Impact of diabetes mellitus and triglyceride glucose index on mortality and cardiovascular outcomes in patients with chronic coronary syndrome undergoing coronary computed tomography angiography.

Background: There is limited knowledge regarding whether an elevated triglyceride glucose (TyG) index can serve as a prognostic marker for mortality and cardiovascular outcomes, independent of diabetes mellitus (DM) and plaque burden, in patients with chronic coronary syndrome (CCS). Methods: Patients with CCS (n = 684) were categorized into subgroups based on the presence of DM, and patients without DM were further divided into two groups based on presence or absence of an elevation of TyG index >8.8. Coronary plaque burden was evaluated using coronary computed tomography angiography. Major cardiovascular adverse event (MACE) was defined as a composite event of nonfatal myocardial infarction, unstable angina or unplanned coronary revascularization, stroke, non-cardiovascular mortality and cardiovascular mortality. Results: Patients without DM exhibited significantly greater plaque and epicardial adipose tissue volumes than those with DM. Multivariable Cox proportional hazards models demonstrated that DM and an elevated TyG index >8.8 were independently associated with the risk of MACE after adjusting for age, sex, and plaque volume. Patients with DM (hazard ratio, 3.74; 95% confidence interval, 1.97-7.08; p < 0.001) and patients without DM with an elevated TyG index (hazard ratio, 1.99; 95% confidence interval, 1.01-3.91; p = 0.045) had an increased risk of MACE. Conclusion: This study indicates that DM and an elevated TyG index are predictors of MACE, independent of plaque volume, in patients with CCS.

Thoracic Aortic Plaque Burden and Prediction of Cardiovascular Events in Patients Undergoing 320-row Multidetector CT Coronary Angiography.

AIM: Wide volume scan (WVS) coronary computed tomography angiography (CCTA) enables aortic arch visualization. This study assessed whether the thoracic aortic plaque burden (TAPB) score can predict major cardiovascular adverse events (MACE) in addition to and independently of other obstructive coronary artery disease (CAD) attributes. METHODS: This study included patients with suspected CAD who underwent CCTA (n=455). CCTA-WVS was used to assess CAD and the prognostic capacity of TAPB scores. Data analysis included the coronary artery calcification score (CACS), CAD status and extent, and TAPB score, calculated as the sum of plaque thickness and plaque angle at five thoracic aortic segments. The primary endpoint was MACE defined as a composite event comprised of ischemic stroke, acute coronary syndrome, and cardiovascular death. RESULTS: During a mean follow-up period of 2.8±0.9 years, 40 of 455 (8.8%) patients experienced MACE. In the Cox proportional hazards model adjusted for clinical risks (Suita cardiovascular disease risk score), we identified TAPB score (T3) as a predictor of MACE independent of CACS ＞400 (hazards ratio [HR], 2.91; 95% confidence interval [CI], 1.26-6.72; p=0.012) or obstructive CAD (HR, 2.83; 95% CI, 1.30-6.18; p=0.009). The area under the curve for predicting MACE improved from 0.75 to 0.795 (p value=0.008) when TAPB score was added to CACS ＞400 and obstructive CAD. CONCLUSIONS: We found that comprehensive non-invasive evaluation of TAPB and CAD has prognostic value in MACE risk stratification for suspected CAD patients undergoing CCTA.

Evaluations of coronary microvascular dysfunction in a patient with thrombotic microangiopathy and cardiac troponin elevation: a case report.

Background: Thrombotic microangiopathy (TMA) syndromes include thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome, and contribute to myocardial infarction and multiple organ failure. Although coronary microvascular dysfunction (CMD) is the key for understanding the pathophysiology of cardiac involvement in TMA, there is limited knowledge on the recovery from CMD in patients with TMA. Case summary: An 80-year-old woman was brought to the emergency department due to worsening back pain, dyspnoea on exertion, jaundice, and fever. Although she had typical TTP symptoms and elevated cardiac troponin level, ADAMTS13 activity was preserved (34%), leading to the diagnosis of TMA with myocardial infarction. She underwent plasma exchange and was administered aspirin and prednisolone. Magnetic resonance imaging revealed iliopsoas abscess, which is a possible aetiologic factor of sepsis-related TTP. She had impaired coronary flow reserve (CFR) with angiographically non-obstructive epicardial coronary arteries. Improved CFR was observed on follow-up, suggesting existence of transient CMD caused by TMA. After treatment of the iliopsoas abscess with antibiotics for 3 months, she was discharged without any adverse complications. Discussion: Coronary microvascular dysfunction is an underlying mechanism of myocardial infarction, with or without epicardial obstructive coronary artery stenosis. TMA is characterized by pathological lesions caused by endothelial cell damage in small terminal arteries and capillaries, with complete or partial occlusion caused by platelet and hyaline thrombi. CMD and its recovery are keys for understanding the natural history of cardiac involvement in TMA. In vivo evaluations of CMD can provide mechanistic insights into the cardiac involvement in TMA.

Extent of coronary atherosclerosis is associated with deterioration of left ventricular global longitudinal strain in patients with preserved ejection fraction undergoing coronary computed tomography angiography.

Background: This study aimed to investigate the association between the extent and severity of coronary atherosclerosis, epicardial adipose tissue (EAT) accumulation, and left ventricular (LV) global longitudinal strain (GLS) in patients with preserved LV ejection fraction (LVEF) and without LV regional wall motion abnormalities. Methods: This study included 169 preserved LVEF patients without LV wall motion abnormalities who underwent coronary computed tomography (CT) angiography for the assessment of suspected coronary artery disease (CAD). The segment stenosis score (SSS) and segment involvement score (SIS) were calculated to evaluate CAD extent. The EAT volume was defined as CT attenuation values ranging from -250 to -30 HU within the pericardial sac. LVGLS was measured using echocardiography to assess subclinical LV dysfunction. Results: All patients had preserved LVEF of ≥50%, and the mean LVGLS was -18.7% (-20.5% to -16.9%). Mean SSS and SIS were 2.0 (0-5) and 4.0 (0-36), respectively, while mean EAT volume was 116.1 mL (22.9-282.5 mL). Multivariate analysis using linear regression model demonstrated that LVEF (ß, -17.0; 95% CI, -20.9 - -13.1), LV mass index (ß, 0.03; 95% CI, 0.01-0.06), and EAT volume (ß, 0.010; 95% CI, 0.0020-0.0195) were independently associated with LVGLS; however, obstructive CAD was not. The multivariate models demonstrated that SSS (Î, 0.12; 95% CI, 0.05-0.18) and SIS (Î, 0.27; 95% CI, 0.10-0.44) were correlated with deterioration of LVGLS, independent of other parameters. Conclusion: This study demonstrates that EAT volume and CAD extent are associated with the deterioration of LVGLS in this population.

Aortic arch plaque morphology in patients with coronary artery disease undergoing coronary computed tomography angiography with wide-volume scan.

BACKGROUND: Wide-volume scanning with 320-row multidetector computed tomography coronary angiography (CTCA-WVS) enables the assessment of the aortic arch plaque (AAP) morphology and coronary arteries without requiring additional contrast volume. This study aimed to investigate the prevalence of AAPs and their association with coronary artery disease (CAD) and major adverse cardiovascular events (MACEs) in patients who underwent CTCA-WVS. METHODS: This study included 204 patients without known CAD (mean age, 65 years; 53% men) who underwent CTCA-WVS. We evaluated the presence of aortic plaques in the ascending aorta, aortic arch, and thoracic descending aorta using CTCA-WVS. Large aortic plaques were defined as plaques of at least 4 mm in thickness. A complex aortic plaque was defined as a plaque with ulceration or protrusion. MACEs were defined as composite events of cardiovascular (CV) death, nonfatal myocardial infarction, and ischemic stroke. RESULTS: AAPs and large/complex AAPs were identified in 51% ( n = 105) and 18% ( n = 36) of the study patients, respectively. The prevalence of AAPs with large/complex morphology increased with CAD severity (2.1% in no CAD, 12% in nonobstructive CAD, and 39% in obstructive CAD). The univariate Cox hazard model demonstrated that the predictors associated with MACEs were diabetes, obstructive CAD, and large/complex AAPs. Independent factors associated with large/complex AAPs were male sex [odds ratio (OR), 2.90; P = 0.025], stroke history (OR, 3.48; P = 0.026), obstructive CAD (OR, 3.35; P = 0.011), and thoracic aortic calcification (OR, 1.77; P = 0.005). CONCLUSION: CTCA-WVS provides a comprehensive assessment of coronary atherosclerosis and thoracic aortic plaques in patients with CAD, which may improve the stratification of patients at risk for CV events.

Microgravity promotes osteoclast activity in medaka fish reared at the international space station.

The bone mineral density (BMD) of astronauts decreases specifically in the weight-bearing sites during spaceflight. It seems that osteoclasts would be affected by a change in gravity; however, the molecular mechanism involved remains unclear. Here, we show that the mineral density of the pharyngeal bone and teeth region of TRAP-GFP/Osterix-DsRed double transgenic medaka fish was decreased and that osteoclasts were activated when the fish were reared for 56 days at the international space station. In addition, electron microscopy observation revealed a low degree of roundness of mitochondria in osteoclasts. In the whole transcriptome analysis, fkbp5 and ddit4 genes were strongly up-regulated in the flight group. The fish were filmed for abnormal behavior; and, interestingly, the medaka tended to become motionless in the late stage of exposure. These results reveal impaired physiological function with a change in mechanical force under microgravity, which impairment was accompanied by osteoclast activation.

Remote ischemic conditioning improves coronary microcirculation in healthy subjects and patients with heart failure.

BACKGROUND: Remote ischemic conditioning (RIC) is a treatment modality that suppresses inflammation and improves endothelial function, which are factors involved in the pathogenesis of heart failure (HF) with reduced left ventricular ejection fraction. Coronary flow reserve (CFR) is a physiological index of coronary microcirculation and is noninvasively measured by transthoracic Doppler echocardiography (TTDE). This study aimed to investigate the effects of RIC on CFR in healthy subjects and patients with HF, through the assessment by TTDE. METHODS: Ten patients with HF with left ventricular ejection fraction of less than 40%, and ten healthy volunteers were enrolled in this study. RIC treatment was performed twice a day for 1 week. Our custom-made RIC device was programmed to automatically conduct 4 cycles of 5 minutes inflation and 5 minutes deflation of a blood pressure cuff to create intermittent arm ischemia. CFR measurements and laboratory tests were examined before, and after 1 week of RIC treatment. RESULTS: One week of RIC treatment was well tolerated in both groups. RIC treatment increased CFR from 4.0 ± 0.9 to 4.6 ± 1.3 (mean ± standard deviation) in healthy subjects (P=0.02), and from 1.9 ± 0.4 to 2.3 ± 0.7 in patients with HF (P = 0.03), respectively. Systolic blood pressure in healthy subjects, and heart rate in HF patients decreased after RIC treatment (both P<0.01). CONCLUSION: This study demonstrated that a 1 week course of RIC treatment improved coronary microcirculation in healthy subjects and patients with HF associated with reduced left ventricular ejection fraction.

Very rapid effect of pitavastatin on microvascular function in comparison to rosuvastatin: reactive hyperemia peripheral arterial tonometric study.

BACKGROUND: It has been reported that pitavastatin improves endothelial function faster than other statins. Recently introduced reactive hyperemia peripheral arterial tonometry (RH-PAT) provides objective and quantitative assessment of peripheral microvascular function. PURPOSE: This study aimed to investigate whether peripheral microvascular function improved 2 hours after pitavastatin in subjects with coronary artery disease (CAD) using RH-PAT, and the results were compared with those of rosuvastatin. METHODS: This study included 94 subjects with CAD, assigned to a group given 2 mg of pitavastatin (n = 36), a group given 2.5 mg of rosuvastatin (n = 38), and a control group (n = 20). RH-PAT examinations were performed before and 2 hours after statin administration. RESULTS: The RH-PAT index increased 2 hours after pitavastatin administration from 1.82 ± 0.45 to 2.16 ± 0.62 (P = 0.02), whereas there were no differences in the RH-PAT index in the rosuvastatin group (1.79 ± 0.71 to 1.91 ± 0.53, P = 0.09) and the control group (1.68 ± 0.36 to 1.84 ± 0.58, P = 0.4). No significant changes were observed at 2 hours in serum cholesterol levels in each group. CONCLUSION: The present study demonstrated that peripheral microvascular function improved 2 hours after a single clinical dose of pitavastatin, but not after rosuvastatin.

Aorto-renal bypass surgery normalized blood pressure without antihypertensive medications in a young female patient with renal artery occlusion.

We described a 19 year old female case with renovascular hypertension, whose blood pressure was high taking antihypertensive medications. The right renal artery was completely occluded at its ostium, and percutaneous transluminal renal angioplasty was unsuccessful. After aortorenal bypass surgery, blood pressure was normalized without administration of antihypertensive medication.

Circadian variation in coronary flow velocity reserve and its relation to α1-sympathetic activity in humans.

BACKGROUND: The circadian change in coronary microvascular function has not been directly assessed in human beings. Recent advances in transthoracic Doppler echocardiography (TTDE) provide noninvasive, physiological assessment of coronary flow velocity reserve (CFVR). METHODS: This study consisted of 20 young healthy subjects (24 ± 2 years, 20 men) who underwent CFVR examinations at 3 different times; early morning (6AM), late morning (11AM) and late evening (10PM). The flow velocity in the distal portion of the left anterior descending coronary artery was measured with TTDE at baseline and during adenosine infusion to calculate CFVR. These examinations were repeated with the intake of α1-blocker (prazosin 1mg) on the other day. RESULTS: CFVR showed a circadian variation with an increase from the early morning to the late morning, following a decrease to the late evening thereafter (4.4 ± 0.9 at 6AM; 5.2 ± 1.3 at 11AM; 4.2 ± 1.1 at 10PM, p<0.001). In the study with α1-blocker, CFVR was comparable between the early morning and the late morning, whereas CFVR in the late evening was lower than those in other 2 time points (5.0 ± 1.1 at 6AM; 4.9 ± 0.9 at 11AM; 4.3 ± 0.9 at 10PM, p<0.001). CONCLUSIONS: This study demonstrates that CFVR has a circadian variation in humans, with an increase from the late evening to the late morning. Adding α1-blocker ameliorated CFVR only in the early morning, indicating that α1-sympathetic activity plays a heterogeneous and important role in the circadian change of CFVR in humans.

Comparison of coronary microcirculation in female nurses after day-time versus night-time shifts.

Nightshift work, which is known to cause mental stress and disrupt normal biological diurnal rhythms, leads to endothelial dysfunction resulting in increased risk for cardiovascular disease. This study aimed to investigate the acute effect of night-shift work on coronary microcirculation through assessment of coronary flow reserve (CFR) by transthoracic Doppler echocardiography. This study consisted of 36 women nurses who underwent transthoracic Doppler echocardiographic examinations after working a nightshift and on a regular day without previous nightshift work. Flow velocity in the distal portion of the left anterior descending coronary artery was measured at baseline and during adenosine infusion. CFR was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. CFR after night work was lower than that on a regular workday (3.8 ± 0.6 vs 4.1 ± 0.6, p <0.001). Degree of decreases in CFR after night work was correlated to Framingham risk score (r = 0.35, p = 0.036). In conclusion, this study demonstrated that coronary microcirculation was impaired after nightshift work in women nurses.

Left atrial thrombus and prognosis after anticoagulation therapy in patients with atrial fibrillation.

BACKGROUND: Anticoagulation therapy reduces the risk of thromboembolic events by two-thirds in patients with atrial fibrillation (AF). The prevalence of left atrial thrombus (LAT) in AF patients with anticoagulation therapy has not been fully investigated. PURPOSE: To investigate the prevalence of LAT and its impact on the outcomes in patients with nonvalvular AF after anticoagulation therapy. METHODS: This study consisted of 231 patients with nonvalvular AF who had transthoracic (TTE) and transesophageal echocardiographic (TEE) examinations more than 3 weeks after anticoagulation therapy. The clinical and echocardiographic characteristics were evaluated. RESULTS: LAT was observed in 13 (8.8%) of 148 patients with sub-therapeutic anticoagulation, and in 3 (3.6%) of 83 patients with sufficient anticoagulation. The presence of LAT was associated with higher CHADS(2) score, decreased LA volume changes and the presence of spontaneous echocardiographic contrast (SEC) in patients with sub-therapeutic anticoagulation. Patients with LAT after sufficient anticoagulation were male with permanent AF who had decreased left ventricular systolic and diastolic function and dilated LA on TTE and SEC, and reduced appendage flow velocity on TEE. Patients with LAT had worse cardiovascular outcomes compared with those without LAT (p=0.02). CONCLUSIONS: We demonstrated that LAT was a univariate risk factor associated with worse cardiovascular outcomes, which was observed in 8.8% of patients with sub-therapeutic anticoagulation and 3.6% of patients with sufficient anticoagulation.

Aromatherapy alleviates endothelial dysfunction of medical staff after night-shift work: preliminary observations.

Night-shift work causes mental stress and lifestyle changes, and is recognized as a risk of cardiovascular diseases associated with impaired endothelial function. Aromatherapy is becoming popular as a complementary therapy that is beneficial for mental relaxation. The purpose of this study was to investigate the effect of aromatherapy on the endothelial function of medical staff after night-shift work. This study consisted of 19 healthy medical personnel (19 men, mean age 32 ± 7 years), including 11 physicians and 8 technicians. Aromatherapy was performed for 30 min by inhalation of the essential oil of lavender. Flow-mediated dilation (FMD) of the brachial artery was measured three times in each subject: on a regular workday, and after night-shift work before and immediately after aromatherapy. A control study was performed to assess the effect of a 30-min rest without aromatherapy. The mean value of sleep time during night-shift work was 3.3 ± 1.3 h. FMD after night-shift work was lower than on a regular workday (10.4 ± 1.8 vs. 12.5 ± 1.7%, P<0.001), which improved after aromatherapy (11.8 ± 2.5%, P=0.02 vs. before aromatherapy). FMD was stable in the control study (10.1 ± 1.9 vs. 10.1 ± 2.2%, P=0.9). This study demonstrated that night-shift work impaired endothelial function in medical staff, an effect that was alleviated by short-term aromatherapy.

"Passive exercise" using whole body periodic acceleration: effects on coronary microcirculation.

BACKGROUND: The whole body periodic acceleration (WBPA) system has recently been developed as a "passive exercise" device by providing increased pulsatile shear stress for improvement of endothelial function. This study aimed to investigate the short-term effect of WBPA on coronary flow reserve (CFR) through transthoracic Doppler echocardiography (TTDE) in healthy subjects and patients with coronary artery disease (CAD). METHODS: This study consisted of 15 healthy subjects and 20 patients with CAD who underwent CFR examination before and immediately after WBPA. The flow velocity in the distal portion of the left anterior descending coronary artery (LAD) was measured with TTDE at baseline and during adenosine infusion. Coronary flow reserve was calculated as the ratio of hyperemic to basal mean diastolic flow velocity. RESULTS: The WBPA treatment was completed in all 35 subjects without complications. There were no significant differences in heart rate and systolic blood pressure before and after WBPA. Whole body periodic acceleration increased CFR from 3.3 +/- 1.0 to 3.7 +/- 1.1 in the 35 subjects (P < .001). Coronary angiography showed significant LAD narrowing in 8 of the 20 CAD patients, but WBPA increased CFR from 2.4 +/- 0.4 to 2.7 +/- 0.5 in them as well (P < .01). CONCLUSIONS: This study demonstrates that WBPA improves CFR in healthy subjects and patients with CAD.

Developmental status of Aquatic Animal Experiment Facility, Aquatic Habitat (AQH), for International Space Station.

Mitsubishi Heavy Industries (MHI) and Japan Aerospace Exploration Agency (JAXA) have been studying Aquatic Animal Experiment Facility, Aquatic Habitat (AQH), for International Space Station (ISS). The AQH will have the capabilities to accommodate small freshwater fish and amphibian for maximum 90 days on orbit. Three-generations of small freshwater fish (medaka and zebrafish), and egg through metamorphosis of amphibian (African clawed toad) could be experimented by AQH. Various experimental functions such as automatic feeding, air-water interface, day/night cycle, video observation, and specimen sampling mechanism will be also equipped in AQH. The water circulation system was improved from the past aquatic facilities for Space Shuttle experiments under the consideration of the long life-time, and a brand-new specimen chamber was developed to equip the above various experimental functions. Currently the prototype model of water circulation system and specimen chambers have been manufactured and biological compatibility tests are being conducted with medaka. The current developmental status of AQH is summarized.