A novel method for measuring human hepatic lipase activity in postheparin plasma

金沢大学医薬保健研究域医学系The objective of this study was to establish a hepatic lipase (HL) assay method that can be applied to automatic clinical analyzers. Seventy-four hyperlipidemic subjects (men/women 45/29) were recruited. Lipase activity was assayed measuring the increase in absorbance at 546 nm due to quinonediimine dye production. Reaction mixture R-1 contained 50 mM Tris-HCl (pH 9.5), 0.5 mM glycerol-1,2-dioleate, 0.4% (unless otherwise noted) polyoxyethylenenonylphenylether, 3 mM ATP, 3 mM MgCl2, 1.5 mM CaCl2, monoacylglycerol-specific lipase, glycerol kinase, glycerol-3-phosphate oxidase, 0.075% N,N-bis-(4-sulfobutyl)-3-methylaniline-2 Na, peroxidase, ascorbic acid oxidase. Reaction mixture R-2 contained 50 mM Tris-HCl (pH9.5), 0.15% 4-aminoantypirine. Automated assay for activity was performed with a Model 7080 Hitachi analyzer. In the lipase assay, 160 μl of R-1 was incubated at 37°C with 3 μl of samples for 5 min, and 80 μl of R-2 was added. Within-run coefficient of variations was 0.9-1.0%. Calibration curve of lipase activity was linear (r = 0.999) between 0 and 320 U/l. Analytical recoveries of purified HL added to plasma were 96.6-99.8%. HL activity in postheparin plasma measured in this method had a closer correlation with HL mass by a sandwich ELISA (r = 0.888, P , 0.0001) than those in the conventional method using [ 14C-]triolein (r = 0.730, P < 0.0001). This assay method for HL activity can be applied to an automatic clinical analyzer. Copyright © 2007 by the American Society for Biochemistry and Molecular Biology, Inc

Pressure ramp testing for optimization of end-expiratory pressure settings in adaptive servo-ventilation therapy

Clinical outcomes of adaptive servo-ventilation (ASV) therapy have not been rigorously assessed. Optimal device settings ascertained by a pressure ramp test may increase the utility of ASV therapy. Patients with congestive heart failure (CHF) who underwent ASV therapy were prospectively included in the study. Patients in the ramp test group underwent a pressure ramp test, during which the end-expiratory pressure was optimized to maximize cardiac output (assessed using the AESCLONE mini). The control group consisted of age-matched patients who received ASV therapy with a default pressure 5 cmHO. The primary endpoint was a composite of all-cause death and heart failure recurrence, and was compared between the 2 groups. Of a total of 37 patients, 11 each were included in the ramp test and control groups. Median patient age was 73 years (interquartile range 59-75 years) and 16 were men. There were no significant differences in baseline characteristics between the 2 groups. In the ramp test group, end-expiratory pressure was optimized between 2 and 5 cmHO in each patient. The 2-year incidence of the primary endpoint tended to be lower in the ramp test than control group (0% vs. 59%; P=0.080). Pressure ramp testing may be a promising strategy to optimize device pressure settings in patients with CHF undergoing ASV therapy. Larger-scale trials are needed to validate our findings

Association between adaptive servo-ventilation therapy and renal function

Cardio-renal syndrome is a challenging clinical entity to manage, and is often associated with increased morbidity and mortality. We hypothesized that adaptive servo-ventilation (ASV), non-invasive positive pressure ventilation that ameliorates systemic/pulmonary congestion, may improve renal function in patients with symptomatic heart failure complicated by the cardio-renal syndrome. Patients with symptomatic congestive heart failure who underwent ASV therapy for over 1 month were included in this retrospective study. The trajectory of the estimated glomerular filtration ratio (eGFR) between the pre-1 month period and the post-one-month period (on ASV) were compared. A total of 81 patients (median 65 years old, 65 men) were included. eGFR decreased during the pre-1 month period from 52.7 (41.7, 64.6) down to 49.9 (37.3, 63.5) mL/minute/1.73 m2 (P \u3c 0.001) whereas we observed an increase following one-month of ASV therapy up to 53.4 (38.6, 68.6) mL/minute/1.73 m2 (P = 0.022). A reduction in furosemide equivalent dose following the initiation of ASV therapy was independently associated with increases in eGFR with an adjusted odds ratio of 13.72 (95% confidence interval 3.40-55.3, P \u3c 0.001). In conclusion, short-term ASV therapy was associated with the preservation of renal function, particularly when the dose of loop diuretics was concomitantly reduced

Impact of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Heart Failure with Preserved Ejection Fraction

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor is a recently introduced oral medication to treat renal anemia, but its clinical implication in patients with heart failure, particularly heart failure with preserved ejection fraction (HFpEF), remains unknown. We had a 91-year-old woman with HFpEF who was admitted to our institute to treat her worsening heart failure. She initiated HIF-PH inhibitor daprodustat to treat her renal anemia (hemoglobin 8.8 g/dL and estimated glomerular filtration ratio 15.6 mL/min/1.73 m2). Following a 6-month treatment with daprodustat, hemoglobin increased up to 10.4 g/dL, left ventricular mass index decreased from 107 g/m2 to 88 g/m2, and plasma B-type natriuretic peptide decreased from 276 pg/mL to 122 pg/mL, despite doses of other medications remaining unchanged. HIF-PH inhibitors might be a promising tool to ameliorate renal anemia and facilitate cardiac reverse remodeling in patients with HFpEF

Estimation of small dense LDL-cholesterol levels in patients with acute coronary syndrome

Small dense LDL-cholesterol is an established risk factor for atherosclerosis, but it is not routinely measured in clinical practice, and its measurement has not yet been reimbursed. The Sampson equation that uses triglyceride and LDL-cholesterol levels has very recently been proposed to estimate small dense LDL-cholesterol levels. We validated its accuracy in patients with acute coronary syndrome.Serum samples were obtained on admission from hospitalized patients with acute coronary syndrome before heparinization. Small dense LDL-cholesterol levels were measured directly and were also estimated from triglyceride and LDL-cholesterol levels using the Sampson equation. The correlation between the Sampson\u27s equation and direct measurement was investigated.A total of 55 patients were enrolled. The median age was 75 (65, 84) years old, and 35 (64%) were men. There was a moderate correlation between the two methods (r = 0.76, P \u3c 0.001). A lower level of small dense LDL-cholesterol was independently associated with a greater overestimation of the Sampson equation.The Sampson equation is useful for estimating small dense LDL-cholesterol levels in patients with acute coronary syndrome. However, the estimated value may be overestimated in patients with low lipid profiles

Implications of doppler echocardiography-guided heart rate modulation using Ivabradine

Objective Heart rate modulation therapy using ivabradine reduces both morbidity and mortality in patients with systolic heart failure. However, the target heart rate for this patient population remains to be elucidated. Methods In this prospective observational study, we included patients with heart failure and a reduced ejection fraction who received 5.0 mg/day of ivabradine for three days. At baseline and three days later, the overlap length between E-wave and A-wave using trans-mitral Doppler echocardiography, as well as the cardiac output using AESCLONE mini, were simultaneously measured. The associations between Δ overlap length and Δ cardiac output were then investigated. Results Eight patients (77 [53, 87] years old, 2 men) were included. The heart rate decreased from 81 (69, 104) bpm down to 64 (57, 79) bpm (p=0.012). The overlap length increased in four patients and decreased in the other four patients. During the time period of ivabradine therapy, patients who had a greater decrease in overlap length had a greater increase in cardiac output (r=0.84, p=0.009). Conclusion Decreases in the overlap length between E-wave and A-wave by Doppler echocardiography were associated with an increase in the cardiac output while on ivabradine therapy. The implications of Doppler echocardiography-guided heart rate modulation therapy targeting a minimal overlap length therefore require further evaluation in larger, prospective studies

Lung fluid volume during cardiopulmonary exercise testing

Cardiopulmonary exercise testing can be used to quantify exercise capacity in patients with heart failure with reduced ejection fraction (HfrEF). Lung fluid levels as measured non-invasively by remote dielectric sensing (ReDS), often correlate with intracardiac filling pressures. The change in lung fluid levels in patients with HfrEF during cardiopulmonary exercise testing is unknown. Patients with chronic HfrEF who underwent cardiopulmonary exercise testing between October 2021 and March 2022 were prospectively included in this proof-of-concept study, with ReDS values measured before and after testing. Thirteen patients (median age 41 (37, 52) years, 69% men, plasma B-type natriuretic peptide 141 (57, 368) pg/mL) were included. Median peak oxygen consumption was 11.4 (10.7, 14.0) mL/kg/min. During the test, ReDS values increased from 25% to 32% only in one patient on inotropic support, whereas ReDS values remained unchanged in the other 12 patients. The former patient remained hospitalized, whereas the other patients were dischargeable without any new incidence of clinical events during the observational period (median duration 69 (33, 112] days). The ReDS system may be a feasible complementary tool to noninvasively assess the changes in lung fluid levels during cardiopulmonary exercise testing. The clinical implications of ReDS values during exercise needs further investigation

Prognostic Implication of Small Dense LDL-Cholesterol Levels following Acute Coronary Syndrome

Background and Objectives: Small dense LDL cholesterol is a strong risk factor for atherosclerosis. However, few studies have investigated the impacts of this specific lipid profile on the incident risk of adverse cardiovascular events in patients with acute coronary syndrome. Materials and Methods: Patients with acute coronary syndrome, who underwent revascularization, were included and followed for 2 years. The levels of small dense LDL cholesterol were measured at index discharge (day 0) in the setting of newly administered therapies for secondary prevention, including aspirin and statins, during the index hospitalization. The prognostic impact of small dense LDL-cholesterol levels on the risk of a primary composite endpoint, including cardiac death, non-fatal myocardial infarction, unstable angina pectoris, stroke, and heart failure, was investigated. Results: In total, 46 patients (median 75 (59, 83) years old, 63% men) were included. Median small dense LDL cholesterol was 19.4 (13.5, 23.8) mg/dL at index discharge. All patients initiated statin treatment before the index discharge, with a median LDL-cholesterol level of 77 (64, 109) mg/dL. Small dense LDL-cholesterol level was independently associated with an incremental risk for the primary endpoint (p Conclusions: Small dense LDL-cholesterol level was a significant risk factor for cardiovascular events following presentations of acute coronary syndrome

Change in lung fluid volume during exercise in patients with exercise-induced mitral regurgitation

Exercise-induced mitral regurgitation (MR) can be diagnosed during stress echocardiography testing. Remote dielectric sensing (ReDS) is a noninvasive electromagnetic-based modality to measure lung fluid levels. The change in lung fluid levels in patients with MR during stress echocardiography remains unknown. Patients with symptomatic MR at baseline and suspected worsening exercise-induced MR underwent stress echocardiography. ReDS values were measured before and after the tests. A total of four patients (ages ranging between 74 and 84 years old, three women) underwent stress echocardiography testing using a bicycle ergometer. In patient A, MR effective regurgitant orifice area (EROA) remained unchanged and ReDS values decreased. EROA increased significantly with a small incremental change in ReDS values in patient B and patient C, who underwent valve repair with MitraClip later. Patient D had a mild increase in MR EROA but a considerable increase in ReDS values (from 22% to 32%), and eventually received valve repair with MitraClip. The ReDS system may be a complementary tool to conventional stress echocardiography in the evaluation of clinically significant MR and considering mitral valve intervention

Prognostic implication of small dense LDL-cholesterol levels following acute coronary syndrome

Background and Objectives: Small dense LDL cholesterol is a strong risk factor for atherosclerosis. However, few studies have investigated the impacts of this specific lipid profile on the incident risk of adverse cardiovascular events in patients with acute coronary syndrome. Materials and Methods: Patients with acute coronary syndrome, who underwent revascularization, were included and followed for 2 years. The levels of small dense LDL cholesterol were measured at index discharge (day 0) in the setting of newly administered therapies for secondary prevention, including aspirin and statins, during the index hospitalization. The prognostic impact of small dense LDL-cholesterol levels on the risk of a primary composite endpoint, including cardiac death, non-fatal myocardial infarction, unstable angina pectoris, stroke, and heart failure, was investigated. Results: In total, 46 patients (median 75 (59, 83) years old, 63% men) were included. Median small dense LDL cholesterol was 19.4 (13.5, 23.8) mg/dL at index discharge. All patients initiated statin treatment before the index discharge, with a median LDL-cholesterol level of 77 (64, 109) mg/dL. Small dense LDL-cholesterol level was independently associated with an incremental risk for the primary endpoint (p \u3c 0.05 by adjusting for several potential risk factors, including LDL cholesterol) with a cutoff of 32.6 mg/dL. Conclusions: Small dense LDL-cholesterol level was a significant risk factor for cardiovascular events following presentations of acute coronary syndrome