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.

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.

Exercise Cardiovascular Magnetic Resonance: A Review.

While pharmacologic stress cardiovascular magnetic resonance imaging (MRI) is a robust noninvasive tool in the diagnosis and prognostication of epicardial coronary artery disease, clinical guidelines recommend exercise-based testing in those patients who can exercise. This review describes the development of exercise cardiovascular MRI protocols, summarizes the insights across various patient populations, and highlights future research initiatives. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Role of Cardiac MRI Imaging of Focal and Diffuse Inflammation and Fibrosis in Cardiomyopathy Patients Who Have Pacemakers/ICD Devices.

PURPOSE OF REVIEW: This focused report aims to discuss and summarize the use of conventional and emerging methods using cardiovascular magnetic resonance (CMR) imaging in cardiomyopathy patients with implanted cardiac devices to identify diffuse and focal inflammation and fibrosis. RECENT FINDINGS: Many cardiomyopathy patients with diffuse and focal myocardial fibrosis have a unique need for cardiac imaging that is complicated by cardiovascular implantable electronic devices (CIEDs). CMR imaging can accurately image myocardial fibrosis and inflammation using T1 mapping and late gadolinium enhancement (LGE) imaging. CMR imaging in CIED patients, however, has been limited due to severe imaging artifacts associated with the devices. The emergence of wideband imaging variants of LGE and T1 mapping techniques can successfully reduce or eliminate CIED artifacts for the evaluation of myocardial substrate in cardiomyopathy patients. Wideband imaging variants of LGE and T1 mapping techniques provide new tools for imaging focal and diffuse fibrosis and imaging in cardiomyopathy patients with implanted cardiac devices. These emerging techniques have the potential for great impact in clinical care of such patients as well as clinical research where imaging endpoints are desired.

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.

Asymptomatic myocardial ischemia forecasts adverse events in cardiovascular magnetic resonance dobutamine stress testing of high-risk middle-aged and elderly individuals.

BACKGROUND: Current guidelines for assessing the risk of experiencing a hospitalized cardiovascular (CV) event discourage stress testing of asymptomatic individuals; however, these recommendations are based on evidence gathered primarily from those aged < 60 years, and do not address the possibility of unrecognized "silent myocardial ischemia" in middle aged and older adults. METHODS: We performed dobutamine cardiovascular magnetic resonance (CMR) stress testing in 327 consecutively recruited participants aged > 55 years without CV-related symptoms nor known coronary artery disease, but otherwise at increased risk for a future CV event due to pre-existing hypertension or diabetes mellitus for at least 5 years. After adjusting for the demographics and CV risk factors, log-rank test and Cox proportional hazards models determined the additional predictive value of the stress test results for forecasting hospitalized CV events/survival. Either stress-induced LV wall motion abnormalities or perfusion defects were used to indicate myocardial ischemia. RESULTS: Participants averaged 68 ± 8 years in age; 39% men, 75% Caucasian. There were 38 hospitalized CV events or deaths which occurred during a mean follow-up of 58 months. Using Kaplan-Meier analyses, myocardial ischemia identified future CV events/survival (p <  0.001), but this finding was more evident in men (p <  0.001) versus women (p = 0.27). The crude hazard ratio (HR) of myocardial ischemia for CV events/survival was 3.13 (95% CI: 1.64-5.93; p < 0.001). After accounting for baseline demographics, CV risk factors, and left ventricular ejection fraction/mass, myocardial ischemia continued to be associated with CV events/survival [HR: 4.07 (95% CI: 1.95-8.73) p < 0.001]. CONCLUSIONS: Among asymptomatic middle-aged individuals with risk factors for a sentinel CV event, the presence of myocardial ischemia during dobutamine CMR testing forecasted a future hospitalized CV event or death. Further studies are needed in middle aged and older individuals to more accurately characterize the prevalence, significance, and management of asymptomatic myocardial ischemia. TRIAL REGISTRATION: ( ClinicalTrials.gov identifier): NCT00542503 and was retrospectively registered on October 11th, 2007.

Automated assessments of circumferential strain from cine CMR correlate with LVEF declines in cancer patients early after receipt of cardio-toxic chemotherapy.

BACKGROUND: In patients with cancer receiving potentially cardio-toxic chemotherapy, measurements of left ventricular (LV) circumferential or longitudinal strain are often used clinically to identify myocardial dysfunction. Using a new software algorithm, we sought to determine in individuals receiving treatment for cancer the association between automated assessments of LV mean mid-wall circumferential strain and conventional measures of LV ejection fraction (EF) both obtained from cardiovascular magnetic resonance (CMR) cine balanced steady-state free-precession (bSSFP) white-blood acquisitions. METHODS: Before and 3 months after initiating treatment with potentially cardio-toxic chemotherapy, 72 individuals (aged 54 ± 14 years with breast cancer [39%], lymphoma [49%], or sarcoma [12%]) underwent serial CMR cine bSSFP assessments of LV volumes and EF, and mean mid-wall circumferential strain determined from these same cine images as well as from additional tagged CMR images. On the cine images, assessments of strain were obtained using the newly developed deformation-based segmentation algorithm. Assessments of LV volumes/EF from the cine images and strain from tagged CMR were accomplished using commercially available software. All measures were analyzed in a blinded fashion independent of one another. RESULTS: Acceptable measures for the automated assessments of mean mid-wall circumferential strain from the cine images were obtained in 142 of 144 visits (98.6%) with an overall analysis time averaging 6:47 ± 1:06 min. The results from these automated measures averaged -18.8 ± 2.9 at baseline and -17.6 ± 3.1 at 3 months (p = 0.001). Left ventricular EF declined slightly from 65 ± 7% at baseline to 62 ± 7% at 3 months (p = 0.0002). The correlation between strain from cine imaging and LVEF was r = -0.61 (p < 0.0001). In addition, the 3-month changes in LV strain and LVEF were correlated (r = -0.49; p < 0.0001). The correlation between cine and tagged derived assessments of strain was r = 0.23; p = 0.01. CONCLUSIONS: Automated measures of LV mean mid-wall circumferential strain can be obtained in 6¾ minutes from cine bSSFP LV short-axis images (used concurrently to assess LV volumes and EF) in 98.6% of patients receiving treatment for cancer with potentially cardio-toxic chemotherapy. These cine derived measures of circumferential strain correlate with early subclinical declines in LVEF.

Incident comorbidities and all-cause mortality among 5-year survivors of Stage I and II breast cancer diagnosed at age 65 or older: a prospective-matched cohort study.

Five-year breast cancer survivors, diagnosed after 65 years of age, may develop more incident comorbidities than similar populations free of cancer. We investigated whether older breast cancer survivors have a similar comorbidity burden 6-15 years after cancer diagnosis to matched women free of breast cancer at start of follow-up and whether incident comorbidities are associated with all-cause mortality. In this prospective cohort study, 1,361 older 5-year early-stage breast cancer survivors diagnosed between 1990 and 1994 and 1,361 age- and health system-matched women were followed for 10 years. Adjudicated medical record review captured prevalent and incident comorbidities during follow-up or until death as collected from the National Death Index. Older 5-year breast cancer survivors did not acquire incident comorbidities more often than matched women free of breast cancer in the subsequent 10 years [hazard ratio (HR) 1.0, 95 % confidence interval (95 % CI) 0.93, 1.1]. Adjusted for cohort membership, women with incident comorbidities had a higher mortality rate than those without incident comorbidities (HR 4.8, 95 % CI 4.1, 5.6). A breast cancer history continued to be a hazard for mortality 6-15 years after diagnosis (HR 1.3, 95 % CI 1.1, 1.4). We found that older breast cancer survivors who developed comorbidities had an increased all-cause mortality rate even after adjusting for age and prevalent comorbidity burden. Additionally, survivors acquire comorbidities at a rate similar to older women free of breast cancer. These results highlight the association between comorbidity burden and long-term mortality risk among older breast cancer survivors and their need for appropriate oncology and primary care follow-up.

Chronic diuretic therapy attenuates renal BOLD magnetic resonance response to an acute furosemide stimulus.

BACKGROUND: Blood Oxygen Level Dependent (BOLD) magnetic resonance (MR) is a novel imaging tool that detects changes in tissue oxygenation. Increases in renal oxygenation in response to a standard 20 mg intravenous furosemide stimulus have been evaluated to assess kidney viability in patients with renal artery stenosis (RAS). The effect of prior exposure to furosemide on the ability of BOLD MR techniques to evaluate renal function is unknown.This study tested the hypothesis that chronic loop diuretic therapy is associated with attenuated responses in renal tissue oxygenation as measured by BOLD MR with an acute 20 mg intravenous furosemide stimulus in participants undergoing evaluation for RAS. METHODS: Thirty-eight participants referred for evaluation of RAS were recruited for this study. We examined renal cortical and medullary BOLD signal (T2*) intensities before and after a 20 mg intravenous furosemide stimulus. Additionally, we measured changes in renal artery blood flow using phase contrast techniques. RESULTS: After controlling for covariates age, race, gender, diabetes, glomerular filtration rate, body mass index, and stenosis severity, daily oral furosemide dose was an independent, negative predictor of renal medullary T2* response (p=0.01) to a standard 20 mg intravenous furosemide stimulus. Stenosis severity and ethnicity were also significant independent predictors of changes in T2* signal intensity in response to an acute furosemide challenge. Changes in renal blood flow in response to acute furosemide administration were correlated with changes in T2* in the renal cortex (r=0.29, p=0.03) but not the medulla suggesting changes in renal medullary oxygenation were not due to reduced renal medullary blood flow. CONCLUSIONS: Chronic furosemide therapy attenuates BOLD MR responses to an acute furosemide stimulus in patients with RAS being evaluated for renal artery revascularization procedures. Thus, patients who are chronically administered loop diuretics may need a different dosing strategy to accurately detect changes in renal oxygenation with BOLD MR in response to a furosemide stimulus.

Small, short-duration, dobutamine-induced perfusion defects are not associated with adverse prognosis in intermediate-risk individuals receiving cardiovascular magnetic resonance stress imaging.

OBJECTIVE: The objective of this study was to assess the frequency and prognostic utility of small, short-duration left ventricular myocardial perfusion defects during dobutamine cardiovascular magnetic resonance (DCMR) stress imaging. METHODS: We performed first-pass contrast-enhanced DCMR at peak stress in 331 consecutively recruited individuals (aged 68 ± 8 years, 50% men) at intermediate risk for a future cardiac event. Size, location, and persistence of low-signal intensity perfusion defects were recorded. Cardiac events were assessed by personnel blinded to imaging results for a median of 24 months after the DCMR. RESULTS: Among the 55 individuals (16.6%) who exhibited small (<25% myocardial thickness) and short-duration (<5 frames in persistence) perfusion defects, diabetes was more prevalent (P = 0.019) and no cardiac events were observed. Large, persistent perfusion defects were associated with coronary artery disease, prior myocardial infarction, and decreased left ventricular function (P < 0.001 for all) and increased 2-year risk for a cardiac event (hazard ratio, 10.3; P < 0.001; confidence interval, 3.3-33.0). CONCLUSIONS: In individuals with diabetes, hypertension, or coronary artery disease at intermediate risk for a future cardiac event, small, short-duration DCMR perfusion defects are not associated with increased 2-year risk for a subsequent cardiac event.

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.

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.

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.

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.

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.

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction.

PURPOSE: - Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique. METHODS: - Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range. RESULTS: - Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56-72] years. Global stress MBF was 2.43 ml/min/g [2.16-2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07-2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81-0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e' and E/e' respectively). CONCLUSION: - Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

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.