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We describe a first suspected case of fibrosing mediastinitis following anti-programmed death (PD)-1 therapy, pembrolizumab. Multimodality imaging, including cardiac magnetic resonance imaging, and a multidisciplinary team approach were integral to the diagnosis. If further substantiated, systematic surveillance after anti-PD-1 therapy for fibrosing mediastinitis may be warranted. (

Objectives Prior studies have identified a relationship between body mass index (BMI) and intraperitoneal (IP) fat with heart failure; however, in prior studies of cancer patients receiving potentially cardiotoxic chemotherapy, elevations in BMI have not necessarily been associated with decrements in heart function. This study tested the hypothesis that IP fat may be associated with left ventricular ejection fraction (LVEF) decline among cancer patients receiving potentially cardiotoxic chemotherapy. Methods In this prospective study of 61 cancer patients (23 breast cancer, 32 lymphoma, and 6 sarcoma), IP fat and other assessments of body composition, and changes in LVEF from pre‐ to postcancer treatment using noninvasive magnetic resonance imaging was ascertained. Results After accounting for age, baseline LVEF, and confounding variables, pre‐ to 24‐month post‐treatment LVEF changes were inversely correlated with IP fat (r = −0.33; p = 0.02) and positively correlated with measures of subcutaneous (SQ) fat (r = 0.33; p = 0.01). These LVEF changes were not correlated with BMI (r = 0.12; p = 0.37). Conclusion Among patients receiving potentially cardiotoxic chemotherapy, pretreatment IP fat was associated with subsequent declines in LVEF. There was no association between BMI and LVEF decline. These findings may be related to a potential protective effect of SQ fat.

Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) now includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) therapy to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in the non-cancer population is associated with CV disease, including atherosclerosis and coronary artery disease, which can be detected pre-clinically by myocardial perfusion imaging and coronary artery plaques. This, together with the CV morbidity associated with other aspects of BC treatment and future life-years of these women, warrants further investigation with the goal of identifying pre-clinical markers of myocardial compromise. We seek to do this with the following specific aims: 1. Characterize and quantify the extent of coronary microvascular injury and perfusion changes experienced during early NCED therapy. 2. Characterize and quantify the extent of structural and functional alterations to the aorta and left ventricle while on NCED therapy. 3. Identify potential biomarkers and additional risk factors for CV morbidity in patients receiving NCEDTrial Design: This is a federally funded (NHLBI) prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary outcome is myocardial perfusion reserve (MPR) as measured by CMR imaging stress studies. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors, including an emphasis on racial disparities, on study outcomes, and dynamic change in modifiable and treatment related risk factors. Statistical Methods: We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group) for Aims 1 and 2. Comparisons will be made using longitudinal mixed models to examine effects on outcomes measured. The second analyses, for Aim 3, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with MPR. The sample size allows 80% power to address specific aims for between and within group comparisons, including a between group difference of 2.8% in our primary outcome, MPR. Present Accrual: 0 Target Accrual: 90 Contact information: Emily Douglas, MD; edouglas@wakehealth.edu Table 1: Study Procedures Citation Format: Emily Douglas, Nathaniel O’Connell, Mary Hackney, Wendy Bottinor, John Grizzard, Igor Klem, Carolyn Park, Sujethra Vasu, Karl Richardson, Susan Dent, Ralph D’Agostino, Gregory Hundley, Jennifer Jordan, Alexandra Thomas. The CROWN Study (CaRdiac Outcomes With Near complete estrogen deprivation): A multicenter, prospective cohort study of cardiovascular outcomes in premenopausal women treated with ovarian suppression and an aromatase inhibitor [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-05.

Background Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) with aromatase inhibitor therapy; however, abrupt menopause induction, together with further decrements in estrogen exposure through aromatase inhibition, may affect cardiovascular microcirculatory function. We examined adenosine-induced changes in left ventricular (LV) myocardial T1, a potential subclinical marker of LV microcirculatory function in premenopausal women undergoing treatment for breast cancer. Methods Twenty-one premenopausal women (14 with HR-positive breast cancer receiving OFS with an aromatase inhibitor and 7 comparator women with triple-negative breast cancer [TNBC] who had completed primary systemic therapy) underwent serial resting and adenosine cardiovascular magnetic resonance imaging measurements of LV myocardial T1 and LV volumes, mass, and ejection fraction. All statistical tests were 2-sided. Results After a median of 4.0 months (range = 3.1-5.7 months), the stress to resting ratio of LV myocardial T1 declined in women with HR-positive breast cancer (−1.3%, 95% confidence interval [CI] = −3.4% to 0.7%) relative to those with TNBC (3.2%, 95% CI = −1.2% to 7.6%, P = .02). After accounting for age, LV stroke volume, LV ejection fraction, diastolic blood pressure, and breast cancer subtype women with HR-positive breast cancer experienced a blunted T1 response after adenosine relative to women with TNBC (difference = −4.7%, 95% CI = −7.3% to −2.1%, Pdifference = .002). Conclusions Over the brief interval examined, women with HR-positive breast cancer receiving OFS with an aromatase inhibitor experienced reductions in adenosine-associated changes in LV myocardial T1 relative to women who received nonhormonal therapy for TNBC. These findings suggest a possible adverse impact on LV myocardial microcirculatory function in premenopausal women with breast cancer receiving hormone deprivation therapy.

Background The Wake‐Up T2MI Registry is a retrospective cohort study investigating patients with type 2 myocardial infarction (T2MI), acute myocardial injury, and chronic myocardial injury. We aim to explore risk stratification strategies and investigate clinical characteristics, management, and short‐ and long‐term outcomes in this high‐risk, understudied population. Methods From 1 January 2009 to 31 December 2010, 2846 patients were identified with T2MI or myocardial injury defined as elevated cardiac troponin I with at least one value above the 99th percentile upper reference limit and coefficient of variation of 10% (>40 ng/L) and meeting our inclusion criteria. Data of at least two serial troponin values will be collected from the electronic health records to differentiate between acute and chronic myocardial injury. The Fourth Universal Definition will be used to classify patients as having (a) T2MI, (b) acute myocardial injury, or (c) chronic myocardial injury during the index hospitalization. Long‐term mortality data will be collected through data linkage with the National Death Index and North Carolina State Vital Statistics. Results We have collected data for a total of 2205 patients as of November 2018. The mean age of the population was 65.6 ± 16.9 years, 48% were men, and 64% were white. Common comorbidities included hypertension (71%), hyperlipidemia (35%), and diabetes mellitus (30%). At presentation, 40% were on aspirin, 38% on β‐blockers, and 30% on statins. Conclusion Improved characterization and profiling of this cohort may further efforts to identify evidence‐based strategies to improve cardiovascular outcomes among patients with T2MI and myocardial injury.

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 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

Animal models of chemotherapy-induced cardiotoxicity have been instrumental in understanding the underlying mechanisms of the disease. The use of cardiac magnetic resonance (CMR) imaging and nuclear magnetic resonance (NMR) imaging in preclinical models allows the non-invasive study of subclinical pathophysiological processes that influence cardiac function and establish imaging parameters that can be adopted into clinical practice to predict cardiovascular outcomes. Given the rising population of cancer survivors and the current lack of effective therapies for the management of cardiotoxicity, research combining clinically relevant animal models and non-invasive cardiac imaging remains essential to improve methods to monitor, predict, and treat cardiovascular adverse events. This comprehensive review summarizes the lessons learned from animal models of cardiotoxicity employing CMR and tissue characterization techniques and discusses the ongoing challenges and hopes for the future.

To determine the impact of radiation therapy (XRT) in addition to trastuzumab (TZB) adjuvant chemotherapy for HER2+ breast cancer on left ventricular systolic function, we assessed demographics, oncologic treatment history including XRT exposure, and serial measurements of left ventricular ejection fraction (LVEF) in 135 consecutively identified women receiving TZB for treatment of adjuvant breast cancer. Longitudinal mixed effects models were fit to identify baseline to treatment changes in LVEF among those receiving TZB with or without concomitant anthracycline or XRT. Women averaged 53 ± 3 years in age, 77% were white, 62% patients had 1 or more cardiovascular risk factors at baseline, and mean duration of TZB was 11 ± 5 months. Seventy-seven women were treated with XRT and received between 4000 and 5500 cGy of radiation. The LVEF declined by an average of 3.4% after 1 year for those in the study. Relative to baseline upon completion of adjuvant TZB, LVEF remained reduced for those receiving anthracycline with or without XRT (p=0.002 for both), or XRT alone (p=0.002), but not in those without these therapies. Amongst patients treated only with XRT and TZB, LVEF declined 3.1% on average in those with left-sided disease and 6.9% on average in those with right-sided disease (p= 0.06, p= 0.008 respectively). Among women receiving TZB for adjuvant treatment of HER-2 positive breast cancer, the administration of XRT, anthracycline, or the combination of the 2 is associated with a persistent post-treatment as opposed to a temporary treatment related decline in LVEF.

Patients with or receiving potentially cardiotoxic treatment for cancer are susceptible to developing decrements in left ventricular mass, diastolic function, or systolic function. They may also experience valvular heart disease, pericardial disease, or intracardiac masses. Cardiovascular magnetic resonance may be used to assess cardiac anatomy, structure, and function and to characterize myocardial tissue. This combination of features facilitates the diagnosis and management of disease processes in patients with or those who have survived cancer. This report outlines and describes prior research involving cardiovascular magnetic resonance for assessing cardiovascular disease in patients with or previously having received treatment for cancer.

Increased left ventricular (LV) myocardial extracellular volume fraction (ECVF) measured by cardiac magnetic resonance (CMR) is now a recognized consequence of anthracycline chemotherapy ([1][1],[2][2]). It remains unknown, however, whether elevated ECVF may be attributable to an expansion of the LV

In observational studies, left ventricular mass (LVM) and structure are strong predictors of mortality and cardiovascular events. However, the effect of hypertension treatment on LVM reduction and its relation to subsequent outcomes is unclear, particularly at lower blood pressure (BP) targets. In an ancillary study of SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive BP control (target systolic BP target P =0.368), ejection fraction, or native T1 ( P =0.79), but there was a larger decrease in LVM/end-diastolic volume ratio (−0.04±0.01 versus −0.01±0.01; P =0.002) a measure of concentric LV remodeling. There were fewer cardiovascular events in the intensive control group, but no significant association between the reduced events and change in LVM or any other cardiac magnetic resonance imaging measure. In SPRINT-HEART, contrary to our hypothesis, there were no significant between-group differences in LVM, function, or myocardial T1 at 18-month follow-up. These results suggests that mediators other than these LV measures contribute to the improved cardiovascular outcomes with intensive BP control.

Background Patients from racial and ethnic minority groups presenting to the Emergency Department (ED) with chest pain experience lower odds of receiving stress testing compared with nonminorities. Studies have demonstrated that care pathways administered within the ED can reduce health disparities, but this has yet to be studied as a strategy to increase stress testing equity. Methods A secondary analysis from 3 randomized clinical trials involving ED patients with acute chest pain was performed to determine whether a care pathway, ACES (Accelerated Chest pain Evaluation with Stress imaging), reduces the racial disparity in index visit cardiac testing between African American (AA) and White patients. Three hundred thirty-four participants with symptoms and findings indicating intermediate to high risk for acute coronary syndrome were enrolled in 3 clinical trials. Major exclusions were ST-segment elevation, initial troponin elevation, and hemodynamic instability. Participants were randomly assigned to receive usual inpatient care, or ACES. The ACES care pathway includes placement in observation for serial cardiac markers, with an expectation for stress imaging. The primary outcome was index visit objective cardiac testing, compared among AA and White participants. Results AA participants represented 111/329 (34%) of the study population, 80/220 (36%) of the ACES group and 31/109 (28%) of the usual care group. In usual care, objective testing occurred less frequently among AA (22/31, 71%) than among White (69/78, 88%, P = 0.027) participants, primarily driven by cardiac catheterization (3% vs. 24%; P = 0.012). In ACES, testing rates did not differ by race [AA 78/80 (98%) vs. White 138/140 (99%); P = 0.623]. At 90 days, death, MI, and revascularization did not differ in either group between AA and White participants. Conclusions A care pathway with the expectation for stress imaging eliminates the racial disparity among AA and White participants with chest pain in the acquisition of index-visit cardiovascular testing.

Introduction: Premenopausal women with high-risk hormone receptor-positive (HR+) breast cancer (BC) undergo abrupt menopause induction with aromatase inhibitor (AI) anti-estrogen therapy and ovarian function suppression (OFS). This treatment improves recurrence-free survival but may increase cardiovascular (CV) risk associated with early hypoestrogenemia as observed in women with non-cancerous reasons for early loss of ovarian function. We sought to identify if OFS+AI therapy is associated with myocardial perfusion changes, a subclinical marker of coronary heart disease. Methods: We evaluated women with paired adenosine cardiovascular magnetic resonance imaging scans at 3-to 6-month intervals using cines and T1 maps in standard short-axis planes. As increased blood flow from vasodilation increases adenosine stress parametric T1 values of the myocardial tissue, the myocardial perfusion reactivity was calculated from the percent increase of stress versus native (pre-stress) T1 maps. Double-blinded post-processing of images was performed in CircleCVI software. Statistical analyses were performed in MATLAB (p0.05). The cardiovascular stress tests identified two HR+ women (14%) with abnormal results during stress imaging who were sent for further cardiovascular evaluations.Conclusions: Women with HR+ BC treated with OFS+AI exhibited a decline in global microcirculatory perfusion during an adenosine cardiac stress test with normal LV functional parameters. Alternatively, triple negative BC patients trended to have an improvement in LV function during the interval with non-significant improvement in myocardial perfusion. This study demonstrates a decline in myocardial perfusion in premenopausal women on OFS+AI therapy, suggesting subclinical coronary artery effects due to early hypoestrogenemia. Future work should confirm these results, identify women at higher risk, and test strategies to mitigate cardiotoxicity in premenopausal women with HR+ BC. Table: Cardiovascular magnetic resonance (CMR) study measures for HR+ BC patients on OFS+ AI therapy and triple negative BC patientsCMR MeasureHormone Receptor-Positive Breast Cancer(n=14)Triple Negative Breast Cancer(n=7)p-value for difference in change by groupBaselineFollow-upp-valueBaselineFollow-upp-valueLV Ejection Fraction, %56 (51, 61)56 (51, 62)0.8255 (50, 60)60 (55, 65)0.060.12EDVindex, mL/m270.6 (63.7, 77.5)69.9 (63.5, 76.3)0.7365.2 (58.0, 72.3)66.8 (51.4, 82.1)0.740.60ESVindex, mL/m231.3 (26.2, 36.5)30.4 (26.2, 34.5)0.3729.4 (23.8, 35.0)27.1 (19.4, 34.8)0.360.55SVindex, mL/m239.3 (34.3, 44.2)39.5 (33.9, 45.1)0.9035.8 (32.3, 39.3)39.7 (31.2, 48.2)0.230.29Myocardial mass index, g/m248.1 (42.7, 53.6)44.6 (40.0, 49.3)0.0843.5 (40.2, 46.8)41.0 (33.3, 48.7)0.420.77Global myocardial perfusion reactivity, %2.8 (1.1, 4.4)1.4 (-0.4, 3.3)0.191.4 (-0.9, 3.7)4.6 (0.9, 8.4)0.130.02Basal SAX myocardial perfusion reactivity, %2.2 (0.7, 3.7)1.4 (0.3, 2.5)0.261.8 (0.2, 3.4)2.1 (-1.7, 5.9)0.850.46Mid SAX myocardial perfusion reactivity, %2.4 (-.3, 5.2)0.5 (-1.5, 2.7)0.221.2 (-1.9, 4.2)3.3 (-0.9, 7.6)0.360.12Apical SAX myocardial perfusion reactivity, %3.4 (1.2, 5.7)2.1 (-1.4, 5.7)0.490.8 (-2.6, 4.1)8.8 (3.7, 13.9) Citation Format: Alexandra Thomas, Ralph B. D'Agostino, Jr., Katherine C. Ansley, Sung Park, Anuj Kotak, Steven M. Sorscher, Susan Melin, Emily H. Douglas, Sujethra Vasu, Paul A. Romitti, William G. Hundley, Jennifer H. Jordan. Global myocardial perfusion is reduced in premenopausal breast cancer patients treated with ovarian function suppression and aromatase inhibitor therapy: An adenosine stress T1 map CMR study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-02.

Cardiotoxicity is a known risk of certain breast cancer therapies; however, less is known about the differences in cardiotoxicity incidence and associated cardiovascular risk factors (CVDRFs) in African Americans (AAs). In this study, we assessed the incidence and CVDRFs associated with

Background: Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment. Methods and Results: We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non–Anth-bC (n=15), and in 24 cancer-free controls using paired t and χ 2 tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF ( P P =0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups ( P =0.11–0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines ( r =−0.27; P r =0.11; P =0.45). Moreover, this finding was independent of LVEF changes and body weight. Conclusions: Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.

Patients with cancer and concomitant cardiovascular disease frequently need various imaging investigations to arrive at a correct diagnosis.

The study was performed to determine age, sex, and time-dependent changes in aortic wall thickness (AWT) and to evaluate cross-sectional associations between AWT and arterial stiffness in older adults. Three hundred seventy-one longitudinal and 426 cross-sectional measurements of AWT from cardiovascular magnetic resonance imaging studies conducted within the Multi-Ethnic Study of Atherosclerosis were analyzed at 2 points in time, in 2000 to 2002 and then again from follow-up examinations in 2010 to 2012. Aortic wall thickness was determined from a double inversion recovery black-blood fast spin-echo sequence, and aortic stiffness was measured from a phase-contrast cine gradient echo sequence. The thickness of the midthoracic descending aortic wall was measured and correlated to distensibility of the ascending aorta and aortic pulse wave velocity. The average rate of AWT change was 0.032 mm/y. The increase in AWT was greater for those aged 45 to 54 years relative to individuals older than 55 years ( P trendP P =0.012) for hypertensive subjects. After adjustment for traditional risk factors, distensibility of the ascending aorta was significantly related to AWT in participants without hypertension. Hypertension was associated with increased aortic stiffness independent of aortic wall thickness.

Background— In a murine anthracycline-related cardiotoxicity model, increases in cardiovascular magnetic resonance myocardial contrast-enhanced T1-weighted signal intensity are associated with myocellular injury and decreases with left ventricular ejection fraction. We sought to determine whether T1- and T2-weighted measures of signal intensity associate with decreases in left ventricular ejection fraction in human subjects receiving potentially cardiotoxic chemotherapy. Methods and Results— In 65 individuals with breast cancer (n=51) or a hematologic malignancy (n=14), we measured left ventricular volumes, ejection fraction, and contrast-enhanced T1-weighted and T2-weighted signal intensity before and 3 months after initiating potentially cardiotoxic chemotherapy using blinded, unpaired analysis of cardiovascular magnetic resonance images. Participants were aged 51±12 years, of whom 55% received an anthracycline, 38% received a monoclonal antibody, and 6% received an antimicrotubule agent. Overall, left ventricular ejection fraction decreased from 57±6% to 54±7% ( P P P P =0.06). Changes in T1-weighted signal intensity did not differ within the 17 LV myocardial segments ( P =0.97). Myocardial edema quantified from T2-weighted images did not change significantly after 3 months ( P =0.70). Conclusions— Concordant with previous animal studies, cardiovascular magnetic resonance measures of contrast-enhanced T1-weighted signal intensity occur commensurate with small but significant left ventricular ejection fraction declines 3 months after the receipt of potentially cardiotoxic chemotherapy. These data indicate that changes in T1-weighted signal intensity may serve as an early marker of subclinical injury related to the administration of potentially cardiotoxic chemotherapy in human subjects.

Prosthetic valve thrombosis (PVT) is an increasingly recognized complication of bioprosthetic valve replacement, often resulting in abnormal hemodynamic, endothelial, and hemostatic conditions. Bioprosthetic PVT may lead to significant hemodynamic and clinical effects. In hemodynamically stable patients, first-line treatment for bioprosthetic PVT is systemic anticoagulation. However, concomitant cardiovascular pathology may lead to additional clinical sequalae that requires acute therapeutic interventions. We describe two cases in which bioprosthetic PVT leads to hemodynamically significant intracardiac shunting through pre-existing patent foramen ovales requiring percutaneous closure with a Cribriform AMPLATZER occluder device. We also review the treatment for bioprosthetic PVT and discuss important clinical and hemodynamic considerations.

Our objective was to determine if increased cardiovascular (CV) stiffness is associated with disability in middle-aged and older adults at risk for congestive heart failure. CV stiffness (brachial pulse pressure/left ventricular stroke volume indexed to body surface area) and total disability (the summed assessment of activities of daily living, mobility, and instrumental activities of daily living) were measured in 445 individuals. A subset of 109 randomly selected individuals also underwent physical function testing. Total disability was associated with CV stiffness (p = .01), driven by an association with mobility (p = .005), but not activities of daily living (p = .13) or instrumental activities of daily living (p = .61). After accounting for age, these correlations remained significant for men (p = .04), but not for women. CV stiffness was also associated with increased 400-m walk time (p = .02). In middle-aged and elderly men at risk for congestive heart failure, CV stiffness is associated with decreased mobility and physical function, and increased overall disability.

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.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.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 (P0.001 for all) and increased 2-year risk for a cardiac event (hazard ratio, 10.3; P0.001; confidence interval, 3.3-33.0).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.

Vasodilator stress cardiac magnetic resonance (CMR) detects ischemia whereas coronary CT angiography (CTA) detects atherosclerosis. The purpose of this study was to determine concordance and accuracy of vasodilator stress CMR and coronary CTA in the same subjects. We studied 151 consecutive subjects referred to detect or exclude suspected obstructive coronary artery disease (CAD) in patients without known disease or recurrent stenosis or ischemia in patients with previously treated CAD. Vasodilator stress CMR was performed on a 1.5 T scanner. CTA was performed on a 320-detector row system. Subjects were followed for cardiovascular events and downstream diagnostic testing. Subjects averaged 56 ± 12 years (60 % male), and 62 % had intermediate pre-test probability for obstructive CAD. Follow-up averaged 450 ± 115 days and was 100 % complete. CMR and CTA agreed in 92 % of cases (κ 0.81, p

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF. Approximately 90% of new HF cases in older women are HFpEF.1 Adverse outcomes – exercise intolerance, poor quality of life, frequent hospitalizations, and reduced survival – approach those of HF with reduced EF (HFrEF). In contrast to HFrEF, the prevalence of HFpEF is increasing and its prognosis is worsening.2 Despite the strong public health importance of HFpEF, its pathogenesis is poorly understood. Our lack of understanding of HFpEF and its treatment is punctuated by the fact that 6 large, well-designed, randomized, clinical trials and several smaller ones were all neutral on their primary outcomes. The combination of high prevalence and lack of evidence-based treatments makes HFpEF a high-priority topic for research in cardiovascular disease. Article see p 550 A glaring absence among HFpEF studies has been a systematic autopsy-based study. Such studies have become more difficult as autopsy rates have declined with the availability of advanced multimodality imaging and deep-tissue biopsy techniques. Despite the increasing array of modern research techniques, postmortem methods continue to be uniquely valuable because of the ability to perform comprehensive, in-depth, detailed examinations of tissues and organs in humans. In this issue of Circulation , Mohammed and colleagues3 at the Mayo Clinic fill this critical gap with the first autopsy series of HFpEF. From a tissue registry patiently accumulated over a period of 19 years, their multidisciplinary team methodically collected and comprehensively analyzed specimens, medical records, electrocardiograms, and echocardiograms from 255 individuals, including patients with premortem diagnosis of HFpEF (n=124) and HFrEF (n=27), and from age-matched case controls who died of noncardiovascular causes (n=104). Characteristics of the HFpEF patients were relatively similar to community-based reports, including advanced age and a high prevalence of common comorbidities, including hypertension, diabetes …

Background: Decision of intervention for low gradient severe aortic stenosis (AS) with normal left ventricular ejection fraction (LVEF) is clinically challenging. The study was to determine the impact of stroke volume index (SVi) on prognosis in patients (pts) with AS. Methods: We examined 410 pts with moderate or severe AS and normal EF (≥50%). Pts were divided into four groups based on aortic valve area (AVA), mean pressure gradient (MPG) and SVi: Group I: low flow low gradient severe AS (AVA≤1.0cm 2 , MPG2 , n=75); Group II: normal flow low gradient severe AS (AVA≤1.0cm 2 , MPG2 , n=97); Group III: severe AS with matched gradient-AVA (AVA≤1.0cm 2 and MPG≥40mmHg, n=88); Group IV: moderate AS (AVA>1.0cm 2 and MPG>20mmHg, Results: Group I had higher prevalence of atrial fibrillation, more pronounced LV hypertrophy, lower SVi, smaller AVA, higher valvuloarterial impedance (Zva) (Table) and lower 3-year cumulative survival compared to Group II and Group IV (61% vs. 75% and 80%, p=0.004). Group II had a 3-year cumulative survival similar to moderate AS (75% vs. 80%, p>0.05). In pts with medical management, Group I and Group III had lower 3-year cumulative survival in comparison with Group II and Group IV (48% and 56% vs. 73% and 76%, p=0.001). Multivariate analysis showed SVi was a strong predictor of mortality in low gradient severe AS (HR 0.95, CI: 0.91-0.99, P=0.02). However, in gradient-AVA matched severe AS and moderate AS, SVi was not associated with mortality (p>0.05). Conclusions: Without AS intervention, low flow low gradient severe AS with normal EF carries poor prognosis similar to high gradient AS, but normal flow low gradient AS does not, suggesting that SVi may be used to identify the pts benefiting most from AS intervention in pts with low gradient AS.

Background— Cardiovascular magnetic resonance T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities. Methods and Results— We performed blinded cardiovascular magnetic resonance analyses of left ventricular T1 and extracellular volume (ECV) fraction in 327 individuals (65% women, aged 64±12 years). Thirty-seven individuals had breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors who received either anthracycline-based (n=37) or nonanthracycline-based (n=17) chemotherapy 2.8±1.3 years earlier were compared with 236 cancer-free participants. Multivariable analyses were performed to determine the association between T1/ECV measures and variables associated with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058±7 ms) and post- (1040±7 ms) receipt of anthracycline chemotherapy versus comparators (965±3 ms; P P P P =0.17 and P =0.16, respectively). Native T1 and ECV remained elevated in cancer survivors after accounting for demographics (including age), myocardial fibrosis risk factors, and left ventricular ejection fraction or myocardial mass index ( P Conclusions— Three years after anthracycline-based chemotherapy, elevations in myocardial T1 and ECV occur independent of underlying cancer or cardiovascular comorbidities, suggesting that imaging biomarkers of interstitial fibrosis in cancer survivors are related to prior receipt of a potentially cardiotoxic cancer treatment regimen.

Following myocardial injury, the left ventricular (LV) myocardial extracellular matrix (ECM) can undergo abnormal expansion (due to inflammation and interstitial fibrosis) that can be identified with cardiac magnetic resonance (CMR) assessments of extracellular volume fraction (ECV) [(1,2)][1].

Intracardiac thrombus is challenging as the risk of embolization dictates ideal management. We present a case highlighting the clinical rationale behind anticoagulation decisions for a large intracardiac thrombus. A 52 year old lady with metastatic gastroesophageal adenocarcinoma & recurrent DVTs

Background: The impact of advanced chronic kidney disease (CKD) on the outcomes of patients undergoing percutaneous coronary intervention (PCI) in the acute phase of myocardial infarction is poorly understood. We assessed the impact of CKD (stages 3–5) on the in-hospital outcomes of patients undergoing PCI for acute myocardial infarction (AMI) in a statewide registry. Methods: This study evaluated all patients who underwent PCI in New York State between 1997 and 1999. Of the 9,015 patients, 94 (1%) had at least stage 3 CKD (serum creatinine for AMI > 2.5 mg/dL) and were not on dialysis. Patients with advanced CKD were compared with those without advanced CKD using univariate and multivariate methods. The primary outcome of interest was in-hospital mortality. Results: Patients with advanced CKD had a higher incidence of diabetes, hypertension, and peripheral vascular disease. Patients with advanced CKD presented more commonly with cardiogenic shock or heart failure. The unadjusted in-hospital mortality was 23.4% for patients with advanced CKD compared with 4.2% for patients without advanced CKD (P < 0.001). After adjusting for the increased comorbidity and high risk clinical features, advanced CKD remained an independent predictor of in-hospital mortality (odds ratio 2.4, 95% Confidence Interval, 1.002–5.804, P = 0.049). Conclusions: Patients with AMI and advanced CKD who undergo PCI have more comorbidities and significantly worse in-hospital outcomes than patients without advanced CKD. Even after adjusting for these comorbidities, advanced CKD remains an independent predictor of increased in-hospital mortality. ' 2007 Wiley-Liss, Inc.

Background Dobutamine associated left ventricular (LV) wall motion analyses exhibit reduced sensitivity for detecting inducible ischemia in individuals with increased LV wall thickness. This study was performed to better understand the mechanism of this reduced sensitivity in the elderly who often manifest increased LV wall thickness and risk factors for coronary artery disease. Methods During dobutamine cardiovascular magnetic resonance (DCMR) stress testing, we assessed rate pressure product (RPP), aortic pulse wave velocity (PWV), LV myocardial oxygen demand (pressure volume area, PVA, mass, volumes, concentricity, and the presence of wall motion abnormalities (WMA) and first pass gadolinium enhanced perfusion defects (PDs) indicative of ischemia in 278 consecutively recruited individuals aged 69 ± 8 years with pre-existing or known risk factors for coronary artery disease. Each variable was assessed independently by personnel blinded to participant identifiers and analyses of other DCMR or hemodynamic variables. Results Participants were 80% white, 90% hypertensive, 43% diabetic and 55% men. With dobutamine, 60% of the participants who exhibited PDs had no inducible WMA. Among these participants, myocardial oxygen demand was lower than that observed in those who had both wall motion and perfusion abnormalities suggestive of ischemia (p = 0.03). Relative to those with PDs and inducible WMAs, myocardial oxygen demand remained different in these individuals with PDs without an inducible WMA after accounting for LV afterload and contractility (p = 0.02 and 0.03 respectively), but not after accounting for either LV stress related end diastolic volume index (LV preload) or resting concentricity (p = 0.31-0.71). Conclusions During dobutamine stress testing, elderly patients experience increased LV concentricity and declines in LV preload and myocardial oxygen demand, all of which are associated with an absence of inducible LV WMAs indicative of myocardial ischemia. These findings provide insight as to why dobutamine associated wall motion analyses exhibit reduced sensitivity for identifying inducible ischemia in elderly. Trial registration This study was registered with Clinicaltrials.gov (NCT00542503).

Background Abnormal resting arterial stiffness is present in middle‐aged and elderly persons with abnormalities of fasting glucose (diabetes or impaired fasting glucose) and is associated with exercise intolerance. We sought to determine whether these same persons exhibited stress‐related abnormalities of arterial stiffness. Methods and Results We analyzed dobutamine magnetic resonance stress imaging results from 373 consecutively recruited persons aged 55 to 85 years with normal fasting glucose, impaired fasting glucose, or diabetes who were at risk for but without symptomatic heart failure. Personnel blinded to participant identifiers measured arterial stiffness (brachial pulse pressure/left ventricular stroke volume indexed to body surface area, the aortic elastance index [brachial end‐systolic pressure/left ventricular stroke volume indexed to body surface area], and thoracic aortic distensibility) at 80% of the maximum predicted heart rate response for age. Participants averaged 69±8 years of age; 79% were white, 92% were hypertensive, and 66% were women. After accounting for hypertension, sex, coronary artery disease, smoking, medications, hypercholesterolemia, and visceral fat, we observed an effect of glycemic status for stress measures of arterial stiffness in those with diabetes and impaired fasting glucose relative to those with normal fasting glucose ( P =0.002, P =0.02, and P =0.003, respectively). Conclusion Middle‐ and older‐aged individuals with diabetes or impaired fasting glucose have higher stress measures of arterial stiffness than those with normal fasting glucose. These data emphasize the need for future studies with larger sample sizes to determine whether stress‐related elevations in arterial stiffness are related to exercise intolerance and future episodes of heart failure experienced by those with abnormalities of fasting glucose. Clinical Trial Registration URL: http://clinicaltrials.gov/ . Unique identifier: NCT00542503.

OBJECTIVE The assessment of right ventricular (RV) perfusion defects has remained challenging during vasodilator stress perfusion with cardiovascular magnetic resonance (CMR). The significance of RV signal abnormalities during vasodilator stress perfusion and late gadolinium-enhanced CMR is yet uncertain. METHODS Among 61 individuals who underwent adenosine CMR stress testing before cardiac catheterization, we assessed the severity of coronary artery stenoses, mortality, the presence of stress and rest perfusion defects, as well as the presence of late gadolinium enhancement (LGE). RESULTS Right ventricular stress-induced perfusion defects were positively associated with left anterior descending artery and proximal right coronary artery stenoses but were negatively associated with left circumflex artery stenoses. The presence of RVLGE was associated with mortality, but 77% of those with RVLGE also had left ventricular LGE. CONCLUSIONS Proximal right coronary artery and left anterior descending artery stenoses are positively associated, whereas left circumflex artery stenoses are negatively associated with RV stress-induced perfusion defects. Right ventricular LGE was associated with mortality, but further study is needed to determine whether this is independent of left ventricular LGE.

Background Recent studies have shown an association between statin therapy and a reduced risk of heart failure among breast cancer survivors. Our goal was to evaluate whether statin therapy for prevention of cardiovascular (CV) disease would ameliorate declines in the left ventricular ejection fraction (LVEF) that is often observed during anthracycline-based chemotherapy (Anth-bC). Methods There were 51 participants (33 women and 18 men, aged 48 ± 2 years). We obtained cardiovascular magnetic resonance imaging (CMRI) measurements of LVEF before and 6 months after initiation of Anth-bC for patients with breast cancer, leukemia, or lymphoma. Fourteen individuals received statin therapy, and 37 patients received no statins. MR image analysts were blinded to participant identifiers. Results Individuals receiving statins were older and often had diabetes mellitus (DM), hypertension (HTN), and hyperlipidemia (HLD). For those receiving statins, LVEF was 56.6% ± 1.4% at baseline and 54.1% ± 1.3% 6 months after initiating anthracycline treatment ( P = 0.15). For those not receiving statins, LVEF was 57.5% ± 1.4% at baseline and decreased to 52.4% ± 1.2% over a similar 6-month interval ( P = 0.0003). In a multivariable model accounting for age, sex, DM, HTN, HLD, and cumulative amount of anthracycline received, LVEF remained unchanged in participants receiving a statin (+1.1% ± 2.6%) vs a −6.5% ± 1.5% decline among those not receiving a statin ( P = 0.03). Conclusions These data highlight the finding that individuals receiving statin therapy for prevention of cardiovascular disease may experience less deterioration in LVEF with early receipt of Anth-bC than individuals not receiving statins. Further studies with large numbers of participants are warranted to determine if statins protect against LVEF decline in patients receiving Anth-bC.

Background Obesity is associated with cardiovascular morbidity and mortality. This quantitative CMR perfusion study aims to examine the contribution of body mass index (BMI) to decreased myocardial perfusion reserve (MPR). Methods 123 patients with no obstructive epicardial coronary artery disease, defined by coronary computed tomographic angiogram demonstrating < 30% stenosis, underwent regadenoson CMR 1st-pass perfusion imaging, using 0.05 mmol/kg gadolinium (Gd) followed by rest perfusion imaging (also 0.05 mmol/kg Gd) performed 20 minutes later. The subjects were categorized into 4 groups: normal BMI (between 18.5-24.9 kg/m2, overweight (BMI 25-29.9 kg/m2), Class I obese (BMI 30-34.9), and Class II and III obese (BMI≥35). Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution.

Methods Quantitative CMR perfusion was performed at 1.5T in 17 healthy volunteers under baseline (rest) and adenosine hyperemia (stress). Median filters with different kernel size were used to estimate MBF at different resolutions (0.07 g, 0.27 g, 0.61 g, 1.1 g of myocardium). MBF heterogeneity was evaluated as the relative dispersion ([RD] = standard deviation/mean) on basal- and mid-ventricular slices for each subject. Paired t-tests and linear mixed-models were used to account for withinsubject effects. Results All normal volunteers had Framingham scores

Methods 423 studies by 1.5-T whole-body MRI were analyzed. CMRI protocol included cardiac function and late gadolinium enhancement. Only participants with no findings of myocardial scar were included. AWT images were obtained using a double inversion recovery black-blood fast spin-echo sequence and phase contrast cine gradient echo sequence was used to evaluate aortic stiffness. Aortic sagittal oblique plane with black blood sequence was acquired to position the aortic imaging and allowed for the measurement of the distance between the ascending and descending aorta. Images of the ascending and descending aorta were obtained in the transverse plane at the level of the right pulmonary artery perpendicular to the vessel lumen. The thickness of the midthoracic descending aortic wall was measured using electronic calipers at 4 standard positions: 12, 3, 6, and 9 o’clock (QMASS 7.2). The average value of these 4 measurements was calculated. Distensibiliy of the ascending aorta and PWV were performed using validated automated software (ARTFUN. INSERM U678). Results Table 1 lists demographics, AWT, distensibility and PWV stratified by hypertension status. AWT was not different (p = 0.35) but distensibility was lower (p < 0.001) and PWV was higher (p = 0.012) in hypertension. Linear regression analyses (Table 2) demonstrate distensibility was significantly correlated to AWT in the cohort without hypertension. AWT was a predictor for PWV with the basic adjustment (Model 1) in the hypertension group, but this correlation diminished after adjusting for more variables (Model 2, only systolic blood pressure and black race were positively correlated to PWV significantly).

Background Regadenoson, dipyridamole and adenosine are commonly used vasodilators in myocardial perfusion imaging for the detection of obstructive coronary artery disease. There are few comparative studies of the vasodilator properties of regadenoson, adenosine and dipyridamole in humans. The specific aim of this study was to determine the relative potency of these three vasodilators by quantifying stress and rest myocardial perfusion in humans using cardiovascular magnetic resonance (CMR). Methods Fifteen healthy normal volunteers, with Framingham score less than 1% underwent vasodilator stress testing with regadenoson (400 μg bolus), dipyridamole (0.56 mg/kg) and adenosine (140 μg /kg/min) on separate days. Rest perfusion imaging was performed initially. Twenty minutes later, stress imaging was performed at peak vasodilation, i.e. 70 seconds after regadenoson, 4 minutes after dipyridamole infusion and between 3–4 minutes of the adenosine infusion. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution. Results Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 μl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 μl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs. 2.12 ± 0.27, p = NS), but persisted between regadenoson and dipyridamole (2.04 ± 0.34 vs. 1.77 ± 0.33, p = 0.07) and between adenosine and dipyridamole (2.12 ± 0.27 vs. 1.77 ± 0.33, p = 0.01). Conclusions Based on fully quantitative perfusion using CMR, regadenoson and adenosine have similar vasodilator efficacy and are superior to dipyridamole.

Dyspnea is the major symptom experienced by patients with heart failure (HF) and points to the important role of the lungs in this syndrome. Article see p 693 Normal left ventricular diastolic function keeps the left atrial and pulmonary venous pressures low (25 mm Hg), the accumulating fluid enters the alveolar space, producing pulmonary edema. This interferes with gas exchange and results in intrapulmonary shunting, leading to hypoxia. In this way, acute pulmonary edema can produce …

Background Myocardial infarction (MI) documented by late gadolinium enhancement (LGE) has clinical and prognostic importance, but its detection is sometimes compromised by poor contrast between blood and MI. MultiContrast Delayed Enhancement (MCODE) is a technique that helps discriminate subendocardial MI from blood pool by simultaneously providing a T2-weighted image with a PSIR (phase sensitive inversion recovery) LGE image. In this clinical validation study, our goal was to prospectively compare standard LGE imaging to MCODE in the detection of MI. Methods Imaging was performed on a 1.5 T scanner on patients referred for CMR including a LGE study. Prospective comparisons between MCODE and standard PSIR LGE imaging were done by targeted, repeat imaging of slice locations. Clinical data were used to determine MI status. Images at each of multiple time points were read on separate days and categorized as to whether or not MI was present and whether an infarction was transmural or subendocardial. The extent of infarction was scored on a sector-by-sector basis. Results Seventy-three patients were imaged with the specified protocol. The majority were referred for vasodilator perfusion exams and viability assessment (37 ischemia assessment, 12 acute MI, 10 chronic MI, 12 other diagnoses). Forty-six patients had a final diagnosis of MI (30 subendocardial and 16 transmural). MCODE had similar specificity compared to LGE at all time points but demonstrated better sensitivity compared to LGE performed early and immediately before and after the MCODE (p = 0.008 and 0.02 respectively). Conventional LGE only missed cases of subendocardial MI. Both LGE and MCODE identified all transmural MI. Based on clinical determination of MI, MCODE had three false positive MI’s; LGE had two false positive MI’s including two of the three MCODE false positives. On a per sector basis, MCODE identified more infarcted sectors compared to LGE performed immediately prior to MCODE (p < 0.001). Conclusion While both PSIR LGE and MCODE were good in identifying MI, MCODE demonstrated more subendocardial MI’s than LGE and identified a larger number of infarcted sectors. The simultaneous acquisition of T1 and T2-weighted images improved differentiation of blood pool from enhanced subendocardial MI.