Features of portal hypertension are associated with major adverse events in Fontan patients: The VAST study

BACKGROUND: Chronic congestive hepatopathy is known to cause hepatic fibrosis and portal hypertension in patients post-Fontan operation for single ventricle palliation. The clinical significance of these findings is not clear. We hypothesized that features of portal hypertension would be significantly related to major adverse events. METHODS: A retrospective review of 73 adult and pediatric post-Fontan patients referred for a liver evaluation from 2001-2011 was performed. The relationship between features of portal hypertension (VAST score ≥2, 1 point each for Varices, Ascites, Splenomegaly or Thrombocytopenia) and a major adverse event (death, need for transplant, or hepatocellular carcinoma) was examined using logistic regression. RESULTS: 73 post-Fontan patients (30% female, 73% Caucasian, 66% systemic left ventricle (SLV), mean age 24 ±11 years, mean interval from Fontan 17 ±6 years) were included in analysis. Features of portal hypertension (VAST score ≥2) were present in 26 (36%), and there were 19 major adverse events: death (n=12), transplant (n=6), HCC (n=1). A significant relationship was found between VAST score ≥2 and major adverse events (OR=9.8, 95% CI [2.9-32.7]). After adjusting for time since Fontan, SLV, age, hemoglobin and type of failure, VAST score ≥2 remained significant (OR=9.1, 95% CI [1.4-57.6]). CONCLUSION: Fontan patients with features of portal hypertension have a 9-fold increased risk for a major adverse event. Therapies targeted to manage clinical manifestations of portal hypertension, and early referral to heart transplant may help delay major adverse events. Future prospective studies are needed to confirm these findings

Qualitative assessment of Tongue Drive System by people with high-level spinal cord injury

The Tongue Drive System (TDS) is a minimally invasive, wireless, and wearable assistive technology (AT) that enables people with severe disabilities to control their environments using tongue motion. TDS translates specific tongue gestures into commands by sensing the magnetic field created by a small magnetic tracer applied to the user’s tongue. We have previously quantitatively evaluated the TDS for accessing computers and powered wheelchairs, demonstrating its usability. In this study, we focused on its qualitative evaluation by people with high-level spinal cord injury who each received a magnetic tongue piercing and used the TDS for 6 wk. We used two questionnaires, an after-scenario and a poststudy, designed to evaluate the tongue-piercing experience and the TDS usability compared with that of the sip-and-puff and the users’ current ATs. After study completion, 73% of the participants were positive about keeping the magnetic tongue-barbell in order to use the TDS. All were satisfied with the TDS performance and most said that they were able to do more things using TDS than their current ATs (4.22/5)

Prognostic Value of Stress Myocardial Perfusion Positron Emission Tomography: Results From A Multicenter Observational Registry

ObjectivesThe primary objective of this multicenter registry was to study the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) and the improved classification of risk in a large cohort of patients with suspected or known coronary artery disease (CAD).BackgroundLimited prognostic data are available for MPI with PET.MethodsA total of 7,061 patients from 4 centers underwent a clinically indicated rest/stress rubidium-82 PET MPI, with a median follow-up of 2.2 years. The primary outcome of this study was cardiac death (n = 169), and the secondary outcome was all-cause death (n = 570). Net reclassification improvement (NRI) and integrated discrimination analyses were performed.ResultsRisk-adjusted hazard of cardiac death increased with each 10% myocardium abnormal with mildly, moderately, or severely abnormal stress PET (hazard ratio [HR]: 2.3 [95% CI: 1.4 to 3.8; p = 0.001], HR: 4.2 [95% CI: 2.3 to 7.5; p < 0.001], and HR: 4.9 [95% CI: 2.5 to 9.6; p < 0.0001], respectively [normal MPI: referent]). Addition of percent myocardium ischemic and percent myocardium scarred to clinical information (age, female sex, body mass index, history of hypertension, diabetes, dyslipidemia, smoking, angina, beta-blocker use, prior revascularization, and resting heart rate) improved the model performance (C-statistic 0.805 [95% CI: 0.772 to 0.838] to 0.839 [95% CI: 0.809 to 0.869]) and risk reclassification for cardiac death (NRI 0.116 [95% CI: 0.021 to 0.210]), with smaller improvements in risk assessment for all-cause death.ConclusionsIn patients with known or suspected CAD, the extent and severity of ischemia and scar on PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors

Aggregate Risk Score Based on Markers of Inflammation, Cell Stress, and Coagulation Is an Independent Predictor of Adverse Cardiovascular Outcomes

Objectives: This study sought to determine an aggregate, pathway-specific risk score for enhanced prediction of death and myocardial infarction (MI). Background Activation of inflammatory, coagulation, and cellular stress pathways contribute to atherosclerotic plaque rupture. We hypothesized that an aggregate risk score comprised of biomarkers involved in these different pathways - high-sensitivity C-reactive protein (CRP), fibrin degradation products (FDP), and heat shock protein 70 (HSP70) levels - would be a powerful predictor of death and MI. Methods: Serum levels of CRP, FDP, and HSP70 were measured in 3,415 consecutive patients with suspected or confirmed coronary artery disease (CAD) undergoing cardiac catheterization. Survival analyses were performed with models adjusted for established risk factors. Results: Median follow-up was 2.3 years. Hazard ratios (HRs) for all-cause death and MI based on cutpoints were as follows: CRP ≥3.0 mg/l, HR: 1.61; HSP70 >0.625 ng/ml, HR; 2.26; and FDP ≥1.0 μg/ml, HR: 1.62 (p < 0.0001 for all). An aggregate biomarker score between 0 and 3 was calculated based on these cutpoints. Compared with the group with a 0 score, HRs for all-cause death and MI were 1.83, 3.46, and 4.99 for those with scores of 1, 2, and 3, respectively (p for each: <0.001). Annual event rates were 16.3% for the 4.2% of patients with a score of 3 compared with 2.4% in 36.4% of patients with a score of 0. The C statistic and net reclassification improved (p < 0.0001) with the addition of the biomarker score. Conclusions: An aggregate score based on serum levels of CRP, FDP, and HSP70 is a predictor of future risk of death and MI in patients with suspected or known CAD

A Clinical Tool to Identify Candidates for Stress-First Myocardial Perfusion Imaging

Objectives: This study sought to develop a clinical model that identifies a lower-risk population for coronary artery disease that could benefit from stress-first myocardial perfusion imaging (MPI) protocols and that can be used at point of care to risk stratify patients. Background: There is an increasing interest in stress-first and stress-only imaging to reduce patient radiation exposure and improve patient workflow and experience. Methods: A secondary analysis was conducted on a single-center cohort of patients undergoing single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. Normal MPI was defined by the absence of perfusion abnormalities and other ischemic markers and the presence of normal left ventricular wall motion and left ventricular ejection fraction. A model was derived using a cohort of 18,389 consecutive patients who underwent SPECT and was validated in a separate cohort of patients who underwent SPECT (n = 5,819), 1 internal cohort of patients who underwent PET (n=4,631), and 1 external PET cohort (n = 7,028). Results: Final models were made for men and women and consisted of 9 variables including age, smoking, hypertension, diabetes, dyslipidemia, typical angina, prior percutaneous coronary intervention, prior coronary artery bypass graft, and prior myocardial infarction. Patients with a score ≤1 were stratified as low risk. The model was robust with areas under the curve of 0.684 (95% confidence interval [CI]: 0.674 to 0.694) and 0.681 (95% CI: 0.666 to 0.696) in the derivation cohort, 0.745 (95% CI: 0.728 to 0.762) and 0.701 (95% CI: 0.673 to 0.728) in the SPECT validation cohort, 0.672 (95% CI: 0.649 to 0.696) and 0.686 (95% CI: 0.663 to 0.710) in the internal PET validation cohort, and 0.756 (95% CI: 0.740 to 0.772) and 0.737 (95% CI: 0.716 to 0.757) in the external PET validation cohort in men and women, respectively. Men and women who scored ≤1 had negative likelihood ratios of 0.48 and 0.52, respectively. Conclusions: A novel model, based on easily obtained clinical variables, is proposed to identify patients with low probability of having abnormal MPI results. This point-of-care tool may be used to identify a population that might qualify for stress-first MPI protocols

The Tongue Enables Computer and Wheelchair Control for People with Spinal Cord Injury

The Tongue Drive System (TDS) is a wireless and wearable assistive technology, designed to allow individuals with severe motor impairments such as tetraplegia to access their environment using voluntary tongue motion. Previous TDS trials used a magnetic tracer temporarily attached to the top surface of the tongue with tissue adhesive. We investigated TDS efficacy for controlling a computer and driving a powered wheelchair in two groups of able-bodied subjects and a group of volunteers with spinal cord injury (SCI) at C6 or above. All participants received a magnetic tongue barbell and used the TDS for five to six consecutive sessions. The performance of the group was compared for TDS versus keypad and TDS versus a sip-and-puff device (SnP) using accepted measures of speed and accuracy. All performance measures improved over the course of the trial. The gap between keypad and TDS performance narrowed for able-bodied subjects. Despite participants with SCI already having familiarity with the SnP, their performance measures were up to three times better with the TDS than with the SnP and continued to improve. TDS flexibility and the inherent characteristics of the human tongue enabled individuals with high-level motor impairments to access computers and drive wheelchairs at speeds that were faster than traditional assistive technologies but with comparable accuracy

Lipid metabolite biomarkers in cardiovascular disease: discovery and biomechanism translation from human studies

Lipids represent a valuable target for metabolomic studies since altered lipid metabolism is known to drive the pathological changes in cardiovascular disease (CVD). Metabolomic technologies give us the ability to measure thousands of metabolites providing us with a metabolic fingerprint of individual patients. Metabolomic studies in humans have supported previous findings into the pathomechanisms of CVD, namely atherosclerosis, apoptosis, inflammation, oxidative stress, and insulin resistance. The most widely studied classes of lipid metabolite biomarkers in CVD are phospholipids, sphingolipids/ceramides, glycolipids, cholesterol esters, fatty acids, and acylcarnitines. Technological advancements have enabled novel strategies to discover individual biomarkers or panels that may aid in the diagnosis and prognosis of CVD, with sphingolipids/ceramides as the most promising class of biomarkers thus far. In this review, application of metabolomic profiling for biomarker discovery to aid in the diagnosis and prognosis of CVD as well as metabolic abnormalities in CVD will be discussed with particular emphasis on lipid metabolites

Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease

BACKGROUND: Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7 ± 2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P+1 SD and <-1 SD, respectively) were associated with higher mortality (adjusted hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.19-2.21; HR, 2.19; 95% CI, 1.50-3.19; respectively) compared with those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR, 1.92; 95% CI, 1.39-2.64) and was independent of and additive to high-sensitivity C-reactive protein level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS: A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress