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1.  Non-invasive imaging of flow and vascular function in disease of the aorta 
JACC. Cardiovascular imaging  2015;8(9):1094-1106.
With advancements in technology and a better understanding of human cardiovascular physiology, research as well as clinical care can go beyond dimensional anatomy offered by traditional imaging and investigate aortic functional properties and the impact disease has on this function. Linking the knowledge of the histopathological changes with the alterations in aortic function observed on noninvasive imaging results in a better understanding of disease pathophysiology. Translating this to clinical medicine, these noninvasive imaging assessments of aortic function are proving to be able to diagnosis disease, better predict risk, and assess response to therapies. This review is designed to summarize the various hemodynamic measures that can characterize the aorta, the various non-invasive techniques, and applications for various disease states.
PMCID: PMC4788092  PMID: 26381770
aorta; pulse wave velocity; distensibility; aortic disease; aorta hemodynamics
2.  Evolution of aortic wall thickness and stiffness with atherosclerosis: Long-term follow up from the Multi-Ethnic Study of Atherosclerosis (MESA) 
Hypertension  2015;65(5):1015-1019.
The study was performed to determine age, gender, 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 (371) longitudinal and 426 cross-sectional measurements of AWT from cardiovascular magnetic resonance (CMR) imaging studies conducted within the Multi-Ethnic Study of Atherosclerosis (MESA) were analyzed at two points in time: in 2000-2002 and then again from follow-up examinations in 2010-2012. 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 mid-thoracic descending aortic wall was measured and correlated to distensibility of the ascending aorta (AAD) and aortic pulse wave velocity (PWV). The average rate of AWT change was 0.032mm per year. The increase in AWT was greater for those aged 45 to 54 years relative to individuals older than age 55 years (p-trend<0.001). Ascending aortic distensibility was lower (p<0.001) and PWV was higher (p=0.012) for hypertensive subjects. After adjustment for traditional risk factors, AAD was significantly related to AWT in participants without hypertension. Hypertension was associated with increased aortic stiffness independent of aortic wall thickness.
PMCID: PMC4410010  PMID: 25776078
MR imaging; aortic wall thickness; longitudinal changes; arterial stiffness; hypertension
3.  Chronic Statin Administration May Attenuate Early Anthracycline Associated Declines in Left Ventricular Ejection Function 
Recent studies show 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 disease (CVD) would ameliorate declines in left ventricular ejection fraction (LVEF) often observed during anthracycline-based chemotherapy (Anth-bC).
In 51 participants (33 women and 18 men; aged 48±2 years), we performed CV magnetic resonance (CMR) 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 received no statin. MR image analysts were blinded to participant identifiers.
Those receiving statins were older and often had diabetes (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 (p=0.15). For those not receiving a statin, 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%) versus a −6.5±1.5% decline among those not receiving a statin (p=0.03).
In conclusion, these data highlight that individuals receiving statin therapy for prevention of CVD may experience less deterioration in LVEF upon early receipt of Anth-bC than individuals not receiving a statin. Further studies with large numbers of participants are warranted to determine if statins protect against LVEF decline in patients receiving Anth-bC.
PMCID: PMC4410009  PMID: 25662284
statin; heart failure; anthracycline
4.  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 
In a murine anthracycline-related cardiotoxicity model, increases in cardiovascular magnetic resonance (CMR) myocardial contrast-enhanced T1-weighted signal intensity are associated with myocellular injury and decreases in left ventricular ejection fraction (LVEF). We sought to determine if T1- and T2-weighted measures of signal intensity associate with decreases in LVEF 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, EF, and contrast-enhanced T1-weighted and T2-weighted signal intensity prior to and 3 months after initiating potentially cardiotoxic chemotherapy using blinded, unpaired analysis of CMR 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, LVEF decreased from 57±6% to 54±7% (p<0.001) due to 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 prior to 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).
Concordant with previous animal studies, CMR measures of contrast-enhanced T1-weighted signal intensity occur commensurate with small but significant LVEF declines 3 months after 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.
PMCID: PMC4241241  PMID: 25273568
cardiotoxicity; cardiovascular magnetic resonance imaging; left ventricular ejection fraction; T1-weighted and T2-weighted imaging
5.  Cancer and Its Association With the Development of Coronary Artery Calcification: An Assessment From the Multi‐Ethnic Study of Atherosclerosis 
Although cancer and its corresponding therapies are associated with increased ischemic heart disease, the temporal relationship between cancer and the development of coronary artery calcium (CAC), a marker of subclinical atherosclerosis, is unknown.
Methods and Results
Among 3122 men and women free of cardiovascular disease and cancer in the Multi‐Ethnic Study of Atherosclerosis trial, CAC scoring was performed at baseline (2000–2002) and at follow‐up (2010–2012). Over this 10‐year period, 85 men (age 63.6±8.3 years) and 50 women (age 62.1±9.8 years) were diagnosed with cancer (predominantly breast, lung, or uterine [52%] in women and prostate or colorectal [78%] in men). The other 2987 subjects (age 59.6±9.2 years for men, 59.7±9.4 years for women) remained cancer free. The incidence of new CAC (baseline Agatston score of zero converting to detectable CAC) was modeled with relative risk regression and compared for cancer versus no cancer. Increase in pre‐existing CAC was compared in these groups using linear regression of log transformed CAC. The incidence of CAC was independently associated with cancer history (relative risk 1.32 [P=0.04] and 1.29 [P=0.01] for women and men, respectively). In participants with CAC at baseline, a clear difference of CAC progression was not observed between cancer and noncancer participants (P=0.6 for women, P=0.2 for men).
A diagnosis of cancer is associated with the development of CAC even after accounting for atherosclerotic risk factors. However, in individuals with pre‐existing CAC, it is not clear whether the presence of cancer accelerates CAC over time.
PMCID: PMC4845242  PMID: 26553214
cancer; cardiotoxicity; coronary artery calcium; subclinical atherosclerosis risk factor
6.  Visceral Adiposity and Left Ventricular Remodeling: the Multi-Ethnic Study of Atherosclerosis 
Background and Aims
Visceral fat (VF) is a source of pro-inflammatory adipokines implicated in cardiac remodeling. We sought to determine the impact of visceral fat (VF) and subcutaneous fat (SQ) depots on left ventricular (LV) structure, function, and geometry in the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods and Results
We performed a post-hoc analysis on 1,151 participants from MESA with cardiac magnetic resonance quantification of LV mass and LV mass-to-volume ratio (LVMV, an index of concentricity) and computed tomographic-derived SQ and VF area. Multivariable regression models to estimate association between height-indexed SQ and VF area (per cm2/m) with height-indexed LV mass (per height2.7) and LVMV were constructed, adjusted for clinical, biochemical, and demographic covariates. We found that both VF and SQ area were associated with height-indexed LV mass (ρ =0.36 and 0.12, P<0.0001, respectively), while only VF area was associated with LVMV (ρ =0.28, P<0.0001). Individuals with above-median VF had lower LV ejection fraction, greater indexed LV volumes and mass, and higher LVMV (all P < 0.001). In multivariable models adjusted for weight, VF (but not SQ) area was associated with LV concentricity and LV mass index, across both sexes.
Visceral adiposity is independently associated with LV concentricity, a precursor to heart failure. Further study into the role of VF in LV remodeling as a potential therapeutic target is warranted.
PMCID: PMC4468023  PMID: 26033394
Obesity; Cardiac magnetic resonance imaging; Visceral Adiposity; Remodeling
7.  Noninvasive Imaging of Cardiovascular Injury Related to the Treatment of Cancer 
JACC. Cardiovascular imaging  2014;7(8):824-838.
The introduction of multiple treatments for cancer, including chemotherapeutic agents and radiation therapy, has significantly reduced cancer-related morbidity and mortality. However, these therapies can promote a variety of toxicities, among the most severe being the ones involving the cardiovascular system. Currently, for many surviving cancer patients, cardiovascular (CV) events represent the primary cause of morbidity and mortality. Recent data suggests that CV injury occurs early during cancer treatment, creating a substrate for subsequent cardiovascular events. Researchers have investigated the utility of noninvasive imaging strategies to detect the presence of CV injury during and after completion of cancer treatment because it starts early during cancer therapy, often preceding the development of chemotherapy or cancer therapeutics related cardiac dysfunction. In this state of the art article, we review the utility of current clinical and investigative CV noninvasive modalities for the identification and characterization of cancer treatment-related CV toxicity.
PMCID: PMC4183055  PMID: 25124015
Chemotherapy-related cardiotoxicity; noninvasive imaging; cardiovascular imaging
8.  Pharmacological Stress Cardiovascular Magnetic Resonance 
Postgraduate medicine  2011;123(3):162-170.
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.
PMCID: PMC3767031  PMID: 21566427
stress CMR; dobutamine; adenosine; myocardial ischemia
9.  Prediction of Cardiac Events in Patients with Reduced Left Ventricular Ejection Fraction Using Dobutamine Cardiovascular Magnetic Resonance Assessment of Wall Motion Score Index 
To assess the utility of dobutamine cardiovascular magnetic resonance (DCMR) results for predicting cardiac events in individuals with reduced left ventricular ejection fraction (LVEF).
It is unknown whether DCMR results identify a poor cardiac prognosis when the resting LVEF is moderately to severely reduced.
Two-hundred consecutive patients aged 30 to 88 (average 64) years with a LVEF ≤55% that were poorly suited for stress echocardiography, underwent DCMR in which LV wall motion score index (WMSI), defined as the average wall motion of the number of segments scored, was assessed at rest, during low dose, and after peak intravenous infusion of dobutamine/atropine. All participants were followed for an average of 5 years after DCMR to ascertain the post testing occurrence of cardiac death, myocardial infarction (MI), and unstable angina or congestive heart failure warranting hospitalization.
After accounting for risk factors associated with coronary arteriosclerosis and MI, a stress induced increase in WMSI during DCMR was associated with future cardiac events (p< 0.001). After accounting for resting LVEF, a DCMR stress induced change in WMSI added significantly to predicting future cardiac events (p=0.003), but this predictive value was confined primarily to those with a LVEF >40%.
In individuals with mild to moderate reductions in LVEF (40% to 55%), dobutamine induced increases in WMSI forecast MI and cardiac death to a greater extent than an assessment of resting LVEF. In those with a LVEF < 40%, a dobutamine induced increase in WMSI does not predict MI and cardiac death beyond the assessment of resting LVEF.
PMCID: PMC3666037  PMID: 18634983
magnetic resonance imaging; cardiac prognosis; myocardial ischemia; dobutamine stress imaging
10.  Small, short duration, dobutamine induced perfusion defects are not associated with adverse prognosis in intermediate risk individuals receiving CMR stress imaging 
To assess the frequency and prognostic utility of small, short duration left ventricular (LV) 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 of 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 DCMR.
Among the fifty-five 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 (CAD), prior myocardial infarction, and decreased LV function (p<0.001 for all) and increased 2-year risk of cardiac event (HR 10.3, p<0.001, CI 3.3–33.0).
In individuals with diabetes, hypertension, or CAD at intermediate risk for a future cardiac event, small, short duration DCMR perfusion defects are not associated with an increased 2-year risk of subsequent cardiac event.
PMCID: PMC4103171  PMID: 24651743
coronary artery disease; dobutamine cardiac magnetic resonance; prognosis
11.  The Relationship of Cigarette Smoking with Inflammation and Subclinical Vascular Disease: The Multi-Ethnic Study of Atherosclerosis 
We sought to assess the impact of smoking status, cumulative pack-years, and time since cessation (the latter in former-smokers only) on three important domains of cardiovascular disease (CVD): inflammation, vascular dynamics and function, and subclinical atherosclerosis.
Approach and Results
The MESA cohort enrolled 6,814 adults without prior CVD. Smoking variables were determined by self-report and confirmed with urinary cotinine. We examined cross-sectional associations between smoking parameters and; 1) inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and fibrinogen); 2) vascular dynamics and function (brachial flow-mediated dilation [FMD] and carotid distensibility by ultrasound, as well as aortic distensibility by MRI); and 3) subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness [CIMT], and ankle-brachial index [ABI]). We identified 3,218 never-smokers, 2,607 former-smokers, and 971 current-smokers. Mean age was 62 years and 47% were male. There was no consistent association between smoking and vascular distensibility or FMD outcomes. In contrast, compared to never-smokers, the adjusted association between current-smoking and measures of either inflammation or subclinical atherosclerosis was consistently stronger than for former-smoking (e.g. odds-ratio (OR) for hs-CRP > 2mg/L of 1.7 [95%CI, 1.5-2.1] Vs. 1.2 [1.1-1.4], OR for CAC > 0 of 1.8 [1.5-2.1] Vs. 1.4 [1.2-1.6], respectively). Similar associations were seen for IL-6, fibrinogen, CIMT, and ABI. A monotonic relationship was also found between increasing pack-years exposure and elevated inflammatory markers. Further, current smokers with hsCRP > 2mg/L were more likely to have increased CIMT, abnormal ABI, and CAC > 75th percentile for age, sex and race (relative to smokers with hsCRP < 2mg/L, interaction p < 0.05 for all three outcomes). In contrast, time since quitting in former-smokers was independently associated with lower inflammation and atherosclerosis (e.g. OR for hsCRP > 2mg/L of 0.91 [0.88-0.95] and OR for CAC > 0 of 0.94 [0.90-0.97] for every 5-year cessation interval).
These findings expand our understanding of the harmful effects of smoking and help explain the cardiovascular benefits of smoking cessation.
PMCID: PMC4484586  PMID: 25745060
Smoking; Inflammation; Atherosclerosis; Coronary Artery Calcium
12.  Abnormal Stress‐Related Measures of Arterial Stiffness in Middle‐Aged and Elderly Men and Women With Impaired Fasting Glucose at Risk for a First Episode of Symptomatic Heart Failure 
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).
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: Unique identifier: NCT00542503.
PMCID: PMC4330048  PMID: 25589534
arterial stiffness; diabetes; dobutamine; elderly
13.  Cigarette Smoking and Cardiovascular Events: Role of Inflammation and Subclinical Atherosclerosis 
To examine the contemporary impact of smoking in a multi-ethnic sample, and to explore the respective contributions of inflammation and subclinical atherosclerosis to the cardiovascular consequences of smoking.
Approach and Results
We studied 6,814 participants free of cardiovascular disease (CVD) and coronary heart-disease (CHD) from MESA. Smoking status and cumulative exposure were determined by self-report and confirmed by urinary cotinine. Multivariable Cox-regression was used to estimate the association between smoking parameters and; All-cause CVD; All-cause CHD; and Hard CHD events. We further adjusted for high-sensitivity C-reactive protein (hsCRP) and coronary artery calcium (CAC) in hierarchical Cox-models. We identified 3,218 never-smokers, 2,607 former-smokers, and 971 current-smokers. Median follow-up was 10.2 years. Compared to never-smokers, adjusted Hazard-ratios (HRs) in current-smokers were 1.7 (95% CI, 1.3-2.2) for All-cause CVD, 1.6 (1.1-2.1) for All-cause CHD, and 1.7 (1.2-2.4) for Hard CHD. Similarly, among current-smokers, HRs were higher in the 4th vs 1st quartile of pack-years (e.g. All-cause CHD HR=2.7 [1.1-6.6]). Both CAC>100 and hsCRP≥3mg/L identified higher relative-risk among current-smokers (e.g. All-cause CHD HR of 3.0 [1.5-6.0, compared to CAC=0] and 2.6 [1.4-4.8, compared to hsCRP<2mg/L], respectively). However, CAC was a stronger mediator of events and adversely modified the effect of smoking on events (e.g. p-interaction=0.02 for Hard CHD). Compared to never-smokers, former-smokers (median cessation interval=22 years) had similar adjusted hazard for events.
In this multi-ethnic cohort, current smoking and cumulative exposure remain important modifiable determinants of CVD. Both hsCRP≥3mg/L and particularly CAC>100 identified high-risk smokers who may benefit from more intensive smoking-cessation efforts.
PMCID: PMC4404404  PMID: 25573855
Smoking; Inflammation; Coronary Artery Calcium; Cardiovascular Outcomes
14.  Relation of Pre-anthracycline Serum Bilirubin Levels to Left Ventricular Ejection Fraction After Chemotherapy 
The American journal of cardiology  2015;116(11):1752-1755.
Myocardial injury because of oxidative stress manifesting through reductions in left ventricular ejection fraction (LVEF) may occur after the administration of anthracycline-based chemotherapy (A-bC). We hypothesized that bilirubin, an effective endogenous antioxidant, may attenuate the reduction in LVEF that sometimes occurs after receipt of A-bC. We identified 751 consecutively treated patients with cancer who underwent a pre-A-bC LVEF measurement, exhibited a serum total bilirubin level <2 mg/dl, and then received a post-A-bC LVEF assessment because of symptomatology associated with heart failure. Analysis of variance, Tukey’s Studentized range test, and chi-square tests were used to evaluate an association between bilirubin and LVEF changes. The LVEF decreased by 10.7 ± 13.7%, 8.9 ± 11.8%, and 7.7 ± 11.5% in group 1 (bilirubin at baseline ≤0.5 mg/dl), group 2 (bilirubin 0.6 to 0.8 mg/dl), and group 3 (bilirubin 0.9 to 1.9 mg/dl), respectively. More group 1 patients experienced >15% decrease in LVEF compared with those in group 3 (p = 0.039). After adjusting for age, coronary artery disease/myocardial infarction, diabetes mellitus, hematocrit, and the use of cardioactive medications, higher precancer treatment bilirubin levels and lesser total anthracycline doses were associated with LVEF preservation (p =0.047 and 0.011, respectively). In patients treated with anthracyclines who subsequently develop symptoms associated with heart failure, pre-anthracycline treatment serum bilirubin levels inversely correlate with subsequent deterioration in post-cancer treatment LVEF. In conclusion, these results suggest that increased levels of circulating serum total bilirubin, an intrinsic antioxidant, may facilitate preservation of LVEF in patients receiving A-bC for cancer.
PMCID: PMC4747334  PMID: 26433273
15.  The Role of Cardiovascular Magnetic Resonance (CMR) and Computed Tomography (CCT) in Facilitating Heart Failure Management 
Opinion Statement
Cardiovascular magnetic resonance (CMR) and cardiac computed tomography (CCT) offer advantages for detecting left or right ventricular dysfunction in patients with or suspected of heart failure. CMR does not expose patients to ionizing radiation, and thus is well-suited for functional assessments and serial studies. CCT provides high spatial resolution, making it useful for the identification of coronary arteriosclerosis associated with ischemic cardiomyopathy. In this review, the clinical applications of CMR and CCT are individually discussed, with comparisons made between them to examine the strengths of each modality. The major techniques for each modality are outlined, as well as their uses for the evaluation of cardiomyopathy in heart failure patients with reduced left ventricular ejection fraction, preserved left ventricular ejection fraction, and valvular heart disease. Finally, we review the utility of CMR and CCT in determining which patients will benefit from cardiac resynchronization therapy.
PMCID: PMC3767383  PMID: 23817725
Cardiovascular Magnetic Resonance; Cardiac Computed Tomography; Heart Failure; Cardiomyopathy; Valvular Heart Disease
16.  Low to Moderate Dose Anthracycline-Based Chemotherapy is Associated with Early Noninvasive Imaging Evidence of Subclinical Cardiovascular Disease 
JACC. Cardiovascular imaging  2013;6(8):877-885.
To determine if low to moderate doses of anthracycline-based chemotherapy (Anth-bC) are associated with subclinical cardiovascular (CV) injury.
Cancer survivors that receive Anth-bC experience premature CV events. It is unknown whether low to moderate doses of anthracyclines a) promote early subclinical CV disease manifested by deteriorations in left ventricular ejection fraction (LVEF) or increases in aortic stiffness, or b) are associated with change in quality of life (QOL).
In 53 men and women with breast cancer, leukemia, or lymphoma, we assessed left ventricular volumes, LVEF, circumferential strain, aortic pulse wave velocity (PWV), late gadolinium enhancement, serum B-type natriuretic peptide (BNP), troponin I (TnI), and the impact of treatment on QOL before, and 1, 3, and 6 months after receipt of Anth-bC.
Participants averaged 50±2 (range 19–80) years in age, 58% were women, 17% were black, and they each received a range of 50 to 375 mg/m2 of doxorubicin equivalent chemotherapy. Left ventricular end systolic volume (LVESV; 48±3 to 54±3 ml; p=0.02), left ventricular strain (−17.7±0.4 to −15.1±0.4; p=0.0003), PWV (6.7±0.5 to 10.1±1 m/sec; p=0.0006), and QOL deterioration (15.4±3.3 to 28.5±3.9; p=0.008) increased, while 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.
Low to moderate doses of Anth-bC are 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.
PMCID: PMC3745801  PMID: 23643285
Cardio-oncology; chemotherapy; cardiotoxicity
17.  Adiposity Is Associated with Gender-Specific Reductions in Left Ventricular Myocardial Perfusion during Dobutamine Stress 
PLoS ONE  2016;11(1):e0146519.
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.
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.
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.
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.
PMCID: PMC4709095  PMID: 26751789
18.  Left Ventricular Dilation and Incident Congestive Heart Failure in Asymptomatic Adults without Cardiovascular Disease. MESA 
Journal of cardiac failure  2014;20(12):905-911.
Limited data exist on the association between LV dilation/remodeling and incident heart failure (HF), especially in adults without prior myocardial infarction and valvular heart disease. We assessed the association between left ventricular (LV) dilation and remodeling, and incident heart failure in a multi ethnic cohort
4974 of 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) had cardiac magnetic resonance imaging and complete data. Kaplan-Meier (KM) and Cox proportional hazard analyses were used to assess the association between LV end diastolic diameter (LVEDD) and adjudicated HF.
During the 12 years of follow up (mean 9.4 years), 177(3.6%) HF events occurred, 126(71.2%) HFref and 51(28.8%) HFpef. LV dilation (LVEDD >52mm or >95th percentile) was associated with HF in univariate [HR (95%CI): 1.21(1.08 – 1.46) p=0.007] and multivariable Cox models [HR (95%CI): 1.28(1.09–1.57) p=0.01] adjusting traditional risk factors, medication use, LV ejection fraction (LVEF) and interim MI. We found a significant multiplicative interaction between LVEDD and LV ejection fraction in our full multivariable models. Participants with dilated LV and normal ejection fraction had increase risk [HR (95%CI):2.22(1.46–3.37), p=0.006) and those with dilated LV and decreased ejection fraction having the worse prognosis [HR (95%CI): 7.35(2.36 – 22.85), p=0.0006] compared with normal size LV and normal ejection fraction. High proportion of participants with LV dilation had eccentric remodeling; a risk factor for HF. Concentric hypertrophy also a risk factor for HF was common in normal LV group.
LV dilation predicts incident HF independent of risk factors, LV EF and interim MI
PMCID: PMC4250423  PMID: 25225112
left ventricular dilation; left ventricular remodeling; heart failure; risk factors; left ventricular ejection fraction
19.  Prognostic utility of cardiovascular magnetic resonance upright maximal treadmill exercise testing 
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.
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).
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).
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.
PMCID: PMC4660781  PMID: 26608545
Coronary artery disease; Exercise testing; Cardiovascular magnetic resonance; Stress; Prognosis
20.  Intraperitoneal Fat Is Associated With Thickening of the Thoracic Aorta in Individuals at High Risk for Cardiovascular Events 
Obesity (Silver Spring, Md.)  2011;19(9):10.1038/oby.2011.188.
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.
PMCID: PMC3814164  PMID: 21720433
21.  Aging reduces left atrial performance during adrenergic stress in middle aged and older patients 
Cardiology journal  2012;19(1):45-52.
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.
PMCID: PMC3767009  PMID: 22298167
aging; left atrial function; adrenergic stress; cardiac MRI
22.  Simultaneous Measurement of Left and Right Ventricular Volumes and Ejection Fraction During Dobutamine Stress Cardiovascular Magnetic Resonance 
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.
PMCID: PMC3666038  PMID: 21926858
Hypertension  2010;56(5):901-906.
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.
PMCID: PMC3634339  PMID: 20837881
Renal sinus; intraperitoneal fat; hypertension; blood pressure; body mass index
24.  The use of cardiovascular magnetic resonance to identify adverse cardiac prognosis: An important step in reducing image related heathcare expenditures 
PMCID: PMC3634341  PMID: 20883931
coronary artery disease; cardiovascular magnetic resonance; adverse cardiac prognosis; cardiovascular computer tomography
25.  Impaired Left Ventricular Stroke Volume Reserve During Clinical Dobutamine Stress 
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.
PMCID: PMC3634344  PMID: 21310321
Stroke volume; heart failure; dobutamine cardiovascular magnetic resonance

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