The clinical value of hepatojugular reflux on congestive heart failure: A meta-analysis.

Background: Hepatojugular reflux is a cardiac physical examination with a long history of use in heart failure diagnosis across many clinical settings. However, the development of new diagnostic methods has thrown the clinical role of hepatojugular reflux into question. Our meta-analysis aimed to determine the diagnostic accuracy of hepatojugular reflux and assess its usefulness in diagnosing congestive heart failure among at-risk patients. Methods: This meta-analysis of studies reporting diagnostic hepatojugular reflux values of patients at risk for congestive heart failure followed PRISMA guidelines. We searched MEDLINE, EMBASE, Web of Science, CENTRAL, and Google Scholar for eligible studies from inception through February 1, 2021. After QUADAS-2 quality assessment, we conducted data synthesis using the random effects model and a hierarchical summary receiver operating characteristic model. As an additional analysis, we sorted the studies by clinical setting and performed synthesis again. We submitted our protocol to PROSPERO (International Prospective Register of Systematic Reviews; ID No. CRD42020215004). Results: The literature search provided 4121 studies for evaluation. Seven studies and their 5195 participants were deemed eligible for synthesis. Clinical diagnosis was the most frequent reference standard. Bivariate random-effects analysis found hepatojugular reflux sensitivity of 0.12, 95% confidence interval (CI) [0.07-0.19], and specificity of 0.96, 95% CI [0.95-0.97]. The DOR was 29.7, 95% CI [18.4-45.3]. The additional analysis of the emergency settings provided a sensitivity of 0.14, 95% CI [0.12-0.17] and specificity of 0.95, 95% CI [0.93-0.96]. Conclusions: Our meta-analysis suggests that hepatojugular reflux has practical value for diagnosis of congestive heart failure with high specificity.

Direct comparison of the reproducibility of in-office and self-measured home blood pressures.

OBJECTIVE: The aim was to compare short-term and long-term reproducibilities of in-office unattended blood pressure (BP), namely automated office blood pressure (AOBP), conventionally measured attended office BP, and self-measured home BP. METHODS: A multicentre, clinical study was conducted in Japan, and 287 Japanese outpatients on antihypertensive drug medication were followed-up for 1 year. RESULTS: The intensity of drug treatment was sustained consistently throughout the study period (defined daily doses, 1.62-1.68; P = 0.12). The mean SBP differences between baseline and 1 month later, as well as baseline and 1 year later, were less than 1.5 mmHg, whereas the standard deviations of the differences for home, AOBP, and attended office measurements for the 1-year interval were 7.7, 14.5, and 15.3 mmHg, respectively. The coefficients of variation were significantly smaller for home BP than for AOBP among all patients at both 1-month and 1-year intervals (P < 0.0001). In the 1-month interval, partial correlation coefficients of home BP (r, 0.73/0.88 for systolic/diastolic measures) were significantly higher than of conventional BP (r, 0.47/0.69). However, the correlations converged to the modest level regardless of BP information (r, 0.49-0.54/0.63-0.73) when the 1-year interval was assessed. Results were confirmatory when patients on the same drug regimen (n = 167) were analysed. CONCLUSION: A higher reproducibility of home BP was demonstrated compared with in-office BP, including AOBP. However, the modest correlations for the 1-year interval support the importance of regular assessment of BP, regardless of in-office or home measurements for treatment of hypertension.

Effects of Low-Dose Colchicine on Serum High-Sensitivity C-Reactive Protein Level in Coronary Artery Disease Patients with Type 2 Diabetes Mellitus and Enhanced Inflammatory Response Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase 2, Dose-Finding Study.

Although cardiovascular mortality in Japan is lower than in other industrialized countries, clinical outcomes in coronary artery disease (CAD) patients with type 2 diabetes mellitus (T2DM) remain poor despite multiple evidence-based drug therapies and interventions. We assumed that part of residual risk in these patients may be attributable to enhanced inflammation, which can be inhibited presumably by colchicine. However, dose-responsiveness of anti-inflammatory effect of colchicine has not been elucidated. Therefore, we designed a multicenter, randomized, double-blinded, parallel-group study to explore the dose-dependent effects of low-dose colchicine on serum high-sensitivity C-reactive protein (hs-CRP) concentration and safety in CAD patients with T2DM and enhanced inflammatory response as a phase 2 study. Enhanced inflammatory response was defined as peripheral white-blood cell count ≥7,000/µL. Patients (N = 63) will be randomly assigned to two doses of colchicine 0.25 mg/day, 0.5 mg/day, or placebo in a 1:1:1 ratio once daily for 12 weeks. Changes in serum hs-CRP levels will be evaluated as the primary endpoint, and changes in flow-mediated vasodilation and plasma myeloperoxidase levels will be evaluated as secondary endpoints. The results of this study will contribute to the development of a protocol for a planned future phase 3 trial to estimate the reduction in CAD. The present study describes the rationale, design, and methods of the trial.

Effects of Perioperative Administration of Acetaminophen on Postoperative Shivering: A Randomized, Triple-Blind, Placebo-Controlled Trial.

BACKGROUND: In this randomized, triple-blind, placebo-controlled trial, we tested the hypothesis that perioperative acetaminophen administration has a prophylactic effect on postoperative shivering. METHODS: Forty-five women scheduled for gynecological laparotomy were randomized to either the acetaminophen or the placebo groups. After induction of general anesthesia, the test drug (acetaminophen 15 mg/kg) or placebo (0.9% saline) was intravenously administered over 15 minutes. The primary outcome measure was the incidence of severe postoperative shivering (ie, shivering score >2) in the postanesthesia care unit, where patients stayed for 30 minutes after their emergence from anesthesia. For the secondary outcomes, core body temperature (BT) was recorded at the forehead just before anesthesia induction (time 0 [T0]), at the start of surgery (time 1 [T1]), at the end of surgery (time 2 [T2]), at the initiation of postoperative observation in the postanesthesia care unit (time 3 [T3]), and 30 minutes after T3 (time 4 [T4]). At 1 hour after T4 (ie, time 5 [T5]), the BT was recorded from the axilla (BTA). Primary outcome was analyzed using a χ test. BT recorded at the forehead (BTF) and BTA were analyzed using a 2-way repeated-measures analysis of variance (ANOVA) and a 2-sample t test, respectively. For all comparisons, a P value <.05 was considered statistically significant. RESULTS: The study duration was 2 years. Of the 45 patients initially enrolled, 8 patients were excluded. The acetaminophen and placebo groups included 18 and 19 patients, respectively. The incidence of severe postoperative shivering in the postanesthesia care unit was significantly lower in the acetaminophen group (22.2%) than in the placebo group (73.7%) (relative risk, 0.302; 95% confidence interval, 0.122-0.746; P = .005). Two-way repeated-measures ANOVA showed a significant effect of time (F4,140 = 54.8; P < .001) and a significant time by treatment interaction (F4,140 = 9.61; P < .001) but did not show a main effect of the treatment (F1,35 = 1.83; P = .185) in BTF. Moreover, BTA at T5 was significantly lower in the acetaminophen group (mean [standard deviation {SD}], 37.2°C [0.48°C]) than in the placebo group (37.9°C [0.63°C]; P < .001). CONCLUSIONS: Our findings in patients undergoing gynecological laparotomy suggest that perioperative acetaminophen administration can prevent postoperative severe shivering. This prophylactic effect might be due to suppressing the postoperative increase in the BT set point, rather than lowering the threshold for shivering, as observed with clonidine.

Comparison of blood pressure values-self-measured at home, measured at an unattended office, and measured at a conventional attended office.

Self-measured blood pressure (BP) at home (HBP) has been commonly used in clinical practice. Although the unattended office BP (UBP), in which a patient is left alone before and during the measurement, has been investigated, the advantages of UBP over HBP or conventionally measured attended office BP obtained using automated devices (CBP) remain unclear. We performed a multicenter clinical study in Japan to compare the UBP, CBP, and HBP among 308 patients with hypertension at 3 clinics (women, 57.8%; mean age 71.8 years; under antihypertensive drug therapy, 96.4%). The patients measured HBP twice in the morning and twice in the evening for 5 days according to the Japanese Society of Hypertension guidelines. Using the Omron HEM-907 cuff-oscillometric device, the UBP and CBP were measured in line with the protocol in the Systolic blood PRessure INtervention Trial (SPRINT) and in accordance with the guidelines, respectively. Correlation coefficients were ≤0.16 for the comparison of UBP versus morning and evening HBP for the systolic measurement, whereas they were approximately 0.5 (P < 0.001) for the diastolic measurement. The difference between UBP minus HBP was small on average but varied among individuals (mean ± SD for UBP minus morning HBP: 0.9 ± 17.8/-4.5 ± 10.5 mmHg; UBP minus evening HBP: 5.7 ± 17.8/-0.1 ± 11.3 mmHg). In contrast, the measurement values of CBP and UBP were highly correlated (r ≥ 0.72), but the difference between CBP minus UBP was 10.4 ± 12.0/4.2 ± 6.5 mmHg. Based on the low correlations and wide range of differences, UBP cannot be used as an alternative to HBP.

Rationale and design of a multicenter placebo-controlled double-blind randomized trial to evaluate the effect of empagliflozin on endothelial function: the EMBLEM trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by systemic metabolic abnormalities and the development of micro- and macrovascular complications, resulting in a shortened life expectancy. A recent cardiovascular (CV) safety trial, the EMPA-REG OUTCOME trial, showed that empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, markedly reduced CV death and all-cause mortality and hospitalization for heart failure in patients with T2DM and established CV disease (CVD). SGLT2 inhibitors are known to not only decrease plasma glucose levels, but also favorably modulate a wide range of metabolic and hemodynamic disorders related to CV pathways. Although some experimental studies revealed a beneficial effect of SGLT2 inhibitors on atherosclerosis, there is a paucity of clinical data showing that they can slow the progression of atherosclerosis in patients with T2DM. Therefore, the EMBLEM trial was designed to investigate whether empagliflozin treatment can improve endothelial function, which plays a pivotal role in the pathogenesis of atherosclerosis, in patients with T2DM and established CVD. METHODS: The EMBLEM trial is an ongoing, prospective, multicenter, placebo-controlled double-blind randomized, investigator-initiated clinical trial in Japan. A total of 110 participants with T2DM (HbA1c range 6.0-10.0%) and with established CVD will be randomized (1:1) to receive either empagliflozin 10 mg once daily or a placebo. The primary endpoint of the trial is change in the reactive hyperemia (RH)-peripheral arterial tonometry-derived RH index at 24 weeks from baseline. For comparison of treatment effects between the treatment groups, the baseline-adjusted means and their 95% confidence intervals will be estimated by analysis of covariance adjusted for the following allocation factors: HbA1c (<7.0 or ≥7.0%), age (<65 or ≥65 years), systolic blood pressure (<140 or ≥140 mmHg), and current smoking status (nonsmoker or smoker). Key secondary endpoints include the change from baseline for other vascular-related markers such as arterial stiffness, sympathetic nervous activity, and parameters of cardiac and renal function. Importantly, serious adverse effects independently on the causal relationship to the trial drugs and protocol will be also evaluated throughout the trial period. DISCUSSION: EMBLEM is the first trial to assess the effect of empagliflozin on endothelial function in patients with T2DM and established CVD. Additionally, mechanisms associating empagliflozin-mediated actions with endothelial function and other CV markers will be evaluated. Thus, the trial is designed to elucidate potential mechanisms by which empagliflozin protects CV systems and improves CV outcomes. Trial registration Unique Trial Number, UMIN000024502 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028197 ).