Clinical Feasibility of Biofunctionalized Magnetic Nanoparticles for Detecting Multiple Cardiac Biomarkers in Emergency Chest Pain Patients.

BACKGROUND: The rapid diagnosis of acute myocardial infarction (AMI) is a clinical and operational priority in emergency departments. Serial serum levels of cardiac biomarkers play a crucial role in the evaluation of patients presenting with acute chest pain, so that an accurate and rapidly responsive assay of cardiac biomarkers is vital for emergency departments. METHODS: Immunomagnetic reduction (IMR) has been developed for rapid and on-site assays with a small sample volume. IMR kits for three biomarkers [myoglobin, creatine kinase-MB (CK-MB), and troponin-I] have been developed by MagQu Co., Ltd., Taiwan (US patent: US20190072563A1). In this study, we examined correlations between IMR signals and biomarker concentrations. The measurement threshold of the IMR kits, dynamic ranges, interference tests in vitro, and reagent stability were tested. Clinical cases were included with serial IMR measurements to determine the time course and peak of IMR-measured cardiac biomarkers after AMI. RESULTS: The correlations between IMR signals and biomarker concentrations fitted well to logistic functions. The measurement thresholds of the IMR kits (1.03 × 10-8 ng/mL for myoglobin, 1.46 × 10-6 ng/mL for CK-MB, and 0.08 ng/mL for troponin-I) were much lower than the levels detected in the patients with AMI. There was no significant interference in vitro. The peak times of IMR-detected myoglobin, CK-MB, and troponin-I after AMI were 8.2 hours, 24.4 hours, and 24.7 hours, respectively. CONCLUSIONS: IMR is an accurate and sensitive on-site rapid assay for multiple cardiac biomarkers in vitro, and may play a role in the early diagnosis of AMI. Clinical trials are needed.

Cassegrain-based concentrator with tailored mirrors.

In this study, we design a Cassegrain-based concentrator with tailored mirrors. The proposed concentrator comprises a primary optical element (POE) and a secondary optical element (SOE). The POE is a parabolic concave mirror and the SOE is a hyperbolic convex mirror. In order to achieve uniform irradiance distribution without a homogenizer, the POE is tailored and tilted to generate a uniform distribution by overlapping the energy well. The Cassegrain-based concentrator with tailored mirrors can achieve a geometric concentration ratio of 1236×, a concentration ratio of 1034×, an optical efficiency of 83.66%, an acceptance angle of ±0.38∘, a uniformity of 7.87, and an aspect ratio of 0.254.

Serum Angiopoietin-Like Protein 2 Concentrations Are Independently Associated with Heart Failure.

OBJECTIVE: Angiopoietin-like protein 2 (ANGPTL2), which is mainly expressed from adipose tissue, is demonstrated to be involved in obesity, metabolic syndrome, and atherosclerosis. Because several adipocytokines are known to be associated with heart failure (HF), here we investigated the association of ANGPTL2 and HF in Taiwanese subjects. METHODS AND RESULTS: A total of 170 symptomatic HF patients and 130 age- and sex-matched controls were enrolled from clinic. The echocardiography was analyzed in each patient, and stress myocardial perfusion study was performed for clinical suspicion of coronary artery disease. Detailed demographic information, medications, and biochemical data were recorded. Circulating adipocytokines, including tumor necrosis factor-alpha (TNF-α), adiponectin, adipocyte fatty acid-binding protein (A-FABP) and ANGPTL2, were analyzed. Compared with the control group subjects, serum ANGPTL2 concentrations were significantly higher in HF group patients. In correlation analyses, ANGPTL2 level was positively correlated to creatinine, fasting glucose, triglyceride, hsCRP, TNF-α, NT-proBNP and A-FABP levels, and negatively correlated with HDL-C and left ventricular ejection fraction. In multiple regression analysis, A-FABP, hsCRP, and HDL-C levels remained as independent predictors for ANGPTL2 level. To determine the association between serum ANGPTL2 concentrations and HF, multivariate logistic regression analyses were performed with subjects divided into tertiles by ANGPTL2 levels. For the subjects with ANGPTL2 levels in the highest tertile, their risk of HF was about 2.97 fold (95% CI = 1.24-7.08, P = 0.01) higher than those in the lowest tertile. CONCLUSION: Our results demonstrate a higher circulating ANGPTL2 level in patients with HF, and the upregulating ANGPTL2 levels might be associated with metabolic derangements and inflammation.

Association of Plasma Thrombospondin-1 Level with Cardiovascular Disease and Mortality in Hemodialysis Patients.

BACKGROUND: Thrombospondin-1 (TSP-1) is known to be involved in the regulation of angiogenesis, inflammation, and vascular function. Clinical studies have demonstrated its correlation with peripheral artery disease, coronary artery disease, and pulmonary hypertension. In this study, we explored its potential roles in the background of end-stage renal disease (ESRD). METHODS: A total of 140 ESRD outpatients (ages 61.0 ± 12.4 years) were prospectively followed for 34 ± 7 months. Their TSP-1 levels were analyzed from pre-hemodialysis blood sample. Cardiovascular survey included ankle- brachial index (ABI), echocardiography and Tl-201 dipyridamole single-photon emission computed tomography (SPECT). RESULTS: Plasma TSP-1 levels were higher in those patients with preexisting clinical evidence of cardiovascular disease (CVD) than those without (p = 0.002). TSP-1 concentrations were also correlated with ABI, left ventricular ejection fraction, and scar burden in SPECT. Stepwise logistic regression analysis revealed that TSP-1 level was independently associated with the presence of CVD, with an odds ratio of 1.38 [95% confidence interval (CI), 1.09-1.75, p = 0.008]. In survival analyses, 31 patients (22%) died during the follow-up, 16 (52%) arising from cardiovascular causes. Cox hazards analysis revealed that the patients with TSP-1 levels in the highest tertile had a 5.32- and 6.75-fold higher risk for all-cause and cardiovascular mortality than those in the lowest tertile. This predictive value for all-cause mortality still persisted after multivariate adjustment (hazard ratio, 8.71; 95% CI, 1.36-55.68; p = 0.02). CONCLUSIONS: This study hallmarks the association of elevated TSP-1 level with CVD and adverse outcome among hemodialysis patients. KEY WORDS: Thrombospondin-1; End-stage renal disease; Cardiovascular disease; Mortality.

Association of lower extremity arterial calcification with amputation and mortality in patients with symptomatic peripheral artery disease.

OBJECTIVE: The clinical implication of the coronary artery calcium score (CS) is well demonstrated. However, little is known about the association between lower extremity arterial calcification and clinical outcomes. METHODS AND RESULTS: Eighty-two patients with symptomatic peripheral artery disease (age 61.0±12.4 years) were followed for 21±11 months. CSs, ranging from the common iliac artery bifurcation to the ankle area, were analyzed through noncontrast multidetector computed tomography images retrospectively. The primary endpoints of this study were amputation and mortality. Old age, diabetes, hyperlipidemia, and end-stage renal disease were associated with higher CSs. Patients with more advanced Fontaine stages also tended to have significantly higher CSs (p = 0.03). During the follow-up period (21±11 months), 29 (35%) patients underwent amputation, and 24 (29%) patients died. Among the patients who underwent amputation, there were no significant differences in CSs between the amputated legs and the non-amputated legs. In the Cox proportional hazard model with CS divided into quartiles, patients with CS in the highest quartile had a 2.88-fold (95% confidence interval [CI] 1.18-12.72, p = 0.03) and a 5.16-fold (95% CI 1.13-21.61, p = 0.04) higher risk for amputation and all-cause mortality, respectively, than those with CS in the lowest quartile. These predictive effects remained after conventional risk factor adjustment. CONCLUSION: Lower extremity arterial CSs are associated with disease severity and outcomes, including amputation and all-cause mortality, in patients with symptomatic peripheral artery disease. However, the independent predictive value needs further investigation in large scale, prospective studies.

Association between serum adipocyte fatty-acid binding protein concentrations, left ventricular function and myocardial perfusion abnormalities in patients with coronary artery disease.

BACKGROUND: Adipokines, including adipocyte fatty acid-binding protein (A-FABP), have been demonstrated to be involved in the pathogenesis of atherosclerosis. In the present study, we investigated the association of circulating A-FABP level with severity of myocardial perfusion abnormalities analyzed by Tl-201 dipyridamole single-photon emission computed tomography. METHODS: A total of 170 patients with coronary artery disease (CAD) from cardiovascular clinics were enrolled in the study. Serum A-FABP levels, echocardiography, and stress myocardial perfusion imaging results were analyzed. RESULTS: Compared with the patients with mild CAD (summed stress score [SSS] ≤ 8), those with moderate to severe CAD (SSS > 8) had significantly higher A-FABP concentrations. However, the difference was attenuated in the subgroup of patients with heart failure. In the correlation analyses, A-FABP level was correlated with age, body mass index, waist circumference, levels of creatinine, fasting glucose, high-sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, adiponectin, and several echocardiographic parameters, including left ventricular ejection fraction. Multivariate logistic regression analysis demonstrated that the A-FABP level was not only associated with higher SSS (odds ratio, 1.30; 95% confidence interval [CI], 1.01-1.69; P = 0.048), but also an independent risk factor for heart failure (odds ratio 2.71, 95% CI, 1.23-5.94; P = 0.013). CONCLUSIONS: Serum A-FABP levels not only were associated with myocardial perfusion abnormalities and left ventricular function, but also predicted the presence of heart failure in our patients with CAD.

Serum adipocyte fatty acid-binding protein levels in patients with critical illness are associated with insulin resistance and predict mortality.

INTRODUCTION: Hyperglycemia and insulin resistance are commonplace in critical illness, especially in patients with sepsis. Recently, several hormones secreted by adipose tissue have been determined to be involved in overall insulin sensitivity in metabolic syndrome-related conditions, including adipocyte fatty-acid binding protein (A-FABP). However, little is known about their roles in critical illness. On the other hand, there is evidence that several adipose tissue gene expressions change in critically ill patients. METHODS: A total of 120 patients (72 with sepsis, 48 without sepsis) were studied prospectively on admission to a medical ICU and compared with 45 healthy volunteers as controls. Various laboratory parameters and metabolic and inflammatory profiles were assessed within 48 hours after admission. Clinical data were collected from medical records. RESULTS: Compared with healthy controls, serum A-FABP concentrations were higher in all critically ill patients, and there was a trend of higher A-FABP in patients with sepsis. In multivariate correlation analysis in all critically ill patients, the serum A-FABP concentrations were independently related to serum creatinine, fasting plasma glucose, total cholesterol, TNF-alpha, albumin, and the Acute Physiology and Chronic Health Evaluation II scores. In survival analysis, higher A-FABP levels (> 40 ng/ml) were associated with an unfavorable overall survival outcome, especially in sepsis patients. CONCLUSIONS: Critically ill patients have higher serum A-FABP concentrations. Moreover, A-FABP may potentially serve as a prognostic biomarker in critically ill patients with sepsis.

The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers.

PURPOSE: (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has the potential to track vascular inflammation and monitor therapeutic response. The purpose of this study was to determine the association between arterial inflammation, calcification and serological biomarkers in subjects with atherosclerosis, and to assess their therapeutic response to 12-week atorvastatin treatment. METHODS: Forty-three statin-naïve subjects with atherosclerosis received atorvastatin (40 mg/day) for 12 weeks and underwent (18)F-FDG PET/CT, coronary calcification and abdominal adipose tissue volume measurements. A panel of serological biomarkers was analysed. Arterial inflammation was measured at seven arterial segments and normalized to venous FDG activity to produce target to background ratios (TBR). Thirty-four subjects without cardiovascular disease who repeated PET 1-4 years apart for routine health check-ups were retrospectively evaluated for comparison. RESULTS: The baseline mean TBR values in atherosclerotic patients were positively correlated with age (R = 0.36), body mass index (R = 0.54), abdominal visceral adipose tissue volume (R = 0.65), coronary calcification score (R = 0.40), levels of low-density lipoprotein cholesterol (R = 0.54), matrix metalloproteinase (MMP)-9 (R = 0.46) and fatty acid binding protein 4 (FABP4) (R = 0.67, all p < 0.05). The TBR as well as high-sensitivity C-reactive protein (hsCRP), E-selectin, MMP-9, monocyte chemotactic protein 1, FABP4 and follistatin values were reduced significantly after the 12-week atorvastatin treatment. The TBR reduction marginally correlated with changes in MMP-9 levels (R = 0.56, p = 0.05). The control group, whose median age was younger, by comparison had lower hsCRP and arterial TBR than the subjects with atherosclerosis (all p < 0.05), and moreover had a slight but insignificant increase in mean TBR at their 2.5±0.8 year follow-up. CONCLUSION: The medium dose of atorvastatin over a 12-week period resulted in a significant reduction of arterial inflammation as well as various circulating biomarkers.

The application of infrared thermography in evaluation of patients at high risk for lower extremity peripheral arterial disease.

OBJECTIVE: We investigated the usefulness of infrared thermography in evaluating patients at high risk for lower extremity peripheral arterial disease (PAD), including severity, functional capacity, and quality of life. METHODS: A total of 51 patients (23 males; age 70 ± 9.8 years) were recruited. They completed three PAD-associated questionnaires, including walking impairment, vascular quality of life, and 7-day physical activity recall questionnaires before a 6-minute walking test (6MWT). Ankle-brachial index (ABI) and segmental pressure were analyzed for PAD diagnosis and stenotic level assessment. The cutaneous temperature at shin and sole were recorded by infrared thermography before and after the walk test. Detailed demographic information and medication list were obtained. RESULTS: Twenty-eight subjects had abnormal ABI (ABI <1), while PAD was diagnosed in 20. No subjects had non-compressible artery (ABI >1.3). Demographic profiles and clinical parameters in PAD and non-PAD patients were similar, except for age, smoking history, and hyperlipidemia. PAD patients walked shorter distances (356 ± 102 m vs 218 ± 92 m; P < .001). Claudication occurred in 14 patients, while seven failed in completing the 6MWT. The rest temperatures were similar in PAD and non-PAD patients. However, the post-exercise temperature dropped in the lower extremities with arterial stenosis, but was maintained or elevated slightly in the extremities with patent arteries (temperature changes at sole in PAD vs non-PAD patients: -1.25 vs -0.15°C; P < .001). The exercise-induced temperature changes at the sole were not only positively correlated with the 6MWD (Spearman correlation coefficient = 0.31, P = .03), but was also correlated with ABI (Spearman correlation coefficient = 0.48, P < .001) and 7-day physical activity recall scores (Spearman correlation coefficient = 0.30, P = .033). CONCLUSION: By detecting cutaneous temperature changes in the lower extremities, infrared thermography offers another non-invasive, contrast-free option in PAD evaluation and functional assessment.

Continuous intravenous infusion of prostaglandin E1 improves myocardial perfusion reserve in patients with ischemic heart disease assessed by positron emission tomography: a pilot study.

OBJECTIVE: Recent investigation has demonstrated that prostaglandin E(1) (PGE(1)) therapy increased capillary density in explanted hearts. Dynamic (13)N-ammonia positron emission tomography (PET) is reliable for non-invasive measurement of myocardial blood flow and myocardial perfusion reserve (MPR). The aim of this study was to investigate the effects of PGE(1) therapy during 4 weeks on reduction of myocardial perfusion abnormalities and increase of MPR in the patients with ischemic heart disease. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 11 patients who had symptomatic heart failure and documented myocardial ischemia to 4 weeks intravenous infusion of PGE(1) (2.5 ng/kg/min; 8 patients, age 60 ± 13 years) or saline (3 patients, age 57 ± 13 years). Dynamic (13)N-ammonia PET scans at rest and during adenosine stress were obtained at baseline and 12 weeks after treatment completion. Quantitative size/severity of perfusion defects and MPR change from baseline to follow-up PET were determined using a 17-segment model. RESULTS: Compared with the control group, baseline MPR in the PGE(1) group was significantly lower (1.96 ± 0.78 vs. 2.71 ± 0.73; P < 0.001). MPR significantly improved 12 weeks after completion of PGE(1) infusion (1.96 ± 0.78 to 2.16 ± 0.77; P < 0.001). In contrast, MPR declined significantly in the placebo group (2.71 ± 0.73 to 2.01 ± 0.58, P < 0.001). CONCLUSION: Four weeks of PGE(1) infusion sustained MPR improvement in patients with ischemic heart disease. This may be an attractive therapeutic approach for no-option patients with severe ischemic cardiomyopathy.

Endovascular management of post-traumatic innominate artery transection with pseudo-aneurysm formation.

Although catheter-based endovascular techniques have been used with increasing frequency for the management of vascular trauma, reports about innominate artery repair were limited. Here we describe a case of blunt traumatic injury with innominate artery transection. Endovascular stent-graft deployment through femoral artery was performed successfully without any neurologic deficit.

Usefulness of paradoxical systolic blood pressure increase after exercise as a predictor of cardiovascular mortality.

Exercise treadmill testing (ETT) is a well-accepted examination for patients with suspected coronary artery disease (CAD), and exercise induced ST-segment deviation is commonly used for CAD detection. However, recent evidence shows that systolic blood pressure (SBP) changes during and after exercise were associated with CAD severity, risk of acute myocardial infarction and stroke, new-onset hypertension, and even cardiovascular mortality. We retrospectively assessed 3,054 patients referred for ETT in 1996. Blood pressure and heart rate were recorded at rest, during peak exercise, and 1 and 3 min after exercise. SBP at 3 min of recovery equal to or higher than that at 1-min of recovery was defined as paradoxical SBP increase. These patients were categorized into 4 groups according to ETT ST-segment change and postexercise SBP change. After 10 years of follow-up, 346 patients (11%) died, with 129 (4%) dying from cardiovascular disease (CVD). Among the 4 groups, patients with ischemic ST-segment change and paradoxical SBP increase were associated with a higher risk for mortality, with odds ratios of 1.86 (95% confidence interval 1.31 to 2.65) for all-cause mortality and 3.18 (95% confidence interval 1.94 to 5.20) for CVD mortality, respectively. Patients with isolated paradoxical SBP increase still had a higher risk of CVD mortality (odds ratio 1.80, 95% confidence interval 1.70 to 3.04), even after controlling other cardiovascular risk factors. In subgroup analysis of 346 mortality subjects, patients with ischemic ST-segment change and paradoxical SBP increase would be more likely to die from CVD. In conclusion, compared with ischemic ST-segment change, paradoxical SBP increase after exercise is an important and significant predictor of CVD mortality.