Significant impact of left ventricular assist device models on the value of flow-mediated dilation: effects of LVAD on endothelial function.

The precise physiological changes associated with the use of left ventricular assist device (LVAD) are not well characterized. We examined the impact of changes in hemodynamic state using LVAD on endothelial function. We measured flow-mediated vasodilation (FMD) to evaluate endothelial vasodilator function of the brachial artery in 53 patients (dilated cardiomyopathy: 39, ischemic cardiomyopathy: 4, and others: 10) with an implanted LVAD (DuraHeart, EVAHEART, or HeartMate II). We found that FMD value in the HeartMateII LVAD group (9.3% ± 2.9%) was significantly higher than those in the other two groups (EVAHEART: 6.7% ± 2.8% and DuraHeart: 6.2% ± 4.0%). Other factors that affected the FMD value were age (r = - 0.31, p = 0.026), Brinkman index (r = - 0.30, p = 0.029); however, aortic opening, aortic regurgitation, and other hemodynamic parameters such as cardiac index or pulmonary capillary wedge pressure did not correlate with FMD. Multivariate analyses revealed that the difference among the LVAD models most significantly affected the FMD values after adjusting for age and smoking status (t = 2.6, p = 0.014). Event free survival rate of death and cerebral infarction was not significantly different according to the value of FMD. The difference among the LVAD groups most significantly affected the state of endothelial function and it had more impact than other clinical factors.

The Clinical Efficacy of Endothelin Receptor Antagonists in Patients with Pulmonary Arterial Hypertension.

Therapeutic strategies for pulmonary arterial hypertension (PAH) have made remarkable progress over the last two decades. Currently, 3 types of drugs can be used to treat PAH; prostacyclins, phosphodiesterase 5 inhibitors, and endothelin receptor antagonists (ERA). In Japan, the first generation ERA bosentan was reimbursed in 2005, following which the 2nd generation ERAs ambrisentan and macitentan were reimbursed in 2009 and 2015, respectively. The efficacy of each ERA on hemodynamics in PAH patients remains to be elucidated. The aims of this study were to evaluate the hemodynamic effects of ERAs and compare these effects among each generation of ERAs.We retrospectively examined the clinical parameters of 42 PAH patients who were prescribed an ERA (15 bosentan, 12 ambrisentan, and 15 macitentan) and who underwent a hemodynamic examination before and after ERA introduction at our institution from January 2007 to July 2019.In a total of 42 patients, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were significantly decreased and cardiac index was significantly increased after ERA introduction (P < 0.001) and the World Health Organization-Functional class (WHO-Fc) was significantly improved after ERA introduction (P = 0.005). Next, in a comparison between 1st and 2nd generation ERAs, 2nd generation ERAs were found to have brought about greater improvements in hemodynamic parameters (mPAP and PVR. P < 0.01), heart rate, brain natriuretic peptide, arterial oxygen saturation, and mixed venous oxygen saturation than the 1st generation ERA bosentan.We conclude that all ERAs could successfully improve the hemodynamics of PAH patients and that the newer generation ERAs, ambrisentan and macitentan, seemed to be preferable to bosentan.

Clinical impact of newly developed atrial fibrillation complicated with longstanding ventricular fibrillation during left ventricular assist device support: A case report.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) improve survival and morbidity in patients with stage D heart failure. Management of LVADs for longer durations is necessary in some clinical settings, and a better understanding of the hemodynamics of patients using LVADs is warranted. Arrhythmia, including atrial (AA) and ventricular (VAs) arrhythmias, is a modifying factor of hemodynamics that is highly prevalent among patients with LVADs. However, the clinical impact of arrhythmias in various clinical settings in patients with LVAD, in which the hemodynamic load is likely to present as worsening of right heart failure, remains to be completely elucidated. CASE PRESENTATION: We describe the case of a patient under sustained ventricular fibrillation for extraordinarily long duration who was stabilized using LVAD support and in whom newly developed atrial fibrillation led to a significant worsening of right heart failure while using an LVAD. CONCLUSION: This case demonstrates the substantial clinical impact of AAs in the management of right heart failure using an LVAD.

The potential of cardiac rehabilitation as a method of suppressing abdominal aortic aneurysm expansion: a pilot study.

This study is a prospective evaluation of the effectiveness of cardiac rehabilitation (CR) in terms of clinical outcomes for small abdominal aortic aneurysms (AAA) that were previously reported in a retrospective cohort study. We conducted a prospective non-randomized trial on patients with small AAA (N = 40; mean age 75.0 ± 6.6 years). Patients were enrolled into one of two groups, rehabilitation (CR) or non-rehabilitation (non-CR) group. Only CR group participated in a supervised-CR program including bicycle ergometer for 150 days. The AAA expansion rate and the risk of AAA repair were compared between two groups. We also researched the relationship between AAA expansion rate and body composition, blood IL-6 and TGFß1 levels. The CR (N = 15) and non-CR groups (N = 25) were comparable in terms their baseline data. The CR group had a significantly smaller change in the maximal AAA size (- 1.3 ± 2.4 mm/years) compared to the non-CR group (2.0 ± 3.6 mm/years) (p < 0.01). The IL-6, and TGFß1 levels were unrelated to the changes in AAA size. There was mild positive correlation between the change in systolic blood pressure from rest to exercise and the AAA expansion rate (p = 0.06). The risk of AAA repair after 12 months was lower in the CR group compared to the non-CR group (0% vs. 28%, respectively). CR in patients with small AAA significantly suppressed AAA expansion and resulted in a lowered risk of AAA repair.Clinical trial Trial name: The study of the profitability and protective effect of cardiac rehabilitation on abdominal aortic aneurysm. Number: UMIN000028237. UTL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R0000323.

Correction to: The potential of cardiac rehabilitation as a method of suppressing abdominal aortic aneurysm expansion: a pilot study.

In the original publication of the article, under the result section.

Surface moisture influence on etch-and-rinse universal adhesive bonding.

PURPOSE: To evaluate whether surface moisture would influence the bonding effectiveness of universal adhesives in etch-and-rinse mode. METHODS: All-Bond Universal (AB), G-Premio Bond (GP) Prime&Bond Active (PB) and Scotchbond Universal Adhesive (SU) were evaluated. Shear bond strengths after 24 hours and 10,000 thermal cycles of universal adhesives to moist and dry enamel and dentin in etch-and-rinse mode were determined. Scanning electron microscopy observations of the adhesive interfaces were conducted. RESULTS: The bond durability of universal adhesive to dentin in etch-and-rinse mode was influenced by the surface moisture, unlike bond durability to enamel. The bond durability of AB and GP, but not PB and SU, to dentin in etch-and-rinse mode was different depending on the surface moisture. Surface moisture did not influence the thicknesses of the adhesive or hybrid layer of resin-dentin interfaces, but the length of resin tags in the moist group was longer than in the dry group. CLINICAL SIGNIFICANCE: Some universal adhesives, with the addition of specific components and optimization of water content, can achieve stable bonds regardless of surface moisture, but the surface moisture of dentin, although not enamel, is still a significant factor for universal adhesive bonding in etch-and rinse mode.

High-intensity aerobic interval training can lead to improvement in skeletal muscle power among in-hospital patients with advanced heart failure.

This study investigated the effectiveness and safety of interval training during in-hospital treatment of patients with advanced heart failure. Twenty-four consecutive patients with advanced symptomatic heart failure who were referred for cardiac transplant evaluation were recruited. After performing aerobic exercise for approximate intensity, high-intensity interval training (HIIT) was performed. The protocol consisted of 3 or 4 sessions of 1-min high-intensity exercise aimed at 80% of peak VO2 or 80% heart rate reserve, followed by 4-min recovery periods of low intensity. In addition to the necessary laboratory data, hand grip strength and knee extensor strength were evaluated at the start of exercise training and both at the start and the end of HIIT. Knee extensor strength was standardized by body weight. The BNP level at the start of exercise training was 432 (812) pg/mL and it significantly decreased to 254 (400) pg/mL (p < 0.001) at the end of HIIT. Hand grip strength did not change during course. By contrast, knee extensor strength significantly increased during HIIT [4.42 ± 1.43 â†’ 5.28 ± 1.45 N/kg, p < 0.001], whereas the improvement of knee extensor strength was not significant from the start of exercise training to the start of HIIT. In addition, the change in knee extensor strength during HIIT was significantly associated with the hemoglobin A1c level at the start of exercise (R = - 0.55; p = 0.015). HIIT has a positive impact on skeletal muscle strength among in-hospital patients with advanced heart failure.

Correction to: High-intensity aerobic interval training can lead to improvement in skeletal muscle power among in-hospital patients with advanced heart failure.

In the original publication of the article, the unit of hand in Fig. 2 was wrongly given as "N/kg" instead of "kg".

An exploratory study on the efficacy and safety of a BCAA preparation used in combination with cardiac rehabilitation for patients with chronic heart failure.

BACKGROUND: Sarcopenia is generally complicated with patients with chronic heart failure (CHF) and its presence negatively affects the course of heart failure, however effective nutritional intervention had not been elucidated yet. The primary objective of this study is to explore whether the addition of a branched-chain amino acid (BCAA) preparation for cardiac rehabilitation (CR) of patients with CHF further improves cardiopulmonary functions, skeletal muscle functions, and metabolism in comparison with conventional CR. METHODS: This is a randomized, parallel-group comparative study. The elderly patients that were participated in CR and complicated with left ventricular systolic or diastolic dysfunction are randomized into two groups, CR + BCAA and CR. 20 weeks later, the second randomization is performed, which divide subjects into two groups with and without BCAA intervention without CR. Primary outcome measure is the rate of change of the anaerobic threshold workload from baseline to post-intervention. Secondary outcome include parameters of exercise capacity, cardiac function and psychological status. DISCUSSION: In the current study the effect of a promising new intervention, BCAA, will be assessed to determine whether its addition to CR improve exercise capacity in patients with heart failure, who are generally complicated with sarcopenia. TRIAL REGISTRATION: This clinical trial was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR; JPRN-UMIN R000022440 ).

Comparison of enamel bond fatigue durability of universal adhesives and two-step self-etch adhesives in self-etch mode.

PURPOSE: To comparatively evaluate universal adhesives and two-step self-etch adhesives for enamel bond fatigue durability in self-etch mode. METHODS: Three universal adhesives (Clearfil Universal Bond; G-Premio Bond; Scotchbond Universal Adhesive) and three two-step self-etch adhesives (Clearfil SE Bond; Clearfil SE Bond 2; OptiBond XTR) were used. The initial shear bond strength and shear fatigue strength of the adhesive to enamel in self-etch mode were determined. RESULTS: The initial shear bond strengths of the universal adhesives to enamel in self-etch mode was significantly lower than those of two-step self-etch adhesives and initial shear bond strengths were not influenced by type of adhesive in each adhesive category. The shear fatigue strengths of universal adhesives to enamel in self-etch mode were significantly lower than that of Clearfil SE Bond and Clearfil SE Bond 2, but similar to that OptiBond XTR. Unlike two-step self-etch adhesives, the initial shear bond strength and shear fatigue strength of universal adhesives to enamel in self-etch mode was not influenced by the type of adhesive. CLINICAL SIGNIFICANCE: This laboratory study showed that the enamel bond fatigue durability of universal adhesives was lower than Clearfil SE Bond and Clearfil SE Bond 2, similar to Optibond XTR, and was not influenced by type of adhesive, unlike two-step self-etch adhesives.

The association between orthostatic increase in pulse pressure and ischemic heart disease.

The clinical meaning of changes in PP with posture remains unclear. We performed treadmill exercise testing on 144 subjects to diagnose ischemic heart disease, and measured the PPs in the supine and standing positions. The differences in the two PPs ranged between -35 and 45 mmHg. Eleven subjects were diagnosed with significant coronary ischemia. The differences in the PPs were significantly increased, and PP in the standing position was significantly elevated in these subjects. A large difference in the PPs in the standing and supine positions was associated with significant coronary ischemia, independent of significant covariables.

Brachial artery diameter has a predictive value in the improvement of flow-mediated dilation after aortic valve replacement for aortic stenosis.

Aortic stenosis (AS) is the most common valvular disease and aortic valve replacement (AVR) is one of its most effective interventions. AS affects not only the left ventricle, but also vascular function beyond the stenotic valve, which can lead to various types of vascular dysfunction. However, research evaluating the effect of AS on aortic vascular function is limited. In this study, we investigated clinical meaning to evaluate endothelial function in subjects with AS. From April 2011 to April 2012, 20 consecutive adult patients with degenerative AS (mean age, 74.7 ± 7.4 years; range 50-83 years) who underwent AVR at our institution were included in the study. We measured flow-mediated dilation (FMD) to evaluate the effect of AS on endothelial function. The difference between brachial artery diameter (BAD) before (4.0 ± 0.7 mm) and after AVR (3.9 ± 0.6 mm) was not significant (p = 0.043), but FMD significantly improved after AVR (from 3.1 ± 1.8 to 6.0 ± 2.7 %, p < 0.0001). We also analyzed FMD × BAD index, endogenous vasodilatory capability independent of BAD, resulting that it also significantly increased after AVR (12.3 ± 7.0-22.5 ± 9.3, p < 0.0001). We divided patients into two groups by pre- to post-AVR change in FMD (ΔFMD); large-ΔFMD group [ΔFMD >3.0 % (median value)] and small-ΔFMD group (ΔFMD <3.0 %). There were no significant changes in age, blood pressure, heart rate, B-type natriuretic peptide, or echocardiographic parameters in either group. In contrast, BAD was significantly larger in the small ΔFMD group (4.3 ± 0.7 mm) than in the large ΔFMD group (3.7 ± 0.7 mm) (p = 0.030). In addition, cardio-thoracic ratio was significantly greater in the small ΔFMD group (58.4 ± 7.1 %) than in the large ΔFMD group (53.7 ± 4.6 %) (p = 0.048). Receiver operating characteristic curve analysis of BAD to differentiate large and small ΔFMD demonstrated an area under the curve of 0.750 (p = 0.059) and that optimal cutoff for BAD was 4.28 mm (70 % sensitivity, 80 % specificity). AVR in subjects with AS is associated with a significant improvement in FMD in the brachial artery. Measurement of the BAD may be helpful in distinguishing whether the impairment of FMD in AS derives from a stenotic valve or vascular remodeling.

The association between orthostatic increase in pulse pressure and ischemic heart disease.

The clinical meaning of changes in PP with posture remains unclear. We performed treadmill exercise testing on 144 subjects to diagnose ischemic heart disease, and measured the PPs in the supine and standing positions. The differences in the two PPs ranged between -35 and 45 mmHg. Eleven subjects were diagnosed with significant coronary ischemia. The differences in the PPs were significantly increased, and PP in the standing position was significantly elevated in these subjects. A large difference in the PPs in the standing and supine positions was associated with significant coronary ischemia, independent of significant covariables.

Angiotensin II impairs endothelial nitric-oxide synthase bioavailability under free cholesterol-enriched conditions via intracellular free cholesterol-rich membrane microdomains.

Vascular endothelial function is impaired in hypercholesterolemia partly because of injury by modified LDL. In addition to modified LDL, free cholesterol (FC) is thought to play an important role in the development of endothelial dysfunction, although the precise mechanisms remain to be elucidated. The aim of this study was to clarify the mechanisms of endothelial dysfunction induced by an FC-rich environment. Loading cultured human aortic endothelial cells with FC induced the formation of vesicular structures composed of FC-rich membranes. Raft proteins such as phospho-caveolin-1 (Tyr-14) and small GTPase Rac were accumulated toward FC-rich membranes around vesicular structures. In the presence of these vesicles, angiotensin II-induced production of reactive oxygen species (ROS) was considerably enhanced. This ROS shifted endothelial NOS (eNOS) toward vesicle membranes and vesicles with a FC-rich domain trafficked toward perinuclear late endosomes/lysosomes, which resulted in the deterioration of eNOS Ser-1177 phosphorylation and NO production. Angiotensin II-induced ROS decreased the bioavailability of eNOS under the FC-enriched condition.

Diurnal body temperature rise is reduced in diabetes with autonomic neuropathy.

We conducted a retrospective study of 60 patients with ischemic heart disease (31 with diabetes and 29 without diabetes) to investigate the impact of diabetes on diurnal body temperature patterns. We found that the increase of axillary body temperature in the evening was reduced in the presence of diabetes, which was associated with autonomic neuropathy.

Impairment of flow-mediated dilation correlates with aortic dilation in patients with Marfan syndrome.

Marfan syndrome is an inherited disorder characterized by genetic abnormality of microfibrillar connective tissue proteins. Endothelial dysfunction is thought to cause aortic dilation in subjects with a bicuspid aortic valve; however, the role of endothelial dysfunction and endothelial damaging factors has not been elucidated in Marfan syndrome. Flow-mediated dilation, a noninvasive measurement of endothelial function, was evaluated in 39 patients with Marfan syndrome. Aortic diameter was measured at the aortic annulus, aortic root at the sinus of Valsalva, sinotubular junction and ascending aorta by echocardiography, and adjusted for body surface area (BSA). The mean value of flow-mediated dilation was 6.5 ± 2.4 %. Flow-mediated dilation had a negative correlation with the diameter of the ascending thoracic aorta (AscAd)/BSA (R = -0.39, p = 0.020) and multivariate analysis revealed that flow-mediated dilation was an independent factor predicting AscAd/BSA, whereas other segments of the aorta had no association. Furthermore, Brinkman index had a somewhat greater influence on flow-mediated dilation (R = -0.42, p = 0.008). Although subjects who smoked tended to have a larger AscAd compared with non-smokers (AscA/BSA: 17.3 ± 1.8 versus 15.2 ± 3.0 mm/m(2), p = 0.013), there was no significant change in flow-mediated dilation, suggesting that smoking might affect aortic dilation via an independent pathway. Common atherogenic risks, such as impairment of flow-mediated dilation and smoking status, affected aortic dilation in subjects with Marfan syndrome.

Simultaneous heart rate variability monitoring enhances the predictive value of flow-mediated dilation in ischemic heart disease.

BACKGROUND: Endothelial dysfunction and autonomic nervous system imbalance are both risk markers of atherosclerotic vascular damage. The relationship between these 2 factors, however, has not been clarified concisely. METHODS AND RESULTS: Flow-mediated dilation (FMD) was measured in 47 patients with ischemic heart disease (IHD; mean age, 68.1±7.1 years) using an ultrasound semi-automatic measuring system (UNEXEF18G), and autonomic nervous system activity was evaluated by simultaneous measurements of heart rate variability. FMD was significantly correlated with standard deviation of normal-to-normal beats (r=0.33, P=0.022) and the power ratio of low-frequency power to high-frequency power (LF/HF; r=-0.38, P=0.0087). Furthermore, multiple regression analysis indicated that LF/HF was the most important predictor of the magnitude of FMD. This interaction was severely blunted by ß-blockers and the presence of diabetes. Moreover, standardized FMD according to autonomic nervous system activity was a better predictor of future cardiovascular events than FMD. Subjects with cardiovascular events had a significantly smaller corrected FMD (event (+), 3.62±0.41; event (-), 5.10±2.35; P=0.001), and the higher corrected FMD was associated with longer event-free survival. CONCLUSIONS: Autonomic nervous system activity is an important regulatory factor of FMD in subjects with IHD. Assessment of this interaction can help provide more accurate risk stratification of subjects with IHD.

Differences in body temperature variability between subjects with and without diabetes and predictive value for cardiovascular events.

BACKGROUND: Differences in regulating factors and the clinical implications of body temperature variability (BTV) between subjects with and without diabetes have not been clarified to date. METHODS AND RESULTS: In 66 subjects with ischemic heart disease (33 with diabetes and 33 without diabetes), BTV, the difference between the highest and lowest temperature measurements, and body temperature standard deviation (BT SD) were measured from axillary body temperature (ABT) records of 3 consecutive days and followed for 16.4±8.4 months. In subjects without diabetes BTV and BT SD were closely associated with endothelial function as evaluated on flow-mediated dilation (BTV, R=0.33, P=0.026; BT SD, R=0.41, P=0.029), whereas there was a poor association in subjects with diabetes. In the absence of an interrelationship between vascular function and thermoregulation, the contribution of inflammation to BTV was increased in subjects with diabetes (BTV, 0.59±0.21°C for C-reactive protein [CRP] <0.08 mg/dl vs. 0.79±0.28°C for CRP >0.08 mg/dl, P=0.014). Event-free survival analysis showed that in subjects with diabetes higher BT SD was associated with shorter event-free survival (log-rank P=0.012), but this relationship was not found in subjects without diabetes. CONCLUSIONS: In subjects with diabetes, the interrelationship between thermoregulation and vascular function was disrupted and the effect of inflammation on thermoregulation was enhanced, so that BTV had a sufficient predictive value for cardiovascular events in diabetic subjects.

Ability of barrier coat S-PRG coating to arrest artificial enamel lesions in primary teeth.

PURPOSE: To evaluate the effects of a surface pre-reacted glass-ionomer (S-PRG) filled coating material to arrest artificial enamel lesions in primary teeth. METHODS: Buccal and lingual enamel was demineralized in 0.1 M lactic acid buffer solution (pH 4.75) for 5 days and then divided in the PRG-applied and non-PRG areas. Proximal surfaces were used as a control area without demineralization and coating application. Teeth were divided into three groups (n = 4) according to the 1-week immersion in different solutions: Group 1 (distilled water), Group 2 (demineralizing solution) and Group 3 (artificial saliva). Hardness and Young's modulus by nano-indentation test, and elemental contents and ultrastructure by SEM/EDX analysis were obtained. Data were statistically analyzed using ANOVA and Fisher's PLSD at alpha = 0.05. RESULTS: Only for the non-PRG area in Group 1, the hardness and Young's modulus of the demineralized surface enamel were significantly lower than those of the enamel 30-60 microm beneath the surface. Demineralized enamel of non-PRG and PRG-applied areas showed similar SEM views. Only for the non-PRG area in Group 2 and control area in Group 3, the Ca/P of the surface enamel was significantly higher than that of the enamel 5-10 microm beneath the surface. There was no significant difference of the Ca/P among the measuring points from the surface to 10 microm depth of enamel for the PRG applied area in Group 2.