Over the past decade, cardiovascular magnetic resonance (CMR) has evolved into a cardiac stress testing modality that can be used to diagnose myocardial ischemia using intravenous dobutamine or vasodilator perfusion agents such as adenosine or dipyridamole. Because CMR produces high-resolution tomographic images of the human heart in multiple imaging planes, it has become a highly attractive noninvasive testing modality for those suspected of having myocardial ischemia. The purpose of this article is to review the clinical, diagnostic, and prognostic utility of stress CMR testing for patients with (or suspected of having) coronary artery disease.
stress CMR; dobutamine; adenosine; myocardial ischemia
coronary artery disease; cardiovascular magnetic resonance; adverse cardiac prognosis; cardiovascular computer tomography
Older heart failure patients with preserved ejection fraction (HFpEF) have severely reduced exercise capacity and quality of life. Both brachial artery flow-mediated dilation (FMD) and peak exercise oxygen uptake (peak VO2) decline with normal aging. However, uncertainty remains regarding whether FMD is reduced beyond the degree associated with normal aging and if this contributes to reduced peak VO2 in elderly HFpEF patients.
Sixty-six older (70 ± 7 years) HFpEF patients and 47 healthy participants (16 young, 25 ± 3 years, and 31 older, 70 ± 6 years) were studied. Brachial artery diameter was measured before and after cuff occlusion using high-resolution ultrasound. Peak VO2 was measured using expired gas analysis during upright cycle exercise.
Peak VO2 was severely reduced in older HFpEF patients compared with age-matched healthy participants (15.2 ± 0.5 vs 19.6 ± 0.6 mL/kg/min, p < .0001), and in both groups, peak VO2 was reduced compared with young healthy controls (28.5 ± 0.8 mL/kg/min; both p < .0001). Compared with healthy young participants, brachial artery FMD (healthy young, 6.13% ± 0.53%) was significantly reduced in healthy older participants (4.0 ± 0.38; p < .0002) and in HFpEF patients (3.64% ± 0.28%; p < .0001). However, FMD was not different in HFpEF patients compared with healthy older participants (p = .86). Although brachial artery FMD was modestly related to peak VO2 in univariate analyses (r = .19; p = .048), it was not related in multivariate analyses that accounted for age, gender, and body size.
These results suggest that endothelial dysfunction may not be a significant independent contributor to the severely reduced exercise capacity in elderly HFpEF patients.
Exercise capacity; Aging; Flow-mediated dilation; Heart failure with preserved ejection fraction; Endothelial function
Limited data exist on the prevalence, associations and prognosis of individuals with asymptomatic left ventricular systolic dysfunction (ALVSD), especially in populations without prior clinical cardiovascular disease (CVD).
Methods and Results
Kaplan-Meier and Cox proportional hazard analyses were used to assess the association between ALVSD, defined as left ventricular ejection fraction less than 50%, and adjudicated incident congestive heart failure (CHF), all-cause mortality, and CVD events.
Out of 5004 participants, 112 participants had CHF, 321 had a CVD event, and 278 died after 9 years of follow-up. The overall prevalence of ALVSD was 1.7%, with a higher prevalence in African Americans (2.6%). ALVSD had worse cardiovascular risk profile and was also associated with increased risk in unadjusted and adjusted models for incident CHF [HR (95%): 12.0(7.04 – 20.3), p<0.0001 and 8.69(4.89 – 15.45), p<0.001 respectively], CVD [HR (95%):3.32(1.98 -5.58), p<0.001 and 2.21(1.30 – 3.73), p=0.003 respectively] and all-cause mortality [HR(95%):3.47(2.03 – 5.94), p<0.0001 and 2.00(1.13-3.54), p=0.017 respectively]. A 10% decrement in LVEF at baseline was associated with increase in risk in unadjusted and adjusted models for clinical CHF [HR (95%CI): 2.17(1.82 -2.63), p<0.0001 and 2.13(1.73 - 2.51), p<0.001 respectively] and all-cause mortality [HR (95%CI): 1.22(1.05 – 1.41), p=0.009 and 1.17(1.00 – 1.36), p=0.047 respectively]. Among the subset of participants with ALVSD, LVMI was particularly informative about risk for incident CHF (c- index = 0.74).
ALVSD is uncommon in individuals without prior clinical CVD, but is associated with high risk for CHF, CVD, and all-cause mortality. LVMI had good discrimination for incident CHF in MESA participants with ALVSD.
heart failure; death; cardiovascular diseases; magnetic resonance imaging; population
The aim of the present study was to evaluate how torsion is influenced by left ventricular (LV) remodeling associated with age, gender and hypertension in a large community-based population.
Methods and Results
Myocardial shortening and torsion were assessed by tagged cardiac magnetic resonance (CMR) in 1478 participants without clinically apparent cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Torsion was defined as the difference between apical and basal rotation, divided by slice distance. In multivariable linear regression models, older age was associated with lower stroke volume (−3.6 ml/decade, p<0.001) and higher LV mass –to-volume ratio (0.03 g/ml/decade, p<0.001) along with lower circumferential shortening (−0.17%/decade, p<0.05). Torsion, however, was greater at older ages (0.14 °/decade, p<0.001) and in women (0.37°/cm vs. men, p<0.001). Hypertensive participants had higher LV mass and LV mass –to-volume ratio (15.5g and 0.07 g/ml, respectively, p<0.001 for both). Circumferential shortening was lower in hypertensive (−0.42%, p<0.01), whereas torsion was higher after adjustment for age and gender (0.17°/cm, p<0.05).
Older age is associated with lower LV volumes and greater relative wall thickness, and accompanied by lower circumferential myocardial shortening, whereas torsion is greater with older age. Hypertensive individuals have greater LV volumes and relative wall thickness and lower circumferential shortening. Torsion, however, is greater in hypertension independent of age and gender. Torsion may therefore represent a compensatory mechanism to maintain an adequate stroke volume and cardiac output in the face of progressively reduced LV volumes and myocardial shortening associated with hypertension and aging.
Torsion; Hypertension; Age; remodeling; Cardiac Magnetic Resonance
Although clear algorithms for diagnosis and treatment of patients with chest pain at low or high risk for an acute coronary syndrome (ACS) exist, they are less well delineated for patients presenting with chest pain with an intermediate risk for ACS. In patients presenting acutely or subacutely to emergency departments (EDs) at high risk for ACS, such as those with ST segment elevation on their 12-lead electrocardiogram (ECG), immediate contrast coronary angiography is performed. On the other hand, chest pain observation units (OUs) are recommended for managing those with chest pain at low risk for an ACS event. In this setting, these OUs are associated with lower healthcare resource utilization and improved cost-effectiveness. Cost-effective diagnosis and treatment options are important goals in healthcare delivery systems. The presentation of patients at intermediate risk for ACS represents an emerging source of resource utilization for EDs. These patients often exhibit pre-existing coronary artery disease, may have sustained prior myocardial infarction, and exhibit multiple comorbidities such as diabetes and hypercholesterolemia. Importantly, however, they will not have evidence of ST elevation on their 12-lead ECG nor will they exhibit serum markers (troponin or creatinine kinase elevations) indicative of ACS. As a consequence of existing co-morbidities, their management becomes time-consuming and may require inpatient monitoring, observation, and cardiac stress testing. Cardiovascular magnetic resonance (CMR) is a powerful tool for risk stratification and prognosis determination in patients in need of stress testing at intermediate risk of ACS. For those who present with acute chest pain syndromes, the combination of CMR in an OU setting represents a potentially attractive option for reducing healthcare-related expenditures without compromising patient outcomes. Recent study results from single centers suggest that CMR-OU care may result in fewer unnecessary hospital admissions and invasive procedures in those presenting with intermediate risk ACS. Further research utilizing stress CMR testing from multiple centers in OU settings is needed to determine if this model of care improves efficiency, reduces healthcare costs, and delivers optimum care in individuals presenting to EDs with chest pain at intermediate risk of ACS.
Cardiac magnetic resonance; Observation units; Cost reduction; Stress testing
Increased intraperitoneal (IP) fat is associated with increased cardiovascular (CV) risk, but mechanisms for this increase in risk are not completely established. We performed this study to assess whether IP fat is associated with ascending aortic wall thickness (AOWT), a risk factor for CV events. Four hundred and forty-one consecutive participants, aged 55–85 years, with risk factors for CV events underwent magnetic resonance measures of AOWT and abdominal fat (subcutaneous (SC) fat + IP fat). For the ascending aorta, mean wall thickness of the 4th quartile of the IP fat was higher relative to the 1st quartile (P ≤ 0.001). This difference persisted after accounting for SC fat (P ≤ 0.001), as well as age, gender, height, weight, smoking, diabetes, hypertension, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and C-reactive protein (CRP) (P < 0.03). Elevated IP fat volume is associated with an increase in ascending AOWT, a condition that promotes CV events in middle aged and elderly adults.
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.
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.
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.
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.
aging; left atrial function; adrenergic stress; cardiac MRI
Noninvasive imaging modalities are often used to manage patients with cardiovascular disease. Cardiovascular magnetic resonance (CMR) is increasingly used for diagnosing and evaluating myocardial ischemia and viability; moreover, stress CMR study results can be used to determine cardiac prognosis. In this article, we review recently published material regarding the performance of stress testing with CMR including a brief update regarding techniques, stress agents, diagnostic accuracy, prognosis, economic implications, and ongoing trials and future developments.
CMR; Ischemia; Testing; Prognosis
While cancer-free survival has improved over the past 20 years for many individuals with prostate, renal, breast, and hematologic malignancies, the increasingly recognized prevalence of cardiovascular (CV) events in cancer survivors has been an unintended consequence of many of the therapies that have improved these survival rates. The increase in CV events threatens to offset the improvement in cancer related survival. As a result, there is an emerging need to develop methods to identify those individuals treated for cancer at increased risk of cardiovascular events. With its inherent ability to characterize myocardial tissue and identify both cardiac and vascular dysfunction, cardiovascular magnetic resonance (CMR) has the potential to identify both subclinical and early clinical CV injury before the development of an overt catastrophic event such as a myocardial infarction, stroke, or premature cardiac death. Early identification provides an opportunity for the implementation of primary prevention strategies to prevent such events, thereby improving overall cancer survivorship and quality of life. This article reviews the etiology of CV events associated with cancer therapy and the unique potential of CMR to provide early diagnosis of subclinical CV injury related to the administration of these therapies.
Cardiotoxicity; Chemotherapy; Cancer; Cardiovascular magnetic resonance
We determine whether imaging with cardiac magnetic resonance imaging
(MRI) in an observation unit would reduce medical costs among patients with
emergent non-low-risk chest pain who otherwise would be managed with an
inpatient care strategy.
Emergency department patients (n=110) at intermediate or high
probability for acute coronary syndrome without electrocardiographic or
biomarker evidence of a myocardial infarction provided consent and were
randomized to stress cardiac MRI in an observation unit versus standard
inpatient care. The primary outcome was direct hospital cost calculated as
the sum of hospital and provider costs. Estimated median cost differences
(Hodges-Lehmann) and distribution-free 95% confidence intervals (Moses) were
used to compare groups.
There were 110 participants with 53 randomized to cardiac MRI and 57
to inpatient care; 8 of 110 (7%) experienced acute coronary syndrome. In the
MRI pathway, 49 of 53 underwent stress cardiac MRI, 11 of 53 were admitted,
1 left against medical advice, 41 were discharged, and 2 had acute coronary
syndrome. In the inpatient care pathway, 39 of 57 patients initially
received stress testing, 54 of 57 were admitted, 3 left against medical
advice, and 6 had acute coronary syndrome. At 30 days, no subjects in either
group experienced acute coronary syndrome after discharge. The cardiac MRI
group had a reduced median hospitalization cost (Hodges-Lehmann estimate
$588; 95% confidence interval $336 to $811); 79% were managed without
Compared with inpatient care, an observation unit strategy involving
stress cardiac MRI reduced incident cost without any cases of missed acute
coronary syndrome in patients with emergent chest pain.
Increased left ventricular myocardial thickness (LVMT) is a feature of several cardiac diseases. The purpose of this study was to establish standard reference values of normal LVMT with cardiac MR (CMR) and to assess variation with image acquisition plane, demographics and LV function.
Methods and Results
End-diastolic LVMT was measured on CMR steady-state free precession cine long and short axis images in 300 consecutive participants free of cardiac disease (169 women; 65.6±8.5 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Mean LVMT on short axis images at the mid-cavity level was 5.3±0.9mm and 6.3±1.1mm for women and men, respectively. The average of the maximum LVMT at the mid-cavity for women/men were 7mm/9mm (long axis) and 7mm/8mm (short axis). Mean LVMT was positively associated with weight (0.02mm/kg, p=0.01) and body-surface-area (1.1mm/m2, p<0.001). No relationship was found between mean LVMT and age or height. Greater mean LVMT was associated with lower LV end-diastolic volume (0.01mm/ml, p<0.01), a lower LV end-systolic volume (−0.01mm/ml, p=0.01) and lower LV stroke volume (−0.01mm/ml, p<0.05). LVMT measured on long axis images at the basal and mid-cavity level were slightly greater (by 6% and 10%, respectively) than measurements obtained on short axis images; apical LVMT values on long axis images were 20% less than those on short axis images.
Normal values for wall thickness are provided for middle-aged and older subjects. Normal LVMT is lower for women than men. Observed values vary depending on the imaging plane for measurement.
magnetic resonance imaging; myocardial thickness; normal values
During cardiovascular stress, if right ventricular (RV) 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 right and LV stroke volume during dobutamine stress.
Thirteen healthy subjects (5 women) aged 53±10 years without medical conditions and taking no medications underwent 2 CMR exams at 1.5 T separated by 4 to 8 weeks in which right and LV stroke volume were determined during intravenous dobutamine and atropine infused to achieve 80% of the maximum predicted heart rate response (MPHRR) for age.
The right and LV stroke volume 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 both exam 1 and 2.
Simultaneous change in right and left ventricular stroke volume can be assessed in a highly reproducible manner throughout the course of dobutamine CMR stress administered to achieve 80% of MPHRR for age. This technology may help identify discrepancies in right and LV stroke volume during cardiovascular stress that are associated with the development of pulmonary edema.
Background and aims
There are no data showing whether or not age-related declines in physical function are related to in vitro properties of human skeletal muscle. The purpose of this study was to determine whether physical function is independently associated with histologic and metabolic properties of skeletal muscle in elderly adults.
The study was a cross-sectional observational study of 39 sedentary, older (60–85 yrs) men and women. A needle biopsy of the vastus lateralis for assessment of muscle fiber type, fiber area, capillary density and citrate synthase and aldolase activities was performed. Physical function tests included the Short Physical Performance Battery (balance, walking speed, and chair rise time), as well as self-reported disability.
Total fiber area (R=−0.41, p=0.02), number of Type II fibers (R=−0.33, p=0.05), and aldolase activity (R=−0.54, p=0.01) were inversely related to age. Persons who reported greater difficulty with daily activities had lower capillary density (R=−0.51, p=0.03) and lower citrate synthase activity (R=−0.66, p=0.03). Walking speed was directly related to fiber area (R=0.40, p=0.02), capillary density (R=0.39, p=0.03), citrate synthase (R=0.45, p=0.03) and aldolase (R=0.55, p<0.01) activities, even after adjustment for age, BMI and disease status.
In older adults, skeletal muscle capillary density and metabolic enzymatic activity are independent predictors of lower extremity physical function.
Capillary density; enzyme activity; physical function; skeletal muscle
A high degree of non-compacted (trabeculated) myocardium in relationship to compact myocardium (T/M ratio >2.3) has been associated with a diagnosis of left ventricular non-compaction (LVNC). The purpose of this study was to determine the normal range of the T/M ratio in a large population-based study and to examine the relationship to demographic and clinical parameters.
Methods and Results
The thickness of trabeculation and the compact myocardium were measured in eight LV regions on long axis cardiac magnetic resonance (CMR) steady-state free precession cine images in 1000 participants (551 women; 68.1±8.9 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Of 323 participants without cardiac disease or hypertension and with all regions evaluable 140 (43%) had a T/M ratio >2.3 in at least one region; in 20/323 (6%), T/M>2.3 was present in more than two regions. Multivariable linear regression model revealed no association of age, gender, ethnicity, height and weight with maximum T/M ratio in participants without cardiac disease or hypertension (p>0.05). In the entire cohort (n=1000) LVEF (β=−0.02/%; p=0.015), LVEDV (β=0.01/ml; p=<0.0001) and LVESV (β=0.01/ml; p<0.001) were associated with maximum T/M ratio in adjusted models while there was no association with hypertension or myocardial infarction (p>0.05). At the apical level T/M ratios were significantly lower when obtained on short- compared to long-axis images (p=0.017).
A ratio of trabeculated to compact myocardium of more than 2.3 is common in a large population based cohort. These results suggest reevaluation of the current CMR criteria for LVNC may be necessary.
cardiovascular magnetic resonance imaging; cardiomyopathy; non-compaction; trabeculation
Fat in the renal sinus (RS), a region of the kidney in which low pressure venous and lymphatic vessels are present, may indirectly influence blood pressure (BP). The purpose of this study was to assess the association between RS fat and control of BP upon receipt of antihypertensive medications.
Two hundred-five (205) participants aged 55 to 85 years at risk for cardiovascular (CV) events underwent magnetic resonance imaging assessments of abdominal and RS fat, measurement of blood pressure, and determination of the number of prescribed antihypertensive medications. Multivariable linear regression was used to determine associations between RS fat, blood pressure, and the number of prescribed antihypertensive medications.
Abdominal fat averaged (416 ± 160 cm3, median and interquartile range (IQR) of 396 cm3 and 308 to 518 cm3); intraperitoneal (IP) fat averaged (141 ± 73 cm3, median and IQR of 129 cm3 and 86 to 194 cm3); and RS fat averaged (4.6 ± 3.2 cm3, median and IQR of 4.2 cm3 and 2.2 to 6.6 cm3). After accounting for age, gender, height, body mass index (BMI), and IP fat, RS fat correlated with the number of prescribed antihypertensive medications (p=0.010), stage II hypertension (p=0.02), and renal size (p=<0.001).
In conclusion, after accounting for other body fat depots and risk factors for hypertension, renal sinus fat volume is associated with the number of prescribed antihypertensive medications and stage II hypertension. These results indicate that further studies are warranted to determine if fat accumulation in the renal sinus promotes hypertension.
Renal sinus; intraperitoneal fat; hypertension; blood pressure; body mass index
To determine if dobutamine induced abnormal stress induce changes in left ventricular (LV) stroke volume (SV) and aortic stiffness predict future pulmonary edema.
Heightened aortic stiffness that reduces LV stroke volume during adrenergic stress may serve as a marker for future pulmonary edema (P edema).
We measured LVSV, ventriculo-vascular stiffness (pulse pressure/LVSVi), and aortic distensibility (AoD) at rest and during intravenous dobutamine using cardiovascular magnetic resonance (DCMR). Personnel blinded to DCMR followed participants longitudinally over time to identify those admitted to the hospital with P edema. Data from 44 participants who experienced a hospital admission for P edema were compared to data from 72 participants of similar age, gender, and resting LV ejection fraction who remained free of P edema.
Expressed as median and interquartile range, participants with versus without P edema exhibited a reduced ratio of stress/rest LVSV (0.9 [0.7,1.1] versus 1.0 [0.9,1.2], respectively, p= 0.002); an increased ventriculo-vascular stiffness stress/rest ratio (1.4 [1.0,1.6] versus 1.0 [0.8,1.3], respectively, p= ≤ 0.001); and a reduced stress induced measure of AoD (0.8 [0.3,1.3] versus 1.6 [1.2,3.2] mmHg−3, respectively, p=0.002). After accounting for age, gender, LVEF, risk factors for P edema and the presence of dobutamine induced ischemia, LVSV reserve and the stress/rest ventriculo-vascular stiffness ratio remained different (p<0.008 for both) between those with and without P edema.
In patients without inducible ischemia during dobutamine stress, in whom one might otherwise assume a favorable prognosis, the failure to increase LV stroke volume, or an increase in ventriculo-vascular stiffness indicates patients at risk for subsequent P edema.
Stroke volume; heart failure; dobutamine cardiovascular magnetic resonance
Elevated serum glucose from diabetes mellitus (DM) or impaired fasting glucose (IFG) shares many mechanisms with aging that decrease aortic distensibility (AD), such as glycation of the extra-cellular matrix. However, little data compares the simultaneous effects of elevated serum glucose and aging on AD. To study this, we examined the relationship between fasting glucose status, age, and AD in the Multi-Ethnic Study of Atherosclerosis (MESA): a multi-ethnic cohort of individuals aged 45-84 years without clinical cardiovascular disease. In MESA, participants with normal fasting glucose (NFG; n = 2270), IFG (n = 870), and DM (n = 412) underwent MRI assessment of proximal thoracic aortic distensibility. This sample was 46% male, 42% white, 30% AA, 11% Asian, and 17% Hispanic. The relationship between glucose status, age, and AD was analyzed with general linear models by adjusting for factors influential on AD. An interaction term was used to determine if age modified the effect of glucose status on AD. AD was lowest among those with DM. The interaction term was significant (p = 0.024). Comparing participants less than 65 years of age, AD was different between NFG and DM (p < 0.01), and between NFG and IFG (p = 0.02). In those older than 65, fasting glucose group was no longer a significant predictor of AD. Our data indicate that there are overall differences in AD between DM, IFG, and NFG. However, age modified the effect of glucose status such that differences between the groups diminished with advancing age.
aging; aorta; diabetes mellitus; glucose; magnetic resonance imaging