Effects of Bisoprolol Transdermal Patches for Prevention of Perioperative Myocardial Injury in High-Risk Patients Undergoing Non-Cardiac Surgery　- Multicenter Randomized Controlled Study.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of transdermal ß-blocker patches, which offer stable blood concentration and easy availability during operation, for prevention of perioperative myocardial injury (PMI) in high-risk patients.Methods and Results:In this randomized controlled trial, patients aged >60 years with hypertension and high revised cardiac risk index (≥2) undergoing non-cardiac surgery were randomly assigned to a bisoprolol patch or control group. Primary efficacy outcome was incidence of PMI, defined as postoperative high-sensitivity cardiac troponin T (hs-cTnT) >0.014ng/mL and relative hs-cTnT change ≥20%. Secondary efficacy outcomes were number of cardiovascular events and 30-day mortality. From November 2014 to February 2019, 240 patients from 5 hospitals were enrolled in this study. The incidence of PMI was 35.7% in the bisoprolol patch group and 44.5% in the control group (P=0.18). Incidence of major adverse cardiac events including non-critical myocardial infarction, strokes, decompensated heart failure and tachyarrhythmia was similar between the 2 groups. Tachyarrhythmia tended to be higher in the control group. There were no significant differences in safety outcomes including significant hypotension and bradycardia requiring any treatment between the 2 groups. CONCLUSIONS: Bisoprolol patches do not influence the incidence of PMI and cardiovascular events in high-risk patients undergoing non-cardiac surgery, but perioperative use of these patches is safe.

Influence of skin blood flow on near-infrared spectroscopy signals measured on the forehead during a verbal fluency task.

Brain activity during a verbal fluency task (VFT) has been the target of many functional imaging studies. Most studies using near-infrared spectroscopy (NIRS) have reported major activation in the frontal pole, but those using PET or fMRI have not. This led us to hypothesize that changes in the NIRS signals measured in the forehead during VFT were due to changes in skin blood flow. To test this hypothesis, we measured NIRS signals and the Doppler tissue blood flow signals in the foreheads of 50 participants. The measurements were performed while each participant produced words during two 60-s periods with an interval of 100 s. In addition to a conventional optode separation distance of 30 mm (FAR channels), we used a short distance--5mm (NEAR channels)--to measure NIRS signals that originated exclusively from surface tissues. The oxygenated hemoglobin (oxyHb) concentration in the FAR and NEAR channels, as well as the Doppler blood flow signal, increased in a similar manner during the two periods of word production; the signal increase in the first period was twice as high as that in the second period. Accordingly, the mean changes in oxyHb concentration in the FAR channels were correlated closely with the changes in the NEAR channels (R(2) = 0.91) and with the integrated Doppler skin blood flow signal (R(2) = 0.94). Furthermore, task-related NIRS responses disappeared when we blocked skin blood flows by pressing a small area that covered a pair of optodes. Additionally, changes in the FAR channel signals were correlated closely with the magnitude of pulsatile waves in the Doppler signal (R(2) = 0.92), but these signals were not highly correlated with the pulse rate (R(2) = 0.43). These results suggest that a major part of the task-related changes in the oxyHb concentration in the forehead is due to task-related changes in the skin blood flow, which is under different autonomic control than heart rate.

Preventative effects of bisoprolol transdermal patches on postoperative atrial fibrillation in high-risk patients undergoing non-cardiac surgery: A subanalysis of the MAMACARI study.

BACKGROUND: Perioperative atrial fibrillation (POAF) after non-cardiac surgery is a risk factor for cardiovascular events including stroke and death. The aim of this subanalysis of the MAMACARI study, a multicenter randomized control study on the effectiveness of a bisoprolol transdermal patch for prevention of perioperative myocardial injury in high-risk patients undergoing non-cardiac surgery, was to identify the predictors of POAF after non-cardiac surgery in high-risk patients and to determine changes in blood pressure and heart rate during bisoprolol patch administration in the perioperative period. METHODS AND RESULTS: Patients aged over 60 years with hypertension and a high revised cardiac risk index (≥2) who were scheduled to undergo non-cardiac surgery were randomly assigned to a bisoprolol patch group (n = 120) or a control group (n = 120). We divided the patients into two groups: patients with POAF (POAF group; n = 16) and patients without POAF (non-POAF group; n = 206). Multivariate analysis showed that bisoprolol patch therapy (OR: 0.30, 95% CI: 0.092-0.978) and surgery time of 250 min or more (OR: 4.99, 95% CI: 1.37-18.2) were independently associated with POAF. Although systolic blood pressure did not differ significantly between the two groups throughout the perioperative period, treatment with a bisoprolol patch significantly reduced heart rate throughout the perioperative period compared with that in the control group. CONCLUSIONS: Low dose of a bisoprolol patch in the perioperative period was effective for prevention of POAF after non-cardiac surgery in high-risk patients, while long surgery time was an independent risk factor for POAF. It is expected that low dose of a bisoprolol patch can prevent POAF without causing hypotension.

A case of biventricular thrombi in a patient with dilated cardiomyopathy: Utility of multimodality imaging for diagnosis and management of treatment strategy.

A 54-year-old man was transferred to our hospital due to congestive heart failure and left ventricular thrombi. Transthoracic echocardiography (TTE) showed mobile "ball-like" not only left ventricular but also right ventricular thrombi associated with severe impaired left and right ventricular function. Contrast-enhanced computed tomography (CT) and cardiac magnetic resonance imaging (MRI) also detected biventricular apical thrombi complicated with right renal infarction. Coronary angiography showed non-significant stenosis. Due to the mobility of thrombi and complication of systemic infarction, the surgical transatrial video-assisted removal of biventricular thrombi was performed and postoperative course has been uneventful over a period of 6 months. Endomyocardial biopsy performed during an operation showed no specific findings such as endomyocarditis, indicating the diagnosis of dilated cardiomyopathy (DCM). This is a rare case of DCM complicated with biventricular apical thrombi detected clearly by multimodality imaging such as TTE, contrast-enhanced CT and cardiac MRI, and surgical removal was performed successfully. .

Bayesian calibration of simultaneity in audiovisual temporal order judgments.

After repeated exposures to two successive audiovisual stimuli presented in one frequent order, participants eventually perceive a pair separated by some lag time in the same order as occurring simultaneously (lag adaptation). In contrast, we previously found that perceptual changes occurred in the opposite direction in response to tactile stimuli, conforming to bayesian integration theory (bayesian calibration). We further showed, in theory, that the effect of bayesian calibration cannot be observed when the lag adaptation was fully operational. This led to the hypothesis that bayesian calibration affects judgments regarding the order of audiovisual stimuli, but that this effect is concealed behind the lag adaptation mechanism. In the present study, we showed that lag adaptation is pitch-insensitive using two sounds at 1046 and 1480 Hz. This enabled us to cancel lag adaptation by associating one pitch with sound-first stimuli and the other with light-first stimuli. When we presented each type of stimulus (high- or low-tone) in a different block, the point of simultaneity shifted to "sound-first" for the pitch associated with sound-first stimuli, and to "light-first" for the pitch associated with light-first stimuli. These results are consistent with lag adaptation. In contrast, when we delivered each type of stimulus in a randomized order, the point of simultaneity shifted to "light-first" for the pitch associated with sound-first stimuli, and to "sound-first" for the pitch associated with light-first stimuli. The results clearly show that bayesian calibration is pitch-specific and is at work behind pitch-insensitive lag adaptation during temporal order judgment of audiovisual stimuli.