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

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

The safety of Lipistart, a medium-chain triglyceride based formula, in the dietary treatment of long-chain fatty acid disorders: a phase I study.

BACKGROUND: Children with long-chain fatty acid ß-oxidation disorders (LCFAOD) presenting with clinical symptoms are treated with a specialist infant formula, with medium chain triglyceride (MCT) mainly replacing long chain triglyceride (LCT). It is essential that the safety and efficacy of any new specialist formula designed for LCFAOD be tested in infants and children. METHODS: In an open-label, 21-day, phase I trial, we studied the safety of a new MCT-based formula (feed 1) in six well-controlled children (three male), aged 7-13 years (median 9 years) with LCFAOD (very long chain acyl CoA dehydrogenase deficiency [VLCADD], n=2; long chain 3-hydroxyacyl CoA dehydrogenase deficiency [LCHADD], n=2; carnitine acyl carnitine translocase deficiency [CACTD], n=2). Feed 1 (Lipistart; Vitaflo) contained 30% energy from MCT, 7.5% LCT and 3% linoleic acid and it was compared with a conventional MCT feed (Monogen; Nutricia) (feed 2) containing 17% energy from MCT, 3% LCT and 1.1% linoleic acid. Subjects consumed feed 2 for 7 days then feed 1 for 7 days and finally resumed feed 2 for 7 days. Vital signs, blood biochemistry, ECG, weight, height, food/feed intake and symptoms were monitored. RESULTS: Five subjects completed the study. Their median daily volume of both feeds was 720 mL (range 500-1900 mL/day). Feed 1 was associated with minimal changes in tolerance, free fatty acids (FFA), acylcarnitines, 3-hydroxybutyrate (3-HB), creatine kinase (CK), blood glucose, liver enzymes and no change in an electrocardiogram (ECG). No child complained of muscle pain or symptoms associated with LCFAOD on either feed. CONCLUSIONS: This is the first safety trial reported of an MCT formula specifically designed for infants and children with LCFAOD. In this short-term study, it appeared safe and well tolerated in this challenging group.

Cancer and Its Association With the Development of Coronary Artery Calcification: An Assessment From the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: 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). CONCLUSIONS: 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.

Relation of Pre-anthracycline Serum Bilirubin Levels to Left Ventricular Ejection Fraction After Chemotherapy.

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.

Noninvasive Imaging of Flow and Vascular Function in Disease of the Aorta.

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 diagnose 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 noninvasive techniques, and applications for various disease states.

Comparison of left and right atrial volume by echocardiography versus cardiac magnetic resonance imaging using the area-length method.

Increased atrial volumes predict adverse cardiovascular events. Accordingly, accurate measurement of atrial size has become increasingly important in clinical practice. The area-length method is commonly used to estimate the volume. Disagreements between atrial volumes using echocardiography and other imaging modalities have been found. It is unclear whether this has resulted from differences in the measurement method or discrepancies among imaging modalities. We compared the right atrial (RA) and left atrial (LA) volume estimates using the area-length method for transthoracic echocardiography and cardiovascular magnetic resonance (CMR) imaging. Patients undergoing echocardiography and CMR imaging within 1 month were identified retrospectively. For both modalities, the RA and LA long-axis dimension and area were measured using standard 2- and 4-chamber views, and the volume was calculated using the area-length method for both atria. The echocardiographic and CMR values were compared using the Bland-Altman method. A total of 85 patients and 18 controls were included in the present study. The atrial volumes estimated using the area-length method were significantly smaller when measured using echocardiography than when measured using CMR imaging (LA volume 35 ± 20 vs 49 ± 30 ml/m², p <0.001, and RA volume 32 ± 23 vs 43 ± 29 ml/m², p = 0.012). The mean difference (CMR imaging minus echocardiography) was 14 ± 14 ml/m² for the LA and 10 ± 16 ml/m² for the RA volume. Similar results were found in the healthy controls. No significant intra- or interobserver variability was found within each modality. In conclusion, echocardiography consistently underestimated the atrial volumes compared to CMR imaging using the area-length method.