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To evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography.A retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD.Of 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD-, 86% in MAC-/MVD+, and 92% in MAC-/MVD-. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P.001). There was no significant interaction between MAC and MVD for mortality (P=.10).In a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD.

Objective Percutaneous patent foramen ovale (PFO) closure is a procedure widely used to prevent recurrence of cryptogenic stroke. Since December 2019, the Amplatzer PFO occluder device has been available in Japan through medical insurance. However, data on the clinical experience with this device are lacking, as it has been approved for use in only a limited number of institutions. This study assessed the clinical data of Japanese patients who underwent PFO closure using the Amplatzer PFO occluder. Methods Between February and October 2020, 14 patients at our institution underwent percutaneous PFO closure using the Amplatzer PFO occluder. The procedural characteristics, safety, and adverse events were retrospectively analyzed. Results The mean age of the patients was 52.4±13.3 years old, and 57.1% were women. Deep vein thrombosis was revealed in 2 patients, and the risk of paradoxical embolism score was 6.6±1.2 points. The PFO height and tunnel length were 2.3±1.4 mm and 11.5±4.1 mm. All patients had a PFO during the bubble study of grade >3 at the Valsalva maneuver on transthoracic echocardiography or transesophageal echocardiography. The average diameter of the PFO measured using a stiff guidewire and sizing balloon was 5.1±1.3 and 7.9±2.3 mm, respectively. Almost all cases (92.9%) were performed with a 25-mm device and without significant complications within approximately 1 hour. Conclusion Percutaneous closure using Amplatzer PFO occluder is a safe procedure for Japanese patients. However, further investigations with a larger sample and longer follow-up are needed to confirm this result.

Aims Concurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR. Methods and results In patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm2 prior to AVR were evaluated. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all‐cause mortality of patients with and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm2), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00–4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm2 in functional MR (OR 3.28, 95% CI 1.13–9.47; P = 0.028). In the overall cohort, mitral annulus diameter

Grit-blasted/acid-etched titanium dental implants have a moderately roughened surface that is suitable for cell adhesion and exhibits faster osseointegration. However, the roughened surface does not always maintain stable fixation over a long period. In this study, a simple heat treatment at 600°C was performed on a commercially available dental Ti implant with grit-blasting/acid-etching, and its effect on mineralization capacity was assessed by examining apatite formation in a simulated body fluid (SBF). The as-purchased implant displayed a moderately roughened surface at the micrometer scale. Its surface was composed of titanium hydride accompanied by a small amount of alumina particles derived from the grit-blasting. Heat treatment transformed the titanium hydride into rutile without evidently changing the surface morphology. The immersion in SBF revealed that apatite formed on the heated implant at 7 days. Furthermore, apatite formed on the Ti rod surface within 1 day when the metal was subjected to acid and heat treatment without blasting. These indicate that apatite formation was conferred on the commercially available dental implant by simple heat treatment, although its induction period was slightly affected by alumina particles remaining on the implant surface. The heat-treated implant should achieve stronger and more stable bone bonding due to its apatite formation.

Oral health is associated with atherosclerotic cardiovascular disease (ACVD). We previously identified the salivary microbiota characteristics of patients with ACVD. However, whether salivary microbiota is characteristic under impaired vascular endothelial function before ACVD onset remains unclear. Therefore, we aimed to evaluate the characteristics of salivary microbiota associated with peripheral microvascular endothelial dysfunction.We collected saliva samples from 172 community-dwelling elderly individuals without a history of ACVD and performed 16S rRNA metagenomic analysis. We assessed the peripheral microvascular endothelial function using reactive hyperemia index (RHI) and compared the salivary microbiota in the groups with normal (RHI ≥ 2.10), borderline, and abnormal (RHI ＜1.67) peripheral endothelial function. Furthermore, we applied machine learning techniques to evaluate whether salivary microbiota could discriminate between individuals with normal and abnormal endothelial function.The number of operational taxonomic units (OTUs) was higher in the abnormal group than in the normal group (p=0.037), and differences were found in the overall salivary microbiota structure (unweighted UniFrac distances, p=0.038). The linear discriminant analysis (LDA) effect size (LEfSe) algorithm revealed several significantly differentially abundant bacterial genera between the two groups. An Extra Trees classifier model was built to discriminate between groups with normal and abnormal vascular endothelial function based on the microbial composition at the genus level (AUC=0.810).The salivary microbiota in individuals with endothelial dysfunction was distinct from that in individuals with normal endothelial function, indicating that the salivary microbiota may be related to endothelial function.

The importance of oral health in type 2 diabetes mellitus (T2DM) is widely recognized; however, oral microbiota characteristics associated with T2DM in the elderly population are not well-understood. This study was conducted to evaluate the characteristics of the salivary microbiota in elderly Japanese patients with T2DM. Saliva samples were collected from 42 elderly Japanese patients with T2DM and 42 age- and sex-matched subjects without T2DM (control). 16S ribosomal RNA metagenomic analysis and comparative analysis of both groups were performed. Random forest classification by machine learning was performed to discriminate between the salivary microbiota in the two groups. There were significant differences in the overall salivary microbiota structure between the T2DM and control groups (beta diversity; unweighted UniFrac distances, p = 0.001; weighted UniFrac distances, p = 0.001). The phylum Firmicutes was abundant in patients with T2DM, whereas the phylum Bacteroidetes was abundant in controls. The T2DM prediction model by random forest based on salivary microbiota data was verified with a high predictive potential in five cross-validation tests (area under the curve (AUC) = 0.938 (95% CI, 0.824–1.000)). Characterization revealed that the salivary microbiota profile of the elderly patients with T2DM is significantly distinct from that of the controls. These data indicate the necessity of oral health management based on the characteristics of the salivary microbiota in elderly patients with T2DM. Our findings will contribute to future research on the development of new diagnostic and therapeutic methods for this purpose.

Objectives The aims of this study were to: 1) develop a formula for projected transmitral gradient (TMG), expected gradient under normal heart rate (HR), and stroke volume (SV); and 2) assess the prognostic value of projected TMG. Background In mitral stenosis (MS), TMG is highly dependent on hemodynamics, often leading to discordance between TMG and mitral valve area. Methods All patients with suspected MS based on echocardiography from 2001 to 2017 were analyzed. Data were randomly split (2:1); projected TMG was modeled in the derivation cohort, then tested in the validation cohort. The composite endpoint was death or mitral valve intervention. Results Of 4,973 patients with suspected MS, severe and moderate MS, defined as mitral valve area ≤1.5 and >1.5 to 2.0 cm2, were present in 437 (9%) and 936 (19%), respectively. In the derivation cohort (n = 3,315; age 73 ± 12 years; 34% male), corresponding gradients were TMG ≥6 and 4 to Conclusions The novel concept of projected TMG, constructed using the observed impact of HR and SV on TMG, significantly improved the concordance of gradient and valve area in MS and provided better risk stratification than TMG.

Background Prevalence of calcific mitral stenosis (MS) increases with age; however, its natural history and relation to cardiac symptoms or comorbidities are not well defined. Objectives This study assessed the prevalence of symptoms, comorbidities, and determinants of all-cause mortality in patients with severe calcific MS. Methods The authors retrospectively investigated adults with isolated severe calcific MS and mitral valve area ≤1.5 cm2 from July 2003 to December 2017. Inactivity was defined as requirement for assistance with activities of daily living. Results Of 491 patients with isolated severe MS, calcific MS was present in 200 (41%; age 78 ± 11 years, 18% men, 32% with atrial fibrillation). Charlson Comorbidity Index was 5.1 ± 1.7 and 14 (7%) were inactive. Mitral valve area and transmitral gradient (TMG) were 1.26 ± 0.19 cm2 and 8.1 ± 3.8 mm Hg, respectively. Symptoms were present at baseline in 120 (60%); 20 (10%) developed symptoms during follow-up of 2.8 ± 3.0 years. Kaplan-Meier survival at 1 year was 72% without intervention. Inactivity (hazard ratio [HR]: 6.59; 95% confidence interval [CI]: 3.54 to 12.3; p 5 (HR: 1.53; 95% CI: 1.04 to 2.26; p Conclusion Patients with isolated severe calcific MS had a high burden of comorbidities, resulting in high mortality without intervention. Symptoms were reported in 60%, but not associated with mortality. TMG ≥8 mm Hg and right ventricular systolic pressure ≥50 mm Hg were independently associated with mortality.

Accessory tricuspid valve is rare congenital abnormality. We describe a case of cryptogenic stroke in teenager boy caused by patent foramen ovale with thrombophilia and accessory tricuspid valve.

The 2016 American Society of Echocardiography guidelines have been widely used to assess left ventricular diastolic function. However, limitations are present in the current classification system. The aim of this study was to develop a data-driven, unsupervised machine learning approach for diastolic function classification and risk stratification using the left ventricular diastolic function parameters recommended in the 2016 American Society of Echocardiography guidelines; the guideline grading was used as the reference standard.Baseline demographics, heart failure hospitalization, and all-cause mortality data were obtained for all adult patients who underwent transthoracic echocardiography at Mayo Clinic Rochester in 2015. Patients with prior mitral valve intervention, congenital heart disease, cardiac transplantation, or cardiac assist device implantation were excluded. Nine left ventricular diastolic function variables (mitral E- and A-wave peak velocities, E/A ratio, deceleration time, medial and lateral annular e' velocities and E/e' ratio, and tricuspid regurgitation peak velocity) were used for an unsupervised machine learning algorithm to identify different phenotype clusters. The cohort average of each variable was used for imputation. Patients were grouped according to the algorithm-determined clusters for Kaplan-Meier survival analysis.Among 24,414 patients (mean age, 63.6 ± 16.2 years), all-cause mortality occurred in 4,612 patients (18.9%) during a median follow-up period of 3.1 years. The algorithm determined three clusters with echocardiographic measurement characteristics corresponding to normal diastolic function (n = 8,312), impaired relaxation (n = 11,779), and increased filling pressure (n = 4,323), with 3-year cumulative mortality of 11.8%, 19.9%, and 33.4%, respectively (P .0001). All 10,694 patients (43.8%) classified as indeterminate were reclassified into the three clusters (n = 3,324, n = 5,353, and n = 2,017, respectively), with 3-year mortality of 16.6%, 22.9%, and 34.4%, respectively. The clusters also outperformed guideline-based grade for prognostication (C index = 0.607 vs 0.582, P = .013).Unsupervised machine learning identified physiologically and prognostically distinct clusters on the basis of nine diastolic function Doppler variables. The clusters can be potentially applied in echocardiography laboratory practice and future clinical trials for simple, replicable diastolic function-related risk stratification.

Background Ventricular‐arterial coupling predicts outcomes in patients with heart failure. The arterial elastance to end‐systolic elastance ratio (Ea/Ees) is a noninvasively assessed index that reflects ventricular‐arterial coupling. We aimed to determine the prognostic value of ventricular‐arterial coupling assessed through Ea/Ees after transcatheter aortic valve replacement to predict clinical events. Methods and Results We retrieved data on 1378 patients (70% women) who underwent transcatheter aortic valve replacement between October 2013 and May 2017 from the OCEAN‐TAVI (Optimized transCathEter vAlvular iNtervention) Japanese multicenter registry. We determined the association between Ea/Ees and the composite end point of hospitalization for heart failure and cardiovascular death by classifying the patients into quartiles based on Ea/Ees values (group 1: 0.666) during the midterm follow‐up after transcatheter aortic valve replacement. During a median follow‐up period of 736 days (interquartile range, 414–956), there were 247 (17.9%) all‐cause deaths, 89 (6.5%) cardiovascular deaths, 130 (9.4%) hospitalizations for heart failure, and 199 (14.4%) composite events of hospitalization for heart failure and cardiovascular death. The incidence of the composite end point was significantly higher in group 2 (hazard ratio [HR], 1.76; 95% CI, 1.08–2.87 [ P =0.024]), group 3 (HR, 2.43; 95% CI, 1.53–3.86 [ P P P =0.015]). Conclusions These findings suggest that a higher Ea/Ees at discharge after transcatheter aortic valve replacement is associated with adverse clinical outcomes during midterm follow‐up. Registration URL: https://www.upload.umin.ac.jp/ . Unique identifier: UMIN000020423.

Background Mitral stenosis (MS) is often concomitant with aortic stenosis (AS). However, little is known about the functional status following transcatheter aortic valve replacement (TAVR) alone in patients with severe AS and MS and the impact of TAVR for AS on MS hemodynamics. Methods We enrolled 11 patients (age 83.6 ± 4.7 years, eight women) with severe AS and MS who underwent TAVR. We compared New York Heart Association (NYHA) functional class and mean transmitral pressure gradient (MPG), mitral valve area (MVA), and stroke volume (SV) measured by transthoracic Doppler echocardiography between baseline and after TAVR. We also examined the calcification of the mitral annulus and mitral leaflet opening. Results NYHA functional class improved after TAVR in all 11 patients. As SV increased after TAVR (52 ± 12 mL to 63 ± 18 mL, p = 0.041), MPG decreased and MVA increased (6.9 ± 3.8 mmHg to 5.1 ± 2.5 mmHg, p = 0.011 for MPG and 1.12 ± 0.25 cm2 to 1.49 ± 0.43 cm2, p = 0.035 for MVA). However, MPG increased in one patient in whom calcification extended into the entire anterior mitral leaflet (AML) and AML mobility was severely reduced. Conclusions NYHA functional class and hemodynamic status of MS improved after TAVR in patients with severe AS and MS. TAVR might provide therapeutic efficacy for selected symptomatic severe AS patients with MS.

We have encountered a rare case in which the subject underwent maxillary sinus floor elevation at another hospital, and a screw to fix the grafted bone substitute was forced into the maxillary sinus and intruded into the bone. Various different foreign bodies have been reported as being forced into the maxillary sinus due to dental treatment, and these foreign bodies are often retained on the maxillary sinus mucous membrane. However, no reports have described a screw forced in and intruded into the peculiar position in the bone, as seen in the present case, which we report here with additional discussion.

Aims Oral bacteria have been reported to be associated with the pathogenesis of atherosclerosis; however, the relationship between the oral microbiota and atherosclerosis remains unclear. The present study aimed to investigate whether or not salivary microbiota of patients with atherosclerotic cardiovascular disease (ACVD) differs from that of subjects without ACVD, and to characterize the salivary microbiota of patients with ACVD. Methods This study included 43 patients with ACVD and 86 age- and sex-matched non-ACVD individuals. 16S rRNA metagenomic analysis were performed using DNA isolated from the saliva samples of the participants. To select unique operational taxonomic unit (OTU) sets of ACVD, we conducted the random forest algorithm in machine learning, followed by confirmation via 10-fold cross-validation Results: There was no difference in richness or evenness between the ACVD and non-ACVD groups (alpha diversity; observed OTU index, p=0.503; Shannon's index, p=0.478). However, significant differences were found in the overall salivary microbiota structure (beta diversity; unweighted UniFrac distances, p=0.001; weighted UniFrac distances, p=0.001). The Actinobacteria phylum was highly abundant in patients with ACVD, while the Bacteroidetes phylum was less abundant. The random forest classifier identified 43 OTUs as an optimal marker set of ACVD. In a 10-fold cross validation using the validation data, an area under the curve (AUC) of 0.933 (95% CI, 0.855-1.000) was obtained. Conclusions The salivary microbiota in patients with ACVD was distinct from that of non-ACVD individuals, indicating that the salivary microbiota may be related to ACVD.

Background Transmitral gradient (TMG) is highly dependent on hemodynamic state, leading to discordance between TMG and mitral valve area (MVA). The effect of heart rate (HR) and stroke volume (SV) on TMG among patients with mitral stenosis (MS) is poorly understood. Purposes We aimed to (1) develop a formula for projected TMG (proTMG) for assessment of MS severity under varying hemodynamics; (2) assess the prognostic value of proTMG in patients with MS. Methods All patients evaluated for suspected MS without ≥moderate other valve disorder at our tertiary center between 2001 and 2017 were analyzed. Projected TMG is the expected gradient under normal flow (SV 80–94 ml and HR 60–79 bpm), and was modeled based on the observed impact of HR and SV on TMG by multiple regression analysis. The data were randomly split (2:1) into training and testing sets. The improvement in agreement between MVA and proTMG was evaluated. Composite cardiac events including all-cause death and mitral valve interventions were compared according to TMG grade using TMG and proTMG. Severe and moderate MS were defined as MVA ≤1.5 cm2 and 1.5–2.0 cm2 respectively, by the continuity equation. MVA ≤1.0 cm2 was considered as very severe MS. Results Of 4973 patients with suspected MS (age 73±12 years, 33% male), severe MS was present in 437 (9%, including 98 with very severe MS) and moderate MS in 934 (19%). In 838 patients with normal HR and SV, very severe, severe and moderate MS corresponded to TMG ≥12 mmHg, ≥6 mmHg and 4–6 mmHg, respectively. In the training set (n=3315), the median [interquartile range] of HR and SV were 70 [61–80] bpm and 97 [83–113] mL in men (n=1120), and 72 [63–82] bpm and 84 [71–97] mL in women (n=2195), respectively. The impact of HR and SV on TMG for men and women were 0.07 and 0.08 mmHg per 1 bpm increase in HR (95% confidence interval [CI] 0.06–0.07 and 0.07–0.08), and 0.03 and 0.05 mmHg per 1 mL increase in SV (95% CI 0.03–0.03 and 0.04–0.05), respectively. Therefore, the final formula to calculate proTMG was: proTMG=TMG-0.07(HR-70)-0.03(SV-97) in men and proTMG=TMG-0.08(HR-72)-0.05(SV-84) in women. In the testing set (n=1658), the proTMG (kappa=0.63, 95% CI 0.60–0.66) had better agreement with MS severity by MVA than TMG (kappa=0.28, 95% CI 0.24–0.32). To explore the prevalence of patients reclassified using proTMG, in 98 with TMG ≥12 mmHg, proTMG remained ≥6 mmHg. Of 657 with TMG 6–12 mmHg, proTMG remained ≥6 mmHg in 356 (54%), and decreased to Conclusion We propose a novel concept of projected TMG defined as the expected transmitral gradient at normal HR and SV levels. This improved the diagnostic yield of Doppler TMG measurements for MS severity assessment and identified a low-risk subset of patients with elevated TMG due to high HR or SV. Funding Acknowledgement Type of funding source: None

Background There is a paucity of data about the prevalence and natural history of mitral annular calcification (MAC). Purposes In a large cohort of patients undergoing clinically-indicated echocardiography, we aimed to evaluate the prevalence and the natural history of MAC, and the frequency of associated mitral valve dysfunction (MVD). Methods Retrospective review of all patients who underwent echocardiographic evaluation at our institution between January 1st and December 31st 2015. The patients were stratified into 3 groups: MAC with MVD, MAC without MVD, no MAC. MVD was defined as moderate or greater mitral regurgitation (MR) or stenosis (MS). The 3 groups were compared for baseline clinical and echocardiographic characteristics and all-cause mortality during follow-up. Results Of 24,415 evaluated patients, 5478 (22%) had MAC. Patients with MAC were older (75±10 vs. 60±16 years, p Conclusion In a large cohort of patients undergoing echocardiographic evaluation, the prevalence of MAC was 22%. MV dysfunction was more than twice as prevalent in patients with MAC as without. Patients with MAC had higher all-cause mortality than patients without MAC. Among patients with MAC and mitral valvular dysfunction, adjusted mortality was two-fold higher compared to those without MAC. Funding Acknowledgement Type of funding source: None

Background Prevalence of calcific mitral stenosis (MS) increases with age. Mitral valve interventions for calcific MS are often delayed until symptoms are severely limiting because the natural history of calcific MS and its relation to cardiac symptoms or comorbidities have not been well assessed. Objectives We assessed the prevalence of symptoms, comorbidities and determinants of all-cause mortality in patients with severe calcific MS. Methods We retrospectively investigated adults with echocardiographic isolated severe MS, defined as mitral valve area (MVA by the continuity equation) ≤1.5 cm2, from July 2003 to December 2017. Among them, calcific MS was identified as obstruction of left ventricular inflow due to degenerative calcification of the mitral annulus using echocardiography and, whenever available, operative findings including histopathological examination. Inactivity was defined as requirement for assistance with activities of daily living. Follow up was obtained by review of medical records. Results Of 491 patients with isolated severe MS, calcific MS was present in 200 (41%; age 78±11 years, 18% men, 32% with atrial fibrillation). Charlson Comorbidity Index (CCI) was 5.1±1.7 and 14 (7%) were inactive. MVA and transmitral gradient (TMG) were 1.26±0.19 cm2 and 8.1±3.8 mmHg, respectively. Symptoms were present at baseline in 120 (60%) including dyspnea in 97, chest discomfort in 12, syncope in 3, lower extremity edema in 3, thrombosis in 3 and fatigue in 2. Of them, mitral valve interventions including surgical or transcatheter mitral valve replacement and mitral valve bypass were performed in 27 (23%): within 1 year after index TTE in 23 (19%) and at 2, 4, 5 and 6 years in 1 each. Of 80 patients without symptoms at index TTE, 20 (25%) developed symptoms at mean 2.9±3.2 years and interventions were performed in 5 (6%). Of 168 who did not receive interventions, 60 (36%) did not develop symptoms during follow up, 58 (35%) were considered to have moderate MS, 46 (27%) were not offered surgery because of high risk due to advanced age, multiple comorbidities or heavy calcification, and 2 (1%) declined interventions. During follow-up of 2.8±3.0 years, Kaplan-Meier survival at 1 and 3 years without intervention were 72% and 52%, respectively (Fig. A). Inactivity, CCI >5, left ventricular ejection fraction (LVEF) Conclusion Patients with isolated severe calcific MS had a high burden of comorbidities and had high mortality without intervention. Symptoms were common (60%), but were not associated with mortality. TMG ≥8 mmHg, RVSP ≥50 mmHg, LVEF5 and inactivity were independently associated with mortality. Funding Acknowledgement Type of funding source: None

The additive manufacturing (AM) technique has attracted attention as one of the fully customizable medical material technologies. In addition, the development of new surface treatments has been investigated to improve the osteogenic ability of the AM titanium (Ti) plate. The purpose of this study was to evaluate the osteogenic activity of the AM Ti with mixed-acid and heat (MAH) treatment. Fully customized AM Ti plates were created with a curvature suitable for rat calvarial bone, and they were examined in a group implanted with the MAH-treated Ti in comparison with the untreated (UN) group. The AM Ti plates were fixed to the surface of rat calvarial bone, followed by extraction of the calvarial bone 1, 4, 8, and 12 weeks after implantation. The bonding between the bone and Ti was evaluated mechanically. In addition, AM Ti plates removed from the bone were examined histologically by electron microscopy and Villanueva&ndash, Goldner stain. The mechanical evaluation showed significantly stronger bone-bonding in the MAH group than in the UN group. In addition, active bone formation was seen histologically in the MAH group. Therefore, these findings indicate that MAH resulted in rapid and strong bonding between cortical bone and Ti.

Background Previous studies have demonstrated that three-dimensional (3D) transesophageal echocardiography (TEE) is an alternative to multi-detector computed tomography (MDCT) for aortic valve sizing in transcatheter aortic valve replacement (TAVR). However, conventional cross-sectional analysis of aortic annulus by 3D TEE has some limitations such as lengthy analytical time. A novel software for automated valve measurement has been developed for 3D TEE. We evaluated the accuracy and analytical time of aortic annular measurements using this novel automated software in the clinical setting. Methods We retrospectively studied 43 patients with symptomatic severe aortic stenosis (AS) who underwent TAVR. All patients underwent intraoperative TEE and MDCT. We measured aortic annular area by automated, semi-automated, and cross-sectional methods using 3D TEE datasets. These measurements were compared to the corresponding MDCT reference values. We also compared the analytical time of the three methods. Results Automated and semi-automated analyses required significantly shorter analytical time compared to cross-sectional analysis (automated: 30.1 ± 5.79 s, semi-automated: 74.1 ± 15.0 s, manual: 81.8 ± 18.5 s, p 2 ), annular areas measured by automated and cross-sectional methods were significantly smaller (automated: 380.6 ± 77.1 mm 2 , cross-sectional: 374.7 ± 76.8 mm 2 , p 2 ). Annular areas determined by semi-automated and cross-sectional analyses had narrower limits of agreement (LOA) with MDCT measurements, compared to automated analysis (automated: −68.6 to 94.7 mm 2 , semi-automated: −48.3 to 60.2 mm 2 , cross-sectional: −40.0 to 77.9 mm 2 ). Measurements by all three methods using 3D TEE showed high correlation with MDCT measurement (automated: r = 0.86, semi-automated: r = 0.94, cross-sectional: r = 0.93). Conclusions For aortic annular measurements using 3D TEE in AS patients, semi-automated analysis using the novel automated software reduced analytical time while maintaining similar accuracy compared to the conventional cross-sectional analysis. This automated software may have acceptable feasibility in the clinical setting.

Purpose To compare the diagnostic accuracy of different computed tomographic (CT) fractional flow reserve (FFR) algorithms for vessels with intermediate stenosis. Materials and Methods This cross-sectional HIPAA-compliant and human research committee-approved study applied a four-step CT FFR algorithm in 61 patients (mean age, 69 years ± 10; age range, 29-89 years) with a lesion of intermediate-diameter stenosis (25%-69%) at CT angiography who underwent FFR measurement within 90 days. The per-lesion diagnostic performance of CT FFR was tested for three different approaches to estimate blood flow distribution for CT FFR calculation. The first two, the Murray law and the Huo-Kassab rule, used coronary anatomy; the third used contrast material opacification gradients. CT FFR algorithms and CT angiography percentage diameter stenosis (DS) measurements were compared by using the area under the receiver operating characteristic curve (AUC) to detect FFRs of 0.8 or lower. Results Twenty-five lesions (41%) had FFRs of 0.8 or lower. The AUC of CT FFR determination by using contrast material gradients (AUC = 0.953) was significantly higher than that of the Huo-Kassab (AUC = 0.882, P = .043) and Murray law models (AUC = 0.871, P = .033). All three AUCs were higher than that for 50% or greater DS at CT angiography (AUC = 0.596, P < .001). Correlation of CT FFR with FFR was highest for gradients (Spearman ρ = 0.80), followed by the Huo-Kassab rule (ρ = 0.68) and Murray law (ρ = 0.67) models. All CT FFR algorithms had small biases, ranging from -0.015 (Murray) to -0.049 (Huo-Kassab). Limits of agreement were narrowest for gradients (-0.182, 0.147), followed by the Huo-Kassab rule (-0.246, 0.149) and the Murray law (-0.285, 0.256) models. Conclusion Clinicians can perform CT FFR by using a four-step approach on site to accurately detect hemodynamically significant intermediate-stenosis lesions. Estimating blood flow distribution by using coronary contrast opacification variations may improve CT FFR accuracy. © RSNA, 2017 Online supplemental material is available for this article.

Purpose We carried out guided bone regeneration of cranial bone defects in rats using the bovine bone substitute Bio-Oss and a collagen membrane and performed histological observations of the bone repair process. Materials and methods Bone defects were created in the cranial bones of 30 15-week-old Sprague-Dawley rats. We made 3 groups. A is unfilled, B is Bio-Oss, and C is Bio-Oss plus a collagen membrane. At 4 or 8 weeks postoperatively, tissue samples were taken. The Kawamoto technique was used for histological evaluation. Results There was no new bone formation in group A. In groups B and C, new bone formation was evident around the Bio-Oss. In group C, new bone formation was evident in the centers of the bone defects, detached from the cut edge of the cranial bone. Conclusion Our results suggested that the Bio-Oss acts as a scaffold for bone repair, and the use of a collagen membrane may anchor the Bio-Oss closely to the cranial bone and assist the bone repair response.

The practical use of additive manufacturing to create artificial bone as a material for repairing complex bone defects is currently attracting attention. In this study, we compared the osteogenic capacity of materials composited by the method developed by Kokubo et al. of treating 3D-printed titanium (Ti) mesh with a mixture of H2SO4 and HCl and heating (mixed-acid and heat treatment) with that of materials subjected to conventional chemical treatment. Ti plates treated with this method have been found to promote highly active bone formation on their surface when inserted into rabbit tibial bone defects. No previous study has compared this method with other surface treatment methods. In this study, we used histological and other observations to compare the bone formation process in bone defects when Ti meshes prepared by the selective laser melting technique (SLM) and treated either with mixed acids and heat or with conventional chemical Ti surface treatments were implanted in a rat calvarial bone defect model. We found that both micro-computed tomography and observations of undecalcified ground sections showed that the best bone formation was observed in rats implanted with mesh treated with mixed acids and heat. Our results suggest that mixed-acid and heat-treated Ti mesh prepared by SLM may have a high osteogenic capacity in bone defects.

Jaw reconstruction using an additive-manufacturing titanium artificial bone (AMTAB) has recently attracted considerable attention. The synthesis of a titanium artificial bone is based on three-dimensional computed tomography images acquired before surgery. A histological evaluation of porous AMTAB (pAMTAB) embedded in rat calvarial bone defects was conducted. This study examined three groups: rats implanted with mixed-acid and heat-treated pAMTAB, rats implanted with untreated pAMTAB, and rats with no implant. In both pAMTAB groups, bone defects were created in rat calvarial bones using a 5-mm trephine bar, followed by pAMTAB implantation. The pAMTAB was fixed to the defect using the fitting force of the surrounding bones. The rats were sacrificed at 4, 8, and 16 weeks after implantation, and the skull was dissected. Undecalcified ground slides were prepared and stained with Villanueva Goldner. Compared with the no implant control group, both pAMTAB groups exhibited new bone formation inside the defect, with greater bone formation in the mixed-acid and heat-treated pAMTAB group than in the untreated pAMTAB group, but the difference was not significant. These data suggest that pAMTAB induces bone formation after implantation in bone defects. Bone formation appears to be enhanced by prior mixed-acid and heat-treated pAMTAB.

The new methods for diagnosing the ischemia with coronary computed tomographic angiography (CTA) as a noninvasive test have been investigated. To compare the relative plaque volume to quantitative CTA and quantitative coronary angiography (QCA) for detecting flow-limiting coronary artery stenoses. We studied 49 patients with 55 intermediate lesions (30-69% diameter stenosis) who underwent CTA, coronary angiography (CAG), and FFR. CTA and QCA measures included lesion length, percent diameter stenosis (%DS), minimal lumen diameter (MLD), target main vessel percent plaque volume (%PV), lesion %PV, target main vessel percent lumen volume (%LV), and lesion %LV. FFR ≤0.80 was considered diagnostic of a flow-limiting lesion. The area under the receiver-operating characteristic curve (AUC) was used to determine the accuracy of detecting flow-limiting lesions. We also investigated the AUC of discrimination of flow-limiting lesion according to calcium score. Eighteen of 55 lesions (32.7%) had an FFR ≤0.80. Only vessel %PV differentiated between lesions with and without flow obstruction (67.6 vs. 62.7%, p = 0.018). The AUC for vessel %PV was greatest (0.76; 95% CI 0.61-0.87). The AUC for the discrimination of the flow-limiting lesions according to low calcium score (≤400) improved to 0.82 (95% CI 0.57-0.94). In intermediate coronary artery stenoses, vessel %PV is more accurate than conventional stenosis assessment for detecting flow-limiting lesions. In low calcium score, vessel %PV is more useful for diagnosis of ischemic heart disease compared with conventional quantitative measures.

This study aims to establish a computed tomography (CT)-based scoring system for grading mitral annular calcification (MAC) severity and potentially aid in predicting valve embolization during transcatheter mitral valve (MV) replacement using balloon-expandable aortic transcatheter heart valves.Transcatheter MV replacement is emerging as an alternative treatment for patients with severe MAC who are not surgical candidates. Although cardiac CT is the imaging modality of choice in the evaluation of candidates for valve-in-MAC (ViMAC), a standardized grading system to quantify MAC severity has not been established.We performed a multicenter retrospective review of cardiac CT and clinical outcomes of patients undergoing ViMAC. A CT-based MAC score was created using the following features: average calcium thickness (mm), degrees of annulus circumference involved, calcification at one or both fibrous trigones, and calcification of one or both leaflets. Features were assigned points according to severity (total maximum score = 10) and severity grade was assigned based on total points (mild ≤3, moderate 4 to 6, and severe ≥7 points). The association between MAC score and device migration/embolization was evaluated.Of 117 patients in the TMVR in MAC registry, 87 had baseline cardiac CT of adequate quality. Of these, 15 were treated with transatrial access and were not included. The total cohort included 72 (trans-septal = 37, transapical = 35). Mean patient age was 74 ± 12 years, 66.7% were female, and the mean Society of Thoracic Surgery risk score was 15.4 ± 10.5%. The mean MAC score was 7.7 ± 1.4. Embolization/migration rates were lower in higher scores: Patients with a MAC score of 7 had valve embolization/migration rate of 12.5%, MAC score ≥8 had a rate of 8.7%, and a MAC score of ≥9 had zero (p = 0.023). Patients with a MAC score of ≤6 had 60% embolization/migration rate versus 9.7% in patients with a MAC score ≥7 (p 0.001). In multivariable analysis, a MAC score ≤6 was in independent predictor of valve embolization/migration (odds ratio [OR]: 5.86 [95% CI: 1.00 to 34.26]; p = 0.049).This cardiac CT-based score provides a systematic method to grade MAC severity which may assist in predicting valve embolization/migration during trans-septal or transapical ViMAC procedures.

Background: Mitral stenosis frequently coexists in patients with severe aortic stenosis. Mitral stenosis severity evaluation is challenging in the setting of combined aortic stenosis and mitral stenosis because of hemodynamic interactions between the 2 valve lesions. The impact of aortic valve replacement (AVR) for severe aortic stenosis on mitral stenosis is unknown. This study aimed to assess the effect of AVR on mitral stenosis hemodynamics and the clinical outcomes of patients with severe aortic stenosis with and without mitral stenosis. Methods: We retrospectively investigated patients who underwent surgical AVR or transcatheter AVR for severe aortic stenosis from 2008 to 2015. Mean transmitral gradient by Doppler echocardiography ≥4 mm Hg was identified as mitral stenosis; patients were then stratified according to mitral valve area (MVA, by continuity equation) as >2.0 cm 2 or ≤2.0 cm 2 . MVA before and after AVR in patients with mitral stenosis were evaluated. Clinical outcomes of patients with and without mitral stenosis were compared using 1:2 matching for age, sex, left ventricular ejection fraction, method of AVR (surgical AVR versus transcatheter AVR) and year of AVR. Results: Of 190 patients with severe aortic stenosis and mitral stenosis (age 76±9 years, 42% men), 184 were matched with 362 with severe aortic stenosis without mitral stenosis. Among all mitral stenosis patients, the mean MVA increased after AVR by 0.26±0.59 cm 2 (from 2.00±0.50 to 2.26±0.62 cm 2 , P 2 (odds ratio [OR] 2.40; 95% CI, 1.15–5.01; P =0.020) and transcatheter AVR (OR, 2.36; 95% CI, 1.17–4.77; P =0.017) were independently associated with increase in MVA. Of 107 with significant mitral stenosis (MVA ≤2.0 cm 2 ), MVA increased to >2.0 cm 2 after AVR in 52 (49%, pseudo mitral stenosis) and remained ≤2.0 cm 2 in 55 (51%, true mitral stenosis). During follow-up of median 2.9 (0.7–4.9) years, true mitral stenosis was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.88; 95% CI, 1.20–2.94; P Conclusions: MVA improved after AVR in nearly half of patients with severe aortic stenosis and mitral stenosis. MVA remained ≤2.0 cm 2 (true mitral stenosis) in nearly half of patients with severe aortic stenosis and significant mitral stenosis; this was associated with worse survival among patients undergoing AVR for severe aortic stenosis.