Antimicrobial effect of oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol against intraoral pathogenic microorganisms.

OBJECTIVE: Deterioration of oral hygiene is closely related to an increase in severity and mortality of corona virus disease-19 (COVID-19), and also contributes to the development of various diseases such as aspiration pneumonia or Alzheimer's. Oral care is attracting high interest in Japan, which has entered a super-aging society. In this study, we aimed to investigate whether commercially available Hinora® (HO), an oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol (IPMP), has biofilm formation inhibitory and antimicrobial activities against various intraoral pathogen microorganisms. METHOD: Candida species, Aggregatibacter actinomycetemcomitans, Staphylococcus aureus, and Pseudomonas aeruginosa were selected during the study period, all of which were analyzed using antimicrobial disc, microorganism turbidity, and crystal violet assays. In addition, the germ tube test using Candida albicans (C. albicans) was performed with a modification of Mackenzie's method. Images for morphological observation of the germ tubes were acquired using an inverted microscope. For comparison between products, we used Refrecare® (RC), which only contains hinokitiol (not containing IPMP). RESULTS: All the intraoral pathogenic microorganisms showed drug susceptibility against undiluted forms of HO and/or RC. In particular, HO was more effective at lower concentrations than RC. In the HO-added group, inhibition circles were observed in all bacteria except P. aeruginosa when added at a concentration of 0.5 g/mL or more. The optical density values at 590 nm (crystal violet) and/or 600 nm (microorganism turbidity) of all the fungi and bacteria were significantly lower when cultured in medium with HO. Inhibition of growth or biofilm formation was observed when HO was added at a concentration of 0.05 g/mL or higher. To investigate the action mechanism of HO, germ tube tests were performed in C. albicans. The results showed that culturing C. albicans in soybean-casein digest broth with HO (0.05 g/mL) significantly suppressed germ tube formation. CONCLUSIONS: These data suggest that oral care gel-containing hinokitiol and IPMP has strong biofilm formation inhibitory activity, as well as antifungal and antimicrobial effects against Candida fungi and multiple intraoral pathogenic microorganisms. Therefore, it may be a promising treatment option for oral infections.

Activation recovery interval as an electrocardiographic repolarization index to detect doxorubicin-induced cardiotoxicity.

BACKGROUND: It has been reported that early detection and treatment of cancer therapy- related cardiac dysfunction (CTRCD) improves its prognosis. The detailed relationships between electrocardiographic repolarization indices and decreased left ventricular function in CTRCD have not been elucidated. We closely assessed such relationships in patients with doxorubicin (DOX)-induced CTRCD. METHODS: This retrospective, single-center, cohort study included 471 consecutive patients with malignant lymphoma who received chemotherapy including DOX. Of them, 17 patients with CTRCD and 68 patients without CTRCD who underwent 12­lead electrocardiogram and an echocardiogram before and after chemotherapy were eventually analyzed. The fluctuations of the following electrocardiographic repolarization indices were evaluated in lead V5: QT, JT, T peak to T end interval (Tp-e), and activation recovery interval (ARI). These indices were corrected by heart rate with the Fridericia formula. RESULTS: The median period from the end of chemotherapy to the diagnosis of the CTRCD group was 346 days (IQR 170-1283 days). After chemotherapy, the QT interval was significantly prolonged in both with and without CTRCD groups compared with that before chemotherapy (pre QTc vs. post QTc in CTRCD group, 386 ±â€¯27 ms vs. 411 ±â€¯37 ms, p = 0.03, pre QTc vs. post QTc in non-CTRCD group, 388 ±â€¯24 ms vs. 395 ±â€¯25 ms, p = 0.04, respectively). ARIc after chemotherapy was characteristically observed only in the CTRCD group (pre ARIc vs. post ARIc in CTRCD group, 258 ±â€¯53 ms vs. 211 ±â€¯28 ms, p = 0.03, pre ARIc vs. post ARIc in non-CTRCD group, 221 ±â€¯19 ms vs. 225 ±â€¯23 ms, NS, respectively) and had negative correlations with left ventricular ejection fraction (r = -0.56, p < 0.001). Using the receiver-operating characteristic curve, the relationship between ARIc and CTRCD morbidity was examined. The optimal cut-off point of ARIc prolongation between before and after chemotherapy was 18 ms (sensitivity 75 %, specificity 79 %, area under the curve 0.76). CONCLUSIONS: ARIc prolongation may be useful in the early detection of developing late-onset chronic DOX-induced CTRCD and lead to early treatment for cardiac protection.

Significance of mitral L-waves in predicting late recurrences of atrial fibrillation after radiofrequency catheter ablation.

BACKGROUND: The mitral L-wave, a prominent mid-diastolic filling wave in echocardiographic examinations, is associated with severe left ventricular diastolic dysfunction. The relationship between the mitral L-wave and outcome of catheter ablation (CA) in patients with atrial fibrillation (AF) has not been established. This study aimed to evaluate the predictive value of mitral L-waves on AF recurrence after CA. METHODS: This was a retrospective and observational study in a single center. One hundred forty-six patients (mean age; 63.9 [56.0-72.0] years, 71.9% male) including 66 non-paroxysmal AF patients (45.2%) who received a first CA were enrolled. The mitral L-waves were defined as a distinct mid-diastolic flow velocity with a peak velocity ≥20 cm/s following the E wave in the echocardiographic examinations before CA. The patients enrolled were divided into groups with (n = 31, 21.2%) and without (n = 115, 78.8%) mitral L-waves. Univariate and multivariate analyses were carried out to determine the predictive factors of late recurrences of AF (LRAFs), which meant AF recurrence later than 3 months after the CA. RESULTS: During a follow-up of 28.8 (15.0-35.8) months, the ratio of LRAFs in patients with mitral L-waves was significantly higher than that in those without mitral L-waves (15 [46.9%] vs. 16 [14.0%], p < .001). A multivariate analysis using a Cox proportional hazard model revealed that the mitral L-waves were a significant predictive factor of LRAFs (hazard ratio: 3.09, 95% confidence interval: 1.53-6.24, p = .002). CONCLUSION: The appearance of mitral L-waves could predict LRAFs after CA.

Physical oral care prevents ventilator-associated pneumonia in Vietnam: A prospective interventional study.

BACKGROUND: Ventilator-associated pneumonia (VAP) has emerged as a critical issue in the intensive care unit (ICU) because of its high burden on patients and medical staff. Here, we examined the potential for reducing VAP incidence through physical oral care interventions without any medication. METHODS: This prospective interventional study compared VAP incidence during an 8-month baseline period (usual oral care) and a 9-month intervention period (physical oral care with sponge brush) among patients who received mechanical ventilation for >48 h in a tertiary care hospital in Vietnam from 2017 to 2019. Physical oral care was provided by general ICU nurses who had been trained by dentists and infection control nurses. VAP was diagnosed using the Clinical Pulmonary Infection Score. RESULTS: In total, 423 patients were enrolled in the baseline group and 454 patients were enrolled in the intervention group; 303 and 300 patients, respectively, were included in the analysis. Two hundred thirty-eight VAP episodes were identified: 135 (44.6%) during the baseline period and 103 (34.3%) during the intervention period. Univariate analysis revealed significant reduction of VAP occurrence in the intervention period (odds ratio = 0.65; 95% confidence interval = 0.47-0.90; P = 0.010). The incidences of VAP per 1000 ventilator-days were 63.4 (135/2128) during the baseline period and 48.4 (103/2128) during the intervention period (P = 0.038). CONCLUSIONS: Physical oral care without any medication (e.g., chlorhexidine) reduced VAP incidence in the ICU. This method could be used to reduce VAP incidence, particularly in countries with limited medical resources.

Communication training for pharmacy students with standard patients using artificial intelligence.

INTRODUCTION: The objective structured clinical examination (OSCE) is among validated approaches used to assess clinical competence through structured and practical evaluation. Most studies of OSCE have used standardized patients (SPs). However, to our knowledge, there is limited information regarding the specific communication skills enhanced by providing communication training (CT) with SPs. Recently, an artificial intelligence (AI) technology was developed. The aim of this study was to evaluate the experience and outcomes of CT with SPs and impact of using AI for this training. METHODS: This study targeted fourth-year students participating in a pre-learning course for pharmacy practice experience offered at a Japanese university in 2020. The ENcode, Decode, Control, and REgulate model, which evaluates 24 communication skills, was utilized as a questionnaire-based survey. The survey was conducted prior to CT, following CT, and after a second CT session six weeks later with AI. RESULTS: Seven skills, namely "desire suppression," "expectation acceptance," "facial expression," "emotional communication," "dominance," "maintaining relationships," and "dealing with disagreements," were enhanced by the CT with SPs. These skills were included in the broad categories of "management" and "expression" skills. They were not significantly enhanced by following AI training. However, differences observed between the students who underwent AI training and those who did not demonstrated a positive effect in almost all skills, suggesting that AI training can enhance certain skills. CONCLUSIONS: CT with SPs enhances students' "management" and "expression" skills. Additionally, AI shows potential for improving the effect of CT.

[Growth and Control of Catheter-related Bloodstream Infection Causing Bacteria in Nutrient Solutions].

Among healthcare-associated infections, catheter-related bloodstream infection (CRBSI) shows a high case fatality rate and is serious threat. CRBSI are a problem to be eradicated. This study was conducted to reveal the growth characteristics of the causative microorganisms of CRBSI and investigate relevant control methods. The effects of biotin on growth of Candida albicans (C. albicans) in the nutrient solutions were investigated. Upon comparing general solutions and biotin-containing solutions, C. albicans showed auxotrophy against biotin, resulting in significant proliferative potential. CRBSI is caused by biofilm formation in the catheter lumen and subsequent proliferation. The effect of biotin on the colonization of C. albicans in the catheter lumen was evaluated. Candida albicans colonization in the catheter lumen and subsequent proliferation were significantly higher than those in control solutions. To investigate methods for CRBSI control, effects on pathogenic microorganisms were examined by screening for nutrient solutions with antimicrobial activity, using a catheter-lumen contamination model. A commercially available solution (PLAS-AMINO® injection; PA) containing the highest amount of sodium bisulfite was selected. Gram-positive or negative bacteria and C. albicans were used as the causative microorganisms of CRBSI in the study. Dripping PA into each catheter-lumen contamination model demonstrated bactericidal effects against all bacteria tested and strong growth-inhibitory effects on C. albicans. By using PA for contamination inside the catheter, sterilization and suppression of bacterial growth can be expected without having to remove central venous catheters and/or central venous access devices. This review provides valuable findings for the development of novel control methods for CRBSI.

Myocarditis Following a COVID-19 Messenger RNA Vaccination: A Japanese Case Series.

COVID-19 vaccine-related myocarditis has been reported worldwide. We herein report two Japanese cases with suspected vaccine-related myocarditis. A 27-year-old man was admitted with chest pain 4 days after the second vaccination. An electrocardiogram (ECG) did not reveal any significant abnormalities. The second patient, a 37-year-old man, was admitted with chest pain 9 days after the first vaccination. His ECG exhibited ST-elevation in multiple leads. In both cases, cardiac magnetic resonance imaging findings were consistent with myocarditis. They recovered with symptomatic relief within a few days. These cases suggest that the benefit of COVID-19 vaccination exceeds the risk of vaccine-related myocarditis.

[Survey of Nurse and Community Pharmacist Collaboration and Expectations of Nurses in Community Care Systems].

The purpose of this study was to clarify the current status of collaboration between nurses and community pharmacists as well as the requests and expectations that community pharmacists have of nurses in community-based comprehensive care systems. Questionnaires requiring open-ended responses were sent to 867 pharmacies throughout Fukushima prefecture (excluding four suspended pharmacies). We asked one pharmacist at each facility to answer the questions. We then analyzed the collected questionnaires using descriptive statistics, including the current status of nurse cooperation and the basic information about the pharmacies. Additionally, the open-ended descriptions of nurses' requests and expectations were analyzed quantitatively and qualitatively. The questionnaire collection rate was 32% (278 cases), and the breakdown of pharmacies that responded was 68.0% for facilities with 1 or 2 full-time pharmacists and 27.0% for facilities with 3 to 5 pharmacists. About 30% of respondents reported contact with the nursing profession at least once a week, while about 50% reported no contact at all or several times a year. The types of nurses collaborating with the pharmacies were clinic nurses (54.6%) and visiting nurses (43.4%). Some pharmacists had expected nurses to work cooperatively and rely on pharmacists. These results indicate that only about half of the pharmacists had opportunities to cooperate with nurses. For trust to be established between nurses and pharmacists, it is necessary for nurses to ask the pharmacists about medication and consult with them about patient medication management.

[Construction of Pre-clinical Practice and Survey of Consciousness for Pharmacy Students with Hearing Disability].

Various types of pre-learning-including pre-learning for practical training-provide pharmacy students with practical training and sufficient knowledge, skills, and attitudes for practical work. Opportunities in the medical field, including for pharmacists, have been greatly expanded for students with a hearing disability, and we have responded with appropriate training for such students. In this study, we report on the results of an evaluation of a survey on the preparatory training conducted by the students and the changes in their consciousness, such as in their level of understanding, knowledge, and self-confidence. Before the training, the participants' anxiety concerning items related to dispensing and communication were quite high; after the training, however, these anxiety levels were reduced. In addition, we were able to encourage the participant's concern for people and to face the difficulty of expressing words in letters, as well as to drive enthusiasm for the Objective Structured Clinical Examination (OSCE) and practical training. These results suggest that having a teacher as an assistant is useful for helping students with hearing disability in practical training.

Prognostic impact of transcatheter mitral valve repair in patients with exercise-induced secondary mitral regurgitation.

AIMS: Although exercise-induced secondary mitral regurgitation (MR) is known to have a poor prognosis, the therapeutic strategy towards this condition remains to be investigated. In the present study, we aimed to investigate the prognostic impact of transcatheter mitral valve repair (TMVr) using the MitraClip in patients with exercise-induced secondary MR. METHODS AND RESULTS: Of the 200 consecutive patients with secondary MR who underwent exercise stress echocardiography, 46 (23%) that presented with exercise-induced secondary MR [i.e. increase in effective regurgitant orifice area (EROA) of ≥ 0.13 cm2] were enrolled in the present investigation. The composite endpoints of all-cause mortality and hospitalization for heart failure were evaluated. Of the 46 patients included in the current cohort, 19 (41%) underwent TMVr and 27 (59%) were medically managed (control group). Although the TMVr group tended to present with a greater EROA at rest (0.26 ± 0.10 vs. 0.20 ± 0.08 cm2, P = 0.047), there were no differences in the EROA changes during exercise between the two groups (0.18 ± 0.10 vs. 0.18 ± 0.04 cm2, P = 0.940). While the TMVr group reported a higher event-free survival rate after the 13-month follow-up period (log-rank P = 0.017), the Cox proportional-hazard analysis suggested the TMVr to be associated with clinical outcomes (hazard ratio: 0.419, P = 0.044). CONCLUSION: As opposed to the medical management, TMVr treatment was associated with a lower risk of composite endpoints in patients with exercise-induced secondary MR. Exercise stress echocardiography is considered to have played an important role in decision-making for secondary MR.

Impact of Prosthesis-Patient Mismatch on Hemodynamics During Exercise in Patients With Aortic Stenosis After Transcatheter Aortic Valve Implantation With a Balloon-Expandable Valve.

BACKGROUND: There is no evidence of hemodynamic performance during exercise in patients with aortic stenosis (AS) after transcatheter aortic valve implantation (TAVI). This study aimed to investigate the changes in kinematic hemodynamics during exercise and determine the impact of prosthesis-patient mismatch (PPM) on the hemodynamics of transcatheter heart valves using exercise stress echocardiography (ESE) in AS patients after TAVI. METHODS AND RESULTS: This study enrolled 77 consecutive patients (mean age 82 ± 5 years, 50.6% male) who underwent ESE 3-6 months after TAVI with a balloon-expandable valve. The effective orifice area index at rest was significantly correlated with the mean pressure gradient (PG) during exercise (p <0.001). The patients were divided into two groups according to the presence of PPM (PPM and non-PPM groups). During exercise, the patients with PPM had a higher left ventricular ejection fraction (74.6 ± 6.1% vs. 69.7 ± 9.6%, p = 0.048), a lower stroke volume index (47.2 ± 14.0 ml/m2 vs. 55.6 ± 14.5 ml/m2, p = 0.037), a significantly higher mean transvalvular PG (21.9 ± 9.1 mmHg vs. 12.2 ± 4.9 mmHg, p = 0.01) and an increased mean PG from rest to exercise (5.7 ± 3.5 mmHg vs. 2.3 ± 2.8 mmHg, p <0.001) compared with patients without PPM. Patients with PPM had a higher pulmonary artery systolic pressure (SPAP) during exercise (57.3 ± 13.8 mmHg vs. 49.7 ± 10.9 mmHg, p = 0.021) and a higher incidence of exercise-induced pulmonary hypertension (43.8 vs. 15.0%, p = 0.037) than patients without PPM. PPM was strongly associated with exercise-induced pulmonary hypertension (hazard ratio: 3.570, p = 0.013). CONCLUSIONS: AS patients with PPM after TAVI showed a disproportionate increase in the transvalvular PG and SPAP during exercise, and PPM was associated with exercise-induced pulmonary hypertension.

Thrombectomy for Small-Artery Occlusions with the Small-Diameter Stent Retriever, Tron Fx 2 mm × 15 mm: A Case Series.

Objective: The safety and efficacy of thrombectomy for small-artery occlusions is still controversial. In April 2019, Tron Fx, a stent retriever with an expansion diameter of 2 mm, became reimbursed by health insurance in Japan. We report on cases of thrombectomy for small-artery occlusions performed using this device in seven patients. Methods: The subjects were seven patients who underwent thrombectomy between July 2019 and June 2020 using Tron Fx with 2 mm in diameter. We analyzed clinical results including recanalization and complications. Results: The mean age of the seven patients was 80.1 years, and the subjects included six men. The sites of occlusion were the middle cerebral artery M2 (n = 4), M4 (n = 1), anterior cerebral artery A2 (n = 1), and A3 (n = 1). One of the seven patients had an M2 occlusion that was formed during coil embolization for a ruptured cerebral aneurysm. In five cases, four cases were of primary occlusion and one case was of emboli into a new territory, treating with only Tron Fx 2 mm resulted in thrombolysis in cerebral infarction (TICI) 2b-3 in four cases. There was one case of grade 0, which was M4 occlusion. Finally, TICI 2b-3 were achieved in six of seven cases. No symptomatic intracranial hemorrhage occurred. Symptoms improved in five of six patients, excluding a vascular occlusion that occurred during surgery. Conclusion: Tron Fx with 2 mm diameter can be used safely for small-artery occlusion. The introduction of Tron Fx with 2 mm diameter may contribute to expand indications for thrombectomy for small-artery occlusions.

Biotin Regulates Colonization and Growth of Candida albicans in the Catheter Lumen During Nutrient Infusions.

Bacterial and fungal catheter-related bloodstream infections (CRBSI) cause high fever and blindness due to fungal endophthalmitis. Candidal CRBSI have a particularly high mortality rate and needs attention. In this study, we examined the effect of biotin on the colonization and growth of Candida albicans in the lumen of the catheter used for nutrient infusions. In the current study, nutrient infusion-1: commercially available peripheral parenteral nutrition (PPN) infusion solution with vitamin B1 (control), nutrient infusion-2: biotin added to the PPN infusion, nutrient infusion-3: water-soluble vitamins (B2, B6, B12, C, folic acid, nicotinamide, panthenol) except biotin added to the PPN infusion, and nutrient infusion-4: commercially available PPN infusion with all water soluble vitamins (B1, B2, B6, B12, C, folic acid, nicotinamide, biotin, panthenol) were used. Candida albicans suspension was injected into a Planecta infusion set, which was connected to one of the test solutions, and the infusions flow pass was blocked for approximately 30 minutes. Subsequently, the infusions were resumed, and the test solution was collected at 24 hours, 48 hours, and 72 hours to estimate the Candida albicans colony-forming units in each infusion. We demonstrated that nutrient infusion with biotin promoted colonization and proliferation in the catheter lumen, whereas those without biotin had no effect. These results suggest that biotin may accelerate the colonization and growth of Candida albicans in catheter lumen and using biotin-containing nutrient infusions may increase the risk of CRBSI.

[Evaluation of Capturing Accurate HbA1c Value Using Medical Information and Communication Technology by Pharmacist].

The medical information and communication technology "Kibitan Health Net" was introduced as a part of the medical reconstruction assistance national project in Fukushima. However, its effect on the performance of the pharmacists has not yet been validated in community pharmacy. In this study, we investigated the usefulness of acquisition and utilization of precise medical information from diabetic patients using Kibitan Health Net. The subjects of this study were 18 patients having type 2 diabetes mellitus with a mean HbA1c level of 7.4±1.0 (%). We compared the HbA1c level captured by the pharmacists from the patients (total 72 times) with that updated on Kibitan Health Net (41 times correctly captured by the pharmacists). We next compared the HbA1c levels between the "group that could listen to accurate laboratory data" and the "group that could not listen to accurate laboratory data" using intergroup analysis. After factor analysis between the two groups, we demonstrated that the proportion of patients who could not precisely communicate laboratory results was significantly higher among the elderly population (p<0.05). Recent studies have reported that elderly diabetic patients have a higher risk of cognitive decline and Alzheimer-type dementia resulting in higher brain dysfunction. The utilization of Kibitan Health Net enabled the capturing of precise patient information. These data could make it possible to provide instruction for proper compliance and guidance for recuperation among the elderly diabetic patients, and prevent their cognitive decline due to poor glycemic control, as well as set future therapeutic goals and improve adherence.

[Survey on the Pharmacists Perceptions of Clinical Trial Literature Accessibility].

The purpose of this study is to understand the reading habits of Japanese pharmacists regarding clinical trial literature in 2014. Questionnaires were mailed to 1997 pharmacists in Miyagi Prefecture. Six hundreds and five [342 (56.5%) hospital pharmacists and 254 (42.0%) community pharmacists] responded to questionnaires (Response rate: 30.3%). Regarding the question, "Do you habitually read clinical trial literature?", 19.5% of hospital and 8.3% community pharmacists responded "yes", respectively, which showed both pharmacists are not habitual readers of clinical trial literature. That would be because they did not study critical reading of clinical trial literature at pharmacy schools as well as their work environments to access and retrieve clinical trial literature were limited.

Bactericidal and Antiproliferative Effects of Peripheral Parenteral Nutrition Solutions with Sodium Bisulfite on Pathogenic Microorganisms in Catheter Lumens.

Catheter-related bloodstream infections (CRBSIs) due to pathogenic microorganisms pose a major threat to patients requiring parenteral nutrition (PN). Additives contained in medicines and foods have antiproliferative and bacteriostatic effects on pathogenic microorganisms. Therefore, PN solutions containing additives may also have an antibacterial effect. However, so far, there have been no reports on or observations of a PN solution with bactericidal activity. In this study, we assessed several nutrition solutions with antimicrobial activities and investigated their effects on pathogenic microorganisms colonizing catheter lumens. We selected the highly acidic Plas-Amino® (PA), which contains a large amount of sodium bisulfite as a preservative and potentially has an antimicrobial effect. In this study, we used the following pathogenic bacteria as the main causatives of CRBSIs: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Serratia marcescens, Pseudomonas aeruginosa, and Candida albicans. We then created a catheter lumen microorganism contamination model and evaluated the antibacterial effect of PA; we found that all bacteria in the control group grew significantly in the catheter lumen in a time-dependent manner at 48 and 72 h. On the other hand, we demonstrated that PA has bactericidal effects on S. aureus, S. epidermidis, B. cereus, S. marcescens, and P. aeruginosa in the catheter lumen and confirmed that it has a remarkable antiproliferative effect on C. albicans. Hence, we concluded that highly acidic PN solutions that contain a preservative like sodium bisulfite have bactericidal and growth inhibition effects on microorganisms in the catheter lumens of patients with CRBSIs and patients with totally implantable central venous access devices, in whom it is difficult to remove the catheter.

Value of Transvalvular Flow Rate during Exercise in Asymptomatic Patients with Aortic Stenosis.

BACKGROUND: The optimal management of asymptomatic aortic stenosis (AS) remains controversial. Although exercise stress echocardiography (ESE) has been applied to nonischemic heart disease, the evidence of the prognostic value for asymptomatic AS has been limited. This study aimed to investigate the value of ESE in patients with asymptomatic AS. METHODS: This retrospective observational study included consecutive asymptomatic patients with at least moderate AS (mean pressure gradient ≥ 20 mm Hg or aortic valve area < 1.5 cm2) and preserved left ventricular ejection fraction (≥50%) who underwent ESE. Of these, 10 patients who were referred for aortic valve replacement without symptoms were excluded. A final 99 conservatively managed patients (73 ± 13 years; 54% male) were enrolled in this study. All patients were followed for AS-related events. RESULTS: During the mean follow-up period of 14 ± 11 months, 23 patients underwent from AS-related events. Although no differences were found between the patients with and without adverse events in terms of mean pressure gradient during exercise, the transvalvular flow rate during exercise (Ex-FR) was lower in the patients who experienced adverse events (236 ± 55 vs 274 ± 64 mL/sec, P = .01). Multivariate Cox regression analysis showed a decrease in Ex-FR (<270 mL/sec) independently associated with adverse events in patients with asymptomatic AS (hazard ratio = 3.53, P < .01). CONCLUSIONS: The result of the present study suggests that Ex-FR measured by ESE could play a crucial role in the risk stratification of patients with asymptomatic AS.