primary health settings about the diversity of those with eating disorders to enable them to look beyond the stereotype of what an eating disorder looks like, and to take seriously the concerns of whaiora and whanau who present with disordered eating concerns. There is also a need for thorough assessment and early referral for eating disorder treatment to ensure the benefits of early intervention are enabled for Maori. Attention given to these findings will ensure a place for Maori in specialist eating disorder services in New Zealand.

Eating disorders are at least as common in Maori (Indigenous people of New Zealand) when compared to their non-Maori counterparts, however, a recent study investigating specialist service use data identified lower-than-expected service use for Maori. This paper explores the lived experiences of Maori with eating disorders and their whanau (family/support network) to understand the barriers and enablers to accessing treatment. Participants in this study identified both systemic and social barriers to accessing treatment for eating disorders; Systemic barriers included the idiosyncratic use of assessment methods by health practitioners, and inaccessible service locations, including the number of available inpatient beds. While social barriers included the stereotype of what an eating disorder looks like, shame, stigma, and discrimination; support networks were described as both an enabler and barrier to accessing specialist treatment for eating disorders. The findings from this study suggest thorough assessment and early referrals are needed for Maori presenting with disordered eating concerns. Moreover, more education is needed for those working in primary healthcare settings about the diversity of eating disorders to ensure they move beyond the stereotype of what an eating disorder looks like.

Reproducibility assessment of a biomechanical model-based elasticity imaging method for identifying changes in left ventricular mechanical stiffness.

Purpose: Cardiotoxicity of antineoplastic therapies is increasingly a risk to cancer patients treated with curative intent with years of life to protect. Studies highlight the importance of identifying early cardiac decline in cancer patients undergoing cardiotoxic therapies. Accurate tools to study this are a critical clinical need. Current and emerging methods for assessing cardiotoxicity are too coarse for identifying preclinical cardiac degradation or too cumbersome for clinical implementation. Approach: In the previous work, we developed a noninvasive biomechanical model-based elasticity imaging methodology (BEIM) to assess mechanical stiffness changes of the left ventricle (LV) based on routine cine cardiac magnetic resonance (CMR) images. We examine this methodology to assess methodological reproducibility. We assessed a cohort of 10 participants that underwent test/retest short-axis CMR imaging at baseline and follow-up sessions as part of a previous publicly available study. We compare test images to retest images acquired within the same session to assess within-session reproducibility. We also compare test and retest images acquired at the baseline imaging session to test and retest images acquired at the follow-up imaging session to assess between-session reproducibility. Results: We establish the within-session and between-session reproducibility of our method, with global elasticity demonstrating repeatability within a range previously demonstrated in cardiac strain imaging studies. We demonstrate increased repeatability of global elasticity compared to segmental elasticity for both within-session and between-session. Within-subject coefficients of variation for within-session test/retest images globally for all modulus directions and a mechanical fractional mechanical stiffness anisotropy metric ranged from 11% to 28%. Conclusions: Results suggest that our methodology can reproducibly generate estimates of relative mechanical elasticity of the LV and provides a threshold for distinguishing true changes in myocardial mechanical stiffness from experimental variation. BEIM has applications in identifying preclinical cardiotoxicity in breast cancer patients undergoing antineoplastic therapies.

Cardiac MRI assessment of anthracycline-induced cardiotoxicity.

The objective of this review article is to discuss how cardiovascular magnetic resonance (CMR) imaging measures left ventricular (LV) function, characterizes tissue, and identifies myocardial fibrosis in patients receiving anthracycline-based chemotherapy (Anth-bC). Specifically, CMR can measure LV ejection fraction (EF), volumes at end-diastole (LVEDV), and end-systole (LVESV), LV strain, and LV mass. Tissue characterization is accomplished through T1/T2-mapping, late gadolinium enhancement (LGE), and CMR perfusion imaging. Despite CMR's accuracy and efficiency in collecting data about the myocardium, there are challenges that persist while monitoring a cardio-oncology patient undergoing Anth-bC, such as the presence of other cardiovascular risk factors and utility controversies. Furthermore, CMR can be a useful adjunct during cardiopulmonary exercise testing to pinpoint cardiovascular mediated exercise limitations, as well as to assess myocardial microcirculatory damage in patients undergoing Anth-bC.

Influence of extracellular volume fraction on peak exercise oxygen pulse following thoracic radiotherapy.

BACKGROUND: Radiation-induced myocardial fibrosis increases heart failure (HF) risk and is associated with a restrictive cardiomyopathy phenotype. The myocardial extracellular volume fraction (ECVF) using contrast-enhanced cardiac magnetic resonance (CMR) quantifies the extent of fibrosis which, in severe cases, results in a noncompliant left ventricle (LV) with an inability to augment exercise stroke volume (SV). The peak exercise oxygen pulse (O2Pulse), a noninvasive surrogate for exercise SV, may provide mechanistic insight into cardiac reserve. The relationship between LV ECVF and O2Pulse following thoracic radiotherapy has not been explored. METHODS: Patients who underwent thoracic radiotherapy for chest malignancies with significant incidental heart dose (≥5 Gray (Gy), ≥10% heart) without a pre-cancer treatment history of HF underwent cardiopulmonary exercise testing to determine O2Pulse, contrast-enhanced CMR, and N-terminal pro-brain natriuretic peptide (NTproBNP) measurement. Multivariable-analyses were performed to identify factors associated with O2Pulse normalized for age/gender/anthropometrics. RESULTS: Thirty patients (median [IQR] age 63 [57-67] years, 18 [60%] female, 2.0 [0.6-3.8] years post-radiotherapy) were included. The peak VO2 was 1376 [1057-1552] mL·min- 1, peak HR = 150 [122-164] bpm, resulting in an O2Pulse of 9.2 [7.5-10.7] mL/beat or 82 (66-96) % of predicted. The ECVF, LV ejection fraction, heart volume receiving ≥10 Gy, and NTproBNP were independently associated with %O2Pulse (P < .001). CONCLUSIONS: In patients with prior radiotherapy heart exposure, %-predicted O2Pulse is inversely associated markers of diffuse fibrosis (ECVF), ventricular wall stress (NTproBNP), radiotherapy heart dose, and positively related to LV function. Increased LV ECVF may reflect a potential etiology of impaired LV SV reserve in patients receiving thoracic radiotherapy for chest malignancies.

Statins and Left Ventricular Ejection Fraction Following Doxorubicin Treatment.

BACKGROUND: Statins taken for cardiovascular indications by patients with breast cancer and lymphoma during doxorubicin treatment may attenuate left ventricular ejection fraction (LVEF) decline, but the effect of statins on LVEF among patients with no cardiovascular indications is unknown. METHODS: A double-blind, placebo-controlled, 24-month randomized trial of 40 mg of atorvastatin per day administered to patients with breast cancer and lymphoma receiving doxorubicin was conducted within the National Cancer Institute Community Oncology Research Program across 31 sites in the United States. At pretreatment and then 6 and 24 months after initiating doxorubicin, we assessed left ventricular (LV) volumes, strain, mass, and LVEF through cardiac magnetic resonance imaging, along with cognitive function and serum markers of inflammation. The primary outcome was the difference in 24-month LVEF between placebo and treatment groups, adjusted for pretreatment LVEF. RESULTS: A total of 279 participants were enrolled in the trial. Participants had a mean (±SD) age of 49±12 years; 92% were women; and 83% were White. The mean (±SD) LVEF values were 61.7±5.5% before treatment and 57.4±6.8% at 24 months in the placebo group and 62.6±6.4% before treatment and 57.7±5.6% at 24 months in the atorvastatin group. On the basis of a multiple imputed data set for missing data and adjusted for each individual's pretreatment LVEF, 24-month declines in LVEF averaged 3.3±0.6 percentage points and 3.2±0.7 percentage points, for those randomly assigned to placebo versus statins, respectively (P=0.93). Across both treatment arms, similar percentages of individuals experienced changes of more than 10 percentage points in LVEF, LV strain, LV mass, cognition, and inflammation biomarkers, including among those with greater than 90% drug compliance. CONCLUSIONS: In patients with breast cancer and lymphoma with no existing indication for statin therapy, prospective statin administration did not affect LVEF declines 2 years after doxorubicin. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01988571.).

Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART).

BACKGROUND: Sarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis. METHODS: Building on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis. DISCUSSION: The current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities. Trial Registration The trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936.