Quantifying Cardiothoracic Variation with Posture and Respiration to Inform Cardiac Device Design.

PURPOSE: With extravascular implantable cardioverter defibrillator leads placed beneath the sternum, it is important to quantify heart motion relative to the rib cage with postural changes and respiration. METHODS: MRI scans from five males and five females were collected in upright and supine postures at end inspiration [n = 10 each]. Left and right decubitus [n = 8 each] and prone [n = 5] MRIs at end inspiration and supine MRIs at end expiration [n = 5] were collected on a subset. Four cardiothoracic measurements, six cardiac measurements, and six cardiac landmarks were collected to measure changes across different postures and stages of respiration. RESULTS: The relative location of the LV apex to the nearest intercostal space was significantly different between the supine and decubitus postures (average ± SD difference: - 15.7 ± 11.4 mm; p < 0.05). The heart centroid to xipho-sternal junction distance was 9.7 ± 7.9 mm greater in the supine posture when compared to the upright posture (p < 0.05). Cardiac landmark motion in the lateral direction was largest due to postural movement (range 23-50 mm) from the left decubitus to the right decubitus posture, and less influenced by respiration (5-17 mm). Caudal-cranial displacement was generally larger due to upright posture (13-23 mm caudal) and inspiration (7-20 mm cranial). CONCLUSIONS: This study demonstrates that the location of the heart with respect to the rib cage varies with posture and respiration. The gravitational effects of postural shifts on the heart position are roughly 2-3 times larger than the effects of normal respiration.

Effect of Intensive Blood Pressure Control on Aortic Stiffness in the SPRINT-HEART.

[Figure: see text].

Semiautomatic morphometric analysis of skeletal muscle obtained by needle biopsy in older adults.

Analysis of skeletal muscle mass and composition is essential for studying the biology of age-related sarcopenia, loss of muscle mass, and function. Muscle immunohistochemistry (IHC) allows for simultaneous visualization of morphological characteristics and determination of fiber type composition. The information gleaned from myosin heavy chain (MHC) isoform, and morphological measurements offer a more complete assessment of muscle health and properties than classical techniques such as SDS-PAGE and ATPase immunostaining; however, IHC quantification is a time-consuming and tedious method. We developed a semiautomatic method to account for issues frequently encountered in aging tissue. We analyzed needle-biopsied vastus lateralis (VL) of the quadriceps from a cohort of 14 volunteers aged 74.9 ± 2.2 years. We found a high correlation between manual quantification and semiautomatic analyses for the total number of fibers detected (r2 = 0.989) and total fiber cross-sectional area (r2 = 0.836). The analysis of the VL fiber subtype composition and the cross-sectional area also did not show statistically significant differences. The semiautomatic approach was completed in 10-15% of the time required for manual quantification. The results from these analyses highlight some of the specific issues which commonly occur in aged muscle. Our methods which address these issues underscore the importance of developing efficient, accurate, and reliable methods for quantitatively analyzing the skeletal muscle and the standardization of collection protocols to maximize the likelihood of preserving tissue quality in older adults. Utilizing IHC as a means of exploring the progression of disease, aging, and injury in the skeletal muscle allows for the practical study of muscle tissue down to the fiber level. By adding editing modules to our semiautomatic approach, we accurately quantified the aging muscle and addressed common technical issues.

Effect of Intensive Blood Pressure Reduction on Left Ventricular Mass, Structure, Function, and Fibrosis in the SPRINT-HEART.

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 <120 mm Hg) versus standard BP control (<140 mm Hg), cardiac magnetic resonance imaging was performed at baseline and 18-month follow-up to measure: LVM, volumes, ejection fraction, and native T1 mapping for myocardial fibrosis. At baseline, 337 participants were examined (age: 64±9 years, 45% women); 300 completed the 18-month exam (153 intensive control and 147 standard control). In the intensive versus standard BP control group at 18 months, there was no difference in change in LVM (mean±SE =-2.7±0.5 g versus -2.3±0.7 g; 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.

Beta-Blocker Use Is Associated with Higher Renal Tissue Oxygenation in Hypertensive Patients Suspected of Renal Artery Stenosis.

BACKGROUND: Chronic renal hypoxia influences the progression of chronic kidney disease (CKD). Blood oxygen level-dependent (BOLD) magnetic resonance (MR) is a noninvasive tool for the assessment of renal oxygenation. The impact of beta-blockers on renal hemodynamics and oxygenation is not completely understood. We sought to determine the association between beta-blocker use, renal cortical and medullary oxygenation, and renal blood flow in patients suspected of renal artery stenosis. METHODS: We measured renal cortical and medullary oxygenation using BOLD MR and renal artery blood flow using MR phase contrast techniques in 38 participants suspected of renal artery stenosis. RESULTS: Chronic beta-blocker therapy was associated with improved renal cortical (p < 0.001) and medullary (p = 0.03) oxygenation, while the use of calcium channel blockers or diuretics showed no association with either cortical or medullary oxygenation. Receipt of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with reduced medullary oxygenation (p = 0.01). In a multivariable model, chronic receipt of beta-blockers was the only significant predictor of renal tissue oxygenation (ß = 8.4, p = 0.008). Beta-blocker therapy was not associated with significant changes in renal artery blood flow, suggesting that improved renal oxygenation may be related to reduced renal oxygen consumption. CONCLUSIONS: In addition to known benefits to reduce cardiovascular mortality in patients with renal disease, beta-blockers may reduce or prevent the progression of renal dysfunction in patients with hypertension, diabetes, and renovascular disease, partly by reducing renal oxygen consumption. These observations may have important implications for the treatment of patients with CKD.

Anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors.

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<0.0001 for both). Age-adjusted ECV, a marker of myocardial fibrosis, was elevated in anthracycline-treated cancer participants (30.4±0.7%) compared with either pretreatment cancer (27.8±0.7%; P<0.01) or cancer-free comparators (26.9±0.2%; P<0.0001). T1 and ECV of nonanthracycline survivors were no different than pretreatment survivors (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<0.0001 for all). 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.

Adiposity Is Associated with Gender-Specific Reductions in Left Ventricular Myocardial Perfusion during Dobutamine Stress.

BACKGROUND: Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women. METHODS: Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress. RESULTS: We observed inverse relationships between female gender (r = -0.35, p = 0.003), pericardial fat (r = -0.36, p = 0.03), intraperitoneal fat (r = -0.37, p = 0.001), and retroperitoneal fat (r = -0.36, p = 0.002) and myocardial perfusion index. Visceral fat depots were not associated with reduced myocardial perfusion at peak dose dobutamine in men. However, in women, BMI (r = -0.33, p = 0.04), pericardial fat (r = -0.53, p = 0.02), subcutaneous fat (r = -0.39, p = 0.01) and intraperitoneal fat (r = -0.30, p = 0.05) were associated with reduced myocardial perfusion during dobutamine stress. CONCLUSIONS: Higher visceral fat volumes are associated with reduced left ventricular myocardial perfusion at peak dose dobutamine stress in women but not in men. These findings suggest that visceral fat may contribute to abnormal microcirculatory coronary artery perfusion syndromes, explaining why some women exhibit more anginal symptoms despite typically lower grade epicardial coronary artery stenoses than men.

Prognostic utility of cardiovascular magnetic resonance upright maximal treadmill exercise testing.

BACKGROUND: Left ventricular wall motion abnormalities (LVWMA) observed during cardiovascular magnetic resonance (CMR) pharmacologic stress testing can be used to determine cardiac prognosis, but currently, information regarding the prognostic utility of upright maximal treadmill induced LVWMA is unknown. Our objective was to determine the prognostic utility of upright maximal treadmill exercise stress CMR. METHODS: One hundred and fifteen (115) men and women with known or suspected coronary arteriosclerosis and an appropriate indication for cardiovascular (CV) imaging to supplement ST segment stress testing underwent an upright treadmill exercise CMR stress test in which LVWMA were identified before and immediately after exercise. Personnel blinded to results determined the post-test incidence of cardiac events (cardiac death, myocardial infarctions [MI], and unstable angina warranting hospital admission or coronary arterial revascularization). RESULTS: All participants completed the testing protocol, with 90% completing image acquisition within 60 s of exercise cessation. MI or cardiac death occurred in 3% of individuals without and 17% of individuals with inducible LVWMA (p = 0.024). The combination of MI, cardiac death, and unstable angina warranting hospitalization occurred in 14% of individuals without and 47% of individuals with inducible LVWMA (p = 0.002). The addition of CMR imaging identified those at risk for future events (p = 0.002), as opposed to the electrocardiogram stress test alone (p = 0.63). CONCLUSIONS: In patients with or suspected of coronary arteriosclerosis and appropriate indication for imaging to supplement ST segment analysis during upright treadmill exercise, the presence of inducible LVWMA during treadmill exercise stress CMR supplements ST segment monitoring and helps identify those at risk of the future combined endpoints of myocardial infarction, cardiac death, and unstable angina warranting hospitalization.

A Method to Quantify Supine to Prone Thoracoabdominal Deformation and Organ Migration in a Set of Healthy Young Adults.

Medical image data used for the development of computational human body models are often retrospectively acquired, and researchers are unlikely to encounter scans of healthy individuals in specific postures. We prospectively acquired scans in both prone and supine postures from 22 healthy young adults; M:F 1:1, with age, height, and weight of 28.8±7.0 years, 173.0±7.8 cm, and 70.6±10.9 kg. While prone, subjects’ arms were superior to the head and supported by a foam insert at axilla. Breath held, T1-weighted MRI scans were acquired using a Siemen’s Skyra 3T with an in-plane resolution of 1.56 mm (TR: 4.10 ms, TE: 1.23 ms, thickness: 2 mm, matrix: 256x256, FOV: 400 mm). Gross thoraco-abdominal compression was considered as the change in perpendicular distance in the transverse plane measured from the anterior margin of L4/L5 to the table (for prone) or exterior body surface (for supine). Gross thoraco-abdominal, liver and spleen compression were found to be 8.5% (71.6±12.9 mm prone vs. 78.7±12.4 mm supine; p=0.0013), 17.7% (110.4±4.1 mm prone vs. 134.8±2.6 mm supine; p<0.0001), and 3.5% (53.8±1.9 mm prone vs. 57.3±2.9 mm supine) respectively. Gender and spleen compression differences were not noted. The liver and spleen migrated on average 8.3 mm posteriorly, 11.4 mm rightward, 15.1 mm superiorly and 4.1 mm anteriorly, 6.1 mm rightward, 1.7 mm superiorly respectively. The data obtained from this set may be of use in computational biomechanics, surgical simulation, and medical device design.

Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function.

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.

Increased cardiovascular stiffness and impaired age-related functional status.

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.

Longitudinal assessment of concurrent changes in left ventricular ejection fraction and left ventricular myocardial tissue characteristics after administration of cardiotoxic chemotherapies using T1-weighted and T2-weighted cardiovascular magnetic resonance.

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<0.001) because of an increase in end-systolic volume (P<0.05). T1-weighted signal intensities also increased from 14.1 ± 5.1 to 15.9 ± 6.8 (P<0.05), with baseline values trending higher among individuals who received chemotherapy before study enrollment (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.

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.

Stress CMR reduces revascularization, hospital readmission, and recurrent cardiac testing in intermediate-risk patients with acute chest pain.

OBJECTIVES: The aim of this study was to determine the effect of stress cardiac magnetic resonance (CMR) imaging in an observation unit (OU) on revascularization, hospital readmission, and recurrent cardiac testing in intermediate-risk patients with possible acute coronary syndromes (ACS). BACKGROUND: Intermediate-risk patients commonly undergo hospital admission with high rates of coronary revascularization. It is unknown whether OU-based care with CMR is a more efficient alternative. METHODS: A total of 105 intermediate-risk participants with symptoms of ACS but without definite ACS on the basis of the first electrocardiogram and troponin were randomized to usual care provided by cardiologists and internists (n = 53) or to OU care with stress CMR (n = 52). The primary composite endpoint of coronary artery revascularization, hospital readmission, and recurrent cardiac testing at 90 days was determined. The secondary endpoint was length of stay from randomization to index visit discharge; safety was measured as ACS after discharge. RESULTS: The median age of participants was 56 years (range 35 to 91 years), 54% were men, and 20% had pre-existing coronary disease. Index hospital admission was avoided in 85% of the OU CMR participants. The primary outcome occurred in 20 usual care participants (38%) versus 7 OU CMR participants (13%) (hazard ratio: 3.4; 95% confidence interval: 1.4 to 8.0, p = 0.006). The OU CMR group experienced significant reductions in all components: revascularizations (15% vs. 2%, p = 0.03), hospital readmissions (23% vs. 8%, p = 0.03), and recurrent cardiac testing (17% vs. 4%, p = 0.03). Median length of stay was 26 h (interquartile range: 23 to 45 h) in the usual care group and 21 h (interquartile range: 15 to 25 h) in the OU CMR group (p < 0.001). ACS after discharge occurred in 3 usual care participants (6%) and no OU CMR participants. CONCLUSIONS: In this single-center trial, management of intermediate-risk patients with possible ACS in an OU with stress CMR reduced coronary artery revascularization, hospital readmissions, and recurrent cardiac testing, without an increase in post-discharge ACS at 90 days. (Randomized Investigation of Chest Pain Diagnostic Strategies; NCT01035047).

Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease.

OBJECTIVES: The goal of this study was to determine if low to moderate doses of anthracycline-based chemotherapy (Anth-bC) are associated with subclinical cardiovascular (CV) injury. BACKGROUND: Cancer survivors who receive Anth-bC experience premature CV events. It is unknown whether low to moderate doses of anthracyclines promote early subclinical CV disease manifested by deteriorations in left ventricular ejection fraction (LVEF) or increases in aortic stiffness, or if these doses are associated with changes in quality of life (QOL). METHODS: In 53 men and women with breast cancer, leukemia, or lymphoma, we assessed left ventricular volumes, LVEF, circumferential strain, aortic pulse wave velocity, late gadolinium enhancement, serum B-type natriuretic peptide, troponin I, and the impact of treatment on QOL before and 1, 3, and 6 months after receipt of Anth-bC. RESULTS: Participants averaged 50 ± 2 (range 19 to 80) years in age, 58% were women, 17% were black, and they each received a range of 50 to 375 mg/m(2) of doxorubicin-equivalent chemotherapy. Left ventricular end-systolic volume (48 ± 3 ml to 54 ± 3 ml; p = 0.02), left ventricular strain (-17.7 ± 0.4 to -15.1 ± 0.4; p = 0.0003), pulse wave velocity (6.7 ± 0.5 m/s to 10.1 ± 1 m/s; p = 0.0006), and QOL deterioration (15.4 ± 3.3 to 28.5 ± 3.9; p = 0.008) increased, whereas LVEF (58 ± 1% to 53 ± 1%; p = 0.0002) decreased within 6 months after low to moderate doses of Anth-bC. All findings persisted after accounting for age, gender, race (white/black), doxorubicin-equivalent dose, doxorubicin administration technique, comorbidities associated with CV events, and cancer diagnosis (p = 0.02 to 0.0001 for all). There were no new late gadolinium enhancement findings after 6 months. CONCLUSIONS: In these study patients, low to moderate doses of Anth-bC were associated with the early development of subclinical abnormalities of cardiac and vascular function that in other populations are associated with the future occurrence of CV events.

Aging reduces left atrial performance during adrenergic stress in middle aged and older patients.

BACKGROUND: During adrenergic stress, the influence of age on left atrial (LA) function is unknown. We hypothesized that aging decreases LA total emptying fraction (LAEF) during maximal adrenergic stress. The aim of the study was to determine the influence of aging on LA function during adrenergic stress in middle aged and older patients. METHODS: We enrolled 167 middle aged and elderly participants, and measured LA and left ventricular (LV) volumes using a multi-slice three-dimensional cine white blood cardiovascular magnetic resonance (CMR) technique before and during intravenous dobutamine infused to achieve 80% of the maximum heart rate response for age. Paired sample t-test was used to detect differences in LA and LV volumes between baseline and peak dose stage of dobutamine stress CMR, and multivariable linear regression was used to identify predictors of LA function. RESULTS: Participants averaged 68 ± 8 years in age, 53% were men, 25% exhibited coronary artery disease, 35% had diabetes, 9% had a remote history of atrial fibrillation, 90% had hypertension, and 11% had inducible LV wall motion abnormalities indicative of ischemia during dobutamine CMR. Increasing age correlated with LA volumes (maximal and minimal) and inversely correlated with LAEF at rest and after peak adrenergic stress. Age was an independent predictor of LAEF during adrenergic stress, even after accounting for gender, LV volumes, and other co-morbidities including inducible ischemia. CONCLUSIONS: Age is associated with a decrease in LA function during adrenergic stress even after adjusting for co-morbidities associated with cardiovascular disease and LV function.

Provider-directed imaging stress testing reduces health care expenditures in lower-risk chest pain patients presenting to the emergency department.

BACKGROUND: Among intermediate- to high-risk patients with chest pain, we have shown that a cardiac magnetic resonance (CMR) stress test strategy implemented in an observation unit (OU) reduces 1-year health care costs compared with inpatient care. In this study, we compare 2 OU strategies to determine among lower-risk patients if a mandatory CMR stress test strategy was more effective than a physicians' ability to select a stress test modality. METHODS AND RESULTS: On emergency department arrival and referral to the OU for management of low- to intermediate-risk chest pain, 120 individuals were randomly assigned to receive (1) a CMR stress imaging test (n=60) or (2) a provider-selected stress test (n=60: stress echo [62%], CMR [32%], cardiac catheterization [3%], nuclear [2%], and coronary CT [2%]). No differences were detected in length of stay (median CMR=24.2 hours versus 23.8 hours, P=0.75), catheterization without revascularization (CMR=0% versus 3%), appropriateness of admission decisions (CMR 87% versus 93%, P=0.36), or 30-day acute coronary syndrome (both 3%). Median cost was higher among those randomly assigned to the CMR-mandated group ($2005 versus $1686, P<0.001). CONCLUSIONS: In patients with lower-risk chest pain receiving emergency department-directed OU care, the ability of a physician to select a cardiac stress imaging modality (including echocardiography, CMR, or radionuclide testing) was more cost-effective than a pathway that mandates a CMR stress test. Contrary to prior observations in individuals with intermediate- to high-risk chest pain, in those with lower-risk chest pain, these results highlight the importance of physician-related choices during acute coronary syndrome diagnostic protocols. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00869245.

Simultaneous measurement of left and right ventricular volumes and ejection fraction during dobutamine stress cardiovascular magnetic resonance.

OBJECTIVE: During cardiovascular stress, if right ventricular (RV) stroke volume exceeds left ventricular (LV) stroke volume, then a large volume of blood is displaced into the pulmonary circulation that may precipitate pulmonary edema. We sought to determine the metrics by which cardiovascular magnetic resonance (CMR) could measure simultaneous displacement of RV and LV stroke volumes during dobutamine stress. METHODS: Thirteen healthy subjects (5 women) aged 53 ± 10 years without medical conditions and taking no medications underwent 2 CMR examinations at 1.5 T separated by 4 to 8 weeks in which RV and LV stroke volumes were determined during intravenous dobutamine and atropine infused to achieve 80% of the maximum predicted heart rate response for age. RESULTS: The RV and LV stroke volumes were highly correlated at each level of stress (rest: r = 0.98, P = 0.007; low stress: r = 0.87, P = 0.001; and peak stress: r = 0.88, P = 0.001), and the mean difference in SV at each level of stress (rest, low stress, and peak stress was 0 to 2 mL on examinations 1 and 2. CONCLUSIONS: Simultaneous change in right and left ventricular stroke volumes can be assessed in a highly reproducible manner throughout the course of dobutamine CMR stress administered to achieve 80% of maximum predicted heart rate response for age. This technology may help identify discrepancies in RV and LV stroke volumes during cardiovascular stress that are associated with the development of pulmonary edema.

Stress CMR imaging observation unit in the emergency department reduces 1-year medical care costs in patients with acute chest pain: a randomized study for comparison with inpatient care.

OBJECTIVES: This study sought to compare the direct cost of medical care and clinical events during the first year after patients with intermediate risk acute chest pain were randomized to stress cardiac magnetic resonance (CMR) observation unit (OU) testing versus inpatient care. BACKGROUND: In a recent study, randomization to OU-CMR reduced median index hospitalization cost compared with the cost of inpatient care in patients presenting to the emergency department with intermediate risk acute chest pain. METHODS: Emergency department patients with intermediate risk chest pain were randomized to OU-CMR (OU care, cardiac markers, stress CMR) or inpatient care (admission, care per admitting provider). This analysis reports the direct cost of cardiac-related care and clinical outcomes (myocardial infarction, revascularization, cardiovascular death) during the first year of follow-up subsequent to discharge. Consistent with health economics literature, provider cost was calculated from work-related relative value units using the Medicare conversion factor; facility charges were converted to cost using departmental-specific cost-to-charge ratios. Linear models were used to compare cost accumulation among study groups. RESULTS: We included 109 randomized subjects in this analysis (52 OU-CMR, 57 inpatient care). The median age was 56 years; baseline characteristics were similar in both groups. At 1 year, 6% of OU-CMR and 9% of inpatient care participants experienced a major cardiac event (p = 0.72) with 1 patient in each group experiencing a cardiac event after discharge. First-year cardiac-related costs were significantly lower for participants randomized to OU-CMR than for participants receiving inpatient care (geometric mean = $3,101 vs. $4,742 including the index visit [p = 0.004] and $29 vs. $152 following discharge [p = 0.012]). During the year following randomization, 6% of OU-CMR and 9% of inpatient care participants experienced a major cardiac event (p = 0.72). CONCLUSIONS: An OU-CMR strategy reduces cardiac-related costs of medical care during the index visit and over the first year subsequent to discharge, without an observed increase in major cardiac events. (Cost Comparison of Cardiac Magnetic Resonance Imaging [MRI] Use in Emergency Department [ED] Patients With Chest Pain; NCT00678639).